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Objective: To define a semiquantitative classification of finger pulp blood flow (FPBF) and to evaluate whether this classification could be used to assess FPBF in healthy controls and in systemic sclerosis (SSc) patients. Methods: Thirty controls and 86 SSc patients were consecutively included. A classification of FPBF including 5 grades (from grade 0 [no signal] to 4 [signal detected on the entire finger pulp, including the subepidermal vascular network]) was evaluated. This classification was explored in basal conditions and after hand baths in hot and cold water in controls. Its relevance was also assessed at room temperature in SSc patients. Results: In controls, power Doppler ultrasonography (PDUS) of FPBF was improved after hot challenge (P = 0.024), whereas cold challenge decreased FPBF (P = 0.001). FPBF correlated with the vasodilation status assessed by the resistivity index of radial arteries (Spearman's correlation coefficient = –0.50, P = 0.0049). Grade 0 was more frequent in SSc patients than in controls (22.1% versus 3.3%; P < 0.05). In SSc patients, grade 0 was associated with severity markers of the digital vasculopathy such as digital ulcers (DUs) (current or past) (P < 0.05) or ulnar artery occlusion (P < 0.05). On the other hand, DUs were less frequent in patients with grade 4 (P < 0.05). A pathologic threshold of <2 (grade 0 or 1) was significantly associated with DUs (odds ratio 6.67 [95% confidence interval 2.31–19.21], P < 0.0001). Conclusion: PDUS allowed a semiquantitative evaluation of FBPF in SSc patients and controls. Further studies are warranted to validate these results in independent SSc populations and to compare PDUS to existing tools assessing digital blood flow. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of ulnar artery occlusion (UAO) assessed using Doppler ultrasound (DUS) with the severity markers of systemic sclerosis (SSc). Methods: Two hundred four unselected patients fulfilling the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria for SSc were included in this cross‐sectional multicenter study. All patients underwent bilateral hand DUS to evaluate the presence of UAO and clinical/paraclinical visceral evaluation according to current guidelines. Univariable and multivariable ordinal regression models were applied, grading the severity of UAO as "no UAO," "only one UAO," and "UAO on both hands," and assessing its association with clinical features of SSc. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: UAO was found in 76 patients (37.3%) and was bilateral in 49 patients (24%). UAO as an ordinal event was significantly associated with disease duration, history of fingertip ulcers, telangiectasia, higher modified Rodnan skin thickness score (MRSS), worse diffusing capacity for carbon monoxide (DLco) values, higher tricuspid jet velocity, late capillaroscopic pattern, and positivity for anticentromere antibodies (ACAs) (univariable analysis). In the adjusted multivariable ordinal model, UAO was less frequent in women (OR 0.35 [95% CI 0.15–0.83], P = 0.017) and in patients receiving steroids (OR 0.24 [95% CI 0.09–0.62], P = 0.0034). In multivariable analyses, significant association with UAO was retained for history of fingertip ulcers (OR 2.55 [95% CI 1.24–5.21], P = 0.011), higher MRSS (OR 1.65 [95% CI 1.06–2.56], P =0.025), lower DLco values (OR 0.85 [95% CI 0.78–0.94], P = 0.0015), and ACA positivity (OR 2.89 [95% CI 1.36–6.11], P = 0.0056). Conclusion: UAO may represent a relevant severity marker of vasculopathy in SSc. Its predictive value for the onset of severe vascular manifestations such as pulmonary arterial hypertension, and its association with mortality, remain to be determined in longitudinal studies. [ABSTRACT FROM AUTHOR]

A defect in the apoptotic cell clearance (efferocytosis) by phagocytic cells may participate in autoimmunity and chronic inflammation. The mechanisms leading to the emergence of autoimmunity in systemic sclerosis (SSc) are still to be determined. In this study, the efferocytosis capacities of blood monocyte‐derived macrophages (MDM) from patients with SSc were evaluated. Blood monocytes obtained from patients with SSc and healthy donors (HD) were differentiated in vitro into macrophages. The capacities of MDM to engulf CFSE+ apoptotic Jurkat human T lymphocytes were compared between SSc MDM and HD using flow cytometry. The expression of classical engulfing receptors in SSc MDM and HD MDM was also evaluated and their involvement in the modulation of efferocytosis was confirmed using a siRNA approach. The mean phagocytic index (PI) reflecting efferocytosis capacities of SSc MDM (PI = 19.3 ± 3.0; n = 21) was significantly decreased in comparison with the PI of HD MDM (PI = 35.9 ± 3.0; n = 31; P < 0.001). In comparison with HD, SSc MDM exhibited a downregulated expression of scavenger receptor (SR)‐B1, SR‐A1 and integrin β5 (ITGβ5). In HD MDM, the extinction of these receptors was followed by a reduction of efferocytosis only for the repression of ITGβ5, suggesting a possible selective role of this integrin in the impaired efferocytosis observed in SSc. As efferocytosis may be at the crossroads of inflammation, autoimmunity and fibrosis, in showing impaired efferocytosis capacities of blood MDM in SSc, our study offers new pathogenesis considerations for the involvement of macrophages in the autoimmune processes driving this disorder. Efferocytosis capacities are strongly decreased in monocyte‐derived macrophages from systemic sclerosis (SSc) patients. A downexpression of integrin β5 in proinflammatory and in SSc macrophages may explain a deficient efferocytosis. Impaired efferocytosis of macrophages may play a key role in autoimmune processes in SSc. [ABSTRACT FROM AUTHOR]

Objective: To compare microvascular damages on nailfold capillaroscopy (NFC) with macrovascular manifestations evaluated by hand power Doppler ultrasonography (PDUS) in systemic sclerosis (SSc) patients, and to assess the associations of these damages with the main digital manifestations of the disease: digital ulcers, acroosteolysis, and calcinosis.Methods: NFC, hand radiographs, and PDUS were systematically performed in 64 unselected SSc patients. PDUS evaluation with assessment of ulnar artery occlusion (UAO) and finger pulp blood flow (FPBF) were performed blinded for the results of radiographs and NFC.Results: UAO and pathologic FPBF were associated with severe capillary loss (<4 capillaries/mm) on NFC (odds ratio [OR] 4.04 [95% confidence interval (95% CI) 1.23-13.29]; P < 0.05, and OR 3.38 [95% CI 1.03-11.05]; P < 0.05, respectively). Digital ulcer history was associated with UAO (OR 10.71 [95% CI 3.36-34.13]; P < 0.0001), pathologic FPBF (OR 7.67 [95% CI 2.52-23.28]; P < 0.0001), late NFC pattern (OR 6.33 [95% CI 2.03-19.68]; P = 0.001), and severe capillary loss (OR 8.52 [95% CI 2.15-33.78]; P = 0.001). Acroosteolysis was also associated with UAO (OR 15.83 [95% CI 3.95-63.54]; P < 0.0001), pathologic FPBF (OR 5.52 [95% CI 1.71-17.90]; P = 0.003), late NFC pattern (OR 6.86 [95% CI 2.18-21.53]; P = 0.001), and severe capillary loss (OR 7.20 [95% CI 2.16-24.02]; P = 0.001). Calcinosis on radiographs was associated with late NFC pattern (OR 5.41 [95% CI 1.82-16.12]; P = 0.002), severe capillary loss (OR 12.69 [95% CI 3.14-51.26]; P < 0.0001), and UAO (OR 3.19 [95% CI 1.14-8.92]; P = 0.025). Combination of UAO and severe capillary loss in the same patient was especially associated with digital ulcer history (OR 18.60 [95% CI 2.24-154.34]; P = 0.001) and acroosteolysis (OR 10.83 [95% CI 2.56-45.88]; P = 0.001).Conclusion: Microvascular damages evaluated by NFC and macrovascular features like UAO assessed by PDUS show concordant associations with the main digital manifestations of the disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relevance of power Doppler ultrasonography (PDUS) as a predictive tool of 1-year digital ulcer (DU) occurrence in systemic sclerosis (SSc).Methods: A total of 55 SSc patients and 19 controls underwent PDUS of both hands to evaluate the prevalence of ulnar artery occlusion (UAO) at baseline. Finger pulp blood flow (FPBF) of the third and fourth fingers was also assessed and considered as pathologic if a defect of the Doppler signal on a finger pulp was observed. All patients were clinically re-evaluated 6 and 12 months later and new ischemic DU occurrences in the meantime were retrospectively recorded. Patients were also asked to call if new DUs occurred between consultations.Results: PDUS parameters were normal in all controls. The prevalence of UAO was 36.4% and was bilateral in 70% of the SSc cases. A total of 56.4% of SSc patients had a pathologic FPBF. UAO and pathologic FPBF were associated with a history of multiple DU episodes (odds ratio [OR] 8.98 [95% confidence interval (95% CI) 2.52-32.01], P < 0.001, and OR 4.69 [95% CI 1.30-16.93], P = 0.014, respectively) and the occurrence of new DUs during the followup in the univariable model (OR 8.73 [95% CI 2.00-38.16], P = 0.005, and OR 12.65 [95% CI 1.50-106.77], P = 0.005, respectively). The association of UAO and pathologic FPBF in the same patient was a predictive factor of new DUs in the multivariable analysis (P = 0.015).Conclusion: This study suggests that UAO and pathologic FPBF are associated with a history of multiple DUs and are predictors of new ischemic DUs. These parameters could be used as prognostic factors and considered in further studies evaluating DU treatment strategies. [ABSTRACT FROM AUTHOR]