N-Terminal pro-Brain Natriuretic Peptide is a biomarker for cardiovascular damage in systemic lupus erythematous: a cross-sectional study.

OBJECTIVES: Prediction models based on traditional risk factors underestimate cardiovascular (CV) risk in systemic lupus erythematosus (SLE). In a large sample of unselected SLE patients, we investigated cross-sectional associations of NT-proBNP with cardiovascular damage (CVD). METHODS: Serum NT-proBNP was measured in SLE patients enrolled in the MUHC Lupus Clinic registry. Serum were collected between March 2022 and April 2023 at annual research visits. The primary outcome was CVD identified on the SLICC Damage Index. Factors associated with CVD and NT-proBNP levels were determined. RESULTS: Overall, 270 SLE patients (female 91%, median age 50.7 [1st quartile- 3rd quartile : 39.6-62.1] years) were analyzed for the primary outcome. Among them, 33 (12%) had CVD. The ROC curve for NT-proBNP demonstrated strong associations with CVD (AUC 0.78, 95% CI 0.69-0.87) with a threshold of 133 pg/ml providing the best discrimination for those with/without CVD. Hypertension (OR 3.3, 95% CI 1.2-9.0), dyslipidaemia (OR 3.6, 95% CI 1.3-9.6) and NT-proBNP > 133 pg/ml (OR 7.0, 95% CI, 2.6-19.1) were associated with CVD in the multivariable logistic regression model. Increased NT-proBNP levels were associated with age (OR 4.2, 95% CI 2.2-8.3), ever smoking (OR 1.9, 95% CI 1.0-3.5), reduced eGFR (4.1, 95% CI 1.3-13.1), prior pericarditis/pleuritis (OR 2.5, 95% CI 1.4-4.5) and aPL antibodies (OR 2.6, 95% CI 1.4-4.9). CONCLUSION: NT-proBNP is a biomarker for CV damage in SLE. The novel associations of NT-proBNP levels with prior pericarditis/pleuritis and aPL antibodies suggest new avenues for research to better understand what drives CV risk in SLE.

Skin disorders and interstitial lung disease: Part II-The spectrum of cutaneous diseases with lung disease association.

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases.

Serologic phenotypes distinguish systemic lupus erythematosus patients developing interstitial lung disease and/or myositis.

OBJECTIVES: To determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis. METHODS: Adult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary fibrosis item. New-onset myositis was identified using the SLICC Damage Index muscle atrophy/weakness item, the SLEDAI-2K item for myositis, and annual creatinine kinase testing. Chart review confirmed ILD/myositis cases and randomly sampled SLE patients from baseline formed our sub-cohort (N = 72). Cases and sub-cohort were compared regarding myositis-related biomarkers at baseline and at a randomly selected follow-up between baseline and end of observation (date of ILD/myositis diagnosis or Dec. 31, 2017). Descriptive analyses and hazards ratios (HRs) were generated for ILD/myositis incidence, focusing on baseline serology and adjusting for sex, race/ethnicity, age at SLE diagnosis, and SLE duration. RESULTS: Fourteen SLE patients developed ILD (N = 9), myositis (N = 3), and/or both (N = 2). Thirteen of those (92.9%) developing ILD/myositis had at least one biomarker at baseline, versus 47 (65.3%) SLE patients who never developed myositis/ILD. The most common biomarkers in myositis/ILD were KL-6, anti-Ro52, and anti-Ku. Baseline biomarkers tended to remain positive in follow-up. In multivariate Cox regressions, SLE patients had higher risk of developing myositis/ILD with elevated baseline KL-6 (adjusted hazard ratio 3.66; 95% confidence interval 1.01, 13.3). When updating biomarkers over time, we also saw correlations between anti-Smith and ILD/myositis. CONCLUSIONS: Baseline myositis-related biomarkers were highly associated with ILD/myositis incidence. This is the first identification of biomarker phenotypes with ILD/myositis risk in SLE.

Clinical Significance of Raynaud Phenomenon in Systemic Lupus Erythematosus.

OBJECTIVE: There are limited reports of the clinical significance of Raynaud phenomenon (RP) in systemic lupus erythematosus (SLE), with some suggesting RP is associated with less severe lupus. Since most prior studies were small and/or focused on a specific race/ethnic demographic, it is unclear if those results are generalizable. We evaluated whether RP was associated with demographic and clinical factors in a large multiethnic SLE cohort. METHODS: We studied Montreal General Hospital SLE cohort patients who are followed with standardized annual assessments. We included patients with at least 1 visit across 2011-2018 and assessed demographic and clinical variables (using the 1997 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) at their first visit. We present multivariate logistics regression analyses of cross-sectional associations between these variables and RP in SLE. RESULTS: Of 489 SLE patients, most were female (n = 445, 91%). Mean age at SLE diagnosis was 31.5 (standard deviation, 13.5) years, and 169 (34.6%) had RP. In our fully adjusted model, female sex (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.07-6.03), White race/ethnicity (OR, 1.85; 95% CI, 1.10-3.17), neurological/neuropsychiatric manifestations (OR, 1.98; 95% CI, 1.10-3.56), and anti-RNP antibodies (OR, 3.03; 95% CI, 1.73-5.38) were positively associated with RP, whereas hemolytic anemia and cellular casts were negatively associated. CONCLUSIONS/DISCUSSION: Over one third of our large multiethnic North American SLE cohort had RP. This study confirmed associations between RP and a specific SLE phenotype.

Predictors of Unsuccessful Hydroxychloroquine Tapering and Discontinuation: Can We Personalize Decision-Making in Systemic Lupus Erythematosus Treatment?

OBJECTIVE: Hydroxychloroquine (HCQ) is a key systemic lupus erythematosus (SLE) drug, making concerns of drug shortages grave. Our objective was to evaluate factors associated with poor outcomes after HCQ taper or discontinuation in SLE. METHODS: We studied 5 Canadian SLE cohorts between 1999 and 2019, following patients from the date of HCQ tapering (cohort 1) or discontinuation (cohort 2). A composite outcome was defined as any of the following: a need for therapy augmentation, an increase (of at least 4 points) in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, or hospitalization for SLE. In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events. A third cohort continuing to receive HCQ was also studied, to assess whether the same factors influenced the outcome even when the HCQ dose was unchanged. RESULTS: The poor outcome rate, per 100 person-years, was 35.7 (95% confidence interval [95% CI] 31.6-40.3) in the HCQ taper cohort (n = 398), 29.0 (95% CI 25.5-33.0) in the discontinuation cohort (n = 395), and 16.1 (95% CI 13.2-19.6) in the maintenance cohort (n = 395). In patients tapering HCQ, baseline prednisone use was independently associated with greater risk of poor outcomes. In the discontinuation cohort, the risk of poor outcomes was greater for Black patients and those diagnosed with SLE at age ≤25 years. Among those maintaining HCQ, baseline immunosuppressive use and First Nations ethnicity were associated with poor outcomes. CONCLUSION: We identified demographic and clinical factors associated with poor outcomes after HCQ taper/discontinuation. This information is critical in the current setting of potential shortages, but over the long term, such information could inform personalized therapies.

Association between chronic obstructive pulmonary disease, smoking, and interstitial lung disease onset in rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis (RA), respiratory manifestations include chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We assessed whether baseline COPD and smoking were associated with RA-ILD onset. METHODS: We identified new-onset ILD in incident RA subjects within the MarketScan Commercial Claims database, using physician and/or hospitalisation diagnostic codes. Smoking data (current, past, never) were available for a subset via a health questionnaire. Kaplan-Meier analyses assessed time to ILD onset, stratified by prior COPD and smoking. Multivariate Cox regression models were adjusted for age, sex, and (in the subset) smoking. Sensitivity analyses adjusted for past RA drugs. RESULTS: Among 373,940 new RA subjects, 6343 (1.7%) developed ILD (8.1 events per 1000 person-year, 95% CI 7.9, 8.3). ILD was more common among subjects with baseline COPD. Adjusting for age and sex, the hazard ratio (HR) between baseline COPD and incident ILD was 2.15, 95% CI 1.93, 2.39. We could not establish a clear relationship between current smoking and ILD; in the subset with smoking data, the HR point estimate for COPD was similar but the 95% CI was wider (due to fewer subjects) and included the null value. Adjusting for baseline RA drugs did not change results. CONCLUSIONS: Pre-existing COPD in incident RA subjects was associated with higher risk of future ILD. While a trend persisted after adjusting for smoking, we were limited by reduced sample size. Our study highlights the importance of ongoing assessments of potentially complicated relationships between smoking, COPD, and other factors in RA-associated ILD.

Fine particulate matter components and interstitial lung disease in rheumatoid arthritis.

BACKGROUND: Exposure to ambient fine particulate matter with an aerodynamic diameter <2.5 µg·m-3 (PM2.5) is a risk factor for pulmonary and systemic autoimmune diseases; however, evidence on which PM2.5 chemical components are more harmful is still scant. Our goal is to investigate potential associations between major PM2.5 components and interstitial lung disease (ILD) onset in rheumatoid arthritis (RA). METHODS: New-onset RA subjects identified from a US healthcare insurance database (MarketScan) were followed for new onset of RA-associated ILD (RA-ILD) from 2011 to 2018. Annual concentrations of ambient PM2.5 chemical components (i.e. sulfate, nitrate, ammonium, organic matter, black carbon, mineral dust and sea salt) were estimated by combining satellite retrievals with chemical transport modelling and refined by geographically weighted regression. Exposures from 2006 up to 1 year before ILD onset or end of study were assigned to subjects based on their core-based statistical area or metropolitan division codes. A novel time-to-event quantile-based g (generalised)-computation approach was used to estimate potential associations between RA-ILD onset and the exposure mixture of all seven PM2.5 chemical components adjusting for age, sex and prior chronic obstructive pulmonary disease (as a proxy for smoking). RESULTS: We followed 280 516 new-onset RA patients and detected 2194 RA-ILD cases across 1 394 385 person-years. The adjusted hazard ratio for RA-ILD onset was 1.54 (95% CI 1.47-1.63) per every decile increase in all seven exposures. Ammonium, mineral dust and black carbon contributed more to ILD risk than the other PM2.5 components. CONCLUSION: Exposure to components of PM2.5, particularly ammonium, increases ILD risk in RA.

Treatment patterns and control of hypertension in systemic lupus erythematosus (SLE): a cross-sectional study.

OBJECTIVE: Hypertension (HTN) is common in systemic lupus erythematosus (SLE), representing a key risk factor for cardiovascular and renal disease. We described HTN treatment patterns in SLE, evaluated uncontrolled HTN according to Canadian and American guidelines and identified factors associated with uncontrolled HTN. METHODS: We performed a cross-sectional study, identifying all McGill Lupus Clinic registry patients with an annual visit between January 2017 and May 2019 who were taking HTN medications. We excluded those taking medications only for another indication (eg, Raynaud's). We determined the frequency of uncontrolled HTN according to Canadian and American College of Cardiology/American Heart Association guidelines. Multivariate logistic regression (adjusted for age, sex and race/ethnicity) evaluated if uncontrolled HTN was more common with high body mass index (BMI), longer SLE duration, high disease activity, renal damage, multiple concomitant antihypertensives, prednisone and non-steroidal anti-inflammatory drugs. RESULTS: Of 442 patients with SLE, 108 were taking medications to treat HTN, and 38 took multiple medications concurrently. Angiotensin-receptor blockers were most common, followed by calcium channel blockers, diuretics, angiotensin-converting enzyme inhibitors and beta blockers. Among the 108 patients, 39.8% (n=43) had blood pressure (BP) >140/90 mm Hg, while 66.7% (n=72) had BP >130/80 mm Hg. In multivariate analyses, uncontrolled HTN (>130/80 mm Hg) was more likely in Caucasians (OR 2.72, 95% CI 1.12 to 6.78) and patients with higher BMI (OR 1.08, 95% CI 1.00 to 1.19). Patients with renal damage had better HTN control (OR 0.39, 95% CI 0.16 to 0.97). We could not draw definitive conclusions regarding other variables. CONCLUSION: Caucasians and patients with higher BMI had more uncontrolled HTN. The negative association with renal damage is reassuring, as controlled BP is key for renal protection.

American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.

Myositis in systemic lupus erythematosus.

OBJECTIVES: Myositis is an infrequent feature of SLE and may often be overlooked. We aimed to estimate the incidence of myositis in SLE, and to determine demographic and clinical factors associated with it. METHODS: Within our lupus cohort, we identified potential myositis cases using the SLICC Damage Index for muscle atrophy or weakness, the SLEDAI-2K item for myositis, and annually measured serum creatinine kinase. Cases were confirmed through chart review. We performed descriptive analyses of prevalent myositis cases as of January 2000. From that point onward, we studies patients without myositis to determine risk of incident myositis, using cohort analyses adjusted for demographic variables (age, sex, race/ethnicity). RESULTS: As of January 2000, there were 5 prevalent myositis cases in our SLE cohort. Among 560 SLE patients with a study visit from January 2000 onward, with no history of myositis at baseline, 5 new cases (4 females, 1 male) were identified over an average follow-up of 8.5 years (incidence 1.05 cases per 1000 person-years). There was a higher proportion of Caucasians in the non-myositis group versus myositis group, with a trend for fewer females in the myositis cases. Arthritis, Raynaud's phenomenon, and anti-Smith antibodies were common pre-existing features, occurring in all incident myositis cases. In Cox regression analyses adjusting for age, race/ethnicity and sex, non-Caucasian patients had a markedly increased risk of developing myositis. CONCLUSION: We found a low incidence of myositis in our SLE cohort. A cluster of variables, particularly non-Caucasian race/ethnicity, arthritis, Raynaud's phenomenon, and anti-Smith antibodies were associated with risk of developing myositis in SLE. These variables may aid clinicians in identifying SLE patients at highest risk for this important complication.

CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update.

OBJECTIVE: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. METHODS: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation. RESULTS: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations. CONCLUSION: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.

A multimodal intervention increases influenza vaccine uptake in rheumatoid arthritis.

Annual influenza vaccination is recommended for patients with rheumatoid arthritis (RA), but coverage is suboptimal. We assessed the impact of an implementation strategy in enhancing vaccination uptake in RA. We evaluated a multimodal implementation strategy at rheumatology clinics that included 3 approaches: patient recalls, a nurse providing vaccines, and physician reminders. We compared patient-reported vaccination rates after implementation with those reported before the implementation strategy in a nonequivalent control group. In multivariate analyses, we assessed factors potentially associated with influenza vaccine uptake. One hundred and sixteen RA patients were vaccinated during the intervention. The influenza vaccination rate in RA increased from 48.5% (65/136) before implementation to 62.6% (67/107) after implementation (difference of 14.1, 95% CI 1.5, 26.1). In multivariate analyses, older age, biologics use, and physician recommendation for vaccination were associated with influenza vaccine uptake. A multimodal intervention was associated with increased influenza vaccine coverage among RA patients. Older patients and those on biologics were more likely to be immunized against influenza. Physician's recommendations are important to promote vaccine coverage. Key Points • Despite current recommendations, influenza vaccine uptake among rheumatoid arthritis (RA) patients is suboptimal. • A multimodal implementation strategy facilitating access to influenza vaccine and raising awareness through vaccination reminders improved immunization uptake in RA. • Physicians play a key role in promoting annual seasonal influenza vaccination. • The reasons for vaccine hesitancy in RA should be addressed to reach a vaccination target of 80% required to reduce the burden of this preventable infection.

Retinal Complications in Patients with Systemic Lupus Erythematosus Treated with Antimalarial Drugs.

OBJECTIVE: Hydroxychloroquine (HCQ) and chloroquine (CQ) are key drugs in systemic lupus (SLE) and related diseases. Retinal toxicity remains the most worrisome complication. We studied factors potentially associated with retinal toxicity, using case-control analyses. METHODS: Within our SLE clinic cohort, we identified patients with retinal changes using the Systemic Lupus International Collaborating Clinics Damage Index. We confirmed HCQ/CQ retinopathy with chart review, and selected up to 3 SLE controls for each case, matched by age at SLE diagnosis and SLE duration. RESULTS: Over an average 12.8 years of followup, within 326 patients exposed to antimalarial drugs, 18 (5.5%) developed retinal toxicity. The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years (maximum 33 yrs). Median HCQ/CQ duration was statistically similar in cases [19 yrs, interquartile range (IQR) 14-20] and controls (16 yrs, IQR 11-22), likely due to our matching on SLE duration. Versus controls, cases tended to have more renal disease (cases 22.2%, controls 14.8%) and were slightly less likely to be white (cases 61.1%, controls 74.1%), but neither variable reached statistical significance. Among patients with retinal toxicity, the number previously exposed to CQ was more than 3 times that in controls. CONCLUSION: Just over 5% of patients developed antimalarial retinal complications, over an average of 12.8 years. No cases were detected in the first 5 years of therapy. Past CQ use was more common in cases versus controls. Future studies using larger cohorts are under way to better define the roles of therapy duration, race/ethnicity, and other factors.

Marital status and age of systemic lupus erythematous diagnosis: the potential for differences related to sex and gender.

OBJECTIVES: Chronic rheumatic diseases can challenge social and family relationships. We compared marital status in patients with systemic lupus erythematous (SLE) with their general population counterparts, stratified by sex and age of SLE onset. METHODS: We performed a cross-sectional analysis of a cohort of 382 patients with SLE at our centre (349 females, 33 males). We determined how many were married or living common-law at the time of last study visit. Patients were then divided into: SLE diagnosis before 18, between 18 and 30, between 31 and 44 and after 45 years of age. We then compared marital status among male and female patients with SLE, to Quebec age-specific marital statistics. RESULTS: Of 382 patients with SLE, 202 (52.9%) were married or living common-law, which was 9% lower than general population rates (95% CI 2% to 16%). One-third of women with paediatric-onset SLE were married or living common-law, which was 28% lower than their general population counterparts (95% CI 6% to 46%). Half of women diagnosed between age 18 and 30 were married or living common law, which was 14% less than general population rates (95% CI 4% to 25%). We could not establish significant differences for women diagnosed after age 30, or for males, versus their general population counterparts. CONCLUSIONS: Women diagnosed with SLE before age 30 were less likely to be married/living common-law, versus general population rates. This was not apparent for those diagnosed later in life. We did not clearly establish this effect in males, possibly due to power issues (vs a true effect of sex/gender). Additional studies (eg, focus groups) could elucidate reasons for our findings.

Use of combined hormonal contraceptives among women with systemic lupus erythematosus with and without medical contraindications to oestrogen.

OBJECTIVES: To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. METHODS: This observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. RESULTS: A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. CONCLUSION: CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

Risk of Ocular Anomalies in Children Exposed In Utero to Antimalarials: A Systematic Literature Review.

OBJECTIVE: To determine whether offspring from mothers with systemic lupus erythematosus (SLE), exposed in utero to antimalarials, have an increased risk of ocular anomalies during childhood versus unexposed SLE offspring. METHODS: We systematically performed searches of PubMed, Embase, and Web of Science databases for original human data on fetal and/or child ocular outcomes following exposure to antimalarials during pregnancy and/or lactation, from their inception until March 2017. RESULTS: A total of 10 cohort studies and 2 randomized controlled trials, ranging in size from 6 to 444 exposed infants studied, and 3 case reports met the inclusion criteria for our systematic review. Collectively, 1,477 infants were studied, 789 of which were exposed to hydroxychloroquine or chloroquine. In all, 563 exposed infants had follow-up visits after delivery (ranging from <3 months to 19 years), and 331 of these exposed infants underwent ophthalmologic examinations during the follow-up period. Our review of the literature suggests a low-to-nonexistent risk of visual abnormalities in offspring exposed to antimalarials. CONCLUSION: In children exposed to appropriate doses of antimalarials antenatally, the risk of ocular toxicity appears low to nonexistent. The potential benefits and risks of antimalarials should be discussed in all SLE pregnancies, and high dosages should continue to be avoided.

Brief Report: Risk of Childhood Rheumatic and Nonrheumatic Autoimmune Diseases in Children Born to Women With Systemic Lupus Erythematosus.

OBJECTIVE: Several autoimmune diseases have familial aggregation and, possibly, common genetic predispositions. In a large population-based study, we evaluated whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of rheumatic and nonrheumatic autoimmune diseases versus children born to mothers without SLE. METHODS: Using the Offspring of SLE Mothers Registry, we identified children born live to SLE mothers and their matched controls, and ascertained autoimmune diseases based on ≥1 hospitalization or ≥2 physician visits with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetric complications, calendar birth year, and sex of child. RESULTS: A total of 509 women with SLE had 719 children, while 5,824 matched controls had 8,493 children. The mean ± SD follow-up period was 9.1 ± 5.8 years. Children born to mothers with SLE had a similar frequency of rheumatic autoimmune diagnoses (0.14%; 95% confidence interval [95% CI] 0.01-0.90) versus controls (0.19% [95% CI 0.11-0.32]). There was a trend toward more nonrheumatic autoimmune diseases in SLE offspring (1.11% [95% CI 0.52-2.27]) versus controls (0.48% [95% CI 0.35-0.66]). In multivariate analyses, we did not see a clear increase in rheumatic autoimmune disease (odds ratio [OR] 0.71 [95% CI 0.11-4.82]), but children born to mothers with SLE had a substantially increased risk of nonrheumatic autoimmune disease versus controls (OR 2.30 [95% CI 1.06-5.03]). CONCLUSION: Although the vast majority of offspring have no autoimmune disease, children born to women with SLE may have an increased risk of nonrheumatic autoimmune diseases versus controls. Additional studies assessing offspring through to adulthood would be additionally enlightening.