A retrospective review of patients referred for thermographic evaluation of RP symptoms at our unit between 2010 and 2012 was undertaken. Local research and development approval was obtained for the study (Ref RBB389). We received written confirmation from the National Research Ethics Service confirming that Research Ethics Committee approval was not required for a retrospective review of data obtained under normal clinical practice [under UK-wide Governance Arrangements for Research Ethics Committees (GAfREC)].
Subjects
A retrospective case note review of patients referred for thermographic evaluation of RP symptoms was undertaken to determine diagnosis. A diagnosis of primary RP was based on a final clinician diagnosis of “primary RP”, but also required the absence of clinical features of an underlying rheumatic disease or CTD and a negative ANA (immunofluorescence on Hep-2 cells negative at >1:160 dilution). A diagnosis of FMS required was based on documentation of widespread pain and tenderness of at least 11 of the 18 FMS trigger points using 1990 ACR criteria [11] and/or a final clinician diagnosis of FMS.
Patient questionnaire
All patients referred for thermographic assessment of RP symptoms complete a short questionnaire during 20-min acclimatization at 23 °C. The questionnaire captures clinical characteristics of RP using criteria derived from the consensus view of the UK Scleroderma Study Group in an earlier validation study [2]. The questionnaire records whether fingers are sensitive to cold, whether they show digital colour changes (white, red, blue and purple), whether patients experience numbness or paraesthesia in response to cold and the presence of symptoms in the absence of cold exposure. The questionnaire also collects relevant information including smoking history, cardiovascular risk factors (diabetes mellitus, dyslipidaemia and hypertension) and vasodilator medication use to aid subsequent interpretation of microvascular imaging studies.
Thermal imaging protocol and analysis
All patients had undergone a cold stress test (CST) under the same standardized conditions. Following 20-min acclimatization (at 23 ± 0.5 °C), thermographic images were taken of the dorsum of the hands (Thermovision Camera, FLIR systems, Danderyd, Sweden). Patients then submerged their hands (in polythene gloves to avoid evaporative cooling) to the level of the radio-carpal joint into a water bath cooled to 20 °C (±0.1 °C) for 60 s. A second thermal image of the dorsum of the hands was captured 10 min following cold challenge. Images were processed using commercially available software (CTHERM, version 2.3, University of Glamorgan). Regions of interest encompassing the 2nd–5th digits (distal to metacarpophalangeal joints) and dorsum of hand were prepared and the mean surface skin temperature within each region of interest recorded. The thermal gradient (TG) was calculated by subtracting the mean temperature of the dorsum of the hands from the mean temperature of the digits. A mean thermal gradient of both hands was calculated at both baseline and following cold challenge. In healthy controls, the TG is typically positive (~+1 to 2 °C) as the digital temperature (~33 °C) is typically greater than the dorsum of the hand (~31 °C) at baseline assessment and following cold challenge due to the action of thermoregulatory arteriovenous anastomoses (AVAs) within glabrous regions of the fingertips. In Raynaud’s phenomenon, the TG is typically negative (−1 to 3 °C) due to a lower digital temperature (~26–28 °C) in comparison with the dorsum of the hand (~31 °C) due to closure of thermoregulatory AVAs in resting state or in response to cold provocation. The TG (and related thermographic parameters such as the distal dorsal difference) has been successfully applied to differentiate disease states in populations of healthy controls, primary RP and secondary RP.
Nailfold capillaroscopy protocol and analysis
NC (when requested at the discretion of the treating clinicians) was performed at the index, middle and ring fingers of each hand using a pillar-mounted 1.3 megapixel camera (PL-A742, PixeLINK) at a magnification of 200×. Images were analysed using PixeLINK Capture OEM software. NC images of all digits were reviewed (without knowledge of diagnosis) by two blinded assessors (BV and MS), and patients were categorized as having either normal, mild non-specific abnormalities or scleroderma-pattern abnormalities using classification criteria proposed by Cutolo et al. [10]. Indeterminate cases were reviewed by a blinded third assessor (JP) and consensus reached.
Statistical analysis
Comparisons were made between the two patient groups for baseline demographics (age, smoking history, vasodilator medication use and cardiovascular disease), RP symptom characteristics, thermographic analysis at baseline and following CST (absolute skin temperature at digits, dorsum and thermal gradient) and NC changes (when available). Additional analyses were undertaken to evaluate potential associations between the type and number of digital colour changes reported by patients and the outcome of thermographic assessments. Categorical variables are reported as numbers and/or percentages and were compared using Chi-square test. Quantitative variables are reported as medians (interquartile range), and differences were assessed using Mann–Whitney U test. All analyses were two-tailed, and a p value of ≤0.05 was considered statistically significant.