Laser Speckle Contrast Analysis: Functional Evaluation of Microvascular Damage in Connective Tissue Diseases. Is There Evidence of Correlations With Organ Involvement, Such as Pulmonary Damage?

Laser speckle contrast analysis (LASCA) is a non-contact technique able to quantify peripheral blood perfusion (PBP) over large skin areas. LASCA has been used to study hand PBP in several clinical conditions. These include systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) and LASCA showed that PBP was significantly lower in these conditions than in healthy subjects (HS). Moreover, it has been demonstrated that LASCA is a safe technique also able to monitor digital ulcer perfusion and their evolution in SSc patients, during systemic and local treatment. The use of LASCA, coupled with reactivity tests is commonplace in the field of microvascular function research. Post-occlusive hyperemia reactivity (POHR) and local thermal hyperemia, associated with laser techniques are reliable tests in the evaluation of perfusion in SSc patients. Other studies used laser speckled techniques, together with acetylcholine and sodium nitroprusside iontophoresis, as specific tests of endothelium function. In conclusion, LASCA is a safe, non-contact reliable instrument for the quantification of PBP at skin level and can also be associated with reactivity tests to monitor disease progression and response to treatment in different connective tissue diseases.

Laser speckle contrast analysis predicts major vascular complications and mortality of patients with systemic sclerosis

Objectives The aim of study was to evaluate peripheral blood perfusion and the proximal-distal gradient (PDG) of the hands as biomarkers of SSc major vascular complications (digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis) and mortality by laser speckle contrast analysis. Methods In this retrospective observational study, 176 SSc patients [158 female, median age 53 (51–57) years] and 142 healthy controls [115 female, median age 53 (48–55) years] were enrolled. Clinical data were collected at baseline and annually through 5 years of follow-up. Hand dorsum perfusion images were divided into three regions of interest (ROI): ROI1 included the second, third, and fourth fingers distal to the proximal interphalangeal finger joint; ROI2 included the area between the proximal interphalangeal finger joint and the metacarpophalangeal joint; ROI3 included the hand dorsum. PDG was identified when the perfusion mean difference between ROI1 and ROI2 was >30 perfusion units. Results Median peripheral blood perfusion was significantly lower for SSc patients than healthy controls. PDG was present in 51.5% of SSc patients and in 98.6% of healthy controls. Using the final multivariate model, nailfold videocapillaroscopy (NVC) pattern [hazard ratio (HR) 0.065 (0.015–0.283), P <0.0001] and PDG [HR 0.376 (0.194–0.727), P <0.01] were found to be risk factors for major vascular complications. By multivariate analysis, age [HR 1.051 (1.014–1.088), P <0.01), NVC pattern [HR 0.001 (0.000–3.111), P >0.05], and PDG [HR 0.207 (0.073–0.589), P <0.01] were found to be risk factors for 5-year SSc mortality. Conclusion PDG predicts major vascular complication and 5-year mortality of SSc patients.

THU0334 LASER SPECKLE CONTRAST ANALYSIS FOR MEASUREMENT OF PERIPHERAL BLOOD PERFUSION IN SYSTEMIC SCLEROSIS PATIENTS: CAN IT PREDICT FUTURE ISCHEMIC DIGITAL TROPHIC LESIONS?

Background:Vasculopathy is a hallmark of systemic sclerosis (SSc). Laser speckle contrast analysis (LASCA) is a research tool to assess peripheral blood perfusion (PBP) (1). At this moment, its reliability has been attested in SSc patients, but its predictive value for future ischemic digital trophic lesions (DTL) is unknown (1).Objectives:To investigate in an unselected, prospective SSc cohort if baseline LASCA PBP measurements can discriminate between patients who will develop ischemic DTL (iDTL) and those who will not.Methods:Patients (fulfilling 2013 ACR/EULAR criteria and/or 2001 LeRoy and Medsger criteria) were recruited during the period of December 2017 to September 2018. LASCA was performed at baseline, in standardized conditions (1). Regions of interest (ROIs) (diameter 1 cm) were outlined at the 2nd-5thfingertip both volar and dorsal. The ‘average PBP’ of these ROIs was calculated (expressed in arbitrary perfusion units [PU]). A monthly telephone survey was conducted for 1 year to investigate DTL occurrence. DTL were considered ‘ischemic’ if not related to calcinosis. Logistic regression and ROC analysis were used to assess if average PBP is predictive of future iDTL.Results:Of the 106 patients with complete follow-up (92 women [86,8%]; 18 limited SSc [17,0%], 82 limited cutaneous SSc [77,4%], 6 diffuse cutaneous SSc [5,7%]), 29 patients (27,4%) had a DTL history. Forty-nine patients (46,2%) were on vasodilator therapy. Only 7 patients developed at least 1 iDTL during follow-up (6,6%) (Figure 1a). Performing univariate logistic regression (ULR), average PBP was not predictive for future iDTL (Table 1). Of note, analyzing only the patients not taking vasodilators, average PBP in the ‘iDTL group’ (n = 3) was median 46,8 PU (min. 45,6 - max. 68,8) vs. median 141,4 PU (min. 24,4 - max. 269,5) in the ‘no iDTL group’ (n = 54) (Figure 1b). In this subgroup, all 3 patients who developed iDTL (100%) had an average PBP ≤ 70 PU whereas only 9 of the 54 patients without iDTL development (16,7%) had such PBP values.Table 1.Results of ULRSummary statisticsULRVariableiDTL cases(n = 7)Non-iDTL cases(n = 99)ParameterOR(95% CI)pROC AUC(95% CI)Average PBP (PU) mean (+/- SD)123,0 (74,6)142,9 (61,9)Average PBP (linear)0,995(0,982-1,007)0,4180,597(0,352-0,843)Conclusion:In this pilot study with an unselected day-to-day SSc population, where patients were allowed to continue vasodilators, there was an unexpected low iDTL incidence, undermining the power of our study. Even though, the observations in the subgroup of patients not taking vasodilators deserve future investigation to assess whether low PBP values, as measured by LASCA, are associated with a higher iDTL incidence.References:[1]Cutolo M, Vanhaecke A, et al. Autoimmun Rev. 2018;17(8):775-80.Figure 1.Distribution of ‘average PBP’ as measured by LASCA for ‘no iDTL group’ and ‘iDTL group’Disclosure of Interests:Claire Debusschere: None declared, Amber Vanhaecke: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Ellen Deschepper: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl