Description of therapeutic strategies in severe systemic lupus erythematosus-associated immune thrombocytopenia: a retrospective cohort study of response and relapse.

OBJECTIVES: To describe the response and relapse of severe thrombocytopenia in patients with systemic lupus erythematosus (SLE) with different treatments. METHOD: We performed a retrospective cohort study, which included SLE patients who were hospitalized for thrombocytopenia of less than 30,000/µL platelets, from January 2012 to December 2021. Demographic and clinical information was obtained from clinical records. Kaplan-Meier and logrank test were performed. RESULTS: Forty-seven patients, mostly women (83%) with a median age of 31 years, were included in the study. Eight patients (17%) relapsed within a median period of 35.7 weeks. Initial acute treatment with prednisone at 1 mg/kg/day was as effective as glucocorticoid pulses. However, induction treatment with cyclophosphamide (CYC) had the lowest remission rate (43%, p = 0.034). There was no significant difference in relapse-free survival (RFS) among the acute glucocorticoid treatments. CYC induction was associated with lower RFS compared to rituximab (RTX) (CYC 43.6 weeks vs. RTX 51.8 weeks, p = 0.040) or azathioprine (AZA) (CYC 43.6 weeks vs. AZA 51.2 weeks, p = 0.024). Administration of antimalarials was associated with longer RFS (51.6 weeks vs. 45.0 weeks, p = 0.021). Factors such as antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, renal and additional hematologic SLE activity during follow-up significantly reduced RFS. CONCLUSIONS: Despite similar response of acute glucocorticoid regimens, induction therapy with AZA or RTX resulted in a longer RFS compared to CYC. Adding an antimalarial also improved RFS. Our study provides evidence that may help develop better treatment strategies for severe thrombocytopenia in SLE patients. Key Points • Induction therapy with azathioprine or rituximab provided longer relapse-free survival in SLE thrombocytopenia compared with cyclophosphamide. • Antimalarial administration was associated with longer relapse-free survival in SLE thrombocytopenia. • Antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, as well as renal and additional hematologic SLE activity during follow-up, decreased relapse-free survival.

A cross sectional study assessing steatotic liver disease in patients with systemic lupus erythematosus.

Patients with immune-mediated inflammatory diseases are prone to steatotic liver disease (SLD), which has been observed in patients with psoriasis and hidradenitis suppurativa. We aimed to assess whether systemic lupus erythematosus (SLE) was associated with SLD and to define factors associated with SLD in SLE. This was a cross-sectional study, we included 106 consecutive patients with SLE who were seen in the rheumatology clinic between June 2021 and March 2022 and we chose two sex-paired controls for each SLE. All the participants underwent FibroScan and anthropometric assessments. SLD was defined as a controlled attenuation parameter ≥ 275dB/m. Prevalence of SLD was lower in patients with SLE (21.7% vs 41.5%, p < 0.001). Patients with SLE and SLD had a lower frequency of hydroxychloroquine use (65% vs 84%, p = 0.04), and higher C3 levels [123mg/dl (IQR 102-136) vs 99mg/dl (IQR 78-121), p = 0.004]. Factors associated with SLD in SLE were body mass index (BMI), waist circumference, glucose, and C3; hydroxychloroquine use was a protective factor. On univariate analysis, SLE was associated with a reduced risk of SLD (OR 0.39, 95%CI 0.23-0.67); however, after adjusting for age, BMI, waist, glucose, triglycerides, high-density cholesterol, low-density cholesterol, leukocytes, and hydroxychloroquine, it was no longer associated (OR 0.43, 95%CI 0.10-1.91). In conclusion, the prevalence of SLD in patients with SLE was not higher than that in the general population, and SLE was not associated with SLD. The factors associated with SLD were anthropometric data, glucose, hydroxychloroquine, and C3 levels.

Addressing the unspoken: sexual dysfunction in men with systemic lupus erythematosus, a call to action for rheumatologists.

INTRODUCTION: Sexual dysfunction (SD) is highly prevalent and multifactorial; nevertheless, recent research has shed light on a notable phenomenon: male patients with systemic lupus erythematosus (SLE) exhibit an elevated prevalence of sexual function disorders compared with the general population. Despite this recognition, the precise nature and extent of this association remain incompletely understood. OBJECTIVES: This comprehensive review aims to clarify the link by providing an overview of the fundamental components of normal male sexual function, delving into the pathogenesis of male SD and exploring the primary factors predisposing male SLE patients to SD. Additionally, the review offers insights into potential screening, diagnostic, and treatment strategies based on the current body of literature. METHODS: A meticulous search of relevant literature was conducted using the PubMed and Google Scholar databases. RESULTS: Studies exploring the correlation between SLE and SD in both genders have revealed a nearly 2-fold increased risk of SD among individuals with SLE compared with healthy counterparts. Moreover, these studies suggest that male SLE patients may have a higher susceptibility to SD, with reported prevalence ranging from 12% to 68%, compared with 0% to 22% in healthy individuals. Male patients with SLE are influenced by a spectrum of pathological factors, including pharmacological, psychological, and disease-related determinants, which, through their intricate interplay, elevate the likelihood of developing SD. CONCLUSION: Healthcare professionals must remain vigilant in understanding the intricacies of human sexuality and its dysfunction, particularly in males with SLE. The objective is to establish effective and potentially standardized methods for promptly diagnosing and optimally managing SD, recognizing its significant impact on the quality of life for males living with SLE. The pivotal role of rheumatologists in initiating discussions about sexual health, diagnosing SD, investigating causes, and implementing tailored strategies is underscored as crucial in addressing this multifaceted issue.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

Neutrophil extracellular trap-associated carbamylation and histones trigger osteoclast formation in rheumatoid arthritis.

OBJECTIVE: Neutrophil infiltration into the synovial joint is a hallmark of rheumatoid arthritis (RA), a disease characterised by progressive bone erosion. However, the mechanisms by which neutrophils participate in bone destruction remain unclear. Carbamylation is a posttranslational modification linked to increased bone erosion in RA and we previously showed that carbamylation is present in RA neutrophil extracellular traps (NETs). However, it remains unclear whether NETs and their carbamylated protein cargo directly promote bone destruction and alter osteoclast biology. METHODS: NETs and carbamylated NETs (cNETs) were assessed for their capacity to induce osteoclast formation in CD14+ monocytes. Chemical inhibitors and neutralising antibodies were used to elucidate the pathway by which NETs induce osteoclastogenesis. HLA-DRB1*04:01 mice received intra-articular injection of cNETs for 4 weeks. Joints were isolated and assessed for osteoclast formation. Plasma and synovial fluid samples from patients with RA (n=32) were assessed for the presence of carbamylated histone, and correlations to disease specific outcomes were performed. RESULTS: We found that NETs, when cNETs, instruct monocytes to undergo rapid osteoclast formation. NET-mediated osteoclastogenesis appears to depend on Toll-like receptor 4 signalling and NET-associated proteins including histones and neutrophil elastase. In vivo, we identified that the number of osteoclasts increased following immunisation with cNETs in HLA-DRB1*04:01 transgenic mice. Furthermore, carbamylated histones are increased in plasma and synovial fluid from patients with RA and correlate with active bone resorption and inflammatory markers. CONCLUSIONS: Our results suggest that NETs have a direct role in RA-associated bone erosion by promoting osteoclast formation.

Patient-reported outcomes in ANCA-associated vasculitis: a cross-sectional study to explore the interactions between patients' and physicians' perspectives.

To evaluate associations between the domains of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) instrument and clinical variables. Patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), or renal-limited vasculitis (RLV) were recruited from a tertiary care center in Mexico City. Demographic, clinical, serological, and treatment-related data were retrieved. Disease activity, damage, patient and physician global assessments (PtGA and PhGA) were evaluated. All patients completed the AAV-PRO questionnaire, male patients also completed the International Index of Erectile Function (IIEF-5) questionnaire. Seventy patients (44 women and 26 men) were included, with a median age of 53.5 years (43-61), and a disease duration of 82 months (34-135). Moderate correlations were identified between the PtGA and the AAV-PRO domains: social and emotional impact, treatment side effects, organ-specific symptoms, and physical function. The PhGA correlated with the PtGA and prednisone doses. Subanalyses of the AAV-PRO domains according to sex, age, and disease duration showed significant differences in the treatment side effects domain, with higher scores in women, in patients < 50 years, and in patients with disease duration < 5 years. The domain of concerns about the future showed a higher score in patients with disease duration < 5 years. A total of 17/24 (70.8%) of men who completed the IIEF-5 questionnaire were classified as having some degree of erectile dysfunction. The domains of AAV-PRO correlated with other outcome measures, while differences were found between some of the domains according to sex, age, and disease duration.

Posterior reversible encephalopathy syndrome during convalescence from COVID-19.

Background and aim: With an ever-increasing population of patients recovering form severe coronavirus disease 2019 (COVID-19), recognizing long-standing and delayed neurologic manifestations is crucial. Here, we present a patient developing posterior reversible encephalopathy syndrome (PRES) in the convalescence form severe coronavirus disease 2019 (COVID-19).Case presentation: A 61-year-old woman with severe (COVID-19) confirmed by nasopharyngeal real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) required invasive mechanical ventilation 24-hours after admission. During her intensive care unit stay, she developed transient acute kidney injury and septic shock. She was extubated after 22 days. On day 25, she developed generalized tonic-clonic seizures. Magnetic resonance imaging (MRI) of the brain showed bilateral subcortical lesions on the parietal and occipital lobes and multiple micro-and macro-bleeds, consistent with PRES. At this point, RT-PCR for SARS-CoV-2 in a respiratory specimen and cerebrospinal fluid was negative. She was discharged home 35 days after admission on oral levetiracetam. Control MRI five months after discharge showed bilateral focal gliosis. On follow-up, she remains seizure-free on levetiracetam.Conclusions: PRES has been observed before as a neurological manifestation of acute COVID-19; to our knowledge, this is the first PRES case occurring in a hospitalized patient already recovered from COVID-19. A persistent proinflammatory/prothrombotic state triggered by SARS-CoV-2 infection may lead to long-standing endothelial dysfunction, resulting in delayed PRES in patients recovering from COVID-19. With a rapid and exponential increase in survivors of acute COVID-19, clinicians should be aware of delayed (post-acute) neurological damage, including PRES.

Splenectomy outcomes in patients with autoimmune cytopenias and persistent antiphospholipid antibodies.

BACKGROUND: Splenectomy is a therapy for patients with treatment-refractory autoimmune cytopenias. Antiphospholipid antibodies (aPL) can be identified in 25%-85% of these patients. In this study, we sought to identify whether the presence of aPL was associated with worse outcomes in autoimmune cytopenia's patients who had undergone splenectomy. METHODS: We conducted a retrospective cohort study of patients who underwent splenectomy from 2000 to 2018. We describe clinical characteristics and outcomes in patients with autoimmune cytopenia's diagnosis with positive determinations of aPL. Additionally, we performed a case-control sub-analysis 1:1 of the cases with autoimmune cytopenia's matched control patients with negative aPL determination. RESULTS: A splenectomy was performed in 707 patients, of which we included 34 for the analysis. The median age at the time of splenectomy was 37 years (range 19-61), 53% corresponded to immune thrombocytopenia (ITP) and 47% to autoimmune hemolytic anemia (AIHA). Compared with controls (n = 34), patients had more treatment lines in addition to steroids (p = .02). There were no differences in complete response rate, 65% in cases and 80% in controls (p = .17). However, there was numerically a higher incidence of early infections (21% of cases vs. 3% controls, p = .05). During the entire follow-up, 15% of aPL patients compared with 9% of control patients had a thrombotic event (p = .70). DISCUSSION: Splenectomy for treatment-refractory autoimmune cytopenia's patients with persistent aPL is an effective treatment despite some safety concerns related to early infections. These results suggest that the presence of aPL should not impact the decision to undergo splenectomy.

Determinants of sexual function in male patients with systemic lupus erythematosus.

OBJECTIVES: Our study aims to describe the association between SLE and sexual function, analysing demographic variables, comorbidities and other disease-related factors. As an exploratory objective, the impact of asking about sexual function during outpatient consultation was evaluated. METHODS: From 2018 to 2019, we invited sexually active men diagnosed with SLE to complete questionnaires that evaluated their sexual function and quality of life. Additionally, patients were asked if they believed they had sexual dysfunction, whether they would be interested in receiving specialized sexual care, and if they considered SLE to be detrimental to their sexual function. Epidemiological and disease-related data were retrieved from the patients' clinical records. RESULTS: We included 124 men with SLE. Twenty-two (18%) patients answered positively when asked if they believed they had sexual dysfunction. These patients had lower overall erectile function scores and lower physical function scores than those who did not consider they had sexual dysfunction. In the multivariable analysis, factors that were associated with better sexual function were high physical function (B = 0.126, p = .031), lower BMI (B = 0.53, p = .010) and the patient's perception of normal sexual function (B = 13.0, p < .001). Comorbidities associated with worse sexual function were type 2 diabetes (B = -8.1, p = .017) and a history of thrombosis (B = -5.12, p = .019). CONCLUSION: Sexual function of male patients with SLE is impaired, independently of disease activity, chronic disease damage or pharmacological treatment. A simple question about perception of sexual function in the outpatient clinic can be used to help determine which patients could benefit from a multidisciplinary intervention to improve sexual health.

Primary meningococcal septic arthritis associated with joint calcium oxalate crystals: A case report and review of the literature.

Primary meningococcal septic arthritis (PMSA) is an extremely rare local infection by Neisseria meningitidis in the absence of meningitis or meningococcaemia syndrome. A 30-year-old healthy, immunocompetent man presented with arthralgia, fever, chest rash, and significant swelling of the right knee. On admission, a disseminated maculopapular and purpuric rash, oligoarthritis, neutrophilia, and elevated acute phase reactants were documented. Following arthrocentesis of the right knee, isolation of N. meningitidis and the presence of calcium oxalate crystals in the synovial fluid were reported. The diagnosis of PMSA was made. Histological analysis of the skin lesion showed leucocytoclastic vasculitis. He was treated with intravenous ceftriaxone plus open surgical drainage and ambulatory cefixime with adequate response. After 1 month, he presented resolution of the pathological process. We performed an extensive review of the literature, finding that the key elements supporting the diagnosis of PMSA are prodromal upper respiratory tract symptoms and skin involvement prior to or synchronous with the arthritis. Also, the most frequently involved joint is the knee. This report is the first case of a patient presenting with PMSA associated with calcium oxalate crystals in the synovial fluid. Herein, we discuss the most frequent clinical manifestations, the unusual histological features, the recommended treatment, and the reported prognosis of this rare entity.

COVID-19-related diffuse posthypoxic leukoencephalopathy and microbleeds masquerades as acute necrotizing encephalopathy.

BACKGROUND: The complications of coronavirus disease 2019 (COVID-19), the clinical entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are not limited to the respiratory system. Leukoencephalopathy with microbleeds is increasingly seen in patients with COVID-19. New information is needed to delineate better the clinical implications of this infectious disease. CASE REPORT: A 46-year-old man with confirmed SARS-CoV-2 infection was admitted to the intensive care unit (ICU) with severe COVID-19. After transfer to the general wards, the patient was noted drowsy, disorientated, with slow thinking and speech. A brain MRI showed bilateral symmetrical hyperintense lesions in the deep and subcortical whiter matter, involving the splenium of the corpus callosum, as well as multiple microhemorrhages implicating the splenium and subcortical white matter. No contrast-enhanced lesions were observed in brain CT or MRI. CSF analysis showed no abnormalities, including a negative rtRT-PCR for SARS-CoV-2. An outpatient follow-up visit showed near-complete clinical recovery and resolution of the hyperintense lesions on MRI, without microbleeds change. CONCLUSION: We present the case of a survivor of severe COVID-19 who presented diffuse posthypoxic leukoencephalopathy, and microbleeds masquerading as acute necrotizing encephalopathy. We postulate that this kind of cerebral vasogenic edema with microbleeds could be the consequence of hypoxia, inflammation, the prothrombotic state and medical interventions such as mechanical ventilation and anticoagulation.

Rheumatological Adverse Events of Cancer Therapy with Immune Checkpoint Inhibitors.

Latin America is experiencing a demographic and epidemiological transition, with an increase in non-communicable diseases such as cancer. One of the greatest advances in the therapeutic approach to cancer has been the discovery of immunotherapy, and specifically of checkpoint inhibitors (CPIs). Since inhibition of CTLA-4 and PD-1/PD-L1 enhances the immune response, cancer immunotherapies are associated with a new class of toxicities of autoimmune and/or autoinflammatory origin. These immune-related adverse events (irAEs) result in a broad spectrum of clinical events including rheumatic clinical syndromes, which may resemble classic rheumatic diseases. The most common rheumatic manifestations include inflammatory arthritis, myositis, vasculitis, and sicca syndrome. Recognizing rheumatologic irAEs is challenging due to the wide spectrum of clinical presentations that often do not fulfill traditional classification criteria of rheumatic diseases. A delayed diagnosis and treatment can lead to long-term disability, and disorders may become chronic and require ongoing immunosuppressive therapy. The management of irAEs includes the prompt detection and appropriate grading since their management is dictated by their severity. The growing use of CPIs, and the ensuing increase in irAEs, warrants an increasing collaboration between rheumatologists and oncologists. Understanding the pathophysiology, diagnosis, grading, and therapeutic implications of irAEs in patients with cancer is thus a requirement for Latin American oncologists and rheumatologists alike.

Anti-Carbamylated LL37 Antibodies Promote Pathogenic Bone Resorption in Rheumatoid Arthritis.

Objective: Antibodies against carbamylated proteins (anti-CarP) are associated with poor prognosis and the development of bone erosions in rheumatoid arthritis (RA). RA neutrophils externalize modified autoantigens through the formation of neutrophil extracellular traps (NETs). Increased levels of the cathelicidin LL37 have been documented in the synovium of RA patients, but the cellular source remains unclear. We sought to determine if post-translational modifications of LL37, specifically carbamylation, occur during NET formation, enhance this protein's autoantigenicity, and contribute to drive bone erosion in the synovial joint. Methods: ELISA and Western blot analyses were used to identify carbamylated LL37 (carLL37) in biological samples. Anti-carLL37 antibodies were measured in the serum of HLA-DRB1*04:01 transgenic mice and in human RA synovial fluid. Results: Elevated levels of carLL37 were found in plasma and synovial fluid from RA patients, compared to healthy controls. RA NETs release carLL37 and fibroblast-like synoviocytes (FLS) internalized NET-bound carLL37 and loaded it into their MHCII compartment. HLA-DRB1*04:01 transgenic mice immunized with FLS containing NETs developed autoantibodies against carLL37. Anti-carLL37 antibodies were present in RA sera and synovial fluid and they correlated with radiologic bone erosion scores of the hands and feet in RA patients. CarLL37-IgG immune complexes enhanced the ability of monocytes to differentiate into osteoclasts and potentiated osteoclast-mediated extracellular matrix resorption. Conclusions: NETs are a source of carLL37 leading to induction of anti-carbamylated autoantibody responses. Furthermore, carLL37-IgG immune complexes may be implicated in the bone damage characteristic of RA. These results support that dysregulated NET formation has pathogenic roles in RA.

Mental health in patients with rheumatic diseases related to COVID-19 pandemic: Experience in a tertiary care center in Latin America.

OBJECTIVE: To determine the factors associated with anxiety, depression, and concern within the COVID-19 pandemic in a population with autoimmune diseases. METHODS: A telephonic survey was conducted during the early stages of the pandemic in a tertiary care center, which included patients with systemic autoimmune diseases. Mental health variables were assessed with Patient Health Questionnaire 2, General Anxiety Disorder 7 scores, and pandemic-related concern questions. Sociodemographic aspects were also evaluated. RESULTS: Of the total 334 participants, 291 (87.1%) were women, with a median age of 46 years; systemic lupus erythematosus (SLE) was the most frequent diagnosis (144, 43.2%); 44 patients (13.2%) showed depression and 32 (9.6%) anxiety. The variables associated with depression were all the pandemic concern items, body mass index, anxiety, and a higher COVID-19 symptom score. Anxiety was associated with depression, all pandemic concern items, and a higher COVID-19 symptom score. Women presented higher scores in all concern items. The SLE group presented higher scores in concern questions and difficulty finding medication. CONCLUSION: During the COVID-19 outbreak, rheumatic patients are vulnerable to psychiatric conditions, which makes it imperative for physicians who treat these patients to pay careful attention in order to detect them promptly and to settle coping strategies.

Cutaneous manifestations are frequent and diverse among patients with rheumatoid arthritis and impact their quality of life: a cross-sectional study in a cohort of patients with recent-onset disease.

INTRODUCTION/OBJECTIVES: Cutaneous involvement is often overlooked in rheumatoid arthritis (RA). We described cutaneous findings in outpatients attending a recent-onset cohort and identified factors associated with skin involvement and reduced (R) dermatological quality of life (DQoL). METHODS: Skin and rheumatological examinations were performed in 122 patients. DQoL was assessed through the Dermatology Life Quality Index (DLQI). Skin findings were classified as RA-specific and RA-nonspecific. Multiple regression analysis identified factors associated to skin involvement and RDQoL (DLQI score > 1). RESULTS: Patients were middle-aged females (91%), with a 1-year mean disease activity score in 28 joints as 2.0 (interquartile range: 1.5-2.6). There were 94 (77%) patients in whom at least one cutaneous finding was observed: 17 (13.1%) had RA-specific findings (all were rheumatoid nodules) and 91 (96.8%) had at least one RA-nonspecific finding, further classified into skin diseases (35.2%), hair diseases (20.9%), and skin-related signs (76.9%, among whom 94.3% had xerosis). Age (odds ratio [OR]: 1.054, 95% confidence interval [CI]: 1.015-1.094) and skin-health concerns (OR: 5.657, 95% CI: 1.771-18.070) were associated with cutaneous involvement, whereas increased age and DLQI score were associated with a higher number of skin findings/patient. There were 29 patients (24.2%) with RDQoL, which were associated with the Short Form-36 emotional component (OR: 0.955, 95% CI: 0.923-0.988) and the number of skin findings/patient (OR 2.873, 95% CI 1.723-4.791). Pruritus and hair diseases were the individual categories associated with RDQoL. CONCLUSIONS: Cutaneous manifestations are frequent in RA patients and have the potential to impact the emotional component of health-related quality of life. Key Points • Up to 77% of the RA patients with substantial follow-up, from a recent-onset disease cohort, had cutaneous manifestations; these were primarily RA-nonspecific findings, whereas 13.1% had RA-specific findings. • Skin-health concerns and age were associated with cutaneous involvement; meanwhile, increased age and Dermatology Life Quality Index (DLQI) score were associated with a higher number of cutaneous findings/patient. • Reduced dermatological quality of life (RDQoL) was documented in one in four patients and was associated with the SF-36 emotional component and the number of cutaneous findings/patient.

Risk factors for ischemic antiphospholipid syndrome: A case-control study.

OBJECTIVE: The objective of this study was to identify clinical and laboratory risk factors for ischemic stroke (IS) in primary antiphospholipid syndrome (APS) patients. MATERIALS AND METHODS: We performed a case-control study with consecutive primary APS patients divided into two groups, those who presented with IS, vs. those with no history of stroke. Demographics, vascular risk factors, therapeutic approaches, laboratory, imaging and functional outcomes were recorded. RESULTS: Fifty-three confirmed primary APS patients with IS and sixty-six non-stroke primary APS controls were recruited. Most patients were female (65.5 %), with a median age of 33 years. The main vascular risk factors for primary APS-associated stroke were hypertension (11.3 %), diabetes (11.3 %) and hypercholesterolemia (9.4 %). Among patients with stroke, median NIHSS score was 6; 15.1 % of these patients presented a recurrent stroke, and 88.8 % had a good functional outcome at the final follow-up. Positive lupus anticoagulant (OR = 6.1, 95 %CI 2.7-13.5), anti-ß2 glycoprotein IgG (OR = 3.6, 95 %CI 1.7-7.9), and anticardiolipin IgG (OR = 2.8, 95 %CI 1.3-5.9) were more prevalent in non-stroke primary APS, with a triple-positive antibody presence in 46.4 % of controls vs. 22.2 % of patients with stroke (OR = 3.0, 95 %CI 1.3-6.7). At the time of the index event (arterial or venous), 14 known primary APS patients were using vitamin K antagonists, but only 35.7 % of them had achieved therapeutic INR. CONCLUSION: Patients with primary APS and IS have similar vascular risk factors and lower antibody positivity than those with extracranial thrombosis.

Common hematological values predict unfavorable outcomes in hospitalized COVID-19 patients.

COVID-19 can range from asymptomatic to life-threatening. Early identification of patients who will develop severe disease is crucial. A number of scores and indexes have been developed to predict severity. However, most rely on measurements not readily available. We evaluated hematological and biochemical markers taken on admission and determined how predictive they were of development of critical illness or death. We observed that higher values of readily available tests, including neutrophil:lymphocyte ratio; derived neutrophil index; and troponin I were associated with a higher risk of death or critical care admission (P < 0.001). We show that common hematological tests can be helpful in determining early in the course of illness which patients are likely to develop severe forms, as well as allocating resources to those patients early, while avoiding overuse of limited resources in patients with reduced risk of progression to severe disease.

Posterior reversible encephalopathy syndrome: A neuropsychiatric manifestation of systemic lupus erythematosus.

Posterior Reversible Encephalopathy Syndrome (PRES) is an acute neurological syndrome clinically characterized by seizures, altered mental status, headache, and visual disturbances. It is caused by a variety of abnormalities in the endothelial function that ultimately result in vasogenic edema in the circulation of the central nervous system. This is reflected by the neuroimaging findings, that most often show reversible parieto-occipital edema. An important proportion of patients with PRES present with Systemic Lupus Erythematosus (SLE), and its complications, as their sole risk factors. This review describes the relationship between these two clinical entities and explains the pathophysiological models that have been proposed to describe the development of PRES. We explain how SLE can cause alterations in every pathway implicated in the development of PRES. Given the relatively high frequency and the distinct clinical course, PRES in the setting of SLE might be best described as a distinct neuropsychiatric syndrome associated with SLE.

Toenail abnormalities in rheumatoid arthritis patients are associated with radiographic damage and impact disability: a cross sectional study nested within a cohort.

OBJECTIVES: Cutaneous involvement is an extra-articular manifestation of rheumatoid arthritis (RA). This includes nail abnormalities, which are often overlooked. We described nail findings in RA patients currently attending an early arthritis cohort (n=145), and associated them with disease activity and/or damage, as well as patient-reported outcomes. METHODS: A standardised nail examination was performed in 122 patients (84.1% of the cohort), concomitant to the rheumatic assessment. Disability, quality of life and perceived nail-related health were also assessed. Nail findings and their location were recorded and classified according to standardised definitions. Logistic and linear regression models were used to investigate predictors of nail findings and to identify the impact of toenail findings on disability, which was evaluated with the HAQ. Patients consented to participate. RESULTS: Patients were primarily middle-aged females, with median follow-up of 9 years, and had disease under control. Most patients (62.3%) had at least one nail finding and these patients scored lower their nail-related health. The median (IQR) of findings/abnormalities per patient was 3 (2-5) and the number of nails affected per patient was 10 (2-12). Age (OR: 1.04, 95%CI: 1.007-1.074) and erosive disease (OR: 2.26, 95%CI: 1.1-5.1) were associated with nail findings. Toenail involvement was consistently associated with HAQ score out of normal range (OR=3.4, 95%CI=1.24-9.35, p=0.02). There was a linear association between the number of toenails affected and the HAQ score. CONCLUSIONS: Nail abnormalities are common and heterogeneous findings in RA patients; they are associated with erosive damage and impact disability.

Neutrophil-mediated carbamylation promotes articular damage in rheumatoid arthritis.

Formation of autoantibodies to carbamylated proteins (anti-CarP) is considered detrimental in the prognosis of erosive rheumatoid arthritis (RA). The source of carbamylated antigens and the mechanisms by which anti-CarP antibodies promote bone erosion in RA remain unknown. Here, we find that neutrophil extracellular traps (NETs) externalize carbamylated proteins and that RA subjects develop autoantibodies against carbamylated NET (cNET) antigens that, in turn, correlate with levels of anti-CarP. Transgenic mice expressing the human RA shared epitope (HLADRB1* 04:01) immunized with cNETs develop antibodies to citrullinated and carbamylated proteins. Furthermore, anti-carbamylated histone antibodies correlate with radiographic bone erosion in RA subjects. Moreover, anti-carbamylated histone-immunoglobulin G immune complexes promote osteoclast differentiation and potentiate osteoclast-mediated matrix resorption. These results demonstrate that carbamylated proteins present in NETs enhance pathogenic immune responses and bone destruction, which may explain the association between anti-CarP and erosive arthritis in RA.