Blau Syndrome

What is Blau syndrome?

Blau syndrome is a rare inflammatory disease that affects your child’s skin, joints and eyes. Children inherit a gene change (mutation) that causes Blau syndrome. Symptoms like skin rashes and arthritis typically appear before your child turns 5. It can also cause uveitis, a problem that affects vision.

What does the term “Blau syndrome” mean?

You may better understand Blau syndrome when you break down what each word means:

• Blau: Wisconsin pediatrician Dr. Edward Blau published a research paper in 1985 about four generations of a family affected by this syndrome.
• Syndrome: In medical terms, “syndrome” refers to multiple conditions that cause numerous symptoms that affect different parts of your child’s body.

What are the symptoms of Blau syndrome?

Symptoms of Blau syndrome can appear during infancy and are usually evident by age 5. The symptoms primarily affect your child’s skin, joints and eyes.

Skin symptoms of Blau syndrome

The first sign of Blau syndrome is an inflammatory skin rash called granulomatous dermatitis. The rash usually forms on an infant’s arms, legs or torso during their first year of life.

Signs of this type of dermatitis include:

• Hard lumps or nodules called granulomas that you can feel underneath your child’s skin.
• Scaly skin.
• Red, yellow or tan bumps on the outer layer of your child’s skin (epidermis).

Joint symptoms of Blau syndrome

Blau syndrome can inflame the lining (synovium) of your child’s joints. Your child may develop arthritis in their hands, wrists, feet and ankles when they’re between 2 and 4 years old.

Signs of arthritis include:

• Joint pain.
• Musculoskeletal pain, especially in tendons.
• Swollen or stiff joints.

Eye symptoms of Blau syndrome

Up to 80% of children diagnosed with Blau syndrome develop an eye condition called uveitis. Uveitis causes swelling in the eye’s middle layer (uvea). It may also affect their retinas and optic nerves. Your child can develop uveitis in both eyes, which can impair their vision.

Signs of uveitis include:

• Blurred vision (low vision).
• Eye floaters.
• Eye pain or pressure.
• Red eye.
• Sensitivity to light (photosensitivity).
• Swollen eyes.

How else does Blau syndrome affect the body?

Although rare, your child with Blau syndrome may develop potentially life-threatening inflammation in their:

• Blood vessels.
• Brain.
• Heart.
• Liver.
• Lymph nodes (lymphatic system).
• Spleen.

What are the complications of Blau syndrome?

Inflammation from Blau syndrome can lead to:

• Cataracts, glaucoma, cystoid macular edema, retinal detachment and vision loss.
• Mobility issues and permanent bending of affected joints.
• Kidney disease and kidney failure.
• Heart inflammation.
• Enlarged spleen.
• Neuropathy.
• Pulmonary hypertension.
• Vasculitis.

What causes Blau syndrome?

A change to the NOD2 gene causes Blau syndrome. In most people, the NOD2 gene produces a NOD2 protein that helps their immune system fight off germs and infections.

When your child has Blau syndrome, the NOD2 protein is overactive and alters how their immune system works. This overreaction triggers an extreme inflammatory response (inflammation) that affects your child’s eyes, skin and joints.

Who is at risk for Blau syndrome?

A child who has one parent with Blau syndrome (or the gene mutation that causes it) has a 50% chance of inheriting the changed gene and developing the syndrome. A child only needs to inherit one altered gene to develop the disease. This means it’s an autosomal dominant disorder.

A child may inherit the gene mutation and not develop Blau syndrome. But they have a 50% chance of passing the mutated gene to each of their future children.

Which healthcare providers diagnose and treat Blau syndrome?

Depending on your child’s symptoms, they may receive care from a team of healthcare providers, including:

• Rheumatologist for arthritis and joint issues.
• Dermatologist for skin diseases.
• Ophthalmologist for vision problems.

How do healthcare providers diagnose Blau syndrome?

Diagnostic tests for Blau syndrome vary depending on your child’s symptoms. A genetic test (blood test) can detect the changed NOD2 gene that causes Blau syndrome.

Your child may also get one or more of these tests:

• Eye exam, including optical coherence tomography (OCT) and visual field testing.
• Imaging tests like an MRI, CT scan, ultrasound or X-rays to view joints and other organs based on your symptoms.
• Skin biopsy.

Can prenatal tests detect Blau syndrome?

Prenatal tests like chorionic villus sampling or amniocentesis don’t test for NOD2 gene mutation specifically.

What are other names for Blau syndrome?

Your child’s healthcare provider may refer to Blau syndrome by one of these names:

• Pediatric granulomatosis arthritis.
• Arthrocutaneouveal granulomatosis.
• Familial granulomatosis.
• Familial juvenile systemic granulomatosis.
• Granulomatous inflammatory arthritis, dermatitis and uveitis.

How rare is Blau syndrome?

Blau syndrome is extremely rare. It affects fewer than 1 in 1 million children worldwide.

How do healthcare providers treat Blau syndrome?

Your child’s team of healthcare providers will treat the various conditions to ease symptoms and keep them from reoccurring (a disease flare-up). Treatments vary by condition and severity and may include:

• Immunosuppressants like corticosteroids, methotrexate and tumor necrosis factor (TNF) inhibitors.
• Anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs (NSAIDs).
• Topical eye medications and/or eye surgeries for cataracts and glaucoma.
• Physical and occupational therapies.

Can you prevent Blau syndrome?

If you or your partner has the gene mutation that causes Blau syndrome, you may want to meet with a genetic counselor before having children. This specialist can discuss your risk of future generations inheriting the changed NOD2 gene.

What is the outlook for someone with Blau syndrome?

While there isn’t a cure for Blau syndrome, treatments can ease symptoms and help your child enjoy a good quality of life up to and through adulthood. The condition affects everyone differently. One study found that 40% of children with Blau syndrome had mild symptoms and were able to function as well as their peers. But the disease caused severe symptoms for 10% of children. When Blau syndrome affects the vital organs, it may shorten a person’s life expectancy.

When should I call the doctor?

Call your healthcare provider if your child has:

• Difficulty grasping items, bending joints or moving.
• Extreme pain.
• Vision problems.

What should I ask my provider?

You may want to ask your healthcare provider:

• What caused my child to have Blau syndrome?
• What medications and therapies can help my child?
• Should my partner and I get genetic testing?
• Should I look for signs of complications?

What’s the difference between Blau syndrome and early-onset sarcoidosis?

Blau syndrome and early-onset sarcoidosis are the same disease with the same symptoms. But children with Blau syndrome inherit the gene change that causes the disease. Children with early-onset sarcoidosis have no family history of Blau syndrome. The NOD2 gene changes or mutates sporadically for no known reason (a de novo gene mutation).

A note from Cleveland Clinic

Raising a child with a chronic condition like Blau syndrome can be challenging. If you also have Blau syndrome, you can use your personal experiences to better advocate for your child’s care. You can also use your insights to help your child cope with this lifelong disease. It’s important to seek care from experts familiar with arthritis, uveitis and skin diseases that comprise Blau syndrome. These healthcare providers can help manage your child’s symptoms, ensuring your child has the best childhood possible.