Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Association of Behets Disease with Familial Mediterranean Fever
Cosan1, Fulya, Abaci2, Neslihan, Esen1, Bahar Artim, Cakiris2, Aris, Ustek2, Duran, Aral1, Orhan, Gul1, Ahmet
Behçet's Disease (BD) is a systemic inflammatory disorder, and it has a strong genetic contribution in its pathogenesis. Familial Mediterranean fever (FMF) is an autosomal recessively inherited autoinflammatory disorder caused by mutations in the MEFV gene. There are patients presented with the clinical features of both BD and FMF. However, it is still controversial that whether there is an association between BD and FMF. We herein aimed to analyse the genetic and clinical features of a group of patients with BD+FMF in a cohort of 1235 BD patients.
The main study group consisted with BD+FMF, and we used the findings of 288 patients with BD (170 male, 118 female) and 289 patients with FMF (134 male,155 female). All BD patients fulfilled the ISG criteria, and all FMF patients fulfilled the Tel-Hashomer criteria. We isolated genomic DNA from all subjects, and genotyping for the MEFV gene M694V, V726A, M680I, E148Q mutations was done by PCR-RFLP. Clinical features of patients were recorded using a standard form. Study protocol was approved by local ethics committee, and all subjects provided written informed consent prior to blood collection.
We identified increased frequency of FMF patients (n=21, 8 male, 13 female; 1.7%) in the BD cohort amongst to other accompanying disorders. Genetic analysis of 21 patients with BD+FMF for 4 common MEFV mutations showed that 42.8% of them had two mutations, 28.6% had one mutation, and 28,6 % had no mutation. The frequency of four MEFV mutations was not significantly different from FMF patients (71.4% vs 85.5%), however the frequency of E148Q was significantly higher in BD+FMF group compared to the frequency in FMF patients (31.3% vs 6.2%, P = 0.003). We compared BD-related clinical finding of BD+FMF patients with the findings of BD patients. We found that arthritis was significantly higher (85.7% vs 55.2%, P = 0.006, OR = 4.9, 95% CI 1,416,9), and eye involvement was significantly lower (33.3% vs 57.9%, P = 0.028, OR = 0.36, 95% CI 0,14-0,9) in BD+FMF group compared to BD patients. There was no BD+FMF patient with neurological or intestinal involvement. When we grouped the patients according to disease severity, patients with mild disease were significantly higher in BD+FMF group (52.4% vs 22%, P = 0,006, OR = 3.9, 95% CI 1.69.7). We did not observe any association between MEFV mutations and BD-related clinical findings including vascular involvement. Also, in the BD patient group with no FMF findings (n=288), BD patients carrying MEFV mutations was found to be significantly higher (27%) compared to the frequency in healthy controls (10%) (P<0.001, OR = 3,35, %95 CI 1,76, 8). We observed no association between the MEFV mutations and any of the BD manifestations, nor the disease severity in this BD group.
This study shows that patients presenting with the clinical features of both BD+FMF run less severe disease course with more frequent articular features and less frequent uveitis. We also observed that the frequency of E148Q mutation was higher in BD+FMF patients compared to FMF patients. Further analysis of BD+FMF patients may provide clues to understand the association of BD with FMF and the role of inflammasome in BD pathogenesis.
To cite this abstract, please use the following information:
Cosan, Fulya, Abaci, Neslihan, Esen, Bahar Artim, Cakiris, Aris, Ustek, Duran, Aral, Orhan, et al; Association of Behets Disease with Familial Mediterranean Fever [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1846