title: Clinical and genetic aspects of Blau syndrome: a 25-year follow-up of one family and a literature review.
abstract: Blau syndrome (BS) is a rare familial disease transmitted as an autosomal dominant trait, characterized by arthritis, uveitis, skin rash and granulomatous inflammation. Until now BS has been observed in 136 persons belonging to 28 families as well as in 4 sporadic cases. The gene responsible for BS has recently been identified in the nucleotide-binding domain (NBD) of caspase recruitment domain (CARD15/NOD2), also involved in the pathogenesis of Crohn's disease. In addition to three missense mutations (R334Q, R334W and L469F) previously identified, a new CARD 15 mutation (E383K) has recently been described in a family followed by us for the past 25 years. The characteristics of this family which, to our knowledge, is the only one affected with BS in Italy, are the object of this manuscript. Both the proband and her daughter were originally affected with a papulonodular skin eruption and then with mild arthritis of the hands and feet. The proband, but not the daughter, complained of severe chronic bilateral uveitis, followed by glaucoma and, a few years later, by cataracts. Histological examination of skin biopsies from both subjects and a joint biopsy (daughter only), showed non-caseating granulomas with multinucleated giant cells which, at electron microscopy, revealed "comma-shaped bodies" in epithelioid cells, thought to be a marker for BS. The disease is presently well controlled with low doses of prednisone for the mother and non-steroidal anti-inflammatory drugs (NSAIDs) plus low doses of prednisone, when necessary, for the daughter. As in Crohn's disease, CARD15/NOD2 mutation is believed to be responsible for the granulomatous autoinflammatory reactions probably triggered by microorganisms in BS.
authors: Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Italy. punzireu@unipd.it
authors: Leonardo
authors: L
authors: Punzi
authors: Antonio
authors: A
authors: Furlan
authors: Marta
authors: M
authors: Podswiadek
authors: Alessandra
authors: A
authors: Gava
authors: Marialuisa
authors: M
authors: Valente
authors: Mario
authors: M
authors: De Marchi
authors: Andrea
authors: A
authors: Peserico
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001168:Arthritis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D025063:Chromosome Disorders / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D005076:Exanthema / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005799:Genes, Dominant / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007558:Italy; D008297:Male; D020125:Mutation, Missense; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology / Q000378:metabolism; D010375:Pedigree; D011110:Polymorphism, Genetic; D013577:Syndrome; D013997:Time Factors; D014605:Uveitis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C089765:NUBP1 protein, human; D053473:Nod2 Signaling Adaptor Protein