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Objectives: Colchicine forms the mainstay of treatment in FMF. Approximately 5-10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis., Methods: FMF patients (0-18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses., Results: A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P < 0.05). Multivariate logistic regression analysis in the training cohort (n = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n = 671), its sensitivity was 93.5% and specificity was 53.8%., Conclusion: We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Familial Mediterranean fever (FMF) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases and anti-inflammatory agents are used in their treatment. This study evaluates the periodontal status and cytokine response in pediatric patients with FMF or sJIA., Materials and Methods: Forty-eight FMF/sJIA patients were under treatment/control and in attack-free period; 20 systemically healthy children participated in the study. FMF/sJIA patients were divided into two subgroups based on the treatment they received: receiving anti-IL-1 therapy (anti-IL-1 ( +)) and not receiving anti-IL-1 therapy (anti-IL-1 ( -)). The clinical periodontal indices were recorded. Gingival crevicular fluid (GCF) and serum samples were collected. Cytokine levels (IL-1β, IL-1α, TNF-α, IL-6, IL-8, IL-10, IL-17, IL-33) in GCF and serum were measured using ELISA kits., Results: There was no significant difference between the groups in terms of GCF IL-1β and IL-1α levels although, BoP and GI were significantly lower in the anti-IL-1 ( +) group compared to the control group. GCF IL-10 level was higher in the anti-IL-1 ( -) group than in the control group; GCF IL-8 levels were lower in both FMF/sJIA subgroups versus controls. There was no significant difference between serum cytokine levels of FMF/sJIA subgroups., Conclusions: Considering the significant decrease in GI, BoP, and GCF IL-8 levels in the anti-IL-1 ( +) group, it can be concluded that anti-IL-1 medications may suppress periodontal inflammation clinically and immunologically., Clinical Relevance: Anti-IL agents are not currently used in periodontal therapy. However, this study demonstrated the positive effect of anti-IL-1 medications on periodontal inflammation in pediatric patients with FMF or sJIA., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Differentiating PFAPA (periodic fever, aphthosis, pharyngitis, and adenitis) syndrome from familial Mediterranean fever (FMF) could be challenging in some cases. Galectin-3 is a lectin with regulatory functions in apoptosis and inflammation. We aimed to test whether galectin-3 could be a biomarker for differentiating PFAPA syndrome from FMF. Patients with PFAPA syndrome, FMF, cryopyrin-associated periodic syndrome (CAPS), and streptococcal pharyngitis, and healthy controls were included in this study. Serum galectin-3 levels were measured using enzyme-linked immunosorbent assay. Eighty-seven patients (36 with PFAPA, 39 with FMF, 8 with CAPS, 4 with streptococcal pharyngitis), and 17 healthy controls were included. Blood samples were drawn during attacks from 20 PFAPA and 7 FMF patients and attack-free periods from 22 PFAPA, 35 FMF, and 8 CAPS patients. The median serum galectin-3 level in the PFAPA-attack group (1.025 ng/ml) was significantly lower than the levels in healthy control (2.367 ng/ml), streptococcal pharyngitis (3.021 ng/ml), FMF attack (2.402 ng/ml), and FMF-attack-free groups (2.797 ng/ml) (p = 0.006, 0.03, 0.01, and < 0.001, respectively). PFAPA-attack-free group had lower galectin-3 levels than the FMF-attack-free group (1.794 vs. 2.797 ng/ml, respectively; p = 0.01). Galectin-3 levels did not differ significantly between CAPS and attack-free PFAPA patients (1.439 ng/ml vs. 1.794 ng/ml, respectively; p = 0.63). In our study, for the first time, we defined galectin-3 as a promising biomarker that differs between PFAPA and FMF patients during both disease flares and attack-free periods. Further studies with high number of patients could validate its role as a biomarker., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Colchicine is the main treatment for FMF. Although a number of individuals with FMF are intolerant/resistant to colchicine, there is no standard definition of colchicine resistance/intolerance. We developed a set of evidence-based core statements defining colchicine resistance/intolerance in patients with FMF that may serve as a guide for clinicians and health authorities., Methods: A set of statements was identified using a modified-Delphi consensus-based approach. The process involved development of an initial colchicine resistance/intolerance-related questionnaire derived from a systematic literature review. The questionnaire, which was completed by an international panel of 11 adult and paediatric rheumatologists with expertise in FMF, was analysed anonymously. The results informed draft consensus statements that were discussed by a round-table expert panel, using a nominal group technique to agree on the selection and wording of the final statements., Results: Consensus among the panel was achieved on eight core statements defining colchicine resistance/intolerance in patients with FMF. A definition of resistance was agreed upon that included recurrent clinical attacks (average one or more attacks per month over a 3-month period) or persistent laboratory inflammation in between attacks. Other core statements recognize the importance of assessing treatment adherence, and the impact of active disease and intolerance to colchicine on quality of life., Conclusion: Based on expert opinion, a set of evidence-based core statements defining colchicine resistance/intolerance in patients with FMF were identified to help guide clinicians and health authorities in the management of patients with FMF., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory disease. We aimed to investigate the oral health status and oral hygiene habits in children with FMF., Methods: In this cross-sectional study, 199 children with FMF, aged between 3-18 years, were included. Demographic findings and oral hygiene habits of children were questioned by face-to-face interview. Oral health status of patients was evaluated using decay-missing-filled index [DMFT (decay-missing-filled teeth), DMFS (decay-missing-filled teeth) for permanent; dmft, dmfs for primary teeth], the International Caries Detection and Assessment System (ICDAS-II) index, PUFA / pufa index [the presence of severely decayed teeth with visible pulpal involvement (P/p), ulceration caused by dislocated tooth fragments (U/u), fistula (F/f) and abscess (A/a)], gingival (GI) and plaque index (PI). In addition to these, occlusion, oral soft and hard tissues were examined., Results: One-hundred-nine (54.8%) of children had at least one decayed permanent tooth and 81.2% of children had at least one decayed primary tooth. The mean DMFT was 1.91±2.45, DMFS was 3.1±4.49, dmft was 3.95±3.54, dmfs was 8.62±8.88, PI was 1.17±0.44, GI was 0.85±0.39. Aphthous mouth ulcer occurred in 19 (9.5%) patients. Recurrent aphthous mouth ulcers were more frequent among patients with one exon-ten and one exon-two mutations than patients with one exon-10 mutation, two exon-ten mutations, or two exon-2 mutations (61.1% vs. 47.9%, 26.1%, 20%, respectively p < 0.001). Tooth decay was more frequent among patients who had attacks in the last six months than those who did not have any attacks during the last six months (97.4% vs. 87.7%, p=0.017)., Conclusion: Dental caries and periodontal disease, which are public health problems, were seen at a high percentage of children with FMF in our study.

Objectives: FMF is the most common periodic fever syndrome, characterized by recurrent episodes of fever and serosal inflammation accompanied with high acute phase reactants. The analysis of possible comorbidities is important to understand the impact of these conditions on clinical care and whether they share a common aetiological pathway. In this study, we aimed to evaluate the comorbidities associated with FMF patients in a large genetically diagnosed cohort., Methods: We retrospectively evaluated the medical and genetic records of FMF patients who were followed up by rheumatologists in Hacettepe University for 15 years. The FMF patients who had homozygous or compound heterozygous mutations were included in the study. Comorbidities associated with FMF were divided into three groups: (i) comorbidities directly related to FMF, (ii) comorbidities due to increased innate inflammation, and (iii) comorbidities that were regarded as being incidental., Results: A total of 2000 patients with a diagnosis of FMF were enrolled in the study. Among them 636 were children (31.8%) and M694V was the most common mutation in patients with associated inflammatory conditions. The frequency of AS, Iga Vasculitis (Henoch-Schönlein purpura), juvenile idiopathic arthritis, polyarteritis nodosa, multiple sclerosis and Behçet's disease were increased in patients with FMF when compared with those in the literature., Conclusion: This study represents the largest genetically confirmed cohort and compares the frequencies with existing national and international figures for each disease. The increased innate immune system inflammation seen in FMF may be considered as a susceptibility factor since it predisposes to certain inflammatory conditions., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Although chronic inflammation has been associated with increased cancer risk in various disease including hepatitis or inflammatory bowel disease, a lower incidence of cancer has been reported recently in familial Mediterranean fever (FMF) which is an auto-inflammatory disease with persistent inflammation. We have assessed cancer incidence among FMF patients with or without amyloidosis to investigate this hypothesis. We performed a retrospective review of FMF patients, diagnosed and treated in Hacettepe University hospitals between 2001 and 2018. We identified patients from the hospital medical records using the ICD-10 code for FMF. We collected data on demographic and clinical features, drug history, the presence of amyloidosis and subsequent diagnosis of cancer. The expected cancer incidence was estimated using age- and gender-specific standardized incidence rates (SIRs) in comparison with the general Turkish population according to Turkish National Cancer Registry data at 2014. Total of 3899 FMF patients (120 patients had also amyloidosis) were included. Median age was 22 and 56% were females. Thirty-eight patients were diagnosed with cancer during 100,283 person-years of follow-up. The most common cancer was breast cancer in females (7/28 patients) and leukemia (2/10 patients) in males. The overall cancer incidence among patients with FMF was significantly lower in both males {SIR 0.42 [95% confidence interval; (CI) 0.21-0.75], p = 0.019} and females [SIR 065 (95% CI 0.44-0.93), p = 0.002]. The overall cancer incidence among patients with FMF and amyloidosis was [SIR 1.21 (95% CI 0.49-2.52), p = 0.73] without gender difference. Cancer incidence was significantly lower in FMF patients compared with the general Turkish population. We found no increased cancer incidence in FMF patients having amyloidosis. Possible underlying mechanisms need to be explained.

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease in the world. The disease characteristics may vary in different age groups. In this study, we aimed to compare disease characteristics and treatment compliance according to the age of pediatric FMF patients. This is a single-center, cross-sectional study. Between August and October 2016, patients who were diagnosed with FMF, participated to the study. 378 pediatric FMF patients were enrolled in the study. Among those, age at symptom onset was ≤ 5 years in 69%, 6-11 years in 26% and ≥ 12 years in 5%. Patients older than 12 years old at symptom onset, had significantly less frequent fever attacks than the patients from other age groups. Patients younger than 5 years old at symptom onset had significantly higher international severity scoring system for FMF (ISSF) than other patients. And M694V homozygosity was significantly more frequent in patients with younger age at symptom onset. Patients younger than 5 years old were using their drugs more regularly than the other age groups (p = 0.002). Drug compliance was 90.5% in patients ≤ 5 years, 64.4% in patients 6-11 years, 58.3% in patients ≥ 12 years. The disease characteristics of FMF may differ between patients with different age at symptom onset. Younger age at disease onset seems to be related with more severe course; thus these patients should be followed-up more closely. In addition, treatment compliance which is critical for prevention of amyloidosis in FMF should be questioned especially in adolescent patients.

Objectives: Colchicine is the main therapy for familial Mediterranean fever (FMF); however, 5-10% of patients are colchicine-resistant. There is no standard and validated definition for colchicine resistance. We aimed to compare the existing definitions for colchicine resistance in both adult and paediatric FMF patients to find out the best definition to determine colchicine-resistant patients., Methods: 385 FMF patients were evaluated and patients receiving anti-interleukin-1 treatment were included. The anti-IL-1 therapy had been initiated by the experts in the past based on their experience. Eleven different definitions (found out after PubMed search for colchicine resistance in FMF) were applied to all patients. Results were re-analysed after excluding the patients who had no clinical attacks but persistently high acute phase reactants (APRs) and/or amyloidosis., Results: Sixty patients (40 adults/20 children) who had been using anti-IL-1 therapy were included into this study as colchicine-resistant patients. The highest percentage of patients fulfilled definition 5 (93.3%). Definition 9 had the poorest performance (26%). Significantly, a higher percentage of adult patients met definitions 4 and 6 than paediatric patients (87.5% vs. 50%, p=0.002; 75% vs. 40%, p=0.008, respectively). After excluding patients without clinical attacks, the highest percentage of patients fulfilled definition 2 (94.4%). We combined the attack frequency (>1 typical episode/3 months) in definition 2 and presence of amyloidosis/APR increase (increase in ≥2/3 APRs) in definition 5 to create a new definition which was met by 59 (98.3%) colchicine-resistant FMF patients., Conclusions: Definition of colchicine resistance is still controversial. Definitions with both clinical and laboratory criteria were met by a higher percentage of resistant patients than those without laboratory criteria. However, the proper definitions for the attack-free period and persistence of APRs are still lacking.

Aim: Familial Mediterranean fever (FMF) results from MEFV gene mutations. E148Q is a variant of unknown significance in MEFV. We aimed to define characteristics of FMF patients homozygous for E148Q, check for other MEFV variants in a subgroup, and compare the characteristics with FMF patients carrying other mutations., Methods: Thirty FMF patients homozygous for E148Q were reviewed. MEFV variant analysis was performed with strip assay. All MEFV exons were screened by direct DNA sequencing in 14 randomly selected E148Q/E148Q patients. E148Q was also checked in 100 healthy adolescents. We compared the characteristics of FMF patients between three groups: E148Q/E148Q (n = 30), M694V/E148Q (n = 19) and exon 10/exon 10 MEFV mutations (n = 48)., Results: Among 30 FMF patients (E148Q/E148Q), the median age at disease onset and diagnosis were 60 (12-168) and 94 (41-196) months, respectively. Fifteen (50%) patients had mild, 14 (46.7%) moderate and one (3.3%) had severe disease. Twenty-two (73.3%) patients had complete, seven (23.3%) had incomplete response to colchicine, while only one was unresponsive. The detected MEFV variants in 14 E148Q/E148Q FMF patients were as follows: R314R (n = 9; 64.3%), E474E (n = 13; 92.9%), Q476Q (n = 13; 92.9%), D510D (n = 13; 92.9%), and P588P (n = 8; 57.1%). The E148Q allele frequency was 6.5% in healthy adolescents. When compared to FMF patients with other MEFV mutations, disease onset was later, disease was less severe and the ratio of patients responding completely to colchicine was higher in E148Q/E148Q patients., Conclusion: Patients homozygous for E148Q and negative for other pathogenic MEFV variants may display FMF phenotype and may experience moderate/severe disease activity, although the disease may be milder when compared to FMF patients with other mutations., (© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: Phenotypic heterogeneity in familial Mediterranean fever (FMF) disease indicated that FMF is not a simple monogenic disease. Therefore it has been suggested that epigenetic factors can be one of the reason for the variations. We undertook this study to test potential involvement of miRNAs in the pathogenesis of FMF., Methods: miRNA array was performed on whole blood RNA samples from 6 healthy controls (-/-), 6 FMF patients (M694V/M694V), 6 carriers who displayed the disease phenotype (M694V/-) and 6 healthy carriers (M694V/-). The raw data was analysed by Multi Experiment Viewer (MeV) and candidate miRNAs were determined according to fold change (more than 2.0 or less than -2.0). The validation of differentially expressed miRNAs was done by qRT-PCR. Then we performed pathway analyses with using bioinformatics tools., Results: 14 miRNAs were found to be significant among groups through the analysis with MeV. miR-20a-5p, miR-197-3p, let-7d-3p and miR-574-3p were found to be associated with inflammatory pathway related genes according to DAVID analysis. MiR-20a-5p (FDR: 0,00, FCH: 5.55) was significantly up regulated whereas miR-197-3p (FDR: 0,00, FCH: -2.27) was down regulated in homozygotes patients. Both let-7d-3p (FDR: 0.00, FCH: 28.75) and miR-574-3p (FDR: 0.00, FCH: 3.95) were up regulated in heterozygote patients group., Conclusions: We showed that there are several differentially expressed miRNAs both in homozygote and heterozygote FMF patients compared to controls and healthy carriers. Thus we suggest that these miRNAs, related with inflammatory pathways may be responsible for the expression of the disease in FMF.

Objectives: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease manifesting with self-limited recurrent febrile attacks and polyserositis. Acute recurrent monoarthritis is the most common form of musculoskeletal involvement in FMF; however, up to 5% of FMF patients may develop chronic joint diseases including sacroiliitis. It is difficult to distinguish whether sacroiliitis is a musculoskeletal finding of FMF or whether this is the coexistence of two diseases, FMF and SpA. In this study, we aimed to evaluate FMF patients with sacroiliitis, and compare their features with juvenile spondyloarthropathy (SpA) patients, all of whom had sacroiliitis., Methods: 15 paediatric FMF patients with sacroiliitis and 30 patients with juvenile SpA followed between 2014-2016 at the Department of Paediatric Rheumatology at Hacettepe University, Ankara, were included in the study., Results: The median (min-max) age at diagnosis of sacroiliitis was 11 (7-15) for FMF+sacroiliitis, and 11.5 (7-16) years for juvenile SpA patients. All patients suffered from hip pain and morning stiffness. Only two FMF+sacroiliitis patients had enthesitis, while nearly half of juvenile SpA patients (46.7%) had enthesitis. Four FMF patients suffered from lower back pain, although none of them had spinal involvement. On the other hand, approximately one third of juvenile SpA patients had spinal involvement. The median white blood cell count, erythrocyte sedimentation rate, and C reactive protein values in FMF+sacroiliitis patients were higher (10.1x103/mm3 vs 7.8x103/mm3, p = 0.002; 41 vs 28 mm/h, p<0.001; 4.6 vs 1.3 mg/dl, p<0.001; respectively) than juvenile SpA patients. HLA B27 positivity was more common in juvenile SpA than FMF+sacroiliitis patients (86.6% vs 26.7%, respectively, p=0.001). The most common MEFV (MEditerranean FeVer) mutation was M694V in FMF patients. All juvenile SpA patients but one were negative for MEFV mutations. One juvenile SpA patient was heterozygous for E148Q., Conclusions: We demonstrated that paediatric patients with FMF+sacroiliitis showed different characteristics (higher inflammatory markers, less frequent spinal and enthesitis involvement and HLA-B27 positivity) from patients with juvenile SpA. Whether FMF is a triggering factor for SpA or sacroiliitis is a feature of FMF, is still a matter of debate.

Familial Mediterranean fever (FMF) is inherited autosomal recessively; however, heterozygotes may express FMF phenotype. We aimed to define the characteristics of FMF patients heterozygous for MEFV (MEditerranean FeVer) mutations in whom colchicine was stopped after a period of treatment, with close follow-up. We reviewed the charts of 182 children who were heterozygous for MEFV variants. We excluded the patients (n = 34) heterozygous for MEFV variants of unknown significance and patients with typical periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (n = 2). All patients were followed up with their routine analysis and serum amyloid A levels every 6 months while on colchicine treatment and every 3-6 months thereafter. MEFV gene variant analysis was performed with Sanger sequencing. Twenty-two out of 146 heterozygotes initially had FMF phenotype, but colchicine was discontinued after a treatment period. The most common MEFV variant was M694V (86.3 %). The median age at diagnosis/initiation of colchicine was 76 (24-144) months. The median duration of colchicine treatment was 36 (24-110) months. The median age at colchicine cessation was 120 (55-172) months. At the time of colchicine cessation, the median attack- and inflammation-free period was 27 (24-84) months. The median follow-up after colchicine cessation was 22.5 (6-102) months. We re-started colchicine in only two patients because of recurrence of symptoms. Individuals with one mutation only can display FMF phenotype and require colchicine for the clinical and laboratory inflammation. However, in some of these patients, colchicine may be discontinued with very careful follow-up.

Objectives: The aim of the study was to compare the cochlear functions of children diagnosed with familial Mediterranean fever (FMF) with healthy controls and to determine their cochlear functions according to their disease severity., Methods: Seventy-three children with FMF and 30 healthy controls were included in the study. All the patients and controls were evaluated by audiologic evaluation, including high-frequency pure-tone audiometry and distortion product otoacoustic emission tests (DPOAE). The disease severity was evaluated by scoring systems adapted from those used by Pras et al. and with severity scoring systems from the Sheba Medical Center., Results: High-frequency pure-tone audiometry and DPOAE levels were normal in both patients and controls. Significant differences in the hearing levels of FMF patients were not found, according to both adapted severity scoring systems., Conclusions: Cochlear functions in children with FMF had been evaluated by previous studies, but in our study we evaluated hearing functions according to both controls and disease severity. As a unique study comparing cochlear functions according to severity scores, no significant differences were shown between the groups and controls., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The systemic autoinflammatory diseases are inflammatory disorders characterized by uncontrolled inflammation of the innate immune system. A common monogenic autoinflammatory disease is familial Mediterranean fever (FMF), associated with mutations in the MEFV gene. Another autoinflammatory disease group is cryopyrin-associated periodic syndromes (CAPS), which are characterized by urticarial rash and mutations of the gene NLRP. Systemiconset juvenile idiopathic arthritis (soJIA) is classified as a multifactorial autoinflammatory disease. We report two cases of systemic autoinflammatory disease with homozygous E148Q mutation in the FMF gene. They had unusual features, such as urticarial rash, non-erysipeloid erythema, lymphadenopathy, and hepatosplenomegaly, and neurological findings in one. These patients met the "definition" criteria for FMF with two mutations in the MEFV gene. They fit the "description" criteria for CAPS with their fever, urticaria, and other clinical features. They also met the "classification" criteria for soJIA, with the fever, rash, arthritis, and accompanying systemic features.

Objective: To evaluate the response to treatment of autoinflammatory diseases from an international registry and an up-to-date literature review., Methods: The response to treatment was studied in a web-based registry in which clinical information on anonymised patients with autoinflammatory diseases was collected retrospectively as part of the Eurofever initiative. Participating hospitals included paediatric rheumatology centres of the Paediatric Rheumatology International Trial Organisation network and adult centres with a specific interest in autoinflammatory diseases. The following diseases were included: familial Mediterranean fever (FMF), cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF)-receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), pyogenic arthritis pustulosis acne (PAPA) syndrome, deficiency of interleukin-1 receptor antagonist (DIRA), NLRP12-related periodic fever and periodic fever aphthosis pharyngitis adenitis (PFAPA) syndrome. Cases were independently validated by experts for each disease. A literature search regarding treatment of the abovementioned diseases was also performed using Medline and Embase., Results: 22 months from the beginning of the enrolment, complete information on 496 validated patients was available. Data from the registry in combination with evidence from the literature confirmed that colchicine is the treatment of choice for FMF and IL-1 blockade for DIRA and CAPS. Corticosteroids on demand probably represent a valid therapeutic strategy for PFAPA, but also for MKD and TRAPS. Patients with poorly controlled MKD, TRAPS, PAPA or FMF may benefit from IL-1 blockade; anti-TNF treatment may represent a possible valuable alternative., Conclusions: In the absence of high-grade evidence, these results could serve as a basis for therapeutic guidelines and to identify candidate drugs for future therapeutic trials.

Secondary amyloidosis is the most severe complication of familial Mediterranean fever (FMF). Since the M694V mutation was associated with clinical severity, it was expected to be associated with amyloidosis as well. However, a number of contradicting reports have been published, especially pertinent to Turkish patients nearly 10years ago. The aim of this study was to analyze recent data regarding the association between M694V mutation and amyloidosis among FMF patients in Turkey. We conducted a comprehensive review of the literature regarding the role of M694V mutation in the development of amyloidosis secondary to FMF. Twenty-seven papers from 20 centers including 3505 Turkish subjects were reviewed. Four-hundred patients had amyloidosis and homozygous M694V was detected in 189 (47%) of the 400 amyloidotic patients which was significantly higher than that in the FMF patients not developing amyloidosis (p<0.0001). In the presented analysis we were able to reach a patient number of 400 which is much higher than all those published hitherto. Our findings confirmed that homozygous M694V is associated with amyloidosis in the Turkish population as well similar to Armenia, Israel, and Arabian countries. The necessity to treat asymptomatic or mildly symptomatic FMF patients with this genotype, even in countries where amyloidosis is rare, should be considered carefully., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β). Recent studies have shown that pyrin recognizes bacterial modifications in Rho GTPases, which results in inflammasome activation and increase in IL-1β. Pyrin does not directly recognize Rho modification but probably affected by Rho effector kinase, which is a downstream event in the actin cytoskeleton pathway. Recently, an international group of experts has published the recommendations for the management of FMF. Colchicine is the mainstay of FMF treatment, and its regular use prevents attacks and controls subclinical inflammation in the majority of patients. Furthermore, it decreases the longterm risk of amyloidosis. However, a minority of FMF patients fail to response or tolerate colchicine treatment. Anti-interleukin-1 drugs could be considered in these patients. One should keep in mind the possibility of non-compliance in colchicine-non-responders. Although FMF is a relatively well-described AID and almost 20 years has passed since the discovery of the MEFV gene, there are still a number of unsolved problems about it such as the exact mechanism of the disease, symptomatic heterozygotes and their treatment, and the optimal management of colchicine resistance. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease, and it is characterized by recurrent attacks of fever and polyserositis. The disease is associated with mutations in the MEFV gene encoding pyrin, which causes exaggerated inflammatory response through uncontrolled production of interleukin 1. The major long-term complication of FMF is amyloidosis. Colchicine remains the principle therapy, and the aim of treatment is to prevent acute attacks and the consequences of chronic inflammation. With the evolution in the concepts about the etiopathogenesis and genetics of the disease, we have understood that FMF is more complicated than an ordinary autosomal recessive monogenic disorder. Recently, recommendation sets have been generated for interpretation of genetic testing and genetic diagnosis of FMF. Here, we have reviewed the current perspectives in FMF in light of recent recommendations. [ABSTRACT FROM AUTHOR]

Purpose: To describe the relation between global Quality of Life (QL) and psychiatric symptoms in adolescents with systemic lupus erythematosus (SLE) and familial Mediterranean fever (FMF), and to analyze the perceptions of parents and adolescents. Methods: This study included 51 adolescents diagnosed with SLE (n=25) and FMF (n=26), and 51 healthy adolescents. The Health Related QL (HRQL) of SLE patients was rated by parents and adolescents using the Simple Measurement of Impact of Lupus Erythematosus in Youngsters© (SMILEY©). The global QL of FMF patients and healthy adolescents was rated by the response given to the first question of the SMILEY© by each parent and adolescent. All participants completed the Brief Symptom Inventory (BSI), which measures psychiatric symptoms. Results: In total, 92.3% with FMF, 56% with SLE and 76.5% of healthy adolescents reported their global QL as good and very good using the first question of the SMILEY©. The global QL perceptions of adolescents and their parents did not correlate (FMF, p=0.94; SLE, p=0.16). SLE patients had the highest rate of depression (54.2%), whereas hostility was detected among 54.9% of healthy adolescents. Significant relations were detected between BSI and SMILEY© scores. Conclusion: The global QL perceptions of adolescents with FMF were better than those of healthy adolescents, which may be explained by their perceived relief of anguish they suffer during their short-lived attacks. The global QL perceptions of adolescents with SLE were the worst, most probably due to the chronic course resulting in an awareness of limitations and intense treatment. Adolescents with SLE had similar psychopathological symptom scores when compared with FMF patients and healthy adolescents. This could be explained by developing resilience. Differences in the perception of adolescents versus their parents regarding global QL emphasized the importance of adolescent-specific interviews for chronic illnesses and multidisciplinary follow-up with adolescent medicine. [ABSTRACT FROM AUTHOR]

Background and Aims: Familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD) concordance has been investigated in a few studies. We investigated MEFV mutations and prevalence of FMF disease in Turkish children with IBD and their relationship with the disease severity.Methods: Sixteen patients with ulcerative colitis (UC), 14 with Crohn's disease (CD) and three with indeterminate colitis (IC) were enrolled in the study (median age 13 years, range 0.6-16 years, n = 19 boys). Demographic, clinical and laboratory characteristics of the patients were evaluated as well as the parameters of disease severity. All patients were screened for 12 common MEFV mutations.Results: MEFV mutations were detected in 17 of 66 (25.7%) alleles. Seven patients (four patients with CD, two with IC, and one with UC) were also diagnosed as FMF. FMF disease was found in seven of all IBD patients (21.2%) and four of them had CD. M694V was the leading mutation, and as a disease-causing mutation, it was found to be significantly more frequent in CD patients than UC patients (Fisher's exact test P = 0.03). Demographics, laboratory evaluations, growth parameters, extraintestinal manifestations, and treatment with immunosuppressive agents other than steroids were comparable between the patients with and without FMF in most aspects.Conclusions: Although this is a small cohort, disease-causing MEFV mutations and FMF disease rate were increased among our patients with IBD. The increase was prominent among CD patients, whereas in UC the rate was similar to the Turkish healthy control population. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the controversial issue of amyloidosis susceptibility in familial Mediterranean fever (FMF) by determining the relative contributions of MEFV gene and numerous epidemiologic factors to the risk of renal amyloidosis. It concludes that country of recruitment, rather than MEFV genotype, is the key risk factor for renal amyloidosis in FMF.