Hyper-IgD syndrome

Hyperimmunoglobulinemia D with recurrent fever is a periodic fever syndrome originally described in 1984 by the internist Jos van der Meer, then at Leiden University Medical Centre. No more than 300 cases have been described worldwide. Hyperimmunoglobulinemia D with recurrent fever is a periodic fever syndrome originally described in 1984 by the internist Jos van der Meer, then at Leiden University Medical Centre. No more than 300 cases have been described worldwide. HIDS is one of a number of periodic fever syndromes. It is characterised by attacks of fever, arthralgia, skin lesions including cyclical mouth ulcers, and diarrhea. Laboratory features include an acute phase response (elevated CRP and ESR) and markedly elevated IgD (and often IgA), although cases with normal IgD have been described. It has mainly been described in the Netherlands and France, although the international registry includes a number of cases from other countries. The differential diagnosis includes fever of unknown origin, familial Mediterranean fever (FMF) and familial Hibernian fever (or TNFα reception associated periodic syndrome/TRAPS). Virtually all people with the syndrome have mutations in the gene for mevalonate kinase, which is part of the HMG-CoA reductase pathway, an important cellular metabolic pathway. Indeed, similar fever attacks (but normal IgD) have been described in patients with mevalonic aciduria – an inborn error of metabolism now seen as a severe form of HIDS. It is not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathway, the prenylation chains (geranylgeraniol and farnesol) might play a role. Canakinumab has been approved for treatment of HIDS and has shown to be effective. The immunosuppressant drugs etanercept and anakinra have also shown to be effective. Statin drugs might decrease the level of mevalonate and are presently being investigated. A recent single case report highlighted bisphosphonates as a potential therapeutic option.