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.

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.

Opposite lipemic response of Wistar rats and C57BL/6 mice to dietary glucose or fructose supplementation.

The metabolic effects of carbohydrate supplementation in mice have not been extensively studied. In rats, glucose- and fructose-rich diets induce hypertriacylglycerolemia. In the present study, we compared the metabolic responses to two monosaccharide supplementations in two murine models. Adult male Wistar rats (N = 80) and C57BL/6 mice (N = 60), after 3 weeks on a standardized diet, were submitted to dietary supplementation by gavage with glucose (G) or fructose (F) solutions (500 g/L), 8 g/kg body weight for 21 days. Glycemia was significantly higher in rats after fructose treatment (F: 7.9 vs 9.3 mM) and in mice (G: 6.5 vs 10 and F: 6.6 vs 8.9 mM) after both carbohydrate treatments. Triacylglycerolemia increased significantly 1.5 times in rats after G or F supplementation. Total cholesterol did not change with G treatment in rats, but did decrease after F supplementation (1.5 vs 1.4 mM, P < 0.05). Both supplementations in rats induced insulin resistance, as suggested by the higher Homeostasis Model Assessment Index. In contrast, mice showed significant decreases in triacylglycerol (G: 1.8 vs 1.4 and F: 1.9 vs 1.4 mM, P < 0.01) and total cholesterol levels (G and F: 2.7 vs 2.5 mM, P < 0.05) after both monosaccharide supplementations. Wistar rats and C57BL/6 mice, although belonging to the same family (Muridae), presented opposite responses to glucose and fructose supplementation regarding serum triacylglycerol, free fatty acids, and insulin levels after monosaccharide treatment. Thus, while Wistar rats developed features of plurimetabolic syndrome, C57BL/6 mice presented changes in serum biochemical profile considered to be healthier for the cardiovascular system.

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.

[Echocardiography in the evaluation of cardiac involvement in seronegative spondylo-arthropathies]. / El ecocardiograma en la evaluación del compromiso cardiáco en las espondiloartropatías seronegativas.

To evaluate the involvement of the heart in patients with seronegative spondyloarthropathies by echodopplercardiography, 35 patients including 20 with ankylosing spondylitis, 10 with Reiter's syndrome and 5 with psoriatic arthritis (21 men and 14 women, with ages ranging from 17-68 years and averaging 38.5) were studied. Most were asymptomatic with respect to the cardiovascular system (65.71%) and 12 oligosymptomatic with palpitations as their main complaint. Each patient had an echocardiogram and electrocardiogram. A two-dimensional echocardiogram demonstrated alterations in 19 patients (54.29%), 28.58% asymptomatic and 25.71% symptomatic. This study revealed most of lesions (17/19-84.47%) followed by the Dopplerechocardiography (10/19-52.63%) and the one-dimensional echocardiography (9/19-47.36%). Abnormal aortic valves were found in 10 patients, in 7 thickenning and in 3 calcifications. The mitral valve was involved in 11 patients, in 8 thickenning, in 1 calcification and in 2 valve prolapse. In ankylosing spondylitis aortic valve disease was found in 8 patients. Dopplerechocardiography evidenced the presence of aortic regurgitation in 4 patients and mitral insufficiency in 3. The Q-T interval was increased in 19 patients, there was one first degree auriculoventricular block, one right branch block and one sinus bradicardia. Thus the echocardiogram is an excellent noninvasive method to disclose cardiac disturbances in patients with seronegative spondyloarthropaties.

[Cardiac involvement in systemic lupus erythematosus. An echocardiographic evaluation]. / O envolvimento cardíaco no lúpus eritematoso sistêmico. Uma avaliação ecocardiográfica.

PURPOSE: To study, by a non-invasive method, patients with systemic lupus erythematosus (SLE), to evaluate possible cardiac involvement. METHODS: A hundred-eight lupic patients, 60 of them during activity, were studied, independently of cardiovascular signs and symptoms, by M-mode and two-D echocardiography and Doppler. Among the patients in the acute phase, 19 had never used steroid therapy before. RESULTS: Echocardiographic evaluation showed cardiac involvement in all patients who were in clinical activity. Seven had myocardial involvement with systolic impairment. In 35 patients, pericardial effusion was found, all in the acute phase. Regarding endocardial involvement, there were valve thickening in 54 patients in group I (acute phase), valve vegetations in eight and one with mitral valve prolapse. There were only six with valve thickening in group II (remission). Pulmonary hypertension was observed in 15 patients in the activity group and in two during remission. CONCLUSION: Echocardiogram has showed how frequent cardiac involvement is in SLE, especially during disease activity and being independent of previous steroid therapy. As it is a non-invasive method, it could be used in a routine protocol in the evaluation and follow-up of these patients.

Cardiac tamponade in systemic lupus erythematosus. Report of four cases.

OBJECTIVE: To report and assess the incidence of cardiac tamponade in systemic lupus erythematosus as a cardiac manifestation of the disease. METHODS: We reviewed the medical records of 325 patients diagnosed with systemic lupus erythematosus according to the American Rheumatism Association and their complementary laboratory tests compatible with cardiac tamponade. RESULTS: In the 325 medical records reviewed, we found 108 patients with pericardial effusions corresponding to 33.2% of the total and 54% of the patients studied in the active phase of the disease. Clinical assessment and transthoracic echocardiogram allowed the clinical diagnosis of cardiac tamponade in only 4 (1.23%) patients, 3 of whom were females, white, with ages ranging from 25 to 44 years. The pericardial fluid was hemorrhagic or serosanguineous with high levels of FAN and positivity for LE cells. In the treatment, we successfully used pericardiocentesis associated with high doses of corticosteroids. In clinical and laboratory follow-up performed for a period of 3 years, neither recrudescence of the pericardial effusion nor evolution to constriction occurred. CONCLUSION: Even though rare (1.23%), cardiac tamponade in patients with systemic lupus erythematosus has a benign evolution when properly treated, according to our experience.

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.

Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study.

We conducted a randomized, controlled study to assess the need for hydroxychloroquine (HCQ) during lupus pregnancy and to assess safety. Twenty consecutive pregnant patients with similar characteristics were enrolled. The HCQ group included eight patients with systemic lupus erythematosus (SLE) and two with discoid lupus erythematosus (DLE). The placebo (PL) group included nine patients with SLE and one with DLE. The HCQ group had no flare-ups. SLEPDAI scores were similar at study entry, and at conclusion the placebo group had significantly higher scores. One patient had improvement of skin lesions and another of arthritis, allowing a decrease of prednisone dose. There were no retinal effects. Three patients in the PL group flared up, two with skin rashes, one also with arthritis and uveitis, and one (previously in remission on HCQ) with hemolytic anemia, polyserositis and anti-dsDNA antibody. Toxemia was diagnosed in only three patients in the PL group (one fetal death). Comparing prednisone dosage change, we noted a decrease in the HCQ and an increase in the PL group. Delivery age and Apgar scores were higher in the HCQ group. Neonatal examination did not reveal congenital abnormalities, nor did a neuro-ophthalmological and auditory evaluation at 1.5-3 y of age. In spite of the small number of patients studied, we noted beneficial effects of HCQ during lupus pregnancy, as measured by SLEPDAI and decrease in prednisone dose with no detriment to patients' health.

Opposite lipemic response of Wistar rats and C57BL/6 mice to dietary glucose or fructose supplementation

The metabolic effects of carbohydrate supplementation in mice have not been extensively studied. In rats, glucose- and fructose-rich diets induce hypertriacylglycerolemia. In the present study, we compared the metabolic responses to two monosaccharide supplementations in two murine models. Adult male Wistar rats (N = 80) and C57BL/6 mice (N = 60), after 3 weeks on a standardized diet, were submitted to dietary supplementation by gavage with glucose (G) or fructose (F) solutions (500 g/L), 8 g/kg body weight for 21 days. Glycemia was significantly higher in rats after fructose treatment (F: 7.9 vs 9.3 mM) and in mice (G: 6.5 vs 10 and F: 6.6 vs 8.9 mM) after both carbohydrate treatments. Triacylglycerolemia increased significantly 1.5 times in rats after G or F supplementation. Total cholesterol did not change with G treatment in rats, but did decrease after F supplementation (1.5 vs 1.4 mM, P < 0.05). Both supplementations in rats induced insulin resistance, as suggested by the higher Homeostasis Model Assessment Index. In contrast, mice showed significant decreases in triacylglycerol (G: 1.8 vs 1.4 and F: 1.9 vs 1.4 mM, P < 0.01) and total cholesterol levels (G and F: 2.7 vs 2.5 mM, P < 0.05) after both monosaccharide supplementations. Wistar rats and C57BL/6 mice, although belonging to the same family (Muridae), presented opposite responses to glucose and fructose supplementation regarding serum triacylglycerol, free fatty acids, and insulin levels after monosaccharide treatment. Thus, while Wistar rats developed features of plurimetabolic syndrome, C57BL/6 mice presented changes in serum biochemical profile considered to be healthier for the cardiovascular system.

Avaliação clinica do efeito do verapamil em pacientes hipertensos / Clinical evaluation of the effect of verapamil in hypertensive patients

Os autores estudaram 20 pacientes com hipertensão essencial e função renal normal. O efeito do verapamil, em diferentes associações por períodos de 14 dias, foi avaliado através da determinação da pressão arterial na posição deitada e em pe, da frequência cardíaca e do intervalo P-R. Os vários períodos foram comparados quanto as variáveis estudadas bem como quanto aos efeitos colaterais

El ecocardiograma en la evaluación del compromiso cardiáco en las espondiloartropatías seronegativas. / [Echocardiography in the evaluation of cardiac involvement in seronegative spondylo-arthropathies]

To evaluate the involvement of the heart in patients with seronegative spondyloarthropathies by echodopplercardiography, 35 patients including 20 with ankylosing spondylitis, 10 with Reiters syndrome and 5 with psoriatic arthritis (21 men and 14 women, with ages ranging from 17-68 years and averaging 38.5) were studied. Most were asymptomatic with respect to the cardiovascular system (65.71

) and 12 oligosymptomatic with palpitations as their main complaint. Each patient had an echocardiogram and electrocardiogram. A two-dimensional echocardiogram demonstrated alterations in 19 patients (54.29

), 28.58

asymptomatic and 25.71

symptomatic. This study revealed most of lesions (17/19-84.47

) followed by the Dopplerechocardiography (10/19-52.63

) and the one-dimensional echocardiography (9/19-47.36

). Abnormal aortic valves were found in 10 patients, in 7 thickenning and in 3 calcifications. The mitral valve was involved in 11 patients, in 8 thickenning, in 1 calcification and in 2 valve prolapse. In ankylosing spondylitis aortic valve disease was found in 8 patients. Dopplerechocardiography evidenced the presence of aortic regurgitation in 4 patients and mitral insufficiency in 3. The Q-T interval was increased in 19 patients, there was one first degree auriculoventricular block, one right branch block and one sinus bradicardia. Thus the echocardiogram is an excellent noninvasive method to disclose cardiac disturbances in patients with seronegative spondyloarthropaties.