Setting Of Systemic Lupus Erythematosus Research Articles

Anifrolumab for Moderate and Severe Muco-Cutaneous Lupus Erythematosus: A Monocentric Experience and Review of the Current Literature.

Refractory cutaneous manifestations constitute a significant unmet need in patients with cutaneous lupus (CLE), even in the setting of systemic lupus erythematosus (SLE) with otherwise good control of inflammatory manifestations. Anifrolumab, an anti-interferon I receptor monoclonal antibody has recently been approved for serologically positive SLE with or without CLE, but real-life efficacy and safety data are currently limited. In addition, relatively limited evidence exists about the spectrum of cutaneous manifestations potentially benefitting from anifrolumab treatment and about the optimal clinimetrics to monitor treatment efficacy. While summarising current evidence on the topic in the literature, we report on four patients with SLE and refractory CLE who were successfully treated with anifrolumab. We also describe the potential usefulness and complementarity of the cutaneous lupus activity investigator's global assessment (CLA-IGA) in assessing cutaneous activity in patients treated with anifrolumab.

Massive Right Chylothorax Secondary to a Severe Systemic Lupus Erythematosus Flare With Secondary Evans Syndrome: A Case Report and Literature Review

This case report describes a 23-year-old male patient who presented with right chylothorax as the initial manifestation of a severe flare of systemic lupus erythematosus (SLE) and secondary Evans syndrome. Chylothorax and chylous ascites are rare features of SLE that can occur due to the accumulation of triglyceride-rich fluid in serous cavities. However, they have never been reported as the initial manifestation of a lupus flare. Evans syndrome is a rare disease characterized by autoimmune hemolytic anemia and immune thrombocytopenia, which can be secondary to SLE. The concomitant occurrence of both chylothorax and Evans syndrome in the setting of systemic lupus erythematosus has never been described, and the exact causative mechanisms of both entities are yet to be fully understood. In this report, we discuss our approach to this challenging case to broaden the understanding of the clinical manifestations of systemic lupus erythematosus. Our findings emphasize the importance of considering rare features of systemic lupus erythematosus and secondary diseases when evaluating patients with the disease.

A Case of Cutaneous Vasculitis in the Setting of Systemic Lupus Erythematosus and Cocaine Use.

Cocaine, one of most prevalent illicit substances in the United States, affects a multitude of organ systems and precedes numerous negative health outcomes. Many of the consequences of cocaine are linked to induction of vasoconstriction. For this reason, cocaine users are placed at considerable risk of ischemic stroke, myocardial infarction, and cardiac arrhythmias. Furthermore, a prominent contaminant, levamisole, has been widely implicated in predisposing individuals to developing or exacerbating cutaneous vasculitides. This report details a 31-year-old woman with acute, localized necrotic skin lesions after cocaine use. Her clinical picture was complicated by a 17-year history of systemic lupus erythematosus (SLE) and Raynaud's phenomenon. This case examines the challenge of forming a differential diagnosis, initiating an appropriate workup, and interpreting serologic-based and immunologic-based studies to differentiate between SLE and drug-based etiologies of skin necrosis. Finally, we discuss appropriate treatment plans to mitigate symptoms and reduce future instances of drug-induced vasculitis.

Classification of Systemic Lupus Erythematosus Using Raman Spectroscopy of Blood and Automated Computational Detection Methods: A Novel Tool for Future Diagnostic Testing.

The aim of this study was to explore the proof of concept for using Raman spectroscopy as a diagnostic platform in the setting of systemic lupus erythematosus (SLE). We sought to identify unique Raman signatures in serum blood samples to successfully segregate SLE patients from healthy controls (HC). In addition, a retrospective audit was undertaken to assess the clinical utility of current testing platforms used to detect anti-double stranded DNA (dsDNA) antibodies (n = 600). We examined 234 Raman spectra to investigate key variances between SLE patients (n = 8) and HC (n = 4). Multi-variant analysis and classification model construction was achieved using principal component analysis (PCA), PCA-linear discriminant analysis and partial least squares-discriminant analysis (PLS-DA). We achieved the successful segregation of Raman spectra from SLE patients and healthy controls (p-value < 0.0001). Classification models built using PLS-DA demonstrated outstanding performance characteristics with 99% accuracy, 100% sensitivity and 99% specificity. Twelve statistically significant (p-value < 0.001) wavenumbers were identified as potential diagnostic spectral markers. Molecular assignments related to proteins and DNA demonstrated significant Raman intensity changes between SLE and HC groups. These wavenumbers may serve as future biomarkers and offer further insight into the pathogenesis of SLE. Our audit confirmed previously reported inconsistencies between two key methodologies used to detect anti-dsDNA, highlighting the need for improved laboratory testing for SLE. Raman spectroscopy has demonstrated powerful performance characteristics in this proof-of-concept study, setting the foundations for future translation into the clinical setting.

Epidemiology of interstitial lung disease in systemic lupus erythematosus in France: A nation-wide population-based study over 10 years.

Background and objectiveData regarding interstitial lung disease (ILD) in the setting of systemic lupus erythematosus (SLE) are limited. We used a nationwide database to determine the incidence and the prevalence of ILD in SLE.MethodsCharacteristics of all SLE inpatients admitted between 2011 and 2012 in France were analysed through the French medico‐administrative database. Features associated with the presence of ILD were studied. Cox hazard model was used to measure the impact of ILD on survival from the first stay to 2020. The incidence of ILD in SLE was estimated by analysing the onset of ILD from 2013 to 2020 in SLE patients who had no evidence of ILD in 2013.ResultsBetween 2011 and 2012, 10,460 SLE patients had at least one hospital stay and could be traced until 2020. Among them, 134 (1.2%) had an ILD diagnosed at baseline. The frequency of ILD in SLE was higher in patients who had an associated autoimmune disease such as Sjögren's syndrome or systemic sclerosis (29.9% vs. 5.9%, p < 0.0001). ILD was associated with an increased risk of death in SLE in the multivariable analysis (hazard ratio [95% CI] 1.992 [1.420–2.794]; p < 0.0001). Among the 31,029 SLE patients with no evidence of ILD at baseline, ILD occurred in 795 (2.6%) between 2013 and 2020. The incidence rate of ILD in SLE was 10.26 for 1000 patient‐years [95% CI: 10.24–10.28].ConclusionIn SLE, ILD is exceedingly rare, often associated with another systemic autoimmune disorder and appears as a major risk factor for death.

Regulation of activated T cell survival in rheumatic autoimmune diseases.

Adaptive immune responses rely on the proliferation of T lymphocytes able to recognize and eliminate pathogens. The magnitude and duration of the expansion of activated T cell clones are finely regulated to minimize immunopathology and avoid autoimmunity. In patients with rheumatic autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, activated lymphocytes survive and exert effector functions for prolonged periods, defying the mechanisms that normally curb their capacities during acute and chronic infections. Here, we review the molecular mechanisms that limit the duration of immune responses in health and discuss the factors that alter such regulation in the setting of systemic lupus erythematosus and rheumatoid arthritis. We highlight defects that could contribute to the development and progression of autoimmune disease and describe how chronic inflammation can alter the regulation of activated lymphocyte survival, promoting its perpetuation. These concepts might contribute to the understanding of the mechanisms that underlie the chronicity of inflammation in the context of autoimmunity.

Lupus Vasculitis: An Overview.

Lupus vasculitis (LV) is one of the secondary vasculitides occurring in the setting of systemic lupus erythematosus (SLE) in approximately 50% of patients. It is most commonly associated with small vessels, but medium-sized vessels can also be affected, whereas large vessel involvement is very rare. LV may involve different organ systems and present in a wide variety of clinical manifestations according to the size and site of the vessels involved. LV usually portends a poor prognosis, and a prompt diagnosis is fundamental for a good outcome. The spectrum of involvement ranges from a relatively mild disease affecting small vessels or a single organ to a multiorgan system disease with life-threatening manifestations, such as mesenteric vasculitis, pulmonary hemorrhage, or mononeuritis multiplex. Treatment depends upon the organs involved and the severity of the vasculitis process. In this review, we provide an overview of the different forms of LV, describing their clinical impact and focusing on the available treatment strategies.

P49: Toxic epidermal necrolysis in the setting of systemic lupus erythematosus: a case series

P49: Toxic epidermal necrolysis in the setting of systemic lupus erythematosus: a case series

A RARE CASE OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Systemic lupus erythematosus (SLE) interstitial lung disease (ILD) is a spectrum of disease that is further characterized by histopathology. Among the literature, usual interstitial pneumonia (UIP) appears to be the rarest form. We present a case of a young female with this rare phenomenon. CASE PRESENTATION: A 38 year old female with a history of SLE was evaluated by pulmonology outpatient for progressively worsening dyspnea on exertion. Rest relieved the dyspnea and she could walk approximately 30 feet before having to stop. CT pulmonary angiography was negative for pulmonary emboli but showed peripheral interstitial markings bilaterally, greatest in the lower lobes. Pulmonary function test showed mild to moderate restrictive lung disease. Bronchoscopy, transbronchial biopsy, and serologic workup was negative except for elevated ANA. Since her diagnosis of SLE, she only had known joint involvement. ANA titer was 1:320. A repeat CT chest several months later showed subpleural interstitial markings within both upper lobe zones and more pronounced at the bases. CT surgery evaluated her and performed a video assisted thoracoscopy with biopsy of lower lung. Biopsy revealed a honeycomb pattern suggestive of UIP and idiopathic pulmonary fibrosis (IPF). A second opinion by a pathologist at a large academic center confirmed the initial diagnosis. She required supplemental oxygen for hypoxia on exertion and started mycophenolate with eventual addition of pirfenidone. Her symptoms improved and she is being evaluated for lung transplantation. DISCUSSION: Although SLE-UIP is rare, clinicians should remain diligent about thoroughly reviewing past medical history and having a broad differential for patients presenting with dyspnea. SLE-UIP has multiple forms including acute, subacute, and chronic although most cases have non-specific findings on high resolution CT or histopathology to subclassify the disease [1]. The prognosis is better than IPF/UIP associated with other connective tissue diseases [1,2,3] with a 5 year mortality rate of approximately 85% [1]. Literature on SLE-UIP is predominantly case reports and the ideal treatment has not been identified but most patients receive glucocorticosteroids with addition of immunsuppressive therapy if needed. In our patient, perhaps she will receive a lung transplant. CONCLUSIONS: Usual interstitial pneumonia in the setting of systemic lupus erythematosus is uncommon with few reported cases. To optimize treatment, further studies are warranted. Reference #1: Enomoto N, Egashira R, Tabata K, et al. Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study. Sci Rep. 2019;9(1):7355. Reference #2: Nakamura Y, Chida K, Suda T, et al. Nonspecific interstitial pneumonia in collagen vascular diseases: comparison of the clinical characteristics and prognostic significance with usual interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20(3):235-41. Reference #3: Enomoto N, Suda T, Kato M, et al. Quantitative analysis of fibroblastic foci in usual interstitial pneumonia. Chest. 2006;130(1):22-9. DISCLOSURES: No relevant relationships by Bharat Avirneni, source=Web Response No relevant relationships by Christopher Rosse, source=Web Response No relevant relationships by Christopher Schmitt, source=Web Response

Papulonodular mucinosis in the setting of systemic lupus erythematosus – a diagnostic conundrum

Papulonodular mucinosis in the setting of systemic lupus erythematosus – a diagnostic conundrum

Incidence and characteristics of health care-associated infection in hospitalized patients with rheumatic diseases in Alexandria Main University Hospital

IntroductionHealth care-associated infection (HCAI) is an important cause of morbidity and mortality in patients with autoimmune diseases. Most previous reports investigated HCAI in the setting of systemic lupus erythematosus but lacked reports on other connective tissue diseases.ObjectivesWe aimed to determine the incidence and characteristics of HCAI in patients with rheumatic diseases admitted to the Rheumatology Unit in Alexandria Main University Hospital in 2017.Patients and methodsA 1-year duration prospective observational study was done to elucidate the incidence and characteristics of HCAI in patients with underlying rheumatic diseases who were admitted to our Rheumatology Unit between January 1 and December 31, 2017. Statistical analysis was performed using IBM SPSS Statistics 20. Data are presented as numbers and percentages for categorical variables and means and SDs for continuous variables.ResultsA total of 516 patients [423 (82%) female and 93 (18%) male] with underlying rheumatic diseases and disease duration of 6.03±4.18 years were admitted during the study period. The mean age was 32.18±9.54 years, and the mean length of hospitalizationwas 10.04±5.76 days. HCAI occurred in 14.9%(n=77) of patients, with 81 (15.69%) infection cases (four cases had more than one episode of infection in more than one site with a different organism during the same admission). Gram-negative bacilli were the most commonly isolated organisms (46.3%; n=38), and the urinary tract was the most commonly documented site of infection (39.5%; n=32). Klebsiella spp. (17.9%; n=15) was the most frequently identified infectious agent. Of the total cases with HCAI (n=77), 85.7%(n=66) were cured, 7.8%(n=6) deteriorated, 5.2% (n=4) died, and 1.3% (n=1) referred to another specialized hospital.ConclusionDespite the improvement in health care services, the incidence of HCAI infection in our inpatient population is still high and represents a burden on our resources. Although most cases were treated with appropriate antimicrobials, HCAI is still the cause of deterioration, and death occurred in a considerable percentage of patients with rheumatic diseases.

UnMASking the diagnosis: Acute severe necrotizing pancreatitis in the setting of systemic lupus erythematosus complicated by macrophage activation syndrome

Systemic lupus erythematosus (SLE) is a common rheumatologic condition with known GI involvement. Acute pancreatitis (AP) is a rare GI complication of SLE and is typically associated with increased disease activity. Macrophage activation syndrome (MAS) is an unusual, hyper-inflammatory response to a rheumatologic stimulus characterized by hyperferritinemia, pancytopenia, thermal dysregulation and multi-organ dysfunction. MAS, more commonly seen in children, has been reported to complicate both adult onset SLE and AP. We present a case of necrotizing AP secondary to an SLE flare complicated by MAS in an adult patient successfully treated with anakinra.

Posterior Reversible Encephalopathy Syndrome in Class IV Lupus Nephritis – Case report and brief review of literature

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiographic syndrome characterized clinically by new onset neurological manifestations as well as neuroimaging findings of reversible cerebral edema. We report a case of PRES in the setting of systemic lupus erythematosus (SLE) with new-onset Class IV Nephritis treated with pulse corticosteroids, plasma exchange, intravenous immunoglobulin (IVIG) and cyclophosphamide. We also present a brief review of the associations between PRES and SLE.

Nonbullous neutrophilic lupus erythematosus: A newly recognized variant of cutaneous lupus erythematosus

Neutrophils in the setting of systemic lupus erythematosus (SLE) are commonly associated with bullous disease. Rare cases of nonbullous neutrophilic lesions have been reported in patients with SLE. This study used clinical and histologic findings of 4 patients to further define the newly emerging entity of nonbullous neutrophilic lupus erythematosus (LE). We reviewed the clinical and pathological findings of 4 patients with known SLE who developed urticarial papules, plaques, subcutaneous nodules, or a combination of these. All patients were women with established SLE. Histopathological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, and variable vacuolar alteration along the dermoepidermal junction. Direct immunofluorescence study results in two patients were positive for C3, IgG, and IgM along the basement membrane zone. One patient also presented with neutrophil-rich lupus panniculitis. All clinical lesions resolved with immunomodulating/immunosuppressive agents. This study was limited by the small number of cases. Nonbullous neutrophilic LE is an important entity to consider in the differential diagnosis of neutrophil-mediated eruptions. In addition, the histologic finding of neutrophils in the setting of lupus should alert one to the possibility of systemic disease.

Cigarette Smoking and Response to Antimalarials in Cutaneous Lupus Erythematosus Patients: Evolution of a Dogma

Antimalarial agents ameliorate disease in more than half of patients with cutaneous lupus erythematosus (CLE), regardless of smoking status. The major determinant of responsiveness appears to be severity: more extensive CLE and CLE in the setting of systemic lupus erythematosus (SLE) respond less well to antimalarial therapy. Prospective studies are needed to determine whether antimalarials are more likely to benefit patients--smokers and nonsmokers--who have milder cutaneous lupus. Agreement on a single, validated disease severity measure for CLE would permit comparisons among studies and thereby foster progress in the field.

A woman with severe lupus nephritis and difficult to control diabetes mellitus

A woman with severe lupus nephritis and difficult to control diabetes mellitus

Rituximab Therapy for Refractory Thrombotic Thrombocytopenic Purpura and Autoimmune-Mediated Thrombocytopenia in Systemic Lupus Erythematosus

Thrombotic thrombocytopenic purpura (TTP) rarely occurs in the setting of systemic lupus erythematosus (SLE); when it does occur it has a high mortality rate and is refractory to conventional treatment. No clear treatment guidelines exist when refractory TTP occurs in the setting of SLE. A 24-year-old male patient presented with TTP in the setting of SLE that was refractory to conventional treatment but responded to rituximab.

High prevalence of infections in patients with systemic lupus erythematosus and pulmonary haemorrhage

The main objective of this study is to describe the presence of infections in patients with pulmonary haemorrhage and systemic lupus erythematosus. Patients with systemic lupus erythematosus and pulmonary haemorrhage were thoroughly evaluated in the first 48 hours with imaging plus bronchoscopy and bronchoalveolar fluid analysis. If needed, videoassisted thoracoscopy and lung biopsy were performed too. In all, search for bacterial, mycobacterial and fungal infections proceeded. Appropriate blood, bronchoalveolar fluid and tissue cultures were taken. Patients were treated with antibiotics and corticosteroids in case of infection. Otherwise, they received initial intravenous methylprednsiolone pulses for 3 days as standard therapy for pulmonary haemorrhage in systemic lupus erythematosus. Additional treatment with immunosuppressives was further decided by the treating physicians. Fourteen events in 13 patients were evaluated. In eight events (57%), an infection was demonstrated. Aetiological agents included Pseudomonas sp. and Aspergillus fumigatus. Four patients died, three of them because of the pulmonary infection and one because of cerebral haemorrhage secondary to severe systemic hypertension, 48 hours after methylprednisolone treatment. Patients with systemic lupus erythematosus and pulmonary haemorrhage have a high prevalence of infections. The influence of pulmonary haemorrhage in the setting of systemic lupus erythematosus needs further study to establish adequate treatment and to reduce the high mortality of this complication.

The biology of nitric oxide and other reactive intermediates in systemic lupus erythematosus

Formation of reactive nitrogen and oxygen intermediates (RNI and ROI) is an essential part of the innate immune response. Markers of systemic RNI production are increased in the setting of systemic lupus erythematosus (SLE) activity. Several lines of evidence suggest mechanisms through which the activity of inducible nitric oxide synthase (iNOS) is pathogenic in SLE, including the ability of peroxynitrite (ONOO −, a product of iNOS activity) to modify proteins, lipids, and DNA. These modifications can alter enzyme activity and may increase the immunogenicity of self antigens, leading to a break in immune tolerance. In humans, observational data suggest that overexpression of iNOS and increased production of ONOO − lead to glomerular and vascular pathology. Therapies designed to target iNOS activity or scavenge ROI and RNI are in development and may provide the means to reduce the pathogenic consequences of ROI and RNI in SLE.

Primary versus secondary antiphospholipid syndrome: Is this lupus or not?

Antiphospholipid syndrome is a hypercoaguable state characterized by recurrent venous and/or arterial thrombosis and/or pregnancy complications of fetal loss, pre-eclampsia, or eclampsia in the presence of antiphospholipid antibodies. It was first described in the setting of systemic lupus erythematosus and subsequently recognized to also exist as an independent condition and in conjunction with a variety of other autoimmune, infectious, and malignant illnesses. These diseases have been called primary antiphospholipid syndrome and secondary antiphospholipid syndrome. However, the two conditions can have significant overlapping features. This paper reviews the similarities and the differences between the two conditions.