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Abstract Cutaneous manifestations occur in the course of hematologic malignancies and precede, accompany or occur late in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, immunosuppression resulting from the hematologic disease itself or its treatment. The dermatologist must be aware of these conditions that may be helpful both in the diagnosis of the underlying disease and in reducing patient morbidity. This review (part II) addresses the paraneoplastic dermatological changes associated with systemic hematologic malignancies.
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Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical-immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical-immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.
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Abstract Cutaneous manifestations occur during the course of hematologic malignancies and precede, follow, or are late events in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, and immunosuppression resulting from the hematologic neoplasia itself or its treatment. The dermatologist must be aware of these conditions, which can help both in the diagnosis of the underlying disease and in the reduction of patient morbidity. This review (part I) addresses skin lesions associated with direct infiltration by systemic hematologic malignancies.
RESUMO
Cutaneous manifestations occur in the course of hematologic malignancies and precede, accompany or occur late in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, immunosuppression resulting from the hematologic disease itself or its treatment. The dermatologist must be aware of these conditions that may be helpful both in the diagnosis of the underlying disease and in reducing patient morbidity. This review (part II) addresses the paraneoplastic dermatological changes associated with systemic hematologic malignancies.
Assuntos
Neoplasias Hematológicas , Neoplasias , Dermatopatias , Humanos , Dermatopatias/etiologia , Dermatopatias/patologia , Neoplasias Hematológicas/complicações , AutoanticorposRESUMO
Cutaneous manifestations occur during the course of hematologic malignancies and precede, follow, or are late events in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, and immunosuppression resulting from the hematologic neoplasia itself or its treatment. The dermatologist must be aware of these conditions, which can help both in the diagnosis of the underlying disease and in the reduction of patient morbidity. This review (part I) addresses skin lesions associated with direct infiltration by systemic hematologic malignancies.
Assuntos
Neoplasias Hematológicas , Dermatopatias , Neoplasias Cutâneas , Humanos , Dermatopatias/patologia , Neoplasias Hematológicas/complicações , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologiaRESUMO
This was an open cohort prospective study (2016−2018) that analyzed the prevalence and incidence rates of human Leishmania (L.) infantum chagasi-infection and the evolution of their clinical-immunological profiles in distinct urban and rural scenarios of American visceral leishmaniasis (AVL) in Pará State, in the Brazilian Amazon. These infection profiles were based on species-specific DTH/IFAT-IgG assays and clinical evaluation of infected individuals, comprising five profiles: three asymptomatic, Asymptomatic Infection [AI], Subclinical Resistant Infection [SRI], and Indeterminate Initial Infection [III]; and two symptomatic, Subclinical Oligosymptomatic Infection [SOI] and Symptomatic Infection [SI = AVL]. The two distinct scenarios (900 km away) were the urban area of Conceição do Araguaia municipality and the rural area of Bujaru municipality in the southeast and northeast of Pará State. Human populations were chosen based on a simple convenience sampling design (5−10% in each setting), with 1723 individuals (5.3%) of the population (32,464) in the urban area and 1568 individuals (8.9%) of the population (17,596) in the rural one. A serological survey (IFAT-IgG) of canine infection was also performed in both scenarios: 195 dogs in the urban area and 381 in the rural one. Prevalence and incidence rates of human infection were higher in the urban area (20.3% and 13.6/100 person-years [py]) than in the rural setting (14.1% and 6.8/100-py). The AI profile was the most prevalent and incident in both urban (13.4% and 8.1/100-py) and rural (8.3% and 4.2/100-py) scenarios, but with higher rates in the former. An III profile case evolved to SOI profile after four weeks of incubation and another to SI (=AVL) after six. The prevalence of canine infection in an urban setting (39.2%) was also higher (p < 0.05) than that (32%) in the rural zone. AVL urbanization in Pará State, in the Brazilian Amazon, has led to infection rates significantly higher than those in rural sites, requiring more intense control measures.
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Visceral leishmaniasis (VL), also known as kala-azar, is an anthropozoonotic disease affecting human populations on five continents. Aetiologic agents belong to the Leishmania (L.) donovani complex. Until the 1990s, three leishmanine parasites comprised this complex: L. (L.) donovani Laveran & Mesnil 1903, L. (L.) infantum Nicolle 1908, and L. (L.) chagasi Lainson & Shaw 1987 (=L. chagasi Cunha & Chagas 1937). The VL causal agent in the New World (NW) was previously identified as L. (L.) chagasi. After the development of molecular characterization, however, comparisons between L. (L.) chagasi and L. (L.) infantum showed high similarity, and L. (L.) chagasi was then regarded as synonymous with L. (L.) infantum. It was, therefore, suggested that L. (L.) chagasi was not native to the NW but had been introduced from the Old World by Iberian colonizers. However, in light of ecological evidence from the NW parasite's enzootic cycle involving a wild phlebotomine vector (Lutzomyia longipalpis) and a wild mammal reservoir (the fox, Cerdocyon thous), we have recently analyzed by molecular clock comparisons of the DNA polymerase alpha subunit gene the whole-genome sequence of L. (L.) infantum chagasi of the most prevalent clinical form, atypical dermal leishmaniasis (ADL), from Honduras (Central America) with that of the same parasite from Brazil (South America), as well as those of L. (L.) donovani (India) and L. (L.) infantum (Europe), which revealed that the Honduran parasite is older ancestry (382,800 ya) than the parasite from Brazil (143,300 ya), L. (L.) donovani (33,776 ya), or L. (L.) infantum (13,000 ya). In the present work, we have now amplified the genomic comparisons among these leishmanine parasites, exploring mainly the variations in the genome for each chromosome, and the number of genomic SNPs for each chromosome. Although the results of this new analysis have confirmed a high genomic similarity (~99%) among these parasites [except L. (L.) donovani], the Honduran parasite revealed a single structural variation on chromosome 17, and the highest frequency of genomic SNPs (more than twice the number seen in the Brazilian one), which together to its extraordinary ancestry (382,800 ya) represent strong evidence that L. (L.) chagasi/L. (L.) infantum chagasi is, in fact, native to the NW, and therefore with valid taxonomic status. Furthermore, the Honduran parasite, the most ancestral viscerotropic leishmanine parasite, showed genomic and clinical taxonomic characteristics compatible with a new Leishmania species causing ADL in Central America.
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This work reports on the whole-genome sequencing of Leishmania infantum chagasi from Honduras (Central America) and Brazil (South America).
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The clinical-immunological spectrum of human Leishmania (L.) infantum chagasi-infections in the Brazilian Amazon has been defined using DTH/IFAT-IgG immune assays and the clinical statuses of infected individuals, revealing five profiles: three asymptomatic [Asymptomatic Infection (AI), Subclinical Resistant Infection (SRI), and Indeterminate Initial Infection (III)], and two symptomatic profiles [Subclinical Oligosymptomatic Infection (SOI) and Symptomatic Infection (SI = American visceral leishmaniasis/AVL)]. We evaluated the diagnostic potential of urine qPCR over the entire spectrum of infection. Resine Instagene Matrix® was used for DNA extraction from urinary sediment, with amplification carried out using SYBR® Green Taq with the RV1 and RV2 primers. We examined urine samples from 151 individuals from an endemic area of AVL in Pará State in the Brazilian Amazon, including: 91 (60.3%) with diagnoses of previous infections [13 (14.3%) sharing the AI profile, 13 (14.3%) with the SRI profile, 43 (47.2%) with III, 12 (13.2%) with SI (treated AVL), and 10 (11%) with SI (untreated AVL)]; sixty (39.7%) were DTH(-)/IFAT-IgG(-) (the uninfected group). The urine qPCR was positive in 61.5% of both the AI and SRI profiles, 65% of the III profile, 50% of treated AVL, 100% of untreated AVL, and 6.7% of the uninfected group. Those results confirmed the urine qPCR diagnosis in 100% of untreated AVL cases as well as in more than 60% of the cases with asymptomatic AI, SRI, and III profiles - indicating it as a promising tool for monitoring the evolution of human L. (L.) infantum chagasi-infections in endemic areas.
Assuntos
Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas , Brasil , Feminino , Humanos , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/urina , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
INTRODUCTION: In the Belém Metropolitan Region (BMR), Pará State, Brazil, American cutaneous leishmaniasis (ACL) is endemic; however, very little is known regarding its causative agents. Therefore, we used our standard diagnostic approach combined with an RNA polymerase II largest subunit (RNAPOIILS)-polymerase chain reaction (PCR) followed by analysis of restriction fragment length polymorphism (PCR-RFLP) to identify Leishmania spp. ACL agents in this region. METHODS: Thirty-two Leishmania spp. isolates from patients with ACL in the BMR during 1995-2018 were analyzed. Leishmania spp. DNA samples were amplified using the primers RPOR2/RPOF2, and the 615-bp PCR products were subjected to enzymatic digestion using TspRI and HgaI endonucleases. RESULTS: ACL etiological agents in the BMR comprised Leishmania (Viannia) lindenbergi (43.7%) followed by Leishmania (Viannia) lainsoni (34.4%), Leishmania (Leishmania) amazonensis (12.5%), and Leishmania (Viannia) braziliensis (9.4%). CONCLUSIONS: To our knowledge, the results of the study revealed for the first time that L. (V.) lindenbergi and L. (V.) lainsoni are the main ACL agents in BMR.
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Leishmania braziliensis , Leishmania , Leishmaniose Cutânea , Brasil/epidemiologia , Humanos , Leishmania/genética , Leishmania braziliensis/genética , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Polimorfismo de Fragmento de Restrição , Estados UnidosRESUMO
The clinical-immunological spectrum of human Leishmania (L.) infantum chagasi-infection in Amazonian Brazil has recently been reviewed based on the combined use of the delayed-type hypersensitivity (DTH) and indirect fluorescence antibody test (IFAT-IgG/IgM), both with homologous L. (L.) infantum chagasi-antigens, and associated with the clinical evaluation of infected individuals. This diagnostic approach has allowed to identify the broadest clinical-immunological spectrum of human L. (L.) infantum chagasi-infection composed by five clinical-immunological profiles of infection: three asymptomatic, 1) Asymptomatic Infection (AI) [DTH+/++++, IFAT-], 2) Subclinical Resistant Infection (SRI) [DTH+/++++, IFAT+/++], and 3) Indeterminate Initial Infection (III) [DTH-, IFAT+/++], and two symptomatic ones, 4) Symptomatic Infection (SI) [=American visceral leishmaniasis - AVL] and, 5) Subclinical Oligosymptomatic Infection (SOI), both with the same immune profile [DTH-, IFAT+++/++++]. Herein, we confirm for the third time the preclinical diagnosis of AVL through IgM-antibody response in an early asymptomatic case of infection (profile III), a 17-year-old boy who evolved to AVL (=profile SI) six weeks after the initial infection diagnosis, confirming that the combined use of DTH and IFAT-(IgG/IgM) assays associated with the clinical evaluation of infected individuals is potentially useful for monitoring human L. (L.) infantum chagasi-infection in endemic areas as well as optimizing AVL control.
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In the present study, we reported the natural infection by Leishmania sp. in a domestic cat, in which the amastigote forms of the parasite were observed within a lesion on its ear-tip. Fragment of the lesion was obtained and cultured in NNN medium, and PCR-RFLP analysis of the isolated sample was performed, which revealed that the profile was compatible with Leishmania (L.) amazonensis. This is the first proven case of a cat infected by L. (L.) amazonensis reported in Belém city, Pará state, northern Brazil.
Assuntos
Alopurinol/uso terapêutico , Azitromicina/uso terapêutico , Doenças do Gato/diagnóstico , Leishmania mexicana/isolamento & purificação , Leishmaniose Cutânea/veterinária , Dermatopatias/veterinária , Tripanossomicidas/uso terapêutico , Animais , Brasil , Doenças do Gato/tratamento farmacológico , Doenças do Gato/parasitologia , Gatos , Diagnóstico Diferencial , Feminino , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Dermatopatias/parasitologiaRESUMO
Abstract INTRODUCTION: In the Belém Metropolitan Region (BMR), Pará State, Brazil, American cutaneous leishmaniasis (ACL) is endemic; however, very little is known regarding its causative agents. Therefore, we used our standard diagnostic approach combined with an RNA polymerase II largest subunit (RNAPOIILS)-polymerase chain reaction (PCR) followed by analysis of restriction fragment length polymorphism (PCR-RFLP) to identify Leishmania spp. ACL agents in this region. METHODS: Thirty-two Leishmania spp. isolates from patients with ACL in the BMR during 1995-2018 were analyzed. Leishmania spp. DNA samples were amplified using the primers RPOR2/RPOF2, and the 615-bp PCR products were subjected to enzymatic digestion using TspRI and HgaI endonucleases. RESULTS: ACL etiological agents in the BMR comprised Leishmania (Viannia) lindenbergi (43.7%) followed by Leishmania (Viannia) lainsoni (34.4%), Leishmania (Leishmania) amazonensis (12.5%), and Leishmania (Viannia) braziliensis (9.4%). CONCLUSIONS: To our knowledge, the results of the study revealed for the first time that L. (V.) lindenbergi and L. (V.) lainsoni are the main ACL agents in BMR.
Assuntos
Humanos , Leishmania braziliensis/genética , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Leishmania/genética , Estados Unidos , Brasil/epidemiologia , Leishmaniose CutâneaRESUMO
BACKGROUND: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. OBJECTIVES: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). METHODS: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. RESULTS: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). CONCLUSIONS: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.
Assuntos
Consenso , Urticária/diagnóstico , Urticária/tratamento farmacológico , Adulto , Antialérgicos/uso terapêutico , Brasil , Doença Crônica , Ciclosporinas/uso terapêutico , Dermatologia , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Omalizumab/uso terapêutico , Índice de Gravidade de Doença , Sociedades Médicas , Urticária/prevenção & controleRESUMO
Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.
Assuntos
Humanos , Adulto , Urticária/diagnóstico , Urticária/tratamento farmacológico , Consenso , Sociedades Médicas , Urticária/prevenção & controle , Índice de Gravidade de Doença , Brasil , Doença Crônica , Antialérgicos/uso terapêutico , Ciclosporinas/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Dermatologia , Omalizumab/uso terapêutico , Imunossupressores/uso terapêuticoRESUMO
Leishmania (V.) braziliensis and Leishmania(L.) amazonensis are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCLDTH+/++), borderline disseminated cutaneous leishmaniasis (BDCLDTH±), anergic diffuse cutaneous leishmaniasis (ADCLDTH-), and mucosal leishmaniasis (MLDTH++++). It has recently been demonstrated, however, that while L. (V.) braziliensis shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), L. (L.) amazonensis drives the infection in the opposite direction to ADCL (the lowest T-cell hypersensitivity pole). This study evaluated by immunohistochemistry the expression of Toll-like receptors (TLRs) 2, 4, and 9 and their relationships with CD4 and CD8 T-cells, and TNF-α, IL-10, and TGF-ß cytokines in that disease spectrum. Biopsies of skin and mucosal lesions from 43 patients were examined: 6 cases of ADCL, 5 of BDCL, and 11 of LCL caused byL. (L.) amazonensis; as well as 10 cases of LCL, 4 of BDCL, and 6 of ML caused byL. (V.) braziliensis. CD4+ T-cells demonstrated their highest expression in ML and, in contrast, their lowest in ADCL. CD8+ T-cells also showed their lowest expression in ADCL as compared to the other forms of the disease. TNF-α+showed increased expression from ADCL to ML, while IL-10+and TGF-ß+ showed increased expression in the opposite direction, from ML to ADCL. With regards to TLR2, 4, and 9 expressions, strong interactions of TLR2 and 4 with clinical forms associated with L. (V.) braziliensis were observed, while TLR9, in contrast, showed a strong interaction with clinical forms linked to L. (L.) amazonensis. These findings strongly suggest the ability of L. (V.) braziliensis and L. (L.) amazonensis to interact with those TLRs to promote a dichotomous T-cell immune response in ACL.
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Leishmaniose Cutânea/metabolismo , Receptor 2 Toll-Like/biossíntese , Receptor 4 Toll-Like/biossíntese , Receptor Toll-Like 9/biossíntese , Adulto , Idoso , Brasil , Estudos Transversais , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Interações Hospedeiro-Parasita/imunologia , Humanos , Imuno-Histoquímica , Leishmania braziliensis/imunologia , Leishmania braziliensis/fisiologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Pele/imunologia , Pele/parasitologia , Pele/patologia , Linfócitos T/imunologia , Linfócitos T/parasitologia , Adulto JovemRESUMO
We present here a cross-sectional study analyzing the IgG1 and IgG2 immune responses to natural canine Leishmania (L.) infantum chagasi-infection and their relationships with delayed-type hypersensitivity (DTH) in 50 mongrel dogs with previous positive serodiagnoses (IFAT-IgG) (56% with subclinical status [= apparently healthy] and 44% clinically sick), living in endemic areas for visceral leishmaniasis in the Brazilian Amazon. IgG1 and IgG2 responses were measured using commercial polyclonal antibodies in ELISA, while DTH was elicited by intradermal skin test using cultured promastigotes L. (L.) i. chagasi-antigen. Data analyses used Chi-square and Pearson's r coefficient (95% confidence interval). Regarding DTH and the clinical statuses of dogs, it was noted that 100% of the animals showing positive DTH (n = 8) were from the subclinical group, while 100% showing negative DTH were from the clinically sick group; higher IgG2 than IgG1 responses were observed in both clinical groups. However, when this comparison was made between the subclinical and sick groups, higher IgG1 responses were noted in the dogs from the sick rather than the subclinical group, while no differences were noted between the IgG2 responses in the dogs from both clinical groups. Additionally, we found lower IgG1 responses in dogs from the subclinical group showing positive DTH than in the dogs from the subclinical or sick groups with negative DTH; no differences were found between the IgG2 responses of these two clinical groups. These findings suggest that the IgG1, but not the IgG2, response is associated with susceptibility to canine visceral leishmaniasis (CVL).
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Doenças do Cão/imunologia , Imunoglobulina G/sangue , Leishmaniose Visceral/veterinária , Distribuição por Idade , Animais , Brasil/epidemiologia , Intervalos de Confiança , Estudos Transversais , Suscetibilidade a Doenças/veterinária , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Imunoglobulina G/classificação , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/imunologia , Masculino , Distribuição por Sexo , Estatística como AssuntoRESUMO
The clinical-immunological spectrum of human Leishmania (L.) infantum chagasi infection in Amazonian Brazil was recently reviewed based on clinical, DTH, and IFAT (IgG) evaluations that identified five profiles: three asymptomatic (asymptomatic infection, AI; subclinical resistant infection, SRI; and indeterminate initial infection, III) and two symptomatic (symptomatic infection, SI; American visceral leishmaniasis, AVL; and subclinical oligosymptomatic infection, SOI). TNF-α, IL-4, IL-6, and IL-10 serum cytokines were analyzed using multiplexed Cytometric Bead Array in 161 samples from endemic areas in the Brazilian Amazon: SI [AVL] (21 cases), III (49), SRI (19), SOI (12), AI (36), and a control group [CG] (24). The highest IL-6 serum levels were observed in the SI profile (AVL); higher IL-10 serum levels were observed in SI than in SOI or CG and in AI and III than in SOI; higher TNF-α serum levels were seen in SI than in CG. Positive correlations were found between IL-6 and IL-10 serum levels in the SI and III profiles and between IL-6 and TNF-α and between IL-4 and TNF-α in the III profile. These results provide strong evidence for associating IL-6 and IL-10 with the immunopathogenesis of AVL and help clarify the role of these cytokines in the infection spectrum.
Assuntos
Citocinas/sangue , Leishmania infantum/imunologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/imunologia , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Leishmaniose Visceral/sangue , Masculino , Adulto JovemRESUMO
BACKGROUND: Current guidelines on chronic spontaneous urticaria (CSU) suggest a treatment based on a 3-step approach that aims at total symptom control, starting with H1-antihistamines. However, a significant number of patients present an antihistamine-resistant urticaria that must be treated with an alternative third-line therapy such as omalizumab. METHODS: Patients with a history of CSU who did not respond to treatment with high doses of modern antihistamines were treated with 150 or 300 mg of omalizumab every 4 weeks. The response to treatment was recorded as complete (CR), partial (PR) or no response. A dose adjustment was proposed according to response. RESULTS: We treated 47 CSU patients with omalizumab (40 females), of whom 39.5% had evidence of autoimmunity. The average number of treatments was 11.4 (range 2-87). All patients had been refractory to high-dose modern antihistamines. A CR was seen in 84.6% of patients who started with 300 mg and in 60% of those who started with 150 mg. Only 1 patient had no response to both the 150- and 300-mg doses. In 6 of the PR patients with 150 mg, a higher dose of 300 mg was proposed and 4 had a CR. Four patients discontinued the treatment. No severe adverse events were reported in the patients who finished the study. DISCUSSION: Although good results were seen in both groups, CR rates were higher in those under a high-dose initial treatment. Our data strongly suggest that the therapy should be individualized.
Assuntos
Antialérgicos/uso terapêutico , Omalizumab/uso terapêutico , Urticária/tratamento farmacológico , Urticária/imunologia , Adolescente , Adulto , Idoso , Antialérgicos/administração & dosagem , Brasil , Doença Crônica , Resistência a Medicamentos , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Omalizumab/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Os ferimentos ocasionados por mordeduras animais são comuns e de importância na saúde pública, tendo consequências, como desfiguração, infecção e, até mesmo, a morte em casos mais graves. A conduta frente a essas lesões é controversa, principalmente do ponto de vista do fechamento primário da ferida da profilaxia de doenças infecto-contagiosas, originadas a partir do contato da saliva do animal com a ferida. O atendimento desses doentes na urgência consiste no controle da infecção, reabilitação funcional e, consequentemente, estética, a fim de minimizar danos psíquicos e possibilitar retorno ao convívio social. O presente trabalho relata o caso de ferimento em lábio superior de uma criança decorrente de agressão por mordida canina. A reconstrução foi realizada através da rotação de retalho rombóide da mucosa oral bem como do avanço retilíneo do retalho cutâneo associado aos triângulos de Descarga. Além disso, foi instituída uma antibioticoterapia específica. Dessa maneira, foi obtido um resultado estético e funcional satisfatório, sem complicações infecciosas pós-operatórias ou deiscências de suturas... (AU)
Injuries caused by dog bites are common and have importance in public health, with consequences such as disfigurement, infection and even death in severe cases. The correct approach to these lesions is controversial, especially in primary closure of the point of view of the wound and prophylaxis of infectious diseases originating from the animal's saliva contact with the wound. The care of these patients in the emergency consists in controlling infection, functional rehabilitation and consequently aesthetics in order to minimize possible psychological damage and return to social life. This paper reports the injury case in upper lip of a child resulting from aggression by canine bite. The reconstruction was carried out by retail rhomboid oral mucosa rotation and straight forward skin flap associated with the discharge of triangles. Moreover, a particular antibiotic was introduced. Thus it was obtained a satisfactory aesthetic and functional results without infectious postoperative complications or dehiscence of sutures... (AU)