Hyperimmunoglobulinemia D and periodic fever syndrome in children. Review on therapy with biological drugs and case report

Hyperimmunoglobulinemia D syndrome (HIDS) is a rare, autosomal recessively inherited autoinflammatory disease caused by mutations in the mevalonate kinase gene. HIDS usually starts in infancy with recurrent fever episodes lasting 3-7 days and recurring every 4-6 weeks, with only partial symptom decrease in adulthood. Fever is typically accompanied by abdominal pain, vomiting, diarrhoea and cervical lymphadenopathy, and sometimes by skin and joint symptoms. Blood leukocytes and serum C-reactive protein are elevated during the episode, and in addition, high levels of interleukine-1 (IL-1), IL-6 and tumour necrosis factor (TNF) and respective soluble receptors have been measured. Instead, serum immunoglobulin D (IgD) is usually normal until 3 years of age. Currently, there is no established treatment for HIDS. Thus far, four children have been successfully treated with etanercep, TNF-alpha inhibitor, and three children with anakinra, IL-1 receptor antagonist.

Conclusion: This review summarizes currently available data on the use biological medicines for HIDS in children. A Finnish 1.5-year-old patient with disease onset at 6 months of age, treated successfully with anakinra, is presented.