Two cases of familial Mediterranean fever associated with sarcoidosis (Lofgren's syndrome) and rheumatoid arthritis

Dear Editor, Familial Mediterranean Fever (FMF) is an autosomal recessive disease caused by mutations in the MEFV gene encoding for the pyrin protein which belongs to a class of proteins taking part in the regulation of apoptosis and inflammation. The role of the pyrin domain which provides an uninterrupted inflammatory cascade is blocked by mutations in the MEFV gene. The mutations in the MEFV gene may act as susceptibility factors for diseases with autoinflammatory characteristics through a state of more intense inflammatory response. The impact of MEFV mutations has been shown in inflammatory diseases, namely Henoch-Schonlein purpura, Behçet’s disease, rheumatic heart diseases and rheumatoid arthritis (RA). Sarcoidosis is a chronic, inflammatory disease of unknown etiology and is characterized by the formation of noncaseating granulomas in the affected organs, mostly in the lungs. In this letter, we report two cases of FMF, one of which was associated with sarcoidosis and the other one associated with RA. A 61-year-old woman was admitted to our rheumatology out-patient clinic with widespread bone pain and erythematous skin lesions on the upper and lower limbs. Twenty days prior to admission, she started to complain of chest pain and cough. She had a history of right hip surgery after a fall and was suffering from attacks of abdominal pain and fever for 3 years. On physical examination, she had diffuse, round, subcutaneous, painful, stiff and red nodules in her extremities which were compatible with erythema nodosum (EN). The laboratory test results were as follows: She had a severe acute phase response with erythrocyte sedimentation rate (ESR) 124 mm/h (normal 0–20), C-reactive protein (CRP) 215 mg/L (0–5) and rheumatoid factor (RF) 10.1 U/mL (0–14), angiotensin converting enzyme (ACE) 63.2 U/L (8–52), calcium 9.7 mg/dL (8.6–10), purified protein derivative (PPD) intradermal reaction 9 mm after 72 h. Human leukocyte antigen (HLA)-B27 and pathergy tests were also negative. A chest X-ray showed hilar lympadenopathy. Computed tomography (CT) scan revealed mediastinal lymphadenopathy (LAP) and ground-glass nodules in both lungs. Lung biopsy revealed noncaseified granuloma and epithelioid histiocytes scattered among inflammatory cells (Fig. 1). The patient was diagnosed as having Löfgren’s syndrome, which is a clinical subtype of acute sarcoidosis involving acute arthralgia, bilateral hilar LAP and erythema nodosum. Methylprednisolone 16 mg/day and methotrexate 10 mg/week were prescribed. Erythema nodosum had regressed on follow-up but the patient complained about fever, abdominal and ankle pain and skin rash on her face, neck and back. On genetic analysis, heterozygous mutation for E148Q was detected. Therefore, colchicine was added to methotrexate and steroid treatment. After initiation of colchicine treatment, fever and abdominal pain of the patient recovered. A 28-year-old woman was referred to our rheumatology out-patient clinic with joint pain and swelling in