Blau syndrome is a genetic autoinflammatory condition characterized by a triad of granulomatous dermatitis, uveitis, and arthritis. Blau syndrome is inherited in an autosomal dominant fashion and is caused by a gain-of-function mutation in the NOD2 (CARD15) gene. It may also arise de novo in the absence of a family history. When activated, NOD2 stimulates NFkB, a transcription factor complex that promotes cytokine production and cell survival. In Blau syndrome, the enhanced inflammatory response ultimately drives widespread granulomatous inflammation and tissue damage, particularly in the skin, eyes, and joints.

Blau syndrome is a very rare disorder and is estimated to affect fewer than 1 in one million people.

Blau syndrome most commonly presents in childhood, around age 1-4 years. Cutaneous manifestations often appear within the first 2 years of life as generalized reddish brown micropapules. Later, subcutaneous nodules that may be periarticular or that may resemble erythema nodosum, granulomatous vasculitis, or ichthyosiform eruptions may be seen. Between age 2-4 years, a polyarticular, often symmetric, polyarthritis with prominent synovitis or tenosynovitis of the wrists, metacarpophalangeal, metatarsophalangeal, and proximal interphalangeal joints develops. Larger joints may be involved. Around 4-6 years, patients may report photophobia, eye pain, or blurred vision due to developing uveitis. Around 40% of affected individuals develop the classic triad.

Other less common but potential manifestations include periodic fevers and cranial neuropathies. In atypical instances, however, some patients with Blau syndrome are symptomatic due to incomplete penetrance of the responsible NOD2 mutation.