Identification of the genes involved in hereditary periodic fever syndromes has 
led to the recognition of a new pathophysiological category, the 
autoinflammatory disorders. The main non-hereditary autoinflammatory disease in 
childhood is systemic juvenile idiopathic arthritis (sJIA), others being the 
chronic infantile neurological cutaneous arthropathy (CINCA) syndrome and the 
periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) 
syndrome. Familial Mediterranean fever (FMF) has been traced to mutations in the 
MEFV gene. Mutations in the MVK gene, encoding the enzyme mevalonate kinase, 
cause the hyper-IgD periodic fever syndrome (HIDS). The tumour necrosis 
factor(TNF)-receptor-associated periodic syndromes (TRAPS) have been linked to 
mutations in theTNFRSF1A gene, encoding a TNF-alpha receptor, and the CIAS1 gene 
is mutated in familial cold autoinflammatory syndrome. We discuss how this 
knowledge has influenced diagnosis and treatment of these rare genetic disorders 
and how it might change our approach to the more common rheumatic diseases.