Natalino Hajime Yoshinari

Novel Spotted Fever Group Rickettsiosis, Brazil

We report a clinical case of spotted fever group rickettsiosis acquired in São Paulo, Brazil. Definitive diagnosis was supported by seroconversion between acute-phase and convalescent-phase serum samples. Molecular analysis of skin samples indicated the agent was a novel spotted fever group strain closely related to Rickettsia africae, R. parkeri, and R. sibirica.

The T-Cell Proliferative Assay in the Diagnosis of Lyme Disease

OBJECTIVEnTo determine the sensitivity and specificity of the T-cell proliferative assay as a diagnostic test in Lyme disease.nnnDESIGNnCross-sectional study of patients with Lyme arthritis or chronic neuroborreliosis who had a history of erythema migrans, positive antibody responses to Borrelia burgdorferi by enzyme-linked immunosorbent assay (ELISA), or both; patients with other diseases; and healthy subjects.nnnSETTINGnDiagnostic Lyme disease clinic in a university hospital.nnnPATIENTSnForty-two of the 67 patients with active Lyme arthritis or chronic neuroborreliosis who were seen during the study period; 16 patients with inactive late Lyme disease; 77 patients with other rheumatologic or neurologic diseases; 9 workers from the Borrelia laboratory; and 9 healthy subjects.nnnMEASUREMENTS AND MAIN RESULTSnNineteen of 42 patients with Lyme arthritis or chronic neuroborreliosis and 4 of 77 patients with other diseases had positive T-cell proliferative responses to B. burgdorferi antigens. The sensitivity of the proliferative assay was 45% (95% Cl, 30% to 60%) and the specificity was 95% (95% Cl, 87% to 99%). Twelve of 27 patients with active Lyme arthritis, 7 of 15 patients with chronic neuroborreliosis, 4 of 16 patients with inactive Lyme disease, 4 of 9 healthy Borrelia laboratory workers, and 0 of 9 healthy subjects had positive responses. Three of five patients with Lyme disease who had negative or indeterminant antibody responses by ELISA had positive T-cell proliferative responses.nnnCONCLUSIONnThe T-cell proliferative assay may be a helpful diagnostic test in the small subset of patients with late Lyme disease who have negative or indeterminant antibody responses by ELISA.

Antiganglioside Antibodies in Patients with Neuropsychiatric Systemic Lupus Erythematosus

Antiganglioside antibodies (AGA) were determined in sera and cerebrospinal fluids (CSF) from 50 systemic lupus erythematosus (SLE) patients, and age-matched normal controls. The SLE patients were subdivided according to the type of clinical manifestation into two groups: neuropsychiatric SLE and active SLE without neuropsychiatric manifestation. The presence of these antibodies showed a significant correlation between IgG AGA in the CSF and IgM AGA in the serum and neuropsychiatric SLE. Fifteen patients had this antibody in the CSF without detectable levels in the serum. No correlation was seen between anti cardiolipin antibodies in the serum or CSF and neuropsychiatric SLE. The present work suggests that antibodies against gangliosides may be a marker for neuro psychiatric SLE and that intrathecal antibody production can result in the development of this manifestation.

Neurological manifestations in Baggio-Yoshinari Syndrome (Brazilian Lyme disease-like syndrome)

INTRODUCAO: A doenca de Lyme (DL) e uma doenca de picada de carrapato, causado pela espiroqueta Borrelia burgdorferi sensu lato, transmitida por carrapatos do complexo Ixodes ricinus, que promove multiplas manifestacoes clinicas sistemicas. No Brasil, uma sindrome diferente e descrita e mimetiza sintomas de DL, mas tambem se manifesta com alta frequencia de episodios recorrentes e manifestacoes alergicas e imunologicas. E transmitida pelo carrapato Amblyomma cajennense e o agente etiologico e uma espiroqueta nao cultivavel de forma atipica. Devido a essas particularidades, esta zoonose emergente tem sido denominada sindrome brasileira semelhante a doenca de Lyme ou sindrome de Baggio-Yoshinari (SBY). OBJETIVO: Descrever o espectro da manifestacao neurologica da SBY. PACIENTES: Foram analisados 30 pacientes com SBY e sintomas neurologicos. RESULTADOS: A media de idade dos pacientes foi de 34,2 ± 13,3 anos (6 a 63 anos); 20 eram mulheres e 10 homens. Um alto numero de episodios recorrentes (73,6%) e disturbios psiquiatricos e psicossociais graves (20%) foram caracteristicas tipicas. Eritema migrans similar ao visto em hemisferio norte foi identificado em 43,3% dos pacientes no inicio da doenca. A recorrencia das lesoes cutâneas diminuiu com a progressao da doenca. Sintomas articulares (artrite) aconteceram em aproximadamente metade dos pacientes com SBY no inicio e durante o episodio de recidiva. CONCLUSOES: A SBY e considerada uma nova doenca transmitida por carrapato no Brasil que difere da classica DL observada no hemisferio norte. A SBY reproduz sintomas neurologicos observados na DL, exceto pela presenca adicional de recorrencia de episodios e uma tendencia de causar manifestacoes neurologicas cronicas e articulares.

Borreliose de Lyme simile: uma doença emergente e relevante para a dermatologia no Brasil

Neste trabalho de revisao sao apresentadas doencas relacionadas com espiroquetas do genero Borrelia, agentes etiologicos de diferentes enfermidades comuns ao homem e a animais. Enfatizou-se a Borrelia burgdorferi lato sensu, que inclui diferentes especies causadoras de doencas e com envolvimento sistemico, com interesse em varias especialidades medicas, como dermatologia, reumatologia, cardiologia e neurologia. Considerando que existem diferencas quanto ao agente etiologico, alem dos aspectos clinicos e laboratoriais, quando comparada com a borreliose de Lyme causada pelas Borrelia burgdorferi, B. garinii e B. afzelli, a infeccao no Brasil deve ser referida como borreliose de Lyme simile. O eritema migratorio recidivante e a principal manifestacao clinica da borreliose existente tanto no Brasil como nos demais paises. Essa lesao classica esta relacionada com a picada do carrapato vetor e inicia-se como uma macula ou papula cutânea avermelhada, de carater expansivo, eventualmente surgem lesoes semelhantes multiplas a distância. A manifestacao clinica da enfermidade, em especial o envolvimento cutâneo, e o parâmetro diagnostico mais relevante, e os exames complementares sorologicos confirmam a suspeita clinica.

Colágeno na cartilagem osteoartrótica

A cartilagem articular e um tecido altamente especializado, composto por celulas, os condrocitos, e um conjunto de macromoleculas, como o colageno e os proteoglicanos. O colageno e uma proteina fibrilar que garante resistencia ao tecido, enquanto os proteoglicanos tem a funcao de mola biologica, sendo responsaveis pela compressibilidade da cartilagem. A complexa interacao entre estas duas proteinas garante a elasticidade. Estas caracteristicas especificas da cartilagem sao essenciais para amortecer as grandes forcas de impacto a que as articulacoes diartrodiais estao submetidas, sem muito gasto de energia, visto tratar-se de um tecido avascular. Em processos artrosicos ocorre um desequilibrio entre a producao de componentes da matriz extracelular e destruicao pelas metaloproteases, levando a degradacao e perda do tecido cartilaginoso. A fase inicial da osteoartrose e marcada por perda de fragmentos de proteoglicanos para o liquido sinovial, aumento dos colagenos tipo II e tipo VI, aparecimento dos colagenos I e III, nao tipicos da cartilagem, e diminuicao do colageno tipo IX, que e importante para manter a integridade da matriz extracelular, alem do entumescimento da cartilagem. Como consequencia, a cartilagem perde suas caracteristicas especificas, levando a alteracoes na funcao articular. A evolucao da doenca promove diminuicao significativa das proteinas, ate mesmo do colageno tipo XI, que tem localizacao mais interna na estrutura da fibrila heterotipica, e, portanto levando ate a exposicao do osso. Ate o momento, o tratamento da osteoartrose esta baseado principalmente no controle da dor e/ou inflamacao, nao diminuindo ou impedindo a degradacao da cartilagem articular. Neste aspecto a perspectiva de tratamento futuro da osteoartrose estaria na utilizacao de inibidores das metaloproteases associadas a condroprotetores interferindo no turnover da cartilagem e impedindo, deste modo, o processo de degradacao.

Auto-imunidade e colágeno V

As proteinas da matriz extracelular (MEC) e seus componentes estao sendo amplamente estudados na literatura medica, assim como sua relacao com o remodelamento tecidual presente nas doencas reumaticas. Neste artigo, mostramos a importância do estudo do colageno do tipo V no entendimento da etiologia da esclerodermia, no que se refere ao desencadeamento da auto-imunidade nesta enfermidade. Estudos em nosso laboratorio demonstram que a sensibilizacao com colageno do tipo V em coelhos pode resultar em um modelo animal de esclerodermia. Diante destes fatos, sugerimos que pesquisas neste campo podem ser de grande valia no desenvolvimento de novas condutas terapeuticas.

Serological Reactivity to Borrelia burgdorferi, Borrelia afzelli, and Borrelia garinii Antigens in Patients Afflicted by Peripheral Facial Paralysis in Brazil

Main outcome measure(s) Antibodies to Borrelia burgdorferi were found in 21% of the patients using IMF 1988 and in 19% of the patients using ELISA 10 years later, 1998. The prevalence of antibodies to Borrelia in patients with peripheral facial palsy was 12 times higher when compared to controls. Antibodies to Borrelia in CSF were found in 23% of the seropositive patients 1988 and in 20% of the seropositive patients 1998. No matter what etiology of the palsy, CSF was pathological in 62% of the patients 1988 and 42% in 1998.

Anti-Collagen Type V Antibody in Systemic Sclerosis: A Possible Useful Tool to Asses Disease Activity

Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury, autoimmunity and tissue fibrosis. Usually collagen type V (V Col) is found hidden between the heterotypical fibers. It was discovered in the rheumatology department at the University of Sao Paulo (FMUSP) that deposition of this collagen occurs, however with anomalous morphology in SSc patient’s tissue, suggesting that V Col is an important molecule in fibrosis and autoimmunity process. The V Col molecule, which has atypical morphology aspect, exposed after a nonspecific inflammatory damage could result in formation of immune complexes (V Col - anti-V Col), whose deposition on the vascular endothelium, would cause a vascular damage, allowing the influx of cells of innate immunity into the extracellular matrix, resulting in an enzymatic degradation of the heterotypical fibers, with exposure of more V Col and perpetuation of the disease. nObjectives: Assess whether there is a correlation between anti-V Cols presence in the serum of patients with SSc and indexes of activity, severity and quality of life measured by sHAQ. nMethods: Were evaluated 60 patients with SSc diagnostic during the period of January to December 2014. Were applied Medsger severity criteria, Valentini activity criteria and health assessment questionnaire in SSc (sHAQ) in the patients, at initial assessment (baseline) and after 6 months, correlating the presence of anti-V Col with the clinical and laboratory manifestations found. nResults: Most patients were female (98.3%) and had the limited form of the disease (43.3%), average age 51 years, white, average duration of nine years of disease and modified Rodnan Skin Score of 13.08. The main clinical manifestations observed in each organic system of patients were: skin thickening in the hands (78.3%), Raynauds phenomenon (100%), arthritis (33.3%), esophageal involvement (71.7%), interstitial lung disease (45%), pulmonary arterial hypertension (PAH) (19.4%) and scleroderma renal crisis (SRC) (1.7%). The most significant laboratory abnormalities were elevation of inflammatory markers in 41.7% of patients (ESR and CRP), CPK elevation (15%), low complement (C3 and C4) (3.3%), antinuclear antibody (95%), anti-centromere (41.7%), anti-DNA topoisomerase I antibody (26.7%), anti-RNA polymerase III (11.7%), anti-U1-RNP (16.7%) and anti-Ro (SSA) in 11.7% of patients. The anti-V Col was detected in 5 cases (8.3%) and showed statistical correlation with disease activity and scleroderma renal crisis, besides tendency to association with PAH; however, did not correlate with the severity index of disease or any other clinical manifestation, or with specific SSc antibodies. nConclusions: We suggest that disease activity in SSc patients could be determined by serological analysis, to detect the presence of V Col antibodies in the serum of patients with SSc, facilitating the approach of this serious disease. We suggest further studies with larger number of patients in order to confirm the usefulness of this new marker of disease activity in systemic sclerosis.

Anticorpos antimatriz extracelular e antiaorta em pacientes com arterite de Takayasu

The pathogenic role of the components of extracellular matrix as causative factor of diffuse connective diseases and vasculitis has been studied extensively. The pathogenesis of Takayasu´s arteritis is unknown, and many theories have been proposed to explain the etiology of this disease, involving disturbances of the humoral or cellular immune responses. OBJECTIVE: To research antibodies directed to components of the extracellular matrix and aorta extract. METHODS: Serum from thirteen patients with Takayasu´s arteritis and from eight normal patients was tested to show the presence of autoantibodies directed to anti types I, III, IV and V collagen and anti-aorta employing ELISA methodology. RESULTS: Serum from patients with Takayasu´s arteritis didnt show the presence of antibodies directed to types III and IV collagen and only one patient was positive for type I and V collagen. No serum was reactive with aorta extract in patients with Takayasu´s arteritis as well. CONCLUSIONS: Our results didnt show the presence of antibodies directed to types I, III, IV and V collagen, as well as against aorta extract, suggesting that cell immune mediated disturbance should be the mechanism involved in the etiopathogenesis of this form of vasculitis.