Case reportAnakinra: New therapeutic approach in children with Familial Mediterranean Fever resistant to colchicine
Introduction
Familial Mediterranean Fever (FMF, MIM249100) is the prototype of a group of disorders termed “systemic autoinflammatory diseases” and characterized by seemingly unprovoked episodes of inflammation in the absence of high-titer autoantibodies or antigen-specific T cells [1], [2]. The clinical picture associated with FMF includes short episodes of fever, abdominal, thoracic, and joint pain, and erysipelas-like erythema. Repeated bouts of inflammation may lead to systemic amyloid (AA) protein deposition, especially in the kidney making FMF a potentially fatal disease.
The FMF gene (MEFV), which was discovered in 1997 [3], encodes a protein known as pyrin or marenostrin that is thought to modulate apoptosis, NF-κβ activation, and processing of the potent pyrogenic interleukin-1β (IL-1β) cytokine. More than 70 FMF gene mutations have been reported to date [4]. Although colchicine prophylaxis has dramatically changed the prognosis of FMF by preventing febrile attacks and the production of serum AA [5], some patients are unresponsive or cannot tolerate its side effects.
Knockdown experiments have demonstrated a net inhibitory effect of pyrin on IL-1β processing, and clinical data have substantiated the importance of IL-1β in the pathogenesis of FMF [6]. Therefore, it remains to be seen whether targeting IL-1 can be an effective approach to FMF. Anakinra, a recombinant nonglycosylated homolog of human IL-1 receptor (IL-1Ra), is at present the only drug that competitively inhibits binding of IL-1α and IL-1β to IL-1 receptor type I.
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Case report
The patient's symptoms began when he was 9 years old and consisted of long inflammatory episodes recurring each 2–3 weeks characterized by high fever, urticarial rash, abdominal pain and headache, in addition to arthralgia, myalgia and arthritis. A biologic inflammatory syndrome was observed, with a C-reactive protein (CRP) level of 168 mg/l, an erythrocyte sedimentation rate (ESR) of 95 mm/h and a white blood cell (WBC) count of 16.970/mm3. Exhaustive explorations failed to establish any
Discussion
Daily administration of colchicine is the current therapy of choice for the prophylaxis of attacks and amyloid deposition in FMF. The effect of alternative treatments on patients not responding to prophylactic administration of colchicine (5–10%) has only been reported in individual patients or small series. Although some favourable effects have been obtained with additional thalidomide, interferon-alfa, infliximab and weekly intravenous colchicine, no effective alternative treatment appears to
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