scholarly journals IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Hana Malcova ◽  
Zuzana Strizova ◽  
Tomas Milota ◽  
Ilja Striz ◽  
Anna Sediva ◽  
...  
Keyword(s):  
Periodic Fever ◽  
Tumor Necrosis Factor Receptor ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Clinical Manifestations ◽  
Musculoskeletal Symptoms ◽  
Mevalonate Kinase Deficiency ◽  
Periodic Fever Syndromes ◽  
Therapeutic Uses ◽  
Fever Syndromes ◽  
Mediterranean Fever

Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still’s disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.

Le sindromi autoinfiammatorie: quando non è solo PFAPA

2021 ◽  
Vol 40 (4) ◽  
pp. 221-225
Author(s):  
ALBERTO TOMMASINI ◽  
LOREDANA LEPORE
Keyword(s):  
Periodic Fever ◽  
Mevalonate Kinase Deficiency ◽  
Inflammatory Disorder ◽  
Mevalonate Kinase ◽  
Red Flags ◽  
Periodic Fever Syndromes ◽  
Hereditary Periodic Fever Syndromes ◽  
Hereditary Periodic Fever ◽  
Fever Syndromes ◽  
Mediterranean Fever

PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis) is the most common self-inflammatory disorder in children. The diagnosis of PFAPA is easy, based on Thomas criteria, and the prognosis is good. Differential diagnosis with hereditary periodic fever syndromes (Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TRAPS and CAPS) should be considered only in the presence of red flags such as early onset, severe abdominal complaints, arthritis and severe rashes. Some patients may present distinct clinical entities with periodic fevers that neither meet PFAPA criteria nor hereditary periodic fever syndromes genotypes. Subjects with these “Undifferentiated Periodic Fever” may respond to glucocorticoids or colchicines or to anakinra in the most severe cases and still have an undetermined prognosis.

Periodic fever syndromes: a patient diagnosed with recurrent Kawasaki disease

2020 ◽  
Vol 30 (7) ◽  
pp. 1009-1011
Author(s):  
Sena Turk ◽  
Derya Aydin ◽  
Eser Dogan ◽  
Erturk Levent ◽  
Necil Kutukculer
Keyword(s):  
Kawasaki Disease ◽  
Periodic Fever ◽  
Periodic Fever Syndromes ◽  
System Disease ◽  
Rheumatologic Diseases ◽  
Coronary Artery Involvement ◽  
Fever Syndromes ◽  
Mediterranean Fever ◽  
Systemic Onset ◽  
Children Under 5

AbstractKawasaki disease, known as mucocutaneous lymph node syndrome, is a multi-system disease of unknown aetiology that occurs in young children under 5 years of age. The recurrence rate of Kawasaki disease is as rare as 1–3%. Especially in cases with coronary artery involvement, recurrent Kawasaki disease should be investigated in terms of underlying rheumatologic diseases such as periodic fever syndromes, microscopic polyangiitis, polyarteritis nodosa, and systemic-onset juvenile arthritis. In this study, we report homozygote mutations in mevalonate kinase and familial Mediterranean fever genes in a recurrent Kawasaki disease with coronary dilatation.

Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes

2007 ◽  
Vol 292 (1) ◽  
pp. R86-R98 ◽  
Author(s):  
Anna Simon ◽  
Jos W. M. van der Meer
Keyword(s):  
Periodic Fever ◽  
Innate Immune ◽  
Tnf Receptor ◽  
Inherited Disorders ◽  
Autoinflammatory Syndromes ◽  
General Hypothesis ◽  
Periodic Fever Syndromes ◽  
Fever Syndromes ◽  
Mediterranean Fever ◽  
Pyogenic Arthritis

Familial periodic fever syndromes, otherwise known as hereditary autoinflammatory syndromes, are inherited disorders characterized by recurrent episodes of fever and inflammation. The general hypothesis is that the innate immune response in these patients is wrongly tuned, being either too sensitive to very minor stimuli or turned off too late. The genetic background of the major familial periodic fever syndromes has been unraveled, and through research into the pathophysiology, a clearer picture of the innate immune system is emerging. After an introduction on fever, interleukin-1β and inflammasomes, which are involved in the majority of these diseases, this manuscript offers a detailed review of the pathophysiology of the cryopyrin-associated periodic syndromes, familial Mediterranean fever, the syndrome of pyogenic arthritis, pyoderma gangrenosum and acne, Blau syndrome, TNF-receptor-associated periodic syndrome and hyper-IgD and periodic fever syndrome. Despite recent major advances, there are still many questions to be answered regarding the pathogenesis of these disorders.

scholarly journals TNFRSF1A gene variant identified in a boy with recurrent episodes of fever

2018 ◽  
Vol 146 (9-10) ◽  
pp. 577-580
Author(s):  
Srdja Jankovic ◽  
Goran Djuricic ◽  
Aleksandra Radosavljevic ◽  
Dragana Janic
Keyword(s):  
Fever Of Unknown Origin ◽  
Periodic Fever ◽  
Tumor Necrosis Factor Receptor ◽  
Unknown Origin ◽  
Recurrent Fever ◽  
Diagnostic Challenge ◽  
Periodic Fever Syndromes ◽  
Tnfrsf1a Gene ◽  
Febrile Condition ◽  
Fever Syndromes

Introduction. Fever of unknown origin is an important diagnostic challenge. Although rare, periodic fever syndromes may often present with a chronic or recurrent febrile condition with a variable temporal pattern of occurrence. Although clinical characteristics often indicate the syndrome in question, there are many atypical forms, and the genotype?phenotype relationship is highly complex, warranting in many cases the designation of a ?syndrome spectrum? rather than a syndrome per se. The aim of this paper was to present a boy with recurrent fever of unknown origin. Case outline. We hereby present a boy with recurrent fever of unknown origin who was by clinically guided partial exome sequencing found to have a heterozygous variant 434A>G in the TNFRSF1A gene, otherwise connected with tumor necrosis factor receptor-associated periodic fever syndrome. The patient responded well to short courses of glucocorticoids and is no longer subjected to unnecessary antibiotic treatment he had frequently received in the past. Conclusion. Periodic fever syndromes should be kept in mind as a differential diagnostic possibility in children with fever of unknown origin.

scholarly journals POS1302 THE MUSCULOSKELETAL SYSTEM MANIFESTATIONS IN CHILDREN WITH FAMILIAL MEDITERRANEAN FEVER

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 933.1-933
Author(s):  
F. Demir ◽  
S. Canbek ◽  
B. Sözeri
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Musculoskeletal Symptoms ◽  
Compound Heterozygous ◽  
M694v Mutation ◽  
Musculoskeletal Manifestations ◽  
Mediterranean Fever ◽  
Calf Pain

Background:Familial Mediterranean fever (FMF) is a monogenic inherited periodic fever syndrome presenting with episodes of self-limiting fever and inflammation of serosal membranes. The attacks emerge with arthritis were defined as one of the major diagnostic criteria besides involvement of serosal membranes. Non-specific musculoskeletal findings such as myalgia, arthralgia, transient synovitis, and more rare manifestations like protracted febrile myalgia can also be seen in FMF patients attacksObjectives:We aim to reveal the frequency and genotype association of musculoskeletal manifestations in children with FMF.Methods:The patients diagnosed with FMF between January 1, 2017 and June 1, 2019, and followed for at least 6 months in our pediatric rheumatology clinic were included in the study. Musculoskeletal manifestations of patients were enrolled. The patients were grouped according to the “Mediterranean Fever” (MEFV) gene variants. Musculoskeletal manifestations of the patients were compared between the groupsResults:The study group included 634 children with FMF (336 female and 298 male, F/M: 1.13/1). The clinical manifestations of patients in attack period were as follows: 99% of the patients had fever, 87.3% had abdominal pain, 20.7% had chest pain, 11.3% had vomiting, 10.7% had erysipelas like erythema, and 9.3% had headache. The musculoskeletal symptoms were accompanied by 58.6% (n: 372) of the patients during the attack period. The most common musculoskeletal manifestation was found as arthralgia (32.6%, n: 206). Also, the other musculosceletal manifestations were found as follows during attacks; arthritis in 23.7% (n: 150), myalgia in 20.5% (n: 130), exertional calf pain in 6.5% (n: 41), and protracted febrile myalgia in 1% (n: 7) of the patients. It was observed that the musculoskeletal manifestations were significantly higher in patients with homozygous M694V variant in exon-10 (p=0.017). Also, it was found that the musculoskeletal manifestations are more common in the attack periods of patients carrying the M694V variant in at least one allele (p = 0.019).Conclusion:It was determined that the musculoskeletal manifestations were seen as an attack symptom in more than half of FMF patients. Also, homozygous and compound heterozygous MEFV mutations including M694V variant found as a risk factor for emerge of musculoskeletal manifestations. In children with unexplained and recurrent musculoskeletal symptoms, especially in ethnicities with the high frequency of FMF, analysis of MEFV gene can help reveal the underlying cause.References:[1]Brik R, Shinawi M, Kasinetz L, Gershoni-Baruch R. The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis Rheum 2001;44:1416-9.[2]Jarjour RA, Dodaki R. Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation. Mol Biol Rep 2011;38:2033-6.Disclosure of Interests:None declared

scholarly journals Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever

2016 ◽  
Vol 56 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Maria Teresa R.A. Terreri ◽  
Wanderley Marques Bernardo ◽  
Claudio Arnaldo Len ◽  
Clovis Artur Almeida da Silva ◽  
Cristina Medeiros Ribeiro de Magalhães ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Periodic Fever Syndromes ◽  
Fever Syndromes ◽  
Mediterranean Fever

scholarly journals An International Delphi Survey for the Definition of New Classification Criteria for Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TNF Receptor–associated Periodic Fever Syndromes, and Cryopyrin-associated Periodic Syndrome

2018 ◽  
Vol 46 (4) ◽  
pp. 429-436 ◽  
Author(s):  
Silvia Federici ◽  
Federica Vanoni ◽  
Eldad Ben-Chetrit ◽  
Luca Cantarini ◽  
Joost Frenkel ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Tumor Necrosis Factor Receptor ◽  
Classification Criteria ◽  
Delphi Survey ◽  
Mevalonate Kinase Deficiency ◽  
Evidence Based ◽  
Mevalonate Kinase ◽  
Clinical Criteria ◽  
Mediterranean Fever

Objective.Provisional evidence-based classification criteria for hereditary periodic fever (HPF) have been recently developed. However, no consensus on how to combine clinical criteria, laboratory tests, and results of molecular analysis has been reached. The objective of this study is to understand which variables physicians consider important for the classification of patients with HPF.Methods.Two Delphi surveys were sent to health professionals in the field of autoinflammation. In the first open survey, 124 researchers could list all the variables they consider useful for the diagnosis of each monogenic periodic fever. The variables could be of any type and each researcher could complete the survey for 1 or more diseases. In the second survey, 162 researchers were asked to select, from a list of items coming from the first survey, the 10 top variables and to rank them by assigning a score from 10 to 1.Results.The response rates to the Delphi surveys were 85% for the first session and 87% for the second. The variables selected for each disease (corresponding to the third quartile, considering the total score obtained by the variables after the second Delphi survey) were 21 for mevalonate kinase deficiency, 22 for cryopyrinopathies, 18 for familial Mediterranean fever, and 20 for tumor necrosis factor receptor–associated periodic fever syndrome. A positive genetic test reached the top rank in all the HPF.Conclusion.Our process led to the identification of those features considered the most important as candidate variables to be included in a new set of evidence-based classification criteria for HPF.

scholarly journals Performance of Recent PRINTO Criteria Versus Current ILAR Criteria for Systemic Juvenile Idiopathic Arthritis: A Single-Center Experience

2021 ◽  
Author(s):  
Oya KOKER ◽  
Fatma Gul DEMIRKAN ◽  
Figen CAKMAK ◽  
Nuray AKTAY AYAZ
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Kawasaki Disease ◽  
Pediatric Rheumatology ◽  
Early Recognition ◽  
Periodic Fever ◽  
Tumor Necrosis Factor Receptor ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Autoinflammatory Diseases ◽  
Control Group ◽  
Mevalonate Kinase Deficiency

Abstract Objectives The purpose of this study is to evaluate the performances of recently proposed Pediatric Rheumatology International Trials Organization (PRINTO) criteria versus current International League of Associations for Rheumatology (ILAR) criteria, for systemic juvenile idiopathic arthritis (sJIA). Methods The study was performed at the Department of Pediatric Rheumatology in Istanbul Faculty of Medicine with a retrospective design, covering the date range 2010 to 2021. Patients being followed-up with a diagnosis of sJIA, Kawasaki disease (control group-1), and common autoinflammatory diseases (control group-2) were included in the study. Both the ILAR and PRINTO classification criteria were applied to each patient and compared against expert rheumatologist diagnosis. Results Eighty-two patients with a diagnosis of sJIA compared against 189 [74 Kawasaki disease, 83 familial Mediterranean fever (FMF), 16 mevalonate kinase deficiency (MKD), 10 cryopyrin-associated periodic syndromes (CAPS), 6 tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS)] patients. The PRINTO criteria demonstrated higher sensitivity (62.2% vs 80.5%, p=0.003), but comparable specificity (90.5% vs 91%) as regards the ILAR criteria. Conclusions The revised criteria appear to enhance the ability to provide early recognition and pertinent classification of sJIA. The two criteria were not superior to each other in segregating sJIA from common autoinflammatory diseases and Kawasaki disease, namely in terms of specificity.

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