Qingping Yao1, Felicitas Lacbawan2, Jianbo Li3. 1. Department of Rheumatic and Immunologic Disease, Cleveland Clinic, Cleveland, OH. Electronic address: qingping.yao@stonybrookmedicine.edu. 2. Molecular Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH. 3. Biostatistics, Cleveland Clinic, Cleveland, OH.
Abstract
OBJECTIVE: Systemic autoinflammatory diseases (SAIDs) mainly include monogenic hereditary periodic fever syndromes, and NOD2-associated AID (NAID) is a polygenic SAID. Our aim was to study the disease frequency and report our diagnostic experience. METHODS: A total of 266 adult patients with clinical phenotypes suspicious for SAIDs were studied at the Cleveland Clinic between November 2009 and February 2015. All patients were genotyped for NOD2 mutations or periodic fever syndrome panel. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. RESULTS: Of the 266 patients, 79 (29.7%) were diagnostic of SAIDs, including 54 cases of NAID, 13 familial Mediterranean fever (FMF), 6 tumor necrosis factor receptor-associated periodic syndrome (TRAPS), 5 cryopyrin-associated periodic disease (CAPS), and 1 hyper IgD periodic syndrome (HIDS). NOD2 genotyping had a higher concordance rate with the clinical phenotype for the diagnosis of NAID. Of 29 patients, 13 (44.8%) were clinically suspicious for FMF and had positive genetic testing. Of 66 patients, 6 (9%) were tested positive for TRAPS. Out of 23 patients, 5 (21.7%) were tested positive for CAPS. Only 1 patient tested positive for HIDS. The concordance between the working clinical diagnosis and positive genetic testing varied among the SAIDs. CONCLUSIONS: Our study demonstrates that NAID and FMF are relatively common in adults. TRAPS and HIDS are extremely rare, and the concordance between the working clinical diagnosis and positive genetic testing is considerably disproportional for TRAPS. Ordering of genetic testing for SAIDs should highly consider both the disease frequency and stringent phenotypes.
OBJECTIVE: Systemic autoinflammatory diseases (SAIDs) mainly include monogenic hereditary periodic fever syndromes, and NOD2-associated AID (NAID) is a polygenic SAID. Our aim was to study the disease frequency and report our diagnostic experience. METHODS: A total of 266 adult patients with clinical phenotypes suspicious for SAIDs were studied at the Cleveland Clinic between November 2009 and February 2015. All patients were genotyped for NOD2 mutations or periodic fever syndrome panel. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. RESULTS: Of the 266 patients, 79 (29.7%) were diagnostic of SAIDs, including 54 cases of NAID, 13 familial Mediterranean fever (FMF), 6 tumor necrosis factor receptor-associated periodic syndrome (TRAPS), 5 cryopyrin-associated periodic disease (CAPS), and 1 hyper IgD periodic syndrome (HIDS). NOD2 genotyping had a higher concordance rate with the clinical phenotype for the diagnosis of NAID. Of 29 patients, 13 (44.8%) were clinically suspicious for FMF and had positive genetic testing. Of 66 patients, 6 (9%) were tested positive for TRAPS. Out of 23 patients, 5 (21.7%) were tested positive for CAPS. Only 1 patient tested positive for HIDS. The concordance between the working clinical diagnosis and positive genetic testing varied among the SAIDs. CONCLUSIONS: Our study demonstrates that NAID and FMF are relatively common in adults. TRAPS and HIDS are extremely rare, and the concordance between the working clinical diagnosis and positive genetic testing is considerably disproportional for TRAPS. Ordering of genetic testing for SAIDs should highly consider both the disease frequency and stringent phenotypes.