The familial mediterranean fever (FMF), an autosomal recessive disease described primarily in the Mediterranean littoral, is often complicated by amyloidosis, but rarely associated with rapidly progressive glomerulonephritis, especially in case of heterozygote mutations of the FMF gene (MEFV).
We report the case of a 21-year-old Romanian woman admitted to our department due to pitting edema in her lower limbs. She had been healthy until the age of 10 when she developed recurrent episodes of fever and arthralgias. Upon admission, blood pressure was 120/60 mmHg, pulse rate 80 beats/minute and respiratory rate 24/minute. There was no fever. Lung, heart, neurologic examinations were within normal limits. Laboratory tests showed proteinuria of 4.2 g/24 h and serum creatinine of 5.2 mg/dL. Hemoglobin was 11.6 g/dL, white blood cells 12,600/mm3, platelets 232,000/mm3. Serum protein was 5.8 g/dL and albumin 3.1 g/dL. C-reactive protein and erythrocyte sedimentation rate were elevated. No monoclonal band was present in serum protein electrophoresis. Autoimmune and coagulation parameters were normal, as well as thyroid and liver function tests. Urinalysis revealed microscopic hematuria. Kidney biopsy showed diffuse mesangial expansion, extracapillary proliferation and numerous cellular crescents. Mesangial and perivascular amorphous hyaline material stained weakly with periodic acid Shiff’s and bound Congo red. Crescentic extracapillary glomerulonephritis and renal amyloidosis were diagnosed. Genetic testing for secondary (AA) amyloidosis was performed, and two mutations involving a copy of M694V and a copy of E148Q of MEFV gene were identified. The patient received steroids, colchicine and ramipril. After two weeks, renal function improved and the patient was discharged.
Only few cases of rapidly progressive glomerulonephritis in the setting of FMF have been so far reported.Citation1–3 A case of necrotizing crescentic glomerulonephritis with granulomatous vasculitis was described in a patient with FMF, complicated by amyloidosis.Citation1 Another case of rapidly progressive glomerulonephritis was reported in a patient homozygous for E148Q mutation.Citation2 Rapidly progressive glomerulonephritis has been recently associated with M694V/E148Q compound heterozygote mutation in a patient with both FMF and Henoch–Schönlein vasculitis,Citation3 in the absence of amyloidosis.
To our knowledge, this is the first case of FMF where an M694V/E148Q compound heterozygote mutation is associated with rapidly progressive glomerulonephritis in the absence of other vasculitic disorders. Although amyloidosis is one of the most frequent renal manifestations of FMF, nephrologists should always consider rapidly progressive glomerulonephritis as a possible complication of this syndrome, even in the presence of MEFV heterozygote mutations.
Declaration of interest
The authors report no conflicts of interest.
References
- Cefle A, Kilicaslan I, Gul A, et al. Necrotizing crescentic glomerulonephritis with granulomatous vasculitis in a patient with familial Mediterranean fever and renal amyloidosis. Clin Exp Rheumatol. 2004;22(4 Suppl 34):80
- Topaloglu R, Ozaltin F, Yilmaz E, et al. E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever. Ann Rheum Dis. 2005;64(5):750–752
- Sozeri B, Mir S, Ertan P, et al. Rapidly progressive glomerulonephritis in a child with Henoch–Schönlein vasculitis and familial Mediterranean fever. Pediatr Rheumatol Online J. 2009;7:8