Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus.

OBJECTIVE: To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. METHODS: We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann-Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. RESULTS: Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6-14) in comparison to that at follow-up (6 (4-8), P = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. CONCLUSION: Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study.

BACKGROUND: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. METHODS: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. RESULTS: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1ß (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. CONCLUSION: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study.

Background: Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods: We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results: At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion: A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.

ANCA-associated vasculitis and IgG4-related disease overlap syndrome: a case report and literature review.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are infrequent autoimmune diseases characterized by inflammation of the walls of small vessels leading to tissue and endothelial damage. On the other hand, IgG4-related disease is a fibroinflammatory disease characterized histologically by lymphoplasmacytic infiltrates with IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis that may affect nearly every organ of the body. There are similarities in clinical, serological, radiological, and histopathological features between both diseases, and hence, they usually mimic each other complicating the differential diagnosis. Furthermore, reports of patients with the coexistence of both conditions (overlap syndrome) have been reported. We herein report a patient with an unequivocal diagnosis of ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (posterior uveitis, polyneuropathy, pauci-immune glomerulonephritis with crescent formation and granulomas, and MPO-ANCA positivity) and IgG4-related disease (thoracic aortitis, tubulointerstitial nephritis with prominent IgG4+ plasma cell infiltration, fibrosis, and obliterative arteritis, high levels of serum IgG4, and eosinophilia) overlap syndrome.

Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID).

BACKGROUND: Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated. OBJECTIVE: To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19. DESIGN: We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial. PARTICIPANTS: We recruited 116 hospitalized patients with severe COVID-19 in Mexico. INTERVENTIONS: Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment. MAIN MEASURES: The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients. KEY RESULTS: Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35-1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66-3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A. CONCLUSIONS: Colchicine is safe but not effective in the treatment of severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04367168.

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.

I. THE ROLE OF RESEARCH ETHICS COMMITTEES IN OBSERVATIONAL STUDIES: EPIDEMIOLOGICAL REGISTRIES, CASE REPORTS, INTERVIEWS, AND RETROSPECTIVE STUDIES.

It is often unclear to the clinical investigator whether observational studies should be submitted to a research ethics committee (REC), mostly because, in general, no active or additional interventions are performed. Moreover, obtaining an informed consent under these circumstances may be challenging, either because these are very large epidemiological registries, or the subject may no longer be alive, is too ill to consent, or is impossible to contact after being discharged. Although observational studies do not involve interventions, they entail ethical concerns, including threats such as breaches in confidentiality and autonomy, and respect for basic rights of the research subjects according to the good clinical practices. In this context, in addition to their main function as evaluators from an ethical, methodological, and regulatory point of view, the RECs serve as mediators between the research subjects, looking after their basic rights, and the investigator or institution, safeguarding them from both legal and unethical perils that the investigation could engage, by ensuring that all procedures are performed following the international standards of care for research. The aim of this manuscript is to provide information on each type of study and its risks, along with actions to prevent such risks, and the function of RECs in each type of study.

I. The role of research ethics committees in observational studies: epidemiological registries, case reports, interviews, and retrospective studies

Abstract It is often unclear to the clinical investigator whether observational studies should be submitted to a research ethics committee (REC), mostly because, in general, no active or additional interventions are performed. Moreover, obtaining an informed consent under these circumstances may be challenging, either because these are very large epidemiological registries, or the subject may no longer be alive, is too ill to consent, or is impossible to contact after being discharged. Although observational studies do not involve interventions, they entail ethical concerns, including threats such as breaches in confidentiality and autonomy, and respect for basic rights of the research subjects according to the good clinical practices. In this context, in addition to their main function as evaluators from an ethical, methodological, and regulatory point of view, the RECs serve as mediators between the research subjects, looking after their basic rights, and the investigator or institution, safeguarding them from both legal and unethical perils that the investigation could engage, by ensuring that all procedures are performed following the international standards of care for research. The aim of this manuscript is to provide information on each type of study and its risks, along with actions to prevent such risks, and the function of RECs in each type of study.

Improvement in OMERACT domains and renal function with regular treatment for gout: a 12-month follow-up cohort study.

OMERACT proposed a set of mandatory and discretionary domains to evaluate the effect of treatment in patients with gout. To determine the percentage of improvement and the effect size 6 and 12 months after starting a proper treatment in patients with gout from our cohort (GRESGO) based on the OMERACT proposal for chronic gout. GRESGO is a cohort of consecutive, new patients with gout attending either of two dedicated clinics. This report includes 141 patients evaluated at baseline and 6 months plus 101 of them completing a 12-month follow-up in 2012. Clinical data including the OMERACT domains for chronic gout were collected at baseline and every 6 months. Treatment was prescribed by their attending physician with the purpose of getting < 6 mg/dL of seric uric acid (sUA). Most patients were males (96%) with inappropriate treatment (95%); 66% had tophi, 30% metabolic syndrome, and 32% low renal function. Mean dose of allopurinol at baseline and throughout the study went from 344 ± 168 mg/day to 453 ± 198 at 12 months. Most OMERACT domains and renal function improved significantly; 73% improved > 20% from 6 to 12 months. Greater improvement was observed in the domains: flares, index tophus size, pain, general health assessment, and HAQ score, all of them associated to lower sUA values. Chronic gout patients improve significantly in most OMERACT domains when conventional and regular treatment is indicated. sUA < 6 mg/dL is associated with greater improvement.

A pilot study on dual-energy computed tomography for detection of urate deposits in renal transplant patients with asymptomatic hyperuricemia.

BACKGROUND: An increasing role of dual-energy computed tomography (DECT) scan in tophaceous gout assessment is recognized, whereas its role in asymptomatic hyperuricemia is unknown. OBJECTIVE: The objective of this study was to assess the prevalence of joint and renal monosodium urate deposits by DECT in asymptomatic hyperuricemia. METHODS: Among a renal transplant population with at least 1 year of follow-up, we included 27 patients with sustained hyperuricemia and 11 with normal serum uric acid (SUA) levels. We excluded patients with gout or history of monoarthritis or oligoarthritis. We registered demographic data, drugs, hyperuricemia onset, comorbidities, renal function, and SUA. We used a 128-slice dual-source CT system, and the acquisition protocol included the pelvis and imaging of elbows, wrists, hands, knees, ankles, and feet. The reading process was performed by 2 radiologists. RESULTS: The mean age was 43.7 ± 12 years, 57.8% were males, and median follow-up was 7 years. Hyperuricemia presented after a median time of 0.61 years after transplantation and had persisted for a median of 3.2 years (0.5-16.8 years). For the hyperuricemic group, the median SUA at the DECT scan and the maximum SUA levels were 7.9 and 8.9 mg/dL, respectively. Groups were similar in most of the clinical variables. We did not find any articular or renal deposit; conversely, we demonstrated a quadriceps tendon deposition in 1 patient with hyperuricemia (prevalence of 0.03%; 95% confidence interval, 0.006%-0.17%). CONCLUSIONS: In these patients with asymptomatic hyperuricemia, the prevalence of monosodium urate deposition assessed by DECT was low; however, larger studies need to be performed for further validation.

Female gout: age and duration of the disease determine clinical presentation.

OBJECTIVE: This study aimed to compare data and associated diseases between women and men with gout paired for age and duration of the disease. METHODS: Consecutive patients from outpatient gout clinics of 2 rheumatology departments were included in this case-control study. We identified 37 women with gout diagnosis and paired them by age and duration of the disease with 37 men with gout (American College of Rheumatology criteria). Variables were clinical data, associated diseases, and renal function evaluated by 3 methods: creatinine clearance, modification of diet in renal disease, and Cockcroft-Gault. RESULTS: Mean (SD) age was 54.47 (15.13) years in women versus 53.52 (15.23) years in males, and mean (SD) age at onset 46.77 (16.63) years versus 45.62 (16.16) years in women and men, respectively. Hypertension was found in 26 (73%) of 37 women and in 27 (70%) of 37 men, previous diuretics was found in only 1 man, and no significant differences were found between women and men in gout or associated metabolic diseases. Females had lower creatinine clearance than males did (49.8 [29.7] vs. 67.1 [35.5] mL/min, P = 0.039). But, when it was calculated by methods considering sex, there were no significant differences (Cockcroft-Gault 66.4 [37.6] vs. 78.8 [43.8] mL/min [P = 0.2] and modification of diet in renal disease 73.8 [64.6] vs. 73.1 [35.0] mL/min [P = 0.9], females vs. males, respectively). Thirteen women (35%) were premenopausal at onset, 2 had familial history of gout, and 2 had history of lithiasis; other variables were not different from postmenopausal women. CONCLUSIONS: Factors previously associated to female gout seem to be more related to age than to sex or to the disease itself. In our country, patients with gout (males and females) are younger at onset. Gender should be considered to evaluate renal function in females with gout. One third of our female patients with gout were premenopausal and had unexpected higher frequency of lithiasis; no other differences with postmenopausal women were found.

Radiographic outcome in Hispanic early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs.

OBJECTIVES: To determine rates of incident erosive disease in early rheumatoid arthritis patients, to identify baseline predictors and to evaluate erosion's impact on patient-reported outcomes. METHODS: 82 patients with ≤ 12 months of disease duration, ≥ 3 years of follow-up and conventional treatment were included. Consecutive evaluations assessed swollen and tender joint counts, treatment and comorbidity, acute reactant-phase determinations and patient-reported outcomes. Digitized radiographs of the hands and feet were obtained at baseline and yearly thereafter. RA was defined as erosive when at least one unequivocal cortical bone defect was detected. Descriptive statistics and Cox regression analysis were performed. RESULTS: At baseline, 71 of the patients were ♀, population median (range) age was of 38.7 (16-78.2) years, 58 patients had antibodies and all the patients had active disease and substantial disability. Follow-up cohort was of 299.3 person-years. At last follow-up (49 ± 13.8 months), 28 patients developed erosions. Erosion's location was the feet, in 12 patients. Incident rates of erosive disease at one, two, three and four years were of 8.1, 12.8, 13.8 and 5.6 per 100 person-years, respectively. Higher C-reactive protein (HR: 1.20, 95%CI: 1.04-1.4, p=0.01) and positive antibodies (HR: 5.09, 95%CI: 1.08-23.86, p=0.04) were baseline predictors of incident erosive disease. Erosions had minor impact on patient-reported outcomes. CONCLUSION: Rheumatoid arthritis patients with antibodies and higher C reactive protein at baseline are at risk for incident erosions which appear most frequently at the feet. Up to 1/3 patients conventionally treated develop incident erosions, which minimally impact function.

Inadequate therapy behavior is associated to disease flares in patients with rheumatoid arthritis who have achieved remission with disease-modifying antirheumatic drugs.

OBJECTIVES: (1) To determine 6-month follow-up adherence and persistence with disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis with disease under control. (2) To compare disease flares across adherent, nonadherent, persistent and nonpersistent patients. (3) To identify differences in adherent and persistent rates among therapeutic regimens. (4) To identify baseline prognosticators of poor compliance. METHODS: Ninety-three patients (86% female) had 4 consecutive 2-month apart evaluations during which the 28-joint disease activity score and the Health Assessment Questionnaire were scored, comorbidities and treatment recorded and a compliance questionnaire and a drug record registry applied. Descriptive statistics, Student t and χ tests and logistic regression analysis were used. RESULTS: At the study entry, patients had mean ± standard deviation age of 40.8 ± 13.9 years, the 28-joint disease activity score of 2.1 ± 1.1, the Health Assessment Questionnaire of 0.09 ± 0.2, and 68 of them (73.1%) had remission. During follow-up, 47 patients (50.5%) were adherent and 51 (54.8%) persistent; 14 of 68 patients (20.6%) who achieved remission had a disease flare. Incidence rate and individual risk of a disease flare were significantly greater in nonadherent and nonpersistent patients. Compared with methotrexate monotherapy, therapeutic regimens with >3 disease-modifying antirheumatic drugs had increased risk of nonadherence and nonpersistence (P ≤ 0.02). Higher previous serial erythrocyte sedimentation rate was associated to nonadherence (as was a shorter follow-up at the Clinic) and to nonpersistence (odds ratio: 1.03; 95% confidence interval: 1.01-1.05 for both, P = 0.05 and P = 0.001, respectively). CONCLUSIONS: Therapy behavior of patients with rheumatoid arthritis with mild/no disease activity and disability was poor and translated into disease flares. Higher serologic activity was associated to poor compliance with therapy.

Hypervascular synovitis and American College of Rheumatology Classification Criteria as predictors of radiographic damage in early rheumatoid arthritis.

UNLABELLED: To investigate if serial clinical and ultrasound evaluations differ between early rheumatoid arthritis patients who do or do not develop erosive disease and to identify predictors of erosions. METHODS: Patients with at least 7 consecutive 2-monthly clinical and 3 consecutive 6-monthly ultrasound evaluations were included. Ultrasound (gray scale and power Doppler) assessed synovitis, power Doppler-positive synovitis (PD+) and power Doppler-negative synovitis (PD-) in each of 14 joints of the dominant hand. After 1 and 2 years, erosive disease was defined according to digitized radiography. Areas under the curve (AUCs) for serial assessments were calculated. Multivariate logistic regression analysis was performed. RESULTS: Seventy-one and 38 patients completed 1- and 2-year consecutive assessments. After 2 years (21.5 +/- 6.2 months), 13 patients developed erosions. At baseline, nonerosive patients had shorter duration of symptoms to RA diagnosis, lower number of the American College of Rheumatology (ACR) classification criteria, lesser synovitis and PD+ synovitis than erosive patients. At follow-up, erosive and nonerosive patients showed similar AUC for clinical, serological, and treatment parameters; erosive patients had higher AUCs for synovitis and PD+ synovitis than nonerosive patients. In the multivariate model, the amount of PD+ synovitis (odds ratio, 1.3; 95% confidence interval, 1.11-1.51; P = 0.001) and more ACR classification criteria (odds ratio, 2.3; 95% confidence interval, 1.05-5.02; P = 0.04), both at baseline, predicted erosive disease. CONCLUSIONS: Serial Power Doppler ultrasonography-assessed synovitis was greater in patients who developed erosions than in those who did not. More power Doppler positive (hypervascular) synovitis and more ACR classification criteria, both at baseline, were the only predictors of erosions.

Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability.

INTRODUCTION: Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. METHODS: Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used. RESULTS: The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P < or = 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (> or = 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 +/- 4.6 versus 13.6 +/- 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P < or = 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02). CONCLUSIONS: Discontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome.

Gout in renal allograft recipients according to the pretransplant hyperuricemic status.

BACKGROUND: Studies to date regarding hyperuricemia and gout in the postrenal transplant (RT) setting do not distinguish neither if patients with gout after the allograft had or did not have hyperuricemia before been transplanted nor if data concerning to hyperuricemia correspond to prevalent or incident cases. Among RT patients, we assessed (1) the incidence of gout in recipients with and without hyperuricemia pre-RT and (2) the incidence of hyperuricemia during the follow-up. METHODS: We selected from our RT registry (1989-2003) 236 subjects who were transplanted in our institution, with at least 1 year follow-up, without gout pre-RT, with at least one measurement of serum uric acid pre-RT and two post-RT. Immunosuppressants, demographic, and clinical features were registered. Survival curves for hyperuricemia and gout were derived using the Kaplan-Meier method and were statistically tested by log rank test. RESULTS: The median follow-up was 4.8 years (1.0-14.9), 43% were women, with a mean body mass index of 22.7+/-3.7 kg/m2 and a mean age at the moment of transplant of 32.4+/-11 years. The incidence of hyperuricemia was 315.2 x 1000 patient-years. Hyperuricemia was diagnosed in half of the subjects during the first year of follow-up. The incidence of gout was 19.7 x 1000 and 2.67 x 1000 patient-years in the groups with and without hyperuricemia pretransplant, respectively (Log rank 9.44, P<0.002). The group with hyperuricemia pre-RT also had earlier and more aggressive gout. CONCLUSIONS: Hyperuricemia was a common complication among RT recipients. However, gout incidence varied according to the pretransplant hyperuricemic status.

Inhibidores adquiridos de la coagulación en una paciente con lupus eritematoso sistémico y anticuerpos antifosfolipídicos: respuesta a rituximab / Aquired inhibitors of coagulation in a patient with systemic lupus erythematosus and antiphospholipid antibodies: response to rituximab

Las manifestaciones hematológicas de los pacientes con lupus eritematoso sistémico (LES) son diversas. Aunque el desarrollo de anticuerpos antifosfolipídicos se asocia con una prolongación in vitro de los tiempos de coagulación, las manifestaciones clínicas suelen ser trombóticas. Los anticoagulantes circulantes que aparecen en pacientes sin anomalías previas de la coagulación son consecuencia del desarrollo de autoanticuerpos contra los factores II, V, VII, VIII y IX, XI, XIII, factor de Von Willebrand u otras glucoproteínas de membrana. Todos ellos condicionan coagulopatías poco comunes, 1 caso por millón de personas por año, y que pueden comprometer seriamente la vida de los pacientes. Presentamos el caso de una mujer con LES y anticuerpos antifosfolipídicos, que presentó síndrome de Evans, como primera manifestación, y posteriormente desarrolló un síndrome hemorrágico, presumiblemente por anticuerpos contra múltiples factores de la cascada de coagulación, sin respuesta a dosis altas de esteroides e inmunosupresores, que finalmente respondió a rituximab (AU)

Hematologic signs of systemic lupus erythematosus are diverse (SLE). Although a delayed coagulation time is anti-phospholipid antibody related, thrombotic events are the usual clinical manifestation. Spontaneous appearance of circulating anticoagulant in the absence of a previous coagulation disorder is secondary to the development of antibodies to factors II, V, VIII, IX, XI, XII, vonWillebrand, and other membrane glucoproteins, all of them uncommon causes (1 case per million persons per year) of life threatening coagulopathies. We report a case of SLE and antiphospholipid antibodies in a woman with a hemorrhagic syndrome, probably caused by multiple antibodies to coagulation factors, unresponsive to steroids and high-dose immunosupressive therapy and a favorable response to rituximab (AU)

[Aquired inhibitors of coagulation in a patient with systemic lupus erythematosus and antiphospholipid antibodies: response to rituximab]. / Inhibidores adquiridos de la coagulación en una paciente con lupus eritematoso sistémico y anticuerpos antifosfolipídicos: respuesta a rituximab.

Hematologic signs of systemic lupus erythematosus are diverse (SLE). Although a delayed coagulation time is anti-phospholipid antibody related, thrombotic events are the usual clinical manifestation. Spontaneous appearance of circulating anticoagulant in the absence of a previous coagulation disorder is secondary to the development of antibodies to factors II, V, VIII, IX, XI, XII,vonWillebrand, and other membrane glucoproteins, all of them uncommon causes (1 case per million persons per year) of life threatening coagulopathies. We report a case of SLE and antiphospholipid antibodies in a woman with a hemorrhagic syndrome, probably caused by multiple antibodies to coagulation factors, unresponsive to steroids and high-dose immunosupressive therapy and a favorable response to rituximab.

Chronic destructive elbow arthropathy associated with hydroxyapatite crystals in a patient with systemic lupus erythematosus.

We describe the case of a young woman with systemic lupus erythematosus (SLE) who presented with painful acute swelling and limited motion of the elbow. Analysis of synovial fluid exhibited a noninflammatory cell count, negative cultures, amorphous nonbirefringent particles, and a positive Alizarin red S staining. X-rays showed calcifications, spurring, sclerosis, and despite the short duration of symptoms, loss of radial-humeral and cubital-humeral joint spaces. The diagnosis of an acute attack within a chronic degenerative arthropathy of the elbow associated with hydroxyapatite crystals was established. Such crystal-induced arthropathy can be an occasional explanation for acute arthritis in SLE.