Blau Syndrome - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Blau syndrome is a rare genetic inflammatory disorder. It was first described by pediatricians E. Blau and D Jabs in 1985. E. Blau reported four generations of eleven members of the same family affected by the disorder. Ten family members showed arthritis or inflammation of the joints, and two showed skin, eye, and joint involvement. One of the members showed skin and joint disease, and another showed problems with eye movement and iritis or swelling of the colored part of the eye. It affects various body parts, but skin, joints, and eyes are most commonly affected.

Different other names address it; they are-

• Early onset sarcoidosis.

• Arthrocutaneouveal granulomatosis (ACUG).

• Granulomatosis, familial, blau type.

• Granulomatous inflammatory arthritis, dermatitis, and uveitis.

• Synovitis granulomatous with uveitis and cranial neuropathies.

• Granulomatosis, familial juvenile systemic.

• Jabs syndrome.

It usually affects kids younger than four years of age. Blau syndrome and early-onset sarcoidosis have the same sign and symptoms. The syndrome also affects the liver, spleen, lymph nodes, blood vessels, brain, lungs, and heart. Blau syndrome is a rare condition affecting less than one million children worldwide.

What Are the Symptoms of Blau Syndrome?

The symptoms of Blau syndrome vary from person to person.

• Granulomatous Dermatitis - A type of skin inflammation causing rashes. The rash is in the form of scales or hard lumps under the skin. It can appear on the arms, legs, or trunk.

• Arthritis - Arthritis is the inflammation of the membrane (synovium) of the joints. The inflammation is also known as synovitis. It is associated with inflammation and pain in the joints. It usually starts in the joints of the hands, feet, wrists, and ankles. In due course, the joint movement gets restricted. In some people, the tendons can also be inflamed, leading to tenosynovitis.

• Joint Pain.

• Erythema Nodosum - Painful reddish eruptions on the shins.

• Patchy and dark skin.

• Fluid deposition around joints.

• Uveitis - Swelling of the middle layer (uvea) of the eyes. The uvea consists of the colored part of the eye (iris) and the whitish part of the eye (sclera). Uveitis can irritate and cause pain in the eyes. Blurred vision and increased sensitivity to light (photophobia) can also occur. Inflammation can occur in the eyes' other parts, like the conjunctiva or the outermost protective layer of the eye, tear glands, retina or the part of the eye where image formation occurs, and the optic nerve. Inflammation of any of these parts can lead to vision loss.

• Cataract - It is the clouding of the normal eye lens.

• Extreme sensitivity to light.

• Nephritis - Inflammatory kidney disease.

• Nephrocalcinosis - Calcium accumulation in the kidneys

• Vasculitis - Inflammation of the blood vessels. It can lead to tissue death stopping the blood flow to the tissues and organs.

• Bending of toes and fingers.

• Skin Sores.

• Vision Loss.

• Change in the production and drainage of saliva.

• Inflammation of the lymph nodes.

• High blood pressure.

• Problems with breathing.

• Dryness of the mouth.

• Cranial Neuropathy - Involvement of the nerves in the brain or brain stem.

• Facial Palsy - Facial palsy is the inflammation, and swelling of the facial nerve.

• Interstitial Lung Disease- It is a group of lung disorders characterized by scarring of the lung tissues.

• Blau syndrome rarely causes swelling of the internal organs and blood vessels; this could lead to serious complications.

What Causes Blau Syndrome?

Blau syndrome is caused by a change in a single gene present in all the cells of the body. It results from the mutation or change in the NOD2 gene. The NOD2 gene produces proteins for important immune responses, such as inflammation. During inflammation, the cells responsible for immunity signal white blood cells to attack and kill invaders like microbes or help in wound healing. In Blau syndrome, the mutation causes the gene NOD2 to produce hyperactive proteins, leading to abnormal inflammatory responses.

Blau syndrome is a genetic disorder that can be inherited. A similar mutation in the NOD2 gene was seen in patients with early-onset sarcoidosis. Thus, it was suggested that Blau and early onset Sarcoidosis belong to the same family occurring at frequent intervals. Most of the affected people have at least one parent with the disorder. However, certain individuals with features of Blau syndrome do not have a positive family history. These people are believed to have a non-inherited form of the disorder known as early-onset sarcoidosis.

How Is Blau Syndrome Diagnosed?

• A thorough personal and family medical history is taken to understand the disorder.

• Personal examination to check the symptoms.

• Laboratory tests to rule out other related conditions.

• Genetic Testing - if the baby has the typical joint, eye, or skin symptoms of the condition. To check for the presence of any irregularity in the genes.

• Antenatal and prenatal genetic tests are recommended though it is very rarely performed.

How Is Blau Syndrome Treated?

There is no treatment for Blau syndrome.

The treatment for Blau syndrome is generally symptomatic.

• Steroids: High doses of steroids are given to reduce inflammation during a flare-up. The dosage is reduced in between flare-ups.

• Immunosuppressant Medications: These are given to lower the body's immune response against its cells.

• Adalimumab: This medication is given to reduce inflammation in combination with steroids, immunosuppressant drugs, or both.

How Is the Prognosis of Blau Syndrome?

Blau syndrome is a progressive condition with quite an unpredictable range of severity. In cases with a lot of clinical manifestations, life expectancy is reduced. Uveitis or swelling of the eye's middle layer had a very poor prognosis.

Conclusion:

Blau syndrome is a genetic disorder that gives rise to inflammation all over the body. Signs and symptoms usually start before four years. There is no possible cure for Blau syndrome. However, the treatment is purely symptomatic. Medications can help to reduce the rate of progression and control the symptoms. An extensive study of the NOD2 mutation is essential to understand the disease in depth so that proper treatment modalities can be discovered. If a child or person is suspected of having the syndrome, a quick appointment with the physician should be made without delay. Since it is an inherited disorder, genetic counseling should be performed in case any family member is reported to have the condition.