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 recors 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 pericardicentesis 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.

Echocardiographic Abnormalities and Antiphospholipid Antibodies in Patients with Systemic Lupus Erythematosus

OBJECTIVE: Lupus anticoagulant and anticardiolipin antibodies (aCL) have been associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), but their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between antiphospholipid antibodies (aPL) and echocardiographic abnormalities in patients with SLE. METHODS: A total of 70 consecutive patients and 42 control subjects underwent M-mode, 2-dimensional and Doppler echocardiography and tests for lupus anticoagulant, aCL IgG, IgM, and IgA. Lupus anticoagulant was assayed with the dilute Russell viper venom time, and aCL IgG, IgM, and IgA were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Lupus anticoagulant showed a prevalence of 10%. As a whole, aCL had a prevalence of 44.3% and aPL had a prevalence of 50%. Patients with echocardiographic abnormalities had a prevalence of 54.3% and showed a trend towards an association with aCL IgG (P=0.06). The presence of pulmonary hypertension (PH) was significantly associated with aCL IgG (p=0.02). CONCLUSION: aCL IgG was significantly associated with PH and showed a strong trend towards an association with echocardiographic abnormalities taken together. These findings suggest a role for aCL IgG in the development of lupus cardiovascular disease.

Noninvasive cardiac assessment in children of women with systemic lupus erythematosus

OBJECTIVE: Noninvasive cardiac assessment of newborns and infants of women with systemic lupus erythematosus. The children had no congenital total atrioventricular block and were compared with the children of healthy women. METHODS: We prospectively assessed 13 newborns and infants aged 1 to 60 days, children of women with systemic lupus erythematosus and without congenital total atrioventricular block. These children were compared with 30 children of women who had no lupus or anti-Ro/SSA antibodies, and no risk factors for congenital heart disease either. Their age groups matched. The following examinations were performed: cardiological physical examination, electrocardiography, echocardiography, and signal-averaged electrocardiography. RESULTS: The statistical analysis showed no significant difference in ventricular function or in the cardiac conduction system between the groups. CONCLUSION: In regard to the conduction system and ventricular function in the absence of total atrioventricular block, no statistically significant difference was observed between the children of women with systemic lupus erythematosus and children of healthy women.

Lupus eritematoso sistêmico: novo fator de risco para aterosclerose?

OBJETIVO: Avaliar a prevalência de eventos cardiovasculares (ECV) secundários à aterosclerose em pacientes com lupus eritematoso sistêmico (LES) e correlacioná-los aos tradicionais fatores de risco, tempo de doença e drogas utilizadas na terapia. MÉTODOS: Estudo retrospectivo através da coleta e análise dos dados contidos nos prontuários de pacientes com diagnóstico confirmado há no mínimo dois anos e seguidos desde 1992. Foram considerados ECV: angina do peito (AP), IAM e acidente vascular cerebral (AVC) de causa não relacionada à atividade do LES. Foram computados os fatores de risco para aterosclerose e dados sobre tratamento. RESULTADOS: Foram analisados 71 prontuários. A média de idade dos pacientes foi de 34,2±12,7 anos; 68 mulheres e três homens; 58 caucasóides (81,6%). Dez (14,08%) apresentaram ECV. Os pacientes nos quais os eventos cardiovasculares foram observados apresentavam idade mais elevada (42,7 vs 32,8 anos p=0,0021) e maior tempo de doença (10,8 vs 7,2 anos p=0,011). Os tradicionais fatores de risco, as doses diárias e cumulativas de esteróides, imunossupressores e antimaláricos não apresentaram diferença estatística significante entre pacientes que apresentaram ou não ECV. CONCLUSÃO: A prevalência de secundários à aterosclerose no LES foi semelhante ao da literatura, 14,08%. Os tradicionais fatores de risco não mostraram associação com a ocorrência ou não de ECV no LES. Os pacientes nos quais os eventos cardiovasculares foram observados apresentavam idade mais elevada e maior tempo de doença. É precoce estabelecer-se que o LES possa ser um fator independente no desenvolvimento da aterosclerose.

Alterações hematológicas em cães (Canis lupus familiaris) após tratamento com eletroacupuntura

A acupuntura, é uma terapia que cada vez mais adquire uma credibilidade no mundo ocidental, a sua indicação pode ser para pacientes anêmicos e imunossuprimidos, e outras afecções. O experimento foi realizado com oito cães adultos, sendo 4 fêmeas e 4 machos. O estudo consistiu em análise das concentrações das células vermelhas e brancas avaliado em 4 tratamentos: controle (T0), acupuntura (T1), eletroacupuntura unilateral (T2) e eletroacupuntura bilateral (T3). Os acupontos utilizados foram intestino grosso 4, intestino grosso 11 e estômago 36. Todos os animais passaram por todos os tratamentos com um intervalo de 7 dias para cada tratamento. Os hemogramas séricos foram verificados 20 minutos antes do início do tratamento (M0), logo após o tratamento (M1), e 60 minutos (M2) e 120 minutos (M3) após o tratamento. O resultado da série vermelha não foi significativo, mas notou-se somente uma diminuição significativa da concentração média corpuscular (CHCM) (p<0,05) no tratamento T1 no M1 em comparação aos outros tratamentos; notou-se também uma redução significativa (p<0,05) na concentração plaquetária de T1, T2 e T3 em comparação ao grupo controle. A eletroacupuntura pode levar a uma trombocitopenia, quando estimulado estes pontos, provavelmente por um estímulo parassimpaticomimético.

Association between EcoRI fragment-length polymorphism of the immunoglobulin lambda variable 8 (IGLV8) gene family with rheumatoid arthritis and systemic lupus erythematosus

The human immunoglobulin lambda variable 8 (IGLV8) subgroup is a gene family containing three members, one of them included in a monomorphic 3.7-kb EcoRI genomic fragment located at the major lambda variable locus on chromosome 22q11.1 (gene IGLV8a, EMBL accession No. Z73650) at 100% frequency in the normal urban population. The second is a polymorphic RFLP allele included in a 6.0-kb EcoRI fragment at 10% frequency, and the third is located in a monomorphic 8.0-kb EcoRI fragment at 100% frequency, the last being translocated to chromosome 8q11.2 and considered to be an orphan gene. Our Southern blot-EcoRI-RFLP studies in normal individuals and in patients with rheumatoid arthritis (RA) or with systemic lupus erythematosus (SLE), using a specific probe for the IGLV8 gene family (probe pVL8, EMBL accession No. X75424), have revealed the two monomorphic genomic fragments containing the IGLV8 genes, i.e., the 3.7-kb fragment from chromosome 22q11.1 and the 8.0-kb fragment from 8q11.2, both occurring at 100% frequency (103 normal individuals, 48 RA and 28 SLE patients analyzed), but absence of the 6.0-kb IGLV8 polymorphic RFLP allele in all RA or SLE patients. As expected, the frequency of the 6.0-kb allele among the normal individuals was 10%. These findings suggest an association between the absence of the 6.0-kb EcoRI fragment and rheumatoid arthritis and systemic lupus erythematosus.

Risk factors for ovarian failure in patients with systemic lupus erythematosus

The aim of the present study was to identify the risk factors for ovarian failure in patients with systemic lupus erythematosus. Seventy-one women aged 17 to 45 years with systemic lupus erythematosus were studied. Patients were interviewed and their medical records reviewed. Demographic characteristics, clinical and serologic profiles, and menstrual and obstetric histories were recorded. Disease activity was measured by the systemic lupus erythematosus disease activity index. Serum FSH, LH, estradiol, progesterone, TSH, prolactin, and antimicrosomal and antithyroglobulin antibodies were measured. Patients who developed ovarian failure were compared to those who did not. Ovarian failure occurred in 11 patients (15.5%) and nine had premature menopause (11.3%). Cyclophosphamide administration and older patient age were found to be associated with ovarian failure. The cumulative cyclophosphamide dose was significantly higher in patients with ovarian failure than in those without this condition (18.9 vs 9.1 g; P = 0.04). The relative risk for ovarian failure in patients with cumulative cyclophosphamide dose higher than 10 g was 3.2. TSH levels were high in 100% of patients with ovarian failure who had received pulse cyclophosphamide. Ovarian failure, and premature menopause in particular, is common in patients with systemic lupus erythematosus, with the most important risk factors being cyclophosphamide dose and age. Thyroid problems may be another risk factor for ovarian failure in patients with lupus.

Lung clearance of 99mTc-DTPA in systemic lupus erythematosus

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99mTc-DTPA is increased in SLE patients with active disease.

Use of single photon emission computed tomography and magnetic resonance to evaluate central nervous system involvement in patients with juvenile systemic lupus erythematosus

The objective of the present study was to identify the single photon emission computed tomography (SPECT) and magnetic resonance (MR) findings in juvenile systemic lupus erythematosus (JSLE) patients with CNS involvement and to try to correlate them with neurological clinical history data and neurological clinical examination. Nineteen patients with JSLE (16 girls and 3 boys, mean age at onset 9.2 years) were submitted to neurological examination, electroencephalography, cerebrospinal fluid analysis, SPECT and MR. All the evaluations were made separately within a period of 15 days. SPECT and MR findings were analyzed independently by two radiologists. Electroencephalography and cerebrospinal fluid analysis revealed no relevant alterations. Ten of 19 patients (53%) presented neurological abnormalities including present or past neurological clinical history (8/19, 42%), abnormal neurological clinical examination (5/19, 26%), and abnormal SPECT or MR (8/19, 42% and 3/19, 16%, respectively). The most common changes in SPECT were cerebral hypoperfusion and heterogeneous distribution of blood flow. The most common abnormalities in MR were leukomalacia and diffuse alterations of white matter. There was a correlation between SPECT and MR (P<0.05). We conclude that SPECT and MR are complementary and useful exams in the evaluation of neurological involvement of lupus.

Bone mineral density in juvenile systemic lupus erythematosus

We evaluated spine bone mineral density (BMD) in Brazilian children with juvenile systemic lupus erythematosus (JSLE) in order to detect potential predictors of reduction in bone mass. A cross-sectional study of BMD at the lumbar spine level (L2-L4) was conducted on 16 female JSLE patients aged 6-17 years. Thirty-two age-matched healthy girls were used as control. BMD at the lumbar spine was measured by dual-energy X-ray absorptiometry. Weight, height and pubertal Tanner stage were determined in patients and controls. Disease duration, mean daily steroid doses, mean cumulative steroid doses and JSLE activity measured by the systemic lupus erythematosus disease activity index (SLEDAI) were determined for all JSLE patients based on their medical charts. All parameters were used as potential determinant factors for bone loss. Lumbar BMD tended to be lower in the JSLE patients, however, this difference was not statistically significant (P = 0.10). No significant correlation was observed in JSLE girls between BMD and age, height, Tanner stage, disease duration, corticosteroid use or disease activity. We found a weak correlation between BMD and weight (r = 0.672). In the JSLE group we found no significant parameters to correlate with reduced bone mass. Disease activity and mean cumulative steroid doses were not related to BMD values. We did not observe reduced bone mass in female JSLE.

Immunoglobulin E and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by intense polyclonal production of autoantibodies and circulating immune complexes. Some reports have associated SLE with a Th2 immune response and allergy. In the present study 21 female patients with SLE were investigated for total IgE and IgE antibodies to dust house aeroallergens by an automated enzyme-linked fluorescent assay, and were also evaluated for antinuclear IgE autoantibodies by a modified indirect immunofluorescence test using HEp-2 cells as antigen substrate. Additionally, immunocapture ELISA was used to investigate serum anti-IgE IgG autoantibodies. Serum IgE above 150 IU/ml, ranging from 152 to 609 IU/ml (median = 394 IU IgE/ml), was observed in 7 of 21 SLE patients (33%), 5 of them presenting proteinuria, urinary cellular casts and augmented production of anti-dsDNA antibodies. While only 2 of 21 SLE patients (9.5%) were positive for IgE antibodies to aeroallergens, all 10 patients with respiratory allergy (100%) from the atopic control group (3 males and 7 females), had these immunoglobulins. SLE patients and healthy controls presented similar anti-IgE IgG autoantibody titers (X = 0.37 ± 0.20 and 0.34 ± 0.18, respectively), differing from atopic controls (0.94 ± 0.26). Antinuclear IgE autoantibodies were detected in 17 of 21 (81%) sera from SLE patients, predominating the fine speckled pattern of fluorescence, that was also observed in IgG-ANA. Concluding, SLE patients can present increased IgE levels and antinuclear IgE autoantibodies without specific clinical signs of allergy or production of antiallergen IgE antibodies, excluding a possible association between SLE and allergy.

Risk factors associated with the death of patients hospitalized for juvenile systemic lupus erythematosus

We assessed the risk factors associated with death in patients hospitalized for juvenile systemic lupus erythematosus (JSLE) and evaluated the autopsy reports. A total of 57,159 hospitalizations occurred in our institution from 1994 to 2003, 169 of them involving 71 patients with JSLE. The most recent hospitalization of these patients was evaluated. Patients were divided into two groups based on mortality during hospitalization: those who survived (N = 53) and those who died (N = 18). The main causes of hospitalization were JSLE activity associated with infection in 52% and isolated JSLE activity in 44%. Univariate analysis showed that a greater risk of death was due to severe sepsis (OR = 17.8, CI = 4.5-70.9), systemic lupus erythematosus disease activity index (SLEDAI) ³8 (OR = 7.6, CI = 1.1-53.8), general infections (OR = 6.1, CI = 1.5-25), fungal infections (OR = 5.4, CI = 3.2-9), acute renal failure (OR = 5.1, CI = 2.5-10.4), acute thrombocytopenia (OR = 3.9, CI = 1.9-8.4), and bacterial infections (OR = 2.3, CI = 1.2-7.5). Stratified analysis showed that severe sepsis and SLEDAI ³8 were not confounder variables. In the multivariate analysis, logistic regression showed that the only independent variable in death prediction was severe sepsis (OR = 98, CI = 16.3-586.2). Discordance between clinical diagnosis and autopsy was observed in 6/10 cases. Mortality of hospitalized JSLE patients was associated with severe sepsis. Autopsy was important to determine events not detected or doubtful in dead patients and should always be requested.

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.