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Familial Mediterranean Fever and PFAPA Syndrome: Contemporary Disease management and treatment when partial overlap is present
130
Karananou Panagiota
Haploinsufficiency of A20 protein (HA20) and Deficiency of adenosine deaminase 2 (ADA2) enzyme (DADA2): Immunodeficiencies or Autoinflammatory diseases?
144
Pratsidou-Gertsi Polyxeni
Introduction to Interferonopathies. Aicardi Goutières and CANDLE syndromes: new members in the genetically determined Autoinflammatory diseases family
President A. Constantopoulos
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Koutsonikoli Artemis Monogenic Systemic Lupus Erythematosus (mono-SLE) and SAVI syndrome (STING-Associated Vasculopathy with onset in Infancy)
160
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174 BETWEEN COLLEAGUES
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176 BOOK PRESENTATION
Stelios Antoniadis
180 INSTRUCTIONS TO AUTHORS
K.
e-mail: flkan@auth.gr
Φλωρεντία Κανακούδη-Τσακαλίδου
«General pediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in ordertoguidefurtherexaminationsandreferthepatientstoaspecialistrheumatologist».
ΒΙΒΛΙΟΓΡΑΦΙΑ
1.Κανακούδη-Τσακαλίδου, Φ, Παπαχρήστου, Φ, Δρόσου-Αγακίδου Β, Ζαφειρίου, Δ (2023) Βασική Παιδιατρική, 4η έκδ., University Studio Press.
2. Rood JE, Behrens EM. Inherited Autoinflammatory Syndromes. Annu Rev Pathol 2022 Jan 24;17:227-249
3. di Donato G, d’Angelo DM, Breda L, Chiarelli F. Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives. Int J Mol Sci 2021, 22,6360. https://doi.org/10.3390/ ijms22126360.
4.Crow YJ, Stetson DB. The type I interferonopathies: 10 years on. Nat Rev Immunol 2022;22(8):471-483.
5. Savic S, Caseley EA, Michael F. McDermott MF. Moving towards a systems-based classification of innate immune mediated diseases. Nature Reviews Rheumatology, 2020; 16: 222-237
6. The expanding pathways of autoinflammation: a lesson from the first 100 genes related to autoinflammatory manifestations. Adv Protein Chem Struct Biol 2020;120:1-44. doi: 10.1016/bs.apcsb.2019.11.001. Epub 2019 Dec 12.
K.
e-mail:
Correspondence
Vasiliki Sgouropoulou
Olimpiados 3Β, 57010
Pefka Thessaloniki
Τ. +30 2310676202, M. +30 6972232877
e-mail: vsgouro@hotmail. com
Familial Mediterranean Fever and PFAPA Syndrome: Contemporary Disease management and treatment
when partial overlap is present
Vasiliki Sgouropoulou
Abstract
Familial Mediterranean Fever (FMF) and PFAPA syndrome are the most common autoinflammatory diseases in childhood. FMF is a genetic disorder of the innate immune system, caused by mutations in the MEFV gene. Today, in addition to the former clinical criteria, we have new diagnostic criteria that include genotype, while modern tools are used for disease monitoring. At the same time, in addition to the standard treatment with colchicine, innovative biological agents are used, aiming at complete remission of the disease. PFAPA syndrome is a multifactorial disease with an unknown genetic basis. The onset of the disease in the majority of the cases is observed in early childhood up to 6 years of life, while there are records of onset even in adulthood. The coexistence of the disease with mutations in the MEFV gene is particularly common and has been associated with late onset of the disease and with episodes of shorter duration and lower frequency. The conventional treatment methods with corticosteroids and tonsillectomy have now been replaced by colchicine. The prognosis of the syndrome is excellent, with episodes resolving 3-6 years after onset, while only 20% of patients will continue to have episodes in adulthood.
1st Department of Paediatrics, Paediatric Immunology and Rheumatology Referral Center, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Απλοανεπάρκεια
K.
e-mail: panagiotakarananou@gmail.com
Παναγιώτα
Correspondence
Panagiota Karananou
Aigaiou 41, 55133
Kalamaria, Thessaloniki
Τ. +30 2310249878
M. +30 6974842552
e-mail: panagiotakarananou@gmail.com
Haploinsufficiency of A20 protein (HA20) and Deficiency of adenosine deaminase 2 (ADA2) enzyme (DADA2): Immunodeficiencies or Autoinflammatory diseases?
Panagiota Karananou
Abstract
Haploinsufficiency of A20 protein (HA20) is an autoinflammatory disease caused by highpenetrance loss-of-function germline mutations in TNFAIP3(Τumor Νecrosis Factor α-Induced Protein 3). Patients may present with symptoms of Adamantiades-Behcet-like disease with the main difference of the earlier onset (childhood). Fever is also reported as well as lipodystrophy. However, the hallmark feature of the disease is the recurrent painful oral, genital and/or gastrointestinal ulcers. Other common symptoms that occur at various time points during disease course include gastrointestinal complaints, polyarthritis and/ or arthralgia, skin involvement and less frequently, ocular and cardiovascular and renal involvement.
Deficiency of adenosine deaminase 2 (ADA2) enzyme (DADA2) is a monogenic autoinflammatory disease, with polyarteritis nodosa (PAN)–like features, associated with mutations in ADA2 protein. The first symptoms of the disease occur early, before the age of 10 years. DADA2 can manifest with intermittent fevers, and vasculitis/vasculopathy that are described in the group of rheumatic diseases in older children and adolescents (mainly skin, neurological, gastrointestinal with or without cardiovascular and renal involvement). These manifestations may also be combined with a clinical picture of immunodeficiency.
To date there is no specific treatment for HA20 and DADA2. The treatment depends on the clinical manifestations and severity of the disease. In conclusion, in pediatric patients with manifestations, such as those of Adamantiades-Bechet syndrome at a very young age, as well as the coexistence of polyarteritis nodosa and immunodeficiency in the first decade of life, an autoinflammatory disease should be considered and suspected.
Keywords: Haploinsufficiency of A20 protein (HA20), Deficiency of adenosine deaminase 2 (ADA2) enzyme (DADA2), autoinflammatory diseases, immunodeficiencies.
Panagiota Karananou 4th Department of Pediatrics, Aristotle University of Thessaloniki, School of Medicine, Papageorgiou General Hospital, Ring Road Nea Efkarpia 56403, Thessaloniki, Greece
Κατάλογος
ADA2 enzyme: Adenosine deaminase 2 enzyme,
ADA2: Deficiency of adenosine deaminase 2 (ADA2) enzyme
ΗΑ20: Haploinsufficiency of A20 protein,
JAK: janus kinase, janus
IL: Interleukin,
NF-κB: Nuclear factor of activated B cells
NEMO: NF-κB essen-
tial modifier, NF-κB
NLRP3: NOD-like receptor protein 3
TNF: Tumor necrosis factor, παράγοντας νέκρωσης των
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Ιντερφερονοπάθειες,
Aicardi Goutières (AGS)
CANDLE (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature).
K.
e-mail: jennypratsidou. gertsi@gmail.com
Correspondence
Jenny Pratsidou-Gertsi
Vasilikou 13, 54636
Thessaloniki
Τ. +30 2310204872
M. +30 6944598159
e-mail: jennypratsidou. gertsi@gmail.com
Interferonopathies, Aicardi Goutières and CANDLE syndromes: new members in the genetically determined autoinflammatory diseases Family
Jenny Pratsidou-Gertsi
Abstract
Interferonopathies are heterogeneous diseases resulting from an immune dysregulation of the interferon type I (IFN-I) expression. They are attributed to genetic disorders concerning the production and/or function of IFN-I. Interferonopathies are multisystem overlapping diseases with an early onset, recurrent or persistent inflammatory phenotype indicative of vasculitis, with an increased morbidity and mortality, and no cure. An early recognition is based on gene expression profiling with Next-Generation Sequencing and IFN gene signature, and the genetic monitoring is based on the IFN activity score. Targeted therapy with contemporary biologic agents has improved their outcome. The prototype of interferonopathies is Aicardi Goutières syndrome (AGS) and of proteasomopathies- a subgroup of interferonopathies-, CANDLE syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature). AGS is attributed to mutated genes of the nucleic acid recognition and processing pathway. It has an early onset- even from the neonatal period- with a severe phenotype of neuro-autoinflammation similar to congenital infections. AGS has a progressive course and an increased mortality, with severe disabilities evident in the survivors. The escorting clinical manifestations are limp and ear pernio-like lesions and the laboratory findings reminiscent of Systemic Lupus Erythematosus. Similar manifestations are also recognized in proteasomopathies, entities due to proteasome mutations that lead to an endoplasmic concentration of degraded proteins and intracellular stress. CANDLE syndrome is characterized by fevers, dermatoses, joint contractures, panniculitis, CNS and eye involvement and later, development of metabolic syndrome and hepatic steatosis. It partially responds to biologic therapy with anti-TNF agents; recently, JAK inhibitors are promising.
1st Department of Paediatrics, Paediatric Immunology and Rheumatology Referral Center, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Epub 2023 Jan 11.
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SAVI (STING-Associated Vasculopathy with onset in Ιnfancy)
K.
e-mail:
(chilblain lupus).
Correspondence
Artemis Koutsonikoli
Pantazidou 38, Pylaia
Τ. +30 2310892498
M. +30 6944590243
e-mail: artemis_kou@ yahoo.com
Monogenic Systemic Lupus Erythematosus (monoSLE) and SAVI syndrome (STING-Associated Vasculopathy with onset in Infancy)
Artemis Koutsonikoli
Abstract
Monogenic Systemic Lupus Erythematosus (monoSLE) is an autoinflammatory disease, caused by a single gene’s mutation. The approximately 30 described genes are involved in inflammation and participate in the: a. complement’s activation pathway or b. interferon (IFN) signaling pathway or c. extracellular DNAses’ function or d. mechanisms of immune tolerance. Characteristics of monoSLE are the early onset in children <5 years old and the frequent familial presentation. Depending on the immune pathway, disrupted by each mutation, the pathophysiology, inheritance and clinical picture differ. Patients generally present with symptoms from multiple systems and sometimes the clinical phenotype is reminiscent of an autoimmune disease, like juvenile SLE. Among the most characteristic skin manifestations are chilblains (chilblain lupus). Treatment is challenging, as there is often no response to the standard regimens used in jSLE. SAVI syndrome (STING-Associated Vasculopathy with onset in Infancy) is a rare monogenic autoinflammatory syndrome. It is caused by a mutation in the gene encoding the protein STING (STimulator of INterferon Genes), which leads to its increased activation, overproduction of IFN and induction of systemic inflammation. The syndrome’s onset is often in the neonatal period. The manner of inheritance is autosomal dominant but de novo mutations are more common. SAVI typically manifests with cutaneous signs of severe vasculopathy and interstitial lung disease (with secondary pulmonary fibrosis). Symptoms from other systems may coexist. The prognosis is poor mainly due to the pulmonary involvement. Response to established immunomodulatory agents is inadequate. Encouraging results are emerging from the use of janus kinase (JAK) inhibitors.
ΣYΝΔΡΟΜΟ SAVI (STING-ASSOCIATED VASCULOPATHY WITH ONSET IN INFANCY)
Εικόνα
(STING-Associated Vasculopathy
(STING-Associated Vasculopathy with onset in Ιnfancy)
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