Daodynamica groep

Blau Syndrome (BS) is a rare, inherited autoinflammatory disorder caused by mutations in the NOD2/CARD15 gene, leading to granulomatous inflammation. It is characterized by the classic triad of arthritis, dermatitis, and uveitis. Early recognition is crucial to prevent complications, particularly ocular damage and joint deformities.

In North America, increasing awareness among pediatricians, rheumatologists, and ophthalmologists, combined with the availability of genetic testing, has improved early diagnosis and management of Blau Syndrome.

Etiology and Pathophysiology

• Genetic Basis: Gain-of-function mutations in the NOD2 gene lead to abnormal activation of the innate immune system.

• Inheritance: Autosomal dominant; a single mutated allele is sufficient to cause disease.

• Inflammatory Mechanism: Persistent granulomatous inflammation primarily affects joints, skin, and eyes.

Clinical Features

Classic Triad:

1. Arthritis:

   • Polyarticular, symmetric arthritis often presenting in early childhood.

   • Can lead to joint deformities and functional impairment if untreated.

2. Dermatitis:

   • Papular, nodular, or granulomatous skin lesions.

   • May be misdiagnosed as eczema, sarcoidosis, or other inflammatory skin conditions.

3. Uveitis:

   • Eye inflammation affecting anterior, posterior, or pan-uvea.

   • Risk of cataracts, glaucoma, or permanent vision loss if untreated.

Other Manifestations:

• Intermittent fever and malaise.

• Rare involvement of other organs such as lungs or liver.

Diagnosis

• Genetic Testing: Sequencing of NOD2/CARD15 confirms the diagnosis.

• Clinical Evaluation: Identification of the classic triad and granulomatous lesions.

• Laboratory Tests: Non-specific markers of inflammation (e.g., ESR, CRP) may be elevated.

• Imaging: X-rays or MRI can reveal joint deformities or synovial inflammation.

• Ophthalmologic Assessment: Regular eye exams to detect and manage uveitis early.

Treatment and Management

There is no cure for Blau Syndrome; therapy focuses on controlling inflammation, preventing complications, and improving quality of life.

1. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):

   • For mild arthritis and pain control.

2. Corticosteroids:

   • Systemic or local treatment for severe arthritis or uveitis.

3. Immunosuppressive Therapy:

   • Methotrexate, azathioprine, or cyclosporine for persistent or severe cases.

4. Biologic Agents:

   • TNF inhibitors (e.g., infliximab, adalimumab) and IL-1 blockers for refractory cases.

5. Supportive Care:

   • Physical therapy for joint mobility.

   • Ophthalmologic monitoring for uveitis management.

   • Dermatologic care for skin lesions.