Rituximab in refractory autoimmune diseases: Brazilian experience with 29 patients (2002-2004).

OBJECTIVE: Rituximab, a monoclonal antibody against B-lymphocytes that express CD 20, is already available for the treatment of non-Hodgkin's lymphoma. Due to the increased relevance of B-cell regulation in the pathogenesis of autoimmune diseases, rituximab is being used in the treatment of patients whose condition is refractory to conventional therapy. METHODS: We retrospectively evaluated the short-term efficacy and tolerance of rituximab in patients with various autoimmune diseases who were treated at the Hospital Israelita Albert Einstein in the city of Sao Paulo. RESULTS: During the period 2002-2004, 29 patients with various autoimmune diseases were treated with rituximab 375 mg/m2 for 4 consecutive weeks, or two doses of 1 g 2 weeks apart. We observed remarkable short-term results in all cases, except for one patient with thrombocytopenic purpura. Of note, we describe the results in two patients with diseases not previously treated with rituximab (hypergammaglobulinemic purpura of Waldenstrom and eosinophilic fasciitis with hypergammaglobulinemia). Treatment was well tolerated, with no unexpected adverse events. We also observed a marked reduction in steroid dosage. CONCLUSION: Rituximab seems to be safe and effective in the treatment of patients with a variety of autoimmune diseases that are refractory to other modalities of treatment.

Resource utilization and cost of rheumatic fever.

OBJECTIVE: The socioeconomic effects of rheumatic fever (RF) in Brazil, including direct and indirect costs to patients and their families and to society, are largely unknown. We evaluated the utilization of resources and costs related to RF in a tertiary center caring for low income patients in the city of São Paulo, Brazil. METHODS: One hundred patients with RF, younger than 18 yrs, with followup of at least one year, were sequentially selected to provide complete information on a questionnaire. Additional data were collected from patients' charts. The utilization of resources was evaluated for each patient throughout the entire disease course. Costs were determined for patients and their families as well as for the society, using variables from 3 different systems: the national public health system, used by most lower income groups; the Brazilian Medical Association, which regulates charges and fees utilized by health plans and insurance companies; and costs charged by private practitioners, paid directly by patients. RESULTS: The RF population studied belonged to a low socioeconomic level. The mean monthly family income was $625.20 US. The mean disease duration was 3.9 yrs (range 1-10). Patients had a total of 1657 medical consultations, 22 hospital admissions, and 4 admissions to intensive care unit. Work absenteeism among parents was calculated as 22.9%, equivalent to 901 days of missed work; about 5% of the parents lost their jobs. Patients showed a high rate of school failure (22%). Considering the public system as a reference, direct, indirect, and total costs to society per 100 patients throughout the entire disease duration were $105,860 US ($271/patient/yr), $18,803 US ($48/patient/yr), and $124,663 US (US $319/patient/yr), respectively. When health care plan and private systems were taken as reference, the total costs were $423,550 US and $684,351 US, respectively. CONCLUSION: RF and rheumatic heart disease have an important socioeconomic impact in Brazil; costs of RF made up roughly 1.3% of annual family income. The estimated annual cost of RF for society in Brazil is $51,144,347.00 US.

Bone mineral density of the lumbar spine of Brazilian children and adolescents aged 6 to 14 years

The authors performed a study of bone mass in eutrophic Brazilian children and adolescents using dual-energy X-ray absorptiometry (DXA) in order to obtain curves for bone mineral content (BMC) and bone mineral density (BMD) by chronological age and correlate these values with weight and height. Healthy Caucasian children and adolescents, 120 boys and 135 girls, 6 to 14 years of age, residents of São Paulo, Brazil, were selected from the Pediatric Department outpatient clinic of Hospital São Paulo (Universidade Federal de São Paulo). BMC, BMD and the area of the vertebral body of the L2-L4 segment were obtained by DXA. BMC and BMD for the lumbar spine (L2-L4) presented a progressive increase between 6 and 14 years of age in both sexes, with a distribution that fitted an exponential curve. We identified an increase of mineral content in female patients older than 11 years which was maintained until 13 years of age, when a new decrease in the velocity of bone mineralization occurred. Male patients presented a period of accelerated bone mass gain after 11 years of age that was maintained until 14 years of age. At 14 years of age the mean BMD values for boys and girls were 0.984 and 1.017 g/cm², respectively. A stepwise multiple regression analysis of paired variables showed that the "vertebral area-age" pair was the most significant in the determination of BMD values and the introduction of a third variable (weight or height) did not significantly increase the correlation coefficient

Translation, adaptation and validation of the Roland-Morris questionnaire - Brazil Roland-Morris

The purpose of the present study was to translate the Roland-Morris (RM) questionnaire into Brazilian-Portuguese and adapt and validate it. First 3 English teachers independently translated the original questionnaire into Brazilian-Portuguese and a consensus version was generated. Later, 3 other translators, blind to the original questionnaire, performed a back translation. This version was then compared with the original English questionnaire. Discrepancies were discussed and solved by a panel of 3 rheumatologists and the final Brazilian version was established (Brazil-RM). This version was then pretested on 30 chronic low back pain patients consecutively selected from the spine disorders outpatient clinic. In addition to the traditional clinical outcome measures, the Brazil-RM, a 6-point pain scale (from no pain to unbearable pain), and its numerical pain rating scale (PS) (0 to 5) and a visual analog scale (VAS) (0 to 10) were administered twice by one interviewer (1 week apart) and once by one independent interviewer. Spearman's correlation coefficient (SCC) and intraclass correlation coefficient (ICC) were computed to assess test-retest and interobserver reliability. Cross-sectional construct validity was evaluated using the SCC. In the pretesting session, all questions were well understood by the patients. The mean time of questionnaire administration was 4 min and 53 s. The SCC and ICC were 0.88 (P<0.01) and 0.94, respectively, for the test-retest reliability and 0.86 (P<0.01) and 0.95, respectively, for interobserver reliability. The correlation coefficient was 0.80 (P<0.01) between the PS and Brazil-RM score and 0.79 (P<0.01) between the VAS and Brazil-RM score. We conclude that the Brazil-RM was successfully translated and adapted for application to Brazilian patients, with satisfactory reliability and cross-sectional construct validity

Nail fold capillaroscopy: normal findings in children and adolescents.

OBJECTIVES: Capillaroscopy is a simple diagnostic method that permits noninvasive in vivo study of the capillary network. Studies designed to standardize capillary normality in children are limited. This article presents the capillaroscopic findings in healthy children and adolescents, thus making the application of this methodology viable for patients in this age range. MATERIAL AND METHODS: Healthy children were recruited from a private elementary school and junior high school. Nail fold capillaroscopy was performed using a stereomicroscope at 16 times magnification, addressing the following parameters: capillary morphology, capillary enlargement, devascularization, microhemorrhage, and subpapillary venous plexus visibility (PVS). These parameters were related to age, sex, ethnicity, and local periungal conditions. RESULTS: The sample comprised 329 individuals with mean age of 8.2 years. We observed atypical capillary morphology in 118 of the studied cases (36%), mainly bizarre capillaries in 90 (27%), meandering capillaries in 32 (10%), and bushy capillaries in 20 (6%). The enlarged capillary phenomenon was uncommon, being observed in 30 cases (9%). The number of capillaries per millimeter varied from five to nine. Deletion areas were detected in only seven individuals (2%). The subpapillary venous plexus was not visualized in 13 (4%) cases. Younger children presented higher PVS scores and fewer capillaries/mm as compared with older children. PVS scores were lower in males and in nonwhite children. Other variables were not associated with sex or ethnicity. CONCLUSIONS: The normal nail fold capillary network in children resembles that observed in adults with some differences, such as a lower number of loops per millimeter, a higher PVS score, and a higher frequency of atypical loops. This information is important for the diagnostic evaluation of children in the context of autoimmune rheumatic diseases.

Gastroduodenal lesions in children with juvenile rheumatoid arthritis.

BACKGROUND/AIMS: There are few studies about gastrointestinal abnormalities in patients with juvenile rheumatoid arthritis-probably due to the fact that this association is not frequently recognized. The aim of our study was to observe the prevalence of endoscopic gastroduodenal lesions in these patients. METHODOLOGY: Fourteen patients with juvenile rheumatoid arthritis, all of them using non-steroidal anti-inflammatory drugs associated or not with methotrexate, were assessed clinically and by endoscopy. Gastric antrum biopsy and Helicobacter pylori search were also performed. RESULTS: The mean age of the patients was 10.6 years (7 boys). Abdominal pain was observed in 27% of them. Macroscopic endoscopic lesions were found in 43% and infection by Helicobacter pylori in 57%. The correlation between anemia and endoscopic abnormalities was statistically significant (p < 0.05). CONCLUSIONS: Our data show that patients with juvenile rheumatoid arthritis have considerable susceptibility to gastroduodenal lesions, especially if they are using any drug association and present anemia.

Sarcoidosis of the external nose mimicking rhinophyma. Case report and review of the literature.

A 52-year-old man with a large external nasal mass is presented. Initially, the mass was thought to be rhinophyma, but biopsy of the mass revealed noncaseating granulomata consistent with sarcoidosis. The mass resolved following several steroid injections. The case is discussed in detail, along with a review of the literature pertaining to sarcoidosis of the nose and nasal cavity.

Association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis in a child.

The authors report the case of a 15-year-old, HLA-B27-positive male patient who presented a rare association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis, which resulted in death. A brief review of the literature is provided.

Determinaçäo dos níveis séricos de ácido úrico em uma amostra populacional da regiäo de Marília-SP e suas correlaçöes com algumas variáveis demográficas e bioquímicas / Serum uric acid levels in a populational sample in Marília county - Säo Paulo State and correlation with some biochemical and demographic parameters

Este trabalho é um estudo epidemiológico que procura estabelecer correlaçöes entre a concentraçäo sérica de ácido úrico e outros fatores, como localizaçäo geográfica, etnia, idade, sexo e obesidade. Foram estudados 958 indivíduos da regiäo da Alta Paulista, no Estado de Säo Paulo, Brasil, submetidos a anamnese, exames clínicos, reumatológico e laboratoriais. Encontraram-se níveis de ácido úrico sérico significantemente mais elevados na populaçäo urbana quando comparados com a populaçäo rural. Nas duas populaçöes, tanto urbana quanto rural, os níveis séricos de ácido úrico foram significantemente mais elevados no grupo masculino que no feminino. Näo houve correlaçäo entre níveis séricos de ácido úrico e idade, embora entre as mulheres se observasse aumento significante da urecemia a partir dos 40 anos. Näo houve diferença quanto à urecemia entre as raças branca e näo branca. Indivíduos obesos apresentaram níveis maiores de urecemia em relaçäo aos näo obesos, embora essa diferença tenha sido estatisticamente significante apenas na amostra de origem urbana. Näo houve correlaçäo entre os níveis séricos de ácido úrico e trigliceridemia, colesterolemia e glicemia

Well-differentiated thyroid carcinomas: p53 mutation status and microvessel density.

BACKGROUND: Risk-stratification schemes exist for well-differentiated thyroid carcinoma and include prognostic factors such as age, sex, extent of tumor, size of tumor, and presence of metastasis. Controversy continues, however, over the aggressiveness of initial surgical intervention because of anecdotal experiences of poor clinical outcomes in low-risk patients. Our objective is to determine the prognostic significance of two biologic tumor markers, the p53 gene mutation and CD34 microvessel density (MVD) count, in well-differentiated tumors of thyroid gland. METHODS: We selected 38 patients with well-differentiated thyroid carcinomas from the University of Illinois Tumor Registry. Patients had an average clinical follow-up of 10 years. Paraffin-embedded tumor specimens were available for all patients. Immunohistochemistry was performed to identify mutations of the p53 gene (Ab 1801) and to determine the MVD count (CD34). RESULTS: There were significant increases in MVD counts within thyroid tumor tissue, when compared with surrounding, normal thyroid tissue. There was no significant correlation noted, however, between increased MVD and histology or recurrence rates. There was a trend toward higher MVD counts in tumor specimens of patients initially seen with metastatic lymphadenopathy. The incidence of p53 mutation expression was 28%, and there was no correlation between p53 status and histology, sex, recurrence rate, or survival. CONCLUSIONS: This study supports the concept of tumor neovascularization but fails to correlate MVD with clinical behavior or pathologic features in well-differentiated thyroid carcinoma. Furthermore, we found that the p53 mutation status was not an independent prognosticator of tumor behavior in these lesions.

Human papillomavirus expression and p53 gene mutations in squamous cell carcinoma.

OBJECTIVES: To determine the incidence of human papillomavirus (HPV) infection and p53 gene mutation expression in squamous cell carcinomas (SCCs) of the oral cavity and tonsils, to correlate the presence of HPV and p53 gene mutation with known clinical and pathological features of SCC, and to determine whether infection with HPV or the presence of p53 gene mutations are independent prognosticators of patient survival. DESIGN: To accomplish this goal, 58 patients with SCCs of the oral cavity and 42 patients with SCCs of the tonsils were randomly examined. The cases examined met the criteria of 5-year clinical follow-up, availability of complete staging information and treatment history, and the presence of paraffin-embedded tumor specimens. Immunohistochemical tests were performed to identify the mutant p53 protein. Human papillomavirus identification was accomplished with polymerase chain reaction, with confirmation via restriction fragment length polymorphisms. RESULTS: The incidence of p53 gene mutation expression for this series was 66%. Human papillomavirus infection was found in 11 patients (11%). There was a trend toward increased p53 gene mutation expression with advancing stage of tumor in the oral cavity cancer group, although this was less evident in the tonsil cancer population. The p53 gene mutation status was found not to correlate with the histological grade of the tumor, patient age or sex, recurrence rates, or survival status. Like p53 expression, there were no correlations found between the presence of HPV and age, sex, histological grade, or recurrence rates. However, a correlation did exist between HPV and survival status in the tonsil cancer group, with improved survival noted among patients with tonsil cancers infected with HPV compared with those not infected with HPV. A significant correlation existed with both p53 gene mutation status and HPV status with respect to alcohol and tobacco use. The presence of the p53 gene mutation positively correlated with increased tobacco and alcohol use, whereas infection with HPV predicted a significantly lower rate of alcohol and tobacco consumption. CONCLUSIONS: Human papillomavirus infection is an independent risk factor for the development of oral cavity and tonsil SCCs in those patients with a relatively low alcohol and tobacco use history. Conversely, there is a strong association between heavy alcohol and tobacco use and mutation of the p53 gene. Neither p53 gene mutation nor HPV infection serve as prognosticators of tumor behavior in SCCs of the oral cavity or tonsils, with the exception of improved survival noted among patients with tonsil cancers infected with HPV.

Negative-pressure pulmonary edema in the otolaryngology patient.

It is estimated that 11% of all patients requiring active intervention for acute upper airway obstruction develop negative-pressure pulmonary edema. This pathologic process typically has a benign and rapidly resolving clinical course with the prompt use of mechanical ventilation and positive end expiratory pressure. A review of the literature, however, has revealed a morbidity and mortality rate of 11% to 40% in reported series. During the years 1991 through 1993, six patients were identified in whom negative-pressure pulmonary edema developed after various otolaryngologic procedures. Five (84%) of the six patients had complete resolution of the pulmonary edema within 24 hours, and the sixth patient progressed to prolonged mechanical ventilation and eventual death. In an effort to further understand the pathophysiology of this disease, a cardiac evaluation was performed by use of echocardiography on all six patients. In three of the six patients, studies revealed an underlying cardiac anomaly not previously identified by history or physical examination. Findings included one case of hypertrophic cardiomyopathy and two cases of pulmonary and tricuspid valvular insufficiency. This 50% incidence of cardiac anomalies is striking, in contrast to the less than 1% incidence of these anomalies in the general adult population. To our knowledge, this is the first study to implicate an underlying cardiac cause for the generation of negative-pressure pulmonary edema. On the basis of this study, we recommend that echocardiography be a part of the routine evaluation of all patients who manifest negative-pressure pulmonary edema.

Juvenile fibromyalgia: clinical and polysomnographic aspects.

OBJECTIVE: To identify the child-mother diagnostic correlation in fibromyalgia (FM), to study sleep disturbance in juvenile FM, and to compare clinical aspects and sleep disorders between these groups. METHODS: We studied 34 children with confirmed FM aged 11 +/- 1 years, 10 children with diffuse pain, and 17 age and sex matched asymptomatic controls. The respective 61 mothers were included: 34 asymptomatic and 27 with FM. All participants were subjected to clinical evaluation, a sleep questionnaire, and nocturnal polysomnography, preceded by a night of adaptation. Sleep scoring was done visually and a computerized analysis was performed for alpha, theta, and delta waves in slow wave sleep (SWS). RESULTS: A significant predominance of mothers with FM was observed in the group of children with FM (71%) compared to children with diffuse pain (30%) and asymptomatic children (0%). According to the sleep questionnaire, the complaints of superficial sleep and nonrestorative sleep were more prominent in mothers with FM than in children with FM, whereas motor agitation during sleep was more frequent in the children with FM. Polysomnographic anomalies were also more prominent in mothers with FM than in children with FM in terms of decrease in sleep efficiency, increase of number of arousals during sleep, and alpha intrusion in SWS. Both FM groups presented an increased alpha + theta time/delta time index during SWS compared to respective controls, and mothers with FM also showed an increase in alpha time/delta time index during SWS, compared to asymptomatic mothers. A correlation was found between alpha + theta time/delta time index during SWS and intensity of clinical manifestations of pain and sleep anomalies in children and their mothers. CONCLUSION: Significant concordance was observed regarding FM diagnosis in children and their mothers. Sleep complaints and polysomnography findings were less prominent in affected children compared to mothers with FM. In addition, we observed a significant correlation between polysomnographic indexes, sleep anomalies, and pain manifestations in children and their mothers.

Pseudotumor of infancy--the role of ultrasonography.

Pseudotumor of infancy (POI) occurs within the first month of life as a benign neck mass and affects 0.4% of all newborns. Differentiating these lesions from a malignancy or a congenital anomaly requiring surgical intervention can represent a diagnostic challenge for the clinician. While 80-90% of these masses resolve spontaneously within the first six months of life, there is still considerable time expended and cost incurred in the evaluation of POI. We have established and implemented a protocol for the evaluation of these patients consisting of a complete history and physical exam, ultrasonography and routine follow-up every four to six weeks. Seventeen patients were identified who had been evaluated and followed in the aforementioned manner. Two patients underwent diagnostic imaging studies prior to referral, consisting of magnetic resonance imaging (MRI) and computed tomography (CT). Ultrasonography appeared identical in 80% of the cases of POI with a heterogeneous pattern of internal echogenicity and a hypoechoic surrounding rim. The remaining ultrasound studies differed only subtly with regard to the internal echo pattern. There were no patients with pseudotumor of infancy in whom the ultrasound was normal. We concluded that a work-up including a history and physical exam and ultrasound is an accurate and cost-effective method for evaluating newborns with a neck mass, when suspicious for POI. Ultrasonography has a 100% sensitivity for the diagnosis of POI in this clinical scenario.

Bifid epiglottis.

The true bifid epiglottis is a rare congenital anomaly typically discovered during the evaluation of stridor in an infant or newborn. While it is not classified as a specific syndrome, there are frequent associations of other congenital anomalies with the bifid epiglottis. These include midline defects (such as microphallus, hypospadius, imperforate anus, and midline laryngeal cleft), endocrine disorders (including congenital hypopituitarism), and central nervous system neoplasms, including hypothalamic hamartoblastoma. The embryogenesis and options for surgical management of this anomaly are reviewed, and one case is presented in detail.

Epidermal dendritic cells in murine lupus

O lúpus eritematoso sistêmico (LES) é uma síndrome auto-imune multissistêmica. O acometimento cutâneo é freqüente e constitui manifestaçao clínica importante. O polimorfismo das lesoes cutâneas presume o envolvimento de diversos fatores etiopatogênicos. As células de Langerhans epidérmicas (CLs) têm funçoes imunorregulatórias importantes e participam de um modo decisivo na fisiopatologia de várias doenças dermatológicas inflamatórias, existindo evidência de seu envolvimento da patogênese da lesao cutânea lúpica. O camundongo F1 (NZB x NZW) um dos mais completos modelos experimentais de LES, nao desenvolve lesoes de pele. A ausência de dados na literatura referentes as CLs no camundongo F1 (NZB x NZW) motivou-lhes a realizar o presente estudo, que demonstrou, de forma original, a presença de CLs na epiderme do modelo F1, tanto por técnica citoquímica quanto por microscopia eletrônica de transmissao. Utilizando a técnica citoquímica da ATPase, estudamos as CLs no camundongo F1 (NZB x NZW) antes e após irradiaçao com luz ultravioleta B (UVB). As CLs no modelo F1 apresentaram-se em maior número e com alteraçoes morfológicas (dendritos curtos e menos ramificados) quando comparadas com os animais dos grupos-controles (BALB/c e C57BL/6). A irradiaçao UVB induziu alteraçoes morfológicas e reduçao no número das CLs do camundongo F1 em extensao semelhante ao observado no camundongo BALC/c. Nossos resultados sugerem possível alteraçao funcional nas CLs do camundongo F1 (NZB x NZW) e fornecem evidências de que estas células nao apresentam maior sensibilidade à luz UVB em comparaçao às de outras raças de camundongos. Estudos adicionais sao necessários para se testar possível associaçao entre essas alteraçoes fenotípicas das CLs e a ausência de manifestaçoes cutâneas nos camundongos F1 (NZB x NZW)

Lymphoma of unknown origin located in paravertebral muscles: an unusual cause of low back pain in children.

The authors report a case of an adolescent with a poorly differentiated lymphoma of unknown origin located at paravertebral muscles, whose presently symptom was low back pain.

Buoyant density of neutrophils in patients with juvenile rheumatoid arthritis

A densidade de neutrófilos polimorfonucleares (PMN) está diminuída em doenças difusas do colágeno, provavelmente devido a interaçoes com imunocomplexos, complemento ou outros mediadoes solúveis. Conseqüentemente, as suspensoes de linfócitos obtidas de pacientes com doenças do colágeno, mediante centrifugaçao de leucócitos do sangue periférico em gradiente de densidade de Ficoll-Hypaque (FH), d = 1,076, estao "contaminadas" com PMN. Estudamos 30 crianças com artrite reumatóide juvenil (ARJ) e encontramos aumento significante (p<0,01) no número de PMN nas suspensoes celulares de interfase FH em relaçao aos controles normais, apenas para a forma poliarticular. Esta diferença foi ainda maior quando se comparou a proporçao entre linfócitos e PMN. O soro de pacientes com ARJ poliarticular induziu in vitro diminuiçao da densidade de PMN de indivíduos normais. A diferença encontrada na densidade de PMN entre as formas pauci e poliarticular da ARJ pode estar relacionada a mecanismos fisiopatológicos distintos envolvidos em cada uma das formas dessa doença

Levodopa, melanoma, and Parkinson's disease.

Previous reports and the Physicians' Desk Reference caution against the use of levodopa in Parkinson's disease (PD) patients with melanoma. A critical review of the literature reveals only anecdotal evidence to support a link between levodopa and melanoma. In fact, levodopa has an antitumor effect on melanoma. We report nine patients with PD and melanoma who were treated with levodopa/carbidopa (L/C). Current evidence suggests that L/C can be used safely in PD patients with a history of melanoma.