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Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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SESSION TITLE: Rare Cases with Masquerading Pulmonary Symptoms SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Paget-Schroetter (PS) syndrome, also known as venous thoracic outlet syndrome, is a primary thromboembolic sequela of compression of the subclavian vein. CASE PRESENTATION: A previously healthy 24 year old male presented with shortness of breath and cough. He had recently been exposed to COVID. He denied fever, diarrhea, vomiting, leg swelling, and rashes. On physical exam he was tachycardic, had no murmurs or JVD, and was CTAB with no wheezing or rales. Labs were significant for a WBC of 17k, and troponin of 0.033. CTA of the chest showed multiple filling defects in the pulmonary arteries consistent with Pulmonary Embolism (PE). He was started on a heparin drip. All COVID testing was negative. Lower extremity venous doppler ultrasounds (US) were negative for DVT. His respiratory status improved, and he was discharged on apixaban with the diagnosis of PE provoked by possible COVID infection. He returned approximately 2 months later with exertional dyspnea and upper extremity swelling and was found to have recurrent PE despite having been compliant with his apixaban. Upper extremity venous doppler US was significant for DVT in his right subclavian vein. He was placed on warfarin. At this time his hypercoagulable workup was also negative. Symptoms persisted despite being on warfarin with outpatient monitored INR. A venogram was ordered to evaluate upper torso blood flow. The venogram was remarkable for high-grade stenosis of the right subclavian vein. This finding led to the consideration of thoracic outlet syndrome aka Paget-Schroetter (PS). DISCUSSION: PS is a rare clinical entity that results from stress placed on the endothelium of the subclavian vein as it passes between the junction of the first rib and the clavicle. It can predispose otherwise healthy patients to recurrent venous thromboembolisms that are refractory to anticoagulation. The clinical features usually include upper extremity swelling and pain which is exacerbated by repetitive or strenuous exercise. Venous collaterals can also be seen in some patients. Evaluation should include some form of upper extremity Doppler and a CT/MR venogram or venography to make the final diagnosis. Treatment may involve anticoagulation, thrombolysis, and/or surgical decompression. Best results are seen with early thrombolysis and surgical decompression. If caught early and treated appropriately, PS has a good outcome with few long-term sequela. CONCLUSIONS: Our goal was to describe a patient with an uncommon cause for recurrent venous thromboembolisms that were refractory to anticoagulation. Our patient's presentation of PS serves to describe many aspects of the disease process, evaluation, diagnosis, and management as seen in the case presentation. The patient's demographic fit the epidemiological profile age of 20s-30s with typical imaging findings and pertinent negative workup which would lead providers to this rarer diagnosis. Reference #1: Saleem T, Baril DT. Paget Schroetter Syndrome. [Updated 2022 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK482416/ Reference #2: Alla VM, Natarajan N, Kaushik M, Warrier R, Nair CK. Paget-schroetter syndrome: review of pathogenesis and treatment of effort thrombosis. West J Emerg Med. 2010;11(4):358-362. Reference #3: Karl A. Illig, Adam J. Doyle, A comprehensive review of Paget-Schroetter syndrome, Journal of Vascular Surgery, Volume 51, Issue 6, 2010,Pages 1538-1547,ISSN 0741-5214, https://doi.org/10.1016/j.jvs.2009.12.022. DISCLOSURES: No relevant relationships by Jonathan Marks No relevant relationships by Zachary Stachura