title: A cold-response index for the assessment of Raynaud's phenomenon.
abstract: BACKGROUND
  Quantification of Raynaud's phenomenon (RP) is a prerequisite in the evaluation of novel therapeutic strategies. Fingertip rewarming in response to local cold provocation has been used in many studies but not been systematically validated. We have previously described the time elapsed before 63% of pre-cooling temperature is reached as a RP activity index.
  
  
  OBJECTIVE
  A comprehensive evaluation of fingertip rewarming in primary and scleroderma-associated RP.
  
  
  METHODS
  We defined a cold-response index (CRI) as the log transformation of the 63% rewarming time upon cold challenge.
  
  
  RESULTS
  The CRI shows high intra-individual reproducibility. The mean CRI values were (mean+/-S.D.): 2.4+/-0.3 in controls (n=53) versus 2.7+/-0.3 in RP (n=50, p<0.0001 versus controls), and 2.7+/-0.3 in scleroderma patients (n=46, p<0.0001). In addition, baseline fingertip temperature was also found to be significantly reduced both in primary as well as scleroderma-associated RP. Kinetic analysis of rewarming temperature curves demonstrates that the CRI is independent of individual rewarming patterns. Finally, the CRI decreases significantly upon a single low-level systemic hyperthermia treatment in scleroderma patients (2.68+/-0.28 before versus 2.45+/-0.33 after, p=0.0003), while the extent of cooling remained unchanged, thus demonstrating sensitivity to change.
  
  
  CONCLUSIONS
  Our results provide a solid basis for using the cold-response assay as an endpoint in addition to clinical activity scores in RP treatment trials.
authors.affiliation: Klinik für Dermatologie, Charité, Charitéplatz 1, 10117 Berlin, Germany. john.foerster@charite.de
authors.forename: John
authors.initials: J
authors.lastname: Foerster
authors.forename: Anja
authors.initials: A
authors.lastname: Kuerth
authors.forename: Eyline
authors.initials: E
authors.lastname: Niederstrasser
authors.forename: Esther
authors.initials: E
authors.lastname: Krautwald
authors.forename: Ruth
authors.initials: R
authors.lastname: Pauli
authors.forename: Raik
authors.initials: R
authors.lastname: Paulat
authors.forename: Markus
authors.initials: M
authors.lastname: Eweleit
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
mesh_terms: D000328:Adult; D000368:Aged; D003080:Cold Temperature; D005260:Female; D005385:Fingers; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D011928:Raynaud Disease / Q000175:diagnosis* / Q000503:physiopathology*; D015203:Reproducibility of Results; D013817:Thermography / Q000295:instrumentation* / Q000379:methods* / Q000592:standards