Objetivo: Avaliar a freqüência das células T reguladoras (Tregs) em crianças com diagnóstico novo de Púrpura Trombocitopênica Imune (PTI) e a sua associação com a contagem de plaquetas na ocasião, comparando os achados com os de controles saudáveis. Pacientes e Métodos: Foi realizado um estudo caso-controle, no qual foram incluídos 19 pacientes com diagnóstico novo de PTI e 19 controles. Para cada um dos casos, foram coletadas quatro amostras de sangue em períodos distintos, sendo eles ao diagnóstico – antes da instituição de qualquer terapêutica – e após um, três e seis meses do mesmo. Para os controles, utilizou-se amostra de sangue de 19 pacientes saudáveis, coletadas eletivamente. Em todas as amostras de sangue foi realizada contagem de plaquetas através de hemograma e avaliação dos linfócitos Tregs (CD4+ CD25+ Foxp3) por citometria de fluxo. Resultados: A idade média ao diagnóstico de PTI foi de 6,53 ± 4,14 anos. Dos 17 pacientes tratados, 13 receberam apenas corticosteróide oral e quatro pacientes receberam corticosteróide e imunoglobulina endovenosa associada em algum momento do tratamento. Em relação à evolução da doença, 14 crianças apresentaram remissão completa, duas remissão e três PTI crônica. Houve diferença estatisticamente significativa no número de plaquetas entre os grupos caso e controle nas amostras 1 e 4. Não houve diferença significativa na contagem de Tregs entre os casos e os controles em nenhum momento de coleta. Não foi encontrada correlação estatisticamente significativa entre Tregs e o número de plaquetas entre os casos e os controles, nem nos pacientes do grupo caso ou do grupo controle analisados separadamente. Não houve diferença na contagem de células Tregs entre os grupos de pacientes crônicos e não crônicos. Conclusão: Os achados deste estudo não nos permitiu evidenciar correlação estatisticamente significativa entre Tregs e o número de plaquetas nos grupos caso e controle. As células T CD4+ CD25+ Foxp3 (Tregs) parecem não desempenhar um papel crucial na regulação da auto-imunidade em pacientes pediátricos com diagnóstico de PTI, provavelmente, devido à existência de outros mecanismos responsáveis pela auto-imunidade em crianças, ainda não identificados. / Objective: To assess the frequency of regulatory T cells (Tregs) in children with a new diagnosis of Immune Thrombocytopenic Purpura (ITP), and its association with the counts of platelets on the occasion, and compare with healthy controls. Patients and Methods: A case-control study was conducted, in which 19 patients with new diagnosis of ITP and 19 controls were included. For each case, four blood samples were collected at different point times, that is, at the diagnosis – before the establishment of any treatment – and after one, three and six months. For the controls, electively collected blood samples from 19 healthy patients were used. For all blood samples, platelets were counted through a CBC and assessment of Treg lymphocytes (CD4+ CD25+ Foxp3) by flow cytometry. Results: The mean age at the ITP diagnosis was 6.53 ± 4.14 years. Of 17 treated patients, 13 received oral corticosteroid only, and four patients received corticosteroid and associated intravenous human immunoglobulin at some point in the treatment. Regarding the disease course, 14 children showed full remission, two partial remission, and three chronic ITP. There was a statistically significant difference in the number of platelets between the case and control groups in the samples 1 and 4. There was no significant difference in the counts of Tregs between cases and controls at any collection time. No statistically significant correlation was found between Tregs and number of platelets between cases and controls, neither in patients in the case group nor in the control group who were analyzed separately. There was no difference in the counts of Treg cells between the groups of chronic and non-chronic patients. Conclusion: The findings of this study did not show any statistically significant correlation between Tregs and number of platelets in the case and control groups. The T cells CD4+ CD25+ Foxp3 (Tregs) seems did not play a key role in the regulation of self-immunity in pediatric patients diagnosed with ITP. Other mechanisms, which aren’t still identified, are likely to account for self-immunity in children.

Objetivo: Avaliar a freqüência das células T reguladoras (Tregs) em crianças com diagnóstico novo de Púrpura Trombocitopênica Imune (PTI) e a sua associação com a contagem de plaquetas na ocasião, comparando os achados com os de controles saudáveis. Pacientes e Métodos: Foi realizado um estudo caso-controle, no qual foram incluídos 19 pacientes com diagnóstico novo de PTI e 19 controles. Para cada um dos casos, foram coletadas quatro amostras de sangue em períodos distintos, sendo eles ao diagnóstico – antes da instituição de qualquer terapêutica – e após um, três e seis meses do mesmo. Para os controles, utilizou-se amostra de sangue de 19 pacientes saudáveis, coletadas eletivamente. Em todas as amostras de sangue foi realizada contagem de plaquetas através de hemograma e avaliação dos linfócitos Tregs (CD4+ CD25+ Foxp3) por citometria de fluxo. Resultados: A idade média ao diagnóstico de PTI foi de 6,53 ± 4,14 anos. Dos 17 pacientes tratados, 13 receberam apenas corticosteróide oral e quatro pacientes receberam corticosteróide e imunoglobulina endovenosa associada em algum momento do tratamento. Em relação à evolução da doença, 14 crianças apresentaram remissão completa, duas remissão e três PTI crônica. Houve diferença estatisticamente significativa no número de plaquetas entre os grupos caso e controle nas amostras 1 e 4. Não houve diferença significativa na contagem de Tregs entre os casos e os controles em nenhum momento de coleta. Não foi encontrada correlação estatisticamente significativa entre Tregs e o número de plaquetas entre os casos e os controles, nem nos pacientes do grupo caso ou do grupo controle analisados separadamente. Não houve diferença na contagem de células Tregs entre os grupos de pacientes crônicos e não crônicos. Conclusão: Os achados deste estudo não nos permitiu evidenciar correlação estatisticamente significativa entre Tregs e o número de plaquetas nos grupos caso e controle. As células T CD4+ CD25+ Foxp3 (Tregs) parecem não desempenhar um papel crucial na regulação da auto-imunidade em pacientes pediátricos com diagnóstico de PTI, provavelmente, devido à existência de outros mecanismos responsáveis pela auto-imunidade em crianças, ainda não identificados. / Objective: To assess the frequency of regulatory T cells (Tregs) in children with a new diagnosis of Immune Thrombocytopenic Purpura (ITP), and its association with the counts of platelets on the occasion, and compare with healthy controls. Patients and Methods: A case-control study was conducted, in which 19 patients with new diagnosis of ITP and 19 controls were included. For each case, four blood samples were collected at different point times, that is, at the diagnosis – before the establishment of any treatment – and after one, three and six months. For the controls, electively collected blood samples from 19 healthy patients were used. For all blood samples, platelets were counted through a CBC and assessment of Treg lymphocytes (CD4+ CD25+ Foxp3) by flow cytometry. Results: The mean age at the ITP diagnosis was 6.53 ± 4.14 years. Of 17 treated patients, 13 received oral corticosteroid only, and four patients received corticosteroid and associated intravenous human immunoglobulin at some point in the treatment. Regarding the disease course, 14 children showed full remission, two partial remission, and three chronic ITP. There was a statistically significant difference in the number of platelets between the case and control groups in the samples 1 and 4. There was no significant difference in the counts of Tregs between cases and controls at any collection time. No statistically significant correlation was found between Tregs and number of platelets between cases and controls, neither in patients in the case group nor in the control group who were analyzed separately. There was no difference in the counts of Treg cells between the groups of chronic and non-chronic patients. Conclusion: The findings of this study did not show any statistically significant correlation between Tregs and number of platelets in the case and control groups. The T cells CD4+ CD25+ Foxp3 (Tregs) seems did not play a key role in the regulation of self-immunity in pediatric patients diagnosed with ITP. Other mechanisms, which aren’t still identified, are likely to account for self-immunity in children.

Orientador: Marcelo Addas Carvalho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T03:08:54Z (GMT). No. of bitstreams: 1 Vilela_JosieFadul_M.pdf: 1739915 bytes, checksum: ea1d6c47907a49ccd0e00255b01d3dee (MD5) Previous issue date: 2012 / Resumo: A Púrpura Trombocitopênica Imune (PTI) é uma doença autoimune caracterizada pela presença de autoanticorpos contra as glicoproteínas de membrana plaquetária, tais como GPIIb/IIIa e GPIb/IX. O processo patogênico da PTI envolve uma destruição acelerada das plaquetas pelo sistema retículo-endotelial e a presença de sangramentos mucocutâneos. A reação inflamatória em doenças infecciosas e autoimune é regulada por um balanço entre as citocinas pró e anti-inflamatórias e a PTI tem sido associada com a desregulação das respostas e atividades de citocinas. Uma associação entre os polimorfismos de genes de citocinas que afetam sua produção e secreção foram relatadas em doenças infecciosas, alérgicas, autoimunes, e malignas, tanto na fase de formação quanto no decurso da doença e nas suas respostas ao tratamento. Neste estudo, o objetivo foi avaliar a importância dos polimorfismos IL1B -511C/T, IL1B +3953C/T, IL1RN intron 2 VNTR, IL4 -590C/T, IL4 intron 3 VNTR, IL6 -174G/C, IL10 -1082G/A, IL10 -819C/T e IL10 -592 A/C em pacientes portadores de PTI na região de Campinas, SP e investigar a associação entre os genótipos identificados e a resposta clínica do paciente ao tratamento. Utilizamos o método PCR e digestão com enzima de restrição (PCR-RFLP) ou PCR em Tempo real (RT-PCR) para identificação dos polimorfismos. No total, 216 pacientes adultos diagnosticados com PTI foram pareados com 119 controles saudáveis constituídos por doadores voluntários do Centro de Hematologia e Hemoterapia da UNICAMP. Os dados clínicos como contagem de plaquetas ao diagnóstico, tipo de tratamento e resposta, foram obtidos através dos prontuários médicos. A análise de frequências dos alelos e genótipos dos polimorfismos IL1B - 511C/T, IL1B +3953C/T, IL6 -174G/C, IL10-1082G/A, IL10 -819C/T e IL10 -592A/C de pacientes portadores de PTI comparadas ao grupo controle não mostrou diferenças significativas entre os dois grupos. No entanto, para os polimorfismos IL1RN intron 2 VNTR, IL4 -590C/T, IL4 intron 3 VNTR e para os haplótipos de IL10 houve uma diferença significativa ao compararmos as frequências polimórficas entre os dois grupos. Analisando-se os polimorfismos associados com parâmetros clínicos, este estudo mostrou que o genótipo IL1B -511CC estava mais presente em indivíduos com boa resposta à esplenectomia. Pode-se concluir que o estudo de características genéticas dos pacientes portadores de PTI na região de Campinas, SP pode ajudar a esclarecer o perfil de pacientes acometidos pela doença nesta região, identificando grupos de maior risco e a entender qual polimorfismo pode estar associado a uma melhor resposta clínica, projetando uma nova linha de investigação / Abstract: The immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the presence of autoantibodies against the platelet membrane glycoproteins such as GPIIb/IIIa and GPIb/IX. The pathogenic process of ITP involves an accelerated destruction of platelets by reticuloendothelial system and the presence of mucocutaneous bleeding. The inflammatory reaction in infectious and autoimmune diseases is regulated by a balance between pro and anti-inflammatory cytokines and ITP has been associated with dysregulation of cytokine responses and activities. An association between cytokine gene polymorphisms that affect their production and secretion have been reported in infectious, allergic, autoimmune, and malignant diseases, both during training and during the illness and its response to treatment. The aim of this study was to evaluate the importance of IL1B -511C/T, IL1B +3953 C/T, IL1RN intron 2 VNTR, IL4 -590C/T IL4 intron 3 VNTR, IL6 -174G/C, IL10 -1082G/A, IL10 -819C/T and IL10 -592A/C polymorphisms in patients with ITP in the region of Campinas, SP, and investigate the association between different genotypes and clinical responses to treatment. We used the PCR method and digestion with restriction enzyme (PCR-RFLP) or real-time PCR (RT-PCR) to identify polymorphisms. In total, 216 adult patients diagnosed with ITP were matched with 118 healthy controls. The clinical data such as platelet count at diagnosis, type of treatment and response were obtained from medical records. Analysis of allele and genotypes frequencies of IL1B -511C/T, IL1B +3953C/T, IL6 -174G/C, IL10 - 1082G/A, IL10 -819C/T and IL10 -592A/C polymorphisms in patients with ITP compared to the control group showed no significant differences between the two groups. However, for IL1RN intron 2 VNTR polymorphisms, IL4 -590C/T, IL4 intron 3 VNTR and IL10 haplotypes there were a significant difference when comparing polymorphic frequencies between the two groups. Analyzing the polymorphisms associated with clinical parameters, this study showed that IL1B -511CC genotype was more frequent in individuals with good response to splenectomy. It can be concluded that the study of genetic characteristics of patients with ITP in the region of Campinas, SP should help clarify the profile of patients affected, identifying groups at higher risk and understanding which polymorphism may be associated with better clinical response / Mestrado / Clinica Medica / Mestra em Clínica Médica

Untreated human immunodeficiency virus (HIV) can be complicated by opportunistic infections, including disseminated histoplasmosis (DH). Although endemic to portions of the United States and usually benign, DH can rarely act as an opportunistic infection in immunocompromised patients presenting with uncommon complications such as acute kidney injury and idiopathic thrombocytopenic purpura. We report a rare presentation of DH presenting with acute kidney injury and immune thrombocytopenic purpura in an immunocompromised patient with HIV.

Digital full-text not provided.

Abstract Background: Deficiency of Von Willebrand Factor Cleaving Protease (VWFCP) has been implicated as the cause of Thrombotic Thrombocytopenic Purpura (TTP). TTP is a lifethreatening disease characterised by microangiopathic thrombosis due to accumulation of Ultralarge Von Willebrand Factor (ULVWF) multimers. The clinical features of TTP include microangiopathic haemolysis and thrombocytopenia. TTP is being seen with increased frequency in the context of HIV. However, in the context of HIV infection, cytopenias are often multifactorial in nature and levels of VWFCP in HIV-related thrombocytopenia have not specifically been assessed. This study assessed VWFCP activity in the setting of patients with HIV and thrombocytopenia in the absence of TTP, in order to determine the utility of a VWFCP assay in the diagnosis of HIV-related TTP. Acquired VWFCP deficiency is generally assumed to be due to the presence of autoantibody inhibitors to the enzyme, but limited data are available regarding VWFCP activity in HIV positive TTP patients. There is also currently no assay available for measuring VWFCP activity in our laboratory. Aim of Study: To establish a practical assay for VWFCP activity for routine use in our laboratory. The rapid collagen binding assay, based on the ELISA method of Rick, et al., 2002, was chosen. This was initially used to measure VWFCP activity in patients with HIV with and without thrombocytopenia (of any cause except TTP), in order to ascertain whether assessment of VWFCP activity is likely to be of value in facilitating early diagnosis of HIV related TTP. The ELISA assay was performed to establish cut-off values for VWFCP in HIV negative controls and two HIV positive groups (HIV thrombocytopenia / low platelets and HIV normal platelets). Depending on the outcome of this, the assay could then be performed to assess VWFCP activity in HIV positive patients with TTP. Methods: The rapid collagen binding assay for VWFCP activity was established and optimised for routine use in our laboratory. The cut-off values for percentage Residual Collagen Binding Activity (RCBA) in both HIV negative and HIV positive groups were identified. The assay could then be used to assess VWFCP activity in 20 HIV positive patients with TTP at the time of presentation. In patients with reduced VWFCP activity, patient plasma was mixed with normal pool plasma in a 50:50 mix, to assess for the presence of inhibitors. Correlation of VWFCP activity, inhibitors and other laboratory and clinical parameters were performed. Results: The cut-off values for percentage RCBA in both HIV negative (<37.12%) and HIV positive (<51.51%) patients were established. The % RCBA for the HIV negative control group was statistically significantly different from the HIV positive group with normal platelets (p=0.0001) and from the HIV positive group with low platelets (p=0.0006). The cut-off value in the two HIV positive patient groups was higher than for HIV negative control patients, indicating mildly reduced VWFCP enzyme activity in HIV positive patients (regardless of the platelet count), in the absence of TTP. However, no significant difference in the cut-off value was noted between HIV positive patients with low platelet counts versus HIV positive patients with normal platelet counts (p=0.7783). The assay could therefore be used in HIV positive patients with TTP. VWFCP activity was assessed in twenty HIV positive patients with TTP. Two groups of HIV positive patients with TTP were identified based on VWFCP activity. Six patients (30%) had normal (one borderline) VWFCP activity (RCBA <51.51%), while the remaining 14 patients had severely reduced VWFCP levels (RCBA >90%). Of the patients with reduced VWFCP activity, only 5 patients had a detectable inhibitor, while an inhibitor was not detected in the remaining 8 patients. Conclusion: The rapid collagen binding ELISA assay is a cost effective semi-quantitative assay for the assessment of VWFCP activity. VWFCP activity in HIV positive patients appears to be slightly lower, however is not related to the platelet count. This suggests a slight baseline deficiency of VWFCP in the setting of HIV. The baseline VWFCP cut-off value in HIV allowed assessment of HIV positive patients with TTP. The results suggest heterogeneity of VWFCP activity in HIV-related TTP. A negative result (normal VWFCP activity) does not exclude TTP in patients with HIV-related TTP and other pathogenic factors may therefore be involved.

A púrpura trombocitopênica idiopática (PTI) é uma patologia adquirida que leva à redução da contagem de plaquetas, mediada por mecanismo imunológico. O tratamento inicial é a corticoterapia e, se caracterizada a falência ou dependência desta, a esplenectomia é a segunda opção. Autores recomendam que a esplenectomia seja realizada antes de se completarem 12 meses do diagnóstico, apesar de estudos sugerirem que a resposta após este período é semelhante. Neste estudo, pesquisaram-se a eficácia da esplenectomia tardia, as complicações da manutenção da terapia imunossupressora e as complicações hemorrágicas na população com esplenectomia tardia. Analisaram-se prontuários de 39 pacientes com idade de 4 a 64 anos (mediana de 27 anos) ao diagnóstico, submetidos à esplenectomia como procedimento terapêutico de PTI. Classificaram-se as respostas à esplenectomia, observadas na última visita, após 6 meses da cirurgia, em resposta completa (RC) (mais de 150.000 plaquetas/ l) parcial (RP) (de 50.000 a 150.000 plaquetas/ l) ou sem resposta (SR) (menos de 50.000 plaquetas/ l ou necessidade de medicação para controle da PTI). No período anterior à esplenectomia, a prednisona causou efeitos colaterais em 18% dos pacientes. Uma paciente que utilizou azatioprina desenvolveu carcinoma ductal de mama. Outros efeitos colaterais da azatioprina, danazol, colchicina, levamisol e vincristina reverteram após a suspensão das drogas. Não houve mortalidade relacionada à PTI nem às esplenectomias, mas houve mais hemorragias graves (21%) no período pré-operatório. As esplenectomias foram realizadas após 1 a 174 meses (mediana 36 meses) do diagnóstico e a última visita ocorreu depois de 9 a 300 meses (mediana 25,5 meses) da cirurgia. As respostas finais à esplenectomia foram: 16 (44%) RC, 10 (28%) RP, 10 (28%) SR. A comparação entre as respostas dos pacientes que realizaram a esplenectomia antes e as dos que a realizaram após 36 meses não mostrou diferença significativa (p=0,687). A esplenectomia tardia tem eficácia, aferida pela soma das RC e RP, comparável à citada pela literatura. As medicações imunossupressoras produziram mais efeitos colaterais e ocorreram mais hemorragias graves do que as relatadas pela literatura. / Idiopathic thrombocytopenic purpura (ITP) is an acquired immunologic disorder associated with reduction of platelet count. The primary treatment is prednisone in the majority of cases, and if it fails or if there is a dependence of it, the splenectomy is performed. The surgery is usually indicated within 12 months after diagnosis because of presumed better results. Nevertheless, clinical studies suggest that splenectomy is effective when performed after this 12 months. In this study the hemorrhagic complications of ITP, the side effects of immunossupressive therapy during preoperative period and the efficacy and safety of the procedure were studied in a population with late splenectomy. Thirty nine patients were included with median age of 27 years (range 4 to 64 years) at the diagnosis of ITP. The response to splenectomy were classified as complete response (CR) (platelets counts above 150.000/ l), partial response (PR) (platelet counts of 50.000 to 150.000/ l), and no response (NR) (less than 50.000/ l or use of drugs to maintain platelet count). In the preoperative period, prednisone caused side effects in 18% of patients. One patient who received azathioprine had breast cancer. Other side effects of azathioprine, danazol, colchicin, levamisole and vincristine remitted after drugs withdrawal. The surgeries were performed after 1 to 174 months of diagnosis (median of 36 months). Of the 39 patients, 36 had assessment of response to splenectomy after 9 to 300 months: 16 patients had CR (44%), 10 PR (28%), and 10 NR (28%). The responses of the patients with period of diagnosis to splenectomy of 36 months or more were not different from the patients with this period of less than 36 months (p=0.687). During the preoperative period, 21% of patients had severe hemorrhagic complications of ITP, but there were no death caused by ITP or splenectomy. Although, the favorable response (sum of CR and PR) of late splenectomy was similar, there were more side effects of immunossupressive therapy and severe hemorrhagic complications than the reported in the literature. Splenectomy is a therapeutic option for immune thrombocytopenic purpura (ITP), usually recommend before 12 months after diagnosis. In this study, 39 patients were splenectomized 1 to 174 months (median of 36 months) after the hemorrages and more side effects of prednisone than reported in the literature, but there were death. The favorable responses of late splectomy were similar to the reported in the literature. the favorable responses of the group with period of ITP diagnosis to splenectomy of the 36 months or more were not different from the group with less than 36 months (p=0.687).

A púrpura trombocitopênica idiopática (PTI) é uma patologia adquirida que leva à redução da contagem de plaquetas, mediada por mecanismo imunológico. O tratamento inicial é a corticoterapia e, se caracterizada a falência ou dependência desta, a esplenectomia é a segunda opção. Autores recomendam que a esplenectomia seja realizada antes de se completarem 12 meses do diagnóstico, apesar de estudos sugerirem que a resposta após este período é semelhante. Neste estudo, pesquisaram-se a eficácia da esplenectomia tardia, as complicações da manutenção da terapia imunossupressora e as complicações hemorrágicas na população com esplenectomia tardia. Analisaram-se prontuários de 39 pacientes com idade de 4 a 64 anos (mediana de 27 anos) ao diagnóstico, submetidos à esplenectomia como procedimento terapêutico de PTI. Classificaram-se as respostas à esplenectomia, observadas na última visita, após 6 meses da cirurgia, em resposta completa (RC) (mais de 150.000 plaquetas/ l) parcial (RP) (de 50.000 a 150.000 plaquetas/ l) ou sem resposta (SR) (menos de 50.000 plaquetas/ l ou necessidade de medicação para controle da PTI). No período anterior à esplenectomia, a prednisona causou efeitos colaterais em 18% dos pacientes. Uma paciente que utilizou azatioprina desenvolveu carcinoma ductal de mama. Outros efeitos colaterais da azatioprina, danazol, colchicina, levamisol e vincristina reverteram após a suspensão das drogas. Não houve mortalidade relacionada à PTI nem às esplenectomias, mas houve mais hemorragias graves (21%) no período pré-operatório. As esplenectomias foram realizadas após 1 a 174 meses (mediana 36 meses) do diagnóstico e a última visita ocorreu depois de 9 a 300 meses (mediana 25,5 meses) da cirurgia. As respostas finais à esplenectomia foram: 16 (44%) RC, 10 (28%) RP, 10 (28%) SR. A comparação entre as respostas dos pacientes que realizaram a esplenectomia antes e as dos que a realizaram após 36 meses não mostrou diferença significativa (p=0,687). A esplenectomia tardia tem eficácia, aferida pela soma das RC e RP, comparável à citada pela literatura. As medicações imunossupressoras produziram mais efeitos colaterais e ocorreram mais hemorragias graves do que as relatadas pela literatura. / Idiopathic thrombocytopenic purpura (ITP) is an acquired immunologic disorder associated with reduction of platelet count. The primary treatment is prednisone in the majority of cases, and if it fails or if there is a dependence of it, the splenectomy is performed. The surgery is usually indicated within 12 months after diagnosis because of presumed better results. Nevertheless, clinical studies suggest that splenectomy is effective when performed after this 12 months. In this study the hemorrhagic complications of ITP, the side effects of immunossupressive therapy during preoperative period and the efficacy and safety of the procedure were studied in a population with late splenectomy. Thirty nine patients were included with median age of 27 years (range 4 to 64 years) at the diagnosis of ITP. The response to splenectomy were classified as complete response (CR) (platelets counts above 150.000/ l), partial response (PR) (platelet counts of 50.000 to 150.000/ l), and no response (NR) (less than 50.000/ l or use of drugs to maintain platelet count). In the preoperative period, prednisone caused side effects in 18% of patients. One patient who received azathioprine had breast cancer. Other side effects of azathioprine, danazol, colchicin, levamisole and vincristine remitted after drugs withdrawal. The surgeries were performed after 1 to 174 months of diagnosis (median of 36 months). Of the 39 patients, 36 had assessment of response to splenectomy after 9 to 300 months: 16 patients had CR (44%), 10 PR (28%), and 10 NR (28%). The responses of the patients with period of diagnosis to splenectomy of 36 months or more were not different from the patients with this period of less than 36 months (p=0.687). During the preoperative period, 21% of patients had severe hemorrhagic complications of ITP, but there were no death caused by ITP or splenectomy. Although, the favorable response (sum of CR and PR) of late splenectomy was similar, there were more side effects of immunossupressive therapy and severe hemorrhagic complications than the reported in the literature. Splenectomy is a therapeutic option for immune thrombocytopenic purpura (ITP), usually recommend before 12 months after diagnosis. In this study, 39 patients were splenectomized 1 to 174 months (median of 36 months) after the hemorrages and more side effects of prednisone than reported in the literature, but there were death. The favorable responses of late splectomy were similar to the reported in the literature. the favorable responses of the group with period of ITP diagnosis to splenectomy of the 36 months or more were not different from the group with less than 36 months (p=0.687).

Introdução: Estudos avaliando a prevalência de síndrome de Evans (SE) no lúpus eritematoso sistêmico juvenil (LESJ) bem como possíveis fatores associados são restritos a poucos relatos de caso. Objetivos: Avaliar a prevalência de SE em uma grande população de LESJ, assim como sua possível associação com dados demográficos, manifestações clínicas, características laboratoriais, atividade/dano cumulativo da doença e tratamento. Métodos: Um estudo de coorte multicêntrico retrospectivo foi realizado em 10 serviços de Reumatologia Pediátrica provenientes do Grupo Brasileiro de Lúpus e incluiu 850 pacientes com LESJ. SE foi avaliada ao diagnóstico do LES e definida pela combinação de púrpura trombocitopênica autoimune (PTI) e anemia hemolítica autoimune (AHAI). Os pacientes foram divididos em dois grupos para a avaliação das associações propostas: pacientes que apresentaram SE e pacientes sem SE. Todos foram avaliados ao diagnóstico do LES. Resultados: SE foi observada em 11/850 pacientes de LESJ ao diagnostico (1,3%). A maioria deles tinha doença ativa (82%) e apresentaram manifestações hemorrágicas (58%). Todos os pacientes com SE foram hospitalizados e não houve nenhum óbito. As comparações entre pacientes LESJ com e sem SE ao diagnóstico demonstrou frequências similares do sexo feminino, envolvimento de múltiplos órgãos, perfil de auto-anticorpos semelhantes e complemento baixo (p > 0,05). Pacientes com SE tinham frequências menores de eritema malar (9% vs. 53%, p=0,003) e envolvimento músculo-esquelético (18% vs. 69%, p=0,001) do que aqueles sem esta complicação. A frequência de pulsoterapia com metilprednisolona (82% vs. 43%, p=0,013) e uso de gamaglobulina endovenosa (64% vs. 3%), p < 0,0001) foram significativamente maiores no grupo com SE, com dose atual de prednisona semelhante entre os dois grupos [1,1 (0,76-1,5) vs. 1,0 (0-30) mg/kg/dia, p=0,195]. Conclusões: Este foi o primeiro estudo que evidenciou a possível relação de SE como uma manifestação inicial rara e grave do LESJ, porém com bom prognóstico. O diagnóstico se torna o principal desafio devido à falta de sinais e sintomas característicos de lúpus e a dificuldade de se excluir diagnósticos diferenciais como infecção e imunodeficiência primária / Introduction: Studies evaluating the prevalence of Evans Syndrome (ES) in childhood-onset systemic lupus erythematosus (cSLE) as well as possible associated factors has been rarely reported and restricted to case reports. Objectives: To evaluate the prevalence of ES in a large population of cSLE, and the association with demographic data, clinical manifestations, laboratory characteristics, disease activity, cumulative damage, and treatment. Methods: A retrospective multicenter cohort study was performed in 10 Pediatric Rheumatology services and included 850 patients with cSLE. ES was evaluated at the diagnosis of cSLE and defined as the combination of autoimmune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). The patients were divided into two groups for the evaluation of the proposed associations: patients who presented ES and patients without ES. All were assessed at the cSLE diagnosis. Results: ES was observed in 11/850 (1.3%) cSLE patients. The majority of them had hemorrhagic manifestations (58%) and active disease (82%). All patients with ES were hospitalized and none died. Comparisons of cSLE patients with and without ES at diagnosis revealed similar frequencies of female gender, multi-organ involvement, autoantibodies profile and low complement (p > 0.05). Patients with ES had a lower frequency of malar rash (9% vs. 53%, p=0.003) and musculoskeletal involvement (18% vs. 69%, p=0.001) than those without this complication. The frequencies of intravenous methylprednisolone (82% vs. 43%, p=0.013) and intravenous immunoglobulin use (64% vs. 3%, p < 0.0001) were significantly higher in the former group, with similar current prednisone dose between groups [1.1 (0.76-1.5) vs. 1.0 mg/kg/day (0-30), 0.195]. Conclusions: This was the first study that evidenced the possible relationship of ES as a rare and severe initial manifestation of cSLE, but with a good prognosis. Diagnosis becomes the main challenge due to the lack of signs and symptoms characteristic of lupus and the difficulty of excluding differential diagnoses such as infection and primary immunodeficiency

Introdução: Estudos avaliando a prevalência de síndrome de Evans (SE) no lúpus eritematoso sistêmico juvenil (LESJ) bem como possíveis fatores associados são restritos a poucos relatos de caso. Objetivos: Avaliar a prevalência de SE em uma grande população de LESJ, assim como sua possível associação com dados demográficos, manifestações clínicas, características laboratoriais, atividade/dano cumulativo da doença e tratamento. Métodos: Um estudo de coorte multicêntrico retrospectivo foi realizado em 10 serviços de Reumatologia Pediátrica provenientes do Grupo Brasileiro de Lúpus e incluiu 850 pacientes com LESJ. SE foi avaliada ao diagnóstico do LES e definida pela combinação de púrpura trombocitopênica autoimune (PTI) e anemia hemolítica autoimune (AHAI). Os pacientes foram divididos em dois grupos para a avaliação das associações propostas: pacientes que apresentaram SE e pacientes sem SE. Todos foram avaliados ao diagnóstico do LES. Resultados: SE foi observada em 11/850 pacientes de LESJ ao diagnostico (1,3%). A maioria deles tinha doença ativa (82%) e apresentaram manifestações hemorrágicas (58%). Todos os pacientes com SE foram hospitalizados e não houve nenhum óbito. As comparações entre pacientes LESJ com e sem SE ao diagnóstico demonstrou frequências similares do sexo feminino, envolvimento de múltiplos órgãos, perfil de auto-anticorpos semelhantes e complemento baixo (p > 0,05). Pacientes com SE tinham frequências menores de eritema malar (9% vs. 53%, p=0,003) e envolvimento músculo-esquelético (18% vs. 69%, p=0,001) do que aqueles sem esta complicação. A frequência de pulsoterapia com metilprednisolona (82% vs. 43%, p=0,013) e uso de gamaglobulina endovenosa (64% vs. 3%), p < 0,0001) foram significativamente maiores no grupo com SE, com dose atual de prednisona semelhante entre os dois grupos [1,1 (0,76-1,5) vs. 1,0 (0-30) mg/kg/dia, p=0,195]. Conclusões: Este foi o primeiro estudo que evidenciou a possível relação de SE como uma manifestação inicial rara e grave do LESJ, porém com bom prognóstico. O diagnóstico se torna o principal desafio devido à falta de sinais e sintomas característicos de lúpus e a dificuldade de se excluir diagnósticos diferenciais como infecção e imunodeficiência primária / Introduction: Studies evaluating the prevalence of Evans Syndrome (ES) in childhood-onset systemic lupus erythematosus (cSLE) as well as possible associated factors has been rarely reported and restricted to case reports. Objectives: To evaluate the prevalence of ES in a large population of cSLE, and the association with demographic data, clinical manifestations, laboratory characteristics, disease activity, cumulative damage, and treatment. Methods: A retrospective multicenter cohort study was performed in 10 Pediatric Rheumatology services and included 850 patients with cSLE. ES was evaluated at the diagnosis of cSLE and defined as the combination of autoimmune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). The patients were divided into two groups for the evaluation of the proposed associations: patients who presented ES and patients without ES. All were assessed at the cSLE diagnosis. Results: ES was observed in 11/850 (1.3%) cSLE patients. The majority of them had hemorrhagic manifestations (58%) and active disease (82%). All patients with ES were hospitalized and none died. Comparisons of cSLE patients with and without ES at diagnosis revealed similar frequencies of female gender, multi-organ involvement, autoantibodies profile and low complement (p > 0.05). Patients with ES had a lower frequency of malar rash (9% vs. 53%, p=0.003) and musculoskeletal involvement (18% vs. 69%, p=0.001) than those without this complication. The frequencies of intravenous methylprednisolone (82% vs. 43%, p=0.013) and intravenous immunoglobulin use (64% vs. 3%, p < 0.0001) were significantly higher in the former group, with similar current prednisone dose between groups [1.1 (0.76-1.5) vs. 1.0 mg/kg/day (0-30), 0.195]. Conclusions: This was the first study that evidenced the possible relationship of ES as a rare and severe initial manifestation of cSLE, but with a good prognosis. Diagnosis becomes the main challenge due to the lack of signs and symptoms characteristic of lupus and the difficulty of excluding differential diagnoses such as infection and primary immunodeficiency