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ObjectiveNeutrophil 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.MethodsNETs 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.ResultsWe 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.ConclusionsOur results suggest that NETs have a direct role in RA-associated bone erosion by promoting osteoclast formation.

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.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.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).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.

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.

COVID-19; Registries; Vaccination COVID-19; Registros; Vacunación COVID-19; Registres; Vacunació Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups. HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

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.

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.

We describe the case of a 50-year-old woman with a history of SLE and APS that presented with a spontaneous subdural haematoma, prolonged aPTT, PT and INR and positive LA. The activity of the coagulation factors II, VIII, IX and XI was extremely low, and anti-prothrombin antibody IgG was positive. LAHS was established, with inhibition of the intrinsic pathway, as an acquired haemophilia. The patient received corticosteroids and cyclophosphamide as treatment. To the best of our knowledge, this is one of the few reports of spontaneous intracranial bleeding, an unusual and initial manifestation of LAHS in an adult patient.HighlightsLAHS is characterised by the presence of LA and hypoprothrombinaemia caused by anti-prothrombin antibodies.Prolonged aPTT and INR, and positive LA are important laboratory findings that help the suspicion of LAHS.Intracranial bleeding is an unusual manifestation of LAHS associated with low factor II activity.Corticosteroids are the first-line treatment of LAHS.The prognosis of LAHS is good with adequate treatment, with a reported mortality of 5%.

espanolLos avances terapeuticos en la artritis reumatoide obligan a revision periodica de las guias de tratamiento. Objetivo Actualizar las guias del Colegio Mexicano de Reumatologia del tratamiento farmacologico de la artritis reumatoide. Metodo Participaron reumatologos certificados de diferentes instituciones de salud y regiones del pais. Se conformaron equipos de trabajo que revisaron las guias previas, elaboraron nuevas preguntas, revisaron la literatura y calificaron la evidencia, que fue presentada y discutida en sesion plenaria. Las conclusiones se comentaron con infectologos, ginecobstetras y pacientes. Se emiten recomendaciones basadas en niveles de evidencia de acuerdo con la metodologia GRADE. Resultados Se presentan recomendaciones actualizadas para el empleo de los medicamentos disponibles en Mexico hasta 2017 para el tratamiento de la artritis reumatoide. Se enfatiza la importancia del control adecuado y sostenido de la enfermedad y se describen aspectos relevantes de seguridad. Se incluyen conflictos bioeticos y se invita a la accion gubernamental para fortalecer el tratamiento adecuado de la enfermedad. Conclusiones La actualizacion de las recomendaciones del Colegio Mexicano de Reumatologia del tratamiento farmacologico de la artritis reumatoide integra la mejor informacion disponible para ser utilizada en el sistema de salud de Mexico. EnglishTherapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. Objective To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. Method Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. Results Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. Conclusions The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.

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.

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

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).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 score1).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.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.

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.

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-β2 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.

Carbamylated histone antibodies potentiate osteoclast formation and associate with bone erosion 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.

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.

Systemic lupus erythematosus (SLE) is a multi-organic autoimmune disease with a wide variety of clinical manifestations. However, hepatic dysfunction is not included in the diagnostic criteria for the disease and has not been recognized properly. The spectrum of hepatic involvement described in these patients ranges from abnormalities in liver function tests (LFTs) to fulminant hepatic failure. Usually, abnormalities in LFTs are only mild and transient, have a hepatocellular pattern and are not related to SLE but rather are mostly drug related. The most frequent finding on liver biopsy is steatosis (non-alcoholic fatty liver disease). Patients do not frequently progress to advanced chronic liver disease, and their outcome is favourable. Those who develop cirrhosis have traditional risk factors, such as other non-SLE-related conditions. In this work, we aim to review hepatic manifestations in patients with SLE, as well as the diagnostic and therapeutic approaches used for different liver diseases in these patients.

6 páginas There is a complex, dynamic, and bidirectional connection between autoimmunity and cancer. The underlying mechanisms of carcinogenesis and physiopathological aspects of autoimmune diseases are not fully understood. However, there is a common immunological base related to expression of autoantigens by tumour cells that cause an anti-cancer immune response, thereby, triggering the development of paraneoplastic rheumatic syndromes and autoimmune rheumatic diseases in a genetically predisposed population. The case is reported of a 57 year-old man presenting with pulmonary renal syndrome, and who was diagnosed lung cancer and systemic lupus erythematosus at the same time. Existe una relación compleja, dinámica y bidireccional entre la autoinmunidad y el cáncer. Si bien los mecanismos carcinogénicos y fisiopatológicos de las enfermedades autoinmunes no están claramente dilucidados, existe una base inmunológica común relacionada con la expresión de autoantígenos por parte de las células tumorales que desencadenan una respuesta antitumoral, facilitando el desarrollo de síndromes paraneoplásicos reumáticos y enfermedades autoinmunes reumáticas en población genéticamente susceptible. Se presenta un caso de un hombre que debutó con un síndrome pulmón riñón y se diagnosticó cáncer de pulmón y lupus eritematoso sistémico de forma simultánea.

In patients with systemic lupus erythematosus (SLE), persistent joint activity and treatment with glucocorticoids are associated with musculoskeletal complications. About 30% of these patients become candidates for surgical treatment. The aim of this study was to evaluate postoperative outcomes after total hip arthroplasty (THA) in SLE patients.We performed a retrospective cohort study at a tertiary care center in Mexico City between 1995 and 2013. All patients with SLE who underwent THA during that period were included (n = 58). They were compared with 2 control groups, one from another inflammatory arthropathy (rheumatoid arthritis, n = 58) and other noninflammatory (osteoarthritis, n = 58), matched by gender and date of surgery. The primary outcome was the frequency of postoperative complications during follow-up.We included 174 patients who underwent THA during the study period. Patients with SLE were younger (P.0001), had a longer hospitalization stay (P = .001), and required more transfusions (P = .004). Global complications in THA in patients with SLE were more prevalent than rheumatoid arthritis (36.2% vs 15.5%, P = .029) and osteoarthritis (36.2% vs 5.1%, P.0001) patients. After multivariate analysis, risk factors for THA complications were: SLE (hazard ratio 2.8, 95% confidence interval 1.2-6.8; P = .018) and low postoperative hemoglobin (hazard ratio 0.77, 95% confidence interval 0.73-0.83; P .0001). Long-term complications after THA were similar among groups.This is the largest single-center study regarding clinical outcomes after THA in SLE patients. Our data suggest that SLE is an independent risk factor for adverse postoperative outcomes, mainly immediate complications, but the long-term outcome is good enough to offer surgical treatment that will improve quality of life.

Background: Thrombocytopenia and autoimmune hemolytic anemia (AIHA) are common hematologic manifestations in primary antiphospholipid syndrome (APS). Although splenectomy is considered a second-line treatment in both primary immune thrombocytopenia (ITP) and idiopathic AIHA, its role in APS patients with either one of these manifestations has not been adequately defined, mainly because of the theoretically increased risk of thrombosis for patients with APS who undergo surgery. Objectives: To determine the safety and efficacy of splenectomy for steroid-refractory thrombocytopenia or autoimmune hemolytic anemia in patients with primary APS, when compared to patients with ITP or idiopathic AIHA. Methods: We performed a retrospective, single-center, case-control study. We included patients with primary APS and either thrombocytopenia, or autoimmune hemolytic anemia/Evans syndrome who underwent splenectomy between 2000 and 2018. The control group was made up by patients with primary immune cytopenias (ITP or AIHA) who also underwent splenectomy during that period. Cases and controls were adjusted by age, the hematologic manifestation and date of splenectomy. We recorded demographic, clinical and serologic characteristics at the time of surgery and during follow-up. Results: We included 34 patients in each group. Thrombocytopenia was the indication for splenectomy in 53% of patients, with AIHA or Evans syndrome comprising the remaining 47%. Most patients were female (78%) and median age was 37 years. Among APS patients, 41% had triple antibody positivity. There were no differences regarding comorbidities between groups. Patients with APS received more immunosuppressive treatment lines before splenectomy compared to controls (p=0.02), and there was a trend for more high-dose steroid cycles in the APS group (p=0.07). Median time to splenectomy was 54 months in APS patients and 18 months in controls, but without statistical significance. Regarding splenectomy, most were laparoscopic (88%) and surgical complications were similar between groups (18%). However, patients with APS had a higher incidence of global non-surgical complications in the first month (50 vs 23%, p=0.04), most of them being infections (21 vs 3%, p=0.05). There was no difference in the incidence of postsurgical thrombosis, venous or arterial, between groups. Most patients achieved a global response after one month (85% in APS group, 91% in controls, p=0.7). Complete response was observed in 65% and 79% of cases and controls, respectively (p=0.27). Median follow-up time was 52 months for APS patients and 41 months for controls. There were no differences regarding relapse which required any treatment adjustment between cases and controls (44% and 38%, respectively, p=0.8, Fig 1). However, 47% of APS patients received a prolonged maintenance immunosuppressive treatment, compared with 6% of controls (p Conclusion: Splenectomy is associated with adequate and long-lasting responses in APS patients with cytopenias, which do not differ from patients with non-APS-associated thrombocytopenia and AIHA. Thrombosis was not a common complication in our patients; however, there was a higher incidence of infections in APS patients. This could be related to the higher steroid doses and more intensive previous immunosuppressive therapies. Splenectomy could be considered an earlier treatment option for APS patients with refractory cytopenias, and this could reduce infection risk and post-surgical morbidity. Disclosure of Interests: Ana Barrera-Vargas: None declared, Juan Rangel Patino: None declared, Samuel Govea-Pelaez: None declared, Javier Merayo-Chalico Speakers bureau: Pfizer, Roberta Demichelis-Gomez: None declared, Jorge Alcocer-Varela: None declared

Background: Whereas SLE is uncommon in men, the disease is usually more severe and requires more aggressive immunosuppression in male patients. There are multiple studies regarding sexual aspects in women with SLE, but information about sexual function in male patients is quite scant. Objectives: To determine the relationship between SLE and sexual function alterations in men, through the application of validated questionnaires. Methods: We performed a longitudinal study in a third-level referral center in Mexico City. We included men aged ≥16 years who fulfilled ACR criteria for SLE and who were sexually active. All subjects answered the International Index of Erectile Function-15 (IIEF-15), the SF-36 and the HAQ in two visits. Other clinical, serological and demographic variables were measured. Oxidized LDL was quantified by ELISA. Results: We included 108 male SLE patients. Mean age was 37.2±1.1 years and most patients (87%) were taking immunosuppressive therapy. Comorbidities were present in 58% of subjects, with dyslipidemia and hypertension being the most prevalent (34% and 28%, respectively). The prevalence of sexual dysfunction (SD) was 53%. In the basal visit, the only significant differences between the patients with SD and those without SD were a lower education degree (p=0.007) and persistent lymphopenia (p=0.01). There was a positive correlation between global IIEF-15 score and SF-36 score (r=0.46, p=0.001). The physical function domain had the highest correlation (r=0.50, p=0.001). Likewise, there was a weak negative correlation between IIEF-15 and HAQ score (r=-0.25, p=0.012). Also, the IIEF-15 had a weak correlation with the absolute lymphocyte count (r=0.27, p=0.005) and oxidized LDL (r=0.31, p=0.04). In the follow-up visit the only significant differences between the patients with SD when compared with subjects without SD was a low absolute lymphocyte count (1031±89 vs 1458±119, p=0.005); the correlations mentioned in the baseline visit remained significant. Regarding erectile function, 44% of the subjects had some degree of dysfunction. The rest of the variables are shown in Table 1. Conclusion: Sexual function is affected in men with lupus, regardless of comorbidities and treatment. Interestingly, lymphopenia is persistently associated with an impaired sexual function, which could be related to the role it plays in endothelial dysfunction and atherosclerosis. The patients’ disease perception, which is influenced by their academic level and physical role in their daily activities, seems to affect their sexual performance and quality of life. Disclosure of Interests: Jonathan Campos-Guzman: None declared, Ana Barrera-Vargas: None declared, Samuel Govea-Pelaez: None declared, Diana Gomez-Martin: None declared, Jorge Alcocer-Varela: None declared, Diana Padilla-Ortiz: None declared, Javier Merayo-Chalico Speakers bureau: Pfizer

Background: Cytopenias are common in systemic lupus erythematosus (SLE), and it is fundamental to determine their etiology in order to establish an adequate therapeutic strategy. Objectives: To describe the findings in the bone marrow aspirations (BMA) and biopsies of patients with SLE and cytopenias, as well as clinical and laboratory features associated with the etiology of the hematological abnormalities. Methods: We performed a retrospective study in a third-level hospital in Mexico City. We included patients who fulfilled ACR criteria for SLE, presented with cytopenias and had a BMA and biopsy performed between 2000 and 2016. We described the main aspirate and biopsy findings, and also analyzed the final diagnosis and its association with clinical, laboratory and serological features. Results: We included 101 patients; median age was 32 years and 81.2% were women. Leukopenia ( Regarding bone marrow findings, there was erythroid dysplasia in 50.5% of patients, granulocytic dysplasia in 28.7% and megakaryocytic dysplasia in 16%. Myelofibrosis was found in 2.6%. An increase in plasma cells (≥5%) was found in 21.8%. In 72.3% of patients, bone marrow interpretation was conclusive. The most common diagnoses were disease activity (24.8%) and drug-associated myelotoxicity (28.7%). When compared to other etiologies, in patients with cytopenias secondary to disease activity, it was more frequent for the bone marrow be hypercellular (56 vs 23%, p=0.006) and to have increased megakaryocytes (40 vs 17.4%, p=0.048). Conversely, granulocytic dysplasia was less common in this group of patients (17.4% vs 54.3%, p=0.036) We analyzed factors associated with both activity and toxicity as final diagnoses (Table 1). After multivariate analysis, a neutrophil count Conclusion: The main causes of cytopenias in our SLE patients were disease activity and bone marrow toxicity. Our findings suggest that when patients present with less than 1000 neutrophils/µl, it is unlikely for the cytopenias to be secondary to disease activity. Our study reinforces the diagnostic utility of BMA and biopsy, and the associations we described may assist clinicians to determine the etiology of cytopenias in SLE patients, in order to make appropriate therapeutic decisions. Disclosure of Interests: Ana Barrera-Vargas: None declared, Jonathan Campos-Guzman: None declared, Samuel Govea-Pelaez: None declared, Aldo Garcia-Ramos: None declared, Roberta Demichelis-Gomez: None declared, Christianne Bourlon: None declared, Javier Merayo-Chalico Speakers bureau: Pfizer, Jorge Alcocer-Varela: None declared

Background Whereas SLE is uncommon in men, the disease is usually more severe and requires more aggressive immunosuppression in male patients. There are multiple studies regarding sexual aspects in women with SLE, but information about sexual function in male patients is quite scant. Methods We performed a longitudinal study in a third-level referral center in Mexico City (January–November 2018). We included men aged 16 years who fulfilled ACR criteria for SLE and who were sexually active in the previous six months. All subjects answered the International Index of Erectile Function-15 (IIEF-15), the SF-36 (which determines generic health-related quality of life) and the HAQ in two visits. Other clinical, serological and demographic variables were measured. Oxidized LDL was quantified by ELISA. Results We included 108 male SLE patients. Mean age was 37.2±1.1 years and most patients (87.9%) were taking immunosuppressive therapy. Comorbidities were present in 58.3% of subjects, with dyslipidemia and hypertension being the most prevalent (34.2% and 28.7%, respectively). The prevalence of sexual dysfunction (SD) was 53.7%. In the basal visit, the only significant differences between the patients with SD and those without SD were a lower education degree (p=0.007) and persistent lymphopenia (p=0.01). There was a positive correlation between global IIEF-15 score (gsIIEF-15) and global SF-36 score (r=0.459, p=0.0001). The physical function domain had the highest correlation (r=0.509, p=0.0001). Likewise, there was a weak negative correlation between gsIIEF-15 and HAQ score (r=−0.252, p=0.012). Also, the gsIIEF-15 had a weak correlation with the absolute lymphocyte count (r=0.273, p=0.005) and oxidized LDL (r=0.310, p=0.04). In the follow-up visit the only significant differences between the patients with SD when compared with subjects without SD was a low absolute lymphocyte count (1031±89 vs 1458±119, p=0.005); the correlations mentioned in the baseline visit remained significant. Regarding erectile function, 44% of the subjects had some degree of dysfunction. The rest of the variables are shown in table 1. Conclusions Sexual function is affected in men with lupus (mostly young and with adequate functional capacity), regardless of comorbidities and treatment. Interestingly, lymphopenia is persistently associated with an impaired sexual function, which could be related to the role it plays in endothelial dysfunction and atherosclerosis. The patients disease perception, which is influenced by their academic level and physical role in their daily activities, seems to affect their sexual performance and quality of life. These findings reinforce the need of a multidisciplinary approach for male SLE patients with sexual dysfunction. Funding Source(s): None

Background Cytopenias are a common manifestation in systemic lupus erythematosus (SLE), and it is fundamental to determine their etiology in order to establish an adequate therapeutic strategy. The aim of this study was to determine the relevance of bone marrow aspirations (BMA) and biopsies while studying the cause of cytopenias in SLE patients, as well as describing associated clinical and laboratory features. Methods We performed a retrospective study in a third-level hospital in Mexico City. We included patients who fulfilled ACR criteria for SLE, presented with cytopenias and had a BMA and biopsy performed between 2000 and 2016. We described the main aspirate and biopsy findings, and also analyzed the final diagnosis and its association with clinical, laboratory and serological features. Results We included 101 patients; 81.2% were women. Median age was 32 years. Leukopenia ( In 72.3% of patients, bone marrow interpretation, along with clinical and laboratory findings, lead to a conclusive diagnosis. The most common final diagnoses were disease activity (24.8%) and drug-associated toxicity (28.7%). The agreement between the initial diagnostic impression and the conclusion after BMA was performed was 45.5%. We analyzed factors associated with the most common etiologies (table 1). Regarding BMA findings, when cytopenias were secondary to disease activity, it was more frequent for the bone marrow to be hypercellular (56 vs 23%, p=0.006) and to have increased megakaryocytes (40 vs 17.4%, p=0.048). Conversely, granulocytic dysplasia was less common in this group of patients (17.4% vs 54.3%, p=0.036). After multivariate analysis, a neutrophil count Conclusions The most frequent diagnoses of SLE patients presenting with cytopenias were disease activity and drug-associated bone marrow toxicity. There are clinical characteristics and laboratory findings that may guide the diagnostic approach and thus, choose the most appropriate therapeutic intervention. BMA and biopsy play a key role in complementing the study of cytopenias in SLE patients, allowing for a complete evaluation of the particular context of each patient. Funding Source(s): None

Lymphopenia is strongly associated with autoimmune diseases. The molecular mechanisms that link both phenomena are still unclear, but certain key pathways have been described. Central tolerance is as important as peripheral. In the earlier, epithelial and dendritic cells play a crucial role in the selection of clones. In the latter, regulatory T cells (Tregs) rise as inductors of anergy in order to prevent the development of autoimmune pathology. In lymphopenic conditions, T cells develop the process of lymphopenia-induced proliferation (LIP). A complex interaction between the major histocompatibility complex (MHC) and the T cell receptor (TCR) makes this process possible. Furthermore, IL-7 can act synergistically or in an independent manner to promote LIP. A lack of Transforming Growth Factor-β (TGF-β) was recently described as the second hit needed to develop autoimmunity in a lymphopenic microenvironment, given its actions in Tregs and its interaction with CTLA-4. Regarding autoimmune clinical scenarios, lymphopenia is related to both, systemic and organ-specific diseases. Thus, the molecular study of such patients has been limited and needs to be widened to the pathways shown here to be involved in the development of lymphopenia and autoimmunity.

Background Renal thrombotic microangiopathy (TMA) may be associated with lupus nephritis. Its relationship to other disease factors and its specific effect on prognosis are not precisely known. Evidence regarding these aspects is controversial, and information focusing on kidney-limited TMA in systemic lupus erythematosus (SLE) patients is scarce. Objectives The aims of this study were to identify risk factors for renal TMA in patients with lupus nephritis and to determine its impact on clinical outcomes. Methods A case-control study was performed. We studied 245 renal biopsies from SLE patients. We included patients with renal TMA, as well as control subjects adjusted for glomerulonephritis class, estimated glomerular filtration rate, activity and chronicity indices, and follow-up time. Serological and clinical features were measured at the time of the biopsy and during follow-up. Results Twenty-three patients with renal TMA and 21 control subjects were included. There were no differences in Systemic Lupus Erythematosus Disease Activity Index score, end-stage renal disease, or mortality between groups during follow-up. After multivariate analysis, lymphopenia (odds ratio, 10.69; 95% CI, 1.35-84.74) and anti-Ro antibody positivity (odds ratio, 8.96; 95% CI, 1.49-53.57) remained significantly associated with renal TMA. Conclusions Lymphopenia and anti-Ro positivity are independent risk factors for renal TMA in SLE patients. This increased risk could be a consequence of the potential role of these factors in endothelial dysfunction and damage. Outcomes were similar for patients with the same estimated glomerular filtration rate and biopsy characteristics, regardless of the presence of TMA.

Objective.The aim of this study was to describe the prevalence of erectile dysfunction (ED), as well as associated demographic and clinical features, in men with systemic lupus erythematosus (SLE), by means of a systematic, standardized evaluation.Methods.We performed a transversal study in 8 tertiary care centers in Latin America. We included male patients ≥ 16 years who fulfilled ≥ 4 American College of Rheumatology criteria for SLE and had regular sexual activity, and evaluated them with the International Index of Erectile Function-5 questionnaire. Relevant demographic, clinical, and serological characteristics were recorded. We included 2 control groups: the first was made up of healthy men and the second of men with autoimmune diseases other than SLE (non-SLE group).Results.We included 590 subjects (174 SLE, 55 non-SLE, and 361 healthy controls). The prevalence of ED in the SLE group was 69%. Mean age in that group was 36.3 ± 1.03 years. Among SLE patients with and without ED, these factors were significantly different: the presence of persistent lymphopenia (p = 0.006), prednisone dose (9.3 ± 1.2 vs 5.3 ± 1.3 mg, p = 0.026), and the Systemic Lupus International Collaborating Clinics damage score (1.25 ± 0.14 vs 0.8 ± 0.16 points, p = 0.042). Independent risk factors for ED in patients with SLE were persistent lymphopenia (OR 2.79, 95% CI 1.37–5.70, p = 0.001) and corticosteroid use in the previous year (OR 2.15, 95% CI 1.37–3.37, p = 0.001).Conclusion.Regardless of comorbidities, treatment (excluding steroids), and type of disease activity, patients with SLE have a high prevalence of ED, especially considering that most patients are young. Recent corticosteroid use and persistent lymphopenia, which could be related to endothelial dysfunction, are risk factors for this complication in men with SLE.

Summary Systemic lupus erythematosus (SLE) patients are susceptible to the development of posterior reversible encephalopathy syndrome (PRES). The main theory concerning the physiopathology of PRES suggests that there is brain–blood barrier damage, which is associated with endothelial dysfunction, and characterized by vasogenic oedema. However, current evidence regarding its physiopathogenic mechanisms is quite scant. The aim of this study was to analyse the expression of different serum cytokines, as well as vascular endothelial growth factor (VEGF) and soluble CD40 ligand (sCD40L), in patients with PRES/systemic lupus erythematosus (SLE) and to compare them with levels in SLE patients without PRES and in healthy controls. We performed a transversal study in a tertiary care centre in México City. We included 32 subjects (healthy controls, n = 6; remission SLE, n = 6; active SLE, n = 6 and PRES/SLE patients, n = 14). PRES was defined as reversible neurological manifestations (seizures, visual abnormalities, acute confusional state), associated with compatible changes by magnetic resonance imaging (MRI). Serum samples were obtained during the first 36 h after the PRES episode and were analysed by cytometric bead array, Luminex multiplex assay or enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-6 and IL-10 levels were significantly higher in PRES/SLE patients (P = 0·013 and 0·025, respectively) when compared to the other groups. Furthermore, IL-6 and IL-10 levels displayed a positive correlation (r = 0·686, P = 0·007). There were no differences among groups regarding other cytokines, sCD40L or VEGF levels. A differential serum cytokine profile was found in PRES/SLE patients, with increased IL-6 and IL-10 levels. Our findings, which are similar to those described in other neurological manifestations of SLE, support the fact that PRES should be considered among the SLE-associated neuropsychiatric syndromes.

There are national and international clinical practice guidelines for systemic lupus erythematosus treatment. Nonetheless, most of them are not designed for the Mexican population or are devoted only to the treatment of certain disease manifestations, like lupus nephritis, or are designed for some physiological state like pregnancy. The Mexican College of Rheumatology aimed to create clinical practice guidelines that included the majority of the manifestations of systemic lupus erythematosus, and also incorporated guidelines in controversial situations like vaccination and the perioperative period. The present document introduces the «Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus» proposed by the Mexican College of Rheumatology, which could be useful mostly for non-rheumatologist physicians who need to treat patients with systemic lupus erythematosus without having the appropriate training in the field of rheumatology. In these guidelines, the reader will find recommendations on the management of general, articular, kidney, cardiovascular, pulmonary, neurological, hematologic and gastrointestinal manifestations, and recommendations on vaccination and treatment management during the perioperative period.

Posterior reversible encephalopathy syndrome (PRES) is a well-known but rare complication in patients (1%) with systemic lupus erythematosus (SLE). However, current epidemiological data are quite scant. The aim of the present study was to describe potentially unrecognised risk factors.We performed a multicentre, retrospective case-control study in Mexico between 1999 and 2014. We included a total of 168 patients who accounted for 77 episodes of PRES, as follows: SLE/PRES, 43 patients with 48 episodes; SLE without PRES, 96 patients; and PRES without SLE, 29 patients. SLE diagnosis was considered when patients fulfilled ≥4 American College of Rheumatology criteria. PRES was defined by reversible neurological manifestations and MRI changes.Patients with SLE/PRES were younger, presented with seizures as the most common manifestation (81%) and 18% had the typical occipital MRI finding. Hypertension (OR=16.3, 95% CI 4.03 to 65.8), renal dysfunction (OR=6.65, 95% CI 1.24 to 35.6), lymphopenia (OR=5.76, 95% CI 1.36 to 24.4), Systemic Lupus Erythematosus Activity Index ≥ 6 points (OR=1.11, 95% CI 1.01 to 1.22) and younger age (OR=0.86, 95% CI 0.81 to 0.91, p0.001) were independent risk factors for development of PRES in SLE. Furthermore, dyslipidemia also characterised the association between PRES and SLE (OR=10.6, 95% CI 1.17 to 96.4).This is the largest reported series of patients with SLE and PRES. We were able to corroborate the known risk factors for of PRES, and found two previously undescribed factors (lymphopenia and dyslipidemia), which suggests that endothelial dysfunction is a key element in PRES pathogenesis in lupus patients.

To assess if ubiquitinated proteins potentially present in neutrophil extracellular traps (NETs) can modify cellular responses and induce inflammatory mechanisms in patients with systemic lupus erythematosus (SLE) and healthy subjects.We studied 74 subjects with SLE and 77 healthy controls. Neutrophils and low-density granulocytes were isolated, and NETs were induced. Ubiquitin content was quantified in NETs by western blot analysis, ELISA and immunofluorescence microscopy, while ubiquitination of NET proteins was assessed by immunoprecipitation. Monocyte-derived macrophages from SLE and controls were isolated and stimulated with NETs or ubiquitin. Calcium flux and cytokine synthesis were measured following these stimuli.NETs contain ubiquitinated proteins, with a lower expression of polyubiquitinated proteins in subjects with SLE than in controls. Myeloperoxidase (MPO) is present in ubiquitinated form in NETs. Patients with SLE develop antiubiquitinated MPO antibodies, and titres positively correlate with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (P0.01), and negatively correlate with complement components (P0.01). Stimulation of monocyte-derived macrophages with NETs or with ubiquitin led to enhanced calcium flux. In addition, stimulation with NETs led to enhanced cytokine (tumour necrosis factor-α and interleukin-10) production in macrophages from patients with SLE when compared with controls, which was hampered by inhibition of NET internalisation by macrophages.This is the first study to find ubiquitinated proteins in NETs, and evidence for adaptive immune responses directed towards ubiquitinated NET proteins in SLE. The distinct differences in ubiquitin species profile in NETs compared with healthy controls may contribute to dampened anti-inflammatory responses observed in SLE. These results also support a role for extracellular ubiquitin in inflammation in SLE.

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). At our Institution, patients transplanted using G-CSF-primed bone marrow (G-BM), have a lower incidence of GVHD when compared to other sources. The objective of this study was to analyze and compare T cell subsets and cytokines in donor G-BM and steady-state BM (SS-BM). A prospective study was performed in 48 donor samples. Mononuclear cells were isolated by gradient density. T cell subsets and cytokine production in supernatants were analyzed by multiparametric flow cytometry. Six and 16 patients developed acute and chronic GVHD, respectively. Patients who developed GVHD were characterized by a predominant pro-inflammatory response (IL-17A (10.02 vs 0.43pg/mL, p=0.006), TNF-α (54.57 vs 0.81pg/mL, p=0.001)), in contrast to a deficient suppressor profile (IL-10 (7.87 vs 41.37pg/mL, p=0.003)) and Tregs (0.95% vs 1.52%, p=0.004). G-BM showed an enhanced suppressive phenotype (increased Th2 and Tregs) in comparison to SS-BM. GVHD is associated with an imbalance between pro-inflammatory and suppressor immune responses. G-BM showed a more favorable immunologic profile characterized by diminished pro-inflammatory cytokine production, which was associated with a lower frequency of GVHD in our cohort.

Background Although systemic lupus erythematosus (SLE) has a higher prevalence in women, the disease usually has a more aggressive course in men. Information regarding erectile function in men with SLE is quite scant. Objectives The aim of this study was to describe the prevalence of erectile dysfunction (ED), as well as associated demographic and clinical features, in men with SLE, by means of a systematic, standardized evaluation. Methods We performed a transversal study in eight tertiary care centers in Latin America. We included male patients ≥16 years who fulfilled ≥4 ACR criteria for SLE, and who had regular sexual activity in the previous 6 months. Patients with other rheumatic diseases (except for APS), chronic viral infections and late-onset SLE were excluded. All patients answered the IIEF-5 Questionnaire, which has been validated in Spanish. Other relevant demographic, clinical and serological characteristics were documented. We included two control groups: the first one was made up by healthy men and the second by men with autoimmune diseases different from SLE (non-SLE group). Results We included 279 subjects (174 SLE, 55 non-SLE and 50 healthy controls). The prevalence of ED in SLE group 68% ( vs 22% in healthy group, p=0.001). The mean age of patients with ED in the SLE group was 36.1±1.03, while in patients without ED it was 32.5±1.27 (p=0.022). Whereas there was no difference regarding ED prevalence between SLE patients and the non-SLE group (68 vs 60%, p=0.25), patients with other autoimmune diseases were 10 years older (46.3±1.60 years, p=0.001). Among SLE patients with and without ED, the presence of persistent lymphopenia (≤1000cells/mcl at three consecutive times, p=0.006), the prednisone dose (9.3±1.2 vs 5.3±1.2mg, p=0.026), as well as the SLICC damage score (1.2±0.1 vs 0.8±0.1 points, p=0.026), were significantly different. Comorbidities and other demographic, serological and treatment variables were not different between those groups. Multivariate analysis showed the following independent risk factors for ED in SLE patients: persistent lymphopenia (OR 2.79 CI95% [2.79–5.70], p=0.001) and corticosteroid use (any dose) in the previous year (OR 2.15 CI95% [1.37–3.37], p=0.001). Only 7% of patients had been questioned about their sexual function in the previous three visits to the rheumatologist; also, 81% of subjects considered it would be appropriate to be asked about their sexual function. Conclusions Regardless of comorbidities, treatment (excluding steroids) and type of disease activity, SLE patients have a high prevalence of ED, especially considering most patients are young and sexually active. Rheumatologists should be aware of the relevance of this problem in male SLE patients and should ask about this issues in regular visits. Disclosure of Interest None declared

Background and aims Although SLE has a higher prevalence in women, the disease usually has a more aggressive course in men. Therefore, the aim of this study was to describe the prevalence of erectile dysfunction (ED), as well as associated demographic and clinical features in men with SLE, by means of a systematic, standardised evaluation. Methods We performed a transversal study in six tertiary care centres in Latin America. We included male patients≥16 years who fulfilled ≥4 ACR criteria for SLE, and had regular sexual activity in ≤6 months. Patients with other rheumatic diseases (except for APS), chronic viral infections and late-onset SLE were excluded. All patients answered the IIEF-5 Questionnaire, which has been validated in Spanish. Other relevant demographic, clinical and serological characteristics were documented. Results We included 157 subjects. The prevalence of ED in our study population was 68%, the majority were classified as mild to moderate (17.3±0.36 points; normal score: 22–25 points). The mean age of patients with ED was 35.3±1, while in patients without ED it was 32.9±1.3 (p=0.17). The only significant differences were regarding corticosteroid usage in the past year; the rest of the demographic and clinical variables were similar between both groups. (Table 1). After multivariate analysis, independent risk factors for ED were: persistent lymphopenia, age and corticosteroid use in the past year (Table 2). Conclusions Regardless of comorbidities, medication (excluding corticosteroids) and disease duration, SLE patients, who are mostly young and sexually active, have a high ED prevalence.

Summary The presence of anti-Ro52/tripartite motif 21 (Trim21) autoantibodies has been associated with a distinctive clinical profile and has gained value as a prognostic marker in idiopathic inflammatory myopathies (IIM). The aim of the present work was to analyse Ro52/Trim21 expression in different subsets of peripheral blood mononuclear cells (PBMCs) of patients with IIM, as well as the ubiquitination profile and its association with proinflammatory cytokine production. We included 18 patients with recent-onset IIM and 18 age- and gender-matched healthy donors. PBMCs were isolated and different subsets (CD4+, CD8+, CD14+) were purified by magnetic selection. The expression of Ro52/Trim21 in different PBMC subsets of patients with IIM and healthy donors was analysed by Western blot. We assessed the presence of myositis-specific and associated autoantibodies by enzyme-linked immunosorbent assay (ELISA). Cytokine levels were measured by cytometric bead array. Patients with IIM showed decreased protein expression of Ro52/Trim21 in comparison to healthy controls in PBMC (0·97 ± 0·60 versus 1·84 ± 0·92, P = 0·016), CD4+ lymphocytes (0·79 ± 0·54 versus 2·41 ± 0·78, P = 0·017), and monocytes (0·87 ± 0·35 versus 1·89 ± 0·20, P

Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. Objective To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. Method Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. Results Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasised and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. Conclusions The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.

Renal thrombotic microangiopathy (TMA) may be associated with lupus nephritis. Its relationship to other disease factors and its specific effect on prognosis are not precisely known. Evidence regarding these aspects is controversial, and information focusing on kidney-limited TMA in systemic lupus erythematosus (SLE) patients is scarce.The aims of this study were to identify risk factors for renal TMA in patients with lupus nephritis and to determine its impact on clinical outcomes.A case-control study was performed. We studied 245 renal biopsies from SLE patients. We included patients with renal TMA, as well as control subjects adjusted for glomerulonephritis class, estimated glomerular filtration rate, activity and chronicity indices, and follow-up time. Serological and clinical features were measured at the time of the biopsy and during follow-up.Twenty-three patients with renal TMA and 21 control subjects were included. There were no differences in Systemic Lupus Erythematosus Disease Activity Index score, end-stage renal disease, or mortality between groups during follow-up. After multivariate analysis, lymphopenia (odds ratio, 10.69; 95% CI, 1.35-84.74) and anti-Ro antibody positivity (odds ratio, 8.96; 95% CI, 1.49-53.57) remained significantly associated with renal TMA.Lymphopenia and anti-Ro positivity are independent risk factors for renal TMA in SLE patients. This increased risk could be a consequence of the potential role of these factors in endothelial dysfunction and damage. Outcomes were similar for patients with the same estimated glomerular filtration rate and biopsy characteristics, regardless of the presence of TMA.

OBJECTIVES The aim of this study was to recognize risk factors for extrarenal SLE flares in patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT). METHODS We performed a retrospective, case-control study in a tertiary care hospital in Mexico City from 1993 to 2014. Cases were lupus patients who had any extrarenal flare after RRT. Controls were SLE patients with ESRD but without flares. We recorded demographic features and clinical and immunological parameters. Differences between groups were analysed by Student's t-test. Association was assessed by the odds ratio (OR) and 95% CI. Multivariate analysis was performed by binary logistic regression. RESULTS Eighty-eight patients were included: 38 cases (50 flares) and 50 controls. The proportion of men was higher in cases (24 vs 8%, P = 0.029). The most common flares were haematologic (42%), mucocutaneous (38%) and articular (30%). Independent risk factors for flares included age at RRT start [OR 0.92 (95% CI 0.88, 0.96), P < 0.001], history of haematologic activity [OR 3.79 (95% CI 1.05, 13.7), P = 0.04], anti-cardiolipin IgM [OR 4.39 (95% CI 1.32, 14.6), P = 0.02] and low C4 levels [OR 9.7 (95% CI 2.49, 39.12), P = 0.001]. CONCLUSION SLE patients continue to be at risk for extrarenal activity after RRT. The most common flare was haematologic, which correlated with the history of haematologic activity and anti-cardiolipin positivity as independent risk factors. Lower C4 levels and younger age at the beginning of RRT were also associated. Patients with these characteristics should have a closer follow-up in order to detect and treat SLE flares in a timely manner.

Objective.To evaluate factors associated with mortality and infections in patients with systemic lupus erythematosus (SLE) and diffuse alveolar hemorrhage (DAH).Methods.A retrospective chart review was carried out for medical admissions of patients with a diagnosis of SLE and DAH in 9 hospitals. Clinical and laboratory data were recorded for each patient at DAH diagnosis.Results.We included 57 episodes of DAH of 50 patients (7 recurrences), 49 women (86%), 14 juvenile SLE (24.6%); 24 had died (42.1%). In the chart review we detected infection in 22 episodes (38.6%): 8 invasive fungal infections, 16 bacterial infections, and 2 patients had both types. In the bivariate analysis, factors associated with mortality were high Acute Physiology and Chronic Health Evaluation II scores, requirement of mechanical ventilation (OR 15.0, 95% CI 1.9 to 662.2), infections (fungal or bacterial; OR 3.2, CI 0.9 to 11.1), renal failure (OR 4.9, CI 1.4 to 18.0), and thrombocytopenia (OR 4.3, CI 1.2 to 15.6). We found similar mortality between children and adults. Infections were associated with treatment for SLE, requirement of mechanical ventilation, hypocomplementemia, and high levels of C-reactive protein.Conclusion.Infection is a frequent finding in patients with DAH and SLE; we found similar mortality between adult SLE and juvenile SLE. Factors that we describe associated with infections may influence the therapeutic selection for these patients.

The association of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE) is rare. It is associated with high morbidity and mortality. Information about risk factors and clinical outcomes is scant.A retrospective case-control study was performed in a referral center in Mexico City between 1994 and 2013. Patients were diagnosed with TTP if they fulfilled the following criteria: microangiopathic haemolytic anaemia, thrombocytopenia, high LDH levels, normal fibrinogen and negative Coombs' test. Patients with SLE were diagnosed with ≥ 4 ACR criteria. We included three study groups: group A included patients with SLE-associated TTP (TTP/SLE; cases n = 22, TTP events n = 24); patients with non-autoimmune TTP (NA-TTP; cases n = 19, TTP events n = 22) were included in group B and patients with SLE without TTP (n = 48) in group C.After multivariate analysis, lymphopenia1000/mm3 [OR 19.84, p = 0.037], high SLEDAI score three months prior to hospitalisation [OR 1.54, p = 0.028], Hg7g/dL [OR 6.81, p = 0.026], low levels of indirect bilirubin [OR 0.51, p = 0.007], and less severe thrombocytopenia [OR 0.98, p = 0.009] were associated with TTP in SLE patients. Patients with TTP/SLE received increased cumulative steroid dose vs. NA-TTP (p = 0.006) and a higher number of immunosuppressive drugs (p = 0.015). Patients with TTP/SLE had higher survival than NA-TTP (p=0.033); however, patients hospitalised for TTP/SLE had a higher risk of death than lupus patients hospitalised for other causesLymphopenia is an independent risk factor for TTP/SLE. It is likely that patients with TTP/SLE present with less evident clinical features, so the level of suspicion must be higher to avoid delay in treatment.

Objective.To identify risk factors for developing drug-resistant bacterial infections in patients with systemic lupus erythematosus (SLE).Methods.A retrospective, case-control study was performed. Patients fulfilled American College of Rheumatology criteria for SLE and had an episode of bloodstream infection between 2001 and 2012. Cases were defined as those with bloodstream infection caused by drug-resistant bacteria (Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, or extended-spectrum-β-lactalamase-producing Escherichia coli); while controls had susceptible strains of S. aureus or E. coli. Differences between groups were analyzed by Student t test or Mann-Whitney U test. Association between variables was assessed by OR (CI 95%). Multivariate analysis was performed by binary logistic regression model.Results.Forty-four patients were included in each group. Variables associated with drug-resistant bloodstream infection were history of central nervous system activity; hematological activity, immunosuppressive treatment and prednisone dose at the time of the infection; and low C3 levels, antibiotic use, or hospitalization in the previous 3 months. In multivariate analysis, variables that remained significant were low C3 previous to infection (OR 3.12, CI 95% 1.91–8.22), previous hospitalization (OR 2.22, CI 95% 1.42–4.10), and prednisone dose at the time of infection (OR 1.10, CI 95% 1.04–1.22).Conclusion.Low C3 levels, recent hospitalization, and prednisone dose at time of infection are independent risk factors for acquiring drug-resistant bacteria in patients with SLE. Although the present data do not fully support a change in initial treatment-decision strategies, this information could lead to prospective studies designed to address this issue, which could determine the best approach in clinical practice.

Background Graft versus host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation. It is characterized by an imbalance between the effector and regulatory arms of the immune system which results in the over production of inflammatory cytokines. Regulatory T (T regs) cells and T helper 17 (Th17) cells are two recently described lymphocyte subsets with opposing actions. Both can develop from naïve CD4+ T cell precursors under the influence of TGFβ1. Th17 lymphocytes, are key effector cells in rodent models of human diseases including GVHD. The other subset, T regs, is essential for dominant immunologic tolerance. At our institution, patients transplanted using G-CSF primed bone marrow (G-BM), have a lower incidence of acute and chronic GVHD when compared to those transplanted with peripheral blood and not primed bone marrow. Some microenvironment characteristics of this hematopoietic stem cells (HSC) source remain unknown, as well as the difference between Tregs, Th17 and cytokine levels in patients who develop GVHD and those who do not. Objective To analyze the characteristics of thirty-eight G-BM donor samples, identifying lymphocytes subsets and associated cytokines, and comparing patients who developed chronic GVHD (cGVHD) and those who did not. Materials and Methods A prospective analysis was performed in 38 G-BM samples from donors from 1999 to 2016. Mononuclear cells were defrosted, counted, and viability was evaluated. A 24 hour resting with RPMI, and posterior activation with PMA (50 ng/ml) for 48 hours was performed. Cells were harvested and cytokines were evaluated by flow cytometry (CBA assay). From each sample, one million mononuclear cells were permeabilized, fixed, and stained with CD4-FITC, IL17A-PE, IFN-γ APC, and IL-4 PECy7, for their posterior phenotipication by flow cytometry. The samples were obtained in a BD LSR Fortessa cytometry, and analyzed with the Flow-Jo software. Patients (recipients) information was analyzed using SPSS v.21. Results GVHD incidence was reported as following: Three (8%) patients developed acute GVHD (2 grade II, and 1 grade IV), 11 patients (29%) developed chronic GVHD (9% extensive, and 91% limited), and 24 patients did not present either. Mononuclear cells from G-BM from donors of patients who developed cGVHD showed a pro inflammatory response, characterized by an increased concentration of IL-17A (15.5 vs 0.71 pg/mL, p=0.013), TNF-α (80.27 vs 0.13 pg/mL, p=0.001), and IL-6 (4953.6 vs 11.75 pg/mL, p=0.025), after a mitogenic stimulation, compared to cells from donors of patients who did not developed GVHD. On the other hand, a decreased IL-10 production (2.62 vs 52.81 pg/mL, p=0.001) was documented in mononuclear cells from donors of patients who developed chronic GVHD, compared to donor cells of patients who did not. No significant difference in the production of IL-2, IL-4, and IFN-γ was observed. There was no difference in Th1 and Th2 between both groups, but mononuclear cells from donors of patients who developed chronic GVHD had a higher percentage of Th17 (1.02% vs 0.46%, p Conclusions Patients who develop cGVHD (29%) are characterized by a pro inflammatory response with an increased production of IL-17A, IL-6, and IFN-γ, and also a major percentage of Th17 cells. Also, a decreased suppressive response was documented with reduced IL-10 and Tregs levels. The low incidence of cGVHD show that G-CSF primed bone marrow is an excellent source for allogeneic HSC transplantations, and would be useful to compare these results with other HSC sources. Disclosures No relevant conflicts of interest to declare.