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Blau syndrome
Other Resources UpToDate PubMed

Blau syndrome

Contributors: Chirag Vasavda, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

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.

Codes

ICD10CM:
M04.8 – Other autoinflammatory syndromes

SNOMEDCT:
818950005 – Blau syndrome

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Sarcoidosis – In Blau syndrome, respiratory involvement is rare and hilar adenopathy is often absent.
  • Rheumatoid arthritis – In rheumatoid arthritis, marginal erosion or bone resorption is prominent, whereas x-rays are near normal in Blau syndrome; anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for rheumatoid arthritis.
  • Systemic juvenile idiopathic arthritis (JIA) or adult Still disease (ASD) – JIA / ASD presents with rash and arthritis like Blau syndrome but more commonly results in high-spiking fevers and lymphadenopathy.
  • Lichen scrofulosorum – A tuberculid that can present with similar morphologic and histologic cutaneous findings; tuberculin skin testing or QuantiFERON assessment can be considered to distinguish between lichen scrofulosorum and Blau syndrome.
  • Cyclic neutropenia – Fevers in cyclic neutropenia are truly episodic and predictable, rather than periodic, like in an autoinflammatory syndrome such as Blau syndrome.
  • Other NFkB-mediated autoinflammatory diseases – TNF receptor 1-associated periodic syndrome (TRAPS), haploinsufficiency of A20 syndrome, and NEMO C terminal deletion syndrome.
  • NFkB-deficient diseases – May present with immunodeficiency rather than autoinflammation as the primary symptom.
  • NEMO syndrome – Ectodermal dysplasia in NEMO syndrome presents with conical or absent teeth, fine hair, and hyperhidrosis.

Best Tests

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Management Pearls

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Therapy

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References

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Last Reviewed:04/18/2022
Last Updated:05/04/2022
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Blau syndrome
A medical illustration showing key findings of Blau syndrome (Age 1-4)
Copyright © 2022 VisualDx®. All rights reserved.