Autoinflammatory Syndromes

Abstract

Autoinflammatory syndromes constitute a group of genetic disorders, in which gene mutations coding for significant inhibitory inflammatory molecules have been identified. These disorders can manifest with inflammatory signs and symptoms of one or many organs without an apparent exogenous or endogenous insult. The mutated genes responsible for the main clinical syndromes are the MEFV gene on chromosome 16 in patients with Mediterranean fever; the type I TNF-α receptor (TNFRSF1A) gene on chromosome 12 in patients with TNF-α receptor-associated periodic syndrome (TRAPS); the mevalonate kinase (MVK) gene on chromosome 12 in patients with hyperimmunoglobulin D syndrome (HIDS); the CIAS1 gene on chromosome 1 in patients with cryopyrin-associated periodic syndrome (CAPS); the PSTPIP1 gene on chromosome 15q in patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome; the IL1RN gene, which encodes interleukin-1 receptor antagonist, in patients with deficiency of the interleukin-1 receptor antagonist (DIRA) andthe TMEM173 gene, encoding the stimulator of interferon genes (STING) in patients with STING-associated vasculopathy with onset in infancy (SAVI), a recently described autoinflammatory syndrome. The age onset of the different syndromes is variable. The clinical picture of these syndromes usually manifests with recurrent fevers, skin rashes, mucosal lesions, thoracic or abdominal pains (due to serositis), arthritis, and elevated acute-phase proteins. Cornerstone therapy of these disorders includes colchicine and anti-interleukin-1 receptor antagonist.