Hyperimmunoglobulinemia D(IgD) Syndrome

Hyperimmunoglobulinemia D with recurrent fever (commonly abbreviated as HIDS) is a periodic fever syndrome originally described in 1984 by the internist Prof. Jos van der Meer, then at Leiden University Medical Centre. No more than 300 cases have been described worldwide.

Features

HIDS is one of a number of periodic fever syndromes. It is characterised by attacks of fever, arthralgia, skin lesions, 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).

Cause

Virtually all patients 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 (Drenth et al 1999, Houten et al 1999). 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.

Pathophysiology

Is it not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathyway, the prenylation chains (geranylgeraniol and farnesol) might play a role.

Therapy

The recurring fevers are highly unpleasant for patients, but so far only the immunosuppressant drugs etanercept (Enbrel) and anakinra have been shown to be effective. Statin drugs might decrease the level of mevalonate and are presently being investigated.