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.
HIDS is one of a number of periodic fever syndromes
. It is characterised by attacks of fever
, skin lesions
, and diarrhea
. Laboratory features include an acute phase response
) 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 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.
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
) might play a role.
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.
- van der Meer JWM, Vossen JM, Radl J, van Nieuwkoop JA, Meyer CJLM, Lobatto S, van Furth R. Hyperimmunoglobulinaemia D and periodic fever: a new syndrome. Lancet 1984;I:1087-1090. PMID 6144826.
- Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M. Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet 1999;22:178-81. PMID 10369262.
- Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MMJ, Huijbers WAR, Rijkers GT, Waterham HR, Wanders RJA, Poll-The BT. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nature Genet 1999;22:175-177. PMID 10369261.
- Rigante D, Ansuini V, Bertoni B, Pugliese AL, Avallone L, Federico G, Stabile A. Treatment with anakinra in the hyperimmunoglobulinemia D/periodic fever syndrome. Rheumatol Int. 27 July 2006. PMID 16871408
- HIDSNet homepage