Clinical and genetic analysis of the patients mimicking familial Mediterranean fever

Background/Purpose: Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by recurrent episodes of fever and polyserositis. The differential diagnosis is sometimes difficult because the symptoms of FMF are nonspecific and the disease markers or autoantibody are not existed. We aimed to evaluate the diseases to watch out for differential diagnosis of FMF.

Methods: We analyzed 15 patients initially suspected as having FMF but diagnosed as other disease after the analysis of MEFV gene mutation. All patients were fulfilled diagnostic criteria (Livneh criteria). Their clinical symptoms, final diagnosis, effectiveness of colchicine, and genetic mutations were retrospectively investigated.

Results: The diagnosis of these 15 patients were as follows; Behçetfs disease (n=4), malignant disease (n=2), infectious disease (n=2), periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) (n=2), and Crohnfs disease, adult-onset Stillfs disease, calcium pyrophosphate dihydrate deposition disease, sarcoidosis, and adrenalism (n=1, each). All patients had recurrent fever. Eight patients (53.3%) had abdominal pain, 6 (40%) had chest pain, and 6 (40%) had arthralgia. Colchicine was prescribed for 10 patients and effective for 5 patients (50%) but ineffective for 4 patients (40%). Most of the colchicine-responsive patients had the colchicine effective disease such as Behçetfs disease. Although known MEFV gene mutation were identified in 10 patients (66.7%), exon 10 mutations were not found.

Conclusion: Behçetfs disease, malignancies, infection, and other autoinflammatory disease would be important differential diagnosis of FMF. The frequency of serositis and the prevalence of pathogenic mutations were lower than typical FMF. Patients not having the pathogenic mutation and refractory to colchicine treatment may be needed to re-examine malignancies and infections. Even if colchicine treatment was effective, we might have to pay attention to existence of specific symptoms of other autoinflammatory disease.

Table 1. MEFV mutations of the patients