Familial granulomatous synovitis, uveitis, and cranial neuropathies

CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large‐vessel arteritis and cranial neuropathy

“…Affected individuals typically exhibit one or more of the following granulomatous inflammations, which are variable in terms of age at onset: acute anterior uveitis, arthritis (sometimes associated with camptodactyly), and skin rash. Recent studies on families with Blau syndrome have revealed the involvement of other organs in addition to the skin, joint, and eye, as well as other symptoms such as cranial neuropathies (2), fever (3)(4)(5)(6), cerebral infarction (7), sarcoid-like hepatic granulomata (6), arteritis and/or malignant hypertension (3)(4)(5), and renal lesions (8). The Blau syndrome phenotype therefore may be more complex than previously suspected, and we have suggested that Blau syndrome and related disorders are a subset of the familial granulomatosis syndromes (9).…”

Molecular Signaling and Ocular Inflammation: An Update on the NOD-Like Receptors (NLRs)

“…NOD2 was one of the first NLR family members to be characterized in terms of its structure and function. NOD2 is unequivocally linked with human uveitis, as mutations in NOD2 result in the autosomal dominant multi-organ disease, Blau syndrome, which is characterized by uveitis, arthritis, and dermatitis [37][38][39][40] NOD2 senses the bacterial cell wall component peptidoglycan, or PGN, of which the minimal moiety required for NOD2 activation is muramyl dipeptide (MDP)) [41][42][43], and thus is critical for host defense against intracellular bacterial infection [44]. NOD2 has more recently been shown to participate in MDP-independent responses such as viral infection [45], thereby indicating a more complex role for NOD2 than may have been originally appreciated.…”

Widespread Granulomatous Dermatitis of Infancy

“…60 Permanent sequelae of chronic inflammation in the eyes and/or joints develop in more than 80% of patients with EOS/BS, 14,38 and anticipation (increased severity in successive generations) has been described in familial cases. 17,21 The clinical manifestations of EOS/BS can extend beyond the classic triad. Additional systemic features have included cranial neuropathies 11,17 ; granulomatous large-vessel vasculitis that involves the carotid, renal, and cerebral arteries 11,[14][15][16]19,24,61,62 ; and granulomatous inflammation of the liver, kidneys, lung, heart, and epididymis (typically occurring in later stages of the disease).…”

“…17,21 The clinical manifestations of EOS/BS can extend beyond the classic triad. Additional systemic features have included cranial neuropathies 11,17 ; granulomatous large-vessel vasculitis that involves the carotid, renal, and cerebral arteries 11,[14][15][16]19,24,61,62 ; and granulomatous inflammation of the liver, kidneys, lung, heart, and epididymis (typically occurring in later stages of the disease). 14,16,23,26,30,55,63 Some patients have also presented with recurrent fevers, which are infrequently observed in typical EOS/BS.…”