Self-reported Impact of the Early 2020 COVID-19 Crisis on the Healthcare Pathway During and After Lockdown in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Practical Survey.

Introduction: Global lockdown in the context of the coronavirus disease 2019 (COVID-19) pandemic is an unprecedented experience. We report here the results of an anonymous questionnaire-based survey on the healthcare and control of chronic IMIDs (chronic immune-mediated inflammatory diseases) within the IMMINENT network during the French lockdown (March 17, 2020-May 11, 2020) and the 2-month period following the end of the lockdown (July 11, 2020). Methods: Two anonymous questionnaires were sent by email to 4500 patients who were followed in a university hospital for an IMID in the departments of gastroenterology, rheumatology, dermatology, pneumology, neurology, and internal medicine. Results: A total of 921/4500 (20.46%) responded to the first survey (impact of the lockdown), and 553/4500 (12.28%) to the second (impact at 2-months post-lockdown). Concerning the impact of the lockdown, 420/915 (45.9%) reported affected follow-up. Similarly, after the lockdown, 248/544 (45.6%) declared a negative impact on their follow-up. The repartition by departments of patients' perception of an altered follow-up during (P = .72) and at the end of the lockdown (P = .77) was not statistically different. Our study highlighted the effects of the COVID-19 pandemic and the restriction measures implemented on the self-reported impact felt by patients on the follow-up of their chronic IMIDs without significant differences among all departments. Conclusion: Our study is original by showing that patients, whatever the type of IMID, shared this same negative perception. This transdisciplinary study demonstrated the importance of a collaborative network among all departments.

Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension.

Introduction: Soluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics. Methods: 1. Serum levels of 14 B cell biomarkers (ß2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant. Results: In a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of ß2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); ß2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher ß2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC. Conclusion: Soluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators.

Initial characteristics and follow-up of patients with a diagnosis of angiotensin-converting enzyme inhibitor induced angioedema.

Background: A differential diagnosis between angiotensin-converting enzyme inhibitor (ACEi) angioedema (AE) and histaminergic AE (hAE) might be challenging. Follow-up data may help discriminate these conditions but are scarcely reported. Objective: To report on the follow-up of patients with suspected ACEi-AE and to describe the baseline characteristics of AE attacks in patients with a diagnosis of ACEi-AE after follow-up. Methods: Sixty-four patients with suspected ACEi-AE (i.e., with exposure to ACEi before the first attack, no urticaria associated, and normal C1-inhibitor levels) and at least one follow-up visit were included. Data were retrospectively collected at baseline and during the follow-up. Results: After the follow-up, the diagnosis of ACEi-AE was probable in only 30 patients. The remaining patients were reclassified as having probable hAE (21 patients) or undetermined-mechanism AE (13 patients). Patients with ACEi-AE were mostly men (61%), with a median age of 64 years (interquartile range [IQR] ±17 years), with a highly variable delay from ACEi introduction (median: 23 months; interquartile range: 103 months). Attacks preferentially involved lips (50%), tongue (47%), and throat (30%). Interestingly, patients with probable ACEi-AE after a follow-up also frequently presented with a history of allergy and atopic conditions (20%), attacks with preferential evening onset (25%), and spontaneous resolution in < 24 hours (26%), which are usually considered as suggestive of hAE. ACEi-AE attacks responded to icatibant in 79% of the patients. Conclusion: Patients with probable ACEi-AE were mostly men with facial involvement. A third of the patients with an initial suspected diagnosis of ACEi-AE had a final diagnosis of probable hAE. Although a follow-up of all patients should be a standard of care, it is critical to the correct diagnosis in the case of suspected bradykinin-associated AE, which may actually be due to histamine.

Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort.

BACKGROUND: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. OBJECTIVE: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort. METHODS: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up. RESULTS: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs. LIMITATIONS: No control group, missing data. CONCLUSION: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.

Whole-Body Distribution and Clinical Association of Telangiectases in Systemic Sclerosis.

Importance: In systemic sclerosis (SSc), to date, no study has precisely described the total number and fine distribution of telangiectases (TAs), their clinical association with the disease, and the biological mechanisms causing their development. Objectives: To describe the whole-body distribution of TAs and assess the association between the whole-body TA number and the characteristics of patients with SSc. Design, Setting, and Participants: A single-center, cross-sectional study was conducted between July 11, 2016, and March 15, 2017, at the National Referral Centre for Rare Systemic and Autoimmune Diseases in France. A population-based sample of 106 adults who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc were included; 8 patients who had previously received laser treatment for TAs were excluded. Main Outcomes and Measures: The number of TAs on the whole body (total and those >5 mm) and TA distribution in different areas were recorded. The association with clinical and biological data was studied using univariate and multivariate linear regression. Results: A total of 106 patients (83 [78.3%] women) were enrolled, including 12 with precapillary pulmonary hypertension (PH). Mean (SD) age was 60.6 (13.5) years. Telangiectasia distribution was 37.2% on the face, 33.2% on the upper limbs, including 26.4% on the hands, 28.1% on the trunk, including 17.1% for the upper part of the trunk, and 1.5% on the lower limbs. In analysis using the multivariate linear regression model, the whole-body TA number was independently associated with male sex (percentage change, 144.4%; 95% CI, 7.5% to 455.9%; P = .03), PH (162.8%; 95% CI, 5.6% to 553.8%; P = .04), history of pulmonary embolism (336.4%; 95% CI, 39.0% to 1270.1%; P = .01), glomerular filtration rate (-1.6%; 95% CI, -3.2% to -0.1% per 1-mL/min/1.73 m2 increase; P = .04), and soluble endoglin level (28.2%; 95% CI, 1.2% to 62.5% per 1-ng/mL increase; P = .04). Receiver operating characteristic analyses assessing the ability of TAs to identify the presence of PH revealed that the area under the curve was significant for the TA number on the whole body (0.77; 95% CI, 0.57 to 0.88), on the hands and face (0.81; 95% CI, 0.57 to 0.91), and on the hands (95% CI, 0.77; 95% CI, 0.57 to 0.89). Conclusions and Relevance: In the patients in this study with SSc, TAs were predominantly located on the face, hands, and the upper part of the trunk. Telangiectases appeared to be associated with vasculopathy features of SSc, particularly with PH and soluble endoglin levels.

Factors associated with the 6-minute walk distance in patients with systemic sclerosis.

BACKGROUND: There is an ongoing debate regarding the relevance of the 6-minute walking distance (6MWD) in systemic sclerosis (SSc) assessment, widely used as a usual test in these patients as well as an outcome measure in clinical trials. In this work, we aimed to assess the associations between the 6MWD and various disease parameters in patients with SSc. METHODS: Consecutive patients followed in our SSc National Reference Centre were included in this cross-sectional study if they fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc. Data were systematically collected during a comprehensive standardized evaluation that included a 6-minute walk test, clinical assessment, biological results, pulmonary function tests, transthoracic echocardiography, composite scores (European Scleroderma Study Group Activity Index, Medsger severity score, Health Assessment Questionnaire-Disability Index (HAQ-DI)) and treatments. Associations of the 6MWD with various disease parameters were assessed by linear regression in univariate and multivariate analyses. RESULTS: The study population comprised 298 patients (females 81%; mean age 58.2 ± 13.3 years; limited cutaneous SSc 82%; interstitial lung disease (ILD) 42%; pulmonary arterial hypertension (PAH) 6%). The 6MWD was significantly and independently associated with gender, age, body mass index, baseline heart rate (HR), HR variation during the test, PAH, history of arterial thrombosis and C-reactive protein levels, as well as with the HAQ-DI score in a sensitivity analysis. Muscle involvement, joint involvement and ILD were not independently associated with the 6MWD. CONCLUSIONS: During SSc, the 6MWD is independently associated with initial HR and HR variation; with PAH but not ILD, suggesting that pulmonary vasculopathy may have a greater impact than parenchymal involvement on functional limitation; and with global markers of disease activity and patient disability. These results give clinicians further insight into how to interpret the 6MWD in the context of SSc.