title: A large kindred with familial cold autoinflammatory syndrome.
abstract: BACKGROUND
  Familial cold autoinflammatory syndrome (FCAS), formerly known as familial cold urticaria, is a rare condition characterized by fever, rash, and arthralgias elicited by exposure to cold. Recently, mutations responsible for FCAS were identified in a novel gene (CIAS1), making it possible to confirm the diagnosis in most patients.
  
  
  OBJECTIVE
  We present a summary of clinical data from a large family with FCAS to further define the characteristics of the disorder and to validate previously proposed clinical criteria.
  
  
  METHODS
  A total of 73 participants were evaluated by interview and questionnaire, including 36 affected individuals. Responses from the questionnaire were analyzed and comparisons of proportions were made using the Z test. DNA was isolated and genotyping was performed on all subjects. Affected haplotypes (genotype patterns) were identified and used to confirm the diagnosis. Sequencing of the CIAS1 gene was performed in selected patients to confirm the mutation.
  
  
  RESULTS
  The prevalence of rash, fever/chills, joint complaints, nausea, headache, and thirst were not significantly different from previously reported proportions. There was statistically significant differences in conjunctivitis, sweating, and drowsiness with alpha = 0.01. The mean temperature required to produce symptoms was 22 degrees C, and the average earliest onset of symptoms after exposure was 1.5 hours.
  
  
  CONCLUSIONS
  Applying the proposed clinical criteria, 41% of affected subjects met all six criteria, 90% met five criteria, and 100% met four criteria for FCAS. None of the unaffected subjects met more than two criteria. Using a threshold of 4 of 6 clinical criteria, the data support the diagnostic validity of the proposed clinical criteria.
authors.affiliation: Allergy-immunology Section, Department of Pediatrics, Medical College of Georgia, Augusta, Georgia, USA.
authors.forename: Reid F
authors.initials: RF
authors.lastname: Johnstone
authors.forename: William K
authors.initials: WK
authors.lastname: Dolen
authors.forename: Hal M
authors.initials: HM
authors.lastname: Hoffman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics* / Q000503:physiopathology; D001798:Blood Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003080:Cold Temperature / Q000009:adverse effects*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010375:Pedigree; D017422:Sequence Analysis, DNA; D011795:Surveys and Questionnaires; D014581:Urticaria / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D001798:Blood Proteins; D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human