A Multicenter Study of the Validity and Reliability of Responses to Hand Cold Challenge as Measured by Laser Speckle Contrast Imaging and Thermography: Outcome Measures for Systemic Sclerosis–Related Raynaud's Phenomenon

BACKGROUND: Objective and reliable outcome measures to facilitate clinical trials of novel treatments for systemic sclerosis (SSc)-related Raynaud's phenomenon (RP) are badly needed. Laser speckle contrast imaging (LSCI) and thermography are non-invasive measures of perfusion that show excellent potential. The purpose of this multi-centre study was to determine the reliability and validity of a hand cold challenge protocol using LSCI, standard thermography and low-cost mobile phone-based thermography. METHODS: Patients with RP secondary to SSc were recruited from 6 UK tertiary-SSc centres and underwent cold challenge on 2 consecutive days. Changes in cutaneous perfusion/temperature at each visit were imaged simultaneously using LSCI, standard and mobile phone thermography. Measurements included area under reperfusion/rewarming curve (AUC) and maximum perfusion/rewarming (MAX). Test-retest reliability was assessed using intraclass correlation coefficients (ICC). Estimated latent correlations assessed convergent validity of LSCI and thermography. RESULTS: 159 patients were recruited (84% female, 77% limited cutaneous, median age 63.3 years). LSCI and standard thermography both had substantial reliability, ICCs (95%CI) for AUC were 0.67(0.54-0.76) and 0.68(0.58-0.80) respectively, and for MAX were 0.64(0.52-0.75) and 0.72(0.64-0.81) respectively. Very high latent correlations (95% CI) were present for AUCs of LSCI and thermography [0.94(0.87-1.00)], and for AUCs of standard and mobile phone thermography [0.98(0.94-1.00)]. CONCLUSION: This is the first multi-centre study examining reliability and validity of cold challenge using LSCI and thermography in patients with SSc-related RP. LSCI and thermography demonstrated good potential as outcome measures. LSCI, standard and mobile phone thermography had very high convergent validity.