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.
M04.8 – Other autoinflammatory syndromes
818950005 – Blau syndrome
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.