Effectiveness of pharmaceutical care for drug treatment adherence in women with lupus nephritis in Rio de Janeiro, Brazil: a randomized controlled trial.

OBJECTIVE: Studies have been conducted to determine the causal factors and clinical consequences of non-adherence to treatment in systemic lupus erythematosus (SLE). However, no interventions have been performed to increase drug adherence. Our objective was to assess the effectiveness of pharmaceutical care (PC) for drug treatment adherence in lupus nephritis (LN). METHODS: This was a randomized clinical trial (pragmatic trial) in patients with LN in Rio de Janeiro, Brazil, allocated in two groups: an intervention group (Dader Method for PC) and a control group (institution's usual care). Drug treatment adherence was measured by the combination of five questions normally used in clinical practice. RESULTS: A total of 131 patients were randomized, and 122 completed the study, with a mean follow-up of 12.7 months and use of six drugs per day and 10-12 doses per day. Low adherence was observed at baseline (intervention group: 30%; control group: 29%). PC showed 27% effectiveness (95% confidence interval (CI) -6% to 50%) in the intention to treat analysis and 31% (95% CI 0-52%) in per protocol analysis, considering all drugs. As for adherence to specific drugs for SLE, effectiveness of PC was 64% (95% CI 34-80%) with intention-to-treat analysis and 62% (95% CI 32-79%) in per protocol analysis. CONCLUSIONS: PC was effective for increasing drug treatment adherence in SLE. The detailed account provided by the Dader Method of the difficulties with patients' drug therapy proved invaluable to approach non-adherence.

Gestational outcomes in patients with neuropsychiatric systemic lupus erythematosus.

This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.

Immunogenicity of pneumococcal polysaccharide vaccine in adult systemic lupus erythematosus patients undergoing immunosuppressive treatment.

OBJECTIVE: To evaluate the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adult systemic lupus erythematosus patients undergoing (IS group) and not undergoing (non-IS group) immunosuppressive treatment. METHODS: In this prospective open-label study from February 2013 to April 2014, 54 patients had blood samples collected immediately before PPSV23 immunization and 4-6 weeks thereafter for the ELISA measurement of IgG antibody levels against seven pneumococcal serotypes. Positive vaccine response for each serotype was defined as a four-fold or greater antibody response over baseline levels or as a post-vaccine anti-pneumococcal IgG level ≥1.3 µg/ml when baseline values were <1.3 µg/ml. Patients should have responded appropriately to ≥70% of the tested serotypes. We also calculated the mean ratio of post- to pre-vaccination anti-pneumococcal IgG levels. RESULTS: Twenty-eight patients were classified into the IS group and 26 into non-IS group. The median dose of prednisone at baseline was ≤5 mg/day in both groups. Serotype-specific vaccine response rates were not significantly different between the groups. Less than 40% of patients responded adequately by both vaccine response criteria, being numerically lower among IS patients. The mean ratio of increase in anti-pneumococcal levels was 6.4 versus 4.7 (p = 0.001) in non-IS and IS groups, respectively. CONCLUSION: The vaccine was poorly immunogenic, especially among adult systemic lupus erythematosus patients under immunosuppressive therapy.

Lupus and leprosy: beyond the coincidence.

Systemic lupus erythematous (SLE) is an autoimmune disease that presents an increased susceptibility to infections which may trigger reactivation. Disease flares have been mostly associated with parvovirus B19, cytomegalovirus, EBV and Mycobacterium tuberculosis infections, but it is probable that many other agents may also induce innate and adaptive immune system stimulation including the production of autoantibodies as ANA, anti nDNA and anti-ß2-GPI mainly in lepromatous leprosy. Mycobacterium leprae not only may determine symptoms that mimic lupus flares, including autoantibodies production, but could also act as a trigger for lupus reactivation; however, its association is still not fully explored. As demonstrated for tuberculosis, it is quite possible that molecular mimicry may also be involved in the interface of these two diseases. Some studies reported shared epitopes among idiotypes derived from 8E7 and TH9 lepromatous antibodies and those obtained from SLE patients, and it could partially explain the triggering phenomenon of SLE caused by M. leprae. We report and discuss three Brazilian patients whose disease was inactive and presented disease flares concurrently with the diagnosis of leprosy.

The use of angiogenic and antiangiogenic factors in the differential diagnosis of pre-eclampsia, antiphospholipid syndrome nephropathy and lupus nephritis.

Pre-eclampsia (PE) is a major cause of maternal mortality and morbidity, perinatal deaths, preterm birth and intrauterine growth restriction. Differential diagnosis with antiphospholipid syndrome (APS) nephropathy and systemic lupus erythematosus (SLE) nephritis during pregnancy is difficult, if not sometimes impossible, as all three diseases may present hypertension and proteinuria. Improvement in diagnosis of PE has also offered new paths for differential diagnosis with other conditions and the analysis of angiogenic (vascular endothelial growth factor, placental growth factor) and antiangiogenic factors (serum soluble fms-like tyrosine kinase 1, soluble endoglin) is promising for differentiation between PE, APS nephropathy and SLE nephritis. This article reviews published studies about those factors in non-pregnant and pregnant patients with APS and SLE, comparing with patterns described in PE.

Renal transplantation in lupus nephritis: a Brazilian cohort.

OBJECTIVE: To determine the epidemiological profile and outcome of patients with lupus nephritis (LN) undergoing renal transplantation. METHODS: The archival records of 50 patients with LN and end-stage renal disease (ESRD) treated by kidney transplantation from March 1992 to December 2010 were reviewed. All patients met the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). RESULTS: Fourteen patients were included in the study. The majority were women (85.7%) and non-Caucasian (85.7%); the mean age at diagnosis of SLE and LN was 24 ± 8 and 25 ± 8 years, respectively. Renal biopsy was performed in 12 patients, with 75% of them showing proliferative lesions (class III and IV according to the World Health Organization and International Society of Nephrology/Renal Pathology Society classification). Thirteen patients (93%) underwent intermittent hemodialysis or peritoneal dialysis before transplantation. The median time between the start of dialysis and transplantation was 30 months (range 3-103 months); 67% of the procedures involved deceased donors and 33% involved living-related donors. The graft survival rates were 93.3%, 90.9%, and 85.7% at 1, 5 and 10 years, respectively. Post-transplant immunosuppressive agents were mycophenolate mofetil (84%), azathioprine (17%), tacrolimus (25%), sirolimus (58%) and cyclosporine (8%). Eight episodes of acute rejection were noted in six patients. There was a graft loss due to renal vein thrombosis in the one patient with secondary antiphospholipid syndrome. The mean SLICC by the time of kidney transplantation was 5 ± 2. In total, 13 patients (92.8%) developed at least one infectious event during the follow-up, with one dying in the immediate post-transplant period because of sepsis. Two patients (14%) had a lupus flare. There was no clinical or histological evidence of LN recurrence. CONCLUSION: LN is the major cause of morbidity in SLE, with progression to ESRD in 10-22% of cases. Despite concerns about LN recurrence after renal transplantation, the data obtained in our sample indicate this procedure as a safe alternative therapy for ESRD in this population.

Evaluation of adherence to drug treatment in patients with systemic lupus erythematosus in Brazil.

The objectives of this study were to measure the prevalence of adherence to drug treatment and analyze associations with characteristics pertaining to the treatment, disease, health professionals and services, and socio-demographic issues in patients with systemic lupus erythematosus (SLE) in the city of Rio de Janeiro, Brazil. A sample of 246 women with SLE was analyzed. The data were collected through individual interviews and a review of patient charts. Adherence was estimated according to the Morisk criteria, and the associated factors were analyzed by hierarchical modeling. The percentage of patients classified as adherent to treatment was 31.7%. The reasons cited for non-adherence were: carelessness with drug administration times (52.43%), forgetfulness (38.21%), adverse drug reaction (13.8%), and interruption of treatment due to improvement in symptoms (7.72%). Factors associated with adherence were: behavior towards the presence of adverse drug reaction, hematological alterations, presence of mucocutaneous manifestations, legibility of the medical prescription, schooling, and family support. The study concludes that adherence to drug treatment in SLE is a complex and multifactorial phenomenon, and the results corroborate findings from studies conducted in developed countries. The hierarchical modeling proved to be a good alternative for evaluating adherence, since it allowed visualizing the various stages in the analysis.

Are women with lupus at higher risk of HPV infection?

Human papillomavirus (HPV) is the etiological agent of cervical cancer, the second most prevalent neoplasia among women. Although it has been proven that systemic lupus erythematosus (SLE) patients have higher frequency of cervical dysplasia, few studies have focused on HPV prevalence among them. This study aimed to investigate HPV prevalence among SLE patients and to evaluate associated risk factors, including the use of immunosuppressors (IM). Total DNA extracted from cervical samples of 173 SLE patients and 217 women (control group) submitted to routine cervical cytopathology was used as template in polymerase chain reaction (PCR)-based assays for detection of HPV DNA. HPV genotyping was performed by type-specific PCR, PCR-RFLP and/or DNA sequencing. Statistical methods included univariate analysis and logistic regression. Despite presenting significantly fewer HPV risk factors, SLE patients were found to have a threefold increase in HPV infection, mostly genotypes 53, 58, 45, 66, 6, 84, 83, 61, as compared with controls, who presented types 6, 18 and 61 more frequently. The higher rate of HPV infection was associated with immunosuppressive therapy. This study provides evidence that SLE patients have a high prevalence of HPV infection, which is even higher with the use of IM, a condition that might necessitate a more frequent cervical cancer screening program for these women.

Can lupus flares be associated with tuberculosis infection?

Systemic lupus erythematosus (SLE) is an autoimmune disease that frequently requires treatment with high doses of corticosteroids and immunosuppressive drugs. Primary defects in the innate immunity also contribute to an increased susceptibility to infections. Patients with SLE are at an increased risk for infections with several pathogens, among them Mycobacterium tuberculosis, which is a significant cause of morbidity and mortality, especially in endemic regions. TB infection requires awareness for several reasons: first, TB infection thrives under conditions of immunosuppression, may it be secondary to the disease itself or its treatment. Second, shared antigens by mycobacteria and autoantigens have been described, which may be targets for autoantibodies. We present four Brazilian patients, in whom a diagnosis of tuberculosis was determined during or following persistent flares of their disease. The association of SLE and TB is discussed, as well as different aspects of the tuberculosis infection in this selected population, and its possible role in the course of SLE.