Blau Syndrome

Patients with Blau syndrome suffer from a combination of skin rash, arthritis (inflammation of the joints) and uveitis (eye inflammation), sometimes in combination with a fever. Other organs may be affected as well. Blau syndrome is the term used for familial forms of the disease, but sporadic forms can occur as well and are known as Early Onset Sarcoidosis (EOS). It’s not known how many people have the disease. It is a very rare disease that often affects patients before the age of five years and becomes worse if left untreated. Treatment consists of anti-inflammatory medication.

Cause

Blau syndrome is a genetic disease. The responsible gene is called NOD2 (synonymous with CARD15), which encodes a protein that plays a role in the immune response. If this gene carries a mutation, as in Blau syndrome, the protein does not function properly and patients experience chronic inflammation. This causes the formation of granuloma in various tissues and organs (granulomas are long-lived clusters of inflammatory cells). It is inherited as an autosomal dominant disease. This means that a child has a 50% chance of inheriting the disease from a parent with Blau syndrome. In EOS, the sporadic form of the disease, both parents are healthy and the mutation has emerged in the patient. The disease is genetic and therefore not contagious.

Symptoms

The main symptoms are arthritis (inflammation of the joints), dermatitis (inflammation of the skin) and uveitis (inflammation of the eyes). The disease often begins with a typical skin rash. Arthritis is the most common symptom and usually begins before the age of 10. Uveitis is the most serious manifestation of the disease, since complications (such as cataract and eye pressure) often arise and may cause decreased vision if left untreated.

In addition, granulomatous inflammation may affect all kinds of other organs, causing other symptoms, such as decreased function of the lung or kidney, increased blood pressure or recurrent fever. The course of the disease is not the same in every child. One child may be affected more than another. The severity of the disease may also vary over time.

Diagnosis

1. a) Clinical suspicion: the patient presents typical symptoms.
2. b) Demonstration of granulomas: for this, a biopsy is usually performed (removal of a piece of tissue that is examined under the microscope).
3. c) Genetic analysis: genetic testing of the blood.

Treatment

The disease cannot be cured, but the symptoms can be suppressed with medication that controls the inflammation in the joints, eyes and other affected organs. The aim of the treatment with medication is to control the symptoms and halt the progression of the disease.

Joint problems can often be treated with anti-inflammatory non-steroidal drugs (NSAID) and methotrexate. Uveitis is very difficult to control. Local treatment (steroid eye drops or local steroid injections) is not for all patients sufficient. Methotrexate is not always effective either and sometimes patients need to take oral corticosteroids in order to control a severe eye inflammation.

In patients with inflammation of the eyes and/or joints that is difficult to control and in patients whose internal organs are affected, the use of cytokine-inhibitors, such as TNF-α inhibitors (infliximab, adalimumab) may be effective.

Prognosis

Blau syndrome is a life-long disease. The activity of the disease may fluctuate over time. It is therefore not possible to cure the disease forever, but with proper medical follow-up and treatment, most patients will have a good quality of life. There is limited data available about the prognosis in the long-term. Some children have been followed for more than 20 years and have attained almost normal growth, normal psychomotor development and a good quality of life with well-adjusted medical treatment.

Sports

Patients with Blau syndrome should be encouraged to play sports; limitations depend on the degree to which the disease is under control.