Factors associated with cardiovascular events in systemic lupus erythematosus in a monocentric cohort with up to 40 years of follow-up.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with an increased cardiovascular risk. Several traditional and disease-specific risk factors have been shown to correlate with the occurrence of cardiovascular events (CVE) in patients with SLE. However, results of previous studies are diverse. The objectives of this study were to report number, type and those factors associated with CVE in patients with SLE in a large, single-center, ethnically diverse cohort with a long follow-up duration. METHODS: Medical records of patients treated at the Lupus Clinic at University College London Hospital (UCLH) between 1979 and 2020 were retrospectively reviewed. Data about CVE, traditional cardiovascular risk factors, demographic and disease features, and treatment history were collected. Only patients with complete available information were included in the study. Regression analyses were performed to identify factors associated with CVE. RESULTS: Four hundred and nineteen patients were included in the study. Maximum follow-up length was 40 years. Seventy-one (17%) patients had at least one CVE. Multivariable analysis showed that only antiphospholipid antibody positivity (p-value<0.001) was associated with CVE. When analysing different types of CVE, antiphospholipid antibodies were specifically associated with both venous thromboembolic events (p-value<0.001) and cerebrovascular events (p-value=0.007). Dedicated subanalyses revealed that cumulative glucocorticoid dose (p-value=0.010) and a diagnosis of SLE before 2000 (p-value<0.001) were significantly associated with CVE. CONCLUSIONS: Cardiovascular disease is highly prevalent among patients with SLE and is associated with antiphospholipid antibodies, glucocorticoid therapy, and diagnosis before 2000.

Fracture risk in systemic lupus erythematosus patients over 28 years.

OBJECTIVES: Chronic glucocorticoid use is complicated by osteoporosis and increases the risk of fragility fractures. EULAR guidelines on SLE management recommend reducing chronic glucocorticoid dosage to ≤7.5 mg/day to minimize this risk. We examined the relationship of glucocorticoid dose to fragility fracture risk in a cohort of SLE patients. METHODS: Retrospective analysis of SLE patients attending University College Hospital over 28 years was undertaken. Collected data included consecutive steroid dose, dual-energy X-ray absorptiometry scans and fragility fractures. RESULTS: We collected data on 250 patients with a median of 17 years' follow-up. Fragility fractures were diagnosed in 28 (11.2%) patients and the mean ± s.d. age of first fracture was 51 ± 16 years. A total of 94% received glucocorticoids, the average dose being 6.20 mg/day. Patients with fragility fractures had a lower average daily dose (5.36 vs 6.23 mg/day) but a higher median cumulative dose (25.19 vs 20.96 g). These differences were not significant (P = 0.127 and 0.229, respectively). Some 93% of patients received vitamin D, and 85% received calcium. Cox regression analysis showed older age at SLE diagnosis, osteoporosis and secondary hyperparathyroidism were associated with fragility fractures. Glucocorticoid dose was not significantly associated with the occurrence of fragility fractures. Twenty-two patients with fractures were treated with bisphosphonates, two with denosumab and two with teriparatide. CONCLUSIONS: We found no significant association between glucocorticoid treatment and fragility fractures in our group of patients; however, a prospective study including more patients not treated with CS would be necessary to confirm these results.

Rheumatic manifestations among cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. AIM: To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts. RESULTS: Rheumatic manifestations were encountered in 14 of 400 patients (3.5%) who had received immunotherapy between January 1st 2013 and April 30th, 2017. The most common rheumatic manifestation was inflammatory arthritis (85%) for which a third (4/11) had a clear cut predisposing factor such as a personal or family history of psoriasis, a prior episode of uveitis or ACPA positivity. Pulmonary sarcoidosis and biopsy-proven eosinophilic fasciitis were diagnosed in two additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid therapy was beneficial in doses ≥20 mg/d. Methotrexate enabled steroid tapering without an excess of side effects or tumor progression in the short follow-up available. Overall, rheumatic manifestations tended to occur later in the course of immunotherapy as compared to other iAE. CONCLUSIONS: Our findings underscore that rheumatic iAE are part of the side effect profile of ICIs and require heightened awareness as these therapies are becoming the standard of care for various malignancies. We show that these appear later in the course of iAEs and respond preferentially to high dose steroids. MTX appears effective as a steroid sparing agent.

Plaque morphea with neurological involvement­an extraordinary uncommon presentation.

Localized scleroderma is traditionally considered to be limited to the skin, subcutaneous tissue, underlying bone, and in the craniofacial subtype, also nervous system involvement. However, recent studies have also described other systemic manifestations in these patients. Despite many reports of neurological involvement in patients with the craniofacial linear localized scleroderma, it is extremely rare in patients with the other subtypes of localized scleroderma. Here, we report an extraordinary case of localized scleroderma en plaque (classic morphea), located to the upper trunk and neck, associated with neurological manifestations presented as seizures. Magnetic resonance imaging of the brain showed focal lesions on the contralateral side to the skin involvement. This case is extremely relevant not only due to its rarity, but also because it supports the idea that the pathogenesis of the localized scleroderma is related to a systemic autoimmune process.