Clinical, laboratory and molecular characteristics of children with Familial Mediterranean Fever‐associated vasculitis

Abstract

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurrent self‐limited attacks of fever accompanied by peritonitis, pleuritis and arthritis. Approximately 5% of individuals with FMF have been reported to have Henoch‐Schonlein purpura (HSP) and about 1% have polyarteritis nodosa (PAN). Protracted febrile myalgia is another vasculitis‐associated clinical entity among patients with FMF. Recently, the gene responsible for FMF, MEFV, has been cloned and four missense mutations (M680I, M694V, V726A and M694I) have been described. In this report, we present clinical and laboratory findings and mutation results of 23 children with FMF‐associated vasculitis. HSP, PAN and protracted febrile attacks have been diagnosed in 11, 2 and 10 children, respectively. Mutation analysis shows that 3 children are homozygotes for the M694V mutation and 11 are compound heterozygotes for 2 of the studied mutations. M694V/V726A mutations were identified in 8, M694V/M694I in 2 and M680I/M694V in 1 of these children. In six children only one mutation was found and in three none of the studied mutations were identified. This study confirms that most children with FMF‐associated vasculitis have identifiable mutations in the MEFV gene. Environmental and/or other genetic factors are possibly involved in the pathogenesis of vasculitis in FMF; elucidation of these mechanisms will help to understand pathogenesis of childhood vasculitides. ?Children, Familial Mediterranean Fever, MEFV mutations, vasculitis

The role of MEFV mutations in the concurrent disorders observed in patients with familial Mediterranean fever

“…The prevalence of HSP and PAN in Turkish patients with FMF has been found to be 7% and 1%, respectively (15). The prevalence of HSP in the general population has been found to vary from 0.05% to 0.8% (8,16 Bias is inevitable in our study because the presence of concomitant disorders significantly increases the chance of a disease being detected (Berkon's bias). The inclusion of disease controls in concurrence studies minimizes the impact of this important bias at least to some degree (19).…”

İki Nadir Görülen Hastalığın Birlikteliği: Bir Çocukta Ailevi Akdeniz Ateşi ve Nörofibromatozis Tip 1

“…Although exact pathogenesis of FMFassociated vasculitis remains unknown, increased serum levels of proinflammatory cytokines, including IL1b, IL-6, IL-18, IL-33 and INF-c, and the resultant ECD seem to be important in vasculitis development in FMF patients 11,12 . Among those cytokines, IL-1b is the most prominent one, and extremely high IL-1b activity may favor vasculitis development in FMF patients.…”

Familial Mediterranean fever and membranous glomerulonephritis: report of a case

“…7 Nonamyloidotic renal involvement in the form of diffuse proliferative glomerulonephritis was reported by Tekin et al in three patients with FMF-associated vasculitis. 9 Akpolat et al described a 25-year-old patient, whose proteinuria remitted partially with prednisolone and azathioprine, who had membranoproliferative glomerulonephritis with FMF. 12 Immune complexes are exhibited in 50% of FMF patients.…”

“…5 Renal involvement in FMF, which is usually dependent on secondary AA amyloidosis, may in some untreated patients lead to kidney failure and other organ damage. IgM nephropathy, IgA nephropathy, crescentic rapidly progressive glomerulonephritis, diffuses proliferative glomerulonephritis, minimal change disease, and membranoproliferative glomerulonephritis have also been reported, [6][7][8][9][10] but not membranous glomerulonephritis.…”