CLASSICAL SEROLOGICAL MARKERS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE IN BRAZIL.

BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn's disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. OBJECTIVE: To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. METHODS: Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. RESULTS: A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). CONCLUSION: In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.

Marcadores sorológicos clássicos na doença inflamatória intestinal pediátrica no Brasil / Classical serological markers in pediatric inflammatory bowel disease in brazil

ABSTRACT BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn's disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. OBJECTIVE: To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. METHODS: Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. RESULTS: A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). CONCLUSION: In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.

RESUMO CONTEXTO: Os anticorpos citoplasmáticos anti-neutrófilos perinuclear (p-ANCA) e anticorpos anti-Saccharomyces cereviciae (ASCAs) são utilizados para diferenciar a doença de Crohn (DC) da colite ulcerativa (CU) e mais recentemente para correlacioná-los com o prognóstico da doença. OBJETIVO: 1) Determinar a acurácia diagnóstica dos marcadores sorológicos na identificação de DC e CU pediátrica em São Paulo, Brasil. 2) Correlacioná-los com as características demográficas e clínicas destas duas doenças. MÉTODOS: Estudo multicêntrico transversal em pacientes com diagnóstico estabelecido de doença inflamatória intestinal (DII) determinando a presença dos marcadores sorológicos ASCAs e p-ANCA, correlacionando seus resultados com os dados demográficos e clínicos, e também em pacientes controles isentos de doenças gastrointestinal. RESULTADOS: 122 pacientes, 74 com DII (46% masculinos) em quatro centros de referência em Gastroenterologia Pediátrica, média de idade 13±7 anos, 49 (66%) com DC e 25 (34%) com CU e 48 controles (54% masculinos). O marcador p-ANCA apresenta maior porcentagem de detecção na CU (69,6%), mas também na DC (30,4%) quando comparado ao grupo controle (P<0,001). Os marcadores ASCA IgA (76,2%) e IgG (94,4%) apresentam maiores porcentagens de detecção na DC, quando comparada ao controle (P<0,001) e que a positividade do marcador esteve relacionada ao uso de medicações em pacientes portadores de DC que realizaram cirurgia (26,86±17,99; P=0,032). CONCLUSÃO: Os resultados dos testes sorológicos em crianças com DII em São Paulo, Brasil, foram altamente específicos, mas pouco sensíveis para auxiliar no diagnóstico, embora com correlação positiva com a gravidade da doença.

Clinical manifestations, treatment, and outcomes of children and adolescents with eosinophilic esophagitis.

OBJECTIVE: This study aimed to describe the clinical, endoscopic, and histologic characteristics, as well as the response to conventional treatment of pediatric patients with the classical form of eosinophilic esophagitis (EoE). METHODS: Study of clinical, laboratory, endoscopic, and histologic data and response to conventional treatment of 43 previously followed pediatric patients with the classical form of EoE. RESULTS: A total of 43 patients diagnosed with EoE were included in the study, of which 37 were males (86%), with a mean age of 8.4 years. The most common symptoms were: nausea, vomiting, and abdominal pain (100%) in children younger than 7 years, and loss of appetite (60%), heartburn (52%), and food impaction (48%) in children older than 7 years and adolescents. Regarding the endoscopic findings, 12 (28%) patients had whitish plaques on the esophageal lining, 8 (18.5%) had longitudinal grooves, 2 (4.5%) had concentric rings, 3 (7%) had longitudinal grooves and whitish plaques, and the remaining 18 (42%) had esophageal mucosa with normal appearance. Despite the initial favorable response, 76.7% of patients required more than one course of corticosteroid therapy (systemic or aerosol) and diet (exclusion or elimination of food or elementary allergens). Persistence of eosinophil infiltration was found in some patients despite favorable clinical response. CONCLUSIONS: The classic form of EoE typically shows different symptoms according age range. A significant number of patients required more than one treatment cycle to show clinical remission. Endoscopic and histologic improvement was observed; however, eosinophilic infiltration persisted in some patients.

Manifestações clínicas, terapêutica e evolução de crianças e adolescentes com esofagite eosinofílica / Clinical manifestations, treatment, and outcomes of children and adolescents with eosinophilic esophagitis

OBJECTIVE: This study aimed to describe the clinical, endoscopic, and histologic characteristics, as well as the response to conventional treatment of pediatric patients with the classical form of eosinophilic esophagitis (EoE). METHODS: Study of clinical, laboratory, endoscopic, and histologic data and response to conventional treatment of 43 previously followed pediatric patients with the classical form of EoE. RESULTS: A total of 43 patients diagnosed with EoE were included in the study, of which 37 were males (86%), with a mean age of 8.4 years. The most common symptoms were: nausea, vomiting, and abdominal pain (100%) in children younger than 7 years, and loss of appetite (60%), heartburn (52%), and food impaction (48%) in children older than 7 years and adolescents. Regarding the endoscopic findings, 12 (28%) patients had whitish plaques on the esophageal lining, 8 (18.5%) had longitudinal grooves, 2 (4.5%) had concentric rings, 3 (7%) had longitudinal grooves and whitish plaques, and the remaining 18 (42%) had esophageal mucosa with normal appearance. Despite the initial favorable response, 76.7% of patients required more than one course of corticosteroid therapy (systemic or aerosol) and diet (exclusion or elimination of food or elementary allergens). Persistence of eosinophil infiltration was found in some patients despite favorable clinical response. CONCLUSIONS: The classic form of EoE typically shows different symptoms according age range. A significant number of patients required more than one treatment cycle to show clinical remission. Endoscopic and histologic improvement was observed; however, eosinophilic infiltration persisted in some patients.

OBJETIVO: O objetivo deste estudo foi descrever as características clínicas, endoscópicas e histológicas, assim como a resposta ao tratamento convencional de pacientes pediátricos com a forma clássica de esofagite eosinofílica (EEo). MÉTODOS: Levantamento de dados clínicos, laboratoriais, endoscópicos, histológicos e da resposta ao tratamento convencional de 43 pacientes pediátricos acompanhados previamente com a forma clássica de EEo. RESULTADOS: Foram incluídos 43 pacientes com diagnóstico de EEo, sendo 37 do sexo masculino (86%), com idade média de 8,4 anos. Os sintomas mais encontrados foram: náusea, vômito e dor abdominal (100%) em crianças menores de sete anos; e inapetência (60%), queimação retroesternal (52%) e impactação alimentar (48%) em crianças maiores de sete anos e adolescentes. Em relação aos achados endoscópicos, 12 (28%) pacientes apresentavam placas esbranquiçadas na mucosa do esôfago, oito (18,5%) sulcos longitudinais, dois (4,5%) anéis concêntricos, três (7%) sulcos longitudinais e placas esbranquiçadas, e os outros 18 (42%) apresentavam aparência normal da mucosa esofágica. Apesar da resposta favorável inicial, 76,7% dos pacientes necessitaram realizar mais de um ciclo terapêutico com corticoterapia (aerossol ou sistêmica) e dieta (de exclusão ou eliminação dos alérgenos alimentares ou elementares). Persistência do infiltrado eosinofílico foi encontrada em uma parcela dos pacientes, a despeito da resposta clínica favorável. CONCLUSÕES: A forma clássica da EEo apresenta sintomas diferentes segundo a faixa etária. Parcela expressiva dos pacientes necessitou de mais de um ciclo terapêutico para apresentar remissão clínica. Observou-se melhora endoscópica e histológica; no entanto, a infiltração eosinofílica persistiu em parcela dos pacientes.

Parthenolide sensitizes cells to X-ray-induced cell killing through inhibition of NF-kappaB and split-dose repair.

Human cancers have multiple alterations in cell signaling pathways that promote resistance to cytotoxic therapy such as X rays. Parthenolide is a sesquiterpene lactone that has been shown to inhibit several pro-survival cell signaling pathways, induce apoptosis, and enhance chemotherapy-induced cell killing. We investigated whether parthenolide would enhance X-ray-induced cell killing in radiation resistant, NF-kappaB-activated CGL1 cells. Treatment with 5 microM parthenolide for 48 to 72 h inhibited constitutive NF-kappaB binding and cell growth, reduced plating efficiency, and induced apoptosis through stabilization of p53 (TP53), induction of the pro-apoptosis protein BAX, and phosphorylation of BID. Parthenolide also enhanced radiation-induced cell killing, increasing the X-ray sensitivity of CGL1 cells by a dose modification factor of 1.6. Flow cytometry revealed that parthenolide reduced the percentage of X-ray-resistant S-phase cells due to induction of p21 waf1/cip1 (CDKN1A) and the onset of G1/S and G2/M blocks, but depletion of radioresistant S-phase cells does not explain the observed X-ray sensitization. Further studies demonstrated that the enhancement of X-ray-induced cell killing by parthenolide is due to inhibition of split-dose repair.

Mucopolissacaridose tipo Hunter, com anátomo-patológico hepático de glicogenose / Mucopolyssacaridosis type II (MPSII-Hunter) with a hepatic biopsy

Objetivo: Relatar um caso de Mucopolissacaridose tipo II (MPSII Hunter), com quadro clínico e laboratorial desta doença, porém com biópsia hepática apresentando depósito citoplasmático de glicogênio. Métodos: Estudo do quadro clínico e de exames complementares de uma criança de 8 anos de idade, internada em nosso serviço, com importante hepatoesplenomegalia. Resultados: Foram encontradas alterações clínicas, tais como, fascies grosseira, alterações de ausculta cardíaca, hepatoesplenomegalia, deformidades articulares MMSS e certo grau de deterioração mental. Os achados de exames complementares de imagem (ecocardiográficos, radiológicos e ultrassonográficos) também foram compatíveis com MPS. Laboratorialmente, foi detectado na urina, Dermatan Sulfato de Heparan Sulfato (Teste do Azul de Toluidina - positivo) e ensaios enzimáticos que sugerem MPS tipo II. O resultado anátomo-patológico da biópsia hepática, com acúmulo de glicogênio no citoplasma do hepatócito, demonstra característica encontrada na glicogenose, mas não se correlacionando com os achados clínicos. Conclusão: No diagnóstico das Doenças de Depósito (MPS), a biópsia hepática pode ter apresentação semelhante a uma glicogenose e, portanto, para seu diagnóstico definitivo, é importante associarmos o quadro clínico com dados laboratoriais e histopatológicos.