Periodic fevers and other autoinflammatory diseases.

ABSTRACT

Autoinflammatory diseases represent a relatively new and rapidly evolving group of rare disorders associated with mutations of genes encoding proteins with a key regulatory role in inflammatory response. Gradual discovery of mechanisms that link genetic disorder with its biochemical and immunological consequences leading to continuous or episodic inflammatory stimulation has enabled introduction of directed immunotherapies. Periodic fever syndromes belong to the so far best-known entities familial Mediterranean fever, mevalonate kinase deficiency, cryopyrinopathies and TNF-receptor associated periodic syndrome. These inherited disorders usually manifest in childhood with variably long febrile episodes accompanied with the spectrum of other skin and organ inflammatory features and elevation of laboratory markers of inflammation. Uncontrolled disease may lead to secondary amyloidosis. Directed anti-inflammatory therapy can prevent evolution of organ damage. In children benign syndrome of periodic fever with aphtae, pharyngitis and cervical adenitis is the most common self-limited disorder without clear genetic disposition. Following other autoinflammatory disease groups are described - pyogenic syndromes, disorders with skin and bone manifestations, granulomatous diseases, monogenic vasculopathies and diseases associated with proteasome disorder. Diagnosis of autoinflammatory diseases is often delayed due to their extreme rarity. Increasing efficacy and availability of molecular-genetic testing and centralization of diagnostics and clinical care in a specialized center for children as well as adults can in the future improve quality of care for patients with these rare conditions. Keywords autoinflammatory diseases (AID), periodic fever syndromes, FMF, CAPS, MKD, TRAPS, PFAPA, NGS.