Blau Syndrome
Blau Syndrome
Blau syndrome is a rare autoinflammatory granulomatous disorder characterized by the clinical triad of granulomatous arthritis, dermatitis, and uveitis. It is caused by mutations in the NOD2/CARD15 gene and typically presents in early childhood.
Key Points
- Autosomal dominant inheritance pattern
- Onset typically before 4 years of age
- Characterized by non-caseating granulomas
- Associated with NOD2/CARD15 gene mutations
- Early recognition crucial for preventing complications
Epidemiology
- Extremely rare disorder
- Affects both males and females equally
- No ethnic predisposition
- Approximately 200 cases reported worldwide
Clinical Features
Classic Triad
- Arthritis:
- Symmetric polyarticular arthritis
- Affects wrists, ankles, knees, and metacarpophalangeal joints
- Boggy synovitis with tenosynovitis
- Can lead to joint deformities if untreated
- Dermatitis:
- Tan-colored maculopapular or scaly rash
- Usually appears in first year of life
- Often ichthyosis-like appearance
- Most common on trunk and extremities
- Uveitis:
- Bilateral granulomatous uveitis
- Can affect anterior, intermediate, or posterior chambers
- Risk of permanent vision loss
- Requires regular ophthalmologic monitoring
Additional Manifestations
- Fever and malaise
- Lymphadenopathy
- Hepatosplenomegaly
- Cranial neuropathies
- Interstitial lung disease (rare)
- Arteritis (rare)
Diagnosis & Genetics
Diagnostic Criteria
- Clinical presentation with characteristic triad
- Genetic testing showing NOD2/CARD15 mutations
- Biopsy showing non-caseating granulomas
- Family history (if present)
Laboratory Findings
- Elevated inflammatory markers (ESR, CRP)
- Normal complement levels
- Negative autoantibodies
- Normal ACE levels
Genetic Testing
- NOD2/CARD15 gene sequencing
- Most common mutations:
- R334W
- R334Q
- L469F
- De novo mutations possible
Differential Diagnosis
- Juvenile idiopathic arthritis
- Sarcoidosis
- Chronic granulomatous disease
- CINCA syndrome
- Tuberculosis
Management
Treatment Approach
- Multidisciplinary team required
- Regular monitoring essential
- Early intervention crucial
- Individualized treatment plans
Pharmacological Treatment
- First-line:
- NSAIDs for mild cases
- Systemic corticosteroids
- Methotrexate
- Biological agents:
- TNF-α inhibitors (infliximab, adalimumab)
- IL-1 inhibitors (anakinra, canakinumab)
- Tocilizumab for refractory cases
Specific Management
- Arthritis:
- Physical therapy
- Occupational therapy
- Joint protection strategies
- Uveitis:
- Topical corticosteroids
- Regular ophthalmologic monitoring
- Early intervention for complications
- Skin:
- Topical treatments
- Moisturizers
- Sun protection
Prognosis & Monitoring
Long-term Outcomes
- Variable disease course
- Risk of permanent joint deformities
- Potential for vision loss
- Impact on quality of life
Monitoring Schedule
- Regular rheumatology follow-up (every 3-6 months)
- Ophthalmology screening every 3-4 months
- Annual screening for rare manifestations
- Growth and development monitoring
- Regular laboratory monitoring on immunosuppression
Complications
- Joint contractures
- Visual impairment or blindness
- Growth delays
- Psychological impact
- Secondary amyloidosis (rare)
