Background Familial Mediterranean Fever (FMF) is a relatively rare condition that belongs to the more recent group of autoinflammatory diseases (AIDs)¹. It primarily affects patients with Mediterranean or Middle Eastern origins and its clinical setting includes short, recurrent episodes of fever, serositis, skin rash and a high risk of amyloidosis². FMF is an autosomal recessive transmitted disease and several mutations of the Mediterranean fever gene (MEFV) on chromosome 16 have been identified³. Patients respond well to colchicine therapy or if necessary, biological therapy with anti-IL 1, IL6 or anti-TNF could be initiated⁴. Establishing the right diagnosis might raise difficulties for rheumatologists who are not fully accustomed to this condition.

Objectives To evaluate the clinical course, specific features and treatment difficulties of a male patient diagnosed with FMF in adulthood, based on the description of a case report.

Methods Case-description using patient's medical records and investigations.

Results This is the case report of a 37-year old male patient currently admitted for right knee arthritis and high grade fever (39.1°C). His medical history dates back at age 16 when he presented in the Pediatric Department with recurrent episodes of prolonged fever (up to 40°C), diffuse abdominal pain together with myalgia, arthralgia accompanied by increased acute phase reactants; after various sources of infection and hematological malignancies were excluded, physicians noted positive low titer ANA (1/20) but normal complement fractions, absent lupus (LE) cells. Further medical investigations showed a negative rheumatoid factor, ACPA, negative antibodies' panel (dsDNA, Sm, Ro, U1-RNP) and absent cryoglobulins but a positive HLA B27. No signs of sacroiliitis were detected on the x-ray. Patients' repeated complaints of knee or ankle arthritis together with later finding of positive anti-Salmonella and anti-Shigella antibodies leaded to establishing the diagnosis of reactive arthritis. Due to symptoms' persistence and reoccurrence under non-steroidal anti-inflammatory drugs, he was prescribed high dose corticosteroids and sulfasalazine. At age 20 the patient presented with recurrent arthritis of the knees and ankles, fever (38.5°C) and abdominal pain with markedly elevated inflammatory markers. The abdominal ultrasound highlighted a splenomegaly and peritonitis. Colchicine treatment was initiated and his favorable response led to MEFV genetic testing that revealed a mutation of the 10.1 exon, thus confirming the diagnosis of FMF by fulfilling two major criteria of the Tel-Hashomer diagnostic set. Subsequently, he performed a gingival biopsy that excluded the presence of amyloid deposits. Patient's partial response to colchicine with repeated incomplete attacks of FMF and persistent inflammatory syndrome led to the initiation of biological therapy with Etanercept along with Sulfasalazine and glucocorticoids, due to temporary unavailability of an anti-IL1 agent. Patient's delay in diagnosis and longstanding corticosteroid therapy led to major articular consequences (bilateral aseptic osteonecrosis of the femoral head with requiring hip arthroplasty).

Conclusions This case presentation depicts the hardships of setting the right diagnosis in a case of late onset FMF due to unusual geographical setting, absence of suggestive family history and heterogeneous clinical presentation together with possibilities in therapeutic approach if patients are non or partially responsive to traditional therapies. Furthermore it points out possible drug side effects and comorbidities that require the same quality medical care as the main rheumatic disease.

References

1. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997;40(10):1879–1885. doi:10.1002/1529–0131(199710)40:10<1879::AID-ART23>3.0.CO;2-M.

2. Yalcinkaya F, Ozen S, Ozcakar ZB, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology. 2009;48(4):395–398. doi: 10.1093/rheumatology/ken509.

3. Dogan H, Akdemir F, Tasdemir S, et al. A novel insertion mutation identified in exon 10 of the MEFV gene associated with Familial Mediterranean Fever. BMC Med Genet. 2014;15:74. doi:10.1186/1471–2350–15–74.

4. Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016;75(4):644–651. doi:10.1136/annrheumdis-2015–208690.

References

Disclosure of Interest None declared