Enthesitis may be one of the signs of severe disease in familial Mediterranean fever

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared

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AB0980 CASE-REVIEW ON FAMILIAL MEDITERRANEAN FEVER IN A SPECIALIZED CENTRE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1355 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1784.1-1784

Author(s):

R. Dos Santos Sobrín ◽

M. Martí Masanet ◽

B. Lopez-Montesinos ◽

L. Lacruz Pérez ◽

I. Calvo

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Familial Mediterranean Fever ◽

Periodic Fever ◽

Severe Disease ◽

Strong Association ◽

Mefv Gene ◽

Systemic Juvenile Idiopathic Arthritis ◽

Case Series ◽

Case Review ◽

Mediterranean Fever

Background:Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder caused mostly by mutations in MEFV gene. Its inheritance is autosomal recessive and is the most frequent periodic fever syndrome. First-line treatment is based in colchicine use, so biologics (anti-IL-1) are reserved for refractory cases1, 2.Objectives:To account for clinic and treatment features of patients with FMF in a specialized center as opposed to non-referent centers.Methods:This study was developed in the Pediatric Rheumatology Service in Hospital Universitario y Politécnico La Fe de Valencia. Demographic, clinic and treatment data were collected from patients diagnosed of FMF since January 2004 to September 2019.Results:106 patients met last FMF criteria3. 55% had a pathogenic mutation in genetic analysis. 52% were female. Before 10 years old, 71% of patients had the diagnosis (51% before 4 years old). Arthralgia/myalgia (73%), periodic fever (62%) and abdominal pain (54%) were the most common symptoms. Systemic Juvenile Idiopathic Arthritis (JIA, 6), other forms of JIA (9) and vasculitis (10) were the most prevalent comorbidities. When talking about treatment, 76,4% received Colchicine (60,5% with good response), 22,6% needed a classical disease modifying antirheumatic drug (mostly Methotrexate) and 22 patients got biologic treatment (73% anti-IL-1).Conclusion:When analyzing this case-review, JIA has a strong association with our patients, so it could explain severe disease activity and more articular involvement. This could be an illustration to the higher use of Methotrexate. Also, the most relevant symptom was arthralgia while fever is the most frequent in literature. Likewise, age of diagnosis has been earlier than other case-series (this would be more frequent in other autoinflammatory syndromes, as literature relates)1, 2, 4.References:[1]Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. (2019).[2]Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644-651.[3]Sag E, Demirel D, Demir S, et al. Performance of the new “Eurofever/PRINTO classification criteria” in FMF patients. Semin Arthritis Rheum. 2019;19:30369-5.[4]Rozenbaum M, Rosner I. Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clin Exp Rheumatol. 2004;22:S75-8.Disclosure of Interests:Raquel Dos Santos Sobrín: None declared, Miguel Martí Masanet: None declared, B Lopez-Montesinos: None declared, Lucía Lacruz Pérez: None declared, Inmaculada Calvo Grant/research support from: Bristol-Myers Squibb, Clementia, GlaxoSmithKline, Hoffman-La Roche, Merck Sharpe & Dohme, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, GlaxoSmithKline, Hoffman-La Roche, Novartis

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Clinical and molecular analysis of common MEFV gene mutations in familial Mediterranean fever in Sivas population

Biologia ◽

10.2478/s11756-009-0047-1 ◽

2009 ◽

Vol 64 (2) ◽

Cited By ~ 4

Author(s):

Binnur Koksal ◽

Naim Nur ◽

Musa Sari ◽

Ferhan Candan ◽

Mursit Acemoglu ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Severe Disease ◽

Mefv Gene ◽

Point Mutations ◽

Gene Mutations ◽

Homozygous Mutation ◽

Frequent Mutation ◽

Mefv Mutations ◽

Wide Range ◽

Mediterranean Fever

AbstractFamilial Mediterranean fever (FMF) is the most frequent hereditary inflammatory disease characterized by self-limited recurrent attacks of fever and serositis. The aim of the current study is to determine the frequency of the mutations in 365 suspected FMF patients and to reveal whether there is a correlation between genotype and phenotype of these patients. All patients were clinically examined according to Tell-Hashomer FMF criteria and were screened genetically in terms of common 12 Mediterranean fever gene (MEFV) mutations. Various point mutations were detected in 270 (74%) patients. The most frequent mutation was M694V (26.85% of the alleles) and was followed by E148Q (15.55%), M680I (G/C) (9.62%) and V726A (7.96%). Patients who bear M694V homozygous mutation had most severe disease phenotype and high risk for amyloidosis (P = 0.04). Our results indicate that Sivas population has a wide range of heterozygous mutated carriers of MEFV gene and there is a high frequency of E148Q allele when compared to the other Mediterranean groups.

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Infertility Causes and Pregnancy Outcome in Patients With Familial Mediterranean Fever (FMF) and Controls

The Journal of Rheumatology ◽

10.3899/jrheum.200574 ◽

2020 ◽

pp. jrheum.200574

Author(s):

Pavel Olegovich Sotskiy ◽

Olga Leontevna Sotskaya ◽

Hasmik Sureni Hayrapetyan ◽

Tamara Fadei Sarkisian ◽

Anna Rafaelovna Yeghiazaryan ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Pregnancy Outcome ◽

Severe Disease ◽

Colchicine Treatment ◽

Control Group ◽

Secondary Amyloidosis ◽

Peritoneal Adhesions ◽

Vitro Fertilization ◽

Mediterranean Fever

Objective Recurrent attacks of peritonitis of Familial Mediterranean fever (FMF), may lead to peritoneal adhesions and fallopian tube obstruction. Colchicine - the treatment of choice for FMF - may disturb cell division. Secondary amyloidosis - a complication of untreated FMF - may involve the testes and ovaries. Thus, FMF and colchicine may potentially affect fertility and pregnancy in FMF patients. The aims of the study are to evaluate the causes of infertility and pregnancy outcome in FMF patients and to compare them with two groups: non-FMF patients with peritoneal female genital tuberculosis (FGTB) and normal healthy control. Methods This is a retrospective study in which FMF patients with reproductive disorders were recruited from the National Center of Medical Genetics and Primary Health Care in Yerevan, Armenia. The FGTB patients and the normal control patients with reproductive problems were recruited successively from a large gynecology clinic in Yerevan. Genetic analyses for FMF were performed using ViennaLab Diagnostics GmbH Strip Assay. Results The FMF group (211 patients) resembles the FGTB group (127 patients) regarding etiologies of infertility. However, in vitro fertilization (IVF) success rate and pregnancy outcome were comparable between the FMF patients and the control group (167patients). Infertility in FMF patients was clearly associated with a more severe disease and a lack of adequate colchicine treatment. Conclusion Colchicine medication and controlled FMF disease do not adversely affect the reproductive system and pregnancy outcome. However, a lack of an appropriate colchicine treatment may cause infertility and poor pregnancy outcome.

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APPENDECTOMY HISTORY IS ASSOCIATED WITH SEVERE DISEASE AND COLCHICINE RESISTANCE IN ADULT FAMILIAL MEDITERRANEAN FEVER PATIENTS

TURKISH JOURNAL OF MEDICAL SCIENCES ◽

10.3906/sag-2011-74 ◽

2021 ◽

Keyword(s):

Familial Mediterranean Fever ◽

Severe Disease ◽

Colchicine Resistance ◽

Mediterranean Fever

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Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208671 ◽

2016 ◽

Vol 75 (6) ◽

pp. 1051-1056 ◽

Cited By ~ 32

Author(s):

Erkan Demirkaya ◽

Cengizhan Acikel ◽

Philip Hashkes ◽

Marco Gattorno ◽

Ahmet Gul ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Disease Severity ◽

Severity Score ◽

Characteristic Curve ◽

Severe Disease ◽

Clinical Manifestations ◽

Future Research ◽

Laboratory Findings ◽

Therapeutic Decisions ◽

Mediterranean Fever

ObjectiveTo develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice.MethodsCandidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi survey, the candidate criteria, defined by the survey, were discussed by experts in a consensus meeting. Each expert brought data of clinical manifestations, laboratory findings and physician's global assessments (PGAs) of minimum 20 patients from their centres. We used the PGAs for disease severity as a gold standard. Logistic regression analysis was used to evaluate the predicting value of each item, and receiver operating characteristic curve analysis was performed to demonstrate the success of the criteria set.ResultsA total of 281 patients consist of 162 children and 119 adults with FMF were enrolled and available for validity analysis: Nine domains were included in the final core set of variables for the evaluation of disease severity in FMF. The International Severity Score for FMF (ISSF) may reach a maximum of 10 if all items are maximally scored. The threshold values to determine: severe disease ≥6, intermediate disease 3–5, mild disease ≤2. Area under the curve was calculated as 0.825 for this set in the whole group.ConclusionsThe initial validity of ISSF both in children and adult with FMF was demonstrated. We anticipate that it will provide a robust tool to objectively define disease severity for clinical trials, future research as well as for therapeutic decisions in managing patients with FMF.

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