Periodic fevers and autoinflammatory conditions

Autoinflammatory syndromes (AIS) are a spectrum of immune-mediated disorders that typically present in childhood with recurrent fevers, high inflammatory markers and systemic involvement. The quintessential periodic fever is familial Mediterranean fever, which is relatively common in Middle Eastern populations, but in general, these conditions are rare and diagnostically challenging. As a group of conditions they are typified by a delay in diagnosis of several years with repeated hospital visits, unnecessary investigations and treatment, impact on quality of life and an increased risk of the most severe complication of systemic AA amyloidosis.The purpose of this review is to help clinicians suspect and diagnose AIS in children presenting with (recurrent) fevers or multisystem inflammation of unknown aetiology after common causes such as infection and autoimmune diseases have been excluded. We will identify when to consider AIS through a systematic approach of pattern recognition. We will discuss the presentation and differential diagnosis of recurrent fevers in neonates (the cryopyrinopathies), in childhood (hereditary periodic fevers) and pathognomonic rashes associated with AIS. Although, by no means exhaustive, we will also discuss other forms of AIS and provide an overview of the principles of treatment of AIS.