Abstract Introduction: Fas/FasL system plays an important role in the regulation of cell life and death, and circulating levels of sFasL have been shown to increase in some inflammatory conditions. However, there is no sufficient information about the levels of sFasL in patients with FMF. This study was designed to evaluate the serum sFasL levels in patients with FMF during attack and attack-free periods.

Methods:

Twenty-five FMF patients in attack and forty-four in free-attack period, and 20 age-, sex-, and BMI-matched healthy controls were included in this study. Participants with any chronic diseases were excluded. Blood samples were obtained within the first 24 h of the attack period and between febrile attacks, and levels of WBC, ESR, Fibrinogen, hsCRP and sFasL were determined.

Results:

The levels of traditional acute phase reactants during the attack were significantly higher than the attack-free and controls (p < 0.05). The serum sFasL levels in the FMF study groups did not differ from the control group (0.70 ± 0.08 vs. 0.73 ± 0.12; 0.70 ± 0.08 vs. 0.83 ± 0.14; 0.73 ± 0.12 vs. 0.83 ± 0.14, respectively, p > 0.05). Moreover, the sFasL levels during the attack were not significantly different from those in attack-free patients (0.70 ± 0.08 vs. 0.83 ± 0.14, p > 0.05).

Conclusion:

In this study, we demonstrated that serum sFasL levels were not markedly affected in FMF and cannot be used as a supportive marker to differentiate attacks from attack-free periods. However, further studies are needed to determine its usefulness as a marker in clinical practice.

Familial Mediterranean fever (FMF) is an inflammatory disorder that is leading cause of secondary amyloidosis (AA). This study was designed to investigate the level of mean platelet volume (MPV) in AA. Seventy-four FMF, 29 AA patients and 180 healthy controls, were included. There was no significant difference between the cases in terms of sex and age. MPV levels were measured in all groups. In the FMF group, MPV level was significantly higher when compared to the control group. MPV level was significantly lower in AA group in comparison with the FMF and healthy control groups. In summary, our present study showed low MPV values in AA due to FMF.

Recurrent aphthous stomatitis (RAS) has a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. The Mediterranean fever (MEFV) gene has already been identified as being responsible for familial Mediterranean fever. Because the association between MEFV gene mutations and Behçet's disease has been reported before in several studies, we considered that the role of MEFV gene mutations should be studied in patients with RAS, because of the clinical similarities of both diseases. The aim of this study was to explore the frequency and clinical significance of MEFV gene mutations in a cohort of Turkish patients with RAS. The study population comprised 100 unrelated patients with a clinical diagnosis of RAS and 156 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction and restriction fragment length polymorphism for the four MEFV gene mutations (M694V, M680I, V726A and E148Q). There were statistically significant differences of the MEFV gene mutation carrier rates and allele frequencies between RAS patients and healthy controls (P = 0.042, odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.01-3.41; and P = 0.039, OR = 1.8, 95% CI = 1.02-3.14, respectively). Even if it is not statistically significant, the E148Q allele frequency was higher in patients with RAS than the control group. A statistically significant increased prevalence of MEFV variants in RAS patients was found. This is the first study to report that missense mutations of MEFV is associated with RAS in the Turkish population.

Systemic amyloidosis is one of the serious complications of Familial Mediterranean Fever (FMF). Amyloid accumulation secondary to FMF can cause pressure symptoms in thyroid gland rarely. A 17-year-old male patient with the diagnosis of FMF performed the complaints of dyspnea during his follow-up period. He has demonstrated a rapidly increasing mass localized in front of his neck within the last three months that was diagnosed as a diff use, hyperplasic and pressuring thyroid gland. Total thyroidectomy was performed. Histopathological investigation of the material obtained aft er thyroidectomy revealed diff use lipid infiltration in parenchyma, intense amyloid accumulation around and between the follicles that caused pressure on the follicles, and cystic areas in the tissue. Squamous metaplasia foci in cyst epithelium were detected. Upon these findings the case was diagnosed as amyloid goiter accompanied by metaplastic variations. In conclusion, it can be appropriate to take into account the possibility that metaplastic variations could accompany amyloid goiter in patients with long-term FMF.

Familial Mediterranean fever is an auto-inflammatory disorder. Long term complications of the disease include decreased quality of life. The measurement of quality of life in the patients with chronic disease has become an important research topic during the last years.We aimed to evaluate life quality of the FMF patients by SF-36, and examine its relationship with the disease parameters.One hundred voluntary patients (69 female, 31 male) admitted to the rheumatology clinic were included in the study. The control group consisted of 100 healthy individuals. All subjects in the study were asked to complete SF-36 questionnaire. Age of onset of FMF, age at diagnosis, age at the beginning of colchicine therapy, number of attacks per month, family history of FMF and dialysis were inquired of patients with FMF. Disease severity was determined using the FMF severity score.The mean age of the patient group was 31±12 and that of the control group was 29±9. Sixty-nine patients (69%) were female, and 31 patients were male (31%) in both groups. The mean scores of the physical function, physical role function, emotional role function, mental health, and general health parameters of the patients were statistically significantly lower than those of healthy volunteers (p < 0.05). The difference in social function and vitality between two groups was found to be insignificant (p > 0.05).We have shown that FMF had a negative impact on SF-36. FMF reduces quality of life both in physical and mental dimensions.

Familial Mediterranean fever (FMF) is common among Turkish and Moroccan migrants. We describe three patients with FMF. A 3-year-old girl with recurrent fever and abdominal pain who was diagnosed early with FMF and treated effectively with colchicine. An adolescent girl who required interleukin (IL)-1 blockade to achieve disease remission. And a 37-year-old woman in whom the attacks of FMF had not been recognised, but who developed end-stage kidney failure due to AA amyloidosis. Mutations in the MEFV gene underlie the disease in most but not all patients. Therefore, FMF remains a clinical diagnosis. FMF patients suffer recurrent bouts of inflammation, often with fever, serositis or arthritis. The major complication is AA amyloidosis. The inflammatory process is mediated by IL-1β. When started early, colchicine prophylaxis can prevent amyloidosis. When colchicine fails, IL-1 blockade has shown promising results. Timely diagnosis and treatment can make the difference between near normal health and end-stage kidney failure.

Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10(-5)), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10(-4)), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063-0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10(-12)). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis.

Familial Mediterranean Fever (FMF) is an autosomal recessive disease that is widely spread in the populations of the Mediterranean region. It is characterized by recurrent fever and inflammatory attacks. A total of 1700 suspected patients, belonging to various communities in Israel: Jews (Ashkenazi and non-Ashkenazi), Arabs (Muslims and Christians) and Druze, was subjected to examination for FMF mutation screening. The patients were screened for the most common six MEFV gene mutations namely, M680I, M694V, M694I, V726A, E148Q and K695R. Fifty-five percent of the cases were confirmed to have MEFV mutations. The most common mutations among all the cases studied were M694V, E148Q and V726A. The common mutations in the respective communities were: among the Jews M694V with a frequency of 69.9% (76.8% for non-Ashkenazi Jews and 43.6% for Ashkenazi Jews), among the Arabs V726A with a frequency of 32.7% (32.7% for Muslims and 32.1% for Christians) and among Druze it was E148Q with a frequency of 52.1%. The characteristic mutation present in Jews was K695R and the one in Arabs was M680I, while no characteristic mutation was found in Druze. On the other hand, mutation E148Q was observed to have a considerable occurrence in patients of all ethnic groups studied. Furthermore, our results revealed that homozygous mutations accounted for 168 cases (18%). The homozygote mutation M694V was the most prevalent among Jews and the E148Q mutation was the most common among Druze, while, among Arabs there were three homozygous mutations having maximum prevalence, namely, V726A, M694V and M694I. Our study comprehensively provided a spectrum of FMF mutations in various communities of Israeli society.

This study aims to compare the mean platelet volume (MPV) levels in children and adults diagnosed with familial Mediterranean fever (FMF) during attack-free periods in order to find out whether it reflects the emergence of microalbuminuria/proteinuria and the development of amyloidosis or not. The study consisted of 63 pediatric patients (group 1), 50 adult patients (group 2), 50 healthy children (group 3), and 43 healthy adults (group 4). Demographic data, age at diagnosis, duration of the disease and colchicine treatment, and FMF gene mutations were recorded, and erythrocyte sedimentation rate, C-reactive protein, fibrinogen, hemoglobin, white blood cell count, platelet count, MPV, blood urea nitrogen, creatine, albumin, and urine microalbumin and protein levels were evaluated. According to the presence of microalbuminuria/proteinuria, patient groups were subgrouped into two by themselves as pediatric and adult groups with and without proteinuria. The most frequent mutation was M694V. MPV was significantly higher in FMF patients than those in the healthy control groups. Microalbuminuria/proteinuria were detected in 18 (28.57 %) of 63 pediatric patients and 26 (52 %) of 50 adult patients. Amyloidosis has been identified in 3 (16.6 %) of 18 pediatric patients and 18 (69.23 %) of 26 adult patients with proteinuria. Subgroup comparisons revealed that MPV levels were significantly higher in patients with proteinuria than patients without proteinuria in both pediatric and adult groups. Moreover, MPV levels were also significantly higher in adult patients with or without proteinuria than in pediatric patients with or without proteinuria. There were significant differences in terms of serum albumin levels between the groups with and without proteinuria as expected. The increase in MPV over the years of the disease, especially in groups with proteinuria, may be an important predictor of continuing increase of subclinical inflammation, the emergence of the microalbuminuria/proteinuria, and the developing of amyloidosis, but further studies are needed in order to support this proposal.

OBJECTIVES:

: Familial Mediterranean fever (FMF) and inflammatory bowel disease togetherness is well described in the literature. Abdominal pain and various gastrointestinal manifestations might arise directly from FMF or secondary to FMF-associated diseases such as inflammatory bowel disease, vasculitidies or amyloidosis.

METHODS::

The medical files of the patients who were diagnosed with FMF at Gazi University School of Medicine Department of Pediatric Gastroenterology between 2007 and 2012 were examined retrospectively. FMF diagnosis was made through clinical, laboratory, colonoscopy, endoscopy and genetic analysis.

RESULTS::

Thirty-six patients were diagnosed with FMF disease in this period. Among them, 11 patients admitted with vomiting or diarrhea. Colonoscopy and upper gastrointestinal endoscopy were performed. Colonic inflammation and multiple gastric aphthous ulcerations were observed.

CONCLUSIONS::

In this report we describe 11 patients who presented with gastrointestinal symptoms and eventually diagnosed with FMF. Gastrointestinal mucosal involvement without amyloidosis is documented by endoscopic and histopathologic investigations in these patients. We concluded that mucosal involvement of the gastrointestinal tract might be attacks related manifestations in these patients.