What are the other Names for this Condition? (Also known as/Synonyms)

• Arthrocutaneouveal Granulomatosis (ACUG)
• Familial Granulomatosis, Blau type
• Synovitis Granulomatous with Uveitis and Cranial Neuropathies

What is Blau Syndrome? (Definition/Background Information)

• Blau Syndrome is an uncommon genetic disorder affecting preschool children that is marked by joint inflammation due to arthritis, uveitis, and skin rashes. Severe cases can result in permanent bending of the digits and vision loss
• It is also known as Familial Granulomatous Inflammatory Arthritis, Dermatitis, and Uveitis. Blau Syndrome is one of a family of more than 38 diseases termed autoinflammatory diseases. They share abnormalities in the innate, more primitive reactive immune system
• A management of Blau Syndrome involves topical eye applications, use of skin creams, steroidal medication, physical therapy, use of vision aids, and surgery. The outcomes are dependent upon the severity of Blau Syndrome, and can be only assessed on a case-by-case basis

Who gets Blau Syndrome? (Age and Sex Distribution)

• Blau Syndrome is a rare congenital condition that affects children below the age of four years (preschoolers)
• Both males and females may be affected
• Individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Blau Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Blau Syndrome can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Blau Syndrome? (Etiology)

• Blau Syndrome is a genetic disorder that is inherited in an autosomal dominant manner
• It is caused by mutations involving the NOD2 (or CARD15) gene

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Blau Syndrome?

The signs and symptoms of Blau Syndrome are many and varied. They may be mild or severe and vary significantly from one child to another. These may include:

• Eye abnormalities that include:
  • Anterior uveitis or inflammation of the front part of uvea (a part of the eye structure)
  • Cystoid macular edema
  • Appearance of a band across the cornea
  • Swelling of the iris
  • Light-sensitivity
• Arthritis leading to inflammation of joints causing fluid in the joints, and joint pain
• Contraction of finger and toe joints
• Dryness of skin
• Red skin rashes in the form of papules that appear all over the body
• Eczema
• Cutaneous sarcoidosis
• Cranial nerve abnormalities causing facial palsy with speaking, chewing, and swallowing difficulties
• Swollen lymph nodes

How is Blau Syndrome Diagnosed?

Blau Syndrome is diagnosed on the basis of the following information:

• Physical examination of the individual and medical history evaluation
• Assessment of the presenting signs and symptoms
• Eye and visual examination
• Dermoscopy: Dermoscopy is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Radiological studies of the affected joints
• Fine needle aspiration (FNA) of joint fluid analysis
• Skin biopsy, if necessary: A skin biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
• Molecular genetic testing to check for or confirm specific causative gene mutation(s)
• Prenatal testing including abdominal ultrasound scans
• Diagnostic tests to check for an underlying disorder or condition if present

A differential diagnosis may be necessary to eliminate other conditions that present similar signs and symptoms.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the Possible Complications of Blau Syndrome?

The complications of Blau Syndrome may include:

• Severe arthritis causing permanent bending of the fingers and toes, a condition known as camptodactyly
• Immobility
• Visual impairment from many factors such as:
  • Uveitis
  • Focal posterior synechiae (abnormal attachment of the iris and cornea)
  • Cataract
  • Glaucoma
  • Optic neuritis
• Pulmonary arterial hypertension
• Aortic aneurysm
• Inflammation of the spleen (splenomegaly)
• Chronic kidney disease
• Dysfunction of organs such as heart, kidney, liver, 

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Blau Syndrome Treated?

Presently, there is no cure for Blau Syndrome since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops. This may primarily include:

• Eye drops, oral medications, and topical steroids
• Surgical repair of eye defects
• Conservative measures to manage joint pain and swelling such as heat/ice compress, orthotics, NSAIDs, and physician therapy
• Surgical measures for arthritis may include arthroscopic chondroplasty and joint fusion
• Use of skin moisturizing creams and lotions; ointments containing vitamin D
• Steroid creams and topical retinoids for skin rashes
• Systemic anti-inflammatory medications such as corticosteroids with or without methotrexate
• Medications directed against tumor necrosis factor (TNF) alpha or interleukin 1 beta

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

How can Blau Syndrome be Prevented?

Currently, Blau Syndrome may not be preventable since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Blau Syndrome? (Outcomes/Resolutions)

• The prognosis of Blau Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Children with mild conditions and not showing the involvement of internal organs may have favorable prognosis

Additional and Relevant Useful Information for Blau Syndrome:

• Familial cases of Blau Syndrome were reported by Drs. Blau and Jabs in 1985 and 1982

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/