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Background & objectives Familial Mediterranean Fever (FMF) manifests as a hereditary condition characterized by repeated bouts of fever, abdominal, chest, and joint discomfort, and swelling. Colchicine is the most common form of treatment, but it does not eliminate the disease. The underlying causes of the inflammatory mechanism are still not fully known. Methods A total of 20 healthy controls, 16 individuals with FMF in the attack period, and 14 in the remission period participated in the study. ITGA9, ITGB1, OPN, TNC, VEGF, VCAM-1, TGM2, TSP-1, Emilin-1, and vWF levels were measured by ELISA by obtaining serum from blood samples of individuals. In addition, gene expressions of α9β1 (ITGA9, ITGB1) and its best known ligands (TNC, SPP1) were analyzed by quantitative real-time PCR (qPCR). Results The findings of this study showed that serum levels of α9β1 and its ligands were higher in individuals with FMF in the attack period than in the healthy controls and the FMF group in the remission period (P<0.05). The marker levels of the healthy group were also higher than those in the remission period (p<0.05). In addition, when the gene expressions were compared between the healthy controls and FMF group, no significant difference was found for ITGA9, ITGB1, TNC, and SPP1 genes. Interpretation & conclusions The function of α9β1 and its ligands in FMF disease was investigated for the first time in this study as per our knowledge. Serum levels of these biomarkers may help identify potential new targets for FMF disease diagnosis and treatment approaches.

Background/objectives: YouTube is increasingly being used as an educational tool and is a substantial source of information. This study aimed to assess the quality of the most viewed YouTube videos pertaining to familial Mediterranean fever (FMF)., Methods: A search on YouTube was conducted on January 13, 2022, using the keywords: "familial Mediterranean fever treatment," "familial Mediterranean fever colchicine," and "familial Mediterranean fever colchicine opacalcium." Two rheumatologists independently evaluated the relevance and accuracy of the videos. Redundant or irrelevant videos were excluded. The educational value of YouTube videos was assessed using the Global Quality Scale (GQS). Comparative analyses of video parameters across different cohorts were performed. To assess the reliability and quality of the videos, a modified version of the DISCERN scale and the GQS were employed., Results: Out of the 59 videos reviewed, 43 (72.9%) were of high quality, 10 (16.9%) were of medium quality, and 6 (10.2%) were of low quality. Upon comparing parameters among groups, no significant disparities were observed in terms of daily views, daily favorites, daily dislikes, or daily comments ( p  > 0.05). GQS scores for usefulness and modified DISCERN scores showed significant differences among groups ( p  < 0.001). Additionally, both GQS and modified DISCERN scores exhibited moderately negative correlations ( r  =  - .450 and r  =  - .474, respectively) and high statistical significance ( p  < 0.001 for both) with utility assessment., Conclusion: YouTube is a valuable repository of high-quality videos for FMF patients. Healthcare providers should guide their patients to high-quality video sources to supplement their educational material., Competing Interests: The authors declare there are no competing interests., (©2024 Coşkun et al.)

Background/aim: The distribution of Mediterranean fever (MEFV) gene mutations in Turkish familial Mediterranean fever (FMF) patients varies according to geographic area of Turkey. There is a need for highly representative data for Turkish FMF patients. The aim of our study was to investigate the distribution of the common MEFV mutations in Turkish FMF patients in a nationwide, multicenter study., Materials and Methods: Data of the 2246 FMF patients, from 15 adult rheumatology clinics located in different parts of the country, were evaluated retrospectively. The following mutations have been tested in all patients: M694V, M680I, M694I, V726A, and E148Q., Results: There were 1719 FMF patients with available genetic testing. According to the genotyping, homozygous M694V, present in 413 patients (24%), was the most common mutation . One hundred and fifty-four (9%) of patients had no detectable mutations. Allele frequencies of common mutations were: M694V (n = 1529, 44.5%), M680I (n = 423, 12.3%), V726A (n = 315, 9.2%), E148Q (n = 214, 1%), and M694I (n = 12, <1%)., Conclusion: In this large-scale multicenter study, we provided information about the frequencies of common MEFV gene mutations obtained from adult Turkish FMF patients. Nearly half of the patients were carrying at least one M694V mutations in their alleles.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1β, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10(-12)), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10(-13)). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10(-15)), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10(-8)). Serum IL-1β, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1β and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1β function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy., Competing Interests: The authors have declared that no competing interests exist.

Objective: Approximately 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anti-IL-1) agents. Here we report our experience with the off-label use of anti-IL-1 agents in a large group of FMF patients., Methods: In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL-1 treatment for at least 6 months were reviewed., Results: In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18-68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1-48), and the mean colchicine dose was 1.7 mg/day (range 0.5-4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL-1 treatment was used because of colchicine-resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6-98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, erythrocyte sedimentation rate, and 24-hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced., Conclusion: Anti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients., (© 2017, American College of Rheumatology.)

Aim: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences., Methods: Early (≤ 20 years, Group 1) and late (> 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey., Results: Of the 2246 patients, 1633 (72.7%) were aged ≤ 20 years old (Group 1) and the remaining 613 were older than 20 years (Group 2). Delay in diagnosis was longer in Group 1 and fever, peritonitis, pleuritis, erysipelas-like erythema (ELE), arthritis, family history of FMF and amyloidosis were more common in Group 1. On the other hand, sex distribution, rates of amyloidosis, vasculitis and kidney failure were not different between the groups. Among patients with available genotypes, homozygous and heterozygous M694V mutations were significantly higher and heterozygous E148Q mutation was significantly lower in Group 1 compared to Group 2., Conclusion: Patients with FMF whose symptoms start before 20 years of age seem to have severe symptoms and M694V mutation may be responsible for the early expression of the disease., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: Cardiovascular diseases (CVD) are very common in the general population. Atherosclerosis is the main pathogenesis. Familial Mediterranean fever (FMF) is an autosomal recessive disease. The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils and monocytes. We herein aimed to determine the prevalence of MEFV mutations (all exon 2, 10 mutations) in patients with early coronary heart disease (early CHD) and coronary heart disease (CHD) with multiple risk factors and among the healthy subjects as controls., Methods: A total of 197 patients and 119 healthy subjects were recruited and enrolled into three groups in terms of inclusion criteria. Ninety-one patients diagnosed with early CHD enrolled into group one (men < 45 years of age, women < 40 years of age), 106 patients with CHD (men > 50 years of age) to group two and 119 healthy controls enrolled into group three. None of patients was diagnosed with FMF. The diagnosis of CHD was established on electrocardiographic changes, echocardiography and coronary angiography., Results: Thirty-eight patients (41.8%) with early CHD, 17 patients (16%) with CHD and 24 healthy controls (20.2%) carried at least one mutated MEFV allele. Young patients with CHD have different risk factor profiles, clinical presentations and prognoses than older patients. Young patients with CHD usually have multiple risk factors., Conclusion: This study suggests that MEFV mutations in early CHD patients had significantly increased in contrast to CHD patients and healthy controls., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Introduction: Colchicine is the mainstay for the treatment of FMF, which is an auto-inflammatory disease mainly with relapsing polyserositis. Despite daily doses of 2mg or more each day, approximately 5% to 10% of the patients continue to suffer from its attacks. In this study, we aimed to investigate the depression and attack features in patients with FMF who have colchicine resistance (CR)., Patients E Methods: CR was defined for FMF patients with 2 or more attacks within the last 6 months period while using 2mg/day colchicine. Eighteen patients (9 Female/9 Male) were enrolled into the CR group and 41 patients were enrolled into the control group (12 Male/29 Female). Demographic, clinical e laboratory findings, treatment adherence, and the Beck Depression Inventory (BDI) scores were evaluated., Results: The age of onset of FMF was significantly lower in the CR group (12.3 yrs vs. 16.9 yrs, P=0.03). Disease duration was longer in the CR group (P=0.01). Abdominal and leg pain due to exercise were significantly more frequent in the CR group versus controls (83% vs. 51%; P=0.02 e 88% vs. 60%; P=0.04, respectively). Patients with BDI scores over 17 points were more frequent in the CR group compared to controls (50% vs. 34.1%; P<0.001)., Discussion: We found that: (1) the age of disease onset was lower and (2) the disease duration was longer in CR group. Pleuritic attacks, hematuria e proteinuria were more frequent in CR patients. We propose that depression is an important factor to consider in the susceptibility to CR., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Objective: The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients., Methods: Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens., Results: There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001)., Conclusion: In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

Familial Mediterranean fever (FMF) is a systemic hereditary autoinflammatory disorder. The present study aimed to investigate the relationship of enthesitis to FMF and to search the potential association between enthesitis and MEFV gene missense variations in patients with FMF. The study consisted of 72 FMF patients (mean age 29.12 ± 11.47 years, 32 females), 29 patients with ankylosing spondylitis (AS) (mean age 34.14 ± 11.73 years, 16 females), and 34 healthy volunteers (mean age 23.06 ± 6.41 years, 8 females). FMF patients were classified according to the kind of MEFV gene mutation. Doppler ultrasound was used to determine enthesitis based on the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) scoring system. OMERACT score was significantly different between FMF patients and control group (p < 0.001 in all patients, p = 0.009 in men, and p = 0.002 in women). However, it was not significantly different between FMF and AS patients in both sexes. OMERACT score did not differ between FMF patients with and without M694V gene mutation. The best cutoff point of OMERACT score to predict enthesitis was found as ≥0.5 with sensitivity of 29 %, specificity of 100 %, positive predictive value of 100 %, and negative predictive value of 40 %.

Familial mediterranean fever (FMF) is an autosomal recessive disorder caused by mutations in the FMF gene (MEFV). The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils, and monocytes. Since there are several etiological factors, FMF is the most common periodic fever syndrome. However, it is still unknown what triggers or ends these periodical attacks. As a pleiotropic hormone, vitamin D has immunomodulation effects. The aim of this study was to evaluate the vitamin D levels in FMF patients. The study group was comprised of 26 patients diagnosed with FMF (men/women: 12/14), and 34 healthy control (men/women: 17/17). Vitamin D levels in FMF patients and healthy controls were 11.05 ± 7.11, 17.15 ± 6.49, respectively. FMF patients had significantly decreased vitamin D levels compared with healthy controls (P < 0.001). In conclusion, it is thought that vitamin D deficiency in FMF patients may trigger the attacks. Further studies with larger patient populations need to hold to investigate the vitamin D deficiency in patients with FMF and that may assist to clarify the mechanism behind the colchicines resistant cases.

Objectives: Familial Mediterranean fever (FMF) is an autosomal-recessive disease characterized by recurrent attacks of fever with serositis. Differential diagnosis of a FMF abdominal attack with acute abdomen is difficult. Acute appendicitis is the most common cause of acute abdominal pain that requires surgical treatment. The aim of this study was to investigate frequency of FMF in patients with negative appendectomy., Methods: We assessed 278 patients (female/male 127/151) who were operated with preoperative diagnosis of acute appendicitis. In 250 of the patients, definitive diagnosis of acute appendicitis was established by histo-pathological examination. Patients with negative appendectomy were assessed for FMF by rheumatologist., Results: Negative appendectomy was detected in 28 patients (M/F 5/23, mean age 25.3 ± 8.4 years). Negative appendectomy ratio was 10.1 %. Among 28 patients two had FMF (7.7 %)., Conclusions: FMF were established in 7.7 % of patients with negative appendectomy. Our study suggests patients having negative appendectomy should be evaluated for FMF. Further large sample studies are needed to define the real prevalence of FMF among negative appendectomy patients.