Treatment with anakinra in the hyperimmunoglobulinemia D/periodic fever syndrome

Abstract

Hyperimmunoglobulinemia D/periodic fever syndrome is caused by recessively inherited mutations in the mevalonate kinase gene and is characterized by persistently high polyclonal serum IgD titre and recurrent febrile attacks. No conventional therapy exists for preventing the typical recurrent inflammatory picture of patients. A host of studies have evidenced that elevated levels of various cytokines, such as interleukin-1 (IL-1), mark febrile attacks in this disease and that IL-1 might represent a suitable therapeutic target. We describe the case of a 7-year-old female-child with an established diagnosis of hyperimmunoglobulinemia D/periodic fever syndrome in whom anakinra, IL-1 receptor antagonist, was daily administered at the dosage of 1 mg/kg/day by subcutaneous injection for 18 months after numerous disappointing attempts with non-steroidal anti-inflammatory drugs, steroids, colchicine and etanercept through the years. The clinical response under anakinra treatment was recorded through a standardized diary, whilst inflammation parameters were serially measured in comparison with the half-year before starting anakinra. Frequency and severity of fever attacks were totally reduced by anakinra and this is the first child demonstrating that symptoms of hyperimmunoglobulinemia D/periodic fever syndrome might be at least extenuated by anakinra, though not abolished.

Hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype

“…Infliximab, a humanized monoclonal antibody against TNF-α, and tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, might also be thinkable alternatives. So far, some children have been successfully treated with etanercept and with different anti-IL-1 drugs (Bodar et al, 2011;Caorsi et al, 2012;Galeotti et al, 2012;Hoffman, 2009;Rigante et al, 2006). If either of these treatments are not effective a switch to the other can be considered, because some patients have a good response to anti-IL1 drugs but not to etanercept, and vice versa (Caorsi et al, 2012;van der Hilst and Frenkel, 2010).…”

“…Currently, there is no evidence-based treatment available for HIDS (Korppi et al, 2011). Thus far, some children have been successfully treated with etanercept and others with IL-1 antagonists (Bodar et al, 2011;Caorsi et al, 2012;Galeotti et al, 2012;Hoffman, 2009;Rigante et al, 2006).…”

An Adolescent with Hyperimmunoglobulinemia D and Periodic Fever Syndrome Responding to Simvastatin Treatment

“…[1,11,[14][15][16] Colchicine and prednisolone had no beneficial effect in preventing the recurrence of attacks in our patient. Recent studies with the HMG-CoA-reductase inhibitor simvastatin have brought hopeful results for the treatment of this disease [3,4,17,18] Simon et al [4] reported that six patients with HIDS and proven MVK deficiency were followed up for two treatment periods with simvastatin, 80 mg/day, or placebo for 24 weeks separated by a four-week washout period in a double-blind manner Important reductions in the number of attacks and decreased urinary mevalonate were observed.…”

Current Advances in the Understanding and Treatment of Mevalonate Kinase Deficiency

“…Anakinra (1 g/kg/day) was first shown to reduce the overall number and severity of febrile attacks in a 7-year-old girl with MKD in 2006 (35). Two sisters with MKD also exhibited normal levels of inflammatory markers and a substantially improved quality of life after starting anakinra (36).…”