Periodic Fever Syndromes

Overview

Periodic fevers are characterized by prolonged periodic fever attacks, associated in some cases withperitonitis, pleurisy, arthritis, skinrash, conjunctivitis or systemic amyloidosis. Recently, the geneticcause of some entities was found and the group of periodic fever syndrome was roughly divided intoautosomal recessive and autosomal dominant states. Familial Mediterranean Fever (FMF) andHyper IgD syndromes belong among autosomal recessive disorders. The genes for both entitieswerediscovered 1997 and 1999, respectively, in the course of the Human Genome Project. Gene modifiedin FMF is called MEFV and codes for protein pyrin, sometimes referred as manetostrin. Pyrin isexpressed mainly in granulocytes and monocytes, the fever is caused by alteration in IL-1 regulation.Hyper IgD syndrome is surprisingly caused by mutations in gene coding for mevalonate kinase, anenzyme involved in the cholesterol biochemical pathway. The detailed mechanism of fever pathogenesisis in that case unknown. Autosomal dominant periodic fevers are grouped under the nameTRAPS, TNF receptor-associated periodic syndromes. Individual case-reports known originally forexample as Familial Hybernian Fever or Familial Periodic Fever are now included into the TRAPSgroup according to the genetical analysis in the affected families. Mutated gene codes the subunitof the receptor for TNF, called now TNFSF1A. The probable cause of fever attacks is the diminishedshedding of membrane bound receptor, causing low level of the soluble form which under normalcircumstances might links with free TNF. Blockade of TNF is thus one of the new possible therapeuticaloptions. We followed over the last 5 years 12 children with periodic fever syndromes. Even ifthe clinical characteristics differed among patients, all of them suffered from repeated attacks offevers, lasting for at least one year. We systematically followed IgD and the level of mevalonic acidin children with suspected hyper IgD syndrome and soluble TNF receptor in children suspected forTRAPS. Molecular diagnosis was until now performed in 5 children, hyper IgD syndrome wasconfirmed in 3 patients, critical exons 2, 3 and 4 ofTNFR1 gene were sequenced in another 2 childrenwith clinically suspected TRAPS but no mutation was found in these patients.

Key words:
periodic fever, autoimmunity, child