Gene mutations associated with a number of periodic fevers took centre stage at the 2nd International Workshop on hyper-IgD and periodic fever syndrome (HIDS; Nijmegen, Netherlands; Dec 9-11).
HIDS is a rare familial syndrome in which patients have attacks of fever, abdominal pains, arthralgias, skin lesions, and lymphadenopathy (http://hids.net). A unique characteristic of the syndrome is that patients have high concentrations of serum IgD. Recently, mutations in mevalonate kinase, a key enzyme in cholesterol synthesis, were independently discovered in patients with HIDS by Laurence Cuisset (Hôpital Cochin, Paris, France) and Hans Waterham (Academic Medical Center, Amsterdam, Netherlands), both of whom spoke at the workshop. "This is a textbook case of gene detection by use of forward and reverse genetics", said Jos van der Meer (University Hospital St Radboud Nijmegen, Netherlands), who discovered HIDS. Nevertheless, it is unclear how a defect in cholesterol synthesis could result in a periodic fever with a strong inflammatory response.
Ian Todd and Richard McIntosh (Queen's Medical Centre, Nottingham, UK) presented data on familial Hibernian fever (FHF), an autosomal dominant periodic fever. They described how they had pinpointed the gene for the tumour-necrosis-factor (TNF) receptor as the causative gene for FHF. "There are now families from all over the world with the same genetic defect so I think that we should change the name of FHF to TNF-receptor associated periodic syndrome (TRAPS)", argued Dan Kastner (National Institutes of Health, Bethesda, MD, USA), who also updated delegates on familial Mediterranean fever (FMF).
With the better understanding of these fevers comes the possibility of new treatments. For FMF, colchicine remains "the mainstay treatment", said Avi Livneh (Sheba Medical Center, Tel Hashomer, Israel). For TRAPS, early results were presented on the use of injectable soluble TNF receptors. For HIDS, the potential use of thalidomide was discussed by Richard Powell (Queen's Medical Centre, Nottingham, UK). "It might work, but neuropathy as a side-effect precludes prolonged use", he warned. Statins are another potential treatment for HIDS and a clinical trial on these is to start soon.
Since the first HIDS workshop in 1995, much has been learnt about periodic fever syndromes. But, said Wietse Kuis (Wilhelmina Children's Hospital, Utrecht, Netherlands), "much ground still needs to be covered".
Anna Simon, Joost P H Drenth
Copyright: the Lancet
