Qingping Yao1, Le-Chu Su2, Kenneth J Tomecki3, Lan Zhou4, Bijal Jayakar5, Bo Shen2. 1. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio. Electronic address: yaoq@ccf.org. 2. Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, Ohio. 3. Department of Dermatology, Cleveland Clinic, Cleveland, Ohio. 4. Department of Neurology, Cleveland Clinic, Cleveland, Ohio. 5. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio.
Abstract
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.
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.