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Autoinflammatory DiseasesClinical and Genetic Advances
Sharifeh Farasat, BS;
Ivona Aksentijevich, MD;
Jorge R. Toro, MD
Arch Dermatol. 2008;144(3):392-402.
We conducted a literature review to investigate the recent advances in genetics, molecular biology, clinical manifestations, and therapy of 7 inherited diseases that are characterized by seemingly unprovoked inflammation. These autoinflammatory diseases include familial Mediterranean fever; tumor necrosis factor receptor–associated periodic syndrome; hyperimmunoglobulinemia D with periodic fever syndrome; pyogenic arthritis, pyoderma gangrenosum, and acne syndrome; and the 3 cryopyrinopathies: neonatal-onset multisystem inflammatory disease/chronic infantile neurologic cutaneous and arthropathy syndrome, familial cold autoinflammatory syndrome, and Muckle-Wells syndrome. Recent identification of the susceptibility genes for autoinflammatory diseases has broadened the clinical spectrum as well as the molecular basis of these diseases. The cryopyrinopathies represent a continuum of diseases associated with mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene that encodes cryopyrin. Cryopyrin and pyrin (protein mutated in familial Mediterranean fever) belong to the family of PYRIN domain–containing proteins. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome is associated with mutations in the gene that encodes for CD2-binding protein 1 (CD2BP1), which binds pyrin. Recent studies have shown that activation of the interleukin 1β pathway is a common mechanism in the pathogenesis of autoinflammatory diseases, further unifying these diseases. Recent advances in genetics and molecular biology have advanced our understanding of the pathogenesis of autoinflammatory diseases. Understanding autoinflammatory diseases will further our knowledge of cutaneous as well as systemic inflammation. Anakinra, a recombinant human interleukin 1 receptor antagonist, is a promising new biologic agent for the treatment of cryopyrinopathies as well other autoinflammatory diseases, such as tumor necrosis factor receptor–associated periodic syndrome and hyperimmunoglobulinemia D with periodic fever syndrome.
Author Affiliations: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Ms Farasat and Dr Toro); and Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland (Dr Aksentijevich).
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