title: A Systematic Analysis of Treatment and Outcomes of NOD2-Associated Autoinflammatory Disease.
abstract: OBJECTIVE
  Yao syndrome, formerly named NOD2-associated autoinflammatory disease, is a periodic disease characterized by fever, dermatitis, polyarthritis/leg swelling, and gastrointestinal and sicca-like symptoms associated with specific NOD2 sequence variants. Our aim was to evaluate the treatment and outcomes of the disease.
  
  
  METHODS
  A total of 52 adult patients with autoinflammatory disease phenotype were diagnosed with Yao syndrome and enrolled at the Cleveland Clinic between November 2009 and May 2015. All patients were genotyped for the NOD2 variants, and systematically studied for treatment outcomes.
  
  
  RESULTS
  Among the 52 Yao syndrome patients, all were white, and 72% were women. The mean age at diagnosis was 38.0 ± 12.0 years, and the disease duration was 8.8 ± 5.8 years. In the multi-organ disease, more common and typical manifestations were recurrent dermatitis and inflammatory arthritis with or without distal leg swelling besides recurrent fever. It was genotypically associated with the NOD2 IVS8+158or R702W. Therapeutically, glucocorticoids markedly decreased the disease severity and duration of flares in 19 patients (36.6%), sulfasalazine treatment achieved a significant symptomatic improvement in 22 (42%) patients, and 3 patients received canakinumab or tocilizumab with benefits. Prognostically, 13% of the 52 patients had somewhat physical impairment, and there was no mortality during the follow-up. Associated comorbidities were fibromyalgia, asthma, renal stones, and ventricular hypertrophy.
  
  
  CONCLUSIONS
  As a systemic disease, Yao syndrome uncommonly affects the solid internal organs, but it can be complicated with chronic pain syndrome and even disability. Glucocorticoids or sulfasalazine may be considered as the first-line treatment option, and interleukin (IL)-1/IL-6 inhibitors may be tried for refractory cases. The potential associations between certain comorbidities and Yao syndrome deserve further study.
authors.affiliation: Department of Rheumatic and Immunologic Disease, Cleveland Clinic, Ohio; Division of Rheumatology, Allergy and Immunology, Stony Brook University, NY. Electronic address: qingping.yao@stonybrookmedicine.edu.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Gastroenterology/Hepatology, Cleveland Clinic, Ohio.
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D056660:Hereditary Autoinflammatory Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D012460:Sulfasalazine / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C541220:canakinumab; D012460:Sulfasalazine; C502936:tocilizumab
keywords: IVS8(+158); NOD2-associated autoinflammatory disease; Nucleotide-binding oligomerization domain containing 2 (NOD2); Outcome; Therapy; Yao syndrome