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

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.