Blau Syndrome

Blau syndrome (early onset sarcoidosis when sporadic) is a rare autosomal dominant autoinflammatory granulomatous disease from gain of function NOD2 (CARD15) mutations.

• Onset before age 4 years; the triad of granulomatous dermatitis, symmetric arthritis (polyarticular, tenosynovitis) and uveitis.

• Non-caseating granulomas; NF-kB activation.

• Prevalence is extremely low; complete penetrance in familial form.

• Complications: ocular (cataract, glaucoma, blindness), joint contractures, camptodactyly, large vessel vasculitis, hypertension, hepatic and renal granulomas, fever.

• Skin: fine papular, scaly, ichthyosiform eruption on trunk and limbs, subcutaneous nodules, erythema nodosum.

• Joints: boggy tenosynovitis (cystic swelling over wrists and ankles), camptodactyly (flexion contractures of fingers), polyarthritis.

• Eyes: recurrent panuveitis (granulomatous), chronic and sight-threatening.

• Fever, lymphadenopathy, vasculitis, pulmonary and renal involvement.

• Clinical triad in a child with family history; NOD2 gene sequencing (R334Q/W, R587C common) is confirmatory.

• Biopsy (skin, synovium): non-caseating epithelioid granulomas (not necessarily needed).

• Inflammatory markers (CRP, ESR), normal ACE; ophthalmological examination with slit lamp, fluorescein angiography.

• Imaging: ultrasound/MRI of joints and tendons; angiography (large vessel).

• Exclude juvenile idiopathic arthritis, sarcoidosis (no NOD2 mutation, hilar adenopathy), Crohn disease, tuberculosis.

• Corticosteroids: topical for skin; intra-articular; systemic prednisolone 0.5 to 1 mg/kg short term for uveitis flares.

• Methotrexate 10 to 15 mg/m2 weekly (up to 25 mg) as first steroid sparing agent.

• Biologics for refractory disease: TNF inhibitors (infliximab 5 mg/kg every 4 to 8 weeks, adalimumab 24 mg/m2 every 2 weeks, etanercept) most effective for uveitis and arthritis; IL-1 antagonists (anakinra 1 to 2 mg/kg daily, canakinumab) and tocilizumab if TNF fails; JAK inhibitors (tofacitinib, baricitinib) as emerging options.

• Ophthalmic management: topical steroids and cycloplegics, ocular surgery for cataract/glaucoma when quiescent.

• Physiotherapy and occupational therapy for contractures.

• Screen for hypertension, vasculitis and other organ involvement; growth monitoring.

• Genetic counselling.