Erysipelas-like erythema as the presenting feature of familial Mediterranean fever.

BACKGROUND: 'Erysipelas-like' erythema (ELE) is a well recognized, although uncommon, manifestation of familial Mediterranean fever (FMF), which is frequently mistaken for infectious erysipelas, especially when forming the initial disease presentation. AIM: To clinically and genetically characterize ELE as the first manifestation of FMF. METHODS: FMF patients with ELE as the first disease presentation (study group), were compared with FMF patients with ELE, appearing during the disease course (control group I), and to those FMF patients who never had ELE (control group II). RESULTS: Patients of the study group were comparable to patients without ELE with respect to all demographic, clinical and genetic features studied, and yet differed from patients with ELE appearing later in the disease course in disease severity score (1.7 ± 0.4 vs. 2.4 ± 0.6, P = 0.01), length of diagnosis delay (7.2 ± 6.4 vs. 2.3 ± 3.3 years, P=0.037), age of FMF onset (24.8 ± 19.9 vs. 5.6 ± 5.7 years of age, P=0.014) and rate of homozygosity to the M694V mutation (14.3% vs. 68.7% respectively). ELE traits in the study and control groups were alike. CONCLUSIONS: FMF with ELE as the first disease manifestation form an uncommon subgroup, clinically and genetically diverging from the rest of the FMF-ELE patients.

Diagnosis delay in familial Mediterranean fever (FMF): social and gender gaps disclosed.

OBJECTIVE: To characterize the factors contributing to a greater than 10 year delay in the diagnosis of familial Mediterranean fever (FMF). METHODS: 50 patients, in whom diagnosis of FMF was delayed by more than 10 years, comprised the study population. The clinical, demographic and molecular genetic characteristics were compared to a control group of 50 FMF patients, in whom the diagnosis was made within a reasonable time period (less than 5 years from onset). Additional factors contributing to a delayed diagnosis in the study group, including physician-related factors, patient-related factors, disease-factors and other factors, were studied as well. RESULTS: Overall, attack sites, duration and severity were comparable among study and control groups. No differences in ethnic origin or family history of FMF were noted between the groups. There were significantly more females (p = 0.009), newly-arrived immigrants (p = 0.005) and carriers of unidentified MEFV mutations (p = 0.04) in the study group. Delayed diagnosis of FMF stemmed from misdiagnosis and physician negligence (70%), as well as from patient negligence (70%). The diagnosis was ultimately made mainly due to a change in disease pattern and other causes, such as diagnosis of FMF in a relative. CONCLUSION: The study unveils unexpected causes behind a prolonged delay in the diagnosis of FMF such as social status (immigrant), female gender, physician negligence and lack of patient awareness. The possibility that the delay stems from a milder disease pattern was dismissed.

A single mutated MEFV allele in Israeli patients suffering from familial Mediterranean fever and Behçet's disease (FMF-BD).

Although familial Mediterranean fever (FMF) is an autosomal recessive disorder, preliminary partial mutation analysis suggested that about 60% of FMF patients, who also suffer from Behçet's disease (FMF-BD), have only a single mutated FMF gene (MEFV). In this study, the possibility that patients with FMF-BD may indeed be carriers of a single mutated MEFV is further analysed. The presence of mutations in the coding region of MEFV of eight patients with FMF-BD, representing six families with 47 members, was determined by sequencing. A possible role for the non-carrier chromosome and for BD in the expression of FMF in patients with a single mutated MEFV allele was determined by analysing the association between these variables and the presence of FMF in heterozygous kin. Sequence analysis revealed that all eight patients had indeed only one mutation in the coding region of MEFV. The patients' non-carrier chromosomes converged into three different MEFV haplotypes and were shared by heterozygous unaffected kin in five of six families. BD was found in 10 of 11 carriers with FMF vs one of 16 carriers without FMF (P < 0.001). These results suggest that FMF may be expressed in individuals harbouring only one coding mutation in MEFV. The findings argue against a role for the non-carrier chromosome in the induction of FMF, and suggest that the FMF phenotype in this cohort was associated with the simultaneous presence of BD. These findings may mirror a more generalised rule, that FMF may be precipitated in carriers of a single mutated FMF gene by factors unrelated to the other MEFV allele.

Late-onset familial Mediterranean fever (FMF): a subset with distinct clinical, demographic, and molecular genetic characteristics.

To determine the prevalence and characterize demographic, clinical, and genetic features of familial Mediterranean fever (FMF) of late onset, all patients experiencing their first FMF attack at age 40 years or more were identified using the computerized registry of our FMF clinic, and then thoroughly interviewed and examined. The control group consisted of 40 consecutive FMF patients, who arrived at the FMF clinic for their regular follow-up visit and were 40 years of age or older at the time of the examination. The severity of the disease in patients and controls was determined using a modified score, developed previously. Mutational analysis in the FMF gene was performed using a commercial kit. Only 20 of 4000 (0.5%) patients had late-onset FMF. These patients were mostly men, of non-North African origin, P < 0.05 compared to controls. All had abdominal attacks and in most these were the only manifestation of their disease, P < 0.001. None had chronic or prolonged manifestations of FMF, for example, amyloidosis, chronic arthritis, or protracted myalgia, P < 0.001. The response to treatment was good despite using low colchicine dose, P < 0.05. The overall severity score indicated a mild disease, P < 0.001. Mutational analysis revealed absence of M694V homozygosity, P < 0.01, compared to our regular FMF population. We conclude that the onset of FMF in a late age defines a milder form of disease with typical clinical, demographic, and molecular genetic characteristics.

Musculoskeletal manifestations of brucellosis: a study of 90 cases in Israel.

Rheumatological manifestations are frequently reported in patients with brucellosis. In a retrospective study of 90 patients diagnosed with brucellosis over a period of 18 years, 83 (92%) patients were Bedouins, 55 of whom (61%) reported ingestion of unpasteurized goat milk and goat milk products. The male/female ratio was 1:1, and the adult to child ratio was 3:2. The mean age of the patients was 25 years (range, 1-72 years). Rheumatological manifestations (myalgia, arthralgia, and arthritis) were reported in more than half of the patients. These manifestations started on days 3 and 4 of the disease and were mild to moderate in severity. Myalagia was evident in 49 (54%) patients and was more common in adults than in children (67% versus 37%; P < .01) and in men (67%) than in women (42%; P < .01). Arthralgia was the most common musculoskeletal manifestation, found in 55 (61%) patients, and occurred more often in children than in adults (74% versus 52%; P < .05). Arthritis was detected in 37 (41%) patients. The hip and knee joints were the most common sites of arthritis (31% each) followed by sacroiliac involvement (17%) and shoulder or spine involvement (5% each). Arthritis was also more common in children (63% versus 29%; P < .01). The prevalence of arthritis was similar in men and women. Cure was achieved in all patients after antibiotic therapy.

MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a major cause of AA amyloidosis. Recently, the gene (MEFV) causing this disease was cloned and 16 disease associated mutations have been described. We have analyzed 178 FMF patients, 30 of whom also suffered from amyloidosis, for 4 mutations in MEFV. Mutations were identified in 29 of the FMF amyloidosis patients. 27 FMF amyloidosis patients were homozygous for M694V. One patient was found to be homozygous for both V726A and E148Q. In another patient E148Q and V726A were found on one allele, while V726A was found on the second allele. Amyloidosis was far more common among patients homozygous for M694V compared to patients with other mutations (P < 0.0001). In 3 patients homozygous for M694V, amyloidosis was the sole manifestation of the disease.

Quality of life of patients with familial Mediterranean fever.

OBJECTIVE: The aim of the present study was to assess the quality of life (QOL) of patients with Familial Mediterranean Fever (FMF) and to explore its possible contributing factors. METHODS: One hundred and two FMF patients were evaluated using a QOL Scale, and were compared to 124 healthy controls. The QOL scale includes 16 items, each measured on a 7-point scale (7 indicating maximal satisfaction). RESULTS: The total QOL score of FMF patients was significantly lower than that of the controls: 81.6 +/- 19.2 vs 88.0 +/- 12.8 (p < 0.01). Male and female patients reported similar QOL scores. QOL was inversely correlated with the number of FMF attacks in the last year (r = -0.302, p = 0.002), and with the number of FMF hospitalizations (r = -0.238, p = 0.017). Patients with widespread pain, sleep disturbances and headaches had significantly lower QOL scores than patients without them. CONCLUSIONS: The QOL of FMF patients was found to be impaired compared to healthy controls. Further studies are needed to determine the exact factors affecting the quality of life of FMF patients.

Increased prevalence of joint manifestations in patients with recurrent aphthous stomatitis (RAS)

OBJECTIVE: To characterize the systemic manifestations and joint disease in patents with recurrent aphthous stomatitis (RAS). METHODS: The presence and features of extra-oral manifestations were determined by a rheumatologist, who examined and interviewed 64 patients, referred during 1993 to the oral medicine clinic for treatment of RAS. Controls were 65 medical staff members of a military clinic associated with the hospital. RESULTS: Based on the rheumatologist's findings and published criteria, the patients were diagnosed as suffering from RAS alone (24 patients), Reiter's syndrome (8), Behçet disease (8), familial Mediterranean fever (1), or RAS with undiagnosable extra oral manifestations (23). Thirteen patients in the last group had joint disease (p < 0.01 compared to the controls), characterized by recurrent mono- or oligoarthritis/arthralgia of short duration, affecting mostly the large joints. Conjunctivitis, pustular rash, lower back pain and urethritis/cervicitis were also common in RAS patients, but only the latter was significantly more frequent in RAS patients than in controls (p < 0.02). CONCLUSION: These findings suggest that patients with RAS have an increased frequency of a palindromic type joint disease.