Dermatitis as a characteristic phenotype of a new autoinflammatory disease associated with NOD2 mutations

J Am Acad Dermatol. 2013 Apr;68(4):624-631. doi: 10.1016/j.jaad.2012.09.025. Epub 2012 Oct 24.


Objectives: We sought to characterize a new category of autoinflammatory disease associated with nucleotide-binding oligomerization domain 2 (NOD2) gene mutations.

Methods: A total of 22 patients were identified, inclusive of those reported previously. All had autoinflammatory phenotypes and NOD2 gene mutations that were prospectively studied between January 2009 and February 2012.

Results: All 22 patients were non-Jewish whites (13 women and 9 men). The mean age at diagnosis was 40.1 years (range 17-72), with a mean disease duration of 4.7 years (range 1-13). Three female patients were siblings. Common clinical features were weight loss (13/22), episodic self-limiting fever (13/22), dermatitis (19/22), and inflammatory polyarthritis/polyarthralgia (20/22). Gastrointestinal symptoms occurred in 13 patients, sicca-like symptoms in 9, and recurrent chest pain in 5. All patients carried the NOD2 gene mutations, with the intervening sequence 8(+158) variant in 21 and the R702W variant in 8.

Limitations: The NOD2 allelic frequency may need to be examined in a larger population with systemic autoimmune diseases.

Conclusions: The characteristic clinical phenotype, notably dermatitis, coupled with certain NOD2 variants constitutes a new autoinflammatory disease entity, which we have named as NOD2-associated autoinflammatory disease.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Dermatitis / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Nod2 Signaling Adaptor Protein / genetics*
  • Phenotype
  • Prospective Studies
  • Skin Diseases, Genetic / genetics*
  • Young Adult


  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein