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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Blau syndrome

Reviewed July 2012

What is Blau syndrome?

Blau syndrome is an inflammatory disorder that primarily affects the skin, joints, and eyes. Signs and symptoms begin in childhood, usually before age 4.

A form of skin inflammation called granulomatous dermatitis is typically the earliest sign of Blau syndrome. This skin condition causes a persistent rash that can be scaly or involve hard lumps (nodules) that can be felt under the skin. The rash is usually found on the torso, arms, and legs.

Arthritis is another common feature of Blau syndrome. In affected individuals, arthritis is characterized by inflammation of the lining of joints (the synovium). This inflammation, known as synovitis, is associated with swelling and joint pain. Synovitis usually begins in the joints of the hands, feet, wrists, and ankles. As the condition worsens, it can restrict movement by decreasing the range of motion in many joints.

Most people with Blau syndrome also develop uveitis, which is swelling and inflammation of the middle layer of the eye (the uvea). The uvea includes the colored portion of the eye (the iris) and related tissues that underlie the white part of the eye (the sclera). Uveitis can cause eye irritation and pain, increased sensitivity to bright light (photophobia), and blurred vision. Other structures in the eye can also become inflamed, including the outermost protective layer of the eye (the conjunctiva), the tear glands, the specialized light-sensitive tissue that lines the back of the eye (the retina), and the nerve that carries information from the eye to the brain (the optic nerve). Inflammation of any of these structures can lead to severe vision impairment or blindness.

Less commonly, Blau syndrome can affect other parts of the body, including the liver, kidneys, brain, blood vessels, lungs, and heart. Inflammation involving these organs and tissues can cause life-threatening complications.

How common is Blau syndrome?

Although Blau syndrome appears to be uncommon, its prevalence is unknown.

What genes are related to Blau syndrome?

Blau syndrome results from mutations in the NOD2 gene. The protein produced from this gene helps defend the body from foreign invaders, such as viruses and bacteria, by playing several essential roles in the immune response, including inflammatory reactions. An inflammatory reaction occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair.

The NOD2 gene mutations that cause Blau syndrome result in a NOD2 protein that is overactive, which can trigger an abnormal inflammatory reaction. However, it is unclear how overactivation of the NOD2 protein causes the specific pattern of inflammation affecting the joints, eyes, and skin that is characteristic of Blau syndrome.

Related Gene(s)

Changes in this gene are associated with Blau syndrome.

  • NOD2

How do people inherit Blau syndrome?

Blau syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most affected individuals have one parent with the condition.

In some cases, people with the characteristic features of Blau syndrome do not have a family history of the condition. Some researchers believe that these individuals have a non-inherited version of the disorder called early-onset sarcoidosis.

Where can I find information about diagnosis or management of Blau syndrome?

These resources address the diagnosis or management of Blau syndrome and may include treatment providers.

  • Genetic Testing Registry: Blau syndrome (
  • Genetic Testing Registry: Sarcoidosis, early-onset (
  • Merck Manual Consumer Version: Overview of Dermatitis (
  • Merck Manual Consumer Version: Uveitis (

You might also find information on the diagnosis or management of Blau syndrome in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about Blau syndrome?

You may find the following resources about Blau syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Blau syndrome?

  • arthrocutaneouveal granulomatosis
  • early-onset sarcoidosis
  • familial granulomatosis, Blau type
  • familial juvenile systemic granulomatosis
  • granulomatous inflammatory arthritis, dermatitis, and uveitis, familial
  • pediatric granulomatous arthritis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about Blau syndrome?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding Blau syndrome?

arthritis ; autosomal ; autosomal dominant ; bacteria ; cell ; familial ; family history ; gene ; granulomatous ; immune response ; immune system ; inflammation ; inflammatory arthritis ; inherited ; injury ; joint ; juvenile ; optic nerve ; photophobia ; prevalence ; protein ; retina ; sarcoidosis ; sclera ; sensitivity ; sign ; syndrome ; tissue ; uvea ; uveitis ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Borzutzky A, Fried A, Chou J, Bonilla FA, Kim S, Dedeoglu F. NOD2-associated diseases: Bridging innate immunity and autoinflammation. Clin Immunol. 2010 Mar;134(3):251-61. doi: 10.1016/j.clim.2009.05.005. Epub 2009 May 24. Review. (
  • Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S, Fuji A, Yuasa T, Manki A, Sakurai Y, Nakajima M, Kobayashi H, Fujiwara I, Tsutsumi H, Utani A, Nishigori C, Heike T, Nakahata T, Miyachi Y. Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood. 2005 Feb 1;105(3):1195-7. Epub 2004 Sep 30. (
  • Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Häfner R, Chamaillard M, Zouali H, Thomas G, Hugot JP. CARD15 mutations in Blau syndrome. Nat Genet. 2001 Sep;29(1):19-20. (
  • Punzi L, Furlan A, Podswiadek M, Gava A, Valente M, De Marchi M, Peserico A. Clinical and genetic aspects of Blau syndrome: a 25-year follow-up of one family and a literature review. Autoimmun Rev. 2009 Jan;8(3):228-32. doi: 10.1016/j.autrev.2008.07.034. Epub 2008 Aug 19. (
  • Punzi L, Gava A, Galozzi P, Sfriso P. Miscellaneous non-inflammatory musculoskeletal conditions. Blau syndrome. Best Pract Res Clin Rheumatol. 2011 Oct;25(5):703-14. doi: 10.1016/j.berh.2011.10.017. Review. (
  • Rosé CD, Aróstegui JI, Martin TM, Espada G, Scalzi L, Yagüe J, Rosenbaum JT, Modesto C, Cristina Arnal M, Merino R, García-Consuegra J, Carballo Silva MA, Wouters CH. NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: study of an international registry and a national cohort in Spain. Arthritis Rheum. 2009 Jun;60(6):1797-803. doi: 10.1002/art.24533. (
  • Rosé CD, Doyle TM, McIlvain-Simpson G, Coffman JE, Rosenbaum JT, Davey MP, Martin TM. Blau syndrome mutation of CARD15/NOD2 in sporadic early onset granulomatous arthritis. J Rheumatol. 2005 Feb;32(2):373-5. (
  • Rose CD, Martin TM, Wouters CH. Blau syndrome revisited. Curr Opin Rheumatol. 2011 Sep;23(5):411-8. doi: 10.1097/BOR.0b013e328349c430. Review. (
  • Wang X, Kuivaniemi H, Bonavita G, Mutkus L, Mau U, Blau E, Inohara N, Nunez G, Tromp G, Williams CJ. CARD15 mutations in familial granulomatosis syndromes: a study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathy. Arthritis Rheum. 2002 Nov;46(11):3041-5. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: July 2012
Published: February 8, 2016