Advertisement

Blau Syndrome

  • Rebecca Trachtman
  • Karen B. OnelEmail author
Chapter

Abstract

Blau syndrome is a monogenic inflammatory disease that classically involves the triad of arthritis, uveitis, and dermatitis. This syndrome is the familial form of early-onset sarcoidosis, and the two entities have some shared mutations in the NOD2 gene. Blau syndrome was first described in 1985 and is characterized predominantly by granulomas in the affected areas. Management remains a challenge, as Blau syndrome is rare and evidence is lacking. Here, we describe in greater detail the clinical features, pathophysiology, diagnosis, management, and prognosis of Blau syndrome.

Keywords

Blau Jabs Sarcoidosis Granuloma Arthritis Uveitis NOD2 NACHT CARD15 

References

  1. 1.
    Blau EB. Familial granulomatous arthritis, iritis, and rash. J Pediatr. 1985;107(5):689–93.CrossRefGoogle Scholar
  2. 2.
    Jabs DA, et al. Familial granulomatous synovitis, uveitis, and cranial neuropathies. Am J Med. May 1985;78(5):801–4.CrossRefGoogle Scholar
  3. 3.
    Miceli-Richard C, et al. CARD15 mutations in Blau syndrome. Nat Genet. 2001;29(1):15.  https://doi.org/10.1038/ng720.CrossRefGoogle Scholar
  4. 4.
    Wouters CH, et al. Blau syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatr Rheumatol Online J. 2014;12:33.  https://doi.org/10.1186/1546-0096-12-33.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rosé CD, et al. Pediatric granulomatous arthritis: an international registry. Arthritis Rheum. 2006;54(10):3337–44.  https://doi.org/10.1002/art.22122.CrossRefPubMedGoogle Scholar
  6. 6.
    Rosé CD, et al. Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes. Rheumatology (Oxford, England). 2015;54(6):1008–16.  https://doi.org/10.1093/rheumatology/keu437.CrossRefGoogle Scholar
  7. 7.
    Tromp G, et al. Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16. Am J Hum Genet. 1996;59(5):1097–107.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Ogura Y, et al. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem. 2001;276(7):4812–8.  https://doi.org/10.1074/jbc.M008072200.CrossRefPubMedGoogle Scholar
  9. 9.
    Lecat A, Piette J, Legrand-Poels S. The protein Nod2: an innate receptor more complex than previously assumed. Biochem Pharmacol. 2010;80(12):2021–31.  https://doi.org/10.1016/j.bcp.2010.07.016.CrossRefPubMedGoogle Scholar
  10. 10.
    Caso F, et al. Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis. Autoimmun Rev. 2014;13(12):1220–9.  https://doi.org/10.1016/j.autrev.2014.08.010.CrossRefPubMedGoogle Scholar
  11. 11.
    Rose CD, Martin TM, Wouters CH. Blau syndrome revisited. Curr Opin Rheumatol. 2011;23(5):411–8.  https://doi.org/10.1097/BOR.0b013e328349c430.CrossRefPubMedGoogle Scholar
  12. 12.
    Milman N, et al. A novel mutation in the NOD2 gene associated with Blau syndrome: a Norwegian family with four affected members. Scand J Rheumatol. 2009;38(3):190–7.  https://doi.org/10.1080/03009740802464194.CrossRefPubMedGoogle Scholar
  13. 13.
    Okada S, et al. Cardiac infiltration in early-onset sarcoidosis associated with a novel heterozygous mutation, G481D, in CARD15. Rheumatology (Oxford, England). 2009;48(6):706–7.  https://doi.org/10.1093/rheumatology/kep061.CrossRefGoogle Scholar
  14. 14.
    Sakai H, et al. A case of early-onset sarcoidosis with a six-base deletion in the NOD2 gene. Rheumatology (Oxford, England). 2010;49(1):194–6.  https://doi.org/10.1093/rheumatology/kep315.CrossRefGoogle Scholar
  15. 15.
    van Duist MM, et al. A new CARD15 mutation in Blau syndrome. Eur J Hum Genet: EJHG. 2005;13(6):742–7.  https://doi.org/10.1038/sj.ejhg.5201404.CrossRefPubMedGoogle Scholar
  16. 16.
    Villanueva-Mendoza C, et al. Familial case of Blau syndrome associated with a CARD15/NOD2 mutation. Ophthalmic Genet. 2010;31(3):155–8.  https://doi.org/10.3109/13816810.2010.492818.CrossRefPubMedGoogle Scholar
  17. 17.
    Kanazawa N, et al. Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood. 2005;105(3):1195–7.  https://doi.org/10.1182/blood-2004-07-2972.CrossRefPubMedGoogle Scholar
  18. 18.
    Wang X, et al. 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;46(11):3041–5.  https://doi.org/10.1002/art.10618.CrossRefPubMedGoogle Scholar
  19. 19.
    Barnich N, et al. Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-{kappa}B activation in Muramyl dipeptide recognition. J Cell Biol. 2005;170(1):21–6.  https://doi.org/10.1083/jcb.200502153.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tattoli I, et al. The nodosome: Nod1 and Nod2 control bacterial infections and inflammation. Semin Immunopathol. 2007;29(3):289–301.  https://doi.org/10.1007/s00281-007-0083-2.CrossRefPubMedGoogle Scholar
  21. 21.
    Saulsbury FT, et al. Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigree. Arthritis Rheum. 2009;60(6):1804–6.  https://doi.org/10.1002/art.24532.CrossRefPubMedGoogle Scholar
  22. 22.
    Janssen CEI, et al. Morphologic and immunohistochemical characterization of granulomas in the nucleotide oligomerization domain 2-related disorders Blau syndrome and Crohn disease. J Allergy Clin Immunol. 2012;129(4):1076–84.  https://doi.org/10.1016/j.jaci.2012.02.004.CrossRefPubMedGoogle Scholar
  23. 23.
    Vitale A, et al. Biological treatments: new weapons in the management of monogenic autoinflammatory disorders. Mediat Inflamm. 2013;2013:939847.  https://doi.org/10.1155/2013/939847.CrossRefGoogle Scholar
  24. 24.
    Sfriso P, et al. Blau syndrome, clinical and genetic aspects. Autoimmun Rev. 2012;12(1):44–51.  https://doi.org/10.1016/j.autrev.2012.07.028.CrossRefPubMedGoogle Scholar
  25. 25.
    Yasui K, et al. Thalidomide dramatically improves the symptoms of early-onset sarcoidosis/Blau syndrome: its possible action and mechanism. Arthritis Rheum. 2010;62(1):250–7.  https://doi.org/10.1002/art.25035.CrossRefPubMedGoogle Scholar
  26. 26.
    Chauhan K, Michet C. A case of Blau syndrome. Case Rep Rheumatol. 2014;2014:216056.  https://doi.org/10.1155/2014/216056.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Milman N, et al. Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation. APMIS. 2006;114(12):912–9.  https://doi.org/10.1111/j.1600-0463.2006.apm_522.x.CrossRefPubMedGoogle Scholar
  28. 28.
    Otsubo Y, et al. A long-term follow-up of Japanese mother and her daughter with Blau syndrome: effective treatment of anti-TNF inhibitors and useful diagnostic tool of joint ultrasound examination. Mod Rheumatol. 2017;27(1):169–73.  https://doi.org/10.3109/14397595.2014.964388.CrossRefPubMedGoogle Scholar
  29. 29.
    Aróstegui JI, et al. NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum. 2007;56(11):3805–13.  https://doi.org/10.1002/art.22966.CrossRefPubMedGoogle Scholar
  30. 30.
    Simonini G, et al. Clinical and transcriptional response to the long-acting Interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis Rheum. February 2013;65(2):513–8.  https://doi.org/10.1002/art.37776.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Martin TM, et al. The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. Arthritis Rheum. 2009;60(2):611–8.  https://doi.org/10.1002/art.24222.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Pediatric RheumatologyHospital for Special Surgery/Weill Cornell MedicineNew YorkUSA

Personalised recommendations