Conventional and Novel Therapeutic Options in Children with Familial Mediterranean Fever: A Rare Autoinflammatory Disease

2021 ◽  
Author(s):  
Dimitri Poddighe ◽  
Micol Romano ◽  
Facundo Garcia‐Bournissen ◽  
Erkan Demirkaya
Keyword(s):  
Familial Mediterranean Fever ◽  
Autoinflammatory Disease ◽  
Therapeutic Options ◽  
Mediterranean Fever ◽  
Novel Therapeutic

scholarly journals Abdominal syndrome in monogenic autoinflammatory disease – is it just a familial Mediterranean fever?

2020 ◽  
Vol 14 (4) ◽  
pp. 144-149
Author(s):  
S. O. Salugina ◽  
E. S. Fedorov ◽  
N. G. Volf
Keyword(s):  
Familial Mediterranean Fever ◽  
Autoinflammatory Disease ◽  
Bowel Perforation ◽  
Interleukin 1 ◽  
Diagnostic Features ◽  
Peritoneal Adhesions ◽  
Strict Adherence ◽  
Surgical Interventions ◽  
Abdominal Symptoms ◽  
Mediterranean Fever

Gastrointestinal (GI) manifestations, such as abdominal pain, nausea, vomiting, and diarrhea, are common autoinflammatory disease (AID) symptoms. The abdominal symptomatology reflecting serositis is one of the most important classification and diagnostic criteria for the classic monogenic AID (MAID) – familial Mediterranean fever (FMF). Failure to timely diagnose FMF frequently leads to unjustified surgical interventions. Other periodic fevers may also present as abdominal symptoms; however, the latter are outside their diagnostic features. These diseases include, first of all, tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Interleukin 1 (IL1) inhibitors serve as the major targeted drugs for the treatment of TRAPS. Russia has registered the IL1 inhibitor canakinumab that prevents the development of organ damages, including those in the GI tract. The paper describes a clinical case of the classic manifestations of TRAPS (fever, rash, periorbital edema, arthritis, and elevated levels of acutephase inflammatory markers) concurrent with severe abdominalgia during attacks and with the development of severe peritoneal adhesions, which led to bowel perforation and emergency surgical intervention. The prolonged persistence of inflammatory attacks before the initiation of therapy, as well as violation of the IL1 inhibitor administration regimen facilitated the development of an urgent exacerbation. Thus, TRAPS should be included in the differential diagnostic circle for patients with severe gastrointestinal manifestations characterized by an attack-like course. These patients need timely prescription of targeted therapy, strict adherence to the dosing and intervals between drug administrations, and careful monitoring to prevent serious complications with the visceral organs, including the gastrointestinal tract, and their immediate correction.

scholarly journals Kawasaki disease triggered by EBV virus in a child with Familial Mediterranean Fever

2019 ◽  
Vol 45 (1) ◽  
Author(s):  
Maria Cristina Maggio ◽  
Carmelo Fabiano ◽  
Giovanni Corsello
Keyword(s):  
Kawasaki Disease ◽  
Familial Mediterranean Fever ◽  
Epstein Barr Virus ◽  
Autoinflammatory Disease ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Mediterranean Fever ◽  
Epstein Barr

Abstract Background Familial Mediterranean Fever is a monogenic autoinflammatory disease, secondary to mutation of MEFV gene, and typically expressed with recurrent attacks of fever, serositis, rash, aphthous changes in lips and/or oral mucosa. Kawasaki Disease, an acute systemic vasculitis with persistent fever (5 or more days), rash, stomatitis, conjunctivitis, lymphadenopathy, changes in extremities, is currently considered a multifactorial autoinflammatory disease. An infection, as Epstein Barr virus, can be the trigger of Kawasaki Disease. Case presentation We describe the clinical case of a 3-year-old boy with Kawasaki disease. Successfully treated with intravenous immune globulin, acetyl salicylate acid, he late developed anaemia and thrombocytopenia. The Epstein-Barr virus infection has been demonstrated and he showed a resolution of the clinical manifestations of Kawasaki disease with the persistence of coronaritis, without aneurisms. However, for the personal and familial history of monthly recurrent attacks of fever, pharyngitis, abdominal pain, the genetic study of MEFV was performed and demonstrated 3 heterozygous mutations of MEFV (E148Q, P369S, R408Q). Conclusions Mutations of MEFV can contribute to increase inflammatory expression in other diseases, as Kawasaki disease.

scholarly journals Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation

2016 ◽  
Vol 113 (50) ◽  
pp. 14384-14389 ◽  
Author(s):  
Hanne Van Gorp ◽  
Pedro H. V. Saavedra ◽  
Nathalia M. de Vasconcelos ◽  
Nina Van Opdenbosch ◽  
Lieselotte Vande Walle ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Autoinflammatory Disease ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Microtubule Assembly ◽  
Inflammasome Activation ◽  
Wild Type ◽  
Peripheral Blood Mononuclear ◽  
Mouse Macrophages ◽  
Mediterranean Fever

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type and FMF Pyrin are differentially controlled by microtubules. Diverse microtubule assembly inhibitors prevented Pyrin-mediated caspase-1 activation and secretion of IL-1β and IL-18 from mouse macrophages and human peripheral blood mononuclear cells (PBMCs). Remarkably, Pyrin inflammasome activation persisted upon microtubule disassembly in PBMCs of FMF patients but not in cells of patients afflicted with other autoinflammatory diseases. We further demonstrate that microtubules control Pyrin activation downstream of Pyrin dephosphorylation and that FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks). The discovery that Pyrin mutations remove the obligatory requirement for microtubules in inflammasome activation provides a conceptual framework for understanding FMF and enables immunological screening of FMF mutations.

scholarly journals A Rare Cause of Lymphadenopathy in Children: Autoinflammatory Disease - Familial Mediterranean Fever

2015 ◽  
Author(s):  
Gonca KESKİNDEMİRCİ ◽  
Nuray AKTAY AYAZ ◽  
Deniz TUĞCU ◽  
Mustafa ÇAKAN ◽  
Gönül AYDOĞAN ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Autoinflammatory Disease ◽  
Mediterranean Fever

Familial Mediterranean fever: the molecular pathways from stress exposure to attacks

Rheumatology ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 3611-3621
Author(s):  
Cengiz Korkmaz ◽  
Döndü U Cansu ◽  
Güven Barış Cansu
Keyword(s):  
Familial Mediterranean Fever ◽  
Autoinflammatory Disease ◽  
Inflammasome Activation ◽  
Molecular Pathways ◽  
Stress Exposure ◽  
Sympathoadrenal System ◽  
Mediterranean Fever ◽  
System Activation ◽  
New Perspective ◽  
Stress Mediators

Abstract FMF is an autoinflammatory disease characterized by recurrent attacks and increased IL-1 synthesis owing to activation of the pyrin inflammasome. Although knowledge of the mechanisms leading to the activation of pyrin inflammasome is increasing, it is still unknown why the disease is characterized by attack. The emergence of FMF attacks after emotional stress and the induction of attacks with metaraminol in previous decades suggested that stress-induced sympathoadrenal system activation might play a role in inflammasome activation and triggering attacks. In this review, we will review the possible molecular mechanism of stress mediators on the inflammation pathway and inflammasome activation. Studies on stress mediators and their impact on inflammation pathways will provide a better understanding of stress-related exacerbation mechanisms in both autoinflammatory and autoimmune diseases. This review provides a new perspective on this subject and will contribute to new studies.

scholarly journals Update on the management of colchicine resistant Familial Mediterranean Fever (FMF)

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Georges El Hasbani ◽  
Ali Jawad ◽  
Imad Uthman
Keyword(s):  
Familial Mediterranean Fever ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Autoinflammatory Disease ◽  
Tnf Inhibitors ◽  
Phase Response ◽  
Autoinflammatory Diseases ◽  
Tnf Alpha ◽  
Main Body ◽  
Mediterranean Fever

Abstract Background Familial Mediterranean Fever (FMF), an autoinflammatory disease, is characterized by self-limited inflammatory attacks of fever and polyserositis along with high acute phase response. Although colchicine remains the mainstay in treatment, intolerance and resistance in a certain portion of patients have been posing a problem for physicians. Main body Like many autoimmune and autoinflammatory diseases, many colchicine-resistant or intolerant FMF cases have been successfully treated with biologics. In addition, many studies have tested the efficacy of biologics in treating FMF manifestations. Conclusion Since carriers of FMF show significantly elevated levels of serum TNF alpha, IL-1, and IL-6, FMF patients who failed colchicine were successfully treated with anti IL-1, anti IL-6, or TNF inhibitors drugs. It is best to use colchicine in combination with biologics.

THU0400 Inhibition of IL-6 signalling: A novel therapeutic approach for familial mediterranean fever

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 290.3-290 ◽  
Author(s):  
N. Stein ◽  
M. Witt ◽  
M. Baeuerle ◽  
H. Schulze-Koops ◽  
M. Gruenke
Keyword(s):  
Familial Mediterranean Fever ◽  
Therapeutic Approach ◽  
Mediterranean Fever ◽  
Novel Therapeutic

Current therapeutic options for managing familial Mediterranean fever

2015 ◽  
Vol 3 (9) ◽  
pp. 1063-1073 ◽  
Author(s):  
Ezgi Deniz Batu ◽  
Zehra Serap Arici ◽  
Yelda Bilginer ◽  
Seza Özen
Keyword(s):  
Familial Mediterranean Fever ◽  
Therapeutic Options ◽  
Mediterranean Fever

scholarly journals IL-1β and Caspase-1 Drive Autoinflammatory Disease Independently of IL-1α or Caspase-8 in a Mouse Model of Familial Mediterranean Fever

2017 ◽  
Vol 187 (2) ◽  
pp. 236-244 ◽  
Author(s):  
Deepika Sharma ◽  
Bhesh Raj Sharma ◽  
Peter Vogel ◽  
Thirumala-Devi Kanneganti
Keyword(s):  
Familial Mediterranean Fever ◽  
Mouse Model ◽  
Autoinflammatory Disease ◽  
Caspase 8 ◽  
Caspase 1 ◽  
Mediterranean Fever

scholarly journals The Comparison of Diagnostic Criteria in Children with Familial Mediterranean Fever

2021 ◽  
Author(s):  
Esra Nagehan Akyol Onder ◽  
Kudret Ebru Özcan ◽  
Feride Iffet Sahin ◽  
Kaan Savas Gulleroglu ◽  
Esra Baskin
Keyword(s):  
Familial Mediterranean Fever ◽  
Diagnostic Criteria ◽  
Autoinflammatory Disease ◽  
High Sensitivity ◽  
Clinical Findings ◽  
Classification Criteria ◽  
Laboratory Findings ◽  
Simple Method ◽  
Group A ◽  
Mediterranean Fever

Abstract Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized with recurrent attacks of fever and serositis. The diagnosis is made according to clinical findings and supported by genetic analysis. The most used adult diagnostic criteria are the Tel-Hashomer criteria. The pediatric criteria for the FMF diagnosis of children were described in 2009, but their efficacy should be supported with further reports. In this study, we planned to compare the pediatric criteria and the Tel-Hashomer criteria in our FMF patients. We also aimed to evaluate the importance of the 2019 Eurofever/PRINTO classification criteria in this patient group. A total of 113 patients diagnosed with FMF were included in our study. Demographic features and laboratory findings were retrospectively recorded from the patients’ files. The patients were evaluated with the Tel-Hashomer, pediatric and Eurofever/PRINTO classification criteria. At least two of five new pediatric criteria were as sensitive (88.6%) and specific (84.62%) as the Tel-Hashomer criteria (sensitivity 69.9%, specificity 95.7%). We also evaluated the Eurofever/PRINTO classification criteria in our patients and found its sensitivity 93.8% and specificity 90.6%. Conclusion: Using pediatric criteria in the diagnosis of FMF in children is a feasible and simple method that can diagnose the disease based on at least two criteria. Therefore, our study supports the use of pediatric criteria in the diagnosis of FMF in children. Our results also confirm that the Eurofever/PRINTO classification criteria can be successfully used in the diagnosis of FMF due to their high sensitivity (93.8%) and specificity (90.6%).

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