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Peer Review: An Overview of Psoriasis
PEER REVIEW: PSORIASIS
What is psoriasis?
Psoriasis is a common skin condition that is thought to affect between 2% and 3% of the population of the United Kingdom and Ireland. It is an immune condition which affects the skin but is also associated with a condition called psoriatic arthritis which affects the joints. However, psoriasis is much more than just a skin condition. It can also affect people physically and psychologically. When a person has psoriasis, the skin replacement process speeds up, taking just a few days to replace skin cells that usually take 21-28 days. This results in an accumulation of skin cells on the surface of the skin, in the form of psoriatic plaques. This process is the same wherever it occurs on the body. Psoriasis affects men and women equally and can occur at any point in the lifespan, affecting children, teenagers, adults and older people. However, there seem to be two peaks: from late teens to early adulthood and between the ages of around 50-60. It is a long-term condition that may wax and wane. Sometimes it can appear mild and other times it can be more severe. Although there is no cure, it can be managed and with the right treatment and advice, many people are able to live well with the condition.
Usually, a trigger is required for psoriasis to develop, and this could be a throat infection, an injury to the skin, certain medications or physical or emotional stress. There are also others, as triggers can vary from one person to the next. People who are unfamiliar with the condition sometimes ask whether psoriasis can be transmitted from person to person through contact. The answer is no. Nor can it be transferred from one part of the body to another. However, some people may have a family history of psoriasis and certain genes have been identified as being linked to the condition. Many genes need to be involved though and even if the right combination of genes has been inherited, psoriasis still may not appear.
What does it look like?
Written by Laura Stevenson, Deputy Chief Executive, Psoriasis Association
or dark patches of skin, covered with silvery white scales. These scales are the buildup of skin cells waiting to be shed and the redness is caused by the increase in blood vessels required to support the increase in cell production. Psoriasis can range in appearance from mild to severe.
The plaques can appear in a variety of shapes and sizes, varying from very small to several centimeters in diameter. They have a well-defined edge, making it easy to tell where the psoriasis ends, and non-psoriatic skin begins. For some people, plaques may be thin or flat to the skin surface but for others they may be much thicker. It is not unusual for psoriasis to be itchy, and it can often feel painful or sore. Around 80% of people with psoriasis have plaque psoriasis, with plaques appearing most often on the elbows, knees, lower back and quite often in the scalp. However, there are several different types of psoriasis, and any area of the body can be affected. Guttate psoriasis, which is most often seen in children and teenagers, can result in small and scaly patches (often less than 1cm in diameter). These can be numerous and cover all areas of the body. This type of psoriasis can be triggered by a throat infection. Pustular psoriasis is different again and can take the form of small sterile blisters usually on the hands and feet. Nail psoriasis can result in changes to the appearance and texture of nails. In sensitive areas, such as the armpits and groin, psoriasis is often red and shiny, with little or no scaling.
What causes it?
Traditionally psoriasis was thought to be a condition of the uppermost layer of the skin (the epidermis), but now it is known that the changes in the skin begin in the immune system when certain immune cells (T cells) are triggered and become overactive.
The T cells produce inflammatory chemicals and act as if they were fighting an infection or healing a wound, which leads to the rapid growth of skin cells, causing plaques to form. As a result, psoriasis is sometimes referred to as an ‘auto-immune disease’ or ‘immune-mediated condition’. It is not yet clear what triggers the immune system to act in this way. Links between severe psoriasis and conditions such as diabetes and heart disease have been found but this does not necessarily mean that psoriasis causes these conditions, or that these conditions cause psoriasis. Research is ongoing to try to understand the true nature of this link, why these conditions sometimes occur in the same people and if this is also true of mild or moderate psoriasis.
How can it be treated?
How psoriasis is treated is dependent upon the type and the severity, although the available treatments fall broadly into four main categories. Topical therapies such as creams, lotions, ointments, foams and gels can be prescribed by a GP and are usually tried first by most people with psoriasis. These can include topical steroids, dithranol, vitamin A and D derivatives and coal tar preparations. If psoriasis is particularly widespread or doesn’t respond to topical treatment, a referral to a dermatologist can take place, who can then offer a wider range of treatment options. Phototherapy treatment with ultraviolet light can be considered. UVB is the most commonly prescribed although treatment with UVA and the use of a chemical agent called psoralen can also be prescribed. This is referred to as PUVA therapy. Phototherapy treatment can necessitate attendance at a phototherapy centre 2 to 3 times a week for several weeks.
Systemic treatments, which are treatments that are taken into the body, can also be used for moderate to severe psoriasis. The main types used in the UK are methotrexate, ciclosporin and acitretin. All require ongoing monitoring with blood tests and blood pressure checks. They do
PEER REVIEW: PSORIASIS
Guttate Psoriasis
Plaque Psoriasis have potential risks and some cannot be prescribed in conjunction with other medications or if the individual is thinking of having children within the next two years. Finally, psoriasis treatment has been revolutionised over the last ten years with the increased use of biologics which can be used to treat severe psoriasis that has not responded to any of the abovementioned treatments. Biologics work by blocking the action of certain immune cells (T cells) or the chemicals released by them. People with psoriasis can also be prescribed biologics if the systemic treatments mentioned above cause side effects which means the person should not take them, or if the person has another condition or medication which means that they should not take the other systemic treatments. There are now over 13 biologics approved by the National Institute for Health and Care Excellence (NICE) for treating severe psoriasis currently available. Additionally, there are a number of biosimilars available for adalimumab, etanercept and infliximab. Managing psoriasis extends far beyond applying treatments and taking medications. Learning to cope with a skin condition can take time as the psychological impact is not always related to the clinical severity of psoriasis. It can be reassuring to hear about how other people cope with their psoriasis and live with their condition. The Psoriasis Association, a leading national charity for people affected by psoriasis in the UK, offers help in this regard by funding research, providing information and raising awareness of the condition. The tailored support offered by the charity’s helpline, and peer-to-peer support offered through its website forums and social media platforms can be invaluable.
Everyone has their own way of coping with psoriasis. Some people cover their skin, either with clothing or special skin camouflage make-up, whilst others are comfortable not covering up at all. Some may wear lighter clothes on the top half of their body to hide flakes from scalp psoriasis, whilst for others this is less of an issue. The most important thing is honesty with any healthcare professional offering treatment, especially if experiencing feelings of anxiety or distress due to the impact of psoriasis.
News - Off-Patent Medicines Industry ‘Vital’
The Medicines for Europe annual conference was held recently, during which the organisation launched a report to optimise market policies for the secure supply of medicines. Health systems face tremendous challenges across Europe. The management of COVID-19, war in Ukraine and high inflation rates are challenging supply chains for the most essential medicines. Off patent medicines account for 70% of those dispensed in Europe, treating severe conditions such as cancer, auto-immune conditions, respiratory diseases, and cardiovascular disease. These medicines are clearly part of the solution for resilient health systems. Policy reforms are needed to strengthen health systems in Europe with off-patent medicines. When revising the EU pharmaceutical legislation, the EU must: • Encourage the use of generic, biosimilar and value-added medicines to increase patient access to medicines and ensure budgetary sustainability • Support the off-patent medicines industry response to inflation by revising procurement guidelines for medicines and safeguarding the medicines manufacturing sector in emergency response plans • Commit to durable supply chains and manufacturing for medicines, by allowing access to EU funds • Critically assess the IP infrastructure on medicines, taking action to eliminate abuses, and fully supporting the entry into force of the SPC manufacturing waiver on 01 July 2022. At the Medicines for Europe annual conference, Elisabeth Stampa, President, Medicines for Europe commented, “The role of the EU in health policy took on a new life during the pandemic and should continue to do so if we want our health systems to be resilient. Europeans now expect strong EU leadership on health policy and our industry, as the biggest supplier of medicines to patients in Europe, is ready to play its part. “We consistently bring solutions to improve access to medicines and reduce pressure on healthcare budgets. “Today we are launching a report to optimise market policies for the secure supply of medicines. Our recommendations will ensure that medicines remain available, affordable, and accessible for patients, and also reduce the risk of medicines shortages and increase European strategic autonomy.” Margaritis Schinas, Vice President of the European Commission for Promoting our European way of life, said, “We are revising the pharmaceutical legislation at EU level. The objectives are clear: having medicines at affordable conditions for all, and ensuring European industry remains an innovative world leader. These are not antagonistic objectives, on the contrary, both are possible, and we should make them a reality.” The report titled ‘New pricing models for generic medicines to ensure long-term healthy competitiveness in Europe’ is available by visiting www. medicinesforeurope.com
FOR THE TREATMENT OF MODERATE TO SEVERE
atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy1
MARKETING AUTHORISATION HOLDER: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany. Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.
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 via HPRA Pharmacovigilance; website: www.hpra.ie. LEGAL CLASSIFICATION: POM (S1A). Full Summary of Product Characteristics is available at www.medicines.ie Reference 1. RINVOQ Summary of Product Characteristics, available on www.medicines.ie
©2022 AbbVie Inc. All rights reserved. IE-RNQ_AD-220036 | March 2022
PEER REVIEW: PLEURAL EFFUSION
Written by P. Ridge; D Breen - Interventional Respiratory Unit, Galway University Hospital Corresponding Author: Padraic Ridge, Galway University Hospital, Newcastle, Galway, Ireland Email: P.macaniomaire1@gmail.com
Abstract: Malignant pleural effusion (MPE) is a common clinical entity affecting 40,000 people per year in the UK. MPE can occur with a primary pleural malignancy, typically mesothelioma or more commonly as a metastatic manifestation of a non pleural primary malignancy. In Ireland mesothelioma is an infrequent diagnosis and therefore the majority of cases of MPE represent advanced Stage IV malignant disease.1 In this paper we will review the diagnosis and subsequent management of MPE.
Dr Padraic Ridge Dr David Breen
Introduction
Malignant pleural effusion (MPE) is defined by malignant cells within the pleural space. The pleural space can be involved by malignancy through direct extension of tumour, haematogenous spread or through primary pleural malignancy (mesothelioma).2,3 While any cancer can metastasize to the pleural space the most common in descending order are lung, breast, lymphoma, ovarian and gastric cancer. These account for approximately 80% of MPE.4,5 The incidence of MPE In the UK is circa 40,000 people/year. Median survival from diagnosis of MPE ranges from 3-12 months depending on the tumour type.5 Metastatic involvement of the pleural space by lung cancer is associated with the shortest median survival of 3 months, however novel targeted therapies may improve this prognosis.4 6
Presentation
Patients may present with dyspnoea, orthopnoea or chest pain. Dyspnoea can be very severe and dramatically affect quality of life. However Individuals can often be relatively asymptomatic and MPE may only be incidentally picked up on routine imaging studies.4 The size of the effusion does not reliably predict a patients symptom burden as the fluid can accumulate gradually over time allowing the patient to compensate. Symptoms are more strongly correlated with the rate of fluid accumulation.7
Diagnosis
It is important to note that 50% of pleural effusion in the setting of individuals with cancer are non-malignant.8 These may be caused by bronchial obstruction from tumour or benign causes such as congestive heart failure or infection. These are termed paramalignant or non-malignant pleural effusions. See Figure 1. This has important implications for staging and treatment of individuals.9
Malignant pleural involvement should never be presumed and it is crucial to pathologically stage pleural effusions in the setting of malignancy. Malignant involvement of the pleural space implies stage 4 malignancy thus radical treatment options such as surgery are not an option. For those with para-malignant effusions radical, curative treatments may still be an option.10-12 Assuming malignant involvement in those with a paramalignant effusion could wrongly deny them potentially curative treatment.
Figure 1 Fig 1.
Causes of paramalignant effusions
Direct tumour effect: -Lymphatic obstruction -Bronchial obstruction -Trapped lung -Chylothorax -Superior vena cava obstruction
Complications of therapy: -Radiotherapy -Chemotherapy
Imaging
Chest radiography (CXR): Is the initial imaging for most. The standard posterior-anterior (PA) CXR will only start to become abnormal in the presence of approximately 200ml of pleural fluid.13 The initial sign is costophrenic blunting, which may progress to opacification with a meniscus or even a full “white out” with tracheal deviation away from the effusion.13,14 Lateral films are more sensitive and can detect pleural effusions of 50ml.13 Ultrasound (US): Ultrasound scanning has become the gold standard in diagnostic imaging for MPE. Ultrasound can differentiate pleural effusion from lung collapse or pleural thickening.4 USS outperforms CT at identifying pleural features such as: pleural thickness, nodules and adhesions. Features consistent with malignant pleural effusion on USS include: nodules of the pleura or diaphragm, diaphragmatic thickening (>7mm) and pleural thickening (>1cm). These findings on ultrasound have a sensitivity and specificity of differentiating benign from malignant effusions of 79% and 100% respectively. See Figure 2 15 Ultrasound has also developed a key role in pleural procedures. It has the benefit of not exposing the patient to radiation and being able to be performed at the bedside.
Figure 2: Ultrasound: Malignant pleural effusion with diaphragmatic nodules
Ultrasound should be used to “mark the spot” immediately prior to any form of pleural intervention. As pleural fluid can often be free flowing the patient should be advised to remain as still as possible from the moment of marking the spot until the pleural intervention takes place. The method of marking the spot in the radiology department and then transferring back to the ward for pleural intervention is not recommended.4 For small effusions, or patients who are liable to move post marking, intervention can be performed under real time ultrasonography.5 Ultrasound guidance increases the accuracy and reduces the risk of inadvertent damage to surrounding organs and now is a fundamental requirement for any pleural service.16
Computed Tomography and PET:
Standard CT and PET are important modalities to further investigate an effusion and in particular for further assessment for an underlying primary cancer, assessing extent of disease, and identifying alterative cause of the effusion such as bronchial obstruction, infection or pulmonary embolism. 17 If stage 4 disease is confirmed then PET scan is not pursued. Signs of malignant pleural effusion on CT include pleural thickening, nodular pleural thickening, mediastinal pleural thickening and circumferential pleural thickening.18 Figure 3 CT is also useful for helping the USS operator better conceptualize the pleural effusion.5 However, CT is not as sensitive at detecting pleural thickening or identifying internal septations in a pleural effusion.19
Sampling Aspiration:
Pleural aspiration is the initial method of obtaining pathological confirmation of MPE. It should always be performed with US guidance. It can be performed at the bedside using a 21G needle and a 50ml syringe or as part of a therapeutic thoracentesis.4 The procedure should be performed aseptically and local anaesthetic should be administered particularly superficially and at the pleural surface. The British Thoracic society recommend all pleural samples should be sent to biochemistry for LDH and protein (5ml), microbiology for culture, sensitivity and Acid Fast Bacilli (5ml), and cytology (~40ml). If there is a concern for pleural infection, pleural samples should be inoculated in blood culture bottles as this increases the microbiological yield.20 We also recommend the pH should be checked within an hour by the person performing the aspiration using a standard arterial blood gas (ABG) needle and ABG machine. In the case of MPE PH is predictive of future chemical pleurodesis rates and may add evidence to the diagnosis of MPE.4,5,21,22 For Para-malignant effusions, such as pleural infections, pH in combination with USS features may indicate the need for a chest drain and therefore both are important point of care tests.4 It is important to note pleural aspiration gives a cytological sample. In malignancies such as mesothelioma, where histological samples are recommended, sensitivity of cytological samples can be low as 32%. 23 The overall sensitivity of aspiration for MPE is 60% (range 40-87%).4 Therefore in the right clinical context a negative aspiration should not out-rule MPE and further tests may be required. One study looked at the benefit of repeating aspiration. This study achieved a yield of 65% from initial aspiration, a further 27% from a second aspiration and 5% from a third aspiration.24 Each aspiration meant a repeat procedure for the patient with all its associated risks and increased wait time for results. Also repeated interventions may make the pleural space more complex, making it more difficult to perform a definitive procedure in the future. Therefore, if local resources allow, we recommend proceeding to a more definitive procedure as an alternative to repeated aspirations. (See Figure 4 on page 36).
Biopsy
For patients undiagnosed after initial less invasive methods a biopsy is required. This can be achieved by percutaneous or thoracoscopic methods.
Percutaneous pleural biopsy:
CT guided biopsy has been the favoured method due to its superior sensitivity of 88%. 25 Prior to this blind percutaneous biopsy was traditionally performed with an Abram’s needle. This method is performed less now due to its low sensitivity of 57% and high complication rate. However, recent studies have shown that biopsies taken with an Abrahm’s needle in combination with USS guidance have comparable sensitivity and safety to CT guided pleural biopsies.26,27 Thoracoscopy biopsy: Thoracoscopy allows direct visualisation of the pleura and sampling of abnormal pleural patches. A medical thoracoscopy is performed by a respiratory physician. It can be performed in the endoscopy suite under conscious sedation.28 A Video assisted thoracoscopic surgery is performed by a surgeon and requires a general anaesthetic and single lung intubation. Therefore, a medical thoracoscopy is the preferred method for a frail patient.4 The sensitivity of medical thoracoscopy and VATS for malignancy is 92.6% and 95% respectively.4 An advantage of these procedures is that they can be therapeutic as well which we will outline below.
Management
Once a diagnosis has been obtained, Multiple factors should be considered prior to deciding on definitive treatment such as: symptoms, need for future samples for tumour confirmation or molecular markers, rate of fluid accumulation, life expectancy, tumour type and predicted response to treatment. A potential algorithm is outlined in Figure 5.5 (See figure 5 on page 36). Management should be delivered by a multidisciplinary team including respiratory physicians, oncology, radiation oncology, Thoracic surgeons, palliative care physicians and other supportive staff. Due to the limited life expectancy of those with MPE care should be delivered in a timely and convenient manner to the patient. We aim to provide pleural management in the outpatient setting as much as possible to achieve this goal.5
1) Conservative Monitoring
For those who are asymptomatic we do not perform any invasive intervention as there is no benefit to the patient. We educate the patient, provide them with contact details and arrange regular follow up. If they develop symptoms at a future date then we offer a pleural intervention.
2) Systemic Therapy
Response of the MPE depends on the histology of the primary tumour. Lymphoma, small cell lung carcinoma, germ cell tumours, prostate carcinoma and ovarian cancers typically have a favourable response to systemic chemo-radiotherapy.29
3) Therapeutic Thoracentesis
Breathlessness in malignancy can be multifactorial and even in those with a MPE, it may be due to other causes such as lymphangitis carcinomatosa, bronchial obstruction, pulmonary embolism, chronic lung disease or even ischemic heart disease.4,30
Figure 3: Computed Tomography: Pleural thickening (*) and pleural nodule (N) on CT
Before proceeding with definitive pleural management one should always perform a therapeutic thoracentesis to assess for improvement in dyspnoea. The initial procedure can be both therapeutic and diagnostic. Post thoracentesis, patients should be assessed for radiological expansion of the underlying lung and symptomatic benefit. When
Figure 4
Fig. 5
a lung does not fully expand to oppose the parietal pleura this is termed a trapped lung. Only those who show an improvement in symptoms post thoracentesis should have a definitive pleural procedure performed. Those who do not show an improvement should be investigated for an alternative cause of their symptoms. 4 The minimal amount of fluid to remove to assess for clinical response is 500ml.30 Thoracentesis is associated with a risk of re-expansion pulmonary oedema (RPO). Standard practice is to remove 1.2L in one session. However no maximal volume has ever been identified. Methods of minimising the risk of RPO include pleural manometry and monitoring for chest tightness, cough or dyspnoea during thoracentesis and stopping if they begin to develop. 5,31 As mentioned above, therapeutic thoracentesis allows the identification of individuals who have a trapped lung. This is important as those with a trapped lung do not derive benefit from chemical pleurodesis as there is no pleural opposition to allow this process to occur. Therefore an indwelling pleural catheter is the best option for these patients.
4) Chest Drain Insertion and
Complete Drainage
Chest drain insertion and full drainage of the pleural effusion can be considered for those who accumulate fluid very slowly, have a short life expectancy or choose to not have a definitive procedure. In particular it is a viable option in those who have a chemo-sensitive tumour that is expected to respond to systemic therapy.
5) Chemical Pleurodesis
Chemical pleurodesis can be performed using talc, tetracycline or bleomycin. It induces pleural inflammation resulting in adhesion of the visceral pleura to the parietal
Fig. 5
PEER REVIEW:
pleura. Talc is the most effective and most used agent in Ireland.32 For chemical pleurodesis to be effective the effusion needs to be drained and the lung expanded to allow the apposition of visceral and parietal pleura.4 Talc can be administered at the bedside via a chest drain (talc slurry). (See Figure 6 on page 37). It can also be administered at the time of thoracoscopy (talc poudrage). The thoracoscopy method is more invasive but allows one to examine and sample the pleura, lyse any adhesions and spread the talc more evenly on the pleura which may lead to better control. (See Figure 7 on page 37). However, neither method has been shown to be superior. 33-35 Talc administration can be associated with pain therefore lidocaine is always administered to the pleura beforehand and generous analgesia should be prescribed.36 A study has shown that non-steroidal antiinflammatories do not effect pleurodesis rates.37 It is not unusual for patients to have a temperature post administration due to a systemic inflammatory response.4
6) Indwelling Pleural Catheter
An IPC involves tunnelling a catheter through the skin into the pleural space. This catheter can then remain in place for a prolonged period allowing a family member to intermittently drain the effusion at home using a vacuum bottle (usually every 2nd day). (See Figure 8 on page 37). The drain can be inserted in an outpatient setting and thus does not require admission. It can also be inserted at the time of diagnostic thoracoscopy with or without concomitant talc which is termed an accelerated pleurodesis. 38-40
7) IPC vs Chemical Pleurodesis
An IPC is the only effective option in those with non-expandable or trapped lung where chemical pleurodesis has been shown to be ineffective.4 In those with expandable lung the two methods are comparable in terms of symptom control and safety. Generally we discuss the benefits and drawbacks of each method of managing the pleural fluid with the patient and in turn allow them to make an informed decision based on evidence and personal preference.
Fig. 6
Guide to performing Talc slurry
-Insert small bore chest tube -Drain pleural effusion completely -Confirm lung expanded and drain still in pleural space -Administer analgesia pre procedure -Instill lidocaine into pleural space (3 mg/kg; maximum 250 mg) -Instill 4-5g of sterile graded talc in 50 ml 0.9% saline into pleural space -Clamp drain for 1-2 hours -Remove chest drain within 24-48 hours
Fig. 8
Figure 6
Fig. 7 Figure 7
Fig. 6
Guide to performing Talc slurry
Figure 8 -Insert small bore chest tube -Drain pleural effusion completely -Confirm lung expanded and drain still in pleural space -Administer analgesia pre procedure -Instill lidocaine into pleural space (3 mg/kg; maximum 250 mg) -Instill 4-5g of sterile graded talc in 50 ml 0.9% saline into pleural space -Clamp drain for 1-2 hours -Remove chest drain within 24-48 hours
The advantages of chemical pleurodesis are that it is a one-off procedure, if successful and there is no ongoing management of an indwelling drain for the patient. However it requires chest drain insertion, hospital admission for a few days, can be painful and pleural infection has been reported.5 IPCs are associated with less repeated procedures and fewer days in hospital as it can be inserted as a day case.41 However, IPC insertion’s can be complicated by local skin infections, pleural infection and catheter blockage or fracture. Some patients do not like the burden of managing the drain long term.42 Ultimately the choice between chemical pleurodesis andvs IPC is usually made based on the patients preference for avoiding a hospital admission versuss the burden of the ongoing management of the IPC drain.41,42
8) Palliative
Occasionally patients may be too unwell for an invasive procedure and optimal control of symptoms is best achieved through systemic opioid and benzodiazepine therapy guided by the palliative care services.5
Conclusion
MPE are common, indicate advanced stage and are associated with a high morbidity and mortality. Diagnosis should always be prompt and confirmed pathologically. MPE results in a major burden on the health service and account for significant inpatient days. It’s for this reason that we have developed a pleural service in Galway University Hospital which has been in constant development since 2010. Our service has been pivotal in reducing inpatient days and reducing symptom burden in those suffering from MPE through the provision of the treatment strategies outlined in this review. We believe management of patients with MPE should focus on symptom control, be delivered on an outpatient basis (when possible) and should always be led by patient preference.
