Issuu

UPDATE IMMUN O LO GY

IN ASSOCIATION WITH

VOL 12 | ISSUE 10 | 2026

INFECTIOUS DISEASE

PREVENTION

AUTOIMMUNE DISEASE

Staph aureus bacteraemia Trauma related infections Herpes zoster ophthalmicus

Antimicrobial stewardship The role of vaccines in healthy ageing Dealing with vaccine hesitancy

Atopic dermatitis Inflammatory bowel disease Allergic rhinitis

ical

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References 1. IQVIA. Incentives For Using Biosimilars In France And Europe. Analysis, assessment, and perspectives. Apr 2023. 2. IQVIA. Biosimilars in the United States 2023-2027. Jan 2023. 3. Smolen JS, et al. Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47. RMD Open. 2024;10:e004514. 4. Burmester G, et al. Efficacy and Safety of Biosimilar CT-P47 Versus Reference Tocilizumab: 1-Year Results of a Randomised, ActiveControlled, Double-Blind, Phase III Study in Patients with Rheumatoid Arthritis. Clin Drug Investig. 2025;45(8). 5. Celltrion Inc. Data on File. 6. EMA. Avtozma Summary of Product Characteristics. 7. FDA. Biosimilars improve patient access to quality medicines

Avtozma™ (tocilizumab) ▼ Abbreviated Prescribing Information for healthcare professionals Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentations: Vial containing 20 mg/mL tocilizumab concentrate for solution for intravenous infusion in 80 mg/4 mL, 200 mg/10 mL and 400 mg/20 mL vials. Single-dose pre-filled pen and pre-filled syringe containing 162 mg tocilizumab solution in 0.9 mL for subcutaneous injection. Indications: Rheumatoid arthritis (RA): In combination with methotrexate (MTX), for treatment of adult patients with: severe, active and progressive RA not previously treated with MTX; or moderate to severe active RA and inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor antagonists. Avtozma can be given as monotherapy where continued treatment with MTX is inappropriate or not tolerated. Systemic juvenile idiopathic arthritis (sJIA): Treatment of active sJIA in patients ≥2 years of age with inadequate response to prior therapy with NSAIDs and systemic corticosteroids. Can be given as monotherapy (where MTX is not tolerated or is inappropriate) or in combination with MTX. Polyarticular juvenile idiopathic arthritis (pJIA): In combination with MTX, for the treatment of juvenile idiopathic polyarthritis (pJIA; rheumatoid factor positive or negative and extended oligoarthritis) in patients ≥2 years of age with inadequate response to prior therapy with MTX. Can be given as monotherapy where continued treatment with MTX is inappropriate or not tolerated. Giant Cell Arteritis (GCA): Treatment of GCA in adult patients, in combination with tapering course of glucocorticoids (subcutaneous only). Posology and Method of Administration For intravenous (IV) administration: Avtozma should be initiated by healthcare professionals (HCPs) experienced in the diagnosis and treatment of the conditions for which it is indicated. After dilution, Avtozma should be administered as an intravenous infusion over 1 hour. RA: 8 mg/kg of body weight once every 4 weeks. Doses exceeding 800 mg per infusion are not recommended. sJIA: 8 mg/kg once every 2 weeks in patients weighing ≥30 kg, or 12 mg/kg once every 2 weeks in patients weighing <30 kg. pJIA: 8 mg/kg once every 4 weeks in patients weighing ≥30 kg, or 10 mg/kg once every 4 weeks in patients weighing <30 kg. For subcutaneous (SC) administration: Treatment should be initiated by HCPs experienced in diagnosis and treatment of RA, JIA and/ or GCA. First injection should be performed under supervision of a qualified HCP. A patient or parent/guardian can self-inject Avtozma only if the physician determines that it is appropriate and training in proper injection technique has been provided. Patients weighing <10 kg should not receive Avtozma subcutaneously. The pre-filled pen should not be used for paediatric patients <12 years of age since there is a risk of intramuscular injection due to thinner subcutaneous tissue layer. If transitioning from IV to SC formulation, administer first SC dose instead of the next scheduled IV dose, under HCP supervision. RA: 162 mg SC once every week. GCA: 162 mg SC once every week in combination with a tapering course of glucocorticoids, or alone following discontinuation of glucocorticoids. Avtozma monotherapy should not be used for the treatment of acute relapses. sJIA: 162 mg SC once every week in patients weighing ≥30 kg, or 162 mg once every 2 weeks in patients weighing <30 kg. pJIA: 162 mg SC once every 2 weeks in patients weighing ≥30 kg, or 162 mg once every 3 weeks in patients weighing <30 kg. Contraindications: Hypersensitivity to the active substance or to any of the excipients (contains polysorbate). Active, severe infections. Warnings & Precautions: To improve traceability of biological medicinal products, name and batch number of administered product should be clearly recorded. Infections: Serious, sometimes fatal, infections have been reported in patients receiving immunosuppressive agents including tocilizumab. Do not initiate in patients with active infections. Interrupt treatment if patient develops a serious infection until infection is controlled. Exercise caution when considering Avtozma use in patients with history of recurring/chronic infections or with conditions predisposing to infections. Vigilance for timely detection of serious infection is advised as signs & symptoms of acute inflammation may be lessened, with suppression of the acute phase reaction. Instruct patients or parents/ guardians to contact their HCP immediately if symptoms of infection appear; ensure rapid evaluation & appropriate treatment. Tuberculosis (TB): Screen all patients for latent TB infection prior to starting Avtozma. Treat patients with latent TB with standard anti-mycobacterial therapy before initiating Avtozma. Instruct patients to seek medical advice if signs/symptoms (e.g. persistent cough, wasting/weight loss, low grade fever) suggestive of TB occur during or after therapy. Viral reactivation (e.g. hepatitis B virus) has been reported with biologic therapies for RA. Complications of diverticulitis: Diverticular perforations as complications of diverticulitis have been reported uncommonly with tocilizumab in RA patients. Use with caution in patients with history of intestinal ulceration or diverticulitis. Promptly evaluate patients presenting with symptoms potentially indicative of complicated diverticulitis, which can be associated with gastrointestinal perforation. Hypersensitivity reactions, including anaphylaxis, have been reported in association with tocilizumab. Reactions may be more severe and potentially fatal in patients who had hypersensitivity reactions during previous tocilizumab treatment. If an anaphylactic or other serious hypersensitivity / infusion related reaction occurs, Avtozma should be stopped immediately and permanently discontinued. Active hepatic disease and hepatic impairment: Tocilizumab treatment, particularly when administered with MTX, is associated with elevations in hepatic transaminases. Caution when considering treatment of patients with active hepatic disease or impairment. Hepatotoxicity: Transient or intermittent mild-moderate elevations of hepatic transaminases have been reported commonly with tocilizumab treatment, particularly when potentially hepatotoxic drugs (e.g. MTX) were used in combination. Serious drug-induced liver injury, including acute liver failure, hepatitis and jaundice, have been observed with tocilizumab, from 2 weeks to >5 years after initiation. Advise patients to seek immediate medical help if they experience signs or symptoms of hepatic injury. Caution when considering initiation of Avtozma in patients with elevated ALT or AST. In patients with baseline ALT or AST >5 x ULN, treatment is not recommended. Monitor ALT/AST every 4 to 8 weeks for first 6 months of treatment then every 12 weeks

Avtozma for Update Journal.indd 1

thereafter. For recommended modifications based on transaminase levels, including Avtozma discontinuation, see section 4.2 of the SmPC. Haematological abnormalities: Decreases in neutrophil and platelet counts have occurred following treatment with tocilizumab 8 mg/kg in combination with MTX. Increased risk of neutropenia in patients previously treated with a TNF antagonist. If not previously treated with tocilizumab, initiation is not recommended if absolute neutrophil count (ANC) is <2 x 109/L. Caution when considering tocilizumab in patients with platelet count <100 x 103/μL. In patients who develop ANC <0.5 x 109/L or platelets <50 x 103/μL, continued treatment is not recommended. Neutrophils and platelets should be monitored 4 to 8 weeks after start of therapy in RA or GCA patients, or at the time of second administration in JIA patients, and thereafter according to standard clinical practice. For recommended dose modifications based on ANC and platelet counts, see section 4.2 of SmPC. Lipid parameter elevations were observed in patients treated with tocilizumab. In most patients, there was no increase in atherogenic indices, and total cholesterol responded to lipid lowering agents. Check lipids 4 to 8 weeks after start of therapy and manage as per local guidelines. Neurological disorders: The potential for central demyelination with tocilizumab is currently unknown; be vigilant for symptoms indicative of new-onset demyelinating disorders. Malignancy: Risk of malignancy is increased in patients with RA. Immunomodulatory medicinal products may increase the risk of malignancy. Vaccinations: Live and attenuated vaccines should not be given concurrently with tocilizumab as clinical safety has not been established. Bring patients up to date with all immunisations in line with current guidelines prior to initiating Avtozma. Combination with TNF antagonists: There is no experience with use of Avtozma with TNF antagonists or other biological treatments. Avtozma is not recommended for use with other biological agents. sJIA Patients: Macrophage activation syndrome (MAS) is a serious life-threatening disorder that may develop in sJIA patients. In clinical trials, tocilizumab has not been studied in patients during an episode of active MAS. Excipients with known effect: Each 162 mg pre-filled pen or syringe contains 0.2 mg of polysorbate 80. Each 80 mg vial contains 2 mg, each 200 mg vial contains 5 mg, and each 400 mg vial contains 10 mg of polysorbate 80. Polysorbates may cause allergic reactions. Patients with polysorbate allergy should not take this medicine. Interactions: CYP450 expression may increase when potent cytokine inhibitory therapy, such as tocilizumab, is introduced. When starting or stopping tocilizumab therapy, patients taking medicines which are individually adjusted and metabolised via CYP450 3A4, 1A2 or 2C9 (e.g. methylprednisolone, dexamethasone, (with possibility for glucocorticoid withdrawal syndrome), atorvastatin, calcium channel blockers, theophylline, warfarin, phenytoin, ciclosporin, or benzodiazepines) should be monitored as doses may need to be increased to maintain therapeutic effect. Pregnancy and lactation: Women of childbearing potential must use effective contraception during and up to 3 months after treatment. There are no adequate data on use of tocilizumab in pregnant women. Avtozma should not be used during pregnancy unless clearly necessary. It is unknown whether tocilizumab is excreted in human breast milk. A decision on whether to continue/ discontinue breast-feeding or Avtozma should consider the benefit of breastfeeding to the child and benefit of Avtozma to the woman. Adverse Drug Reactions: The most commonly reported ADRs (occurring in ≥5% of patients) were upper respiratory tract infections, nasopharyngitis, headache, hypertension and increased ALT. The most common serious ADRs were serious infections, complications of diverticulitis, and hypersensitivity reactions. Other Very common (≥ 1/10) or Common (≥ 1/100 to < 1/10) ADR: Hypercholesterolaemia, Cellulitis, Pneumonia, Oral herpes simplex, Leukopenia, Neutropenia, Hypofibrinogenaemia, Conjunctivitis, Cough, Dyspnoea, Abdominal pain, Mouth ulceration, Rash, Pruritus, Urticaria, Peripheral oedema, Hypersensitivity reactions, Hepatic transaminases increased, Weight increased, Total bilirubin increased. Other less common and rare adverse reactions are listed in the SmPC. Date of API: January 2026 Legal Category: POM Marketing Authorisation Numbers: EU/1/24/1896/001-012 Marketing Authorisation Holder: Celltrion Healthcare Hungary Kft., Váci út1-3, WestEnd Office Building B torony, 1062 Budapest, Hungary Marketed by: Celltrion Healthcare Ireland Ltd, 26 Arrow Building, Old Belgard Road, Tallaght, Dublin D24 ND70. Tel: (01) 223 4026 Email: Enquiry_IE@celltrionhc.com Additional information is available on request. ®Avtozma is a registered trademark of Celltrion Inc. and is used under licence. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/ risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to HPRA Pharmacovigilance via www.hpra.ie. Adverse events should also be reported to Celltrion Healthcare Ireland via:. Tel: (01) 564 5074 / Email: medinfoie@celltrionhc.com. © Celltrion Healthcare Ireland Ltd. 2026 IE-AVT-26-00004 Date of Preparation: June 2026

05/06/2026 12:57:44

Immunology

From vaccine hesitancy to allergy services and healthy ageing A message from Dawn O’Shea, Editor

elcome to the annual edition of Update Immunology. In this issue, we look at everything from vaccine hesitancy and sepsis to allergic rhinitis and inf lammatory bowel disease. Dr Cathal O’Connor, Consultant Dermatologist at Cork University Hospital, discusses the not-so-complex relationship between food allergies and atopic dermatitis. The message is that atopic dermatitis, which af fects up to 30 per cent of children in Ireland, is never driven by food allergy. Instead, Dr O’Connor writes, atopic dermatitis represents a complex interplay of epidermal barrier dysfunction, immune dysregulation, and microbial dysbiosis. The article provides practical advice on distinguishing between atopic dermatitis f lares and genuine food allergic reactions, along with evidence-based guidance on the dangers of food elimination, and the

role of allergy testing. In addition, Dr Maria Laf fey from St Vincent’s University Hospital, Dublin, and Mr Michael J Gallagher, Consultant Ophthalmic Surgeon, and Senior Clinical Lecturer at Trinity College Dublin, provide a comprehensive CPD module on herpes zoster ophthalmicus. In it, the authors set out the presentation and dif ferential diagnoses for the condition, along with guidance on potential complications and treatment. To gain CPD points, read the article on page 46 and complete the associated MCQs and True or False questions at doctorCPD.ie. Also in this issue, Dr Ellen Newman, Specialist Registrar in Infectious Diseases at the Mater Hospital, and Prof Eavan Muldoon, National Clinical Lead for Infectious Diseases and OPAT, provide expert guidance on classifying and treating trauma-related infections. Meanwhile, Prof Steven Kerrigan from the Cardiovascular Infection Research Group at the RCSI’s School of Pharmacy, delves into the challenge of protecting organ function in sepsis. He explains why treating the infection may not prevent organ dysfunction and puts forward the case for barrier protection as an essential

component of sepsis care. On page 50, a team from Midland Regional Hospital Portlaoise report on the establishment of a nurse-led oral food challenge and penicillin allergy service at the hospital. Some 86 children underwent an oral food challenge during the f ive-month pilot period, and only 35 per cent had a positive reaction to the tested/ suspected allergen, suggesting that the number of children with proven allergies may be signif icantly lower than anticipated. Even more important was the fact that 96 per cent of the 55 children attending for low-risk penicillin allergy detection were found not to have a penicillin allergy. This signals an alarmingly high rate of penicillin allergy misdiagnosis in Ireland, and supports a need to expand this initiative to other regions. As always, my sincere thanks to our contributors for sharing their knowledge and expertise to promote clinical excellence, evidence-based practice, and optimal patient outcomes. If you would like to contribute to an upcoming issue, please drop me a line at dawn.oshea3@gmail.com.

THIS INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY Ireland’s No.1 preterm formula with the widest, most nutritionally tailored range1,2

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Immunology

Contents

Irish Society for Rheumatology Autumn Meeting

Vaccines and healthy ageing

Editor Dawn O’Shea dawn.oshea3@gmail.com

Nurse-led allergy service

Sub-editors Emer Keogh emer@greenx.ie Elaine Walsh elaine@greenx.ie Creative Director Laura Kenny laura@greenx.ie Managing Director Graham Cooke graham@greenx.ie

Allergic rhinitis: A clinical update

Antimicrobial stewardship for all

Bare above the wrist – the impact

Atopic dermatitis versus food allergy

Childhood uveitis: Diagnosis and treatment

Inf lammatory bowel disease

Barrier protection in sepsis

PVC-related Staph aureus infection

Administration Daiva Maciunaite daiva@greenx.ie

Update is published by GreenCross Publishing Ltd, Unit 1, The Village Mill Enterprise Park, Rathnew, Co Wicklow, A67V186, Ireland. www.greencrosspublishing.ie © Copyright GreenCross Publishing Ltd 2026 Front cover design: Laura Kenny Additional imagery: iStock.com

Carbapenemase-producing Enterobacteriaceae

CPD: Herpes zoster ophthalmicus

Trauma-related infections

Dealing with vaccine hesitancy

The contents of Update are protected by copyright. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means – electronic, mechanical or photocopy recording or otherwise – whole or in part, in any form whatsoever for advertising or promotional purposes without the prior written permission of the editor or publisher. Disclaimer The views expressed in Update are not necessarily those of the publishers, editor or editorial advisory board. While the publishers, editor, and editorial advisory board have taken every care with regard to accuracy of editorial and advertisement contributions, they cannot be held responsible for any errors or omissions contained. GreenCross Publishing is owned by Graham Cooke.

UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

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Immunology

ISR Autumn Meeting A summary of highlights from the Irish Society for Rheumatology Autumn Meeting 2026, which took place at the Europa Hotel, Belfast, 17-18 September All reports: Denise Doherty

Building networks, knowledge, and bones at the ISR The Irish Society for Rheumatology (ISR) warmly received delegates and an esteemed line-up of national and international guest speakers at its 2026 Autumn Meeting in Belfast. Opening the conference, ISR President, Dr Andrew Cairns, Consultant Rheumatologist, Musgrave Park Hospital, Belfast, welcomed attendees to his hometown of Belfast to “renew friendships, make new connections, and gain renewed updates, enthusiasm, and inspiration”. Dr Nazia Chaudhuri, Consultant in Respiratory Medicine, Ulster University and Altnagelvin Hospital, Northern Ireland, launched the clinical presentations with an update on interstitial lung disease in rheumatic disease. Prof Susan Mollan, Professor of Ophthalmology, Queen’s University, Kingston, Ontario, Canada, completed the morning itinerary with a deep dive into ‘the eye of giant cell arteritis’. Among many other highlights from day one of the conference, Prof David Armstrong, Consultant Rheumatologist, Altnagelvin Area Hospital, Western

Health and Social Care Trust, Northern Ireland, described novel ways of “building bone” in his talk: ‘Translating mechanistic differentiation into treatment decisions for menopausal women with severe osteoporosis and imminent fracture risk’. Prof Armstrong emphasised the importance of treatment to prevent vertebral and nonvertebral fractures. “Vertebral fractures can be a disaster for older patients,” he cautioned. Prof Armstrong also expressed the importance of being “confident talking to patients about common and rare effects”, and in discussing the risks and benefits, of treatments. Prof Armstrong then delivered a clinically-grounded overview of the pathophysiology, trial data, and real-world evidence responsible for the paradigm shift in osteoporosis care from primarily anti-resorptive therapy to osteoanabolic approaches over the last two decades. He summarised the evolution of osteometabolic therapy, from teriparatide in 2001 to the latest arrival, romosozumab – the

monoclonal antibody designed to target sclerostin. Prof Armstrong also advocated for equitable care and swift management of an “osteoporosis emergency”, such as a T score of -5. Day two of the meeting kicked off early for some delegates who joined Dr Cairns for a 5km ‘President’s Run’ around Belfast city centre. Among several notable presentations that followed, Dr Gareth Lewis, Consultant Acute Physician, Antrim Hospital, Northern Ireland, filled the conference with fun, philosophy, movies, and mythology is his talk: ‘Artificial intelligence in medicine and medical education’, while Prof Donal O’Shea, Consultant Endocrinologist, St Vincent’s Hospital and University College Dublin, shared his expertise about obesity, glucagon-like peptide-1 drugs, and ‘lessons learned from patients’. The plenary sessions closed with a pertinent debate and subsequent panel discussion entitled: ‘The house believes all polymyalgia rheumatica should see a rheumatologist’.

Health inequalities in SLE: A global challenge Prof Ian Bruce, Pro Vice-Chancellor, Faculty of Medicine, Health and Life Sciences at Queen’s University Belfast, National Institute for Health Research Senior Investigator Emeritus, and Professor of Rheumatology at the

University of Manchester, UK, delivered a talk about health inequalities in systemic lupus erythematosus (SLE) at the Irish Society for Rheumatology 2026 Autumn Meeting. His central message was that outcomes in SLE are influenced not only by

UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

disease biology and clinical management, but also by social determinants, health inequalities, and wider inequities that affect life expectancy, the health conditions people experience, and the care and support available to them.

Immunology

“If you walk a mile from here [Belfast city centre] in two different directions, your life expectancy at birth will differ by up to 10 to 12 years,” Prof Bruce demonstrated the striking effects of socioeconomic deprivation gaps between regions. “I suspect if you do the same in Dublin, you would see the same thing.”

Global epidemiology of SLE Presenting the global epidemiology of SLE, Prof Bruce introduced evidence challenging the long-held belief that the disease is rare among native sub-Saharan and East African populations. Although global epidemiological data remain limited, current indications in fact suggest a particularly high prevalence across these regions, he said. American research also shows higher rates of SLE among several racial and ethnic groups – including Black, indigenous, and Hispanic populations – who are often disadvantaged communities. “Black patients are much less likely to achieve a clinical response to treatment,” Prof Bruce said, adding

that these cohorts also experience higher rates of lupus nephritis, end-stage renal disease, and mortality. Poverty, deprivation, discrimination, and other determinants can further worsen outcomes for these groups. Prof Bruce also highlighted major disparities in access to diagnostics and specialist lupus care globally. He told the conference that Kenya has approximately one rheumatologist per 10 million people, while Nigeria has only 29 rheumatologists for around 220 million people. Poverty combined with limited access to diagnostic services, renal biopsy, and medical care further compounds these inequalities, attendees heard. “We now have EULAR (European Alliance of Associations for Rheumatology) treatment guidelines and an incredible array of drugs approved for lupus, but the elephant in the room is cost,” Prof Bruce said, and explained that treatment could potentially consume an entire monthly wage in Kenya. This limited affordability restricts access to these medications and leads to greater reliance on glucocorticoids for disease control, he said. High-dose

steroids ultimately increase serious infection risk, with Kenya experiencing three times the UK incidence.

Inclusivity Prof Bruce ended by emphasising that “SLE really is a global challenge” in rheumatology. “Around 85 per cent of the world’s population live in low- and middle-income countries, meaning the vast majority of people with lupus live in these settings” that are often impacted by inequality, he said. Prof Bruce also advocated for more “inclusive research” in SLE, saying: “The disease disproportionately affects minoritised populations who remain under-represented in clinical trials; therefore, it’s very hard to make inferences about how treatment is working across different populations.” Improving inclusion requires practical support for participants, culturally competent healthcare professionals, better reporting of ethnicity, registries and real-world data, and meaningful patient and public involvement in study designs, he concluded.

Obesity, gender, and psoriatic arthritis Despite a range of new and existing therapies, most patients with psoriatic arthritis (PsA) do not achieve minimum disease activity, the Irish Society for Rheumatology 2026 Autumn Meeting heard. Dr Lihi Eder, Associate Professor of Medicine and Research Chair in Inflammatory Rheumatic Diseases, University of Toronto, Canada, explored the reasons behind this in her talk: ‘Existing gaps in the management of PsA: Can we do better?’ “Many patients keep cycling through therapies and biologics – why?” Dr Eder explored predictors of poor outcomes in PsA and mechanisms of difficult-to-treat disease, identifying obesity and gender as key drivers. “We tend to focus on targeting

inflammation, but not necessarily metabolic inflammation,” she said. Data show that higher body mass index (BMI) significantly increases the risk of developing PsA and reduces the likelihood of achieving minimal disease activity. Dr Eder proposed adipose tissue dysfunction as a hypothesis to explain this, noting that hypertrophy of adipocytes leads to issues like hypoxia and changes in angiogenesis, further driving inflamed tissue and increased production of cytokines and adipokines. “We have fat tissue in our joints,” she added, and presented findings from osteoarthritis research showing that, in the context of obesity, inflammation of this fatty tissue is associated with increased synovial inflammation.

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“Another potential mechanism that could trigger inflammation is biomechanical stress,” Dr Eder said, adding that obesity can also amplify pain and produce a higher burden of symptoms in PsA. Furthermore, she proposed that dysbiosis of the gut microbiome may also play a role. Dr Eder discussed evidence for nutritional approaches in PsA, including anti-inflammatory and plant-based diets, as adjunctive therapies. She described her research using the Mediterranean diet in the DIPSA trial, which found that weight loss, rather than a specific dietary pattern, was associated with symptom improvement. “Decreases in weight correlated with reductions in DAPSA (disease activity in PsA score),” she said.

Immunology

Dr Eder moved on to present an overview of the emerging data investigating incretinbased therapies in PsA. She acknowledged that “indications for GLP-1 (glucagon-like peptide-1) drugs are accumulating”, but that access to them can be “quite challenging”. She presented results from the TOGETHERPSA trial – a Phase 3b randomised trial evaluating the combination of ixekizumab and tirzepatide in 271 adults with active PsA and overweight or obesity. “Despite the fact that almost 85 per cent of patients lost a substantial amount of weight, only about one-third achieved ACR50 (American College of Rheumatology 50 per cent response criteria), which suggests that in some people, weight may not be the main driver of disease,” Dr Eder said about the results. “There are a lot of gaps, but signals suggest that GLPs may have an adjunctive ef fect, especially alongside interleukin (IL)-17 inhibitors…. Is there a direct anti-inf lammatory ef fect from GLPs? We don’t know yet… if there is, then potentially, these drugs could be used in the context of overweight, not just morbid obesity, or even normal weight

with some abnormalities.” Dr Eder also addressed “questions about safety” around GLP use, “especially sarcopenia, which is prevalent among patients with arthritis in general, and is a risk in people losing a significant amount of their fat mass.” She promoted “counselling around exercise and a protein-rich diet” for these patients.

Gender differences Dr Eder cautioned against a “one-sizefits-all” approach to gender in PsA, noting that failure to account for sex and gender differences has been associated with poorer outcomes in other fields. Delegates heard that women tend to enter clinical trials with a greater burden in painsensitive domains, including higher pain scores, more enthesitis, and more tender joints. Men, by contrast, tend to have more severe psoriasis, higher C-reactive protein levels, and more dactylitis. Gender differences may also influence treatment response, and Dr Eder discussed potential mechanisms for this, such as variations in sex hormones, immune profiles, and inflammatory responses.

There are a lot of gaps, but signals suggest that GLPs may have an adjunctive effect, especially alongside interleukin (IL)-17 inhibitors The talk concluded with an overview of menopause and PsA, “which has received very little attention,” according to Dr Eder. Symptoms can overlap and DAPSA scores increase during perimenopause, she said. There may also be an increasing PASI (psoriasis area and severity index) score during what Dr Eder described as a “clinically vulnerable period” for female patients. “As rheumatologists, we really need to pay attention to women in midlife,” she concluded.

PMR guidelines: The tortoise and the hare The Irish Society for Rheumatology 2026 Autumn Meeting received a practical summary of the latest updates in guidelinedirected care of polymyalgia rheumatica (PMR) from Dr Sarah Mackie, Associate Professor of Vascular Rheumatology, University of Leeds, and Honorary Consultant Rheumatologist, Leeds Teaching Hospitals NHS Trust, UK. Her talk summarised the recent guideline revisions by the European Alliance of Associations for Rheumatology (EULAR) and forthcoming updates from the British Society for Rheumatology (BSR). She described EULAR as taking “perhaps a more radical approach”, while the BSR approach is more aligned with existing practice, likening the

two to the “tortoise and hare”. Dr Mackie opened her talk with a humorous comparison between software and clinical guideline updates, describing how both software and clinical practice can benefit from things like “bug fixes, performance updates, and additional new features”. “Our knowledge about PMR is constantly advancing. Its relationship with other diseases, the way we manage it – it’s all advancing. So, the guidelines need to keep up with all the science, knowledge, and technology out there.”

Myths and challenges in PMR Dr Mackie addressed the long-standing discordance between “standard messaging

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in PMR and what happens in real life”. She challenged the common misconceptions that corticosteroids are the only treatment option and that PMR resolves after two years. “It’s true that the average patient will be off steroids within two years, but this is often misinterpreted that PMR goes away after two years,” she explained. Dr Mackie also identified the challenge of what she termed “the PMR paradox” of corticosteroid treatment. “The treatment is steroids, but we’ve got to get you off the steroids – this is what we tell patients. It’s all quite a contradiction and it doesn’t make sense to them.” Delegates heard that these misunderstandings, alongside a reluctance

Immunology

to reduce steroids, can contribute to a “non-consultation, non-referral vacuum”. Patients may stop consulting their GP because they fear being told to taper their steroids, and at the same time, GPs may be reluctant to refer patients to rheumatology in case the patient is advised to taper their steroids – both concerned that tapering could leave symptoms inadequately controlled. Dr Mackie also noted that “most patients and GPs are unaware that DMARDs (disease-modifying antirheumatic drugs) may be an option”.

To refer or not to refer? EULAR recommends that all patients with suspected PMR should be referred for specialist expertise, and that corticosteroid treatment should be delayed until the diagnosis has been conf irmed. Dr Mackie noted that while these recommendations may be feasible individually, implementing them together could prove challenging in healthcare systems where access to rheumatology is limited. By comparison, the BSR guidance states that uncomplicated cases should be diagnosed and managed by GPs, with rheumatology input when required. Dr Mackie acknowledged that the EULAR guidelines need to be applicable across all EULAR countries, with suspected PMR being routinely referred to rheumatology in many of them, unlike the UK and Ireland, where PMR is primarily managed by the GP. The guidelines do recognise that access to specialist services varies between regions. In England, she noted, expertise in PMR has increasingly developed within primary care “because they’ve been doing it for decades”. Dr Mackie also pointed to differences in

the composition of the two guideline working groups. “We had GPs as well as rheumatologists (in the BSR group); I don’t think they had primary care physicians on the EULAR guideline group,” she said. “BSR guidelines had to be acceptable to primary care because we have to work with primary care.”

Diagnosing PMR Dr Mackie warned of a growing risk of misdiagnosis in PMR, particularly in the absence of a definitive diagnostic test. EULAR states that PMR diagnosis should be based on a combination of typical signs and symptoms, alongside exclusion of potential mimicking conditions, she said. Both EULAR and BSR caution against using classification criteria as a diagnostic algorithm, the conference heard. “We don’t want to overuse classification criteria because there is a risk that it will be used as a diagnostic algorithm, and that’s not what classification criteria were ever developed or intended for. I hope that message is heard.” Artif icial intelligence (AI) is likely to add another dimension to the diagnostic process and to patient-doctor interactions. “AI is really going to af fect how we diagnose,” Dr Mackie said. While liability will remain with clinicians, she noted that the profession will need to work out how best to navigate AI and its “very rapid progression”. Dr Mackie also questioned what constitutes sufficient expertise to manage patients with relapsing-remitting PMR. While EULAR guidance recommends that such patients should be managed in “expert hands”, it does not define what constitutes an expert, she said. The

Dr Mackie warned of a growing risk of misdiagnosis in PMR, particularly in the absence of a definitive diagnostic test UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

guidance also introduces the concept of an “expert centre”, but again without clearly defining what this means in practice. “How do we know a centre is expert?” Dr Mackie said. “Hopefully we’ll hear more from EULAR on that.”

New treatments and advances Turning to treatment advances, Dr Mackie highlighted what she described as an encouraging period for PMR research. “The good news is that there have been loads of trials in PMR for the first time in many decades,” she said about studies that are beginning to identify treatments that can reduce reliance on corticosteroids. Several pivotal trials have evaluated potential glucocorticoid-sparing therapies, including interleukin-6 (IL-6) inhibitors, IL-17 inhibitors, B cell depletion, and Janus kinase (JAK) inhibitors. Among the trials discussed were PMR-SPARE, SEMAPHORE, REPLENISH, and SAPHYR. “Methotrexate is already available as a treatment option,” Dr Mackie continued, noting it is f irst-line in BSR guidance, in contrast to IL-6 inhibition in EULAR guidelines – highlighting another key dif ference between the two. “Methotrexate is recommended for consideration in patients who are prone to relapse,” she said. The BSR guidance encourages GPs to consider an early discussion about steroid-sparing treatment, helping to challenge the perception that corticosteroids are the only available treatment option. Dr Mackie concluded with an overview the recent advances in understanding of underlying biology and presentation of PMR, including the identif ication of symmetrical inflammatory lesions – a potential imaging “signature” of the disease – as well as genetic associations and the diversity of potential symptom triggers, like viruses and vaccines. She f inished on an optimistic note, returning to her earlier comparison between the EULAR and BSR approaches: “No matter whether we use the tortoise or hare approach, I think the prospect for patients will improve.”

Immunology

Allergic rhinitis: A clinical update Author: Theresa Lowry Lehnen, RGN, PG Dip Coronary Care, RNP, BSc, MSc, PG Dip Ed (QTS), M Ed, PhD FFNMRCSI, Advanced Nurse Practitioner General Practice

llergic rhinitis is a common chronic inflammatory disorder of the nasal mucosa, affecting a significant proportion of the Irish population and frequently presenting in general practice. Despite its common occurrence, allergic rhinitis is often underestimated in terms of clinical significance, leading to underdiagnosis and suboptimal management. The condition has a significant impact on quality of life, sleep, cognitive function, and work productivity, and is closely associated with asthma and other upper airway disorders. Effective recognition and management in primary care are important to optimise patient outcomes and reduce long-term morbidity.1,2

Clinical presentation

Diagnosis

Clinically, allergic rhinitis presents with a range of nasal and ocular symptoms that may vary in severity and frequency. Patients commonly report paroxysmal sneezing, nasal itching, watery rhinorrhoea, and nasal congestion, often accompanied by itchy, red, or watery eyes. Postnasal drip, throat clearing, cough, and impaired sense of smell may also occur. Fatigue, poor sleep quality, and reduced concentration are frequently reported, particularly in those with persistent disease. Symptoms may follow a seasonal pattern, particularly in pollenmediated disease, or may be perennial when exposure to allergens such as house dust mites is continuous.1,2

Pathophysiology

Classif ication

Allergic rhinitis is an immunoglobulin (Ig) E-mediated hypersensitivity reaction to inhaled environmental allergens such as grass and tree pollens, house dust mites, mould spores, and animal dander. Initial exposure leads to sensitisation, with production of allergen-specif ic IgE antibodies. On subsequent exposure, allergeninduced cross-linking of IgE on mast cells in the nasal mucosa triggers degranulation and release of inflammatory mediators, including histamine and leukotrienes. This early-phase response results in sneezing, nasal itching, rhinorrhoea, and congestion. A subsequent late-phase response, dominated by eosinophilic infiltration and sustained inflammation, contributes to mucosal oedema, ongoing nasal obstruction, and persistent symptoms.1,2,3

The classification of allergic rhinitis has evolved to better reflect symptom burden and disease impact. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify the condition according to symptom duration and severity rather than seasonal terminology. Disease is described as intermittent when symptoms occur for fewer than four days per week or for less than four consecutive weeks, and persistent when symptoms exceed these thresholds. Severity is categorised as mild or moderate to severe depending on the presence of sleep disturbance, impairment of daily activities, reduced work or school performance, and overall quality of life impact. This classif ication is particularly useful in guiding treatment decisions in primary care.3

Diagnosis of allergic rhinitis is primarily clinical and based on a thorough history and physical examination. A personal or family history of atopic disease, including asthma or eczema, supports the diagnosis. On examination, patients may be observed breathing through the mouth, frequently snif f ing or clearing their throat. Dark circles under the eyes, known as allergic shiners, and a horizontal crease across the bridge of the nose caused by repeated rubbing may be present, particularly in children. Inspection of the nasal passages usually shows swollen nasal lining with clear, watery discharge. The inferior turbinates may appear pale or bluish, and the nasal mucosa can have a cobblestone appearance. Where available, nasal endoscopy can help identify nasal polyps or structural abnormalities. Palpation of the sinuses may cause tenderness in patients with chronic symptoms. Assessment should also include screening for associated conditions such as asthma and atopic dermatitis, and asking about aspirin sensitivity. IgE tests can be useful in confirming allergen sensitisation, particularly where the diagnosis is uncertain or when allergen-specific immunotherapy is being considered.4,5,6

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Differential diagnoses A number of differential diagnoses should be considered when assessing patients with chronic nasal symptoms. Non-allergic rhinitis presents with similar symptoms but lacks an immunological basis and is often triggered by irritants such as smoke, strong odours, or temperature

Immunology

changes. Infective rhinosinusitis should be suspected in the presence of purulent nasal discharge, facial pain, fever, or systemic symptoms. Structural abnormalities including nasal septal deviation, turbinate hypertrophy, and nasal polyposis may cause persistent obstruction. Medicationinduced rhinitis, particularly rhinitis medicamentosa resulting from prolonged use of topical nasal decongestants, is an important and preventable cause of chronic nasal congestion. 5,6 The impact of allergic rhinitis extends beyond nasal symptoms. There is a well-established association between allergic rhinitis and asthma, reflecting the concept of a united airway disease.6 Poorly controlled allergic rhinitis is associated with worsened asthma control, increased exacerbations, and higher healthcare utilisation. Effective management of allergic rhinitis has been shown to improve asthma outcomes, highlighting the importance of integrated airway management in primary care. In children and adolescents, allergic rhinitis may adversely affect school performance, behaviour, and sleep, while in adults it is associated with reduced work productivity and increased absenteeism.1,2,6

Treatment and management Management of allergic rhinitis in general practice is centred on patient education, allergen avoidance, where feasible, and evidence-based pharmacotherapy. While complete avoidance of airborne allergens is rarely achievable, practical measures such as minimising outdoor exposure during high pollen counts, keeping windows closed, using saline nasal

irrigation, and avoiding tobacco smoke can help reduce symptom burden. Education regarding the chronic nature of the condition and the need for regular rather than intermittent treatment is essential to improve adherence and outcomes.1,2,5 Pharmacological treatment should follow a stepwise approach guided by symptom severity and persistence. Second-generation, non-sedating oral antihistamines are ef fective in mild intermittent disease, particularly for relief of sneezing, itching, and rhinorrhoea. However, they are less ef fective for nasal congestion. Intranasal corticosteroids are the most effective monotherapy for moderate to severe or persistent allergic rhinitis due to their potent anti-inflammatory effects on the nasal mucosa. Regular use – rather than as-needed dosing – is required for optimal efficacy, and correct administration technique should be demonstrated and reinforced by healthcare professionals.1,2,6 For patients with inadequate symptom control, combination therapy may be required. Intranasal antihistamines may be used alone or in combination with intranasal corticosteroids to provide rapid symptom relief. Leukotriene receptor antagonists may of fer additional benef it in patients with coexisting asthma, although they are generally less ef fective than intranasal corticosteroids for nasal symptoms. Short-term use of topical or oral decongestants may provide temporary relief of severe congestion, but prolonged use should be avoided due to the risk of rebound congestion and systemic

Medication-induced rhinitis is an important and preventable cause of chronic nasal congestion UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

adverse ef fects.1,5,6 Allergen immunotherapy may be considered in selected patients with confirmed allergen sensitisation who have persistent symptoms despite optimal pharmacotherapy. Both subcutaneous and sublingual immunotherapy have been shown to reduce symptom severity, medication requirements, and long-term disease progression. This treatment is typically initiated and supervised in specialist settings and requires a long-term commitment from the patient.1,2,6

Complications Chronic rhinosinusitis is a recognised complication of allergic rhinitis, although it remains a distinct clinical entity. It is defined by persistent inflammation of the nasal and sinus mucosa, with symptoms such as nasal blockage and nasal discharge lasting longer than 12 weeks. Ongoing inflammation may lead to the development of nasal polyps, which arise from the chronically inflamed mucosa of the paranasal sinuses. These polyps are typically benign and occur bilaterally – the presence of unilateral polyps should prompt further investigation to exclude malignancy. Nasal polyps affect approximately 4 per cent of the general population and are more frequently observed in males. First-line management includes intranasal corticosteroids and saline irrigation, while surgical intervention is generally reserved for individuals who fail to respond to optimal medical treatment.6 Allergic sensitisation in allergic rhinitis can also influence immune activity within the adenoids, leading to adenoidal hypertrophy, particularly in children. Dysfunction of the eustachian tube is commonly associated with allergic rhinitis and may present with symptoms such as a sensation of ear fullness, intermittent ear pain, or popping sensations. There is a well-established association between allergic rhinitis and asthma, with studies indicating that between 10 and 40 per cent of individuals with allergic rhinitis also have asthma. The risk appears to be higher in those with

Immunology

moderate to severe persistent rhinitis, and allergic rhinitis has been identif ied as an independent risk factor for the later development of asthma, especially when diagnosed in early childhood. Additional conditions associated with allergic rhinitis include otitis media with ef fusion, chronic cough, and eosinophilic oesophagitis, although the precise mechanisms linking these conditions require further clarif ication.6 Allergen immunotherapy, while ef fective for selected patients with allergic rhinitis, carries a small risk of adverse reactions. Patients may experience transient worsening of rhinitis or asthma symptoms following treatment and, in rare cases, systemic reactions including anaphylaxis can occur. It is therefore important that healthcare professionals involved in administering allergen immunotherapy are trained in the recognition and management of severe allergic reactions and have immediate access to emergency medications, including adrenaline, as well as appropriate airway management equipment.6

Prevention Prevention of allergic rhinitis focuses on reducing exposure to known allergens and modifying environmental and behavioural risk factors where possible. Although

References 1. Morrow R. About allergic rhinitis. Irish Pharmacy Union. 2024; Available at: www.ipu.ie/ipu-review-article/aboutallergic-rhinitis/. 2. Bull S. Allergic rhinitis: A growing concern. Medical Independent. 24 Feb 2025. Available at: www. medicalindependent.ie/clinical-news/ allergic-rhinitis-a-growing-concern/. 3. Bousquet JJ, Schünemann HJ, Togias A, et al. Next-generation ARIA care pathways for rhinitis and asthma: A model for multimorbid chronic diseases. Clin Transl Allergy. 2019;9:44. doi:10.1186/ s13601-019-0279-2.

Allergen immunotherapy, while effective for selected patients with allergic rhinitis, carries a small risk of adverse reactions complete avoidance of airborne allergens is often impractical, lifestyle and environmental measures can help to decrease overall allergen contact and may reduce symptom burden. Strategies include maintaining indoor environments with lower humidity to limit dust mite and mould growth, using allergen-impermeable bedding covers, implementing high-efficiency particulate air (HEPA) filtration, and keeping windows closed during peak pollen periods, as supported by evidence on environmental control measures and allergen exposure reduction.8 In addition to environmental control, allergen immunotherapy administered over several years in appropriately selected patients with moderate to severe allergic rhinitis has been shown to not only improve symptoms, but also prevents progression to asthma, particularly in children and adolescents sensitised to grass or birch pollens, indicating a

disease-modifying preventive approach.9

4. Scadding GK, Kariyawasam HH, Scadding G, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007). Clin Exp Allergy. 2017;47(7):856-889. doi:10.1111/cea.12953.

rhinitis and its impact on asthma (ARIA) guidelines for allergic rhinitis based on grading of recommendations assessment, development and evaluation (GRADE), and real-world evidence. J Allergy Clin Immunol. 2020;145(1):70-80.e3. doi:10.1016/j.jaci.2019.06.049.

5. Irish College of General Practitioners. Quick Reference Guide: Allergic Rhinitis. Dublin: ICGP; 2023. 6. Akhouri S, House SA. Allergic Rhinitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available at: www.ncbi.nlm.nih.gov/books/ NBK538186/. 7. Bousquet J, Schünemann HJ, Togias A, et al. Next-generation allergic

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Conclusion Allergic rhinitis is a prevalent inflammatory condition that is commonly managed within general practice and has a substantial impact on physical health, sleep quality, and daily functioning. Although symptoms are often perceived as minor, inadequate control can lead to signif icant morbidity and the development of associated conditions, including asthma and chronic rhinosinusitis. Early identification, accurate classification, and evidence-based management are essential to achieving effective symptom control. By adopting a structured, patientcentred approach and recognising when specialist referral is required, primary care teams can deliver high-quality care and improve long-term outcomes for individuals with allergic rhinitis. ●

8. Klimek L, Brehler R, Bergmann KC, et al. Avoidance measures for mite allergy – an update. Allergo J Int 2023;32:18-2. Available at: https://doi.org/10.1007/ s40629-022-00242-5. 9. Halken S, LarenasLinnemann D, Roberts G, et al. EAACI guidelines on allergen immunotherapy: Prevention of allergy. Pediatr Allergy Immunol. 2017;28(8):728745. doi:10.1111/pai.12807.

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The Medicines Management Programme recommends Uzpruvo as a best value biologic medicine for Ustekinumab** « Indicated for Plaque Psoriasis, Paediatric Plaque Psoriasis, Psoriatic Arthritis, adult Crohn’s Disease and paediatric Crohn’s Disease (patients ≥40 kg)1 « Uzpruvo, from Clonmel Healthcare; the first approved ustekinumab biosimilar in Ireland « Uzpruvo offers flexibility with three strength options Uzpruvo® is currently not approved for the ulcerative colitis indication (since the originator still has exclusivity for this indication). PFS - pre-filled syringe. *Stelara®; **https://healthservice.hse.ie/staff/information-healthcare-workers/medicines-management-programme-mmp/best-value-medicines/ 1. Uzpruvo® SmPC

UZPRUVO®  45 & 90 mg SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE. UZPRUVO®  130 mg CONCENTRATE FOR SOLUTION FOR INFUSION. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to HPRA Pharmacovigilance via www.hpra.ie. Composition: Uzpruvo 45 mg: Each pre-filled syringe contains 45 mg ustekinumab in 0.5 mL. Uzpruvo 90 mg: Each pre-filled syringe contains 90 mg ustekinumab in 1 mL. Uzpruvo 130 mg: Each vial contains 130 mg ustekinumab in 26 mL (5 mg/mL). Excipients include histidine, polysorbate 80, sucrose, and water for injections. The pre-filled syringe components are latex free. Pharmaceutical Form: 45 mg and 90 mg: Subcutaneous injection (pre-filled glass syringe). 130 mg: Intravenous infusion (glass vial). Mechanism of Action: Ustekinumab is a fully human IgG1κ monoclonal antibody that targets the p40 subunit shared by interleukin (IL) 12 and IL-23. Indications: Uzpruvo 45 and 90 mg is indicated for the treatment of plaque psoriasis, paediatric plaque psoriasis, psoriatic arthritis (PsA) adult Crohn’s Disease and paediatric Crohn’s Disease (patients ≥40 kg). Uzpruvo 130 mg is indicated for the treatment of adult Crohn’s Disease and paediatric Crohn’s Disease (patients ≥40 kg). Dosage: Uzpruvo is intended for use under the guidance and supervision of physicians experienced in the diagnosis and treatment of conditions for which Uzpruvo is indicated. Refer to Summary of Product Characteristics for information on dosing and administration. Method of administration: 45 and 90 mg: Subcutaneous injection;130 mg: Intravenous use. Contraindications: Hypersensitivity to the active substance or any excipients. Clinically important, active infections (e.g., active TB). Warnings and precautions: Record product name and batch number of the administered product for traceability. Ustekinumab may increase the risk of infections and reactivate latent infections. Patients must be monitored for signs of infection before and during treatment. Tuberculosis screening required prior to treatment. Delay initiation in patients with active infection. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. Uzpruvo may increase the risk of malignancy. All patients, particularly those >60 years of age, or with a history of prolonged immunosuppressant therapy or PUVA, should be monitored for skin cancer. Caution when transitioning from or co-administering with other immunosuppressants. Serious hypersensitivity reactions (including anaphylaxis, allergic alveolitis, eosinophilic pneumonia) have been reported. Regularly assess cardiovascular risk factors. Avoid live vaccines

during and up to 15 weeks after treatment (e.g. BCG). In infants exposed in utero, defer live vaccines for 12 months after birth or until ustekinumab infant serum levels are undetectable. It is not known whether ustekinumab may affect allergy immunotherapy. In patients with psoriasis, exfoliative dermatitis has been reported following ustekinumab treatment. Monitor patients with psoriasis for symptoms of erythrodermic psoriasis or exfoliative dermatitis. Discontinue Uzpruvo if a drug reaction is suspected. Cases of lupus-related conditions have been reported in patients treated with Ustekinumab. Use caution in the elderly due to higher baseline infection risk. Uzpruvo contains polysorbates that may cause allergic reactions. Interactions: Live vaccines should not be given concurrently with Uzpruvo. The pharmacokinetics of ustekinumab was not impacted by concomitant use of MTX, NSAIDs, 6-mercaptopurine, azathioprine and oral corticosteroids in patients with PsA, Crohn’s disease or ulcerative colitis, or prior exposure to anti-TNFα agents, in patients with PsA or Crohn’s disease or by prior exposure to biologics in patients with ulcerative colitis. In psoriasis studies, the safety and efficacy of ustekinumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated. In psoriatic arthritis studies, concomitant MTX use did not appear to influence the safety or efficacy of ustekinumab. In Crohn’s disease and ulcerative colitis studies, concomitant use of immunosuppressants or corticosteroids did not appear to influence the safety or efficacy of Ustekinumab. Fertility, pregnancy and lactation: Women of childbearing potential should use effective contraception during treatment and for at least 15 weeks after the last dose. Data from >450 pregnancies indicate no increased risk of congenital malformations. Ustekinumab crosses the placenta and has been detected in infant serum. Infants may be at increased risk of infection. Live vaccines should be avoided for 12 months post-birth unless ustekinumab levels are undetectable. Ustekinumab is present in breast milk in low concentrations. Risk to breastfed infants is low, but breastfeeding decisions should balance risks and benefits. Effects on fertility have not been evaluated in humans. Driving and Machinery Use: Uzpruvo has no or negligible influence on the ability to drive and use machines. Undesirable Effects: Upper respiratory infections, nasopharyngitis, sinusitis, dizziness, headache, oropharyngeal pain, diarrhoea, nausea, vomiting, pruritus, back pain, myalgia, arthralgia, fatigue, injection site erythema and pain. Refer to SmPC for full adverse reaction list. Adverse Event Reporting: Adverse reactions should be reported via HPRA Pharmacovigilance, website: www.hpra.ie. Pack Sizes: 45 mg and 90 mg: 1 pre-filled syringe. 130 mg: 1 vial. A copy of the Summary of Product Characteristics is available upon request or go to www.clonmelhealthcare. ie. MA Holder: STADA Arzneimittel AG, Stadastrasse 2-18, 61118 Bad Vilbel, Germany. EU/1/23/1784/001, 004, 005. Distributed in Ireland by: Clonmel Healthcare Ltd, Waterford Road, Clonmel, Co. Tipperary. Medicinal product subject to restricted medical prescription. Date of Last Revision: April 2026. Date of preparation: May 2026. 2605/ADV/UZP/202H

Immunology

Antimicrobial stewardship: An imperative across all healthcare settings Author: Theresa Lowry Lehnen, RGN, PG Dip Coronary Care, BSc, MSc, RNP, PG Dip Ed (QTS), M Ed, PhD FFNMRSCI, Advanced Nurse Practitioner General Practice

ntimicrobial resistance (AMR) is widely recognised as one of the most serious threats to global health. As once-reliable antimicrobial treatments become less effective, the management of common infections becomes more complex, and vulnerable patients face increased risks of prolonged illness, complications, and poorer outcomes. The misuse and overuse of antimicrobials in hospitals, community care, long-term care, and outpatient settings are major contributors to this crisis.1 More than 35,000 people die each year due to antibiotic resistance across Europe.2 According to the World Health Organization (WHO) 2025 Global Antibiotic Resistance Surveillance Report, one in six laboratory-confirmed bacterial infections worldwide in 2023 were resistant to standard antibiotic treatments, highlighting the urgent global need for robust antimicrobial stewardship (AMS) practices in all care settings.1 In recognition of the urgent need to curb AMR, the HSE in Ireland developed the Antimicrobial Resistance and Infection Control (AMRIC) 20222025 guidance, which sets out a national

framework for strengthening AMS across all areas of healthcare. This guidance highlights the scale of the challenge and reinforces that effective stewardship must extend beyond prescribing decisions alone. It calls for a whole system, coordinated approach that integrates clinical, organisational, and public health strategies to reduce inappropriate antimicrobial use, and improve infection prevention and control.3,4 AMRIC emphasises that AMS is not solely the responsibility of prescribers. Instead, it requires active engagement from the entire healthcare workforce, including pharmacy, microbiology, infection prevention specialists, healthcare assistants, and organisational leadership. AMS is def ined as a coordinated set of interventions designed to optimise the use of antimicrobial medications, ensuring that patients receive the appropriate agent, dose, route, and duration of therapy while minimising unnecessary use, toxicity, and resistance.3,4 In practice, AMS encompasses activities that span patient assessment, appropriate prescribing, administration, monitoring, infection prevention, education, and evaluation of antimicrobial use. In Ireland, the majority of antibiotic

The HSE Medicines Management Programme, working in partnership with the AMRIC team, introduced a national preferred antibiotics initiative 12

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use occurs outside hospital settings, in community care, residential facilities, and outpatient clinics. These environments often lack the robust AMS oversight found in hospitals, making them particularly important targets for stewardship initiatives. 5 Approximately 80 per cent of antibiotic prescribing in Ireland is conducted in general practice.6 Patient demands, expectation, familiarity with the clinician, and time restraints have been documented as key factors for overprescribing antibiotic therapy in general practice, despite clinical evidence suggesting when it is not necessary.7 Ef forts to reduce unnecessary antibiotic prescribing in Ireland include education and training for prescribing healthcare professionals; implementing decision support tools; using point-of-care testing including C-reactive protein; and supporting evidence-based practice through audit and evaluation. Initiatives also promote delayed prescribing where possible, evaluating its ef fectiveness, identifying barriers, and enhanced adoption through behavioural science approaches.7 All prescribing healthcare professionals have an ethical responsibility to prescribe antibiotics judiciously to reduce the risk of resistance.8 This requires a comprehensive understanding of the core principles of antibiotic selection, including the underlying pathology, and the therapeutic characteristics of the prescribed agents, ensuring that treatment is evidencebased, safe, and cost-efficient.9 Ethical practice also includes a commitment to AMS and the

Immunology

responsibility to effectively communicate with and educate patients when antibiotics are not indicated.7 Practice standards, decision-making frameworks, clinical governance structures, and regulatory bodies outline the criteria for safe and effective prescribing practice. Good prescribing practice should optimise patient outcomes, support patient care, and encourage treatment concordance and adherence, while considering clinical response, tolerability, and lifestyle factors. Patients should be included in clinical decision-making processes, informing them of available options, while ensuring that prescriptive practice is safe, evidencebased, appropriate, and in the patient’s best interest.9,10 The HSE Medicines Management Programme, working in partnership with the AMRIC team, introduced a national preferred antibiotics initiative, commonly referred to as the green/red antibiotic list. This initiative forms a key component of Ireland’s national AMS strategy and aims to standardise antimicrobial prescribing

across primary and community care. By clearly identifying preferred firstline ‘green’ antibiotics, the system guides clinicians toward agents that are effective for common infections, have favourable safety profiles, and present a lower selective pressure for the development of antimicrobial resistance. This approach not only supports safer, evidence-based prescribing, but also reduces unwarranted variation in clinical practice.5,13 The initiative is strengthened by the HSE AMRIC community antimicrobial prescribing guidelines, available at: www.hse.ie/eng/services/list/2/gp/antibioticprescribing/, which provide detailed, condition-specific recommendations to support prescribers in choosing the most appropriate antimicrobial therapy. These guidelines outline when preferred ‘green’ antibiotics should be used, the clinical indications they cover, optimal duration of therapy, and when alternative agents may be required. Equally important, the guidance highlights circumstances in which ‘red’ antibiotics should be avoided

unless there is a clear, evidence-based rationale for their use, typically due to their broader spectrum, higher risk of adverse events, or greater potential to drive resistance. Together, the preferred antibiotics list and accompanying guidelines promote consistency, improve patient safety, and help ensure that antimicrobial use in the community is appropriate, targeted, and aligned with national stewardship priorities.5,12

References

5. Health Service Executive. Community Infection Prevention and Control and Antimicrobial Stewardship Resource Guide. HSE; 2025. Available at: www.hse.ie/eng/ about/who/healthwellbeing/our-priority-programmes/hcai/resources/general/ community-infection-prevention-and-control-and-antimicrobial-stewardship-resource-guide.pdf.

Healthcare Epidemiology. 2023;3(1): e165. doi:10.1017/ash.2023.434.

1. World Health Organization. WHO warns of widespread resistance to common antibiotics worldwide. Geneva: WHO; 2025.Availalble at: www.who.int/ news/item/13-10-2025-who-warns-ofwidespread-resistance-to-commonantibiotics-worldwide 2. Brannigan E. RESIST newsletter. Edition 22. Health Service Executive Antimicrobial Resistance and Infection Control Programme (AMRIC). Dublin: HSE; 2024. 3. Health Service Executive. Antimicrobial Stewardship. HSE; 2025. Available at: www.hse.ie/eng/about/who/healthwellbeing/our-priority-programmes/hcai/ antimicrobial-resistance/antimicrobial-stewardship/ 4. Health Service Executive AMRIC. Antimicrobial Stewardship Guidance for All Healthcare Settings. HSE; 2022. Available at: www.hse.ie/eng/services/list/2/gp/ antibiotic-prescribing/antibicrobial-stewardship-audit-tools/amric-ams-event-andworkshop-presentation-slides.pdf

6. Devine P, O’Kane M, Bucholc M. Trends, variation, and factors influencing antibiotic prescribing: A longitudinal study in primary care using a multilevel modelling approach. Antibiotics (Basel). 2022;11(1):17.

Conclusion Antimicrobial stewardship is a shared responsibility that extends across all healthcare disciplines and settings. In Ireland, the HSE AMRIC guidance recognises this potential and advocates for comprehensive, multi-setting implementation of AMS practices. Through active engagement in patient assessment, specimen management, administration and monitoring, patient education, infection prevention, audit, and multidisciplinary collaboration clinicians can ensure that antimicrobial therapy is safe, effective, and appropriate. ●

9. Nursing and Midwifery Board of Ireland. Practice standards and guidelines for nurses and midwives with prescriptive authority. 4th ed. Dublin: Nursing and Midwifery Board of Ireland; 2019. 10. Health Service Executive. National nurse and midwife medicinal product prescribing guidelines. Dublin: Office of the Nursing and Midwifery Services Director. Health Service Executive; 2020.

7. Murphy R, Ahern E, Deegan A, et al. Changing behaviour: Reducing unnecessary antibiotic prescribing. A systematic review and meta-analysis. Dublin: Department of Health (Ireland); 2024.

11. Nampoothiri V, Bonaconsa C, Surendran S, et al. What does antimicrobial stewardship look like where you are? Global narratives from participants in a massive open online course. JAC Antimicrob Resist. 2021;4(1): dlab186. doi:10.1093/ jacamr/dlab186.

8. Parzen-Johnson S, Toia J, Sun S, Patel S. Antimicrobial stewardship for nurse practitioners and physician assistants: Enhancing patient safety through education. Antimicrobial Stewardship and

12. Health Service Executive. HSE AMRIC community antimicrobial prescribing guidelines. Dublin: HSE. Available at: www. hse.ie/eng/services/list/2/gp/antibiotic-prescribing/

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Immunology

Bare above the wrist, bare below the elbow Author: Dr Jayanta B Sarma, Microbiologist, Mid Yorkshire Teaching NHS Trust

hen people compare healthcare systems, they usually compare waiting lists, staf f ing levels, or funding. After spending more than two decades in the NHS, and the last two years working in the HSE, I have become fascinated by something altogether quieter – language. Sometimes an institution reveals its character not in policy documents or organisational charts, but in the ordinary words it chooses. One example has stayed with me. The NHS speaks of ‘bare below the elbows’. The HSE asks staf f to remain ‘bare above the wrists’. At f irst glance, they describe the same thing. Microbiologically, they largely do. Both seek ef fective hand hygiene, unobstructed wrists and forearms, and the removal of clothing and jewellery that interfere with patient safety. Yet I have often wondered why two neighbouring healthcare systems chose dif ferent words. Perhaps because they reveal something deeper than anatomy. Perhaps they reveal culture.

More than sleeves When I began medical school in India, nobody wore a tie. The prized possessions of a young doctor were the long white coat and, if one could af ford it, a good stethoscope. They were symbols of belonging. When I arrived in Britain to continue my training, I discovered another expectation; doctors wore ties. I learned to knot one properly and bought several because that was simply what doctors did. Then, almost without anyone noticing, the culture changed. The white coats disappeared. The ties

disappeared. Long sleeves disappeared. ‘Bare below the elbows’ became part of everyday professional life. Looking back, I think those practical infection prevention measures quietly redef ined what professionalism looked like. The NHS never announced a cultural revolution, it simply changed everyday habits. Alcohol hand rub appeared outside every patient room; watches disappeared, bracelets disappeared. The tie quietly became unnecessary. Authority no longer resided in appearance. It increasingly resided in behaviour. Today, patients may not notice whether a doctor wears a tie. They are far more likely to notice whether the doctor cleans their hands. During my time in Ireland, one observation has remained constant. The infection prevention and control nurses I have worked alongside have been remarkably diligent. They know the guidance thoroughly. They apply it consistently. They follow it faithfully, often in circumstances that are far from ideal. Yet guidelines are only one part of infection prevention. Culture is the other. Healthcare buildings evolve over decades. Clinical pressures rarely ease. Resources are never unlimited. Long-established

Increasingly, my advice as a microbiologist is to recommend stopping antibiotics UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

professional habits do not disappear simply because a guideline has changed. That is where infection prevention becomes something much larger than compliance. It becomes leadership. Authority rarely comes from hierarchy. It comes from evidence, credibility, consistency, and the quiet conf idence that patient safety must remain the same regardless of who happens to be standing beside the bed. Healthcare remains a profession where seniority matters, where consultants, quite rightly, carry ultimate responsibility for patient care, and where established ways of working can be deeply embedded. Changing culture therefore requires something more persuasive than authority. It requires trust. The quiet leaders rarely command. They persuade, they educate, they remind. Then, they return the next day and begin again. Real cultural change seldom occurs because someone wins an argument; it happens because someone patiently wins confidence. Working in two health systems has also made me reflect on how professional authority evolves. One of the strengths I have observed in Irish hospitals is the respect af forded to consultants. Their leadership is visible, reassuring, and deeply valued. Their opinion often carries influence well beyond the immediate clinical decision. The NHS, too, remains consultantled. Yet over the past two decades that phrase has acquired a dif ferent flavour. Leadership increasingly feels shared. The consultant remains accountable, but decisions emerge through conversations involving nurses, pharmacists, microbiologists, therapists, advanced

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Image: iStock.com/sturti

nurse practitioners, and junior doctors. Perhaps infection prevention has contributed quietly to that evolution. Microorganisms, after all, pay little attention to professional hierarchy. Evidence gradually acquires an authority of its own.

The courage to stop Increasingly, my advice as a microbiologist is to recommend stopping antibiotics. The question is no longer simply: ‘What antibiotic should we prescribe?’ It has become: ‘Does this patient still need one?’ Many younger doctors understand this instinctively, yet they often f ind themselves navigating between newer evidence and older habits. Evidence usually moves f irst, practice follows. Culture is often the last to arrive.

Lessons from two phrases: ‘Bare above the wrists’, ‘bare below the elbows’ – one defines the practical minimum required for effective hand hygiene, the other has come to symbolise an entire professional philosophy. Neither phrase is really about sleeves. Both are about culture. I still have the ties I bought when I f irst arrived in Britain. They have not been worn for more than 20 years. I have never added another. They remain carefully folded in a drawer, neither useful nor discarded. Looking at them now, I no longer see items of clothing. I see reminders that professions evolve quietly; not through dramatic declarations, not through sweeping reforms, but through thousands of ordinary decisions repeated every day by nurses, doctors, healthcare assistants, pharmacists, therapists,

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cleaners, and patients who gradually agree that there is a better way. By the time we notice the change, the culture has already moved on. Policies can be written overnight, evidence can be published in a journal, but culture changes only when people patiently help one another to see the world dif ferently. That is the quiet revolution. ●

Author

Dr Jayanta B Sarma is a Consultant Medical Microbiologist and Infection Prevention Specialist. He served for more than two decades in the NHS before spending the last two years with the HSE at Letterkenny University Hospital, Co Donegal. This reflection draws on his experience of working across both healthcare systems.

Immunology

Chicken or eggzema? The not so complex relationship between food allergies and atopic dermatitis Author: Dr Cathal O’Connor, Consultant Dermatologist, Cork University Hospital

or decades, the relationship between food allergies and eczema/atopic dermatitis (AD) has been one of the most contentious topics in paediatric dermatology and allergy medicine. Parents desperately seeking answers for their child’s inflamed, itchy skin often turn to baseless dietary modifications, while healthcare providers grapple with nonsensical advice about allergy testing and food elimination diets. The simple message is, AD is never caused by food allergies. This assertion, supported by research and clinical experience, has profound implications for how we approach the management of childhood eczema.

A multifactorial disease AD affects up to 30 per cent of Irish children, with approximately 3 per cent experiencing severe disease (O’Connor, C Pediatr Dermatol 2022). Rather than being a simple allergic reaction to foods, AD represents a complex interplay of three primary pathophysiological mechanisms (Figure 1). 1. Epidermal barrier dysfunction: The skin barrier in AD patients is fundamentally compromised, often due to genetic variants such as filaggrin mutations. These defects result in increased transepidermal water loss and enhanced penetration of allergens, irritants, and pathogens. The barrier dysfunction is primary, not secondary, to food exposure. 2. Immune dysregulation: AD is characterised by a predominantly Th2-mediated immune response, with elevated levels of cytokines including

 Oral exposure during the critical window of immune development (f irst months of life) promotes tolerance through regulatory T cell responses. This explains why filaggrin mutations, which cause severe barrier dysfunction, increase the odds ratio for peanut allergy by 5.3-fold while only increasing AD risk by 3.1-fold.

Clinical differentiation FIGURE 1: A multifactorial disease Source: Blicharz L. Int J Mol Sci. 2021

interleukin (IL)-4, IL-13, IL-31, and increased immunoglobulin (Ig)E production. This immune skewing creates a state of chronic inflammation that is self-perpetuating and independent of dietary triggers. 3. Microbial dysbiosis: Patients with AD demonstrate altered skin microbiomes, with increased colonisation by Staphylococcus aureus (S aureus) and decreased microbial diversity. This dysbiosis contributes to inflammation and barrier dysfunction through the production of bacterial toxins and proteases.

The food allergy development pathway Contrary to popular belief, food allergies do not cause AD. Instead, the relationship is inverted – AD predisposes to food allergy development through cutaneous sensitisation (Figure 2). The ‘dual allergen exposure hypothesis’ explains that:  Cutaneous exposure through defective skin barrier leads to Th2-mediated sensitisation and allergy development.

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One of the most critical skills for parents and healthcare providers is distinguishing between AD flares and genuine food allergic reactions. True food allergic reactions are never subtle. AD characteristics:  No temporal relationship to food ingestion  Chronic or subacute course (not hyperacute)  Gradual onset and resolution  Eczematous morphology (not urticarial)  Absence of systemic symptoms. Food allergic reaction features:  Hyperacute onset within minutes of allergen exposure  Clear temporal relationship to allergen exposure  Urticarial/erythematous appearance (not eczematous)  Potential angioedema (lips, eyes, face)  Systemic symptoms may include respiratory distress, cardiovascular changes, or gastrointestinal symptoms  Parents typically recognise these as allergic reactions without prompting. If parents ask whether their children need food allergy testing, then they probably do not. Genuine food allergic reactions are dramatic events that families readily identify as such.

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FIGURE 1: AD predisposes to food allergies through cutaneous sensitisation

Allergy testing Current allergy testing practices present significant challenges in the context of AD:  70 per cent of AD patients are sensitised to one or more foods on specif ic IgE (SpIgE) testing.  Less than 10 per cent are genuinely allergic to those foods.  This creates a massive potential for misdiagnosis and inappropriate dietary restrictions. The term ‘RAST testing’ has been considered obsolete since the year 2005, having been replaced by SpIgE testing using newer generation methods. However, even modern SpIgE testing has limitations:  Results are not binary (positive/ negative), but exist on a continuum.  Predictive values vary signif icantly by allergen and patient age.  Component-resolved diagnostics and skin prick testing may offer better specificity. Total IgE is generally a worthless test for eczema. I only order total IgE measurements when suspecting the ultrarare hyper-IgE syndrome or considering dupilumab therapy for alopecia areata. Total IgE levels do not aid in the diagnosis or management of AD and should be abandoned in routine practice.

The dangers of food elimination Perhaps the most concerning finding is that food elimination can actually cause food allergies. Research demonstrates that:

FIGURE 3: Recommendations on the introduction of peanut butter

 20 per cent of children with AD develop food allergies when previously tolerated foods are removed from their diet.  30 per cent of these newly developed allergies present as anaphylaxis.  Fatal allergic reactions have been reported as consequences of unnecessary food elimination. This phenomenon occurs because continuous oral exposure is necessary to maintain immune tolerance in early childhood. When foods are withdrawn in infancy, the oral tolerance pathway is disrupted, potentially leading to sensitisation upon re-exposure.

The breastfeeding misconception A particular area of concern is the advice given to breastfeeding mothers to eliminate dairy from their diets to ‘treat’ their baby’s eczema. Compelling evidence against this practice includes that:  Human breast milk contains one millionth the β-lactoglobulin concentration of cow’s milk.  This level is too low to trigger reactions, even in most infants with conf irmed cow’s milk protein allergy.  Maternal dairy elimination can lead to maternal nutritional def iciency and psychological distress.  It provides no benef it for infant eczema and any observed response is a placebo response.

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Early food introduction The Learning Early About Peanut Allergy (LEAP) trial fundamentally changed our understanding of food allergy prevention. In children with severe eczema and/or egg allergy:  Early peanut introduction (four-11 months) reduced peanut allergy by 81 per cent.  Peanut allergy prevalence was 17.3 per cent in the avoidance group versus 0.3 per cent in the consumption group.  Earlier introduction was more effective than later introduction. Based on this evidence, my advice is:  Introduce smooth peanut butter at 12 weeks of age (Figure 3).  Continue regular consumption to maintain tolerance.  Do not delay introduction of other allergenic foods.  Use structured introduction protocols (milk ladders, egg ladders) when reintroducing previously inappropriately avoided foods.

Evidence-based treatment of AD I advocate for a targeted approach addressing the three pathophysiological mechanisms: 1. Topical anti-inflammatory therapy  Topical corticosteroids are the foundation of treatment of eczema/ dermatitis.

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 Ointment formulations preferred over creams.  Liberal application (not ‘sparingly’) with suf f icient potency, volume, frequency, and duration.  Induction therapy (once daily) for at least two weeks.  Weaning periods (Tuesday/Thursday/ Saturday/Sunday) for two weeks.  Maintenance therapy (Saturday/ Sunday weekend therapy) to prevent flares for four to six months of clear skin to ensure immune reconstitution.  Topical steroid concerns are unfounded – topical steroids are safe and ef fective for mild to moderate eczema.

2. Barrier repair  Emollients treat xerosis (dry skin) rather than active inflammation. They are not the mainstay of therapy for eczema/dermatitis.  Applied downwards to prevent folliculitis.  Pump dispensers preferred to prevent contamination.  Wet wraps are discouraged due to burden, infection risk, and limited ef f icacy. 3. Antimicrobial therapy  Antiseptic baths (sodium hypochlorite/ Milton solution) twice weekly.  Reduces S aureus colonisation without promoting antibiotic resistance.  Adjunctive therapy, not monotherapy.

Debunking common myths Three persistent ‘nonsenses’ in eczema management: 1. Detergents cause eczema Modern washing machines leave negligible detergent residues. Unless patients wash laundry by hand or apply detergent directly to skin, clothing detergents do not cause eczema. Advising non-biological detergents is unnecessary and potentially anxiety-provoking. 2. Topical steroids are unsafe Topical corticosteroids represent elegant, targeted therapy that avoids systemic

exposure. Twice-weekly maintenance therapy does not cause skin thinning. The major issue is nocebo ef fect and steroid concerns perpetuated by social media misinformation.

skin microbiome’s role in disease pathogenesis.  Development of barrier repair therapies

targeting specific genetic defects.

Conclusion 3. Food allergies cause eczema As extensively discussed, this fundamental misconception leads to inappropriate testing, unnecessary dietary restrictions, and potential harm through induced food allergies.

Social media misinformation Social media misinformation is causing a signif icant negative impact on eczema management. Some posters on platforms like TikTok and Instagram promote dangerous advice including:  Topical steroid concerns  Extreme dietary restrictions  Unproven ‘natural’ treatments  Fear-mongering about established therapies. Healthcare providers must actively counter this misinformation with evidence-based education and clear communication.

Clinical implications and future directions For primary care providers:  Avoid routine allergy testing in AD patients.  Focus on proper topical therapy education.  Encourage early food introduction in all infants.  Refer appropriately for moderate to severe AD requiring systemic therapy. For specialists:  Patient education remains crucial for treatment adherence  Biologics and newer systemic therapies of fer hope for severe cases.

Research priorities  Improved biomarkers for distinguishing sensitisation from clinically relevant allergy.  Better understanding of the

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The directionality of the relationship between food allergies and AD is very dif ferent to what many healthcare professionals were taught in training. Rather than foods causing eczema, AD creates the conditions for food allergy development through barrier dysfunction and cutaneous sensitisation. This paradigm shift has profound implications: 1. Routine allergy testing in AD is unnecessary and potentially harmful. 2. Early food introduction prevents rather than causes allergies. 3. Dietary restrictions may cause more harm than benef it. 4. Topical anti-inflammatory therapy should be the treatment focus. This approach provides a roadmap for evidence-based management that prioritises ef fective treatments while avoiding interventions that may inadvertently worsen outcomes. The chicken (genetic predisposition and barrier dysfunction) comes before the egg (food sensitisation), and understanding this sequence is crucial for optimal patient care. The takeaway for healthcare providers is clear: Focus on treating the underlying disease mechanisms of AD rather than chasing dietary ghosts. We must resist the pressure to order ‘just in case’ allergy tests and instead provide families with the evidence-based education they need to make informed decisions about their child’s care. This approach of fers the best hope for improving outcomes while avoiding the pitfalls of unnecessary restrictions and interventions that may ultimately harm rather than help our patients. This evidence-based knowledge provides truly ef fective management for children suf fering from the misery of AD. ●

Immunology

The keys to a healthier, longer life Author: Pat Kelly

r Stefania Maggi is a renowned geriatrician and epidemiologist and is author of approximately 600 publications in international medical and public health journals. Dr Maggi is Scientific Director of the European Interdisciplinary Council on Aging (EICA) and Past-President of the European Geriatric Medicine Society (EuGMS). She is also a member of several EuGMS Working Groups, a Member of the Board of Directors of the European Scientific Working Group on Influenza, an advisor to the international and independent Adult Immunisation Board, and a member of the Accademia Galileiana di Lettere, Scienze ed Arti in Italy. Dr Maggi is also a Senior Fellow at the Neuroscience Institute Ageing Branch of the National Research Council of Italy. Her research focuses on the epidemiology of ageing and the determinants of healthy ageing across the life course, and she has particular expertise in nutrition, immunisation, and prevention. She was in Ireland recently to deliver a talk at the Irish Gerontological Society 73rd Annual and Scientific Meeting in Cork, the overarching theme of which was ‘Ageing with Innovation: Are We Ready?’ In her presentation, Dr Maggi discussed the impact of vaccine-preventable diseases (VPDs) on older adults, including the indirect effects that are not always recognised. During her visit to Ireland, Dr Maggi spoke with Update about the need to prioritise healthy ageing, VPDs, and more. “I greatly enjoyed my experience of Ireland. I was impressed not only by the warmth and hospitality of the Irish people, but also by the enthusiasm and openness of the new colleagues I met,” said Dr Maggi. “Of course, some others are good friends of mine since long ago. We meet regularly at the EuGMS conferences. Their

contributions to the activities of the European societies are outstanding.” In her presentation, titled ‘Impact of Vaccine-Preventable Diseases in Older Adults’, Dr Maggi focused on the impact of VPDs on the health status of older adults, including beyond the acute phase of illness. She also discussed how vaccines can promote healthy ageing by decreasing both the burden of VPDs and their downstream effects, and by enhancing physical and cognitive function at any age.

Health strategies Bearing in mind the ageing population globally, Dr Maggi was keen to stress the need for healthy ageing to be integral to governmental health strategies. “An ageing population inevitably brings a higher prevalence of chronic diseases, multimorbidity, frailty, and disability. However, ageing itself should not be equated with disease,” Dr Maggi told Update. “A greater focus on prevention and health promotion throughout the life course can help maintain functional capacity, reduce avoidable morbidity, and delay dependence.” This requires a shift from a predominantly disease-centred model towards a life-course, preventionoriented approach, she said. This approach should integrate vaccination, healthy nutrition, physical activity, mental and cognitive health, social participation, and early detection

and treatment of diseases, she added. Importantly, prevention should not stop in older age – it remains valuable throughout the entire ageing process, said Dr Maggi. “Healthy ageing should therefore become a central objective of health systems and public health policies, with specific investments that anticipate the needs of ageing populations rather than responding only after disease, disability, or dependency has developed. Such an approach can benefit individuals, families, and communities while contributing to the long-term sustainability and resilience of health and social care systems that, otherwise, will collapse,” she warned. Dr Maggi also spoke about the burden of VPDs, both for patients and healthcare systems. For patients, VPDs can lead to hospitalisation, functional decline, loss of independence, and prolonged recovery – and infections may precipitate or worsen underlying conditions such as cardiovascular disease, chronic respiratory disease, diabetes, or frailty. In older adults, an apparently acute infection can therefore have consequences that extend well beyond the infectious episode itself, she explained. “From my experience, the burden of VPDs is often underestimated, particularly in adults and older people. We tend to focus on acute infection and mortality, but the impact is much broader,” said Dr Maggi. “The burden is also substantial for healthcare systems. VPDs generate primary care consultations, emergency visits,

For patients, vaccine-preventable diseases can lead to hospitalisation, functional decline, loss of independence, and prolonged recovery UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

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hospitalisations, rehabilitation, and longterm care needs, while also increasing the complexity of managing patients with multimorbidity. During seasonal respiratory infections, this can translate into considerable pressure on hospitals and healthcare professionals.”

Prevention “What is particularly important is that this burden is, at least in part, preventable. Vaccination should therefore be viewed not only as a tool to prevent infection, but as an intervention that can help preserve health and functional capacity, reduce avoidable healthcare utilisation, and protect the sustainability of health systems. “This is why I believe we need to move from thinking of vaccination as an isolated infectious disease intervention, to considering it as an integral component of healthy ageing and chronic disease prevention.” Dr Maggi noted that among healthcare professionals, the level of awareness around VPDs is generally good, “but there is an important gap when we move from childhood vaccination to adult and older adult immunisation”. The challenge for medical professionals is to keep pace with the expanding evidence, new vaccines, and increasingly complex recommendations for older people and those with multimorbidity and frailty. Vaccination needs to become a more routine part of adult healthcare, with doctors feeling conf ident to proactively discuss prevention rather than waiting for patients to ask, she said. Another potential gap in awareness relates to the often unrecognised indirect impact of VPDs, Dr Maggi told Update. “We often measure the burden of VPDs by counting infections, hospitalisations, and deaths. But in older adults, the consequences can be much broader,” she explained. “An infection can destabilise chronic diseases, trigger frailty, accelerate functional decline, and result in loss of independence, even when the patient survives the acute illness. There are also

consequences for families and caregivers and for the healthcare system through rehabilitation, long-term care, and increased healthcare utilisation. “So, when we talk about prevention, we should ask not only how many infections or deaths we prevent, but also how much loss of function and independence we can prevent. This is where vaccination becomes an important component of healthy ageing.”

RSV RSV is recognised as a serious disease in infants and the immunocompromised, and Ireland’s monoclonal antibody programme has significantly reduced hospitalisations. However, RSV also poses serious risks for older adults, and in 2025, there were 43 RSV deaths in Ireland among people aged over 65. Dr Maggi was asked why she feels governments are hesitant to recognise the burden of RSV in older adults. “I think there are several reasons why the burden of RSV in older adults has historically received less attention,” she explained. “First, RSV has been strongly associated with paediatric disease for decades. Bronchiolitis and infant hospitalisation are very visible clinical events, whereas in older adults, RSV may present as pneumonia, exacerbation of heart or lung disease, frailty, or a deterioration of functional status. The infection may therefore be less likely to be recognised as the primary cause of the patient’s decline. “Second, the burden in older adults has been partly hidden by underdiagnosis and competing diagnoses, also in the hospitals,” she continued. “There are studies showing that less than 25 per cent of patients hospitalised with acute respiratory infections are assessed for RSV and, sometimes, even if they test positive, the RSV infection is not reported in the discharge letter. Older patients frequently have multimorbidity, and RSV may be recorded as a respiratory or cardiovascular complication rather than as RSV itself. This can make the true burden appear smaller than it is.”

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However, the evidence is increasingly difficult to ignore, Dr Maggi pointed out. “In Europe, approximately 160,000 adults are hospitalised with RSV each year, with more than 90 per cent of these hospitalisations occurring in people aged 65 years and older. European evidence also shows that older adults are among those at greatest risk of severe outcomes and death. “At the same time, we now have effective and safe vaccines for older adults that we did not have a few years ago,” said Dr Maggi. “RSV vaccines are authorised in Europe, and real-world evidence is already demonstrating reductions in RSV-related hospitalisation in older adults. “So my message to decision-makers would be very simple: We should celebrate the progress made in protecting infants, but we should not allow that success to create the impression that the RSV problem has been solved. The epidemiological reality is that RSV affects vulnerable people at both ends of the age spectrum. We have made major progress in protecting newborns and infants through maternal vaccination and longacting monoclonal antibodies. The mortality in children in the last decade is significantly decreased, but not in older adults. “The next step is to ensure that older adults, particularly those with cardiovascular disease, chronic respiratory disease, diabetes, frailty, or other risk factors are also appropriately protected,” she stressed. On the whole, this type of protection is part of a broader shift towards healthy ageing, Dr Maggi pointed out. “If we are serious about helping people live longer with good health and functional independence, we need to prevent infections that can precipitate hospitalisation, functional decline, and worsening of chronic disease, and RSV is surely one of them. “So I would say to policymakers: The question is no longer whether RSV matters in older adults; the question is how quickly we can translate the evidence we already have into equitable and sustainable prevention programmes. The ECDC itself is now developing EU/EEA technical guidance on RSV vaccination in adults, reflecting the

PROTECT AGAINST RSV## PROTECT AGAINST RSV

Over 3 RSV seasons, a single dose of AREXVY Over 3 RSV seasons, a single doseagainst of AREXVY demonstrated sustained efficacy RSV1,2 demonstrated sustained efficacy against RSVLRTD in adults aged 18 years and older LRTD in adults aged 18 years and older1,2

SEASON 1 OVERALL EFFICACY IN SEASONPROTECTING 1 OVERALL EFFICACY IN AGAINST RSV-LRTD3** PROTECTING

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SEASON 1 EFFICACY IN PROTECTING AGAINST RSV-LRTD FOR PARTICIPANTS WITH AT LEAST SEASON 1 EFFICACY IN PROTECTING AGAINST †3** 1 COMORBIDITY OF INTEREST RSV-LRTD FOR PARTICIPANTS WITH AT LEAST

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Primary Endpoint ² 82.6% (96.95% CI*, 57.9, 94.1)

PrimaryAREXVY Endpoint 82.6% CI*,placebo 57.9, 94.1) (7 ²cases out(96.95% of 12,466), (40 cases out of 12,494) AREXVY (7 cases out of 12,466), placebo (40 cases out of 12,494) Secondary Endpoint ² 94.6% (95% CI, 65.9, 99.9) Secondary Endpoint ² 94.6% 65.9, (18 99.9) AREXVY (1 case out of (95% 4937),CI, placebo cases out of 4861) AREXVY (1 case 1out ofwith 4937), (18 cases **Season data 6.7placebo months follow up. out of 4861) 2 **Season 1 data with 6.7not months up. Vaccination may protectfollow all recipients. 2 # Vaccination may not protect all recipients. RSV=respiratory syncytial virus; RSV-LRTD=respiratory syncytial virus-associated lower respiratory tract # RSV=respiratory syncytial virus; RSV-LRTD=respiratory syncytial virus-associated lower respiratory tract disease CI=Confidence Interval disease†Comorbidities CI=Confidence ofInterval interest1: chronic obstructive pulmonary disease (COPD), asthma, any chronic respiratory/ † 1 pulmonary heart failure, diabetes mellitus type 1 (COPD), or type 2,asthma, and advanced liver or respiratory/ renal disease Comorbidities of disease, interestchronic : chronic obstructive pulmonary disease any chronic (endocrinometabolic). pulmonary disease, chronic heart failure, diabetes mellitus type 1 or type 2, and advanced liver or renal disease Arexvy powder and suspension for suspension for injection. [Respiratory Syncytial Virus (RSV) vaccine (endocrinometabolic). Arexvy(recombinant, powder and adjuvanted)]. suspension for suspension for injection. [Respiratory Syncytial Virus (RSV) vaccine (Please refer to SmPC before prescribing). (recombinant, adjuvanted)]. After reconstitution, one dose (0.5 mL) contains: RSVPreF31 antigen2, 3 120 micrograms. (1RSV (Please Composition: refer to SmPC before prescribing). 2 RSVPreF3 produced recombinant glycoprotein F stabilised in themL) pre-fusion conformation 1= RSVPreF3, 2 3 antigenwith , 120 micrograms. (1RSVin Composition: After reconstitution, (0.5 contains: RSVPreF3 3 adjuvanted Chinese Hamster Ovary cellsone by dose recombinant DNA technology), 2 AS01E containing: plant RSVPreF3 producedlipid in recombinant glycoprotein F stabilised in the pre-fusion conformation = RSVPreF3, extract Quillaja saponaria Molina, fraction 21 (QS-21) 25 micrograms, 3-O-desacyl-4’-monophosphoryl 3 adjuvanted with AS01 containing:for plant ChineseA Hamster Ovary cells byminnesota recombinant DNA technology), E (MPL) from Salmonella 25 micrograms. Therapeutic indications: Active immunization the extract prevention Quillaja saponaria fraction (QS-21) 25 by micrograms, 3-O-desacyl-4’-monophosphoryl lipid of lowerMolina, respiratory tract 21 disease caused RSV in adults 18 years of age and older. The use of A (MPL) from Salmonella minnesota 25 micrograms. Therapeutic indications: Active immunization for the this vaccine should be in accordance with official recommendations. Posology and method of administration: prevention of lower respiratory caused bydeltoid RSV inmuscle. adults Administered 18 years of age older. The of For intramuscular injectiontract only,disease preferably in the as aand single dose of use 0.5 ml. this vaccine should beneed in accordance with Contraindications: official recommendations. Posology method of administration: Revaccination: not established. Hypersensitivity to and the active substances or any of For intramuscular injection preferably in the deltoid Administered a single of 0.5 ml. the excipients. Special only, warnings and precautions for use: muscle. The name and the batchasnumber of dose the administered product need shouldnot beestablished. clearly recorded. Appropriate Hypersensitivity medical treatmenttoand should or be any readily Revaccination: Contraindications: the supervision active substances of availableSpecial in casewarnings of an anaphylactic event.for Vaccination shouldand be the postponed in subjects suffering from an the excipients. and precautions use: The name batch number of the administered severe However, the presence of a treatment minor infection, such as a cold, shouldbenot result productacute should be febrile clearlyillness. recorded. Appropriate medical and supervision should readily in in deferral. protective immune response may notshould be elicited in all vaccinees. Anxiety-related available case ofA an anaphylactic event. Vaccination be postponed in subjects suffering reactions, from an including vasovagal reactions (syncope), hyperventilation or stress-related reactions may should occur. Precautions acute severe febrile illness. However, the presence of a minor infection, such as a cold, not result should in place to avoid injury frommay fainting. Never administer or intradermally; no data in deferral. A be protective immune response not be elicited in all intravascularly vaccinees. Anxiety-related reactions, available on subcutaneous administration. Caution in individuals with thrombocytopenia or any coagulation including vasovagal reactions (syncope), hyperventilation or stress-related reactions may occur. Precautions since bleeding mayfrom occur following intramuscular administration. Safety and immunogenicity should disorder be in place to avoid injury fainting. Never administer intravascularly or intradermally; no data data on Arexvy are not available for immunocompromised individuals. Patients with immunodeficiency or available subcutaneous administration. Caution individuals with response thrombocytopenia anydose coagulation onon immunosuppressive treatment may have ainreduced immune to Arexvy. or Each contains disorder0.18 since bleeding may 80 occur intramuscular administration. Safety and mg of polysorbate whichfollowing may cause an allergic reaction. Interactions: Arexvy mayimmunogenicity be administered data onconcomitantly Arexvy are not for immunocompromised individuals. Patientsvaccine, with immunodeficiency or withavailable a COVID-19 mRNA vaccine, a pneumococcal conjugate herpes zoster vaccine on immunosuppressive treatmentormay have a seasonal reduced influenza immune vaccines response(standard to Arexvy. Each dose contains (recombinant, adjuvanted), inactivated dose unadjuvanted, high 0.18 mgdose of polysorbate 80orwhich may dose causeadjuvanted). an allergic If reaction. administered unadjuvanted, standard Arexvy Interactions: is to be givenArexvy at the may samebetime as another concomitantly with a COVID-19 mRNA should vaccine,always a pneumococcal conjugate vaccine, injection herpes zoster injectable vaccine, the vaccines be administered at different sites. vaccine Fertility, (recombinant, adjuvanted), or There inactivated influenza dose unadjuvanted, high pregnancy and lactation: are noseasonal data on the effects vaccines on human(standard fertility. Arexvy is not recommended dose unadjuvanted, or standard dose adjuvanted). If Arexvy is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites. Fertility, pregnancy and lactation: There are no data on the effects on human fertility. Arexvy is not recommended

during pregnancy or in breast-feeding/lactating women. Effects on ability to drive and use machines:

during in breast-feeding/lactating Effects onUndesirable ability toeffects: drive Very and use machines: Arexvy pregnancy has a minoror influence on the ability to drive women. and use machines. common Arexvy a minormyalgia, influence on the injection ability tosite drive andfatigue. use machines. effects: Very common ( 1/10): has Headache, arthralgia, pain, Common Undesirable ( 1/100 to <1/10): injection (site 1/10): Headache, myalgia, arthralgia, injection pain, fatigue. Common ( 1/100 to <1/10): injection swelling, injection site erythema, fever, chills. site Uncommon ( 1/1000 to <1/100): lymphadenopathy, site swelling, injection site erythema, fever, chills. Uncommon 1/1000 to pain, <1/100): lymphadenopathy, hypersensitivity reactions, nausea, abdominal pain, vomiting, injection( site pruritus, malaise. Very rare: hypersensitivity reactions, nausea, abdominal vomiting, injection siteCategory: pruritus, POM pain, malaise. Very rare: Guillain-Barré syndrome, Frequency unknown: pain, injection site necrosis. Legal A. Marketing Guillain-Barré syndrome, Frequency unknown: injection site necrosis. Legal Category: POM A. Marketing Authorisation Number: EU/1/23/1740/001-002. Marketing Authorisation Holder: GlaxoSmithKline Biologicals Authorisation Number: EU/1/23/1740/001-002. Marketing Authorisation Holder: GlaxoSmithKline Biologicals S.A., Rue de l’institut 89, B-1330 Rixensart, Belgium. Further information is available from GlaxoSmithKline (Ireland) Riverwalk, CitywestRixensart, Business Campus, 24.information Telephone: 01-4955000. Code:GlaxoSmithKline PI-11947. S.A., RueLtd. de 12 l’institut 89, B-1330 Belgium.Dublin Further is available from Date of preparation: July 2026. (Ireland) Ltd. 12 Riverwalk, Citywest Business Campus, Dublin 24. Telephone: 01-4955000. Code: PI-11947. Date of preparation: July 2026. Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their

website: Adverse events should be reported to GlaxoSmithKline 1800 244(HPRA) 255 or on via their Adversewww.hpra.ie. events should be reported directlyalso to the Health Products RegulatoryonAuthority online forum https:/ /gsk.public.reportum.com. website: www.hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255 or via online forum https://gsk.public.reportum.com. ▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Please see full Prescribing Information for AREXVY, on Medicines.ie. References: 1. Arexvy SPC, www.medicines.ie (accessed August 2026). 2. Ison MG, Papi A, Athan E, et al. Efficacy, safety, and immunogenicity of the AS01E-

adjuvanted respiratory syncytial virus prefusion F protein (RSVPreF3 OA) in older adults over three respiratory syncytial virus seasons (ARe SViPlease see full Prescribing Information for AREXVY, onvaccine Medicines.ie. 006): a multicentre, randomised, observer-blinded, placebo-controlled, phase 3 trial. The Lancet Resp E, Med. References: 1. Arexvy SPC, www.medicines.ie (accessed August 2026). 2. Ison MG, Papi A, Athan et al.2025;13(6):517–529. Efficacy, safety, andhttps://doi.org/10.1016/ immunogenicity of the AS01ES2213-2600(25)00048-7. 3. Papi A,virus Ison prefusion MG, Langley JM, et al., for the(RSVPreF3 AReSVi-006OA) Study Group.adults Respiratory syncytial virus prefusion F protein vaccine in(ARe SViadjuvanted respiratory syncytial F protein vaccine in older over three respiratory syncytial virus seasons older aadults. N Engl J randomised, Med. 2023;388(7):595-608. doi:10.1056/ NEJMoa2209604. 006): multicentre, observer-blinded, placebo-controlled, phase 3 trial. The Lancet Resp Med. 2025;13(6):517–529. https://doi.org/10.1016/ S2213-2600(25)00048-7. 3. Papi A, Ison MG, Langley JM, et al., for the AReSVi-006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023;388(7):595-608. doi:10.1056/ NEJMoa2209604.

Immunology

growing evidence base and the need for national strategies.”

Infection and MI In her presentation to the Irish Gerontological Society annual conference, Dr Maggi identified an association between infection and cardiovascular risks.. “What I f ind particularly interesting is that the cardiovascular consequences of infections may be substantially greater than we traditionally recognise,” she said. “Influenza provides one of the clearest examples. Acute influenza can produce a strong systemic inflammatory and prothrombotic response, increase physiological stress, and potentially destabilise an already vulnerable atherosclerotic plaque. “This provides a plausible biological pathway linking an acute respiratory infection with acute myocardial infarction (MI). Recent systematic review evidence estimates that laboratory-conf irmed influenza is associated with approximately a six-fold increase in the short-term risk of acute MI.” The association with Streptococcus pneumoniae is also important, Dr Maggi pointed out. Pneumococcal disease can generate intense systemic inflammation and physiological stress, particularly in older people and those with cardiovascular disease. The interesting question is therefore not simply whether infection causes pneumonia, but whether an infectious episode can act as a trigger for an acute cardiovascular event in a person who is already biologically vulnerable, she posited. “And this phenomenon is not unique to influenza and streptococcus pneumoniae,” she added. “RSV is increasingly recognised as having a cardiovascular dimension. In older adults, RSV infection can be associated with heart failure, myocardial infarction, stroke, and atrial fibrillation. A 2025 Canadian study of adults ≥65 years hospitalised with RSV found that 18.5 per cent experienced a cardiovascular event during the subsequent year. Heart failure was particularly prominent. Importantly,

the association with heart failure was observed both in people with and without pre-existing cardiovascular disease. More recent comparative evidence also suggests that RSV and influenza can both be associated with cardiovascular events in the week after the acute infectious disease symptoms.”

Responsibility She emphasised the overarching objective of promoting healthy ageing for older adults and proactive care for the immunocompromised. This responsibility falls not only on healthcare professionals, but also on governments and policy-makers. “I believe that currently, our Ministries of Health are, indeed, ‘Ministries of Diseases’, and I believe that we should move from a model that mainly responds when people become ill, to one that proactively protects health and function, bringing together vaccination, nutrition, physical activity, cardiovascular and respiratory prevention, and cognitive health during the life course. “The minister for health should not be the minister responsible for all health determinants, but should be the minister who co-ordinates all ministries around a shared health objective,” she added. “The ministry of health would set priorities, ensure equity, monitor outcomes, and evaluate impact, while each ministry would be responsible for the determinants

In older adults, RSV infection can be associated with heart failure, myocardial infarction, stroke, and atrial fibrillation UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

of health within its own sphere.” This means focusing on prevention, vaccination, primary care, chronic disease, and healthy ageing. In education, health literacy, healthy behaviours from childhood, and lifelong learning need to be promoted, while healthy and sustainable food environments, including Mediterranean diet guidelines, should be implemented. Environmental challenges include tackling air pollution, climate issues, and providing green spaces. Healthy working lives, retirement, social participation, and poverty must be addressed, and physical activity across the life course has to be promoted, with all of this backed-up by research and innovation based on evidence, monitoring, and evaluation, she said. “So, I would make healthy ageing a cross-government objective, with the ministry of health co-ordinating, other ministries contributing, and all sectors accountable for their impact on population health,” said Dr Maggi. “And I would measure success not only by diseases treated, but by healthy life expectancy, functional independence, and avoidable hospitalisations. In other words, we should aim to not only treat people as they age, but also to help them age in good health. This has to be a collective effort.”

Take-home messages “I would leave Irish doctors with the following messages,” she said. “First, look beyond the infection itself. The real burden in an older person may be cardiovascular complications, worsening of chronic disease, functional decline, or loss of independence. Secondly, don’t underestimate RSV. It is a significant disease of older adults, not only of infants. “Also, remember that clinical presentation can be misleading, so appropriate testing matters. We should see vaccination as part of healthy ageing, not simply as infectious-disease prevention. And finally, be proactive – don’t wait for older patients to ask about vaccination; start the conversation yourself and train the nurses working with you about it.” ●

Immunology

Biologics and disease-modifying therapy in childhood uveitis: Twenty years on Authors: Anna Macháček, Medical student, School of Medicine, Trinity College Dublin, and Mr Michael J Gallagher, Consultant Ophthalmic Surgeon, Senior Clinical Lecturer, School of Medicine, Trinity College Dublin

hildhood uveitis is a rare but potentially sight-threatening condition, accounting for approximately 1-5 per cent of uveitis cases worldwide, while contributing disproportionately to visual morbidity. The disease is often chronic, asymptomatic, and associated with systemic conditions such as juvenile idiopathic arthritis (JIA), frequently presenting with complications including cataract, glaucoma, and cystoid macular oedema. Historically, management relied heavily on prolonged corticosteroid therapy and conventional immunosuppressive agents, which were associated with significant adverse effects and variable efficacy. Over the past two decades, the introduction of biologic response modifiers (BRMs) has transformed the therapeutic landscape of paediatric non-infectious uveitis. This review examines the evolution of treatment strategies, using early cohort evidence, including the fundamental work of Michael J Gallagher and colleagues, as a reference point, and tracing the shift towards evidence-based, stepwise management algorithms. The emergence of high-quality randomised controlled trials (RCTs), notably SYCAMORE and ADJUVITE, has established anti-tumour necrosis factor alpha (TNF-α) agents, particularly adalimumab in combination with methotrexate (MTX), as the cornerstone of therapy in refractory disease. In addition, this review explores the

expanding role of newer biologic agents targeting alternative inflammatory pathways, including interleukin-6 (IL-6) inhibition with tocilizumab, as well as emerging therapies for treatmentresistant cases. Despite these advances, limitations remain, particularly the lack of largescale paediatric trials and the need for long-term safety data. Overall, the management of childhood uveitis has evolved from empiric immunosuppression to a structured, targeted approach aimed at achieving sustained remission and preventing irreversible visual loss. While childhood uveitis is uncommon, it carries disproportionately high morbidity and poor visual outcomes.1 The disease is often asymptomatic and chronic, frequently presenting late with complications such as cataract, glaucoma, and cystoid macular oedema, which may result in permanent visual loss. This underlines the importance of early detection and regular screening, particularly in children with underlying systemic disease.1,2 The most common systemic association is JIA, an autoimmune condition conferring a high risk of chronic anterior uveitis and its complications.2-4 Noninfectious causes, although less common overall, tend to be more severe, often bilateral, recurrent, and resistant to conventional therapies, requiring a more aggressive immunomodulatory approach.5 First-line treatment remains topical glucocorticoids, preferred over systemic

UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

corticosteroids such as prednisolone.5 However, their role is largely limited to short-term disease control due to significant adverse effects, including cataract formation, raised intraocular pressure, glaucoma, and, with systemic exposure, growth suppression and endocrine complications.6 Consequently, modern management has shifted towards early introduction of steroid-sparing therapies, particularly BRMs.5 One of the earliest structured reports on BRMs in paediatric uveitis was the study by Gallagher et al, which demonstrated benefit in refractory cases across a heterogeneous cohort, albeit with limitations of small sample size and retrospective design.7 Since then, treatment strategies have evolved substantially. BRMs, particularly antiTNF-α monoclonal antibodies, are now established as the key escalation step following failure of conventional immunosuppressive therapy such as MTX.5,8This review examines how the management of childhood uveitis has evolved over the past two decades, focusing on changes in treatment strategies, escalation pathways, safety, and the expanding role of BRMs, using the Gallagher et al study as a reference point.

Where it all began In the early 2000s, BRMs for childhood uveitis were largely limited to three key agents: Infliximab and adalimumab, both TNF-α inhibitors, and daclizumab, an interleukin-2 (IL-2) receptor

Immunology

antagonist.7 These agents dominated early biologic therapy and were supported by the available evidence at the time. However, this evidence base was limited, consisting predominantly of small, retrospective studies with heterogeneous patient cohorts, which restricted the generalisability of f indings.9-12 At a mechanistic level, it had already been established that the pathophysiology of uveitis, particularly in HLAB27-associated and other systemic inflammatory uveitides, involves elevated levels of TNF-α in the aqueous humour.13 This provided a strong biological rationale for the early adoption of anti-TNF therapies. Among these, infliximab had the most robust paediatric evidencebase at the time. High-dose infliximab in refractory non-infectious uveitis demonstrated signif icant reductions in intraocular inflammation and was generally well tolerated in paediatric cohorts.9,10 These f indings were reflected in early reports where infliximab produced some of the most favourable outcomes, including remission in three paediatric cases.7 In contrast, adalimumab appeared less effective in early cohort literature, although interpretation is limited by the small sample size.7 Nonetheless, contemporary studies reported up to an 80.8 per cent reduction in inflammatory activity with no significant adverse effects.11 Additionally, early evidence suggested potential advantages of adalimumab over infliximab, including subcutaneous administration, reduced dosing frequency, and improved cost-effectiveness.12 Despite these theoretical and practical benefits, the absence of robust RCTs at the time meant

that paediatric clinical evidence remained stronger for infliximab. Another TNF inhibitor, etanercept, was also explored for use in childhood uveitis. However, even early studies suggested inferior efficacy compared to monoclonal antibody TNF inhibitors such as infliximab.14 This has since been reinforced by more recent guidelines, which recommend monoclonal anti-TNF agents (infliximab, adalimumab) over etanercept for uveitis management.5 Finally, daclizumab emerged in initial early studies as a promising therapeutic option. As an IL-2 receptor antagonist, it demonstrated ef f icacy across a heterogeneous cohort of paediatric patients.7 Notably, at the time, this study represented the only available clinical evidence evaluating daclizumab in paediatric uveitis. While initial results were encouraging, the limited evidence base and lack of subsequent large scale studies restricted its early clinical adoption.

The evidence shift The key shift in the evidence base supporting biologic therapies in childhood uveitis came with the emergence of large RCTs that were double-blind and placebo-controlled, particularly in paediatric populations. This represented a signif icant advancement from earlier observational and retrospective studies, providing more robust and less biased data on ef f icacy and safety. The most influential of these trials include SYCAMORE (2017) and ADJUVITE (2018), both evaluating the role of adalimumab, particularly in combination with MTX, in JIA-associated uveitis.15,16

The SYCAMORE trial was pivotal in establishing the combination of MTX and adalimumab as a standard of care 24

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In contrast to the Gallagher et al paper, which was exploratory and aimed to establish whether biologics had a safe and effective role in refractory childhood uveitis, these later RCTs were designed to directly assess clinical efficacy using stricter inclusion criteria and significantly larger cohorts.7 Although the early cohort data reported adalimumab as the least effective biologic in its cohort, this finding must be interpreted in the context of small sample size and limited early evidence, as prior supporting studies were not sufficiently powered or comparable.7,11,12 Subsequent large scale RCTs have since redefined treatment guidelines.5 The SYCAMORE trial was a multicentre, double-blind, randomised placebo-controlled trial involving children over the age of two years with active uveitis despite MTX therapy.15 It compared adalimumab plus MTX versus MTX plus placebo. The trial was terminated early due to clear evidence of ef f icacy: Treatment failure occurred in 27 per cent of patients receiving adalimumab compared to 60 per cent in the placebo group, demonstrating a signif icant reduction in disease progression. While adverse events were more frequent in the adalimumab group, they were consistent with the known safety prof ile. This trial was pivotal in establishing the combination of MTX and adalimumab as a standard of care, subsequently reflected in international guidelines. 5,16 Similarly, the ADJUVITE trial, another double-blind RCT, reinforced the f indings of SYCAMORE.17 It evaluated children aged ≥four years with chronic JIAassociated uveitis refractory to MTX. A key methodological strength was the use of laser flare photometry (≥30 photons/ ms) as a sensitive and objective measure of intraocular inflammation. This highlighted the importance of detecting subclinical (‘silent’) inflammation, supporting the need for early and regular screening in paediatric uveitis. Results demonstrated a 56 per cent response rate with adalimumab versus 20 per cent with placebo, with rapid

Immunology

improvement observed within two months. The subsequent open-label phase, in which all patients received adalimumab, showed improvement in the initial placebo group, further reinforcing its efficacy. Importantly, no new safety concerns were identified, strengthening its favourable safety profile in paediatric populations.17 The VISUAL I and VISUAL II trials, although conducted in adult populations, were high quality phase 3 RCTs that further supported the role of adalimumab in non-infectious uveitis.18,19 These studies demonstrated that adalimumab significantly reduced the risk of treatment failure and uveitic flare following glucocorticoid withdrawal, as well as reducing the risk of visual impairment. While not paediatric-specific, their comprehensive framework and large sample sizes provide strong supportive evidence for the broader efficacy of antiTNF therapies in uveitis. In the early 2000s, infliximab had a stronger evidence base in paediatric uveitis, a f inding also reflected in the Gallagher et al paper.7 Early studies demonstrated sustained control of inflammation, although relapses were common upon discontinuation.10 Longterm safety data did not reveal major new toxicities, but these studies highlighted an important limitation being maintenance dependence. Subsequent evidence refined the use of infliximab, particularly regarding dosing strategies. Studies demonstrated that dose escalation (up to four-fold increases) was often required to achieve adequate disease control and was not associated with increased adverse events, with doses <10mg/kg every four weeks often proving insufficient.20 Although later follow-up studies suggested that early high-dose therapy may be beneficial, optimal dosing regimens remained unclear.20 These findings illustrate a progression from initial efficacy signals to a more nuanced understanding of dosing requirements. Despite early data suggesting superior efficacy of infliximab compared to adalimumab, more recent comparative

studies and long-term follow-up data have demonstrated that adalimumab has a more favourable efficacy and safety profile, particularly for long-term management of JIA-associated uveitis.7,21 While infliximab remains effective in reducing inflammation, adalimumab is now generally preferred due to lower adverse event rates and more consistent long-term outcomes. Finally, the potential of daclizumab, highlighted in early observational studies, has not translated into long-term clinical use.7 Post-marketing surveillance identified rare but severe immune-mediated adverse events, including inflammatory encephalitis and meningoencephalitis, some of which were fatal. As a result, daclizumab (Zinbryta) was withdrawn from the European market in 2018 following a review by the European Medicines Agency.22 This highlights an important limitation of early biologic trials: Rare but serious adverse effects may only become apparent through long-term pharmacovigilance, emphasising the need for continued safety monitoring, even after initial trial approval.

Beyond anti-TNF As discussed previously, adalimumab has become the primary first-line BRM in refractory paediatric uveitis. Despite its central role, a number of newer biologic agents have been investigated for cases refractory to anti-TNF-α therapy, several of which are now incorporated into more recent treatment guidelines.16,23 However, the evidence base for these agents remains limited, and they are generally reserved for

One of the most extensively studied second-line agents is tocilizumab,an IL-6 receptor inhibitor UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

failure of first-line anti-TNF therapy, most commonly adalimumab.16,23 One of the most extensively studied second-line agents is tocilizumab, an IL-6 receptor inhibitor that blocks IL6-mediated inf lammatory signalling. 24 Tocilizumab initially demonstrated ef f icacy in rheumatological conditions, particularly systemic JIA, which led to its investigation in uveitis. 25 The APTITUDE trial (2020), a phase 2 study in paediatric patients with JIA-associated uveitis refractory to both MTX and adalimumab, evaluated its ef f icacy in this setting. 25 Although the trial did not meet its primary endpoint, only 33 per cent of patients achieved a predef ined reduction in intraocular inf lammation, clinically meaningful responses were observed in approximately one-third of participants. Notably, among the 19 per cent of patients with cystoid macular oedema, 75 per cent experienced resolution; highlighting a potential role for tocilizumab in macular oedema control. 25 In terms of safety, adverse events were reported in 95 per cent of patients; however, none were classif ied as serious. 25 These f indings suggest that while tocilizumab may not be broadly ef fective for all refractory cases, it has a valuable role in selected patients, particularly those with macular oedema, and is therefore best positioned as a second- or third-line agent. 25,26 This has been ref lected in updated guidelines, where tocilizumab is now recommended following anti-TNF failure, alongside inf liximab. 23,26 Another biologic explored in this context is abatacept, which inhibits T cell activation by binding to CD80/CD86 on antigen-presenting cells, thereby blocking co-stimulatory signalling. 24 Evidence for abatacept in refractory uveitis is limited to small case series and cohort studies, but these suggest a favourable safety prof ile and potential ef f icacy. 27 In one small cohort, the majority of patients tolerated treatment well, with only one out of seven patients discontinuing due to intolerance. 27 While promising, the paucity of data

Immunology

REZZAYO® Prescribing Information REZZAYO (rezafungin) 200 mg powder for concentrate for solution for infusion RoI PRESCRIBING INFORMATION

and absence of controlled trials limit its current role, and abatacept remains an emerging option in highly refractory disease. Golimumab, another anti-TNF-α agent, has also been investigated as an alternative following adalimumab failure.16 As a fully human monoclonal antibody, it offers a theoretical advantage in reduced immunogenicity. Evidence from small cohort studies suggests ef f icacy in refractory uveitis, with intravenous golimumab demonstrating high response rates in JIA, achieving remission in up to 84.6 per cent of patients. 28 However, data specif ic to uveitis remain limited, and its use is currently restricted to selected non-responders.16 Finally, rituximab, which targets CD20-positive B cells, has shown benef it in non-infectious uveitis, particularly in refractory posterior uveitis, Behçet’s disease, and JIAassociated cases unresponsive to TNF-α inhibitors. 24 Retrospective studies suggest that rituximab may be particularly benef icial in oligoarticular and polyarticular JIA-associated uveitis. 29 However, its use is tempered by safety concerns, including infusion reactions and immunosuppression-related risks, and some studies suggest that multiple treatment cycles (up to four) may be required to optimise ef f icacy while mitigating adverse ef fects. 29

Current management The contemporary management of refractory childhood uveitis follows a structured, stepwise escalation approach, signif icantly shaped by the introduction of BRMs. Current international guidelines emphasise early control of inf lammation while minimising corticosteroid-related toxicity. 5,16,30 Topical glucocorticoids, most commonly prednisolone acetate 1 per cent, remain f irst-line for rapid suppression of intraocular

inflammation. However, early tapering and transition to steroid-sparing therapy are strongly recommended to reduce complications such as glaucoma and cataract formation. 5,6,16 Systemic conventional immunomodulatory therapy (DMARDs) is the next step, with MTX as the cornerstone first-line agent. This is supported by the FAST trial, a randomised controlled study demonstrating superior efficacy of MTX over mycophenolate mofetil, albeit in a predominantly adult cohort.31 Other agents, including tacrolimus, cyclosporine, and azathioprine, show comparatively reduced efficacy, with cyclosporine having limited value and tacrolimus retaining a potential role only in refractory cases.32,33 In cases of inadequate response to MTX, escalation to biologic therapy is recommended. Anti-TNF agents are the preferred first-line biologics, with adalimumab as the agent of choice, supported by trials such as SYCAMORE and ADJUVITE.15,17 Infliximab is typically reserved for patients refractory to adalimumab.5,16,30 Some guidelines include golimumab as an alternative, while etanercept is consistently not recommended due to inferior efficacy in uveitis.5,16,30 For persistent disease despite MTX and anti-TNF therapy, a stepwise intensification strategy is advised. Initial measures include dose escalation or increased dosing frequency, followed by within-class switching. If unsuccessful, transition to alternative biologic classes is recommended, most notably IL-6 inhibition with tocilizumab. 23,25 Additional options include switching to or combining with other DMARDs such as mycophenolate mofetil, cyclosporine, or leflunomide. 5,16,30 Escalation is guided by persistent inflammation, inability to taper corticosteroids, or lack of improvement in visual acuity. Longterm disease control is essential,

Refer to Summary of Product Characteristics (SmPC) before prescribing. Presentation: Each vial contains 200 mg rezafungin (as acetate). Powder for concentrate for solution for infusion. White to pale yellow cake or powder. Indication: REZZAYO is indicated for the treatment of invasive candidiasis in adults. Consideration should be given to official guidance on the appropriate use of antifungal agents. Dosage and administration: A single 400 mg loading dose on Day 1, followed by 200 mg on Day 8 and once weekly thereafter. The duration of treatment should be based upon the patient’s clinical and microbiological response. In general, antifungal therapy should continue for at least 14 days after the last positive culture. During clinical trials patients were treated with rezafungin for up to 28 days. The safety information on rezafungin treatment durations longer than 4 weeks is limited. For intravenous use only. After reconstitution and dilution, the solution should be administered by slow intravenous infusion over approximately 1 hour, infusion time may be increased up to 180 minutes to manage any evolving symptoms of infusion-related reaction. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to other medicinal products of the echinocandin class. Warnings and precautions: The efficacy of rezafungin has only been evaluated in a limited number of neutropenic patients. Anaphylactic reactions: Cases of anaphylactic reaction were reported with the use of rezafungin. If an anaphylactic reaction occurs, rezafungin should be discontinued and appropriate treatment administered. Infusion-related reactions: Transient infusion-related reactions have occurred with rezafungin, characterised by flushing, sensation of warmth, nausea, and chest tightness. In clinical trials, infusion reactions resolved within minutes, some without interruption or discontinuation of the infusion. Patients should be monitored during the infusion. If the infusion is stopped due to a reaction, consideration may be given to restarting the infusion at a slower rate after the symptoms have resolved. Hepatic effects: In clinical trials, elevations in liver enzymes have been seen in some patients treated with rezafungin. In some patients with serious underlying medical conditions who were receiving multiple concomitant medications along with rezafungin, clinically significant hepatic dysfunction has occurred; a causal relationship to rezafungin has not been established. Patients who develop elevations in liver enzymes during rezafungin therapy should be monitored and the risk/benefit of continuing rezafungin therapy should be reevaluated. Phototoxicity: Rezafungin may cause increased risk of phototoxicity. Patients should be advised to avoid sun exposure and other sources of UV radiation without adequate protection during treatment and for 7 days after the last administration of rezafungin. Interactions: The drug-drug interaction potential of rezafungin with a number of probe substrates of cytochrome P450 enzymes and/or transporter proteins has been assessed clinically. The need for dose adjustments is considered unlikely for medicinal products that are substrates for the CYP2C8, CYP3A4, CYP1A2, and CYP2B6 enzymes and P-gp, BCRP, OATP, OCT1, OCT2, MATE1, and MATE2 transporter proteins, when administered with rezafungin. The drug-drug interaction potential of rezafungin with a number of coadministered medicinal products has also been assessed clinically. The need for dose adjustments is considered unlikely for tacrolimus, cyclosporine, ibrutinib, mycophenolate mofetil, and venetoclax when administered with rezafungin. In vitro, rezafungin is metabolically stable and was found not to be a substrate for BCRP, P-gp, MRP2, OATP1B1, OATP1B3, OCT1, OCTN1, and OCTN2 transporter proteins. Therefore, the need for dose adjustments of rezafungin is considered unlikely when rezafungin is co-administered with other medicinal products. Fertility, pregnancy and lactation: There are no data from the use of rezafungin in pregnant women. Studies in animals did not show reproductive or developmental toxicity. Rezafungin has been shown to cross the placental barrier in animal studies. The potential risk for humans is unknown. Rezafungin is not recommended to be used during pregnancy and in women of childbearing potential not using contraception unless the benefit outweighs the potential risk to the foetus. There are no data from the use of rezafungin in lactating women. It is unknown whether rezafungin or its metabolites are excreted in human milk. Rezafungin excretion into milk was observed in rats. No data on the effect of rezafungin on human fertility are available. Rezafungin did not affect fertility in female rats or reproductive performance in male rats, despite reversible testicular effects in male rats. Side effects: Based on clinical trial experience, the most frequently reported adverse reactions for rezafungin were anaemia, hypokalaemia, pyrexia, and diarrhoea (very common adverse reactions (≥ 1/10)). Common adverse reactions (≥ 1/100 to < 1/10 ) were: hypomagnesaemia, hypophosphataemia, hypotension, wheezing, vomiting, nausea, abdominal pain, constipation, erythema, rash, blood alkaline phosphatase increased, hepatic enzymes increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased. Transient infusion-related reactions have occurred with rezafungin, characterised by flushing, sensation of warmth, nausea, and chest tightness. Uncommon (≥ 1/1 000 to < 1/100) were: hyperphosphataemia, hyponatraemia, phototoxicity, tremor, increased eosinophil count. Unknown incidence: anaphylactic reactions, urticaria. Refer to the SmPC for details on full side effect profile and interactions. Classification: POM Marketing authorisation (MA): EU/1/23/1775/001 Name and address of MA holder: Mundipharma GmbH, De-Saint-Exupery-Strasse 10, Frankfurt Am Main, 60549, Germany. Tel: 01223424444. Additional information is available on request. For medical information enquiries, please contact medicalinformation@ mundipharma.ie

Adverse events should be reported to: HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie email: medsafety@hpra.ie Adverse events should also be reported to Mundipharma GmbH at drugsafetyUKandROI@mundipharma.com

UPDATE | VOLUME 1 2 | ISSUE 10 | 2026 PI approval code: IE-RZF-2600014 Date of preparation: June 2026

Immunology

REZZAYO® rezafungin a next generation echinocandin for an evolving treatment landscape1-3

Learn more about the benefits of REZZAYO® Visit https://pro.mundipharma.com/ie/rezzayo/rezzayo-introduction Or scan here:

REZZAYO ® is an echinocandin with a differentiated PK/PD prof ile, 4,5 indicated for the treatment of invasive candidiasis in adults. Consideration should be given to off icial guidance on the appropriate use of antifungal agents. 4 Prescribing information can be found overleaf. 1. Thompson GR III, et al. Lancet 2023;401(10370):49–59. 2. World Health Organization. WHO fungal priority pathogens list to guide research, development and public health action, 2022. https://www.who.int/publications/i/ item/9789240060241. Accessed March 2025. 3. Salmanton-García J, et al. J Infect 2024; epub ahead of print. doi: https://doi. org/10.1016/j.jinf.2024.106229. 4. REZZAYO® (rezafungin). Summary of Product Characteristics. Mundipharma 2026. 5. Sandison T, et al. Antimicrob Agents Chemother 2016;61:e01627-16.

Reporting adverse events Adverse events should be reported to HPRA Pharmacovigilance. Reporting forms and information can be found at www.hpra.ie Email: medsafety@hpra.ie Adverse events should also be reported to Mundipharma Pharmaceuticals Limited on +44 1748 828867 or email drugsafetyUKandROI@mundipharma.com

Promotional content for ROI HCPs only UPDATE | VOLUME 1 2 | ISSUE 10 | 2026 ® REZZAYO is a Registered Trademark of Napp Pharmaceutical Group 27 Limited, a Mundipharma network company. Job Code: IE-RZF-2500011(v2.0) | June 2026

Immunology

with guidelines recommending at least two years of remission before tapering systemic therapy. 5,18,30 Given the often asymptomatic nature of paediatric uveitis, regular monitoring is crucial to detect subclinical progression. A key evolution from early 2000s practice is the emphasis on dose optimisation. In the early cohort literature, infliximab dosing ranged from 100-700mg every two weeks initially, then every four to eight weeks.7 Subsequent evidence, including Sukumaran et al, demonstrated that dose escalation up to four-fold may be required for adequate control, a principle now embedded in modern algorithms. 20 Similarly, adalimumab dosing (40mg/ m² every other week) has remained consistent from early studies through to trials such as SYCAMORE.7,15 The major advancement lies not in initial dosing, but in recognising dose escalation as the most ef fective step following treatment failure, now explicitly incorporated into guideline recommendations.

Looking ahead Over the past two decades, the management of paediatric non-infectious uveitis has undergone a fundamental transformation. What was once a condition managed primarily with prolonged corticosteroid therapy and limited immunosuppressive options has evolved into a structured, evidencebased, stepwise approach centred on early introduction of steroid-sparing therapies and targeted biologic agents. 5,16,30 The transition from small retrospective cohorts, such as the original study by Gallagher et al, to high-quality RCTs including SYCAMORE and ADJUVITE

References 1. Chan NSW, Choi J, Cheung CMG. Paediatric uveitis. Asia Pac J Ophthalmol (Phila). 2018;7(3):192-199. 2. Tugal-Tutkun I. An overview of

The major advancement lies in recognisingdose escalation as the most effective step following treatment failure has been pivotal in redef ining clinical practice.7,15,17 These trials, supported by adult data from VISUAL I and II,18,19 have established anti-TNF-α therapy, particularly adalimumab in combination with MTX, as the standard of care in refractory disease, signif icantly improving disease control and long-term visual outcomes. 5,16 Despite these advances, important limitations remain. Paediatric evidence is still relatively limited, with small sample sizes and a lack of direct comparative trials between BRMs, particularly in patients who fail f irst-line anti-TNF therapy. 5,23 This represents a key gap in the current treatment framework and highlights the need for larger, welldesigned paediatric studies to better guide escalation strategies. Emerging therapeutic targets of fer promising avenues for future management. IL-6 inhibition with tocilizumab has demonstrated potential in refractory disease, particularly in cases complicated by cystoid macular oedema, although its ef f icacy appears variable and requires further validation. 23,25,26 Other cytokine pathways, including IL-1 and IL-27, as well as novel approaches such as exosome-based therapies and nanobodies, may allow for more targeted immunomodulation in the future. 24 In addition, translating robust adult trial

paediatric uveitis. Turk Arch Pediatr. 2023;58(Suppl 1):363-370. 3. de Boer J. Visual loss in uveitis of childhood. Br J Ophthalmol. 2003;87(7):879-884.

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data into paediatric populations may help accelerate therapeutic development.18,19 Importantly, the evolution of biologics has not only expanded treatment options, but has reshaped therapeutic goals, shifting focus toward early intervention, sustained remission, and prevention of irreversible visual damage. 5,16 However, long-term safety remains a critical consideration. The withdrawal of daclizumab following rare, but severe, immune-mediated adverse events highlights the importance of continued pharmacovigilance and long-term follow-up in paediatric populations. 22 In conclusion, biologic therapies have transitioned from experimental interventions to a cornerstone of modern management in refractory childhood uveitis. Future progress will depend on strengthening the paediatric evidence base, ref ining treatment algorithms beyond anti-TNF therapy, and ensuring long-term safety while continuing to improve visual outcomes in this high-risk population. ●

Conflict of interest

The authors declare no conflicts of interest. Corresponding author Anna Macháček Email: machacea@tcd.ie

4. Sijssens KM, Rothova A, Van de Vijver DAMC, et al. Risk factors for the development of cataract requiring surgery in uveitis associated with juvenile idiopathic arthritis. Am J Ophthalmol. 2007;144(4):574-579.e1.

Immunology

5. Angeles-Han ST, Ringold S, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritisassociated uveitis. Arthritis Care Res (Hoboken). 2019;71(6):703-716. 6. Belletti M, Izquierdo-Escamez R, Tornero C, et al. Safe use of corticosteroids in noninfectious uveitis. J Inflamm Res. 2025;18:14441-14455. 7. Gallagher MJ, Quinones K, Cervantes-Castañeda RA, et al. Biological response modifier therapy for refractory childhood uveitis. Br J Ophthalmol. 2007;91(10):1341-1344. 8. Modrzejewska M, Zdanowska O, Świstara D, et al. Uveitis in the paediatric population and therapeutic management: A current literature review. Children (Basel). 2024;11(7):769. 9. Rajaraman RT, Kimura Y, Li S, et al. Retrospective case review of paediatric patients with uveitis treated with infliximab. Ophthalmology. 2006;113(2):308-314. 10. Ardoin SP, Kredich D, Rabinovich E, et al. Infliximab to treat chronic noninfectious uveitis in children: Retrospective case series with longterm follow-up. Am J Ophthalmol. 2007;144(6):844-849.e1. 11. Vazquez-Cobian LB, Flynn T, Lehman TJA. Adalimumab therapy for childhood uveitis. J Pediatr. 2006;149(4):572-575. 12. Mansour AM. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007;91(3):274-276. 13. Pérez-Guijo V, Santos-Lacomba M, Sánchez-Hernández M, et al. Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: The involvement of HLA-B27. Curr Med Res Opin. 2004;20(2):155-157. 14. Tynjälä P, Lindahl P, Honkanen V, et al. Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2007;66(4):548-550. 15. Ramanan AV, Dick AD, Jones

AP, et al. Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis. N Engl J Med. 2017;376(17):1637-1646. 16. Constantin T, Foeldvari I, Anton J, et al. Consensusbased recommendations for the management of uveitis associated with juvenile idiopathic arthritis: The SHARE initiative. Ann Rheum Dis. 2018;77(8):1107-1117. 17. Quartier P, Baptiste A, Despert V, et al. ADJUVITE: A double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritisassociated anterior uveitis. Ann Rheum Dis. 2018;77(7):1003-1011. 18. Jaffe GJ, Dick AD, Brézin AP, et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016;375(10):932-943. 19. Nguyen QD, Merrill PT, Jaffe GJ, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): A multicentre, doublemasked, randomised, placebocontrolled phase 3 trial. Lancet. 2016;388(10050):1183-1192. 20. Sukumaran S, Marzan K, Shaham B, et al. High dose infliximab in the treatment of refractory uveitis: Does dose matter? ISRN Rheumatol. 2012;2012:765380. 21. Cecchin V, Zannin ME, Ferrari D, et al. Long-term safety and efficacy of adalimumab and infliximab for uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2018;45(8):1167-1172. 22. European Medicines Agency. Zinbryta [Internet]. Amsterdam: European Medicines Agency; 2018. Available at: www.ema.europa.eu/en/ medicines/human/EPAR/zinbryta. 23. Foeldvari I, Maccora I, Petrushkin H, et al. New and updated recommendations for the treatment of juvenile idiopathic arthritis-associated uveitis and idiopathic chronic anterior uveitis. Arthritis Care Res (Hoboken). 2023 May;75(5):975-982. 24. Chauhan K, Tyagi M. Update on non-infectious uveitis treatment: Anti-TNF-alpha and beyond. Front

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Ophthalmol. 2024 Aug 2;4:1412930. 25. Ramanan AV, Dick AD, Guly C, et al. Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): A multicentre, singlearm, phase 2 trial. Lancet Rheumatol. 2020;2(3):e135-e141. 26. Maccora I, Soldovieri S, Oliverio T, et al. To switch or to swap? Evidence from a meta-analysis for the best treatment approach in childhood chronic uveitis resistant to antiTNF therapy. J Transl Autoimmun. 2024;9:100247. 27. Marrani E, Paganelli V, de Libero C, et al. Long-term efficacy of abatacept in pediatric patients with idiopathic uveitis: A case series. Graefes Arch Clin Exp Ophthalmol. 2015;253(10):1813-1816. 28. Khan S, Saigal K, Sheth S, et al. Intravenous golimumab in the treatment of juvenile idiopathic arthritis and its associated uveitis. Ocul Immunol Inflamm. 2025;33(10):2245-2249. 29. Pellico MR, Pandolfi M, Amati A, et al. The effectiveness and safety of rituximab in juvenile idiopathic arthritis: Hints from the ITHACA monocentric registry. Semin Arthritis Rheum. 2025;74:152774. 30. Heiligenhaus A, Minden K, Tappeiner C, et al. Update of the evidence-based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Semin Arthritis Rheum. 2019;49(1):43-55. 31. Rathinam SR, Gonzales JA, Thundikandy R, et al. Effect of corticosteroid-sparing treatment with mycophenolate mofetil vs methotrexate on inflammation in patients with uveitis. JAMA. 2019;322(10):936-945. 32. Pan I, Lin C, Palestine AG, et al. Use of tacrolimus for the treatment of pediatric noninfectious uveitis. Ophthalmol Ther. 2026;15(1):457-465. 33. Tappeiner C, Roesel M, Heinz C, et al. Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis. Eye (Lond). 2009;23(5):1192-1198.

Immunology

IBD: From diagnosis and treatment to long-term disease management Author: Theresa Lowry Lehnen, PhD, FFNMRCSI, RANP (General Practice), MSc, RNP, MEd, PGDE (QTS), IUHPE HPP, PG Dip Coronary Care, BSc (Hons), RGN

nflammatory bowel disease (IBD) is a chronic, relapsing and remitting disorder of the gastrointestinal tract, with Crohn’s disease (CD) and ulcerative colitis (UC) representing the two forms. Although both conditions are characterised by dysregulated and sustained intestinal inflammation, they differ considerably in their anatomical distribution, pathological characteristics, clinical presentation, and potential complications. IBD can occur at any age, but is frequently diagnosed during adolescence and early adulthood, often at a stage of life when education, employment, relationships, fertility, and social development are particularly important. The management of IBD has changed considerably over recent decades. Treatment has moved from an emphasis on controlling symptoms towards a more proactive approach aimed at controlling intestinal inflammation, achieving sustained remission, preventing structural bowel damage and reducing the risk of hospitalisation and surgery. This shift has been accompanied by major advances in pharmacological treatment, including the increasing use of biologic therapies and targeted small molecules. Current European guidance emphasises individualised treatment, objective assessment of disease activity, and close monitoring of treatment response.1,2, 3 The 2024 European Crohn’s and Colitis Organisation (ECCO) guideline provides updated recommendations for the medical treatment of Crohn’s disease, while the 2026 ECCO guideline provides

an updated evidence base for medical treatment of ulcerative colitis.1,2

relatively non-specif ic symptoms, and the diagnosis cannot be established from symptoms alone. 4,5

CD and UC

The precise cause of IBD remains incompletely understood. It is considered to result from an interaction between genetic susceptibility, environmental influences, intestinal microbiota, and dysregulation of the immune response. IBD should not be regarded as a condition caused simply by stress or diet. Nevertheless, environmental factors, smoking, nutrition, psychological wellbeing, and lifestyle can influence disease experience and management.1,2

CD can involve any part of the gastrointestinal tract, from the mouth to the anus, with the terminal ileum and colon among the most frequently af fected sites. The inflammatory process is typically transmural and discontinuous, with af fected segments of bowel separated by areas of relatively normal-appearing tissue. This characteristic distribution contributes to the complications associated with CD, including strictures, f istulae, abscesses, and penetrating disease.1,4 UC is confined to the colon and characteristically involves the rectum, extending proximally in a continuous pattern. Inflammation principally affects the mucosa and may extend into the submucosa in more severe disease. The extent of ulcerative colitis is commonly described according to whether the disease is limited to the rectum, extends through the left side of the colon or involves more extensive areas of the colon.2,5 The distinction between the two diseases is clinically important, although symptoms frequently overlap. UC commonly presents with bloody diarrhoea, increased stool frequency, urgency, and tenesmus, whereas CD may present with abdominal pain, diarrhoea, weight loss, fatigue, nutritional def iciencies, or symptoms associated with stricturing or penetrating disease. Some patients, however, present with

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Recognising possible IBD Early recognition of IBD is important because persistent untreated intestinal inflammation can result in cumulative bowel damage and disability. Contemporary management places considerable emphasis on early diagnosis and appropriate assessment.1 Persistent or recurrent diarrhoea, rectal bleeding, abdominal pain, nocturnal bowel symptoms, urgency, tenesmus, unexplained weight loss, and persistent fatigue should prompt consideration of an underlying inflammatory gastrointestinal disorder. Anaemia, particularly iron-def iciency anaemia without an obvious explanation, may provide an additional clue.1,2 A detailed clinical history should identify the duration and progression of symptoms, stool frequency, stool consistency, the presence and quantity of blood, urgency, nocturnal symptoms,

Immunology

and abdominal pain. It is important to establish whether the patient has experienced weight loss, anorexia, or reduced dietary intake and whether symptoms are af fecting attendance at work, college, or social activities. 4 Medication history is particularly relevant. Non-steroidal antiinflammatory drugs (NSAIDs) may exacerbate gastrointestinal symptoms in some patients, while the recent use of antibiotics raises the possibility of infectious diarrhoea, including Clostridioides dif f icile. A history of recent travel, gastrointestinal infection, family history of IBD, and previous episodes of unexplained gastrointestinal symptoms should also be explored. 4,5 In a patient with established IBD, a change in symptoms should not automatically be attributed to an inflammatory flare. Infection, medication adverse ef fects, irritable bowel syndrome, bile acid diarrhoea, small intestinal bacterial overgrowth, and other gastrointestinal conditions can produce symptoms resembling active IBD. Objective assessment is therefore essential before treatment is escalated.1,2

Diagnosis and investigation There is no single diagnostic blood test for IBD. Diagnosis requires integration of clinical history, laboratory investigations, stool assessment, endoscopy, histology, and, where appropriate, cross-sectional imaging. 6 Initial blood investigations commonly include a full blood count, inflammatory markers, renal function, electrolytes, liver function, albumin, and iron studies. Vitamin B12 and folate may be particularly relevant in patients with CD involving the terminal ileum or those with nutritional compromise. Vitamin D status may also warrant assessment, depending on the individual clinical situation.6 C-reactive protein (CRP) can provide useful information regarding systemic inflammation, although it is not suf f iciently sensitive or specif ic to be used alone to diagnose

or exclude active IBD. Some patients with signif icant intestinal inflammation may have a relatively normal CRP, while other inflammatory or infectious conditions can result in an elevated result.6 Faecal calprotectin has become an important non-invasive investigation. It is a marker of intestinal inflammation and can assist in distinguishing IBD from functional disorders such as irritable bowel syndrome.6 An elevated result, however, is not specif ic for IBD and may occur with gastrointestinal infection, colorectal neoplasia, NSAID use, and other inflammatory conditions. Interpretation must therefore take place within the clinical context. Endoscopic assessment remains central to diagnosis. Colonoscopy with assessment of the terminal ileum and appropriate biopsies can demonstrate the distribution and severity of inflammation and provides tissue for histological examination. Histology is important in establishing chronicity and supporting the distinction between IBD and other causes of colitis.6 Imaging has particular importance in CD because inflammation may involve areas of small bowel that cannot be adequately assessed by conventional colonoscopy. Magnetic resonance enterography and intestinal ultrasound are increasingly important in assessing bowel inflammation, strictures, f istulae, and other complications. Contemporary diagnostic guidance increasingly recognises the value of non-invasive biomarkers and intestinal ultrasound in monitoring disease activity and reducing unnecessary invasive investigations.7

From symptom control to treat-to-target management One of the most important developments in modern IBD care has been the recognition that symptoms alone do not provide a suf f icient measure of disease control. A patient may feel relatively well despite ongoing objective intestinal inf lammation, while another may experience signif icant gastrointestinal symptoms despite little evidence of active disease. 8 The STRIDE-II treat-to-target framework established a structured approach to def ining treatment goals in IBD.3,8 Short-term objectives include improvement in symptoms and restoration of normal functioning, while intermediate and long-term goals include normalisation of inflammatory biomarkers and endoscopic healing. The overall objective is not simply for the patient to feel better temporarily, but to achieve sustained control of the inflammatory process and reduce the risk of future bowel damage.3,8 This approach has important implications for nursing assessment. A patient’s current symptoms should be compared with their usual baseline. Stool frequency, rectal bleeding, urgency, abdominal pain, nocturnal symptoms, weight, fatigue, and functional capacity should all be considered alongside objective investigations.6,8 The concept of remission should be explained carefully to patients. Symptomatic improvement is important, but it does not necessarily mean that intestinal inflammation has completely

One of the most important developments in modern IBD care has been the recognition that symptoms alone do not provide a sufficient measure of disease control UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

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resolved. Explaining this distinction can improve understanding of why patients may need ongoing medication and monitoring even when they feel well.6,8

Pharmacological management Treatment is individualised according to disease type, anatomical location, disease activity, previous treatment response, prognostic factors, complications, and patient preferences. The therapeutic approach also dif fers between CD and UC.1,2 In mild-moderate UC, 5-aminosalicylates (ASA), particularly mesalazine, remain an important treatment option. Oral and rectal preparations may be used according to disease distribution, and combination therapy may be appropriate where disease extends beyond the rectum. 2 The 2026 ECCO guideline continues to support the use of 5-ASA in appropriate patients with mildly-moderately active UC. 2 In contrast, the role of 5-ASA in CD is very limited. The 2024 ECCO guideline recommends against the use of 5-ASA for induction or maintenance of remission in CD because of insuf f icient evidence of meaningful ef f icacy.1 Corticosteroids remain valuable for inducing remission in selected patients with active disease, particularly where rapid control of inflammation is required. Their use should, however, be limited because of their substantial short- and long-term adverse ef fect prof ile. Prolonged corticosteroid exposure is associated with osteoporosis, infection, hyperglycaemia, hypertension, weight gain, mood disturbance, cataracts, and adrenal suppression. Steroids should therefore generally be regarded as an induction or bridging treatment rather than a long-term maintenance strategy.1,2 Repeated courses of corticosteroids should prompt consideration of whether the patient’s treatment strategy requires review. A patient who repeatedly relapses when corticosteroids are reduced may require steroid-sparing therapy rather than

repeated courses of the same treatment.1,2 Immunomodulators such as azathioprine and mercaptopurine continue to have a role in selected patients, although their use has changed as biologic and targeted therapies have become increasingly available. Treatment requires appropriate laboratory monitoring and patient education concerning infection, adverse ef fects, and the importance of reporting concerning symptoms. 1,2 Biologic therapies have transformed the management of moderate to severe IBD. Anti-tumour necrosis factor therapies, anti-integrin agents, and interleukin-targeted therapies may be used according to the individual clinical circumstances. Targeted small molecules, including Janus kinase inhibitors and other advanced therapies, have further expanded the treatment options available to patients with moderate to severe disease. 1,2 The choice of therapy is no longer simply a decision about which medication is most ef fective. It may involve consideration of previous treatment exposure; comorbidities; safety, route, and frequency of administration; patient preference; pregnancy considerations; lifestyle; adherence; and the individual’s risk of disease progression.1,2

Infection prevention Infection prevention is an important component of IBD management, particularly for patients receiving immunosuppressive or advanced therapies. The updated ECCO guidance on infections in IBD provides recommendations concerning infection prevention, screening, and vaccination.9 Vaccination status should be reviewed proactively rather than waiting until immunosuppressive treatment is commenced. Where possible, vaccination assessment should take place before signif icant immunosuppression begins, because some live vaccines may be contraindicated during immunosuppressive therapy.9

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Influenza, Covid-19, pneumococcal, hepatitis B, and other vaccinations should be considered according to the individual’s age, risk factors, treatment, and national recommendations.9 The precise vaccination programme should be determined in accordance with current Irish immunisation guidance and the patient’s clinical circumstances.

Nutritional assessment and anaemia Nutritional problems are common in IBD and may arise from reduced oral intake, intestinal inflammation, malabsorption, increased nutritional requirements, or self-imposed dietary restriction.1,2,10 Iron-def iciency anaemia is particularly important. It may contribute substantially to fatigue, reduced concentration, and impaired quality of life. Iron def iciency may occur in the presence or absence of anaemia and inflammatory activity can complicate interpretation of ferritin. Assessment therefore requires consideration of the full clinical picture and relevant laboratory parameters.1,2 Vitamin B12 def iciency is particularly relevant in CD involving the terminal ileum and following ileal resection. Folate, vitamin D, and other micronutrients may also require assessment according to the individual’s disease and nutritional status.1,10 Patients frequently modify their diet in an attempt to control symptoms. Some may unnecessarily exclude dairy products, f ibre, gluten, or multiple other foods, resulting in an increasingly restrictive diet. Contemporary ECCO guidance supports personalised dietary management rather than a universal diet for all patients with IBD.10

Extraintestinal manifestations Extraintestinal manifestations of IBD can involve the joints, skin, eyes, liver and biliary system.11 Musculoskeletal manifestations include peripheral arthritis and axial spondyloarthritis. Patients may describe persistent inflammatory back pain, morning

Indicated in: Dermatology1

Rheumatology1

PsA: Psoriatic Arthritis Ps: Plaque Psoriasis PaedPs: Paediatric Plaque Psoriasis (ages 4–17) HS: Hidradenitis Suppurativa from 12 years of age

PsA: Psoriatic Arthritis P-JIA: Polyarticular Juvenile Idiopathic Arthritis (ages 2–17) ERA: Enthesitis-related Arthritis (ages 6–17) nr-axSpA: Non-radiographic Axial Spondyloarthritis AS: Ankylosing Spondylitis RA: Rheumatoid Arthritis

Gastroenterology1 CD: Crohn’s Disease PaedCD: Paediatric Crohn’s Disease (ages 6–17) UC: Ulcerative Colitis PaedUC: Paediatric Ulcerative Colitis (ages 6-17)

Ophthalmology1 Uv: Uveitis PaedUv: Paediatric Chronic Noninfectious Anterior Uveitis (ages 2–17)

HUMIRA is indicated for1: PsA (Psoriatic Arthritis): The treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. P-JIA (Polyarticular Juvenile Idiopathic Arthritis (ages 2–17) in combination with methotrexate): The treatment of active polyarticular juvenile idiopathic arthritis, in patients from the age of 2 years who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). ERA: (Enthesitis-related Arthritis (ages 6–17)): The treatment of active enthesitis-related arthritis in patients, 6 years of age and older, who have had an inadequate response to, or who are intolerant of, conventional therapy. nr-axSpA (Non-radiographic Axial Spondyloarthritis): The treatment of adults with severe axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated CRP and / or MRI, who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs). AS (Ankylosing Spondylitis): The treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy. RA (Rheumatoid Arthritis in combination with methotrexate): The treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to diseasemodifying anti-rheumatic drugs including methotrexate has been inadequate.The treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. Ps (Plaque Psoriasis): The treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy. PaedPs (Paediatric Plaque Psoriasis (ages 4–17)): The treatment of severe chronic plaque psoriasis in children and adolescents from 4 years of age who have had an inadequate response to or are inappropriate candidates for topical therapy and phototherapies. HS (Hidradenitis Suppurativa from 12 years of age): The treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adults and adolescents from 12 years of age with an inadequate response to conventional systemic HS therapy. CD (Crohn’s Disease): The treatment of moderately to severely active Crohn’s disease, in adult patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. PaedCD (Paediatric Crohn’s Disease (ages 6–17)): The treatment of moderately to severely active Crohn’s disease in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including primary nutrition therapy and a corticosteroid and/or an immunomodulator, or who are intolerant to or have contraindications for such therapies. UC (Ulcerative Colitis): The treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies. PaedUC (Paediatric Ulcerative Colitis (ages 6-17)): The treatment of moderately to severely active ulcerative colitis in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies. Uv: Uveitis The treatment of non-infectious intermediate, posterior and panuveitis in adult patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid sparing, or in whom corticosteroid treatment is inappropriate. PaedUv (Paediatric Chronic Non-Infectious Anterior Uveitis (ages 2–17)): The treatment of paediatric chronic non-infectious anterior uveitis in patients from 2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in whom conventional therapy is inappropriate.

Reference: 1. HUMIRA® Summary of Product Characteristics available at www.medicines.ie. Further information is available upon request from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, or from the Summary of Product Characteristics available at www.medicines.ie. Marketing Authorisation Holder: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany. Legal Category: POM (S1A). ©2024 AbbVie Inc. All rights reserved. IE-HUM-240003 | July 2024

Immunology

stif fness, or painful swollen joints. Dermatological manifestations include erythema nodosum and pyoderma gangrenosum, while ocular manifestations include episcleritis and uveitis.11 The distinction between these conditions and unrelated symptoms is clinically important. Acute painful red eye, photophobia, or visual disturbance, for example, warrants urgent ophthalmological assessment because uveitis can threaten vision.11 Primary sclerosing cholangitis is an important hepatobiliary association with IBD and is particularly associated with UC. Abnormal liver function tests should therefore not automatically be attributed to medication or alcohol without appropriate clinical consideration.11 Venous thromboembolism is another important consideration, particularly during active disease and hospitalisation. The inflammatory state associated with IBD can increase thrombotic risk, reinforcing the importance of appropriate assessment and prophylaxis in patients who require hospital admission.11

Acute severe UC Acute severe UC represents a potentially life-threatening complication and requires urgent hospital-based management. Patients may present with frequent bloody diarrhoea, systemic toxicity, fever, tachycardia, anaemia, elevated inflammatory markers, dehydration, and electrolyte disturbance.12 Changes in stool

frequency, rectal bleeding, abdominal pain, abdominal distension, temperature, pulse, blood pressure, hydration status, and overall clinical condition should be carefully monitored.12 Potential complications include severe dehydration, electrolyte abnormalities, signif icant anaemia, toxic megacolon, perforation, sepsis, and venous thromboembolism. Failure to respond appropriately to medical treatment may necessitate rescue therapy or colectomy.12 Acute severe colitis can be frightening and upsetting, particularly when patients are experiencing frequent bloody stools and urgency. Maintaining privacy, dignity, and clear communication is an important component of care.

Complicated CD CD may result in stricturing, penetrating, or f istulising complications. A patient with a known history of CD who develops worsening abdominal cramping, distension, vomiting, or inability to pass stool or flatus requires urgent clinical assessment because these symptoms may indicate intestinal obstruction. 4 Perianal CD can be particularly challenging. Patients may experience pain, drainage, abscess formation, fistulae, and significant psychological distress. Management frequently requires close collaboration between gastroenterologists, colorectal surgeons, radiologists, specialist nurses, and other members of the multidisciplinary team.4 The 2024 ECCO surgical guideline emphasises multidisciplinary management of

The psychological impact of IBD can be substantial. Patients may experience anxiety, depression, fatigue, altered body image, embarrassment, fear of incontinence, sexual difficulties, and social isolation 34

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complicated CD and the importance of controlling sepsis before immunosuppressive treatment is undertaken in patients with septic complications.4 Perianal disease may be associated with embarrassment and reluctance to disclose symptoms, making a trusting therapeutic relationship particularly important.

Colorectal cancer Long-standing colonic inflammation is associated with an increased risk of colorectal neoplasia. Risk is influenced by factors including disease duration, extent of colonic involvement, inflammatory burden, family history, and associated conditions.13 Surveillance colonoscopy is an important element of long-term care for selected patients with colonic IBD. Modern surveillance increasingly focuses on high-quality colonoscopy, careful mucosal assessment, and identif ication of dysplasia.13 The updated British Society of Gastroenterology guideline on colorectal surveillance in IBD provides contemporary recommendations regarding surveillance strategies and dysplasia detection.13 Repeated colonoscopy can be burdensome for patients and may contribute to anxiety, discomfort, and reluctance to undergo further surveillance. Patients should be educated on why surveillance is necessary, addressing concerns about bowel preparation and sedation, and ensuring that patients understand the dif ference between routine monitoring, and investigation of new symptoms.

Psychological wellbeing The psychological impact of IBD can be substantial. Patients may experience anxiety, depression, fatigue, altered body image, embarrassment, fear of incontinence, sexual dif f iculties, and social isolation. Young adults may particularly struggle with the unpredictability of bowel symptoms and the ef fect of disease on education, employment, relationships, and social activities.11,14 The practical burden of urgency should not be underestimated. Patients may plan journeys around access to toilets, avoid eating before leaving home

Immunology

or restrict participation in social events because of fear of an accident. Such experiences may not be identif ied unless specif ically explored.14 A holistic assessment should therefore extend beyond questions about bowel frequency. Asking how the illness is af fecting the patient’s education, employment, relationships, sleep, sexual health, conf idence, and social life can reveal problems that may otherwise remain hidden.14 Mental health support should be regarded as part of comprehensive IBD management rather than an optional addition to gastrointestinal care.11,14

Shared decision-making Adherence is particularly challenging in chronic relapsing diseases. A patient who feels well may question the need for ongoing medication, particularly when treatment has adverse ef fects or requires regular injections or infusions.1,2 It is important for patients to understand that clinical remission does not necessarily mean the absence of underlying inflammation. The purpose of maintenance treatment is to sustain disease control and reduce the risk of relapse and complications.1,3,8 Shared decision-making is increasingly important because several ef fective advanced therapies may be available for an individual patient. Treatment decisions should incorporate evidence of ef fectiveness and safety alongside the patient’s circumstances and preferences. The patient’s lifestyle, work commitments, travel, injection preferences, fertility plans, and willingness to attend hospitalbased treatment may all influence the most appropriate choice.1,2 This approach recognises the patient as an active participant in treatment rather than a passive recipient of medical intervention.

Fertility, pregnancy, and sexual health Fertility and reproductive health should be an integral part of routine IBD care. These discussions should be individualised,

Women and men of reproductive age should have opportunities to discuss fertility, contraception and pregnancy planning as part of routine IBD care sensitive and non-judgemental, with appropriate involvement of the relevant specialist team to support informed decision-making and continuity of care.1,2,5 Patients may be reluctant to raise concerns about fertility, sexual health, or pregnancy, particularly when these issues are sensitive or dif f icult to discuss. It is important to initiate these conversations in a sensitive, non-judgemental manner and ensure that appropriate advice, information, and referral are provided. 5 Active IBD can adversely af fect pregnancy outcomes, while individual medications require careful consideration when planning conception and throughout pregnancy. However, discontinuing ef fective treatment unnecessarily may precipitate a disease flare, which can present greater risks to both the patient and pregnancy than continuing appropriate therapy. It is important to reinforce the value of maintaining disease control when planning pregnancy.1,2,5 Women and men of reproductive age should have opportunities to discuss fertility, contraception and pregnancy planning as part of routine IBD care. This is particularly relevant in primary care because contraception and sexual health consultations may provide an opportunity to identify gastrointestinal symptoms, medication concerns or reproductive health questions that have not previously been discussed.

Patient education Patient education should be individualised and revisited throughout the disease course, reflecting changes in treatment, disease activity, and the

UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

patient’s circumstances. Patients should understand their diagnosis, treatment plan, monitoring programme, and the symptoms or changes that warrant clinical review. Education is particularly important in supporting patients to recognise the dif ference between expected day-today variation and changes that may indicate active disease.¹⁴ Education should also equip patients with practical skills for self-management. Patients benef it from understanding their usual bowel pattern, recognising changes from their baseline, and knowing when to contact their IBD team. Written information supported by personalised f lare management plans can help patients identify early changes in their condition, understand appropriate actions, and seek timely clinical advice.¹⁴ Ef fective education should be delivered in a manner that ref lects the patient’s health literacy, preferences, and individual circumstances. Providing written information alone does not ensure that it has been understood or can be applied in practice. Clinicians should encourage questions, use clear and accessible language, check understanding, and address misconceptions, particularly around diet, medication adherence, and the relationship between symptoms and underlying inf lammation. This approach supports informed decision-making, strengthens self-management, and enables patients to take a more active role in managing their condition. 14

AMGEVITA® (adalimumab) Prescribing Information Please refer to the Summary of Product Characteristics (SmPC) before prescribing Pharmaceutical Form: Single dose pre-filled syringe contains 20 mg adalimumab in 0.4 mL (50 mg/mL) solution, 20 mg adalimumab in 0.2 mL (100 mg/mL) solution, 40 mg adalimumab in 0.8 mL (50 mg/mL) solution, 40 mg adalimumab in 0.4 mL (100 mg/mL) solution, 80 mg adalimumab in 0.8 mL (100 mg/mL) solution, and single dose pre-filled pen (SureClick®) contains 40 mg adalimumab in 0.8 mL (50 mg/mL) solution, 40 mg adalimumab in 0.4 mL (100 mg/mL) solution and 80 mg adalimumab in 0.8 mL (100 mg/mL) solution. Indications and Dosage: please refer to SmPC for full information. For subcutaneous injection. Treatment should be initiated and supervised by specialist physicians experienced in conditions for which AMGEVITA® is indicated. Ophthalmologists should consult with an appropriate specialist before starting treatment. Give patients a Patient Reminder Card. After training in injection technique, patients may self-inject with medical follow-up as necessary. Optimise other concomitant therapies (e.g. corticosteroids and or/immunomodulatory agents). Rheumatoid arthritis (RA): In combination with methotrexate (MTX) for: 1. moderate to severe, active RA in adult patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including MTX; 2. Severe, active and progressive RA not previously treated with MTX. Can be given as monotherapy if intolerance to or when continued treatment with MTX is inappropriate. AMGEVITA® reduces rate of progression of joint damage when given in combination with MTX. Dosage: 40 mg every other week as a single dose via subcutaneous injection. Continue MTX. Glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs, or analgesics can be continued during treatment. In monotherapy, patients may require 40 mg every week or 80 mg every other week if there is a decrease in clinical response. Reconsider treatment beyond 12 weeks if no clinical response. Consider need for dose interruption, e.g. before surgery or if serious infection occurs. Polyarticular juvenile idiopathic arthritis (pJIA): In combination with MTX for active pJIA in patients from the age of 2 years with inadequate response to one or more DMARDs. Can be given as monotherapy if intolerance to or when continued treatment with MTX is inappropriate. Dosage: 10 kg to < 30 kg: 20 mg every other week. ≥ 30 kg: 40 mg every other week. Reconsider treatment beyond 12 weeks if no clinical response. Enthesitis-related arthritis (ERA): treatment of active ERA in patients 6 years and older with inadequate response to, or intolerance to conventional therapy. Dosage: 15 kg to < 30 kg: 20 mg every other week. ≥ 30 kg: 40 mg every other week. Ankylosing spondylitis (AS): treatment of adults with severe active AS with inadequate response to conventional therapy. Axial spondyloarthritis without radiographic evidence of AS: treatment of adults with severe axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated CRP and/or MRI, and an inadequate response to, or intolerance to nonsteroidal anti-inflammatory drugs. Psoriatic arthritis (PsA): treatment of active and progressive psoriatic arthritis in adults with inadequate response to previous DMARD therapy. Dosage: (AS, nr-axSpA, PsA): 40 mg every other week. Reconsider treatment beyond 12 weeks if no clinical response. Psoriasis: treatment of moderate to severe chronic plaque psoriasis in adults wo are candidates for systemic therapy. Dosage: 80 mg at week 0, followed by 40 mg

AMG1003_Amgevita_DPS_Advert_JUL24_04.indd All Pages

every other week from week 1. Reconsider treatment beyond 16 weeks if no clinical response. Paediatric Plaque Psoriasis: treatment of severe chronic plaque psoriasis in children and adolescents from 4 years of age with inadequate response to or if topical therapy and phototherapies are inappropriate. Dosage: 15 kg to < 30 kg: 20 mg followed by 20 mg every other week starting one week after initial dose. ≥ 30 kg: 40 mg then 40 mg every other week starting one week after initial dose. Reconsider treatment beyond 16 weeks if no clinical response. Safety has been assessed in paediatric patients with plaque psoriasis for a mean of 13 months. Hidradenitis suppurativa (HS): treatment of active moderate to severe HS (acne inversa) in adults and adolescents from 12 years of age with inadequate response to conventional systemic HS therapy. Dosage: adult: 160 mg at Day 1, followed by 80 mg at Day 15. At day 29 continue with 40 mg every week or 80 mg every other week. Reintroduction after treatment interruption: 40 mg every week or 80 mg every other week. Dosage: adolescent (≥ 30 kg): 80 mg at week 0 then 40 mg every other week starting at week 1. If response is inadequate, consider increasing to 40 mg every week or 80 mg every other week. Dosage: adult and adolescent: Antibiotics may be continued if necessary. Use concomitant topical antiseptic wash on a daily basis. Reconsider treatment beyond 12 weeks if no improvement. Periodically evaluate the benefit and risk of continued treatment. Crohn’s disease: treatment of moderately to severely active Crohn’s disease in adults with no response despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or intolerance to or have medical contraindications for such therapies. Dosage: Induction: 80 mg at week 0, then 40 mg at week 2. For a more rapid response: 160 mg at week 0, then 80 mg at week 2; risk of adverse events higher during rapid induction. Maintenance: 40 mg dose every other week. Corticosteroids may be tapered in accordance with clinical guidelines. If decrease in clinical response, can increase to 40 mg every week or 80 mg every other week. If no response by week 4 there may be benefit from continued therapy to week 12. Reconsider treatment beyond 12 weeks if no clinical response. Paediatric CD, ≥ 6 years: Moderately to severely active CD with inadequate response to, intolerance to or contraindication to conventional therapy including primary nutrition therapy and a corticosteroid and/or an immunomodulator. Dosage: < 40 kg: Induction: 40 mg at week 0 then 20 mg at week 2. For a more rapid response: 80 mg at week 0 then 40 mg at week 2; risk of adverse events higher during rapid induction. Maintenance starting at week 4: 20 mg dose EOW. If insufficient response, consider 20 mg every week. Dosage: ≥ 40 kg: Induction: 80 mg at week 0 then 40 mg at week 2. For a more rapid response: 160 mg at week 0, then 80 mg at week 2; risk of adverse events higher during rapid induction. Maintenance starting at week 4: 40 mg dose EOW. If insufficient response, consider 40 mg every week or 80 mg EOW. Reconsider treatment beyond 12 weeks if no clinical response. Paediatric Crohn’s disease: treatment of moderately to severely active Crohn’s disease in paediatric patients from 6 years of age with inadequate response to conventional therapy including primary nutrition therapy and a corticosteroid and/or an immunomodulator, or intolerant to or have contraindications for such therapies. Dosage: < 40 kg: Induction: 40 mg at week 0 then 20 mg at week 2. For a more rapid response: 80 mg at week 0 then 40 mg at week 2; risk of adverse events higher during rapid induction. Maintenance starting at week 4: 20 mg dose every

other week. If insufficient response, consider 20 mg every week. Dosage: ≥ 40 kg: Induction: 80 mg at week 0 then 40 mg at week 2. For a more rapid response: 160 mg at week 0, then 80 mg at week 2; risk of adverse events higher during rapid induction. Maintenance starting at week 4: 40 mg dose every other week. If insufficient response, consider 40 mg every week or 80 mg every other week. Reconsider treatment beyond 12 weeks if no clinical response. Ulcerative colitis: treatment of moderately to severely active ulcerative colitis in adult patients with inadequate response to, intolerance to or contraindication for conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA). Dosage: Induction: 160 mg at week 0 and 80 mg at week 2. Maintenance: 40 mg every other week. Corticosteroids may be tapered in accordance with clinical guidelines. If insufficient response, consider increasing to 40 mg every week or 80 mg every other week. Do not continue treatment beyond 8 weeks if no clinical response. Paediatric ulcerative colitis: treatment of moderately to severely active ulcerative colitis in paediatric patients from 6 years of age with an inadequate response to conventional therapy including corticosteroids and/or 6-MP or AZA, or who are intolerant to or have medical contraindications for such therapies. Dosage: < 40 kg: Induction: 80 mg at week 0 and 40 mg at week 2. Maintenance starting at week 4: 40mg EOW. Dosage: ≥ 40 kg: Induction: 160 mg week 0 and 80 mg week 2. Maintenance starting at week 4: 80mg every other week. Patients reaching 18 years should continue their prescribed maintenance dose. Reconsider treatment beyond 8 weeks if no clinical response. No relevant use in children <6 years. Uveitis: treatment of non-infectious intermediate, posterior and panuveitis in adults with inadequate response to corticosteroids, in patients in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate. Dosage: 80 mg at week 0 and 40 mg every other week from week 1. There is limited experience in initiation of treatment with adalimumab alone. Treatment can be initiated in combination with corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant corticosteroids may be tapered starting two weeks after initiating treatment with AMGEVITA®. Evaluate on a yearly basis the benefit and risk of continued treatment. Paediatric uveitis: treatment of paediatric chronic non-infectious anterior uveitis in patients from 2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in whom conventional therapy is inappropriate. Dosage: ≥ 30 kg: 40 mg every other week in combination with MTX. A loading dose of 40 mg (< 30 kg) or 80 mg (≥ 30 kg) may be administered 1 week in advance of maintenance therapy. No clinical data on use of loading dose in patients < 6 years. Evaluate benefit and risk of continued treatment on a yearly basis. Contraindications: Hypersensitivity to the active substance or to any excipients; Active tuberculosis (TB) or other severe infections such as sepsis and opportunistic infections; Moderate to severe heart failure (NYHA class III/IV). Warnings and Precautions: Traceability: Clearly record the name and batch number. Infections: Patients taking TNF-antagonists are more susceptible to serious infections, especially if impaired lung function. Monitor for infections, before, during and for 4 months after treatment. Do not initiate treatment during an active infection, until infection is controlled. Consider risk/benefit prior to treatment in patients exposed to TB or who have travelled in areas of high risk of TB or endemic mycoses. Evaluate new infections and monitor closely. Stop

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PRESCRIBE AMGEVITA® BY BRAND NAME treatment if new serious infection or sepsis and treat. Exercise caution in patients with a history of recurring infections or who are predisposed to infections, including the use of concomitant immunosuppressive medications. Serious Infections: Consult SmPC for details. Serious infections, including those associated with hospitalisation or death, were reported in patients receiving treatment. TB: Reactivation and new onset TB, both pulmonary and extra-pulmonary (disseminated). Screen all patients before therapy initiation for active or inactive (latent) TB. Perform detailed medical assessment and appropriate screening tests for TB in all patients and results recorded on patient reminder card. If latent TB is suspected, consult physician with appropriate expertise Despite prophylaxis, TB reactivation has occurred on adalimumab. If active TB is diagnosed, do not initiate AMGEVITA® treatment. Other opportunistic infections: Opportunistic infections were observed in patients receiving adalimumab. Stop AMGEVITA® in patients with signs and symptoms of such infections. Consult with physician with appropriate expertise for diagnosis and administration of empiric antifungal therapy. Hepatitis B reactivation: Reactivation of HBV has occurred in chronic carriers; some cases were fatal. Test patients for HBV infection before initiating treatment. HBV carriers should consult a specialist physician and be closely monitored for reactivation of HBV infection throughout therapy and for several months after treatment. If reactivation occurs, stop treatment and initiate appropriate antiviral and supportive treatment. Neurological events: Caution in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders. Consider discontinuation if any of these develop. Perform neurologic evaluation in patients with non-infectious intermediate uveitis prior to initiation of treatment and regularly during treatment. Allergic reactions: Reports of serious allergic reactions including anaphylaxis. For serious allergic or anaphylactic reaction, stop AMGEVITA® immediately and initiate appropriate therapy. Malignancies and lymphoproliferative disorders: A possible risk of malignancy, some fatal, including lymphomas and leukaemia, cannot be excluded (see SmPC). Examine all patients, especially those with a medical history of extensive immuno-suppressant therapy or psoriasis patients with a history of PUVA treatment, for non-melanoma skin cancer prior to and during treatment. Melanoma and Merkel cell carcinoma have also been reported. Caution in COPD patients, and in patients with increased risk for malignancy due to heavy smoking. Consider the potential risk with the combination of AZA or 6-MP and AMGEVITA® (hepatosplenic T-cell lymphoma has occurred). Caution in patients with a history of malignancy. Risk of developing dysplasia or colon cancer unknown. Screen patients with UC, history of dysplasia or colon carcinoma, for dysplasia before and during treatment. Haematologic reactions: Adverse events of the haematologic system, including medically significant cytopenia, have been reported. Advise patients to seek immediate medical attention if signs and symptoms of blood dyscrasias develop. Vaccinations: Patients may receive concurrent vaccinations, except for live vaccines. Bring paediatric patients up to date with all immunisations prior to initiating treatment. Congestive heart failure: See contraindications. Caution in mild heart failure (NYHA class I/II). Discontinue treatment if new or worsening symptoms of congestive heart failure. Autoimmune processes: Autoimmune antibodies may form. Stop treatment if development of a lupus-like syndrome with positive antibodies against double-

stranded DNA. Surgery: Consider the long half-life of AMGEVITA® for planned surgical procedures. Monitor closely for infections. There is limited safety experience in patients undergoing arthroplasty or surgical procedures. Elderly patients: Serious infections were higher in patients over 65, some of which were fatal. Consider risk of infections in these patients. Interactions: Antibody formation was lower when AMGEVITA® was given together with MTX rather than as monotherapy. Combination of AMGEVITA® with other biologic DMARDs (e.g. anakinra and abatacept) or other TNF-antagonists is not recommended. Fertility, pregnancy and lactation Only use during pregnancy if clearly needed. Women of childbearing age to consider use of adequate contraception during and for at least 5 months after the last treatment. Administration of live vaccines (e.g. BCG) to infants exposed to AMGEVITA® in utero is not recommended for 5 months following the mother’s last injection during pregnancy. AMGEVITA® can be used during breastfeeding. Effects on ability to drive and use machines: AMGEVITA® may have a minor influence on the ability to drive and use machines. Vertigo and visual impairment may occur. Adverse Reactions: Very common ≥ 1/10: Respiratory tract infections; including lower and upper respiratory tract infection, pneumonia, sinusitis, pharyngitis, nasopharyngitis and pneumonia herpes viral, leukopenia; including neutropenia and agranulocytosis, anaemia, lipids increased, headache, abdominal pain, nausea and vomiting, elevated liver enzymes, rash; including exfoliative rash, musculoskeletal pain, injection site reaction; including erythema. Common ≥ 1/100 to < 1/10: Systemic infections; including sepsis, candidiasis and influenza intestinal infections; including gastroenteritis viral skin and soft tissue infections; including paronychia, cellulitis, impetigo, necrotising fasciitis and herpes zoster ear infections, oral infections; including herpes simplex, oral herpes and tooth infections, reproductive tract infections; including vulvovaginal mycotic infection, urinary tract infections; including pyelonephritis, fungal infections, joint infections, skin cancer excluding melanoma, benign neoplasm, leucocytosis, thrombocytopenia, hypersensitivity, allergies, hypokalaemia, uric acid increased, blood sodium abnormal, hypocalcaemia, hyperglycaemia, hypophosphataemia, dehydration, mood alterations, anxiety, insomnia, paraesthesia; including hypoaesthesia, migraine, nerve root compression, visual impairment, conjunctivitis, blepharitis, eye swelling, vertigo, tachycardia, hypertension, flushing, haematoma, asthma, dyspnoea, cough, GI haemorrhage, dyspepsia, gastroesophageal reflux disease, Sicca syndrome, worsening or new onset of psoriasis; including palmoplantar pustular psoriasis, urticaria, bruising; including purpura, dermatitis; including eczema, onychoclasis, hyperhidrosis, alopecia, pruritus, muscle spasms; including blood creatine phosphokinase increased, renal impairment, haematuria, chest pain, oedema, pyrexia, coagulation and bleeding disorders; including including activated partial thromboplastin time prolonged, autoantibody test positive; including double stranded DNA antibody), blood lactate dehydrogenase increased, impaired healing. Serious adverse reactions have been reported; AMGEVITA® may affect the immune system and the body’s defence against infection and cancer. Fatal and life-threatening infections; including sepsis, opportunistic infections and TB, HBV reactivation and various malignancies (including leukaemia, lymphoma and HSTCL) have also been reported. Serious haematological, neurological and autoimmune reactions have also been reported. These include rare reports of

pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of lupus, lupus-related conditions and Stevens-Johnson syndrome. Pharmaceutical Precautions: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the prefilled syringe or pre-filled pen in the outer carton in order to protect from light. The prefilled syringe or pre-filled pen may be stored up to a maximum of 25C for up to 14 days. The pre-filled syringe or pre-filled pen must be protected from light and discarded if not used within the 14-day period. Legal Category: POM. Presentation and Marketing Authorisation Number: AMGEVITA® 20 mg solution for injection in pre-filled syringe: EU/1/16/1164/001 – 1 pack, AMGEVITA® 40 mg solution for injection in pre-filled syringe: EU/1/16/1164/003 – 2 pack AMGEVITA® 40 mg solution for injection in pre-filled pen: EU/1/16/1164/007 – 2 pack; AMGEVITA® 20 mg/0.2ml solution for injection in pre-filled syringe: EU/1/16/1164/010 – 1 pack, AMGEVITA® 40 mg/0.4ml solution for injection in pre-filled syringe: EU/1/16/1164/012 – 2 pack, AMGEVITA® 40 mg/0.4ml solution for injection in pre-filled pen: EU/1/16/1164/015 – 2 pack, AMGEVITA® 80 mg/0.8ml solution for injection in pre-filled pen: EU/1/16/1164/020 – 1 pack,. Marketing Authorisation Holder: Amgen Europe B.V. Minervum 7061, 4817 ZK Breda, The Netherlands. Further information is available from Amgen Ireland Limited, 21 Northwood Court, Santry, Dublin D09 TX31. AMGEVITA® is a registered trademark of Amgen Inc. Date of PI preparation: May 2024 (Ref: IRL-501-0424-80003) Adverse reactions/events should be reported to the Health Products Regulatory Authority (HPRA) using the available methods via www.hpra.ie. Adverse reactions/events should also be reported to Amgen Limited on +44 (0) 1223 436441 or Freephone 1800 535 160. 1. 2. 3. 4. 5.

Amgen Data on File REF-101991 (last accessed 30th of August 2024). Papp K, et al. J Am Acad Dermatol 2017. Cohen S, et al. Ann Rheum Dis 2017. AMGEVITA® (adalimumab) summary of product characteristics including supporting information. Amgen Data On File Hub-AMB-2000001 (last accessed 30th August 2024). Date of prep to May 2024 IRL-501-0524-80001

04/09/2024 16:19

Immunology

Conclusion IBD is a complex chronic condition requiring long-term, multidisciplinary management. The contemporary approach is no longer focused solely on relieving diarrhoea, abdominal pain, or rectal bleeding. Instead, treatment aims to achieve sustained control of inf lammation, prevent progressive bowel damage, minimise corticosteroid exposure, reduce complications, and enable patients to maintain their quality of life. Recognition of IBD symptoms, appropriate investigation, and timely referral can inf luence the patient’s subsequent disease trajectory. In established disease, careful assessment of symptoms alongside objective markers

References 1. Gordon H, Minozzi S, Kopylov U, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J Crohns Colitis. 2024;18(10):1531-1555. doi:10.1093/ecco-jcc/jjae091. 2. Gisbert JP, Chaparro M, Verstockt B, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis. 2026;20(7):jjag066. doi:10.1093/ecco-jcc/jjag066. 3. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organisation for the Study of IBD (IOIBD): Determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160(5):15701583. doi:10.1053/j.gastro.2020.12.031. 4. Adamina M, Minozzi S, Warusavitarne J, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Surgical Treatment. J Crohns Colitis. 2024;18(10):1556-1582. doi:10.1093/ ecco-jcc/jjae089. 5. Magro F, Gionchetti P, Eliakim R, et al. Third European Evidencebased Consensus on Diagnosis and Management of Ulcerative Colitis.

of inf lammation can help distinguish genuine relapse from other causes of gastrointestinal symptoms. Patients should be monitored for treatmentrelated complications, nutritional def iciencies, psychological distress, and dif f iculties with adherence. Optimal care requires an understanding that the impact of the disease extends well beyond the bowel. For many patients, the greatest burden may be the unpredictability of symptoms, the fear of urgency or incontinence, the disruption to education and employment, concerns about relationships and fertility, or the psychological impact of living with a chronic disease. Modern IBD care requires

Part 1: Definitions, diagnosis, extraintestinal manifestations, pregnancy, cancer surveillance, surgery, and ileoanal pouch disorders. J Crohns Colitis. 2017;11(6):649-670. doi:10.1093/eccojcc/jjx008. 6. Waugh N, Cummins E, Royle P, et al. Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: Systematic review and economic evaluation. Health Technol Assess. 2013;17(55):xv-211. doi:10.3310/hta17550. 7. Kucharzik T, Taylor S, Allocca M, et al. ECCO-ESGAR-ESP-IBUS Guideline on Diagnostics and Monitoring of Patients with Inflammatory Bowel Disease: Part 1. J Crohns Colitis. 2025;19(7):jjaf106. doi:10.1093/ecco-jcc/jjaf106. 8. Lutz M, Horst S, Caldera F. Applying biomarkers in treat-to-target approach for IBD. Curr Gastroenterol Rep. 2025;27(1):41. doi:10.1007/s11894-02500991-7. 9. Yanai H, Ellul P, Verstockt B, et al. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J Crohns Colitis. 2026;20(7):jjag071. doi:10.1093/ ecco-jcc/jjag071.

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clinical expertise, proactive disease management and person-centred care. From early recognition and evidence-based assessment through treatment, monitoring, and long-term management, healthcare professionals must support patients across the full course of CD and UC. Individualised education, proactive monitoring, timely identif ication of deterioration, and continuity of care help to optimise disease control, reduce the risk of complications, and support informed decision-making. Patients should be provided with consistent support throughout the disease journey to achieve the best possible health outcomes and quality of life while living with IBD. ●

10. Svolos V, Gordon H, Lomer MCE, et al. European Crohn’s and Colitis Organisation consensus on dietary management of inflammatory bowel disease. J Crohns Colitis. 2025;19(9):jjaf122. doi:10.1093/ecco-jcc/ jjaf122. 11. Gordon H, Burisch J, Ellul P, et al. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(1):137. doi:10.1093/ecco-jcc/jjad108. 12. Spinelli A, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment. J Crohns Colitis. 2022;16(2):179-189. doi:10.1093/ecco-jcc/jjab177. 13. East JE, Gordon M, Nigam GB, et al. British Society of Gastroenterology guidelines on colorectal surveillance in inflammatory bowel disease. Gut. Published online April 30, 2025. doi:10.1136/gutjnl-2025-335023. 14. Jäghult S, Adamina M, Farrell D, et al. Third N-ECCO Consensus Statements on the nursing roles in caring for patients with inflammatory bowel disease. J Crohns Colitis. 2026;20(7):jjag054. doi:10.1093/ecco-jcc/jjag054.

Immunology

Carbapenemase-producing Enterobacteriaceae: A practice update Author: Maureen Carlin, Clinical Nurse Specialist in Infection Prevention and Control, Letterkenny University Hospital

To complete this module and earn free CPD points, go to www.doctorCPD.ie and complete the questions based on this article.

chieving ef fective control of the spread of multi-drug-resistant organisms (MDROs), such as carbapenemaseproducing Enterobacteriaceae (CPE), is one of the most signif icant problems facing infection prevention and control practitioners worldwide. 1 Aside from the risk of patient-to-patient transfer, colonised drain reservoirs within patient accommodation, such as sinks, showers and toilets, pose a silent risk factor for CPE acquisition that have proven to be the source of numerous outbreaks worldwide and are very challenging to eradicate. 2,3,4,5

What is CPE? CPE refers to a group of Enterobacterales bacteria, such as Escherichia coli, Klebsiella, and Enterobacter, which live within the gut and have evolved to develop the enzymatic capacity (carbapenemase) to convey resistance to vital last-resort broad spectrum antibiotics known as carbapenems. 6,7 There are a number of acquired carbapenemase enzyme types

that dif fer in both function and the antibiotics they resist. Primary CPE types include:  Oxacillinase-48-like (OXA-48-like)  Imipenem-resistant Pseudomonas (IMP)  Klebsiella pneumoniae carbapenemase (KPC)  Verona integron-encoded metallo-β-lactamase (VIM)  New Delhi metallo-betalactamase (NDM). These carbapenemases enzymes have become a particular concern as resistance genes have not only the added capability to move easily across dif ferent Enterobacterales strains, but also vertically within a strain – self-facilitating the rapid spread of carbapenem resistance.7 Of alarm, infections caused by CPE are very challenging to treat, as they can confer further resistance to often already multi-resistant pathogens and result in high mortality rates. 8,9 By 2050, over 10 million deaths are projected to be either associated or attributable to antibiotic-resistant bacteria annually, with CPE-associated death rates currently increasing more than any other gram-negative bacteria globally. 1 In 2021 alone, over one million associated deaths have been attributed to CPE. 1 Currently in Ireland, CPE is predominantly spread within healthcare environments. Individuals are exposed via contact with contaminated hands (patients and healthcare workers),

UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

equipment, and the environment, with colonisation facilitated via the faecal-oral route.6 Individuals who carry CPE in the gut typically have no clinical symptoms and are classif ied as colonised.6 However, research has shown that colonisation with CPE is associated with a 16.5 per cent chance of progressing to the development of infection, rising substantially in elderly and immunocompromised patients. 2 The mortality rate of CPE infections can be signif icant. For example, of those individuals that develop CPE bacteraemia, the 30-day mortality rate can be up to 50 per cent, with some sources reporting much higher rates.9 The most common sources of bacteraemia are urinary tract (21%) and intra-abdominal (42%).10 Certain factors may predispose patients to developing CPE bacteraemia including age >65 years, receiving hospital care, diabetes, heart failure, recent endoscopic procedures, receiving treatment for cancer, or being a transplant recipient.10

A national public health emergency CPE has now become endemic in many countries. However, this is not yet the case in Ireland, and the chance to stop CPE from spreading endemically still exists. Once endemic, achieving control is extremely dif f icult. 11 In response to this threat, Ireland declared a national public health emergency in 2017, and subsequently created both an expert advisory group and a national public health emergency team to inform now proven ef f icacious

Immunology

strategies such as patient screening and CPE management. 12 Recent European surveillance data ref lect our favourable progress in comparison to other countries, with rates of carbapenem resistance in bloodstream infections now reduced by a signif icant 63.6 per cent from 2019 to 2023. 13 However, the opposite is true in the majority of other European countries, with rates increasing dramatically in some. It has been warned that in view of CPE’s ability to proliferate quickly in hospital settings, and because of limited therapeutic options, these organisms will inevitably lead to poor clinical outcomes.7 Additionally, for healthcare providers, the rising prevalence of CPE also has substantial f inancial and operational ramif ications, and action needs to be taken to halt this threat to both medical care and public health.7 Furthermore, ef fective strategies such as stricter infection control measures and antimicrobial stewardship to limit the spread of CPE acquisition, excretion, and persistence in medical facilities has been called for to limit risks to health. 13,14

CPE screening in the acute setting Detection of asymptomatic CPE colonisation may be clinically important for the individual concerned, as this information could be pivotal in guiding the choice of empirical antimicrobial therapy should severe infection subsequently occur. 6 Furthermore, timely identif ication of CPE colonisation has broader public health value, as it facilitates

implementation of actions aimed at limiting transmission within the acute setting, with guidance recommending that screening is undertaken within 24 hours of admission to hospital. 6 CPE screening involves testing a rectal swab or faecal specimen using molecular diagnostics and/or culture methods, with results then subsequently verif ied in a CPE referencing laboratory. The quality of the specimen submitted for diagnostic testing is a key determinant of the validity of the test result and, consequently, of CPE recovery.6 Screening practices are recommended to be either universal (all patients) or risk-based (high-risk patients and areas), with processes based on local resources and epidemiology.13 A review of the clinical epidemiology of CPE highlights risk factors that are positively linked with the colonisation of CPE. These risk factors include exposure to hospital care, CPE exposure, the presence of medical devices, invasive procedures, mechanical ventilation, admission to the intensive care unit (ICU), underlying disease, patient demographic, and the use of quinolone, β-lactam, cephalosporin, glycopeptide, and carbapenem antibiotics. 14,15 Risk-based active surveillance screening of high-risk individuals for asymptomatic carriage is outlined in recent updated guidance from both the HSE and European Centre for Disease Prevention and Control.6,13 Guidelines recommend patients are screened if they:  Have had an overnight stay in any type of healthcare facility within the preceding 12 months.  Have received multiple hospital

treatments or are in receipt of chemotherapy or dialysis within the preceding 12 months.  Are a known contact of CPE.  Have a documented previous CPE

carriage within the preceding 12 months.  Have received considerable exposure

to broad-spectrum antimicrobials.  Are admitted to high-risk clinical

settings/specialties or CPE endemic wards, and regular active surveillance should also be undertaken in these areas based on risk assessment.

Down the drain: A silent source of CPE The prevention of person-to-person transmission of CPE is not suf f icient on its own to tackle the full-scale problem, and the eradication of persistent hospital environmental reservoirs is thought to be key in successful management.11 Colonised drain reservoirs within patient accommodation involving sinks, showers, and toilets pose a particular risk factor for CPE acquisition. These colonised reservoirs have proven to be the source of numerous outbreaks worldwide that resulted in patient deaths and are extremely challenging to eradicate. 2,3,4,5,16 The scale and signif icance of hospital environmental CPE drain reservoirs have been widely studied, varying between wards, hospitals and countries, with some studies detecting CPE in up to:  86 per cent of rooms sampled 17  41 per cent of samples taken within one metre of a water source18  20 per cent of showers 18  30 per cent of sinks 19  And 25 per cent of toilet water samples. 2 At the very core of CPE’s resilience within these reservoirs is a protective and under-appreciated structure known as biof ilm.

Biof ilm

Recent European surveillance data reflect Ireland's favourable progress in comparison to other countries 40

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Biof ilms are extensively abundant throughout health care and two main types exist:  Dry biof ilms, found on equipment and surfaces.

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 Hydrated biof ilms, frequently found

in wet areas such as drains. Biof ilms are complex and resilient ecosystems that can harbour many organisms, not merely CPE. They are made up of microorganisms surrounded in a matrix of extracellular materials (such as lipids, proteins, polysaccharides, metal ions, extracellular enzymes, and eDNA). 20 Biof ilms have multifaceted survival characteristics, are promoted by nutrient availability, and have low levels of susceptibility to cleaning and disinfection, which is why they thrive within healthcare environments that are exposed to many individuals colonised with various organisms. 5,21,22 Furthermore, biof ilm microbe characteristics can lend to increased mutation rates – in addition to resistance gene transfer found in CPE – as they act like a mixing pot in which CPE can f lourish and spread. 23 Dry biof ilms: Research reveals that the bacteria present in healthcare surroundings primarily exist in widespread dry biof ilms on commonly used equipment and surfaces that ef fectively harbour pathogens. 24,25 Dry biof ilm can contain culturable bacteria and it has been conceptualised that biof ilms form over extended periods on dry surfaces from the projection of contaminated biological f luids, surface condensation due to room humidity, or periodic moistening during cleaning and disinfection. 25,26 The contamination of surfaces by dry biof ilm has been shown to play a major role in hospital-acquired infections, with items frequently touched by the hands of patients and healthcare workers of ten acting as a reservoir. 27 Viable Staphylococcus aureus cells from dry biof ilms were found to be signif icantly more virulent and readily transferrable through a touch test, with more cells transferring when biof ilm surfaces were wet. 28 These factors highlight the importance of

regular ef fective cleaning and adequate disinfection of surfaces and equipment. Hydrated biof ilms: Can prof iciently regenerate af ter disinfection treatments, and growth is aided by the addition of nutrients put down the drain. Biof ilm has been shown to grow upwards from contaminated sink traps at the alarming rate of one inch per day, reaching the sink af ter just one week. 29 An examination into outbreak control of CPE from around the world portrays a vast array of both successes and failures in tackling the resilience of CPE biof ilm reservoirs in hospital drains using various disinfectants and remedial works. 30,31 At the route of this resilience appears to be the selected disinfectant product’s ability to tackle these biof ilm matrices which function as sanctuaries within drains – leading to the survival and spread of CPE. 20

CPE spread from wastewater drainage Research has conf irmed that wastewater drainage systems play an integral part in the indirect transmission of CPE via several mechanisms including:  Bioaerosol plumes32  Droplet spread 33  Dif fusion of CPE from both within and between patient rooms through connected pipework. 11 Connections in wastewater plumbing to neighbouring sinks, toilets, and showers are thought to aid in bacterial seeding from colonised areas to new areas, and biof ilms are also known to form and spread upwards within shared pipes, contaminating linked areas. 19,29

A large-scale metagenomic examination of wastewater pipes during a ward remodelling in Ireland discovered no discernible variations in microorganisms between the results of patient and staf f wastewater equipment, which may indicate that microbiological exposure could be multi-directional throughout systems. 33 Toilets have the ability to emit signif icant quantities of micro-aerosols and droplets into the environment on f lushing, particularly when the toilet lid is up, contaminating the surrounding areas. 32 A high incidence of sink drains close to positive toilets have been found to be contaminated with CPE, and it is proposed that during f lushing, generated droplets lead to nearby sink drain and environmental contamination. 34 Furthermore, ongoing sink activities such as healthcare personnel and patients performing hand hygiene, may also play a part in the seeding of sinks. 35 An enlightening video analysis into the behaviours around ICU patient sinks demonstrated a predominance of nonhand hygiene activities, many of which could promote spread and propagation of MDROs. 35 Of 5,614 observed behaviours, 37.4 per cent involved medical care, 29.2 per cent additional behaviours, 7.2 per cent patient nutrition, 5 per cent environmental care, and 4.2 per cent non-medical care. Alarmingly, handwashing accounted for merely 4 per cent of total activities. Furthermore, analysis of videos highlighted 56 activities in which various nutrients were disposed of in sinks, which would undoubtably encourage colonisation of MDROs. 5,22

Biofilm microbe characteristics can lend to increased mutation rates, in addition to resistance gene transfer found in CPE UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

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Spread from sinks Organisms from drain biof ilms in colonised sinks are known to spread via large droplet-sized particles brought on by tap water. 36 Hand washing has been shown to result in the frequent dispersal of microbes from colonised sink drains, contaminating hands and gowns, which may serve as a route of transmission to both staf f and patients. 37 Additionally, if sink drainage is impaired, splashes have been shown to travel over one metre from the sink. 38 Furthermore, the location of the outlet very much inf luences if dispersion will occur, becoming more likely if the tap is positioned directly above the waste trap. 38 In comparison, when the drain is located at the back of the sink, and the water is free draining, there is no dispersal from the waste trap. 38

CPE risk from showers Biof ilm containing CPE can grow upwards from shower drains as it can from sink traps, where CPE can reach the outlet and patients may be exposed while using the shower. 29 Slow draining showers also pose a risk of exposure to patients during use. In this instance, showers should be closed of f until maintenance has resolved the issue and it has been fully disinfected. 39 A study using both high and low velocity shower heads displayed similar complex and widespread droplet patterns, conf irming that showers can generate potentially contaminated aerosols in the respirable range. 40 The concentration ratio of total bacteria in the air during shower operation relative to baseline values varied by day, indicating that while turning on the shower spray could increase the bacterial load in the air released from biof ilms, it could also decrease the total bacterial concentrations with more use.

What is happening to tackle CPE positive drain reservoirs? According to the World Health Organization (WHO) CPE guidelines,

both the collection and analysis of environmental surveillance cultures can require substantial resources in terms of staf f ing, laboratories, information technology, and data management systems. 41 However, they recommend in some cases, particularly for outbreaks, that resources invested are deemed to be worth the net gain. In addition, they add, that to ensure the standardisation of surveillance methods and cleaning techniques, extra training could be required. Guidance from the Irish Expert Advisory Group for CPE emphasises the necessity for infection prevention and control teams to sample the environment appropriately and target hotspots for transmission to mitigate the inherent risks that these reservoirs pose to patients. 11 A multidisciplinary approach that targets biof ilm reservoirs is advocated as necessary to ef fectively manage CPE in both healthcare environments and wastewater systems. 42 The challenges associated with eradicating CPE are highlighted in a report describing ef forts to manage a persistent CPE outbreak in an ICU where sink traps were the source. 30 A multitude of dif ferent approaches were tried in an attempt to gain control. Interventions included the hyperchlorination and heating of the main hospital water chamber and terminal points, repeated changing of sink traps, the f itting of a ‘selfdisinfecting’ sink trap, and trialling of various disinfectants. However, complete elimination was not possible. Sink traps were treated initially once weekly for 10 weeks with 250ml of 25 per cent acetic acid. This decreased the percentage of contaminated sinks from 85 per cent to 28 per cent. In the end, a daily decontamination protocol with 1,000ppm hypochlorite was adopted, further reducing the percentage of positive sinks to a more modest 15 per cent, with no additional CPE cases reported for

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the next year. An argument against replacing plumbing f ittings as a means of eliminating CPE is advocated by results from a culture-based study, which found that the high concentration of organisms detected af ter one week showed that traps were already colonised, and the biof ilm had reestablished by spread from neighbouring piping. 31 As yet, no consensus has been attained on what is the most effective approach or protocol for decontamination of CPE from drains. The literature very much ref lects cases of trial and error which may, in part, be a symptom of the lack of consensus in the field of drain decontamination and evidencebased guidance. Focus is often placed primarily on finding the ideal treatment type and frequency to keep it at bay deep within wastewater drainage systems and safely away from patients. 30 When deciding on which treatment to use, researchers advocate that it is vital to examine the reduction in microbial bioburden along with the time it takes for hydrated biof ilm to regenerate af ter treatments. Fundamentally, this will inform the ef fectiveness, frequency, and duration of the treatment used. 24 Additionally, it has been recommended that treatments should display a dual action, targeting both the removal of the biof ilm structure and the destruction of the microbes within the biof ilm, as this is fundamental to ef fectively eradicating biof ilm CPE contamination. 20 Research is ongoing in the area, with evolving innovative advancements – including biofilm-targeting foams and ultraviolet light treatments, which demonstrate promising potential in tackling CPE. 42 Successful collective management should combine efficacious disinfection protocols, the inclusion of infection prevention practices, and necessary infrastructure upgrades, whilst

Immunology

also embracing evolving advances in both evidenced-based guidance and technology as this will undoubtably prove pivotal to our future success in mitigating CPE in healthcare. 42

What can healthcare professionals do to limit spread?  Ensure qualifying patients are screened within 24 hours of admission to hospital to allow early detection and isolation. 6  Promote prompt isolation of colonised patients. It is important to communicate ef fectively between departments before transporting patients and to routinely check local computerised systems for alert tags. Dif ferent types of CPE require separate isolation. The same types may be cohorted together. 6  Adopt strict standard and contactbased precautions based on a point of care risk assessment before every patient interaction. 43  It is not necessary for visitors to wear personal protective equipment, though it is advised if they are providing personal care to the patient. Hand hygiene should be encouraged before and af ter each visit. 6  Apply door signage for contact precautions. 44  Hand hygiene based on the WHO 5 Moments is one of the single most important things you can both do

References 1. GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: A systematic analysis with forecasts to 2050. Lancet. 2024;404(10459):11991226. doi:10.1016/S01406736(24)01867-11. 2. Hamerlinck H, Aerssens A, Boelens J, et al. Sanitary installations and wastewater plumbing as reservoir for the long-term circulation and transmission of carbapenemase producing

and also promote with your patient population. 45  Use dedicated patient equipment and ensure meticulous decontamination af ter its use. 6  Initiate enhanced environmental cleaning with household service staf f during their stay.  When colonised patients are discharged, it is vital that discharge terminal cleaning is performed, ensuring both the room and bathroom are given a detailed cleaning and disinfection, including treatment of all drainage points. 6  Discourage the placement of patient belongings near sinks. 46  Promote the utilisation of toilet lids to prevent splash contamination when f lushing. 32,46  Do not use shower rooms or bathrooms as storage for equipment or patient supplies. 46  Avoid high pressure direct tap water discharge into sink drains to reduce splashing. 37,46  Promptly close of f and report slow draining outlets to maintenance. Ensure it is disinfected prior to reopening af ter maintenance. 39  Ensure that handwashing sinks are strictly used for handwashing only. Other liquids can encourage biof ilm growth. 5  Prevent and treat any dry biof ilm build-up on surfaces and equipment

to reduce environmental reservoirs by maintaining a clean and safe environment. 24  Ensure tasks on routine cleaning checklists are completed to uphold hygiene standards.  Check mattresses regularly for integrity, and when a patient has been discharged home, by unzipping and checking for any staining or degradation of the cover. 47,48

Citrobacter freundii clones in a hospital setting. Antimicrob Resist Infect Control. 2023;12(1):58. doi:10.1186/s13756023-01261-9.

et al. Acetic acid as a decontamination method for ICU sink drains colonised by carbapenemase-producing Enterobacteriaceae and its effect on CPE infections. J Hosp Infect. 2019;102(1):82-88. doi:10.1016/j.jhin.2018.12.009.

3. Nurjadi D, Scherrer M, Frank U, et al. Genomic investigation and successful containment of an intermittent common source outbreak of OXA-48-producing Enterobacter cloacae related to hospital shower drains. Microbiol Spectr. 2021;9(3):e0138021. doi:10.1128/Spectrum.01380-21. 4. Smolders D, Hendriks B, Rogiers P,

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Conclusion CPE represents one of the most urgent and complex threats facing healthcare. Its resistance to last-resort antibiotics, capacity for silent colonisation, and ability to persist within environmental reservoirs such as drains and biof ilms make it a formidable challenge for infection prevention and control. This review demonstrates that reducing transmission demands far more than isolated interventions; it requires early and ef fective screening, rigorous infection prevention practices, high standards of environmental hygiene, infrastructure vigilance, and sustained multidisciplinary commitment. If these measures are applied consistently and decisively, healthcare services have a genuine opportunity to protect vulnerable patients, preserve the ef fectiveness of remaining treatments, and prevent CPE from becoming further embedded within clinical care environments. ●

5. Otter JA, Vickery K, Walker JT, et al. Surface-attached cells, biofilms, and biocide susceptibility: Implications for hospital cleaning and disinfection. J Hosp Infect. 2015;89(1):16-27. doi:10.1016/j.jhin.2014.09.008. 6. HSE Antimicrobial Resistance and

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Infection Control (AMRIC). Management and control of Carbapenemase-producing Enterobacterales (CPE) in all health and social care settings. Version 1.1. Dublin: HSE; 2025. Available at: www.hpsc.ie/a-z/microbiologyantimicrobialresistance/carbapenemresistantenterobacteriaceaecre/ guidanceandpublications/Management%20and%20Control%20of%20 Carbapenemase%20Producing%20 Enterobacterales%20(CPE)%20in%20 all%20Healthcare%20Settings.pdf 7. UK Health Security Agency. Framework of actions to contain carbapenemase-producing Enterobacterales. London: Department of Health and Social Care; 2022. Available at: www. gov.uk/government/publications/actions-to-contain-carbapenemase-producing-enterobacterales-cpe 8. Paul M, Carrara E, Retamar P, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European Society of Intensive Care Medicine). Clin Microbiol Infect. 2022;28(4):521-547. doi:10.1016/j. cmi.2021.11.025. 9. Lodise TP, Bassetti M, Ferrer R, et al. All-cause mortality rates in adults with carbapenem-resistant Gram-negative bacterial infections: A comprehensive review of pathogen-focused, prospective, randomised, interventional clinical studies. Expert Rev Anti Infect Ther. 2022;20(5):707-719. doi:10.1080/14787 210.2022.2020099. 10. Satlin MJ, Chen L, Patel G, et al. Multicentre clinical and molecular epidemiological analysis of bacteremia due to carbapenem-resistant enterobacteriaceae (CRE) in the CRE epicentre of the United States. Antimicrob Agents Chemother. 2017;61(4):e02349-16. doi:10.1128/AAC.02349-16. 11. Humphreys H, Cormican M, Brennan W, et al. Reflections on a national public health emergency response to carbapenemase-producing Enterobacterales (CPE). Epidemiol Infect. 2022;150:e69. doi:10.1017/S0950268822000218.

12. Vellinga A, Brennan W, Humphreys H, Burns K. Initial impact of a national programme to contain the spread of carbapenemase-producing Enterobacterales in Ireland. J Hosp Infect. 2021;109:107-114. doi:10.1016/j. jhin.2021.01.001. 13. European Centre for Disease Prevention and Control. Carbapenem-resistant Enterobacterales, Third Update. Stockholm: European Centre for Disease Prevention and Control; 2025. Available at: www.ecdc.europa. eu/sites/default/files/documents/ risk-assessment-carbapenem-resistant-enterobacterales-third-update-february-2025_0.pdf 14. Yan L, Sun J, Xu X, Huang S. Epidemiology and risk factors of rectal colonisation of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital. Antimicrob Resist Infect Control. 2020;9(1):155. doi:10.1186/s13756-020-00816-4. 15. van Loon K, Voor in ‘t Holt AF, Vos MC. A systematic review and meta-analyses of the clinical epidemiology of carbapenem-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017;62(1):e01730-17. doi:10.1128/AAC.01730-17. 16. Anantharajah A, Goormaghtigh F, Nguvuyla Mantu E, et al. Longterm intensive care unit outbreak of carbapenemase-producing organisms associated with contaminated sink drains. J Hosp Infect. 2024;143:38-47. doi:10.1016/j.jhin.2023.10.010. 17. Sleiman L, Dananché C, Gardes S, et al. Identification of carbapenemase-producing Enterobacteriaceae reservoirs in wet hospital environments as a potential factor in patient acquisition: A cross-sectional study in a French university hospital in 2023. Infect Dis Now. 2024;54(8):104998. doi:10.1016/j.idnow.2024.104998. 18. Najjar-Debbiny R, Feldman M, Groizberg-Schwartzman D, et al. Unveiling the hidden threat of carbapenemase-producing Enterobacteriaceae in hospital water environments: A sin-

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gle-centre study. Am J Infect Control. 2023;51(11):1279-1281. doi:10.1016/j. ajic.2023.07.006. 19. Lemarié C, Legeay C, Kouatchet A, et al. High prevalence of contamination of sink drains with carbapenemase-producing Enterobacteriaceae in four intensive care units apart from any epidemic context. Am J Infect Control. 2020;48(2):230-232. doi:10.1016/j. ajic.2019.08.007. 20. Maillard JY, Centeleghe I. How biofilm changes our understanding of cleaning and disinfection. Antimicrob Resist Infect Control. 2023;12(1):95. doi:10.1186/s13756-023-01290-4. 21. Nucci A, Rocha EPC, Rendueles O. Latent evolution of biofilm formation depends on life-history and genetic background. NPJ Biofilms Microbiomes. 2023;9(1):53. doi:10.1038/s41522-02300422-3. 22. Kotay SM, Parikh HI, Barry K, et al. Nutrients influence the dynamics of Klebsiella pneumoniae carbapenemase-producing Enterobacterales in transplanted hospital sinks. Water Res. 2020;176:115707. doi:10.1016/j. watres.2020.115707. 23. McCallum GE, Hall JPJ. The hospital sink drain microbiome as a melting pot for AMR transmission to nosocomial pathogens. NPJ Antimicrob Resist. 2025;3(1):68. doi:10.1038/s44259025-00137-9. 24. Ledwoch K, Dancer SJ, Otter JA, et al. Beware biofilm! Dry biofilms containing bacterial pathogens on multiple healthcare surfaces: A multi-centre study. J Hosp Infect. 2018;100(3):e47-e56. doi:10.1016/j. jhin.2018.06.028. 25. Nkemngong C, Teska P. Biofilms, mobile genetic elements, and the persistence of pathogens on environmental surfaces in healthcare and food processing environments. Front Microbiol. 2024;15:1405428. doi:10.3389/ fmicb.2024.1405428. 26. Schapira AJ, Dramé M, Olive C, Marion-Sanchez K. Bacterial viability in dry-surface biofilms in healthcare

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facilities: A systematic review. J Hosp Infect. 2024;144:94-110. doi:10.1016/j. jhin.2023.11.004. 27. Costa DM, Johani K, Melo DS, et al. Biofilm contamination of high-touched surfaces in intensive care units: Epidemiology and potential impacts. Lett Appl Microbiol. 2019;68(4):269-276. doi:10.1111/lam.13127. 28. Amaeze NJ, Akinbobola AB, Kean R, et al. Transfer of micro-organisms from dry surface biofilms and the influence of long survival under conditions of poor nutrition and moisture on the virulence of Staphylococcus aureus. J Hosp Infect. 2024;150:34-39. doi:10.1016/j.jhin.2024.03.023.

of hospital wastewater system microbiomes and clinical isolates from infected patients: Profiling of multi-drug-resistant microbial species. J Hosp Infect. 2023;141:152-166. doi:10.1016/j. jhin.2023.09.001. 35. Buchan BW, Graham MB, Lindmair-Snell J, et al. The relevance of sink proximity to toilets on the detection of Klebsiella pneumoniae carbapenemase inside sink drains. Am J Infect Control. 2019;47(1):98-100. doi:10.1016/j. ajic.2018.06.021.

lines for the prevention and control of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa in healthcare facilities. Geneva, Switzerland: WHO; 2017. Available at: www.who.int/publications-detail-redirect/9789241550178 43. Ali S, Burke LP, Fitzpatrick F, et al. A scoping review of disinfection strategies for carbapenemase-producing Enterobacterales in hospital water systems. J Hosp Infect. 2026;168:1-12. doi:10.1016/j.jhin.2025.10.021. 44. HSE Antimicrobial Resistance and

30. Kotay S, Chai W, Guilford W, et al. Spread from the sink to the patient: In situ study using green fluorescent protein (gfp)-expressing escherichia coli to model bacterial dispersion from hand-washing sink-trap reservoirs. Appl Environ Microbiol. 2017;83(8):e03327-16. doi:10.1128/ AEM.03327-16.

36. Grabowski M, Lobo JM, Gunnell B, et al. Characterisations of handwashing sink activities in a single hospital medical intensive care unit. J Hosp Infect. 2018;100(3):e115-e122. doi:10.1016/j. jhin.2018.04.025. 37. Kotay SM, Donlan RM, Ganim C, et al. Droplet rather than aerosol-mediated dispersion is the primary mechanism of bacterial transmission from contaminated hand-washing sink traps. Appl Environ Microbiol. 2019;85(2):e0199718. doi:10.1128/AEM.01997-18.

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31. Regev-Yochay G, Smollan G, Tal I, et al. Sink traps as the source of transmission of OXA-48-producing Serratia marcescens in an intensive care unit. Infect Control Hosp Epidemiol. 2018;39(11):1307-1315. doi:10.1017/ ice.2018.235.

38. Hajar Z, Mana TSC, Cadnum JL, Donskey CJ. Dispersal of gram-negative bacilli from contaminated sink drains to cover gowns and hands during hand washing. Infect Control Hosp Epidemiol. 2019;40(4):460-462. doi:10.1017/ice.2019.25.

46. World Health Organization. WHO

32. Franco LC, Tanner W, Ganim C, et al. A microbiological survey of handwashing sinks in the hospital built environment reveals differences in patient room and healthcare personnel sinks. Sci Rep. 2020;10(1):8234. doi:10.1038/s41598-020-65052-7.

39. Aranega-Bou P, George RP, Verlander NQ, et al. Carbapenem-resistant Enterobacteriaceae dispersal from sinks is linked to drain position and drainage rates in a laboratory model system. J Hosp Infect. 2019;102(1):6369. doi:10.1016/j.jhin.2018.12.007.

47. Centres for Disease Control and

40. Weinbren M, Inkster T, Lafferty F. Drains and the periphery of the water system – what do you do when the guidance is outdated? Infect Prev Pract. 2021;3(4):100179. doi:10.1016/j. infpip.2021.100179.

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41. Estrada-Perez CE, Kinney KA, Maestre JP, et al. Droplet distribution and airborne bacteria in an experimental shower unit. Water Res. 2018;130:4757. doi:10.1016/j.watres.2017.11.039.

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doi:10.12968/bjon.2012.21.3.152.

33. Barbut F, Couturier J, Rabate M, et al. Évaluation de la dissémination des bactéries à partir des toilettes: Étude expérimentale [Assessment of the spread of bacteria from contaminated toilets: Experimental study]. Hygienes. 2022;30(1):29-35. Available at: www.hygienes.net/publication-scientifique/evaluation-de-la-dissemination-des-bacteries-a-partir-des-toilettes-etude-experimentale 34. Kelly SA, O’Connell NH, Thompson TP, et al. Large-scale characterisation

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Infection Control Team (2022). Point of care risk assessment (PCRA) poster. Available at: www.hpsc.ie/a-z/microbiologyantimicrobialresistance/infectioncontrolandhai/posters/PCRAResist45. Department of Health. National Clinical Guideline No 30: Infection Prevention and Control (IPC). Dublin: DOH; 2023. Available at: www.gov. ie/en/search/?organisation=Department+of+Health&q=guidelines Guidelines on hand hygiene in health care: First global patient safety challenge – clean care Is safer care. Geneva, Switzerland: World Health Organization; 2009. Available at: www.who.int/ publications/i/item/9789241597906 Prevention. Healthcare-associated infections: Reduce risk from water. US: CDC; 2019. Available at: www.cdc.gov/ healthcare-associated-infections/php/ toolkit/water-management.html?CDC_ AAref_Val=https://www.cdc.gov/hai/ 48. Kramer A, Seifert J, Gruber B, et al. S2k Guideline: Hygienic requirements for patient beds, bed linen, bed accessories, and personal protection when handling beds. GMS Hyg Infect dgkh000549. 49. Aziz AM. Mattress cleanliness: The role of monitoring and maintenance. Br J Nurs. 2012;21(3):152-157.

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An overview of herpes zoster ophthalmicus Authors: Dr Maria Laf fey, Mb Bch Bao, Medical Intern, St Vincent’s University Hospital, Dublin; and Mr Michael J Gallagher, MML FRCophth, Consultant Ophthalmic Surgeon, and Senior Clinical Lecturer at Trinity College Dublin

erpes zoster (HZ) ophthalmicus is a viral disease caused by the reactivation of the Varicella Zoster virus (VZV), which commonly causes chickenpox, and typically presents in mid to late adulthood. It is, in essence, ‘shingles’ of the face and eye and is characterised by a painful, unilateral vesicular rash distributed throughout one or more of the dermatomes of the trigeminal nerve. The trigeminal nerve provides sensory innervation to the eye and its structures, as well as providing some sympathetic input. Owing to this shared innervation, the eye and its components lie at risk of viral inf iltration leading to potential vision-threatening complications which develop over days to months.

Aetiology VZV is the herpes virus responsible for chickenpox, an infection which occurs typically in early childhood. When this primary infection resolves, the virus lies dormant in the dorsal root ganglia of the spine in the case of most dermatomes which may be af fected. When the virus reactivates, it presents in the form of HZ. HZ is a descriptor for the development of HZ in the distribution of the trigeminal nerve (cranial nerve V) specifically (Figure 1). The aetiology is the same in HZ, apart from the fact that the VZV reactivates via the sensory ganglia of the trigeminal nerve (CNV) as the cranial nerves lack a dorsal root ganglion.

FIGURE 1: Dermatomal distribution of the trigeminal nerve

Epidemiology HZ’s prevalence incidence steadily increases with age, its rates doubling between the ages of 25 and 60 years. The reactivation of VZV is largely driven by a reduction in cellular-related immunity associated with ageing and states of immunosuppression. HZ rates vary by age, with 1.2-3.4 cases per 1,000 in younger populations and 3.911.8 per 1,000 in adults aged over 65 years old. HZ accounts for approximately 10-25 per cent of all cases of HZ, a significant proportion of the yearly millions of HZ cases globally. Incidence rates vary by ethnicity, with Caucasian individuals experiencing the highest rates, and lower rates seen among those of African and Asian descent.

Risk factors As evidenced by the epidemiology of HZ, the major risk factors for its development, and thus the development of HZ, are those of

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increasing age and immunocompromise. Immunosuppression via malignancy, transplantation or HIV, for example, leads to notably severe, resistant, or recurrent presentations. HZ manifests commonly in patients with HIV/AIDS, seen in roughly one in five patients. In cases of severe or unresolving HZ with no clear source of immunosuppression, HIV serology should always be arranged, and its management is crucial not only to the treatment of HZ, but to the quality and length of the patient’s life. Immunosuppression predisposes patients to the development of rarer and more severe complications of HZ such as acute retinal necrosis (ARN), optic neuritis, and panuveitis among others, and should be borne in mind by the treating clinician when dealing with an immunosuppressed patient. Not only are these rare complications more likely, but they also tend to progress more rapidly and result in worse outcomes.

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Other weaker risk associations include female sex, physiological stress, ethnicity, and co-morbidities such as diabetes mellitus, autoimmune disease, and renal disease.

Presentation HZ classically presents as a painful, unilateral, vesicular rash with a dermatomal distribution. Its clinical course, as with HZ eruptions in all areas of the body, is divided into three stages: Pre-vesicular, vesicular, and post-vesicular/recovery. In the pre-vesicular phase, clinical features commonly include neuropathic pain, usually described as a burning or tingling sensation, which will accompany and frequently precede the rash. Some individuals may experience fevers and headaches in this preceding period also. The pre-vesicular phase is the ideal period of illness to commence antiviral treatment, but the vague nature of the symptoms without any visible abnormality results in infrequent attendance at this point. Over the following two to three days, the classical herpetic vesicles will appear, marking the start of the vesicular phase. These blisters will weep, crust over, and eventually heal. In the context of HZ, extension of the rash to the tip of the nose, known as Hutchinson’s sign (Figure 2), indicates the involvement of the nasociliary branch of

FIGURE 2: Unilateral vesicular rash of HZ, which also demonstrates Hutchinson’s sign by its extension to the nose

the ophthalmic branch of the trigeminal nerve shared by the ocular structures and represents an increased risk of ocular involvement and complications. The post-vesicular phase and recovery from HZ can last many months. HZ breakouts are considered chronic when the associated pain lasts for over four weeks. In cases of HZ, the virallymediated ocular manifestations present over the course of days to months and require follow-up and surveillance.

Ocular manifestations Ocular involvement in HZ affects approximately half of patients, and has the potential to affect every structure of the eye, and results in a range of outcomes from irritation to permanent

vitreous humour

FIGURE 3: Anatomy of the eye

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and severe vision loss. Viral infection and inflammation of the eye typically begins anteriorly and progresses with time towards more posterior structures. The anterior elements of the eye consist of the conjunctiva, cornea, and anterior chamber (Figure 3). The eyelids may also be affected. This initial stage of inflammation may become apparent within one to two weeks of HZ onset and presents with hyperaemia, irritation, and watering of the eye. The eyelids and conjunctiva may additionally be affected by vesicles alongside the skin. A viral conjunctivitis, scleritis or episcleritis may develop, all of which can lead to chronic complications such as scarring of the surrounding skin and conjunctiva, resulting in chronic dry eye, which can severely impact on patient quality of life and comfort. Keratitis is one of the most common ocular manifestations of HZ, with disease beginning in the epithelium and progressing deeper into the structures of the cornea over time if not adequately recognised and treated. Infiltration may begin in the anterior stromal layer within one to two weeks, with deep stromal keratitis taking up to a year to develop. The occurrence of a deep stromal keratitis risks the infiltration of the virus into the anterior chamber, resulting in uveitis. Its appearance under fluoroscopy morphs as it develops. It begins as a superficial punctate pattern and develops into a characteristic and easily recognised pseudodendritic pattern (Figure 4). These pseudodendrites differ in appearance to true corneal dendrites seen in primary HSV infection of the eye, though the distinction is not of great importance as the presence of either should prompt immediate referral to an ophthalmologist. Complications specific to keratitis include neurotrophic keratopathy marked by reduced corneal sensation of the eye. This has the potential to lead to corneal ulcers which may go unnoticed by the patient. If not addressed in time, they can become a chronic issue with potential for bacterial superinfection and clouding of the cornea leading to blindness. If disease is allowed

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to progress to this point, the only curative treatment is corneal transplantation. Anterior uveitis can occur alone or in combination with keratitis. Its onset is most typically two to four weeks after onset of HZO. Uveitis commonly drives inflammation of the trabeculae, impeding the outflow of aqueous humour, and increasing intraocular pressure which, if left untreated, leads to glaucoma. Symptoms to be aware of include blurring of vision, ocular pain, and headache. The posterior segment of the uvea may rarely be affected by ARN, which manifests as patches of retinitis that merge and presents as acute onset vision loss in one eye, redness, photophobia, and floaters, like the presentation of retinal detachment, which often also occurs. As previously mentioned, it predominantly presents as a manifestation in the immunocompromised.

Complications Vision loss: Some degree of visual loss may be seen in up to 20 per cent of HZ patients, with severe and total visual loss being rarer. Visual loss is commonly associated with uveitis, with more severe and total loss being associated with immunosuppression, baseline visual acuity, and older age. Just as a positive Hutchinson’s sign increases the risk of ocular involvement in HZ, it also increases the risk of vision loss. Recurrent or chronic disease: Up to 25 per cent of patients will experience recurrence of HZ at least once. Frequent recurrence may be associated with a signif icant psychological burden along with economic impacts owing to the painful and visible nature of the rash. Additionally, each recurrence risks similar eye involvement and all the accompanying complications. Patient education and antiviral therapy as soon as possible is key to management and patients should be given a back-up prescription to keep at home in the case of further outbreaks. Post-herpetic neuralgia: A potentially disabling complication in which the nerve pain associated with HZ persists beyond

rash, then the following must be ruled out as causes: Migraine: Similar in that the pain is unilateral, however, the timeline of pain is shorter and there may be a preceding aura.

FIGURE 4: Pseudodendrites

resolution of the vesicles. Allodynia and hyperalgesia are common and the pain itself is often refractory and requires a combination of both oral and topical medications to treat, which itself can be a challenge due to side effects. Glaucoma: This is a common complication arising from HZ uveitis. As mentioned previously, inflammation and swelling of the trabeculae leads to impaired aqueous outflow, resulting in increased intraocular pressure and glaucoma development. Scarring of the cornea: Secondary to keratitis. Secondary bacterial infection: Particularly of the cornea. Dissemination to encephalitis: Especially in immunocompromised patients, can also lead to more widespread disseminated zoster infection. Stroke: A rare complication caused by a combination of viral inflammation leading to vasculitis and a pro-thrombotic state.

Differential diagnosis Other diseases may mimic HZ. These may broadly be broken down by focusing on conditions with similar rashes, conditions with similar pain, and conditions with similar ocular findings.

Pain dif ferentials If facial pain and neuralgia is the primary complaint with no evidence of a vesicular

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Cluster headache: These headaches are def ined by short bursts of excruciating facial pain. Several will usually occur over the course of weeks, hence the term ‘cluster’. Compression of the trigeminal nerve: Def ined by episodes of intense shooting or shock-like pain that are triggered by as little as toothbrushing or speaking. Giant cell arteritis: Def ined by tenderness over the temporal region.

Rash differentials HZ, by definition, will not cross the midline of the patient’s face and if it does, an alternative diagnosis should be considered. Important differentials to consider for similar vesicular rashes include: HSV infection: This is an important differential. The main difference in presentation will be the pattern of vesicles – small clusters which may cross the midline as opposed to a rash throughout the dermatomal region. As both conditions are caused by viruses from the herpes family, there is commonly a similar prodromal pattern and pain symptoms. The history may offer insight into differentiating between the two. In the case of HSV infection there may be a history of recent cold sore infection or contact as a source of infection. Regardless, treatment remains the same and of great importance, as similar eye disease and complications can occur as do in HZ. Primary VZV infection: Will have a more widespread distribution and potentially a contact history. Contact dermatitis: History of use of a new detergent, cosmetic, etc, in the region and will likely lie outside a dermatomal distribution based on use history.

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Impetigo: The rash will not conform to a dermatomal distribution, and has a less vesicular appearance, though may crust over similarly.

Ocular dif ferentials All the below have been described earlier in this article. In the case of clinical doubt, patients should be referred to ophthalmology:  Conjunctivitis  Episcleritis/scleritis  Uveitis  Glaucoma.

Early recognition HZ is broadly a clinical diagnosis. PCR swabs can be sent to the lab in cases of diagnostic uncertainty, but should not delay treatment or referral in cases of high clinical suspicion. Presumed HZ should be referred early to an ophthalmologist to help reduce the risk of vision-threatening outcomes. Ideally, all cases should be referred and seen, however, cases which present with Hutchinson’s sign, conjunctival/ciliary pain, conjunctival injection, changes in vision, or abnormal eye movements on exam should be prioritised for referral as these signs indicate a higher likelihood of ocular complications.

Treatment Equally important to early recognition is early and effective treatment of HZ. Prompt use of antivirals, particularly in the pre-vesicular phase, reduces the length and intensity of the outbreak as well as reducing the chance of ocular infection and complications, both visual and non-visual. One study demonstrated a reduction in chronic ocular complications of 40 per cent in those who were treated early with antivirals, highlighting the importance of decisive management. Treatment with antivirals should ideally begin within the first 72 hours of illness, though beginning treatment after this window is still valuable, particularly in cases where there is ongoing creation of new vesicles. Many clinicians will

recognise the difficulty of practising and prescribing within this window, as less than 50 per cent of patients with HZ will present within three days of symptom onset, adding another layer of complexity to the management of this condition.  Antiviral treatment regimens vary, but the most common are as follows:  Acyclovir 800mg f ive times daily for seven days  Famciclovir 500mg three times daily for seven days  Valacyclovir 1,000mg three times daily for seven days. Although more expensive, patient preference may guide the prescription of the latter two due to the less frequent dosing regimen and likely increase in medication compliance, which is essential to effective treatment. Ocular complication rates have been shown to be similar across these three options and thus the choice lies in clinician and patient preference. In patients who are immunocompromised, IV acyclovir in the hospital setting may be preferred and in cases of acyclovir-resistant infection, IV foscarnet may be used. There is currently no strong evidence to support long-term antiviral therapy with a view to prevention of longer-term ocular complications. The ZEDs trial has been the only trial to measure this across time and demonstrated non-significance for overall occurrence of complications with antiviral treatment over the course of a year following HZ versus placebo. Supportive measures such as appropriate analgesia, ocular lubricants, and topical corticosteroids are essential. Topical corticosteroids are effective at reducing inflammation of the eye, yet they must not be used prior to commencement of antiviral therapy and ideally should be prescribed by a specialist. Steroids dampen the body’s natural immune reaction, and their use without antiviral medication gives the virus free rein to proliferate and spread, leading to increased risk of complications, particularly acute

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retinal necrosis, although the overall risk remains low. Follow-up visit frequency is based on the presence or absence of ocular involvement. In eye-sparing disease, follow-up at 10-14 days is appropriate. In cases with ocular involvement, initial follow-up is more frequent and varies based on clinical judgement. Ongoing follow-up at six- to 12-month intervals can be used to screen for further late complications.

Prevention Prevention of HZ is dependent on the general prevention of HZ infection. This is now possible with the introduction of ef fective vaccination. Shingrix, a recombinant vaccine now available on the Irish market, has demonstrated a prevention rate of 97 per cent in those >50 years old and 91 per cent in those over 70 years old (ZOE-50 and ZOE-70 phase 3 trials). Meta-analysis has shown Shingrix to have a prevention ef f icacy of 88 per cent against HZ formation. Vaccination is recommended for those aged over 50 years and those over 18 years who are immunocompromised. GPs and practice nurses play a vital role in recognising patients who are eligible for vaccination, and prompting a discussion with them regarding its benef its.

Summary In summary, HZ represents a potentially vision-threatening clinical entity. It is characterised by a painful vesicular rash across the distribution of the trigeminal nerve and risks ocular involvement throughout all the structures of the eye. Its outcomes range from temporary pain and discomfort to vision loss. Early recognition, referral and treatment are essential to prevent permanent damage to the eye. Prevention of HZ occurrence through appropriate vaccination in atrisk populations is our best treatment and will likely become an increasingly important part of tackling this condition in the future. ● References on request

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The impact of a specialist nurse-led oral food challenge and penicillin de-labelling service Authors: Ms Alison Russell, Paediatric Respiratory and Allergy CNS, Midland Regional Hospital Portlaoise; Ms Eimear O’Sullivan,Paediatric staff nurse, Midland Regional Hospital Portlaoise; Dr Muhammad Tariq, Paediatric Consultant with an interest in Respiratory and Allergy, Midland Regional Hospital Portlaoise; and Ms Lisa Egan, Advanced Nurse Practitioner in Paediatric Respiratory, Midland Regional Hospital Portlaoise, Portlaoise, Co Laois

ood allergy af fects one in every 25 children in Ireland.1 Early recognition and intervention are vital when it comes to successful identif ication and management of food allergy in children. Research has shown that only 50 per cent of oral food challenges (OFCs) are positive in patients suspected of having food allergies. 2 This f igure suggests that half of these patients were living under the assumption of an allergy and were unnecessarily avoiding certain foods before their OFC. Penicillin allergies are reported in 10 per cent of the population internationally, with 95 per cent of these penicillin allergy labels deemed incorrect when tested.3,4 Misdiagnosis of penicillin allergy must be addressed since it increases the risk of antibiotic-resistant infections, the duration of hospital admissions, and significantly impacts healthcare costs.5 Despite the increasing presentation of penicillin and food allergy cases, penicillin and OFC testing is scarce in Ireland. Multiple factors contribute to this testing shortage, including a scarcity of day case beds, an overburdened healthcare system, and a lack of adequately trained medical and administrative staff to support the running of a robust allergy service. OFCs are also widely considered to be cumbersome. In their 2021 study, Byrne et al described OFCs as labourintensive, time-consuming, and in need of adequately trained and experienced staff at all times.6 Such inconveniences should

not impede their usage – however, delaying OFCs results in an increased economic burden on the healthcare system and a diminished quality of life for families living with allergies.7 Historically in the Irish public sector, few tertiary centres with specialist allergy teams performed oral challenges, culminating in huge service demand and lengthy waiting lists. Since penicillin de-labelling and OFCs remain the gold standard for the diagnosis of a penicillin or food allergy, appropriately skilled healthcare professionals must provide a safe and effective service in which to conduct these challenges outside of tertiary centres.7 Due to the development of advanced practitioner and specialist nursing roles, as well as the introduction of the MSc in Allergy and Clinical Immunology in Ireland, a secondary care hospital – Midland Regional Hospital Portlaoise (MRHP) – was able to establish a nurse-led OFC and low-risk penicillin de-labelling service in a safe environment. The literature surrounding the practice and safety of nurse-led oral food and

penicillin challenges is limited. This paper aims to explore and document the effects and safety of a specialist nurse-led OFC and penicillin de-labelling service in MRHP. Ultimately, it is hoped that this small-scale piece of research, and its associated findings, will provide sufficient evidence to support further specialist nurse-led OFCs and penicillin de-labelling initiatives throughout Ireland.

Planning In January 2022, a business case was put forward to the senior management team at MRHP requesting the allocation of beds on the adult day ward two days per week during the summer months – when in-patient activity is typically lower. This service would be specialist nurse-led by an advanced nurse practitioner (ANP) and a clinical nurse specialist (CNS) in paediatric respiratory and allergy, and supported by a general paediatrician with an interest in allergy. For efficiency, the ANP and CNS were required to manage all aspects of the service. Safety protocols (including the Children First programme, paediatric

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INCLUSION

EXCLUSION

INCLUSION

EXCLUSION

Minor gastro-intestinal symptoms

Rash occurring within one hour of the first dose of penicillin

Skin prick test <7mm

Patient reports ‘benign’ rash which developed more than one hour after the first dose of a course of penicillin

Rash lasting more than 24 hours and/ or affecting more than 10 per cent of the body surface

History of anaphylaxis to the offending food

Minor symptoms unrelated to any form of allergic reaction, for example, headache

Rash associated with blisters, skin peeling, mucosal inflammation (eyes, mouth, genitals), purpura

Immunoglobulin E (IgE) level </=15kUa/L

Unable to give informed consent

Family history of penicillin allergy but without personal history of allergy

Patients reporting any symptoms suggestive of a type 1 immediate hypersensitivity reaction to penicillin

Tests performed within six months of the OFC

Unstable cardiovascular disease

AraH2 (Arachis hypogaea 2) </=1.0kUa/L for peanut OFC

Poorly controlled allergic rhinitis, eczema, or asthma

Patient reports a childhood rash with no other history available

Patients who required hospital treatment due to their reaction

Patient cannot remember what happened during the index reaction but was told it was not serious and did not require hospitalisation

Patients who required treatment with adrenaline for their reaction

Patients who cannot remember what happened during the index reaction but were told it was serious and/or required medical attention Unable to give informed consent Severe or uncontrolled asthma Patients who, at the time, are being considered for penicillin de-labelling, are acutely unwell, or clinically unstable Pregnancy Previous penicillin allergy testing which concluded that the patient was allergic to penicillin TABLE 1: Inclusion and exclusion criteria for low-risk penicillin de-labelling3

emergency supplies, and risk assessment) were put in place to ensure the safe management of children on an adult ward. The paediatric medical team and the anaesthetics team were informed of the schedule for food and penicillin challenges, and were available to attend the day ward if requested. All qualifying children for the challenges had met inclusion criteria (Tables 1 and 2) outlined by international and local guidelines.3,8,9

Preparation In the absence of clerical support, the ANP and CNS were responsible for managing

all administrative aspects of running this service. A food challenge waiting list was created on Excel, comprising 120 children awaiting at least one food challenge, with an anticipated wait time of 14 months. Simultaneously, a penicillin waiting list was drawn up, comprising 60 children awaiting a low-risk penicillin challenge with a waiting period of up to two years. Before service commencement, pro formas were developed for each challenge to facilitate pre-assessment, GP and medical note correspondence, communication via parent, and discharge information leaflets and assessment

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Unwell or concurrent illness Antihistamines five days prior to the challenge Antibiotics or steroids two weeks before the challenge Used a shortacting betaagonist within the preceding 48 hours for cough or wheeze Pregnancy TABLE 2: Inclusion and exclusion criteria for OFC

documents. All documentation was approved by the local documentation committee and the senior management team at MRHP. Appointment notif ications and parent information leaflets were sent via post and email three to four weeks before the child’s allocated challenge date. Patient medical charts were requested and prepped with documentation. As per the hospital-based OFC dosing schedule, foods being challenged were prepped the day before the appointment and offending penicillin was made available by the hospital pharmacy. Day

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ward bed spaces were prepared, and all safety and infection control and prevention precautions were observed. 8

Challenges Non-double-blinded, open challenges were performed across a six-bedded day ward space. The ANP and CNS carried out advanced physical assessments on the patients before the commencement of the challenges to ensure they were medically fit. The ratio of nurse to patient was 3:1. The OFCs followed the PRACTALL guidelines of incremental dosing with 20-minute intervals between doses.1 Each interval concluded with a clinical assessment from the CNS/ANP to assess for signs of reaction. Challenged foods were prepared by the CNS/ANP with the exception of a mixed cookie, where the child’s parents received a strict recipe to follow and clear instructions to bring this food item with them on the day of the challenge. Six OFCs were of fered every Tuesday. The child and parent were advised to arrive to the day ward at 08.30 with an estimated discharge time of 15.00. Parents were instructed to bring a light lunch and some books/low-impact games for the child to distract them during the challenge. Food challenge outcomes were documented in the child’s medical notes and correspondence was forwarded to their GP. On Wednesdays, non-double-blinded, open penicillin challenges were performed as per the British Society for Allergy and Clinical Immunology guideline.2 Once the child was assessed and deemed medically fit by the supervising specialist nurse, one dose of the offending penicillin was given and the patient was monitored for onehour post-administration for signs of an anaphylactic reaction. Some patients were given a three-day course of penicillin if their initial offending reaction was on a subsequent dose. These patients were directed to update the CNS /ANP after completion of the three-day course so the documentation and the patient’s GP could be updated on the

challenge results. A total of 12 penicillin challenges were offered every Wednesday, with six arriving at 9am and six arriving at 2pm. Before leaving, patients were given a discharge information sheet which advised on signs of a delayed reaction and contact numbers to call if a reaction occurred.

Outcomes Over a five-month period between July and December 2022, 120 OFCs were offered, with an uptake of 86 appointments. Of the 86 food challenges performed, 56 passed their challenge, 28 failed, and two were deemed inconclusive. Sixty-five per cent of children did not react, a figure that is in keeping with Byrne et al’s study, whereby 474 OFCs were carried out in a vacant Covid-19 step-down facility and 69 per cent of patients did not react.6 A 65 per cent OFC pass rate far exceeds the 50 per cent rate generally cited in the research.2 Of the 86 children who presented for OFC, only 35 per cent had a positive reaction to the tested/suspected allergen, suggesting that the number of children with proven allergies may be significantly lower than anticipated. In terms of age range, 40 per cent of participating patients were under f ive years old, while the remaining 60 per cent were between f ive and 15 years at the time of the challenge. Forty per cent (35) of the OFCs were peanut; 50 per cent (43) were tree nut, and the remaining 10 per cent (8) were f ish, sesame, oat, tomato, kiwi,

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and wheat. Of the 28 failed challenges, nine were peanut, with one requiring adrenaline. Six (7%) patients were treated as per the anaphylaxis protocol; this is also similar to the results found by Byrne et al, whereby 5 per cent were treated with the anaphylaxis protocol. 6 Four patients required one dose of adrenaline, with two reacting to walnut, one to hazelnut, and one to peanut. In all instances, the ANP and CNS assessed, treated, and managed the anaphylaxis safely, and the patient was discharged home that evening, four hours after the treatment had been given, with no adverse effects. Two patients required two doses of adrenaline (cashew x 1 and almond/pine nut mixed cookie x 1). These were the only two patients who required medical review by the paediatric registrar for intravenous cannulation, fluids, and admission for overnight observation to the paediatric ward. They were discharged early the following morning. No child received advanced airway interventions. A total of 18 patients who failed their challenge recovered with antihistamines, while two did not require any treatment, only observation. Moving to the results of the penicillin challenge, there were 72 low-risk penicillin de-labelling appointments offered between July and September 2022 (two-month period), with an uptake of 55, and a total of 53 of these patients passed their penicillin challenge. Two patients failed – one developed three hives at home that evening, and one developed a rash the following day – non-urticarial or itchy. Due to the success of the service, the senior management team extended the day ward facility from a summer-time service to six bed spaces per week, and six OFCs were offered up until December 2023. Subsequently, the OFC waiting list was reduced from 14 months to five months. The waiting list for a low-risk penicillin de-labelling appointment was cleared after the summer of 2022. Due to its success, the senior management team offered these beds again in the summer of 2023 for any new penicillin de-labelling appointments.

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The efficient response of the respiratory and allergy team at MRHP to service needs and patient safety ensured the prompt issuing of appointments and appropriate diagnosis of all children participating in the OFC and low-risk penicillin delabelling clinics. With 96 per cent passing their penicillin challenge and 65 per cent passing their OFC, the impact of these results is far-reaching, culminating in enhanced quality of life, reduced anxiety for the child and their families, and greater health outcomes. The conf irmation of a food allergy resulted in the patient being trained appropriately on food avoidance and ef fective management of an allergic reaction. Demonstrating that a patient was not allergic to penicillin reduced the impact of second-line antibiotics on the individuals, such as antibiotic resistance and longer hospital stays, thus improving safety outcomes and compatible treatment options for individuals attending the paediatric respiratory and allergy service at MRHP.

Discussion At MRHP, the allergy and respiratory team adopted the model of care rolled out by Byrne et al where empty day case beds were used in a vacant Covid-19 step-down facility during periods of pandemic-related inactivity to decrease waiting lists.6 A similar approach was taken in this study – during quieter periods of the year when winter-time respiratory illnesses are typically lower, vacant day case beds were reassigned to maximise an exceptional opportunity to decrease waiting lists for both OFCs and low-risk penicillin delabelling clinics at MRHP.

Of the 86 OFCs performed at MRHP during the f ive-month period, only 35 per cent of children had a positive reaction to their suspected allergen. These results indicate that the rate of verif ied food allergy in children may be signif icantly lower than anticipated and further strengthen the case for increased specialist nurse-led initiatives to expedite OFC testing nationwide and reduce the number of children who are avoiding foods unnecessarily. 2 The 96 per cent pass rate achieved in the 55 low-risk penicillin de-labelling appointments mirrors the findings of Blumenthal et al.5 With less than 5 per cent of allergy labels being deemed correct when tested, this signals an alarmingly high rate of current penicillin allergy misdiagnosis in Ireland. The addition of a highly skilled team with specialist training in food allergy management was instrumental in the success of the initiative to reduce paediatric waiting times for OFCs and low-risk penicillin de-labelling appointments at MRHP. Advanced practice nursing is defined as the ability to practice at a higher level of capability as an independent, autonomous, and expert practitioner, and the CNS’s role encompasses a major clinical focus on patients and their families in hospital, providing expert care, education, and training to the patients in their care.10 A publication titled the ‘Final Evaluation Report on the Impact of Implementing the Policy on Graduate, Specialist, and Advanced Nursing Practice’ demonstrated the positive impact on patients and services through the addition of advanced nurse practitioner and specialist roles.10

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It also highlighted the central role that ANPs and other specialist nursing roles play in creating positive change for patients and services.10 Significantly, the report identified that each ANP removes 3.9 patients per week on average from specialist waiting lists. By combining their knowledge and skillsets, the ANP and CNS significantly impacted paediatric waiting lists and patient outcomes at MRHP. Considering the impact on challenge lead times alone at the hospital, the OFC waiting list was reduced from 14 months to five, while the low-risk penicillin delabelling appointment list was reduced from two years to 0 months. Further allocation of dedicated bed spaces to the OFC offering at MRHP would ensure that waiting lists remain at less than six months at all times. The OFC and penicillin de-labelling service at MRHP was nurse specialist-led, with support from the paediatrician with an interest in allergy and respiratory. By increasing the specialist nursing allergy services within the hospital in the past f ive years, the allergy and respiratory service has been able to double the number of oral challenges conducted. The positive outcome of this initiative advocates for further collaboration between specialist nursing roles in secondary care facilities nationwide. This paper establishes the safety of OFCs and low-risk penicillin de-labelling tools when administered by trained and experienced clinicians, in this case, nursing specialists.6 The appropriate training of nursing staff plays a critical role in the safety of the initiative, ensuring that nursing specialists can deliver a safe, efficient service with the autonomy to make key decisions regarding patient care. With appropriately trained personnel and a safe environment, these challenges and associated outcomes can be replicated in other secondary care facilities across Ireland. This initiative could act as a blueprint for transforming the way hospital management and nursing specialists

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address the OFC and low-risk penicillin waiting list issue in hospitals nationwide. By adopting the model of care demonstrated by Byrne et al,6 the specialist nursing team at MRHP rolled out an innovative OFC and penicillin de-labelling service, facilitated by shortterm access to day case beds during a quieter period. This solution maximised the hospital’s existing resources which ensured the rapid approval and deployment of the service within the hospital. A nationwide roll-out of this initiative would signif icantly reduce waiting lists, demands on allergy services, and the burden on patients living with allergies. A limitation of this study was its small sample size – 86 OFCs and 55 low-risk penicillin de-labelling challenges. When compared to the more robust sample sizes of Byrne et al,6 the signif icance of the results was impacted by the limited scale of the study. Additionally, the lack of available research prevents comparison with other specialist nurse-led challenges, further emphasising a need for significant time and resource investment to encourage

References

1. Irish Food Allergy Network. Food Allergy Overview. Available at: www.ifan. ie/food-allergy-in-summary/. 2. Beigelman A, Strunk RC, Garbutt JM, et al. Clinical and laboratory factors associated with negative oral food challenges. Allergy Asthma Proc. 2012;33(6):467-473. doi:10.2500/ aap.2012.33.3607. 3. Savic L, Ardern-Jones M, Avery A, et al. BSACI guideline for the setup of penicillin allergy de-labelling services by non-allergists working in a hospital setting. Clin Exp Allergy. 2022;52(10):1135-1141. doi:10.1111/ cea.14217. 4. Vyles D, Antoon JW, Norton A, et al. Children with reported penicillin allergy: Public health impact and safety of delabeling. Ann Allergy Asthma Immunol.

more specialist nurse-led initiatives in this area. Only when there is a wealth of robust research demonstrating the effectiveness of specialist nurse-led challenges, will specialist nurse-led solutions be established as reputable, scientifically sound, and trusted routes to addressing these waiting lists and testing issues.

Conclusion This paper demonstrates the feasibility and safety of a specialist nurse-led challenge in a secondary hospital setting in Ireland. Its ability to deliver a full circle of care – encompassing assessment, diagnostics, challenges, and appropriate support following discharge – positions this nurse-led initiative as a new and innovative approach to tackling excessive waiting times for OFC and penicillin delabelling appointments in Ireland. This project has shown that it is possible to safely and efficiently reduce OFC and penicillin de-labelling appointment lead times via a specialist nurse-led strategy. The success of this initiative calls for reformed thinking in hospitals across Ireland. This will ensure that nursing specialists are situated at the heart of safe,

2020;124(6):558-565. doi:10.1016/j. anai.2020.03.012. 5. Blumenthal KG, Huebner EM, Fu X, et al. Risk-based pathway for outpatient penicillin allergy evaluations. J Allergy Clin Immunol Pract. 2019;7(7):2411-2414. e1. doi:10.1016/j.jaip.2019.04.006. 6. Byrne AM, Trujillo J, Fitzsimons J, et al. Mass food challenges in a vacant Covid-19 stepdown facility: Exceptional opportunity provides a model for the future. Pediatr Allergy Immunol. 2021;32(8):1756-1763. doi:10.1111/ pai.13580. 7. Couch C, Franxman T, Greenhawt M. The economic effect and outcome of delaying oral food challenges. Ann Allergy Asthma Immunol. 2016;116(5):420-424. doi:10.1016/j.anai.2016.02.016. 8. Sampson HA, Gerth van Wijk R,

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effective solutions that will address the OFC and penicillin de-labelling service waitlist issue nationwide. The success of this study can be partially attributed to the positive collaboration between nursing specialists and senior management at MRHP. For successful simulation of these results, senior management must foster a supportive environment, empowering specialist nursing staff through the provision of resources, education, and time. ●

The completion of this research paper would not have been possible without the support and guidance of the senior management team in MRHP. We would also like to express our deepest gratitude to our work colleagues for their continuous support. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Bindslev-Jensen C, et al. Standardising double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma, and Immunology – European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012;130(6):1260-1274. doi:10.1016/j. jaci.2012.10.017. 9. Muraro A, Werfel T, HoffmannSommergruber K, et al. EAACI food allergy and anaphylaxis guidelines: Diagnosis and management of food allergy. Allergy. 2014;69(8):1008-1025. doi:10.1111/all.12429. 10. Office of the Nursing and Midwifery Services Director (2020). Evaluation of the impact of implementing a draft policy to develop advanced nurse practitioners (cANP’s/RANPs) to meet health service needs. Final report.

Immunology

Why sepsis attacks the barriers that protect us Author: Steven W. Kerrigan, Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin 2, Ireland.

epsis is a disorder of the host response in which infection triggers processes that damage organs and impair recovery. Inf lammatory activation and inef fective antimicrobial immunity can coexist, making the description of a cytokine storm incomplete. Endothelial and epithelial barriers provide a useful focus for understanding how this dysregulated response becomes tissue injury. Glycocalyx degradation, disruption of cellular junctions, and interactions between platelets, neutrophils, and coagulation can undermine vascular integrity, while epithelial injury compromises organ-specif ic functions. These observations support investigating barrier protection as an adjunct to antimicrobial treatment and organ support. This article examines the rationale, selected experimental evidence, and the patient selection and safety questions that must be resolved before barrier-directed approaches can enter clinical practice.

Why treating infection may not prevent organ dysfunction If we consider a 67-year-old woman with community-acquired pneumonia. She is tachypnoeic, hypoxaemic, and newly confused. Following urgent referral, she receives antimicrobial treatment and physiological support. Over the next 24 hours, however, her oxygen requirement increases, urine output falls, and hypotension develops. She requires critical care despite treatment that appears appropriate for the infection.

This scenario introduces a familiar question. How does an infection in one organ become dysfunction of several organs? Persistent infection, inadequate antimicrobial coverage, and complications remain possible explanations. But deterioration also directs attention towards the biological response to infection and the tissue structures that response can damage. Sepsis is def ined as life-threatening organ dysfunction caused by a dysregulated host response to infection.1 Bloodstream infection is not required. The def inition invites us to consider mechanisms through which the host response undermines organ function, as well as the microorganisms that initiate illness. One potentially modifiable link is the failure of tissue barriers. The argument for targeting these barriers is that preserving their integrity might limit the conversion of immune activation into organ injury while antimicrobial treatment addresses the infection. This is a rationale for therapeutic investigation, with established sepsis care remaining essential.2

Immune dysregulation Recognition of microbial components activates immune pathways that recruit inflammatory cells and support pathogen clearance. This response needs to occur in the appropriate location and at an intensity the surrounding tissue can tolerate. Injured cells release additional danger signals, allowing tissue damage itself to sustain inflammatory activation. The description of sepsis as a cytokine storm captures excessive inflammation but gives an incomplete account of

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immune function. In the Genetic and Inf lammatory Markers of Sepsis (GenIMS) study, patients hospitalised with pneumonia frequently had simultaneous proinf lammatory and antiinf lammatory cytokine responses. High concentrations of both interleukin-6 and interleukin-10 were associated with the greatest mortality risk.3 These measurements describe inf lammatory activity; they do not, by themselves, establish functional immunoparalysis. Human tissue studies also demonstrate impaired immunity. Boomer and colleagues identif ied reduced immunecell responsiveness, lymphocyte depletion, and increased inhibitory signalling in patients who died with sepsis. 4 Although these f indings cannot def ine the immune state of every patient, they help explain why inf lammatory activation and inef fective antimicrobial defence can coexist. The therapeutic problem is therefore more complex than reducing inflammation. A treatment must address a damaging process without aggravating an existing def icit in host defence. Tissue barriers of fer a complementary focus because they are the interfaces at which circulating inflammatory signals, immune cells, and organ physiology meet. Preserving these interfaces could help maintain tissue function even while the immune response remains dysregulated.

Vascular barrier injury The endothelium forms the interface between blood and tissues. It regulates permeability and leukocyte recruitment while contributing to vascular tone and

Immunology

haemostasis. During infection, changes in endothelial behaviour can af fect several of these functions together. Its role in sepsis extends beyond being a passive surface exposed to circulating cytokines. The endothelial glycocalyx is a carbohydrate-rich layer on the vessel’s luminal surface. It contributes to vascular homeostasis and regulates interactions between circulating cells and the vessel wall. Damage to this layer can change the accessibility of endothelial adhesion molecules, creating conditions that favour inflammatory-cell attachment. Schmidt and colleagues demonstrated that heparanase-mediated degradation of the pulmonary endothelial glycocalyx promoted neutrophil adhesion and lung injury in experimental sepsis. 5 The signif icance is the feedback this identifies. Inflammation damages the endothelial surface, and that damage facilitates further inflammatory recruitment. Barrier injury can consequently participate in amplification of the response. Cellular junctions provide another point of vulnerability. VE-cadherin is an important component of endothelial adherens junctions. Changes in signalling and junctional organisation can increase permeability, allowing fluid and plasma proteins to move into surrounding tissues. In experimental SARS-CoV-2 studies, Nader et al linked αVβ3 integrin signalling to disruption of endothelial junctions and showed protection with integrin antagonism. These f indings establish a mechanistic example in viral infection that holds true in bacterial induced sepsis also.6 This biology gives capillary leak a more precise meaning. The structures controlling movement

between blood and tissue have become dysfunctional. The resulting oedema can compromise tissue function, although permeability injury is one contributor among several, including altered vascular regulation and cellular dysfunction. For therapeutic development, the distinction between endothelial activation and destructive barrier failure matters. Leukocyte traf f icking is necessary for infection control. The goal should be to preserve regulated barrier function while allowing an ef fective local immune response, rather than preventing all endothelial responses to infection.

Epithelial dysfunction A focus on tissue barriers should include the epithelium as well as the endothelium. The lung illustrates why. Its alveolar-capillary interface separates circulating blood from the airspaces in which gas exchange occurs. Endothelial permeability and alveolar epithelial function influence dif ferent aspects of fluid movement and recovery. Protecting one side of this interface may be insuf f icient if the other remains severely injured. Alveolar epithelial function includes clearing fluid from the airspaces. In a study of 79 patients with acute lung injury or acute respiratory distress syndrome, Ware and Matthay found impaired alveolar fluid clearance in the majority. Maximal clearance was associated with lower mortality and a shorter duration of mechanical ventilation.7 This observational study does not prove that restoring clearance improves outcomes, but it highlights the clinical relevance of epithelial function alongside vascular permeability.

A mechanism demonstrated in the lung cannot automatically be assumed to operate identically in the kidney or brain 56

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For a patient with pneumonia, this widens the therapeutic question. Could an adjunctive treatment help preserve the interface needed for gas exchange and the epithelial functions needed to resolve oedema? Answering this requires measurements of both permeability and tissue function. A reduction in one marker of vascular injury would not establish recovery of the complete alveolar-capillary barrier. The pulmonary example also helps define the limits of a broad barrier argument. Different organs have different epithelial and endothelial arrangements. A mechanism demonstrated in the lung cannot automatically be assumed to operate identically in the kidney or brain. The case for tissue barrier protection is strongest when the affected interface and its contribution to organ injury are specified.

Platelets and neutrophils Barrier dysfunction occurs within a wider immune and haemostatic response. Platelets and neutrophils can cooperate to contain microorganisms, but these interactions may also promote vascular obstruction when they become extensive or poorly controlled. Clark and colleagues demonstrated that platelet Toll-like receptor 4 signalling promoted neutrophil extracellular trap formation in septic blood. 8 These traps, commonly called NETs, contain DNA, histones, and antimicrobial proteins. They can capture microorganisms and provide a scaf fold for coagulation. McDonald and colleagues subsequently demonstrated NET-platelet interactions promoting thrombin generation and microvascular occlusion in mouse sepsis models.9 These studies connect an antimicrobial mechanism with a potential loss of tissue perfusion. They also caution against treating all immunothrombosis as pathological – its local containment function is part of host defence. Endothelial injury, permeability changes, and coagulation disturbances need to be considered together when evaluating an intervention’s ef fects.

Immunology

Human microcirculatory imaging has shown reduced and heterogeneous smallvessel perfusion in sepsis, with more marked abnormalities in patients with poorer outcomes.10 This helps explain why a satisfactory blood pressure may coexist with impaired perfusion within tissues. It does not establish that barrier protection alone will correct those abnormalities. Trials should assess whether preserving vascular integrity translates into improved organ function, rather than assuming that less leakage necessarily means better perfusion.

The case for barrier protection The evidence supports treating barrier failure as a candidate therapeutic target. It identif ies vulnerable structures, mechanisms of injury, and experimental opportunities to modify them. A barrierdirected approach could complement pathogen clearance by preserving the tissue environment in which recovery must occur. The angiopoietin-Tie2 pathway provides one example. Han and colleagues developed an angiopoietin2-binding antibody that activated the endothelial receptor Tie2. In three mouse sepsis models, the intervention protected vascular integrity and improved survival, with ef fects on the glycocalyx, vascular leakage, and organ damage.11 This is experimental evidence that modifying endothelial signalling can influence the course of sepsis. Whether those ef fects can be reproduced safely in patients remains a clinical question. The glycocalyx of fers another mechanistic focus. The heparanase experiments demonstrate that degradation of the endothelial surface can contribute to inflammatory recruitment and lung injury. 5 They support investigating ways to limit destructive glycocalyx loss. They do not establish that replacing glycocalyx components or inhibiting degradation will provide the same benef it in human sepsis. Integrin signalling provides a further route through which infection can af fect cellular junctions.

Our experimental work on αVβ3 and endothelial barrier disruption in SARSCoV-2 infection illustrates the possibility of interrupting an injury pathway at the tissue interface.6 It sits within the broader case for barrier protection and should be evaluated alongside other approaches. Evidence from a particular pathogen and experimental model cannot establish ef f icacy across the heterogeneous sepsis population. The proposed advantage of barrier protection is preservation of organ function during infection. Its compatibility with antimicrobial defence must be demonstrated. Endothelial and epithelial signalling also supports normal traf f icking and repair, so dose, treatment duration and biological context could determine whether an intervention is protective or harmful. Experience with other host-directed approaches reinforces the need for clinical testing. In the SCARLET randomised trial, recombinant soluble thrombomodulin did not signif icantly reduce 28-day mortality in patients with sepsis-associated coagulopathy. 12 This was a coagulation-directed intervention, rather than a direct test of junctional protection, but it illustrates the distance between a compelling vascular mechanism and an ef fective sepsis treatment. The appropriate claim is therefore specif ic. Barrier protection merits investigation as an adjunctive therapeutic strategy because barrier injury contributes to processes relevant to organ dysfunction. The magnitude of that contribution, its reversibility, and the consequences of modifying it need to be established in the patients selected for treatment.

Identifying patients and treatment window A barrier-directed treatment should be tested in patients whose illness involves the mechanism it is intended to modify. Sepsis includes dif ferent organisms, infection sites, and stages of injury. Host-response genomic studies in pneumonia-associated sepsis have identif ied biological subgroups with dif ferent characteristics and outcomes. 13 A common syndrome def inition does not guarantee a common treatment-responsive state. Biomarkers may help, but prognosis and treatment selection are dif ferent tasks. In a cohort of 757 patients with sepsis, higher early plasma angiopoietin-2 concentrations were associated with acute respiratory distress syndrome and mortality. 14 This supports investigating endothelial biomarkers for trial enrolment. It does not establish a threshold at which Tie2directed or other barrier therapies will work. Soluble urokinase plasminogen activator receptor, or suPAR, has also been studied for prognostic assessment alongside APACHE II. 15 Its prognostic value does not establish that it specif ically identif ies barrier failure or predicts benef it from integrin modulation. A companion diagnostic would need to demonstrate that it helps identify patients who benef it from a particular treatment. Timing deserves equal attention. Preventing junctional disruption before extensive organ injury and promoting recovery af ter established damage are dif ferent therapeutic aims. Trials should def ine which aim they

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Immunology

are testing, conf irm target engagement, and measure patient-centred outcomes such as organ-support requirements and survival. Improved laboratory permeability or a lower biomarker concentration can support a mechanism without establishing clinical benef it.

The sepsis research agenda Returning to the patient with pneumonia, barrier biology of fers a way to connect increasing oxygen requirements and tissue oedema with the host response. It also suggests a therapeutic question that is relevant before infection-associated injury becomes extensive – can vulnerable tissue interfaces be preserved while infection is treated? Current management still depends on prompt antimicrobial treatment, source control where indicated, repeated assessment, and appropriate

References 1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. 2. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2026. Crit Care Med. 2026. 3. Kellum JA, Kong L, Fink MP, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167(15):1655-1663. 4. Boomer JS, To K, Chang KC, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594-2605. 5. Schmidt EP, Yang Y, Janssen WJ, et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med. 2012;18(8):1217-1223.

organ support.2 Investigational barrier therapies would be added to that care. They should be judged on whether they improve meaningful outcomes without compromising infection control or recovery. The case for prioritising this work rests on the position of tissue barriers between immune activation and organ function. Understanding immune dysregulation is essential, but preserving the structures through which that response af fects tissues may of fer an additional opportunity to prevent injury. Barrier protection deserves a def ined place in sepsis research, supported by evidence of the relevant mechanism, a realistic treatment window, and trials designed to establish benef it for patients.

Key messages  Immune activation and impaired antimicrobial defence can coexist in sepsis.  Endothelial and epithelial dysfunction

6. Nader D, Kerrigan SW. Molecular cross-talk between integrins and cadherins leads to a loss of vascular barrier integrity during SARS-CoV-2 infection. Viruses. 2022;14(5):891. 7. Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;163(6):1376-1383. 8. Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13(4):463469. 9. McDonald B, Davis RP, Kim SJ, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129(10):1357-1367. 10. De Backer D, Creteur J, Preiser JC, et al. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166(1):98-104. 11. Han S, Lee SJ, Kim KE, et al. Amelioration of sepsis by TIE2

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provide complementary targets for understanding infection-associated organ injury.  Experimental studies support investigating barrier protection alongside treatment of infection.  Successful translation requires patient selection, evidence of target engagement, and preservation of ef fective host defence.  Clinical benef it must be demonstrated through meaningful patient outcomes. ●

Address for correspondence: Prof Steven W Kerrigan, Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences 123 St. Stephen’s Green, Dublin 2 Email: skerrigan@rcsi.ie

activation-induced vascular protection. Sci Transl Med. 2016;8(335):335ra55. 12. Vincent JL, Francois B, Zabolotskikh I, et al. Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: The SCARLET randomised clinical trial. JAMA. 2019;321(20):1993-2002. 13. Davenport EE, Burnham KL, Radhakrishnan J, et al. Genomic landscape of the individual host response and outcomes in sepsis: A prospective cohort study. Lancet Respir Med. 2016;4(4):259-271. 14. Rosenberger CM, Wick KD, Zhuo H, et al. Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis. Crit Care. 2023;27:234. 15. Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V, et al. Risk assessment in sepsis: A new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care. 2012;16(4):R149.

Immunology

Reducing the rate of S aureus bloodstream isolates associated with PVCs Author: Grace Kinahan, MSc, RGN, RM, ANP, RNP Assistant Director of Nursing Infection Prevention and Control, Midlands Regional Hospital, Tullamore, Co Offaly

eripheral intravenous catheters (PVCs) are frequently linked to complications.¹ Up to 60 per cent of hospitalised patients receive at least one cannulation during an admission.² PVC-related bloodstream infections (PVC-BSIs) can significantly impact patients by increasing morbidity and mortality, prolonging hospital stays, and leading to serious complications such as intensive care admission and death.3,4 Infection prevention and control (IPC) measures have evolved to reduce PVCBSI rates and include the introduction of aseptic non-touch technique (ANTT), care bundles, visual infusion phlebitis scores, and intravenous (IV) care teams. In Model 4 hospitals in Ireland, IV teams have been established in eight sites, in collaboration with the HSE Antimicrobial Resistance and Infection Control (AMRIC) Team, to improve surveillance and national practice. One of the core objectives of the HSE’s RESIST campaign for prevention of peripheral and central venous catheter (CVC)-related infection is to reduce the use of venous catheters in situations where they are not strictly required. The Health Protection Surveillance Centre Point Prevalence Study (2023) reported that 19.7 per cent of 12,650 patients had at least one invasive device in situ, an increase from 18.7 per cent in 2017 and 16.3 per cent in 2012 – indicating that the prevalence of invasive device use among Irish hospital inpatients has increased over time.5 Quality improvement projects (QIPs)/ initiatives that implement, measure, and monitor outcomes are essential to sustain improvements. However, factors

such as hospital model, organisational structure, leadership, patient acuity, and practice gaps must be addressed to improve patient outcomes. This article examines the impact of an IPC QIP, implemented over three years to decrease the incidence of PVC-BSIs, with specific emphasis on Staphylococcus aureus (S aureus), in a Model 3 hospital serving the Midlands region of Tullamore, Co Offaly.

PVCs and BSI Peripheral vascular catheterisation is a fundamental component of modern hospital care – however, it carries a recognised risk of BSI if not managed optimally. PVC-BSIs contribute significantly to patient morbidity but are largely preventable through adherence to evidence-based insertion and maintenance practices.6,7,8 With increasing emphasis on healthcareassociated infections (HAIs), surveillance has become a core function of IPC. The study highlights the importance of sustained institutional ef forts to maintain HAIs – including PVC-related bacteraemia – at the lowest achievable levels. 8,9,10 Healthcare organisations now routinely collect standardised HAI data to monitor internal performance and benchmark outcomes against national and international standards. Robust surveillance systems facilitate early trend detection, inform targeted interventions, and strengthen accountability and patient safety.8 Key performance indicators (KPIs) for acute hospital HCAIs are closely monitored, including structured review processes for rates exceeding targets. These reviews require hospital commentary, root cause analysis where appropriate,

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and documentation of corrective actions undertaken by the IPC team. Sustained improvement depends on continuous monitoring, visible leadership support, multidisciplinary collaboration, and the integration of IPC practices into routine clinical care. Embedding these strategies within organisational culture promotes long-term compliance, reinforces quality improvement, and supports the maintenance of low infection rates over time.6 This QIP aimed to review PVC-associated infection rates over a three-year period. It compared outcomes before and after the introduction of a comprehensive multimodal prevention strategy that maintained a constant focus on improving infection rates at every quarter (Q).

The QIP The project took place in a Model 3 hospital (Midlands Regional Hospital Tullamore [MRHT]) that provides a broad range of acute and regional services to the population of the midland region in Ireland. A retrospective review of hospital infection surveillance data was conducted from January 2022 to December 2025. Aims of the QIP were as follows:  To reduce the number of hospitalacquired and healthcare-associated S aureus BSI (SABSI).  To reduce the use of venous catheters.  To reduce the incidence of other adverse effects resulting from use of venous catheters.  To promote the use of the review tool for hospital acquired S aureus BSI.  To educate staff on ANTT and PVC care.  To update the care bundle process.

Immunology

Implementation of the multimodal interventions began in Q4 2022 (Table 1) with the introduction of the following actions:  Structured staff education and competency  Standardised skin antiseptic and PVC insertion packs  Audit and feedback mechanisms and surveillance. The evaluation occurred in cycles as each new action was introduced.

Competency The staff education component of the QIP was implemented over a three-month period, from February 2023 to April 2023, and occurred in a series of steps: Step 1: February 2023 was designated ‘PVC and ANTT Awareness Month’ across the hospital to raise awareness of best practices in PVC care and ANTT. HSE eLearning portal educational materials and guidance on hand hygiene, aseptic technique, and prevention of PVC- and CVC-related infections were recommended to all staf f to support this training. Step 2: In February 2023, a hospital-wide awareness day was also held to promote the initiative and highlight the importance of preventing PVC-BSIs. The IPC team held an education stand outside the canteen at the start and middle of February to discuss and promote ANTT with all staf f. Over 100

healthcare professionals engaged with the stand and feedback was positive. Step 3: Ward-based nursing staff received ANTT training, focusing on aseptic practice during PVC insertion and ongoing catheter care during this initial period.

Introduction of standard skin antiseptic, PVC packs, and trolleys Step 1: In Q1 2023, a business case was submitted to the drugs and therapeutics department for approval for chlorhexidine 2 per cent in 70 per cent alcohol (ChloraPrep) as the standard skin antiseptic for blood culture collection, PVC insertion, and CVC insertion, in line with national AMRIC guidance. While no financial support was received from the providers of ChloraPrep, the company did assist with the roll out of this initiative by providing education and support to all nursing and medical teams across the hospital. The business case was approved in Q1 of 2023, and Nursing Grand Rounds – formal learning forums that bring together nursing and healthcare professionals to analyse challenging clinical cases, share evidenceinformed approaches, and engage in professional development discussions – was scheduled for Q2 in April to introduce this to all healthcare professionals that had a role in PVC insertion and its management in MRHT.

RECOMMENDATION

RESPONSIBLE PERSON

Ensure medical staff are appropriately trained

Clinical Director

Action plan to IPCN from CNMs following circulation of care bundle results

CNMs

Full completion of PVC documentation on all patients to include insertion/ongoing maintenance details

NCHD/S/N

Incident form to be completed on all patients who develop a SABSI

IPCN/CNM/NCHD

Education of staff on ANTT relating to PVC insertion

IPCN

Sharing of learning from RCA recommendations

Clinical Director/IPC committee

Promote HSeLanD modules on ANTT

IPCN/Clinical Director

Assessment of risks associated with PVC

IPCN/IPC Committee

Quarterly validation in all areas of care bundle compliance

IPCN

Display of AMRIC PVC poster in all wards

IPCN

Display of patient information poster on PVC care

IPCN

TABLE 1: IPC strategy including roles and responsibilities

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Step 2: The key personnel in clinical areas were then contacted to arrange training on best practice in skin antisepsis for all nursing and medical teams. This education ran from April to July (2023). A refresher day was then held in MRHT in October to support IPC Awareness Day. Step 3: Standardised PVC insertion packs were then introduced to ensure that all staff had access to the required equipment (Q3 2023 – Q4 2023). The packs contained the following:  Single use tourniquet  Sterile drape  Sterile gauze  Transparent semi-permeable dressing. Step 4: Existing blood culture packs were aligned with the new PVC packs to promote a consistent approach to skin disinfection and aseptic practice across all vascular access procedures. Step 5: (Q2 2023 – Q4 2023) Each ward was provided with a PVC trolley to ensure ease of access for staff inserting cannulas and taking blood cultures. Managers were provided with advice about ordering the ChloraPrep and PVC/ blood culture packs. Images of what the trolleys should look like, with appropriate labels attached, were provided to each ward manger and the IPC team assisted in the set-up of the trolley. Step 6: (Q2 2023) With the support of the patient safety nurse, a patient information poster was also developed on how to care for their own cannula. The images were created and shared to the wards for patients and staff to view.

Audit, feedback, and surveillance The audit and feedback component of the QIP was implemented as follows: The previous audits and surveillance rates were reviewed for every Q for years 2022, 2023, 2024, and 2025. All results were reported to the IPC committee and to the business intelligence unit, where results are compared with data from the Dublin Midland Hospital group for further learning, and surveillance

Immunology

rates were recorded as a KPI. Step 1: To gain an understanding of how many PVCs were in use, a PVC audit was completed in MRHT in September 2022 (Figure 1). A total of nine inpatient wards housing 157 patients were included in the audit. The results showed that 90 patients had a PVC inserted on the day of the audit (57%). Other concerns noted at the time of the audit were signs of infection and soiled dressings, which highlighted the need to review current practices and the care bundle process that was already in place. Step 2: The existing PVC insertion care bundle was reviewed and updated to ensure alignment with current evidence-based practice and infection prevention guidelines (Q1 2023 and Q1 2024). This required daily assessment of catheter necessity, inspection of the insertion site for signs of infection or complications, assessment of dressing integrity, documentation of ongoing catheter care, and prompt removal of PVCs that were no longer clinically required. Step 3: The PVC care bundle audit process was revised for nursing staff (Q1 2023). Staff nurses were responsible for completing care bundle audits, while clinical nurse managers implemented an action plan if their ward did not achieve 100 per cent compliance.

Step 4: In Q2 2024, the MEG audit tool was introduced to the nursing staff to electronically record audit findings, monitor compliance trends, and facilitate data collection. Step 5: Audit results were reported quarterly to the IPC committee. Quarterly reports were, and still are, communicated to the ward managers. The results were discussed with their teams and displayed on the notice boards. Areas of noncompliance were identified, and feedback was provided to clinical teams to support quality improvement and sustained adherence to best practice. Step 6: Working closely with the surveillance scientists, an enhanced observation of PVC-BSIs was maintained throughout the project to monitor outcomes and evaluate the impact of the interventions.

Interventions and the evidence-base PVC care bundle process Although the care bundle process was already established within the hospital, a review identified opportunities to strengthen compliance monitoring,

documentation, feedback mechanisms, and staff engagement. As a result, the existing process was updated as part of the QIP. Rationale: Evidence has demonstrated that the implementation of PVC care bundles, together with staff education, audit, and feedback, can reduce catheter-related BSIs and improve patient safety.6,7 Effective measures include hand hygiene compliance, staff education and training, surveillance and monitoring, audit and feedback, use of evidence-based care bundles, and improved catheter and device management.7 Therefore, the rationale for reviewing and strengthening the PVC care bundle process at MRHT was to reduce variation in practice, improve compliance with evidence-based care, enhance patient safety, and ultimately reduce the incidence of PVC-BSIs.

Skin asepsis The introduction of 2 per cent chlorhexidine in 70 per cent alcohol for pre-procedure skin asepsis formed an important component of the prevention strategy. Rationale: Research indicates that appropriate skin preparation or cutaneous antisepsis prior to PVC insertion plays a key role in preventing PVC-BSIs.9,10,11 The micro-

FIGURE 1: PVC audit results

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Immunology

organisms most frequently associated with cannula-related infections are those naturally present on the skin, particularly staphylococci.11 Evidence supporting the use of chlorhexidine-alcohol has continued to grow. Findings of the CLEAN randomised controlled trial, involving 1,181 patients and 2,612 catheters, demonstrated that chlorhexidine-alcohol was associated with a lower incidence of catheter-related infections when compared with povidoneiodine alcohol.11 Current best practice guidance therefore recommends a single-use application of 2 per cent chlorhexidine in 70 per cent alcohol isopropyl to disinfect the skin at the insertion site.9,11

Dressing and catheter securement Transparent sterile dressings replaced gauze dressings to secure PVCs post insertion. Images of the appropriate dressings were displayed in clinical areas. Rationale: Gauze dressings do not facilitate observation of the insertion site. Transparent dressings allow healthcare staff and patients to easily inspect the site, and help to control moisture.12,13

Education and documentation Evidence-based cannulation training was delivered to appropriate staff. Approaches included Centre for Nurse and Midwifery education delivered by the IPC team and evidence-based cannulation training with simulation and supervised practice. The patient information poster was developed to teach patients and carers to recognise early signs of infection. They were distributed to patients with a PVC in situ and outlined how to recognise signs of infection such as redness, swelling, pain, or discharge, and when to seek medical review.11 Rationale: Staff education and training are key strategies in reducing PVC-BSIs. Cannulation training which includes theoretical teaching, simulation practice, and supervised competency assessment supports safe insertion practices and

adherence to aseptic technique.11,12 Patient education about signs of infection, and advising that the cannula insertion site should be covered with a sterile dressing to prevent contamination and reduce the risk of infection, is also important for early detection of infection.10,13,14,15

Hand hygiene The emphasis on hand hygiene within this QIP was intended to strengthen compliance with evidence-based infection prevention practices and minimise the risk of PVC infection. Additional measures to minimise infection risk included the consistent presence of IPC nurses (IPCNs), monthly hand hygiene audits, and consistent and strong support from hospital management and the director of nursing on the ‘bare above the wrist’ policy. Rationale: Hand hygiene is the most ef fective measure for preventing healthcare-associated infections and reducing the transmission of microorganisms between patients.15 Inadequate hand hygiene among healthcare workers is a well-recognised risk factor for PVC-associated infections.12 When hand decontamination is not performed ef fectively, healthcare workers’ hands can act as vectors for the transmission of micro-organisms between patients.15

PVC replacement The introduction of clinically indicated PVC replacement, supported by a standardised care bundle, aimed to reduce PVC-BSI by ensuring that catheters were inserted, maintained, and removed according to best practice. No further changes were recommended apart from the ongoing use of the PVC care bundle process. Rationale: Recent evidence suggests that routine replacement does not significantly reduce infection rates and may lead to unnecessary procedures and patient discomfort. Current guidance from HSEAMRIC recommends that PVCs should not be routinely replaced at fixed intervals, but instead removed or replaced when clinically

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indicated, such as in the presence of phlebitis, infiltration, occlusion, suspected infection, or when the device is no longer required.9 This change coincided with the introduction of a PVC care bundle process at MRHT.

Results The baseline PVC audit demonstrated variation in both device utilisation and maintenance practices across the hospital. Of the 157 patients audited prior to implementation of changes, 90 (57%) had a PVC in situ (Figure 1). The findings suggested opportunities to reduce unnecessary catheter use, as some PVCs remained in place without a clear ongoing clinical indication. Of the patients with a PVC in situ, 28 (31.1%) exhibited signs of local infection, including redness and pain at the insertion site. In addition, 14 patients (15.6%) had a soiled or compromised dressing, indicating deficiencies in catheter maintenance and ongoing monitoring. Variation in these findings between wards highlighted inconsistencies in adherence to best practice. These baseline audit results informed the development of targeted interventions, including staff education, enhanced surveillance, and audit processes, regular feedback to clinical teams, and reinforcement of the PVC care bundle. Collectively, these measures aimed to improve adherence to evidence-based practice, reduce variation in care, and minimise the risk of PVCassociated complications and BSI. Following a detailed review of the infection prevention measures, PVCrelated S aureus BSI incidence decreased from 14.8 per cent in 2023 to 5.7 per cent in 2025 per 1,000 PVC days. This resulted in reduction of 9.1 percentage points. There was a significant decline in hospitalacquired BSI from 202214 to 2023.4 The target rate was 0.5, which is below the newly revised national target rate of 0.7. This number has stayed consistently low throughout 20244 and 2025.4 The current number for Q1 2026 is zero. In addition to these improvements,

Immunology

compliance with hand hygiene and aseptic insertion practices improved signif icantly. The hand hygiene compliance audit results increased from 85.5 per cent in 2023 to 87.9 per cent in 2024, and then up to 92.1 per cent in 2025. This represents a total improvement of 6.6 percentage points over three years. A positive f inding from the care bundle audit was that the wards were achieving compliance rates of over 90 per cent. The care bundle audits also demonstrated that there were no signs of infection at the time the assessment was completed. In addition, substantial improvements in PVC care bundle audit results were also demonstrated. PVC

The IPC team in MRHT successfully implemented a quality improvement initiative to optimise patient safety and quality of care for patients with PVCs. This multimodal quality improvement approach signif icantly reduced the incidence of PVC-associated S aureus BSIs, demonstrating the ef fectiveness of policy, targeted education, procedural and monitoring-based interventions in

promoting patient safety. There is a requirement to continuously monitor, evaluate, re-adjust, and adapt interventions to achieve desired results, sustain improvements in patient outcomes, and investigate reasons for non-adherence as keys to achieving desired outcomes. Sustained implementation and ongoing reinforcement of these interventions are vital to maintaining improvements. Continued education, leadership, good governance, regular audit, feedback, and organisational support should be embedded into routine practice to ensure long-term compliance and patient safety outcomes. ●

References 1. Alexandrou E, Ray-Barruel G, Carr PJ, et al. Use of short peripheral intravenous catheters: Characteristics, management, and outcomes worldwide. J Hosp Med. 2018;13(5):10.12788/jhm.3039. doi:10.12788/jhm.3039.

Effectiveness of insertion and maintenance bundles in preventing peripheral intravenous catheter-related complications and bloodstream infection in hospital patients: A systematic review. Infect Dis Health. 2019;24(3):152-168. doi:10.1016/j. idh.2019.03.001.

without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): An open-label, multicentre, randomised, controlled, two-by-two factorial trial. Lancet. 2015;386(10008):20692077. doi:10.1016/S01406736(15)00244-5.

2. Chopra V, Flanders SA, Saint S, et al. The Michigan appropriateness guide for intravenous catheters (MAGIC): Results from a multispecialty panel using the RAND/UCLA appropriateness method. Ann Intern Med. 2015;163(6 Suppl):S1-S40. doi:10.7326/M15-0744.

7. World Health Organisation. Guidelines for the prevention of bloodstream infections and other infections associated with the use of intravascular catheters. Part 1: Peripheral catheters. Geneva: WHO; 2024. ISBN: 978-92-4-009382-9. Available at: www.who.int/publications/i/ item/9789240093829

12. Loveday HP, Wilson JA, Pratt RJ, et al. epic3: National evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect. 2014;86 Suppl 1:S1-S70. doi:10.1016/S0195-6701(13)60012-2.

3. Drugeon B, Guenezan J, Pichon M, et al. Incidence, complications, and costs of peripheral venous catheter-related bacteraemia: A retrospective, single-centre study. J Hosp Infect. 2023;135:67-73. doi:10.1016/j.jhin.2023.02.012. 4. Marsh N, Larsen EN, Ullman AJ, et al. Peripheral intravenous catheter infection and failure: A systematic review and meta-analysis. Int J Nurs Stud. 2024;151:104673. doi:10.1016/j. ijnurstu.2023.104673. 5. Health Protection Surveillance Centre. Point prevalence survey of healthcare-associated infections and antimicrobial use in Irish hospitals: National Report 2023. Dublin: Health Protection Surveillance Centre; 2024. Available at: www.hpsc.ie/ a-z/microbiologyantimicrobialresistance/ infectioncontrolandhai/surveillance/hospitalpointprevalencesurveys/2023/ 6. Ray-Barruel G, Xu H, Marsh N, et al.

audit results increased from 64 per cent compliance in 2022 to 87 per cent in 2025. No other major confounders or environmental changes were observed, suggesting direct correlation with the QIP.

Conclusion

8. Harbarth S, Sax H, Gastmeier P. The preventable proportion of nosocomial infections: An overview of published reports. J Hosp Infect. 2003;54(4):258-321. doi:10.1016/s0195-6701(03)00150-6. 9. Health Service Executive. Antimicrobial Resistance and Infection Control (AMRIC) Action Plan 2022-2025. Dublin: HSE; 2021. Available at: catalogue.nli.ie/Record/vtls000906521 10. Health Information and Quality Authority. National standards for the prevention and control of healthcare-associated infections in acute healthcare services. Dublin: HIQA; 2017. Available at: www. hiqa.ie/hiqa-news-updates/hiqa-publishes-revised-national-standards-prevention-and-control-healthcare 11. Mimoz O, Lucet JC, Kerforne T, et al. Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, with and

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13. Rickard CM, Webster J, Wallis MC, et al. Routine versus clinically indicated replacement of peripheral intravenous catheters: A randomised controlled equivalence trial. Lancet. 2012;380(9847):1066-1074. doi:10.1016/S0140-6736(12)61082-4. 14. Gorski LA, Hadaway L, Hagle ME, et al. Infusion therapy standards of practice, 8th Edition. J Infus Nurs. 2021;44(1S Suppl 1):S1-S224. doi:10.1097/ NAN.0000000000000396. 15. Pittet D, Allegranzi B, Sax H, et al. Evidence-based model for hand transmission during patient care and the role of improved practices. Lancet Infect Dis. 2006;6(10):641-652. doi:10.1016/S14733099(06)70600-4. 16. Author Bios 17. Grace Kinahan, MSc, RGN, RM, ANP, RNP Assistant Director of Nursing Infection Prevention and Control, Midlands Regional Hospital, Tullamore, Co Offaly

Immunology

Classifying trauma-related infections Authors: Prof Eavan Muldoon, Consultant in Infectious Diseases, Mater Misericordiae University Hospital, and National Clinical Lead for the National Clinical Programme for Infectious Diseases & OPAT; and Dr Ellen Newman, Specialist Registrar in Infectious Diseases, Mater Misericordiae University Hospital

‘T

rauma’ has become a buzzword in the tertiary care landscape with the development of the National Trauma Strategy and associated centres; however, traumatic injuries and their associated infections interact with healthcare systems at all levels, from wound management with public health nursing, to early or indolent infection in primary care, to the extremes of patients transferred from the scene by helicopter to one of the two national trauma centres. By their nature, trauma-related infections (TRI) pose a number of different challenges. At the more severe end, penetrating abdominal injuries, open fractures, and large soft tissue deficits demonstrate complexity in their surgical and antimicrobial management. The introduction of hardware such as ORIF into contaminated wounds, and a patient population with often lengthy hospital stays and repeated visits, with increasing risk of multi-drug resistant pathogens. While ‘trauma’ can have a broad definition when it comes to injury, here we are relating to sudden onset injuries that require immediate medical attention, as defined by the National Trauma Strategy. While this cohort of patients’ initial interaction with the healthcare system is typically in the emergency department setting, they may present with infectious complications to their injuries in numerous ways. Crucial to managing these patients are multidisciplinary team (MDT) meetings, involving stakeholder specialties such as trauma and general surgery, orthopaedics, plastics, and infectious diseases. The ability to make plans with consensus opinion, tie

in early review, and have clear perspectives about what is feasible from a surgical or antimicrobial standpoint is essential for timely and efficient care.

Classification TRIs are most easily stratified by injury location and depth.

Skin and soft tissue trauma-related infections: This ranges from cellulitis following skin penetrating injury to post-operative surgical site infection. The most common causative organisms are Staphylococcus aureus and Streptococcus spp, as is the case with non-traumatic skin and soft tissue trauma-related infections. However, there is a much higher incidence of polymicrobial and gram negative pathogens, particularly dependent on mechanism of injury and wound contamination. The history of the injury – in particular, the location, both geographical and anatomical – can offer clues to potential alternative causative organisms. In Ireland, farming injuries are common, and contaminated farm machinery increases the risk of gram negative and environmental organisms being introduced into a penetrating wound. The National Major Trauma audit reported that 3 per cent of major traumas presenting to hospital in 2022 were from the farm setting, approximately 100 per annum. For the majority, treatment involves typical empiric cellulitis cover, but early review and consideration of escalation to broader cover is prudent. For grossly contaminated wounds, whether it be by environmental or inorganic material, or standing water exposure, empiric treatment covering gram positive, gram negative, and anaerobes is advised. Fresh

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versus salt water exposure should also be taken into consideration, for example, Aeromonas spp cover for freshwater or Vibrio spp for salt water contamination. Obtaining samples for culture and susceptibility may seem advantageous, but the benef it of same depends on the wound and quality of sample attainable. Expressible purulent discharge for example, can greatly aid targeted therapy, but swabs of large soft tissue def icits with environmental exposure are more likely to reveal commensal growths and skin flora than true pathogens, and can misguide treatment. Deeper seated infections may represent either progressive infection due to lack of source control, or deeper penetration of injury from index insult. Wounds over joints must be carefully considered and reviewed, for potential septic arthritis or bursitis. This is even more important in patients who may have previously undergone prosthetic joint replacement. Early involvement of the orthopaedic and plastic surgery in the trauma MDT approach is crucial. Soft tissue or intramuscular abscesses require longer duration of antimicrobial therapy. Standard of care would be aspiration for both culture as well as reduction of bacterial burden. Four to six weeks of treatment is normal, with end of treatment imaging to ensure resolution of collections key to preventing infection relapse.

Fracture-related infection: Risk of fracture-related infection (FRI) is related to the mechanism of injury and presentation of trauma. Closed fractures have a 1-2 per cent risk of infection, whilst with open fractures, that risk drastically increases to up to 30 per cent. Open fractures with severe soft tissue

Immunology

deficits or degloving injuries or grossly contaminated from the trauma environment are often managed with external fixation, with the goal of internal fixation with soft tissue coverage within 72 hours if injury, alongside prophylactic empiric or targeted antibiotics. Open fractures without grossly evident infection, or closed fractures, can be harder to diagnose for fracture-related infection. Some may present with surgical site cellulitis or wound dehiscence, or a discharging sinus. However, infection may be more insidious, with boney non-union, disproportionate pain, or new joint effusion all being suggestive signs. A fundamental concept in FRI is the presence of metalware, and the role of surgical management of same in order to achieve source control. Metalware provides a foci for bacterial growth and biofilm formation. Antibiotics alone will commonly fail to cure FRI. They may serve to bridge until union and metalware removal or for long-term suppression in some cases unfit for same, but without removal, the risk of osteomyelitis, relapsing infection, and progressive resistance is challenging. Imperative to the management of FRI is the avoidance of empiric antimicrobials without initial tissue sampling, particularly in later presentation FRI. To do so is to jeopardise the yield of later samples for culture and susceptibility. Targeted antimicrobial therapy is of particular import to patients who may end up requiring longterm suppression of chronic infection, and empiric antibiotics up front can go so far as to risk loss of limb for some populations. While there are some disparities between guidelines, general consensus is that open fractures should receive no more than 72 hours of empiric antimicrobials, or 24 hours

post closure, whichever occurs first. Patients with conf irmed FRI typically receive up to six weeks of antibiotics from def initive management, with some nuances to individual cases. Increasingly, the use of local antimicrobial agents (such as antimicrobial impregnated cement) allows shortened durations of antimicrobial therapy following surgical debridement, and oral agents are preferred where possible.

Intra-abdominal infections/abscesses: To move away from limb and bone trauma-related infections, abdominal injuries present their own unique pathogen risks to consider. Abdominal trauma may be penetrative or blunt force, for example seatbelt contusional injuries may result in splenic rupture and requirement for splenectomy, with implications for the management of encapsulated bacteria and prophylaxis, or resulting in bowel perforation, with associated infections and collections. While immediate empiric antifungal therapy for bowel perforation is not advised, fungal intra-abdominal collections – often in the presence of concurrent polymicrobial bacterial growth – are a common complication of traumatic bowel perforation. Patients can frequently require repeated laparotomy and washout, and abdominal wall closure can be delayed due to the need for “relook” procedures in the immediate days post injury, or due to soft tissue deficit requiring secondary closure. As with deep sof t tissue abscesses, imaging of intrabdominal collections at the end of treatment is pertinent

A fundamental concept in FRI is the presence of metalware, and the role of surgical management of same in order to achieve source control UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

to ensure resolution before cessation of antimicrobials. Infection due to gastrointestinal tract (GIT) trauma can be complex in terms of both causative organisms – with gram positive, gram negative, anaerobes, and fungi – particularly Candida spp – all common and requiring multiple agents that can be difficult to rationalise to a tolerable regimen for both patient and antimicrobial stewardship, but also by the nature of the injury. Trauma to the GIT often results in bowel resection or periods of bowel rest, which limits modality of agents to IV administration in the immediate period. This can also cause concern regarding absorption of oral agents in later stages of treatment, particularly if treatment failure or antimicrobial resistance develops. As the National Trauma Strategy continues to develop, so must a comprehensive approach to associated infections, with early access to specialist care to those in the community who have concerns about infection after hospital discharge, or had intervention in a centre without a dedicated MDT. Clear pathways to trauma centres and infectious diseases services, with follow-up and clear communication to services for those “out of catchment” is crucial for continuity of care and reducing infectious complications and burden, with special consideration to access for those presenting in primary care. Notably though, throughout the National Trauma Strategy steering group report, there is no mention of infection management, the role of infectious diseases and/or clinical microbiology in trauma, or pathways to follow-up, including post-repatriation. One model of care document does mention infection management, but in relation to infectious diseases outbreak in the context of the recent Covid-19 pandemic etc. As the national trauma services develop, infrastructure should support the infectious consequences of traumatic injury, with appropriate pathways and funding, at all levels, from community and primary care to the two national centres. ●

Immunology

Vaccine hesitancy in primary care Author: Theresa Lowry Lehnen, RGN, PG Dip Coronary Care, BSc (Hons), RNP, MSc, RANP, PG Dip Ed (QTS), M Ed, PhD FFNMRCSI, Advanced Nurse Practitioner General Practice

accination remains one of the most effective public health interventions for preventing infectious disease, reducing morbidity and mortality, and improving population health outcomes. Despite the proven benefits of immunisation programmes, vaccine hesitancy has emerged as a significant challenge for healthcare systems worldwide. The concept of vaccine hesitancy refers to the delay in acceptance or refusal of vaccines despite the availability of vaccination services. It is recognised as a complex and context-specif ic phenomenon that varies across time, geographic settings, and specif ic vaccines.1 Several frameworks have been proposed to explain the determinants of vaccine hesitancy. The World Health Organization Strategic Advisory Group of Experts developed the widely used 3Cs model, identifying three key drivers: Confidence, complacency, and convenience.1,2 Conf idence relates to trust in vaccines, healthcare providers, and public health systems. Complacency occurs when individuals perceive the risk of vaccine-preventable diseases as low, reducing perceived need for vaccination. Convenience refers to structural or logistical barriers such as access, cost, or service availability. 2,3 More recent research has expanded this model. Studies exploring Covid-19 vaccine hesitancy in Ireland suggested a 4Cs framework that includes communication as an additional factor influencing public attitudes. 4 Communication includes the influence of media narratives, misinformation, and public health messaging on vaccination decisions.

Understanding these drivers is important because dif ferent forms of hesitancy require dif ferent responses. Concerns about safety, mistrust in institutions, and practical barriers to access require tailored interventions rather than a single universal strategy. 4

A public health challenge In Ireland, vaccination uptake remains generally high, particularly within childhood immunisation programmes. Childhood immunisations protect children from serious diseases such as measles, mumps, rubella, diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), hepatitis B, meningococcal B and C, pneumococcal disease, rotavirus, and human papilloma virus (HPV). Decades of research and realworld experience have consistently demonstrated the safety and ef fectiveness of these vaccines. In addition to extensive research demonstrating vaccine safety and ef f icacy, government agencies regulate vaccines to ensure their safety. However, episodes of declining uptake associated with misinformation or safety concerns have occurred.1 Ireland is not immune to the influence of vaccine hesitancy. The decline in uptake of the HPV vaccine across the country between 2015 and 2017 highlighted the impact that

misinformation and loss of public trust can have on vaccination programmes. Recovery of HPV vaccination rates required sustained public health campaigns and engagement with healthcare professionals, including nurses and general practitioners. 5 Despite historically strong immunisation uptake, recent observations suggest declining coverage for routine childhood vaccines, prompting public health concern. Measles, which had been effectively eliminated in Ireland in 2015, has seen resurgence, with notified cases rising markedly in recent years.6 The national uptake of the measles, mumps, and rubella vaccine for junior infants dropped from 91.2 per cent in 2018/2019 to 87.5 per cent in 2021/2022, with only a partial recovery to 89.8 per cent in 2022/2023 – f igures that remain below the 95 per cent threshold required for herd immunity.6 Another report found that Ireland had one of the lowest childhood vaccination coverage rates in western Europe in 2023, with 91 per cent of children fully vaccinated and nearly 5,000 receiving no vaccines at all.7 These trends signify not only missed protection for susceptible individuals, but also a broader vulnerability to outbreaks of vaccinepreventable diseases.

Despite historically strong immunisation uptake, recent observations suggest declining coverage for routine childhood vaccines UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

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The pandemic highlighted the influence of hesitancy in real time. National surveys revealed that large proportions of the Irish adult population were initially uncertain or resistant towards Covid-19 vaccination. In one study, 26 per cent of Irish respondents were hesitant and 9 per cent were resistant to the Covid-19 vaccine, figures that mirror international hesitancy patterns.8 Research also suggests that the public often underestimates vaccine effectiveness and may not fully appreciate dynamics such as waning immunity, complicating public confidence in vaccination programmes.9 These observations reinforce the need for effective primary care engagement strategies tailored to the populations served. Primary care clinicians play a central role in vaccination delivery and patient education, and have an important role in shaping patients’ perceptions and decisions about vaccination. As trusted healthcare professionals who frequently interact with patients and families, they are uniquely positioned to address vaccine hesitancy through ef fective communication, education, and evidencebased counselling.10

Determinants of vaccine hesitancy Understanding the prevalence and determinants of vaccine hesitancy is important for designing interventions that resonate with communities. In Ireland, vaccine hesitancy has been documented across population groups, including adults and parents of young children. A nationally representative study of the general adult population found that approximately 26 per cent were hesitant and 9 per cent were resistant toward Covid-19 vaccination, with similar patterns noted in pooled research. 8 Internationally, systematic reviews have identif ied a constellation of factors consistently associated with hesitancy, including demographic characteristics, perceptions of vaccine safety, trust in health authorities, misinformation exposure, and previous experiences with healthcare systems.11

Sociodemographic correlates such as age, gender, and socioeconomic status have been linked to vaccine hesitancy. Younger adults and women have demonstrated higher rates of vaccine uncertainty in some studies, while individuals from lower socioeconomic backgrounds may harbour greater mistrust or face informational barriers.12 Psychological and behavioural correlates also play significant roles. Those who exhibit hesitancy often rely more heavily on non-authoritative information sources such as social media, where vaccine misinformation proliferates, and are less likely to seek information from conventional public health channels.8 Perceived risk of disease, civic attitudes, peer influence, and perceived vaccine benefits have emerged as strong predictors of vaccine intentions.12 Barriers to vaccine uptake are not evenly distributed. In certain subpopulations, such as people with chronic neurological conditions such as multiple sclerosis, vaccine hesitancy stems from specif ic concerns regarding safety and interactions with diseasemodifying treatments, alongside gaps in clinician-delivered vaccine promotion.13 Among healthcare workers themselves, hesitancy can be influenced by similar factors, with younger age, female sex, and non-clinical roles associated with lower uptake, highlighting that hesitancy is not conf ined to the general public but af fects the healthcare workforce as well.14 Meta-analytical evidence suggests that safety concerns, complacency, and logistic barriers contribute to hesitancy, indicating the need for targeted professional support to enhance vaccine uptake among providers.15 Together, these findings illustrate that vaccine hesitancy is a multifactorial challenge shaped by information, social context, individual beliefs, and prior experiences. Addressing these determinants requires multifaceted approaches that extend beyond simple education to include communication, trustbuilding, and system-level interventions.

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Impact The decline in vaccination coverage has palpable implications for public health in Ireland. The resurgence of measles serves as a stark reminder of the consequences of sub-optimal immunisation. After achieving elimination, Ireland witnessed only a handful of measles cases for several years. However, last year, notif ied cases soared to 208 from just four in 2023, while pertussis notif ications climbed dramatically from 18 conf irmed cases in 2023 to 713, highlighting a deteriorating immunisation environment.7 Such increases highlight the fragile nature of herd immunity and the ease with which vaccine-preventable diseases can reemerge when uptake falters. Globally, stalled progress in childhood immunisation coverage has placed millions of children at risk of preventable illness and death, with declines reported in both low- and high-income settings. A Lancet analysis found that while vaccination coverage doubled globally between 1980 and 2019, progress has stagnated or reversed in many countries since 2010, partly due to vaccine hesitancy and disruptions from the Covid-19 pandemic.16 In Ireland and across Europe, sustained or rising levels of hesitancy threaten to undermine population health, increase healthcare costs, and erode public trust in health systems. These epidemiological trends highlight the urgency with which primary care practitioners must act to prevent further erosion of immunisation coverage. Nurses and advanced nurse practitioners (ANPs) in primary care are ideally positioned to influence vaccine decision-making through trusted relationships, routine care encounters, and ongoing patient education.

Strategies for addressing vaccine hesitancy Addressing vaccine hesitancy in primary care requires a nuanced blend of communication skills, clinical

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knowledge, cultural awareness, and system support. Practical, evidencebased strategies pivot on four overlapping domains: Communication and counselling, education and training, building trust and partnerships, and system-level interventions. Effective communication is central to addressing vaccine hesitancy. Clinicians should use patient-centred dialogue that explores concerns without judgement and promotes trust. Open-ended questions and reflective listening allow patients to express fears and beliefs while helping clinicians build rapport. A presumptive communication style presenting vaccination as a routine part of care has been shown to increase uptake compared with more tentative approaches.10,15 Motivational interviewing is also valuable in vaccine discussions. This approach helps patients explore their own motivations and resolve ambivalence by emphasising autonomy, empathy, and collaboration rather than persuasion.17 Clinicians trained in motivational interviewing may be more ef fective at addressing concerns without alienating patients. Clinicians should answer questions clearly and honestly. Admitting uncertainty when evidence changes can build trust, while dismissing concerns may increase hesitancy. Presenting information fairly, with risks and benef its explained, helps patients make informed decisions. Patient education is central to addressing vaccine hesitancy, particularly where misconceptions about safety or ef fectiveness exist. Clinicians can use clear, accessible information to address common myths, explain vaccine safety monitoring, and outline the established risk prof iles of vaccines. Providing context on the potential complications and community impact of vaccine-preventable diseases also supports informed decision-making. Professional education is important. Many clinicians report feeling underprepared for conversations about vaccine hesitancy due to limited

training in communication and behavioural strategies.18 Incorporating vaccine communication training into continuing professional development, including guidance on misinformation, motivational interviewing, and patient engagement, can improve clinicians’ conf idence and ef fectiveness. Trust strongly influences vaccine acceptance. Patients who trust healthcare providers and public health institutions are more likely to follow vaccination recommendations. Building this trust requires consistent messaging, transparency about risks and benef its, and cultural sensitivity. In diverse or marginalised communities, collaboration with community leaders and local organisations can help ensure messages are relevant and credible. Clinicians should also recognise the role of social influences in vaccine decisions. Peer influence, civic responsibility, and perceived social norms can shape vaccine intentions.12 Highlighting strong community uptake and framing vaccination as a contribution to collective health may help encourage acceptance. System-level strategies can strengthen vaccination ef forts beyond individual consultations. Reminder and recall systems, such as automated messages for due vaccines, improve timely uptake. Integrating prompts into routine reviews or key consultations also ensures vaccination discussions occur regularly. Recording patient concerns in electronic records supports continuity and follow-up. 19 Interprofessional collaboration is important. Consistent messaging from GPs, nurses, ANPs,

pharmacists, and public health professionals helps prevent confusion. Practice audits of vaccination rates can identify gaps and guide targeted quality improvement initiatives. 19

Challenges and barriers Notwithstanding the availability of effective strategies, primary care clinicians face barriers in implementing them. Time pressures in primary care can limit the depth of conversations about vaccination. They may also encounter resistance rooted in deep-seated beliefs that are resistant to brief educational efforts. Structural issues such as limited access to culturally appropriate resources and language barriers further complicate engagement. Recognition of these challenges highlights the need for organisational support, protected consultation time for vaccine discussions, and access to multidisciplinary resources for complex cases.20

Future directions Ongoing research is needed to improve strategies for addressing vaccinehesitancy in dif ferent populations. Long-term studies can identify the main factors behind hesitancy beyond short-term crises like Covid-19. Digital health tools that counter online misinformation of fer new ways to inf luence vaccine beliefs widely. Evaluating educational programmes for primary care clinicians can help determine the most ef fective training and support. At policy level, using behavioural science in national immunisation plans can better address community concerns. 21

Patient education is central to addressing vaccine hesitancy, particularly where misconceptions about safety or ef fectiveness exist UPDATE | VOLUME 1 2 | ISSUE 10 | 2026

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Conclusion Vaccine hesitancy is a major challenge to maintaining high immunisation coverage and protecting public health. Primary care clinicians play a key role in addressing this through clear

References

1. Brumbaugh KQ, Gellert F, Mokdad AH. Understanding vaccine hesitancy: Insights and improvement strategies drawn from a multi-study review. Vaccines (Basel). 2025;13(10):1003. doi:10.3390/vaccines13101003. 2. MacDonald NE; SAGE Working Group on Vaccine Hesitancy. Vaccine hesitancy: Definition, scope, and determinants. Vaccine. 2015;33(34):4161-4164. doi:10.1016/j. vaccine.2015.04.036. 3. World Health Organisation. Ten threats to global health in 2019. Geneva: WHO; 2019. Available at: www. who.int/news-room/spotlight/tenthreats-to-global-health-in-2019 4. Ingram C, Roe M, Downey V, et al. Exploring key informants’ perceptions of Covid-19 vaccine hesitancy in a disadvantaged urban community in Ireland: Emergence of a ‘4Cs’ model. Vaccine. 2023;41(2):519-531. doi:10.1016/j.vaccine.2022.11.072. 5. Deane A, White C, Morrissey Y, et al. The impact of HPV vaccine disinformation and misinformation in disadvantaged educational settings in Ireland: A multi-year analysis of a school immunisation system. Vaccine. 2025;51:126868. doi:10.1016/j. vaccine.2025.126868. 6. Wayman S. ‘This is a disaster waiting to happen, and it will happen’: Ireland’s falling child vaccine rates. The Irish Times. 2025 Feb 22. Available at: www.irishtimes.com/health/yourfamily/2025/02/22/child-vaccineswhy-have-immunisation-rates-fallenin-ireland/ 7. Mc Hale M. Ireland has second lowest childhood vaccination rate in western Europe. Irish Medical Times. 2025 Jun 25. Available at: www.imt. ie/news/ireland-has-second-lowest-

communication, patient education, trustbuilding, and engagement in primary care. Evidence-based strategies, such as motivational interviewing, empathetic dialogue, tailored education, and systemlevel supports can improve vaccine

acceptance. By using these approaches in routine practice and supporting organisational frameworks, primary care clinicians help strengthen immunisation programmes and protect communities from vaccine-preventable diseases. ●

childhood-vaccination-rate-in-westerneurope-25-06-2025/

hesitancy in the general population: A systematic review of reviews. Z Gesundh Wiss. Published online September 19, 2022. doi:10.1007/ s10389-022-01753-9 GBD 2020.

8. Murphy J, Vallières F, Bentall RP, et al. Psychological characteristics associated with Covid-19 vaccine hesitancy and resistance in Ireland and the United Kingdom. Nat Commun. 2021;12(1):29. 9. Lunn PD, Timmons S. Public misperceptions of Covid-19 vaccine effectiveness and waning: Experimental evidence from Ireland. Public Health. 2023;214:81-84. doi:10.1016/j.puhe.2022.11.002. 10. Schoenfisch C, Kauter K, East L. The nurse practitioner’s immuniser role in primary healthcare: A scoping review. J Clin Nurs. 2025;34(8):3072-3084. doi:10.1111/jocn.17716. 11. Pires C. Global predictors of Covid-19 vaccine hesitancy: A systematic review. Vaccines (Basel). 2022;10(8):1349. doi:10.3390/ vaccines10081349. 12. Walsh JC, Comar M, Folan J, et al. The psychological and behavioural correlates of Covid-19 vaccine hesitancy and resistance in Ireland and the UK. Acta Psychol (Amst). 2022;225:103550. doi:10.1016/j. actpsy.2022.103550. 13. Yap SM, Al Hinai M, Gaughan M, et al. Vaccine hesitancy among people with multiple sclerosis. Mult Scler Relat Disord. 2021; 56:103236. doi: 10.1016/j. msard.2021. 14. Townsend L, Kelly G, Kenny C, et al. Healthcare worker characteristics associated with SARS-CoV-2 vaccine uptake in Ireland: A multicentre crosssectional study. Vaccines (Basel). 2023;11(10):1529. doi:10.3390/ vaccines11101529. 15. Kafadar AH, Tekeli GG, Jones KA, et al. Determinants for Covid-19 vaccine

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16. Vaccine coverage collaborators. Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019: A systematic analysis for the Global Burden of Disease Study 2020. Lancet. 2021;398(10299):503-521. doi:10.1016/ S0140-6736(21)00984-3. 17. Mendonça J, Hilário AP, Gouveia L. Motivational interviewing to address vaccine hesitancy: Insights from an intervention in Portugal. Port J Public Health. 2024;42(3):195-205. doi:10.1159/000539600. 18. Locatelli G, Luciani M, Fabrizi D, et al. Determinants and motivations of vaccination hesitancy and uptake in nurses: A systematic review and meta-analysis. J Clin Nurs. 2025;34(10):4005-4037. doi:10.1111/ jocn.17852. 19. Wheeler SG, Beste LA, Overland MK, Wander PL. Interventions in primary care to increase uptake of adult vaccines: A systematic review. J Public Health (Oxf). 2025;47(2):222-231. doi: 10.1093/pubmed/fdaf008. 20. Holford D, Anderson EC, Biswas A, et al. Healthcare professionals’ perceptions of challenges in vaccine communication and training needs: A qualitative study. BMC Prim Care. 2024;25(1):264. doi:10.1186/s12875024-02509-y. 21. Taubert F, Meyer-Hoeven G, Schmid P, et al. Conspiracy narratives and vaccine hesitancy: A scoping review of prevalence, impact, and interventions. BMC Public Health. 2024;24(1):3325. doi:10.1186/s12889-024-20797-y.

ABRYSVO®: Powerful. Powerful.Proven. Proven. ABRYSVO®: Powerful. Proven. 1,1,22 RSV Protection. 1, 2 RSV Protection. Abrysvo is indicated for: for: - Active immunisation against against lower respiratory Abrysvo is indicated for: lower respiratory tract disease caused by by respiratory respiratorysyncytial syncytial - virus Active(RSV) immunisation against lower respiratory in infants from through from birth birth through tract disease caused by respiratory of age following maternal 6 months following maternal syncytial 1 virus (RSV) in infants from birth 1through during pregnancy. immunisation pregnancy. months of age following maternal18 - 6Active immunisation of of individuals individuals 18years years 1 immunisation during pregnancy. of age and older for the the prevention preventionofoflower lower 11 - Active immunisation of individuals years respiratory tract disease caused RSV. disease causedby by18 RSV. of age and older for the prevention of lower The use use of of this The this vaccine vaccine should shouldbe beininaccordance accordancewith withofficial official 1 respiratory tract disease caused by RSV. 11 recommendations. recommendations. The use of this vaccine should be in accordance with official

RSV==respiratory respiratory syncytial syncytial virus; virus; RSV 1 RSV-LRTD = respiratory syncytial recommendations. RSV-LRTD = respiratory syncytial virus-associated virus-associated lower lowerrespiratory respiratorytract tractdisease disease

Actor portrayal Actor portrayal

PRESCRIBING INFORMATION

PRESCRIBING INFORMATION RSV respiratory ▼This=medicinal productsyncytial is subject tovirus; additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to section 4.8 of the SPC for how to report adverse reactions. ▼This medicinal product is subject tosolution additional monitoring. This will allow quickvirus identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to section 4.8 of the SPC for how to report adverse reactions. Abrysvo®▼ powder and solvent for for injection (Respiratory syncytial vaccinetract [bivalent, recombinant]) RSV-LRTD = respiratory syncytial virus-associated lower respiratory disease Actor portrayal Abrysvo®▼ powder and solvent for solution for injection (Respiratory syncytial virus vaccine [bivalent, recombinant])

Ireland Prescribing Information: Ireland Information: Before Prescribing prescribing Abrysvo please refer to the full Summary of Product Characteristics (SmPC). Presentation: Powder and solvent for solution for injection. The powder is white. Before prescribing Abrysvo pleaseliquid. refer toIndications: the full Summary Characteristics (SmPC). Presentation: and to solvent forinfants solutionfrom for injection. Theto powder is white. The solvent is a clear, colourless AbrysvoofisProduct indicated for; active immunisation of pregnantPowder individuals protect birth through 6 months of age against lower respiratory tract disease caused by respiratory syncytial virus (RSV). PRESCRIBING INFORMATION The solvent is a clear, colourless liquid. Indications: Abrysvo is indicated active immunisation pregnant individuals protect infants birth through 6 months respiratory tract disease by respiratory syncytial virusand (RSV). See SmPC sections 4.2 and 5.1; and active immunisation of individuals 18 for; years of age and older forofthe prevention of lowertorespiratory tract from disease caused by to RSV. The useofofage thisagainst vaccinelower should be in accordance with caused official recommendations. Dosage ▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to 4.8be ofwith the SPC for recommendations. how report reactions. See SmPC sections 4.2 and 5.1; and active immunisation of individuals 18 years of age and older for the prevention of lower respiratory tract disease caused by RSV. The this vaccine should be in section accordance official Dosage and Administration: Pregnant individuals: A single dose of 0.5 mL should be administered between weeks 24 and 36 of gestation (see SmPC sections 4.4 and 5.1). Individuals 18 years ofuse age of and older: A single dose of 0.5 mL should administered. Thetoneed foradverse revaccination Abrysvo®▼ powder and solvent for solution injection syncytial vaccine [bivalent, recombinant]) Administration: Pregnant individuals: A singlefordose of 0.5 (Respiratory mLAshould administered between weeks 24 and 36 ofneed gestation (see SmPC 4.4 and 5.1). Individuals 18 years of age older: A population: single dose The of 0.5safety mL should be administered. need for(from revaccination has not been established. Immunocompromised individuals: singlebe dose of 0.5 virus mL should be administered. The for a second dosesections has not been established (see SmPC section 5.1).and Paediatric and efficacy of AbrysvoThe in children birth Ireland has not Prescribing been18established. individuals: A single of 0.5 mLinshould be administered. Thetheir needinfants for a second dosesection has not5.1). been established (see SmPCAbrysvo section 5.1). population: and efficacy ofthe Abrysvo children (from birth to less than yearsInformation: of age)Immunocompromised have not yet been established. Limited datadose are available pregnant adolescents and (see SmPC Method of administration: is forPaediatric intramuscular injectionThe intosafety the deltoid region of upperinarm. The vaccine Before prescribing Abrysvo please to theestablished. fullmedicinal SummaryLimited of Product Characteristics (SmPC). Presentation: Powder andthesolvent for solution for injection. The powder is SmPC white.Abrysvo to less than ofwith age)any have notrefer yet been dataFor areinstructions available in pregnant adolescents and their of infants (see SmPC section 5.1). Method of administration: forContraindications: intramuscular injection into the deltoid region of the upper arm. should not 18 beyears mixed other vaccines or products. on reconstitution and handling medicinal product before administration, see section is6.6. Hypersensitivity to the active substance or toThe anyvaccine of The solvent is a clear, colourless liquid. Indications: Abrysvo is indicated for; active immunisation of pregnant individuals to protect infants from birth through to 6 months of age against lower respiratory tract disease caused by respiratory syncytial virus (RSV). should not be mixed with any other vaccines or medicinal products. For instructions on reconstitution and handling of the medicinal product before administration, see SmPC section 6.6. Contraindications: Hypersensitivity to the active substance or any of the xcipients listed in SmPC section 6.1. Special Warnings and Precautions: Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivitytoand See SmPC sections 4.2 and 5.1; and active immunisation of individuals 18 years of age and older for the prevention of lower respiratory tract disease caused by RSV. The use of this vaccine should be in accordance with official recommendations. Dosage the xcipients listed in SmPC section 6.1. Special Warnings and Precautions: Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivity anaphylaxis: Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine. Anxiety-related reactions: Anxiety-related reactions, including vasovagal reactions (syncope), and Administration: Pregnant individuals: A singlemay dose of 0.5 should administered weeks 24of and of gestation (seeinjection. SmPC sections 4.4 and 5.1). 18are years of age older: A single dose of 0.5 mLreactions, shouldillness: be including administered. The need revaccination anaphylaxis: Appropriate medical treatment and supervision shouldbe always be readilybetween available in case an36 anaphylactic event following administration of the vaccine. reactions: vasovagal reactions (syncope), hyperventilation or stress-related reactions occur in mL association with vaccination as a psychogenic response to the needle Itthe is important thatIndividuals procedures inAnxiety-related place toand avoid injury fromAnxiety-related fainting. Concurrent Vaccination should beforpostponed has not been established. Immunocompromised individuals: Athe single dose mL should administered. Theshould need for aresult second dosedeferral has notimportant established (see SmPC Paediatric population: TheConcurrent safety efficacy of caution Abrysvotoinshould children (from hyperventilation or stress-related reactions occur in association with of vaccination as a be psychogenic to the injection. It is that procedures are section in place to avoid injury from fainting. Vaccination be postponed in individuals suffering from an acute febrilemay illness. However, presence of0.5 a minor infection, such as aresponse cold, notneedle in the ofbeen vaccination. Thrombocytopenia and5.1). coagulation disorders: Abrysvo shouldand be illness: given with individuals withbirth tothrombocytopenia less than 18suffering yearsorofany age) have not yet beenillness. established. Limited data are available in pregnant adolescents and their infants SmPC section Immunocompromised 5.1). Method of administration: Abrysvo forimmunogenicity intramuscular injection intoassessed the deltoid region of the uppertoarm. The vaccine in individuals from an acute febrile However, presence of a minor infection, such as a cold, should not result in individuals. the deferral of vaccination. Thrombocytopenia andisand coagulation disorders: Abrysvo should bein given with caution individuals with coagulation disorder since bleeding orthe bruising may occur following an intramuscular administration to(see these individuals: Safety have been immunocompromised individuals, should not be mixed with any other vaccines or medicinal products. For instructions on reconstitution and handling of the medicinal product before administration, see SmPC section 6.6. Contraindications: Hypersensitivity to the active substance or to any of thrombocytopenia or any coagulation disorder since bleeding or bruising may following an intramuscular these individuals. Immunocompromised Safety andofimmunogenicity havehas been in immunocompromised individuals, including those receiving immunosuppressant therapy see SmPC sections 4.8occur and 5.1). The efficacy of Abrysvo administration may be lower intoimmunosuppressed individuals. Individualsindividuals: less than 24 weeks gestation: Abrysvo notassessed been studied in pregnant individuals less the xcipients listed in SmPC section 6.1. Special Warnings and Precautions: Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivity and including those receiving immunosuppressant therapy see SmPC sections 4.8 and 5.1). The efficacy of Abrysvo may be lower in immunosuppressed individuals. Individuals less than 24 weeks of gestation: Abrysvo has not been studied in pregnant individuals than 24 weeks of gestation. Since protection of the infant against RSV depends on transfer of maternal antibodies across the placenta, Abrysvo should be administered between weeks and 36 gestation (see SmPC sections 4.2 and 5.1). Limitations of vaccine less anaphylaxis: and supervision shouldmay always beelicited readily available in case ofantibodies an anaphylactic event following the administration of1 the vaccine. Anxiety-related Anxiety-related reactions, including vasovagal reactions (syncope), than 24 weeksAppropriate of gestation. Since treatment protection of the infantresponse against RSV depends on transfer of maternal across the placenta, Abrysvo should administered between weeks 24reactions: and 36isofto gestation (see SmPC sections 4.2 medicinal and 5.1). Limitations of vaccine effectiveness: As with anymedical vaccine, a protective immune not be after vaccination. Excipients: This medicinal product contains less be than mmol sodium (23 mg) per dose, that say essentially ‘sodium free’ . This product contains hyperventilation orwith stress-related mayimmune occur inresponse association vaccination asadministered a psychogenic response towith the needle injection. It vaccines iscontains important are in(23 place avoid injury Concurrent illness: should be postponed effectiveness: AsPolysorbates any vaccine, a protective maywith not be elicited vaccination. Excipients: This medicinal product lessthat thanprocedures 1 mmol sodium mg)todose per dose, thatfrom is tofainting. say free’Vaccination . Thiswith medicinal product contains polysorbate 80. mayreactions cause allergic reactions. Interactions: Abrysvo can beafter concomitantly; seasonal influenza (standard dose adjuvanted or high unadjuvanted), withessentially COVID 19 ‘sodium mRNA vaccines, or without high dose in individuals80. suffering from anmay acute febrile illness. However, presence of a minor as a cold, between shouldwith not result in the deferral of vaccination. Thrombocytopenia and disorders: Abrysvo should be given with caution to individuals with polysorbate Polysorbates cause allergic reactions. Interactions: Abrysvo can beinfection, administered concomitantly; seasonal influenza vaccines dose of adjuvanted highcoagulation doseand unadjuvanted), with COVID 19 (Tdap). mRNA vaccines, with without high dose unadjuvanted influenza vaccine administered concomitantly. Athe minimum interval of two weeks is such recommended administration of Abrysvo and (standard administration a tetanus,ordiphtheria acellular pertussis vaccine There were no or safety concerns thrombocytopenia coagulation disorder since bleeding or bruising may occur an intramuscular to these individuals. Immunocompromised individuals: Safety immunogenicity haveHowever, beenvaccine assessed in immunocompromised individuals, unadjuvanted vaccine administered A minimum interval offollowing two weeks istorecommended between administration and administration of a tetanus, diphtheria andadministration. acellular pertussis There were to nothe safety concerns when Abrysvoinfluenza wasor coany administered with Tdap inconcomitantly. healthy non pregnant women. Immune responses RSV A, RSVadministration B, diphtheria and tetanus onofcoAbrysvo administration were non-inferior to those afterand separate the(Tdap). immune responses pertussis including those receiving immunosuppressant therapy see SmPC sections 4.8 and 5.1). The efficacy of Abrysvo may be lower in immunosuppressed individuals. Individuals less than 24 weeks of gestation: Abrysvo has not been studied in pregnant individuals components on co administration separate administration and didresponses not meet the criteria for non inferiority.and Thetetanus clinical relevance of this finding is unknown. Fertility, pregnancy and lactation: Pregnancy: Data onthe pregnant women (moreto than 000 less when Abrysvowere was lower co administered with Tdapcompared in healthytonon pregnant women. Immune to RSV A, RSV B, diphtheria on co administration were non-inferior to those after separate administration. However, immune responses the4pertussis than 24 weeks of gestation. protectionnor of the infant against RSV depends onand transfer ofmeet maternal antibodies across thedirect placenta, Abrysvo should be administered between weekspregnancy 24 and (see 36 and ofSmPC gestation (see SmPC sections 4.2 and 5.1). of vaccine exposed outcomes) indicate noadministration malformative feto/neonatal toxicity. Results from animal studies with do non not indicate indirect harmful effects with respect to reproductive toxicity section 5.3). In a phase study (Study 1),Limitations maternal components were lower on coSince compared to separate administration did not theAbrysvo criteria for inferiority. Theor clinical relevance of this finding is unknown. Fertility, lactation: Pregnancy: Data3on pregnant women (moreadverse than 4 000 effectiveness: Aswithin with any vaccine, protective response not be elicited after vaccination. Excipients: medicinal product contains less than up 1 mmol (23 mg)The per incidences dose, that isofSmPC to say section essentially ‘sodium free’3. study This medicinal product contains events reported 1 month aftera vaccination were similar intoxicity. themay Abrysvo group andstudies the placebo group (13%). No safety signals detected in infants torespect 24sodium months of age. adverse events5.3). reported within 1 month after1),birth in infants exposed outcomes) indicate no malformative nor immune feto/neonatal Results from(14%) animal with Abrysvo do notThis indicate direct orwere indirect harmful effects with to reproductive toxicity (see In a phase (Study maternal adverse polysorbate 80. Polysorbates may cause allergic reactions. Interactions: Abrysvo can be administered with seasonal or age. high doseincidences unadjuvanted), with mRNA withrespectively) or without dose were similar in the Abrysvo group (38%) and the placebo group Major birth outcomes assessed inconcomitantly; thegroup Abrysvo group toinfluenza placebo included (standard premature birth (207 (6%) and 172 (5%), respectively), birthCOVID weight19 (186 (5%)vaccines, and 158 (4%), events reported within 1 month after vaccination were similar in(35%). the Abrysvo group (14%) and the placebo (13%). Nocompared safety signals were vaccines detected in infants dose up to adjuvanted 24 months of The of low adverse events reported within 1 month after birthhigh inand infants unadjuvanted vaccine administered concomitantly. A(35%). minimum interval of twowhether weeks isAbrysvo recommended between administration of Abrysvo and administration of(207 a tetanus, diphtheria and acellular pertussis vaccineFertility: (Tdap). There were norespectively) safety concerns congenital (205 (6%) 245and (7%),the respectively). Breast-feeding: Itbirth is unknown is excreted in human milk. Notoadverse effects of Abrysvo havebirth been shown breastfed newborns of vaccinated mothers. human data on the effect were similaranomalies ininfluenza the Abrysvo groupand (38%) placebo group Major outcomes assessed in the Abrysvo group compared placebo included premature (6%)inand 172 (5%), respectively), low birth weight (186 (5%)No and 158 (4%), and of Abrysvo on was fertility are available. studies do notnon indicate direct or indirect harmful effects Abrysvo with respect toB,female fertility (see SmPC 5.3). of Undesirable Effects: most reported adverse reactions were the fatigue (33%), vaccination site pain when Abrysvo co (205 administered with Tdap in healthy pregnant women. responses to RSV A,isRSV diphtheria and tetanus onsection co administration werehave non-inferior to those after separate administration. However, immune to the pertussis congenital anomalies (6%) andAnimal 245 (7%), respectively). Breast-feeding: It isImmune unknown whether excreted in human milk. No adverse effects Abrysvo beenThe shown infrequently breastfed newborns of vaccinated mothers. Fertility: Noresponses human data on the effect (27%), headache (24%), myalgia (21%) and arthralgia (10%). The majority of reactions were mild to moderate in severity and resolved within 1-3 days of onset. Immunocompromised individuals 18 years of age and older: Reactogenicity was consistent with the known profile components were lower on co administration compared to separate administration and did not meet the criteria for non inferiority. The clinical relevance of this finding is unknown. Fertility, pregnancy and lactation: Pregnancy: Data on pregnant women (more than 4 000 of Abrysvo on fertility are available. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility (see SmPC section 5.3). Undesirable Effects: The most frequently reported adverse reactions were fatigue (33%), vaccination site pain of Abrysvo. There(24%), were no unexpected safety findings. Refer SmPC section 4.8from forwere further information effects. Category: prescription which to may not be renewed S1A. Package quantities Marketing exposed outcomes) indicate no malformative nor feto/neonatal toxicity. animal withon Abrysvo do not indicate direct indirect harmful with respect reproductive section 5.3). Inand a phase studyAuthorisation (Study 1), maternal (27%), headache myalgia (21%) and arthralgia (10%). Thetomajority ofResults reactions mildstudies to moderate inside severity andLegal resolved withinorProduct 1-3 dayssubject of onset.toeffects Immunocompromised individuals 18toxicity years(A): of(see ageSmPC and older: Reactogenicity was3 consistent with theNumbers: knownadverse profile One dose pack needle; EU/1/23/1752/001. For further information on thisgroup medicine please contact: Pfizer Medical on 1800 633detected 363 or atinmedical.information@pfizer.com. queries regarding product availability Pfizer events reported within 1 month after vaccination were similar the Abrysvo andinformation the placebo (13%). Information No safety signals were up to 24 months age. The incidences of adverse events reported withincontact: 1 month afterHealthcare birthNumbers: in infants of Abrysvo. Therewith were no unexpected safety findings. Refer toinSmPC section 4.8 for(14%) further ongroup side effects. Legal Category: Product subject toinfants prescription which mayofnot beFor renewed (A): S1A. Package quantities andplease Marketing Authorisation Ireland Unlimited Company, The Watermarque Ringsend Road,Major Dublin 4, D04 K7N3 +assessed 353contact: 1 4676500. Marketing Authorisation Holder: Pfizer MA EEIG,birth Boulevard de laand Plaine Bruxelles, Belgium were similar in the Abrysvo (38%) and theBuilding, placebo group (35%). birth outcomes in the Abrysvo group comparedonto placebo included (207 (6%) 17217, (5%), respectively), lowproduct birth weight (186 (5%) and 158 (4%), Pfizer respectively) and One dose pack with needle;group EU/1/23/1752/001. For further information on this medicine please Pfizer Medical Information 1800 633 363Europe or atpremature medical.information@pfizer.com. For1050 queries regarding availability please contact: Healthcare Date ofUnlimited Preparation: 06/2026 congenital anomalies (205 (6%) 245 (7%), respectively). Breast-feeding: It is4,unknown whether is excreted in human milk. NoHolder: adversePfizer effectsEurope of Abrysvo haveBoulevard been shown newborns of vaccinated Ireland Company, Theand Watermarque Building, Ringsend Road, Dublin D04 K7N3 + 353Abrysvo 1 4676500. Marketing Authorisation MA EEIG, deinlabreastfed Plaine 17, 1050 Bruxelles, Belgium mothers. Fertility: No human data on the effect Ref: bAB 9_0 of Abrysvo on fertility06/2026 are available. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility (see SmPC section 5.3). Undesirable Effects: The most frequently reported adverse reactions were fatigue (33%), vaccination site pain Date of Preparation: (27%), headache myalgia (21%) and arthralgia (10%). The majority of reactions were mild to moderate in severity and resolved within 1-3 days of onset. Immunocompromised individuals 18 years of age and older: Reactogenicity was consistent with the known profile Ref: bAB 9_0 (24%), REFERENCES: 1. Abrysvo Summary of Product Characteristics. of Abrysvo. There were no unexpected safety findings. Refer to SmPC section 4.8 for further information on side effects. Legal Category: Product subject to prescription which may not be renewed (A): S1A. Package quantities and Marketing Authorisation Numbers: 2. Hameed SS, Robertson C, Morrison etForal.further Early evidence ofon RSV impact on hospitalisation rates of older people Scotland. Lancet. 2025. https://doi.org/10.1016/S1473-3099(25)00064-7. REFERENCES: 1. Abrysvo Summary of K, Product Characteristics. One dose pack with needle; EU/1/23/1752/001. information thisvaccination medicine please contact: Pfizer Medical Information on 1800 633in363 or at medical.information@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare 2.PP-A1G-IRL-0120 Hameed SS, Robertson C,Watermarque Morrison K, et al. Early evidence ofDublin RSV vaccination on hospitalisation rates of olderHolder: peoplePfizer in Scotland. Lancet. 2025. https://doi.org/10.1016/S1473-3099(25)00064-7. | JUL2026 Ireland Unlimited Company, The Building, Ringsend Road, 4, D04 K7N3impact + 353 1 4676500. Marketing Authorisation Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium Date of Preparation:|06/2026 PP-A1G-IRL-0120 JUL2026 Ref: bAB 9_0

REFERENCES: 1. Abrysvo Summary of Product Characteristics.