Blau syndrome is extremely rare, with only a few hundred cases reported worldwide. It affects individuals of various ethnic backgrounds and does not have a known gender preference. Because of its rarity, it is often misdiagnosed or mistaken for juvenile idiopathic arthritis or other inflammatory disorders.

Blau syndrome is caused by mutations in the NOD2 gene (also known as CARD15), which plays a crucial role in immune system regulation. The protein produced by NOD2 signals for an innate immune response in the case of bacterial infections. When the protein is mutated, it can lead to excessive immune activation, resulting in chronic inflammation and the formation of granulomas—clusters of immune white blood cells that cause tissue damage. Unlike other autoinflammatory diseases, Blau syndrome does not involve autoantibodies, making it a distinct form of immune dysfunction. Blau syndrome is an autosomal dominant genetic disorder, meaning that a copy from one parent causes the disease in offspring (see RareShare Guide on Genetic Inheritance).

The classic triad of Blau syndrome symptoms includes:

• Arthritis: Chronic joint inflammation, swelling, and stiffness, often affecting wrists, ankles, and fingers. Over time, this can lead to joint deformities.

• Uveitis: Inflammation of the uvea (the middle layer of the eye), which can cause eye pain, redness, light sensitivity, and vision loss if untreated.

• Dermatitis: A widespread rash, often with scaly or red patches, typically appearing first before joint and eye symptoms develop.
  Additional symptoms may include fever, enlarged lymph nodes, liver and spleen involvement, and, in some cases, lung or kidney inflammation.

Nephritis: A disease caused by inflammation of the kidneys when tissue inflammation prevents the proper flow of blood into the organs.

Blau syndrome is diagnosed based on clinical symptoms, family history, and genetic testing. Due to its rarity, it is often misdiagnosed as juvenile idiopathic arthritis or sarcoidosis. Early recognition is critical to prevent long-term complications.

• Genetic Testing: Confirms the presence of NOD2 gene mutations associated with Blau syndrome.

• Skin or Joint Biopsy: Identifies granulomas in affected tissues, helping distinguish Blau syndrome from other inflammatory disorders.

• Ophthalmologic Examination: Detects uveitis and evaluates eye inflammation.

• Imaging (X-rays, MRI, Ultrasound): Used to assess joint damage and inflammation.

• Blood Tests: May show markers of inflammation (such as elevated C-reactive protein or erythrocyte sedimentation rate), but autoimmune markers are typically absent.

There is no cure for Blau syndrome, so treatment focuses on managing symptoms and reducing inflammation. Treatment options include:

• Corticosteroids: Used to control acute inflammation, particularly in uveitis and arthritis.

• Immunosuppressive Drugs: Methotrexate and azathioprine may help reduce disease activity.

• Biologic Therapies (TNF Inhibitors, IL-1 or IL-6 Blockers): Medications such as adalimumab, infliximab, or anakinra are used to target specific inflammatory pathways.

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Help relieve joint pain and stiffness.

• Physical Therapy: Maintains joint mobility and function.

• Ophthalmologic Treatment: Regular monitoring and treatment for uveitis to prevent vision loss.

The long-term outlook for individuals with Blau syndrome varies depending on the severity of symptoms and response to treatment. Early diagnosis and aggressive management can help prevent complications such as joint deformities, blindness from uveitis, and systemic organ involvement. While the disease is chronic, many individuals can achieve good quality of life with appropriate treatment and regular medical monitoring.

1. DermNet - Granulomatous dermatitis

2. Medline Plus - Blau syndrome

3. Cleveland Clinic - Blau syndrome