{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:30:43Z","timestamp":1791293443370,"version":"4.1.0"},"reference-count":76,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2015,5,14]]},"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>The recent identification of genetic mutations leading to dysfunction of inflammatory and apoptotic pathways, has allowed to characterise a group of diseases, recognised as monogenic autoinflammatory syndromes. Among those, Blau syndrome (BS) and early-onset sarcoidosis (EOS) have been identified as familial and sporadic phenotypes of the same non-caseating granulomatous form. Both the diseases are caused by mutations in the <jats:italic>CARD15\/NOD2<\/jats:italic> gene, encoding the cytosolic NOD2 protein, one of the key molecules in the regulation of innate immunity. Clinical onset is typically located in the first years of life and phenotype is characterised by simultaneous or less articular, cutaneous and ocular non-caseating granulomatous inflammation, which can be variably associated with a heterogeneous systemic spectrum. The <jats:italic>CARD15\/NOD2<\/jats:italic> gene has also been identified as one of the genes linked to susceptibility to Crohn's disease (CD), a common polygenic inflammatory granulomatous bowel disease. The heightened nuclear factor-\u03baB activity, found in the intestinal tissue of patients affected by CD, has probably a genetic cause related to several <jats:italic>CARD15\/NOD2<\/jats:italic> polymorphisms. Other substitutions in the <jats:italic>CARD15\/NOD2<\/jats:italic> gene have also been found in a recently described disorder, called <jats:italic>NOD2<\/jats:italic>-associated autoinflammatory disease, which shares several clinical characteristics with BS and EOS. This review attempts to describe these diseases on the basis of the most recent evidences. We described genetic and clinical aspects, mainly focusing on BS and EOS, the most representative diseases of autoinflammatory granulomatous diseases, with the ultimate purpose to expand their knowledge.<\/jats:p>","DOI":"10.1136\/rmdopen-2015-000097","type":"journal-article","created":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T21:25:16Z","timestamp":1437427516000},"page":"e000097","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":115,"title":["Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease"],"prefix":"10.1136","volume":"1","author":[{"given":"Francesco","family":"Caso","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy"},{"name":"Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, 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