Alain Lescoat

Vascular Evaluation of the Hand by Power Doppler Ultrasonography and New Predictive Markers of Ischemic Digital Ulcers in Systemic Sclerosis: Results of a Prospective Pilot Study

To evaluate the relevance of power Doppler ultrasonography (PDUS) as a predictive tool of 1‐year digital ulcer (DU) occurrence in systemic sclerosis (SSc).

Intravenous immunoglobulins in systemic sclerosis: Data from a French nationwide cohort of 46 patients and review of the literature

BACKGROUND As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature. METHODS 46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed. RESULTS We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome). CONCLUSION Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing.

Vascular evaluation of the hand by Power Doppler Ultrasonography provides new predictive markers of ischemic digital ulcers in systemic sclerosis

To evaluate the relevance of power Doppler ultrasonography (PDUS) as a predictive tool of 1‐year digital ulcer (DU) occurrence in systemic sclerosis (SSc).

Combination of capillaroscopic and ultrasonographic evaluations in systemic sclerosis: Results of a cross-sectional study

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.

Socioenvironmental factors of communicable and non-communicable diseases

From a clinical case of a tuberculosis diagnosed in Rennes in a Congolese patient, we highlight the need for new socioenvironmental variables to apprehend hazards in social contexts. Beyond the traditional aggregate variables describing socioeconomic characteristics, a collaboration between epidemiology, clinical care, immunology and the social sciences helps rethink a contagious disease as a social one. From industrial fatigue in the 19th factories to other forms of hardship in the 21st century.

Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement

Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc.

Silica-associated systemic sclerosis in 2017: 60 years after Erasmus, where do we stand?

Dear Editor, We read with interest the article entitled BOccupational and environmental scleroderma. Systematic review and metaanalysis^ by Rubio-Rivas et al. [1] which constitutes one of the largest meta-analysis ever done before in occupational and environmental systemic sclerosis (SSc) and concludes that crystalline silica (silicon dioxide, SiO2) and solvents are the two most likely substances related to the pathogenesis of SSc. From these results, authors hypothesize that while silica is involved in particular jobs, solvents are widespread and more people are therefore at risk of having incidental contact with them. This conclusion seems to play down SiO2 involvement in SSc. We would like to discuss this statement. Although it is well recognized that SiO2 is an ubiquitous air contaminant, occupational exposure to this chemical substance probably remains largely underestimated. Its use in many industrial fields and processes may be rather invisible which can contribute to conceal its hazard [2]. Beyond mining industries, exposure to crystalline silica appears to be significant in other sectors such as building activities, agriculture, foundries, or textile transformation (denim sandblasting) [3, 4]. The building collapses due to the attacks on the World Trade Center exposed thousands of rescue/recovery workers and residents to inorganic dusts, leading to a major occurrence of autoimmune disorders in the highly exposed groups [5]. The growing use of high-silica-content (> 90% SiO2) materials in manufacturing artificial stone products, has entailed local clusters of silicosis-associated autoimmune diseases, including silica-associated SSc [6]. Para-occupational and non-occupational exposures to crystalline silica also do exist and include daily life activities such as non-occupational use of scouring powder, handling and washing of dusty clothes, and do-it-yourself hobbies practiced repetitively without protections. These activities are almost never recorded in questionnaires used for case-control or cohort studies [1]. As SiO2 constitutes the major mineral component of earth crust, with heterogeneous silica contents in different types of soils, some authors have suggested that these geological differences could explain some spatial heterogeneity in SSc prevalence, subsequent to different passive environmental exposures by inhalation [7]. In rheumatologic and pathophysiological perspectives, recent studies have highlighted the association between exposure to SiO2 and visceral manifestations of SSc, such as pulmonary fibrosis and diffuse cutaneous involvement [8]. However, in these studies, as in all studies included in Rubio-Rivas’meta-analysis [1], the classification criteria used to select SSc patients were the 1980 ACR or LeRoy’s classification criteria for SSc. The updated 2013 ACR/EULAR classification criteria for SSc offer higher specificity and sensitivity to select patients earlier in the disease process and with a smaller visceral involvement [9]. New cohort studies based on the 2013 criteria are needed to precise the role of SiO2 in * Alain Lescoat alain.lescoat@chu-rennes.fr

From (re-)framing NCDs to shaping public health policies on NCDs and communicable diseases

A senior adviser to the Global Fund taught Richard Horton (July 22, p 346)1 some lessons that were drawn from the struggle against three communicable diseases—tuberculosis, malaria, and AIDS—that keep scourging global health. To raise funds to combat noncommunicable diseases (NCDs), one should “translate [one’s] evidence into clear and simple political (not technical) messages”, “articulate why [one] need[s] money—what exactly will [one] spend it on and what will be the results of that investment”, “break down [one’s] broad global demands into tangible country-specific needs”, and “connect [one’s] case to the big political picture—give it meaning”.

Association between clinical manifestations of systemic sclerosis and esophageal dysmotility assessed by high-resolution manometry

Purpose To characterize esophageal involvement according to high-resolution manometry (HRM) findings using the 3rd version of the Chicago Classification, in a French population of patients fulfilling the ACR/EULAR 2013 classification criteria for systemic sclerosis (SSc). Methods Thirty-six patients were consecutively included in this cross-sectional non-interventional study and had HRM performed in Rennes University hospital. Demographic and clinical characteristics, SSc history and interstitial lung disease (ILD) on CT-scan were assessed, and compared with esophageal motility. Results Sixty-one percent of SSc patients had ineffective peristalsis (55.6% failed peristalsis and 5.6% weak peristalsis), 33.3% had hypotensive esophagogastric junction pressure, 75% did not have a physiologic contraction following multiple rapid swallow (MRS), and 44.4% had an abnormal peristaltic reserve. One patient had type 1 achalasia and another one had Jackhammer esophagus. Failed peristalsis was associated with pyrosis (odds ratio [OR] 7.28, 95% confidence interval [CI] 1.51-35.21, p = 0.009), a higher modified Rodnan skin score (MRSS) (without failed peristalsis: 4.68 ± 2.95 vs. with failed peristalsis: 10.68 ± 9.23; p<0.05), the presence of telangiectasia (OR 7, 95% CI 1.59-30.8, p = 0.007), and low diffusing capacity of the lung for carbon monoxide (DLCO) (p = 0.013). Food in the esophagus and esophageal dilation on CT-scan were associated with failed contractions on HRM (respectively, OR 6.85, 95% CI 1.12-40.82, p = 0.05, and OR 14.67, CI 2.4-88.5, p = 0.002). Conclusions This study confirms that failed peristalsis is frequent in SSc and associated with other organ involvement. We found a concordance between HRM results and CT-scan findings regarding esophageal involvement.