Effect of menopause on the modified Rodnan skin score in systemic sclerosis

INTRODUCTION: We aimed to evaluate the effect of menopause on skin thickening, as measured by the modified Rodnan skin score (mRSS), in women with systemic sclerosis (SSc). METHODS: We identified women with either limited or diffuse SSc, aged ≥ 18 years, enrolled within the Canadian Scleroderma Research Group (CSRG) cohort, between 2004 and 2011. As part of the CSRG cohort, subjects undergo annual assessments with standardized questionnaires and physical examinations. We performed multivariate regression analyses using generalized estimating equation (GEE) to determine the effect of menopause on the mRSS, adjusting for relevant covariates including notably age, follow-up time, and disease duration. RESULTS: We identified 1070 women with SSc, contributing a total of 3546 observations over the study period. Of these women, at baseline, 65% had limited disease and 35% diffuse disease. In multivariate analyses, we observed a substantial effect of postmenopausal status on the mean mRSS in women with diffuse disease subtype [−2.62 units, 95% confidence interval (CI) -4.44, −0.80] and significant interaction between menopausal status and disease subtype (2.04 units, 95% CI 0.20, 3.88). The effect of postmenopausal status on the mean mRSS was smaller in women with limited SSc (−0.58, 95% CI −1.50, 0.34). CONCLUSIONS: Our results suggest that menopause has a substantial effect on skin thickening in diffuse SSc, with postmenopausal status being associated with a lower mean mRSS compared to premenopausal status

Development of Myasthenia Gravis in Systemic Lupus Erythematosus

Objectives: To perform a literature review and estimate MG incidence in an SLE cohort. Materials and methods: We searched MEDLINE and PubMed for case reports of SLE and MG. We also calculated MG incidence within our clinical SLE cohort (females only). Results: Eleven articles met our criteria, providing 13 SLE patients who developed MG. The majority were female (84.6%), with the average ages of 25.6 and 33.5 years at diagnoses of SLE and MG, respectively. In 380 SLE female patients followed for 2,850 person-years, one MG case occurred. Conclusion: MG in SLE is a rare event

Reproductive issues in women with systemic lupus erythematosus: should we be afraid of the Big Bad Wolf?

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder, which can affect almost any organ system and may even be life-threatening. SLE predominantly affects women during their reproductive years, with a prevalence of approximately 1.5/1000 in women of 18-44 years, and is associated with significant morbidity during pregnancy. Many women with SLE ask if the disease will impair their capacity to have children and affect the long-term health of their offspring. Studies assessing these issues are scant and limited by methodological considerations. The first two manuscripts in this thesis present relevant literature reviews.The objectives of this doctoral research were to fill this knowledge deficit by first assessing live births in women with SLE. We conducted two studies estimating live birth rates in women with SLE using standardized incidence ratios (SIR) with general population rates as a reference. Both studies had very different study populations: one relied on an international inception cohort of women with SLE (manuscript #3), the other on an SLE cohort derived from Quebec's administrative databases (manuscript #4). This allowed us to investigate different aspects and predictors of live birth rates in women with SLE. Then, to answer the second research question, we determined if maternal SLE influences the long-term health of the offspring. To do so, we performed two studies within a large population-based cohort of children born to SLE women, the "Offspring of SLE mothers Registry (OSLER)", which we specifically created for this thesis research. These studies respectively evaluated the risk of congenital heart defects (manuscript #5) and autism spectrum disorders (manuscripts #6) in SLE offspring compared to children from the general population.This doctoral research provides novel and much-needed information, which will help physicians provide adequate counseling to women with SLE contemplating pregnancy. We conclude this thesis by discussing potential future directions of additional studies on reproduction in women with SLE and health outcomes in their offspring.Le lupus érythémateux disséminé (LED) est une maladie auto-immune chronique, qui peut toucher presque tous les organes du corps, menaçant parfois la vie des patients atteints. Le LED affecte de façon prédominante les femmes en âge de procréer, ayant une prévalence approximative de 1.5/1000 femmes de 18-44 ans, et est associé à une morbidité significative en grossesse.Plusieurs femmes atteintes de LED demandent si la maladie va diminuer leur capacité à avoir des enfants et influencer la santé à long terme de leurs enfants. Peu d'études adressent ces problématiques et sont limitées dans leur méthodologie. Les deux premiers manuscrits de cette recherche doctorale présentent une revue de la littérature pertinente à ce sujet.Les objectifs de cette thèse étaient de répondre à ce défaut de connaissance, en commençant, premièrement, par évaluer les naissances vivantes survenant chez les femmes avec LED. Pour ce faire, nous avons effectué deux études estimant les taux de naissances vivantes chez des femmes avec LED, au moyen d'un ratio d'incidence standardisé, en utilisant les taux de la population générale comme référence. Ces deux projets comprenaient des populations très différentes: une étude se reposait sur une cohorte internationale de femmes avec LED (manuscrit #3), l'autre sur une cohort de femmes avec LED dérivée des banques de données administratives du Québec (manuscrit #4). Ceci nous a permis d'investiguer différents aspects et prédicteurs des taux de naissances vivantes chez les femmes avec LED. Ensuite, afin de répondre à notre deuxième question de recherche, nous avons déterminé si le LED maternel influençait la santé à long terme des enfants nés de mères atteintes. Pour ce faire, nous avons réalisé deux études à l'intérieur d'une grande cohorte populationnelle d'enfants nés de mères avec LED, la cohorte OSLER ("Offspring of SLE mothers Registry"), que nous avons spécifiquement créée pour cette recherche doctorale. Ces études évaluaient respectivement le risque de malformations cardiaques congénitales (manuscrit #5) et le risque de désordres du spectre de l'autisme (manuscrit #6) chez les enfants de femmes avec LED comparés aux enfants de la population générale. Cette recherche doctorale génère de l'information nouvellle, originale, et nécessaire, qui aidera les cliniciens à conseiller adéquatement les femmes avec LED qui contemplent une grossesse. Nous concluons cette thèse en discutant de directions potentielles et futures d'études additionnelles sur les problématiques de la reproduction des femmes avec LED et de l'état de santé à long term de leurs enfants

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study

Abstract Background Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX). Methods We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011–2020). TMP-SMX prophylaxis was defined as a $$\ge$$ ≥ 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities. Results Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83–248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ( $$\ge$$ ≥ 20 mg/day vs none, OR 3.96; 95% CI 3.0–5.2; 1–19 mg/day vs none, OR 2.63; 95% CI 1.8–3.8), and methotrexate use (OR 1.48, 95% CI 1.04–2.1), intensive care (OR 1.95; 95% CI 1.4–2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2–2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5–0.8) was negatively associated with TMP-SMX use. Conclusions TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV

Outcomes in mothers with rheumatic diseases and their offspring workshop

This conference report describes six presentations that were given during a Canadian Institutes for Health Research-funded workshop. The goal of the workshop was to discuss key knowledge gaps in the study of outcomes in mothers with rheumatic diseases and their offspring. Presentations focused on epidemiological and methodological issues associated with the reproductive and perinatal health of women with rheumatic diseases. Discussions of relevant recent research allowed for discovery of potential data sources that could facilitate interdisciplinary research and created the opportunity for future collaborations