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INTRODUCTION: Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198). METHODOLOGY: The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients. RESULTS: We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects. CONCLUSIONS: The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.
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Predisposição Genética para Doença , Hanseníase Virchowiana , Polimorfismo de Nucleotídeo Único , Receptores Tipo II do Fator de Necrose Tumoral , Receptores Tipo I de Fatores de Necrose Tumoral , Fator de Necrose Tumoral alfa , Humanos , México , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hanseníase Virchowiana/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Adulto Jovem , Idoso , Frequência do Gene , Polimorfismo de Fragmento de Restrição , Estudos de Casos e Controles , Genótipo , Adolescente , Reação em Cadeia da PolimeraseRESUMO
Los fenómenos reaccionales de la lepra son complicaciones inflamatorias que a menudo se presentan como verdaderas emergencias médicas durante el curso del tratamiento o incluso después de culminarlo. A menudo, los síntomas sistémicos como la fiebre pueden aparecer antes que las manifestaciones cutáneas y desconcertar al médico. Se realiza la presentación del caso de un paciente masculino, 39 años, sano, que acude con cuadro de 2 meses de evolución de fiebre, pérdida de peso, con posterior aparición de manchas rojas en todo el cuerpo. Se realizaron biopsia de piel y baciloscopia, con los cuales se pudieron llegar al diagnóstico de lepra.
The reactional phenomena of leprosy are inflammatory complications that often present as true medical emergencies during treatment or even after completion. Often, systemic symptoms such as fever can appear before skin manifestations and baffle the doctor. The case presented is a 39-year male patient, healthy, who consult with a 2-month history of fever, and weight loss, with subsequent appearance of red spots all over the body. A skin biopsy and smear microscopy were performed, with which leprosy was diagnosed.
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Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Hanseníase Virchowiana/imunologia , Antígenos CD , Imunofenotipagem , Lobomicose/patologia , Hanseníase Virchowiana/patologia , Receptores de Superfície Celular , Óxido Nítrico Sintase Tipo II , Lobomicose/imunologia , MacrófagosRESUMO
Background: The lepromatous leprosy (LL) disease is caused by Mycobacterium leprae and Mycobacterium lepromatosis which is characterized by inadequate response to treatment, a propensity to drug resistance, and patient disability. We aimed to evaluate current immunomodulatory medicines and their target proteins collectively as a drug repurposing strategy to decipher novel uses for LL. Methods: A dataset of human genes associated with LL-immune response was retrieved from public health genomic databases including the Human Genome Epidemiology Navigator and DisGeNET. Retrieved genes were filtered and enriched to set a robust network (≥10, up to 21 edges) and analyzed in the Cytoscape program (v3.9). Drug associations were obtained in the NDEx Integrated Query (v1.3.1) coupled with drug databases such as ChEMBL, BioGRID, and DrugBank. These networks were analyzed in Cytoscape with the CyNDEx-2 plugin and STRING protein network database. Results: Pathways analyses resulted in 100 candidate drugs organized into pharmacological groups with similar targets and filtered on 54 different drugs. Gene-target network analysis showed that the main druggable targets associated with LL were tumoral necrosis factor-alpha, interleukin-1B, and interferon-gamma. Consistently, glucosamine, binimetinib, talmapimod, dilmapimod, andrographolide, and VX-702 might have a possible beneficial effect coupled with LL treatment. Conclusion: Based on our drug repurposing analysis, immunomodulatory drugs might have a promising potential to be explored further as therapeutic options or to alleviate symptoms in LL patients.
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Hanseníase Virchowiana , Humanos , Hanseníase Virchowiana/tratamento farmacológico , Reposicionamento de Medicamentos , Mycobacterium leprae/genética , Interferon gamaRESUMO
OBJECTIVES: Leprosy is caused by Mycobacterium leprae or Mycobacterium lepromatosis. This study reviews literature on M lepromatosis and reports on a Mexican family with this infection. METHODS: The review included all primary studies. Family history and surveys were used to uncover the infection cluster. Genome-based differential polymerase chain reactions were designed to detect etiologic agents. RESULTS: Since the discovery of M lepromatosis in 2008, 154 cases of M lepromatosis infection from 11 countries in the Americas and Asia have been reported, with most cases coming from Mexico. These cases included diffuse lepromatous leprosy (DLL) and other leprosy forms. Genomes of M lepromatosis strains have lately been sequenced, revealing 3,271,694 nucleotides and approximately 15% mismatches with M leprae. The Mexican family with leprosy involved the grandfather, mother, and 2 grandsons. The index was the oldest grandson, who manifested DLL and likely contracted the infection from his maternal grandfather approximately 13 years earlier. Family surveys diagnosed DLL in the index patient's mother and borderline leprosy in his brother; both were likely infected by the index patient. M lepromatosis was identified from archived biopsies from the index patient and his mother, while M leprae was excluded. CONCLUSIONS: M lepromatosis is a significant cause of leprosy in Mexico and requires better surveillance and control.
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Hanseníase Virchowiana , Hanseníase , Mycobacterium , Masculino , Humanos , Hanseníase/diagnóstico , Hanseníase/microbiologia , Mycobacterium/genética , Mycobacterium leprae/genética , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologiaRESUMO
Resumen: Introducción: la enfermedad de Hansen es una enfermedad infecciosa crónica, causada por Mycobacterium leprae, que afecta principalmente piel y nervios periféricos. Las reacciones leprosas son eventos agudos que se asocian a un aumento de la morbimortalidad de la enfermedad. Objetivo: presentar el caso clínico de un paciente con fenómeno de Lucio, a través del cual se llegó al diagnóstico de enfermedad de Hansen, y remarcar la importancia de tener presente esta enfermedad, poco frecuente en nuestro país, para su correcto diagnóstico. Discusión: el fenómeno de Lucio es un tipo de reacción leprosa mediada por inmunocomplejos. Se caracteriza clínicamente por máculas o placas eritematovioláceas, de aparición súbita, que evolucionan a úlceras necróticas y curan dejando cicatrices estrelladas atróficas. De no mediar tratamiento, puede ser fatal, debido a sobreinfección y sepsis. Este se basa en el tratamiento específico de la infección, asociado a prednisona y un correcto manejo de las heridas.
Summary: Introduction: Hansen disease is a chronic infectious disease caused by Mycobacterium leprae, which mainly affects the skin and peripheral nerves. Leprosy reactions are acute events associated to an increase in the morbimortality of the disease. Objective: the study aims to present the clinical case of patient with Lucio´s phenomenon, which allowed the diagnosis of Hansen disease, and to emphasize on the importance of having this disease in mind for an appropriate diagnosis, despite it being rather unusual in our country. Discussion: Lucio´s phenomenon is a kind of leprosy reaction mediated by immune complexes. Clinically, it is characterized by the sudden onset of macules or blue hemorrhagic plaques, with a rapid evolution to necrotic ulcers, and it heals leaving star-shaped atrophic scars. If it is not treated, it may be fatal due to superinfection and sepsis. Treatment is based on specific medication for the infection, associated to prednisone and the correct handling of injuries.
Resumo: Introdução: a hanseníase é uma doença infecciosa crônica causada pelo Mycobacterium leprae, que acomete principalmente pele e nervos periféricos. As reações hansênicas são eventos agudos que estão associados ao aumento da morbimortalidade da doença. Objetivo: apresentar o caso de um paciente com fenômeno de Lúcio, por meio do qual se chegou ao diagnóstico de hanseníase, e ressaltar a importância de se ter em mente esta doença, rara em nosso meio, para seu correto diagnóstico. Discussão: o fenômeno de Lúcio é um tipo de reação hansênica mediada por imunocomplexos. Caracteriza-se clinicamente por máculas ou placas eritêmato-violáceas de início súbito que evoluem para úlceras necróticas e cicatrizam, deixando cicatrizes estreladas atróficas. Sem tratamento pode ser fatal, devido a superinfecção e sepse; a terapia está baseada no tratamento específico da infecção, associado à prednisona e no manejo correto da ferida.
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Humanos , Masculino , Pessoa de Meia-Idade , Hanseníase Virchowiana/complicações , Hanseníase/complicaçõesRESUMO
El fenómeno de Lucio es un estado reaccional grave, poco frecuente, mediado por inmunocomplejos que se observa típicamente en los casos de lepra lepromatosa difusa. En Paraguay, corresponde aproximadamente al 2% de los casos de lepra diagnosticados en la mayoría de los casos, se presenta como debut de la enfermedad. Se manifiesta con lesiones en la piel de tipo máculas y placas purpúricas poligonales, generalmente sin compromiso visceral. El diagnóstico lo confirma el estudio histopatológico y es fundamental realizar el diagnóstico diferencial con vasculitis de otras etiologías.
Lucio's phenomenon is a rare and severe reactional state mediated by immune complexes that is commonly seen in cases of diffuse lepromatous leprosy. In Paraguay, it represents approximately 2% of leprosy diagnosed cases, mainly as a debut of the disease. It manifests with macule-type skin lesions and polygonal purpuric plaques, generally without visceral involvement. The diagnosis is confirmed by the histopathological study and it is essential to consider differential diagnosis such as vasculitis of other etiologies.
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Hanseníase , Hanseníase VirchowianaRESUMO
Mycobacterium leprae, the etiologic agent of leprosy, is an acid-fast-staining and slow-growing bacilli that infect macrophages and Schwann cells individually or through forming globi. The clinical presentation of leprosy is broad and depends on the host immune response. We report a case of a 42-year-old Brazilian man presenting with fever of unknown origin (FUO), anemia, wasting syndrome, and neuropathy. The diagnosis of lepromatous leprosy was made after an extensive investigation revealed the presence of M. leprae in the bone marrow. Bone marrow involvement in leprosy is rare and some authors believe the presence of M. leprae in the bone marrow can act as a reservoir of the disease facilitating future relapses. It is important to investigate bone marrow involvement in leprosy, especially when the patient presents with cytopenias and positive epidemiologic history.
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Febre de Causa Desconhecida , Hanseníase , Síndrome de Emaciação , Adulto , Medula Óssea , Caquexia , Humanos , Hanseníase/diagnóstico , Hanseníase/microbiologia , Masculino , Mycobacterium lepraeRESUMO
The causative agents of leprosy are Mycobacterium leprae and M. lepromatosis. Mycobacterium lepromatosis was found in 2008 to cause diffuse lepromatous leprosy in Mexican patients. This study aimed to identify M. leprae and M. lepromatosis in paraffin-embedded skin samples from Caribbean patients with leprosy. A total of six skin samples were obtained from the Dominican Republic. All cases presented the multibacillary form; five were nodular lepromatous leprosy, and one was borderline lepromatous leprosy. All patients received multidrug therapy. Molecular identification was achieved using the M. leprae-specific repetitive element for M. leprae and the hemN gene for M. lepromatosis. Mycobacterium leprae was identified in two lepromatous leprosy cases, and one borderline lepromatous leprosy case; M. lepromatosis was found in one nodular lepromatous leprosy case. Both Mycobacterium species were present in two nodular lepromatous leprosy cases. This is the first report of M. lepromatosis in the Dominican Republic.
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Hanseníase Virchowiana , Hanseníase , República Dominicana , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Mycobacterium , Mycobacterium leprae/genéticaRESUMO
BACKGROUND The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.
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BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Patients have distinct clinical forms, and the host´s immunological response regulate those manifestations. In this work, the presence of the myeloid-derived suppressor cell and the regulatory protein annexin A1 is described in patients with multibacillary leprosy and with type 1 and 2 reactions. METHODS: Patients were submitted to skin biopsy for histopathological analysis to obtain a bacilloscopic index. Immunofluorescence was used to detect myeloid-derived suppressor cells and annexin A1. RESULTS: The data demonstrated that the presence of granulocytic and monocytic myeloid-derived suppressor cells in leprosy patients. A high number of monocytic myeloid-derived suppressor cells were observed in lepromatous leprosy and type 2 reactional patients. The presence of annexin A1 was observed in all myeloid-derived suppressor cells. In particular, the monocytic myeloid-derived suppressor cell in the lepromatous patients has higher levels of this protein when compared to the reactional patients. This data suggest that the higher expression of this protein may be related to regulatory response against a severe infection, contributing to anergic response. In type 1 reactional patients, the expression of annexin A1 was reduced. CONCLUSIONS: Myeloid-derived suppressor cell are present in leprosy patients and annexin A1 might be regulated the host response against Mycobacterium leprae.
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Anexina A1 , Hanseníase Virchowiana , Hanseníase , Células Supressoras Mieloides , Anexina A1/genética , Humanos , Mycobacterium lepraeRESUMO
Resumen La lepra o enfermedad de Hansen es una de las clásicas enfermedades olvidadas que aún persiste en Perú. La infección es ocasionada por Mycobacterium leprae. La enfermedad varía en un amplio rango de manifestaciones desde la lepra tuberculoide (paucibacilar) hasta la lepromatosa (multibacilar). Se presenta el caso de un varón de 55 años, agricultor y extractor de madera, procedente de la Amazonia peruana, con lesiones cutáneas antiguas infiltrantes en la cara, cuello, tórax, abdomen y extremidades. La baciloscopia y estudio histológico de una biopsia de piel confirmaron la presencia de bacilos ácido-alcohol resistentes. Se concluyó, en forma tardía, que fue un caso de lepra lepromatosa nodular. Recibió terapia con rifampicina, dapsona y clofamizina por dos años con una lenta mejoría; no obstante, cursó con un eritema nodoso leproso (reacción tipo 2) con buena respuesta a corticoesteroides y talidomida.
Abstract Leprosy or Hansen's disease is one of the classic neglected diseases that still persists in Peru. The infection is caused by Mycobacterium leprae. The disease varies in a wide range of manifestations from tuberculoid (paucibacillary) to lepromatous (multibacillary) leprosy. We present the case of a 55-year-old man, farmer and wood extractor, from the Peruvian Amazon with old infiltrating cutaneous lesions on the face, neck, thorax, abdomen and extremities. The smear and biopsy examinations confirm the presence of acid-alcohol-resistant bacilli compatible with leprosy. It is concluded, with a long delay, it was a case of nodular lepromatous leprosy. He received therapy with rifampicin, dapsone and clofamizine for two years with slow progressive improvement; however, he presented an erythema nodosum leprosum (type 2 reaction) with response to corticosteroids and thalidomide.
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Humanos , Masculino , Pessoa de Meia-Idade , Hanseníase Virchowiana/diagnóstico , Eritema Nodoso/diagnóstico , Eritema Nodoso/patologia , Peru , Hanseníase Virchowiana/tratamento farmacológico , Eritema Nodoso/tratamento farmacológico , Diagnóstico Tardio , HanseníaseRESUMO
The enzyme IDO-1 is involved in the first stage of tryptophan catabolism and has been described in both microbicidal and tolerogenic microenvironments. Previous data from our group have shown that IDO-1 is differentially regulated in the distinctive clinical forms of leprosy. The present study aims to investigate the mechanisms associated with IDO-1 expression and activity in human monocyte-derived dendritic cells (mDCs) after stimulation with irradiated Mycobacterium leprae and its fractions. M. leprae and its fractions induced the expression and activity of IDO-1 in human mDCs. Among the stimuli studied, irradiated M. leprae and its membrane fraction (MLMA) induced the production of proinflammatory cytokines TNF and IL-6 whereas irradiated M. leprae and its cytosol fraction (MLSA) induced an increase in IL-10. We investigated if TLR2 activation was necessary for IDO-1 induction in mDCs. We observed that in cultures treated with a neutralizing anti-TLR2 antibody, there was a decrease in IDO-1 activity and expression induced by M. leprae and MLMA. The same effect was observed when we used a MyD88 inhibitor. Our data demonstrate that coculture of mDCs with autologous lymphocytes induced an increase in regulatory T (Treg) cell frequency in MLSA-stimulated cultures, showing that M. leprae constituents may play opposite roles that may possibly be related to the dubious effect of IDO-1 in the different clinical forms of disease. Our data show that M. leprae and its fractions are able to differentially modulate the activity and functionality of IDO-1 in mDCs by a pathway that involves TLR2, suggesting that this enzyme may play an important role in leprosy immunopathogenesis.
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Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Tolerância Imunológica , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Hanseníase/etiologia , Hanseníase/metabolismo , Mycobacterium leprae/imunologia , Receptor 2 Toll-Like/metabolismo , Biomarcadores , Citometria de Fluxo , Humanos , Hanseníase/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Leprosy is a spectral disease. Its two polar forms, tuberculoid (TT) and lepromatous (LL), are distinct presentations of the disease, both from a clinical and histopathological/bacilloscopic point of view. In this chapter, the histopathological characteristics that define the two polar forms (TT and LL), are presented, and their main differential diagnoses are discussed. These two forms also have significant differences in their treatment protocol. Histopathological recognition of both forms of the disease is important for choosing the correct treatment. Also, there are a large numbre of disease that can have a clinical presentation similar to the TT and LL forms of leprosy. In this context, histopathological examination is essential for defining the diagnosis of leprosy.
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Hanseníase Virchowiana/diagnóstico , Hanseníase Tuberculoide/diagnóstico , Hanseníase Virchowiana/patologia , Hanseníase Tuberculoide/patologia , Diagnóstico DiferencialRESUMO
Leprosy is an infectious disease that has a broad spectrum of clinical manifestations. Lepromatous leprosy has a deficient cellular immune response and high bacillary multiplication. It has epidemiological importance, as it is the most contagious clinical form of the disease. Its manifestation in children and adolescents is unusual. In the present study, we report two cases of leprosy at an early age, manifesting the lepromatous clinical form, highlighting the auricular involvement in one case. Early diagnosis is an essential tool to avoid deformities and deficiencies.
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Hanseníase Virchowiana/diagnóstico , Adolescente , Humanos , Imunidade Celular , Hanseníase Virchowiana/imunologia , MasculinoRESUMO
RESUMEN Introducción: la lepra es una enfermedad infectocontagiosa causada por el mycobacterium leprae, llamada también enfermedad de Hansen en honor a quien descubrió la bacteria en 1873, presenta varias formas clínicas y estados reaccionales que dependen de la inmunidad especifica del huésped. Presentación de caso: paciente masculino de 12 años con diagnóstico de lepra lepromatosa macular caracterizada por máculas hipocrómicas anestésicas y neuritis periférica bilateral y simétrica de los nervios: auricular mayor y cubital, la baciloscopia negativa y el resultado de la histología probablemente lepra. Discusión: en el campo de la Dermatopediatría la lepra sigue siendo una patología poco descrita y subvalorada en la consulta diaria, por ello se convierte en un desafío diagnóstico, debido a la diversidad de manifestaciones clínicas que se pueden presentar, es necesario un minucioso examen cutáneo-neural en todo niño, que presente lesiones cutáneas sugestivas y fuente infecciosa sospechosa. Conclusiones: la presencia de máculas hipocrómicas anestésicas y neuritis periférica bilateral y simétrica de los nervios: auricular mayor y cubital, la presencia antecedentes familiares con la enfermedad y histología probablemente lepra contribuyeron al diagnóstico de una lepra lepromatosa macular.
ABSTRACT Introduction: leprosy is an infectious disease caused by mycobacterium leprae, also called Hansen's disease in honor of the one who discovered the bacteria in 1873. It has several clinical forms and reaction states that depend on the specific immunity of the host. Case presentation: a 12-year-old male patient with a diagnosis of lepromatous macular leprosy, characterized by hypochromic anesthetic macules and bilateral symmetric peripheral neuritis of the nerves: major and ulnar auricular, negative smear and the result of probably leprosy histology. Discussion: in the field of Dermatopediatrics, leprosy is still a pathology that is little described and undervalued in the daily practice, therefore it becomes a diagnostic challenge, due to the diversity of clinical manifestations that may occur, a thorough skin examination is necessary -neural in every child, presenting suggestive skin lesions and suspicious infectious source. Conclusions: the presence of hypochromic anesthetic maculae and bilateral symmetric peripheral neuritis of the nerves: major and ulnar auricular, presence of family history with the disease and probably leprosy histology contributed to the diagnosis of lepromatous macular leprosy.
RESUMO Introdução: A hanseníase é uma doença infecciosa causada pelo Mycobacterium leprae, também chamada de doença de Hansen em honra de quem descobriu a bactéria em 1873, tem várias formas clínicas e estados reacionais que dependem de imunidade do hospedeiro específico. Relato de caso: Paciente do sexo masculino de 12 anos com diagnóstico de lepromatous macular caracterizada por máculas hipocrômicas e neurite periférica bilateral simétrica anestésico eo nervo: auricular e ulnar, o resultado esfregaço negativo e histologia provavelmente lepra. Discussão: No campo da Dermatopediatría lepra é ainda um pouco descrita e subestimado na prática patologia diária, portanto, torna-se um desafio diagnóstico por causa da diversidade de manifestações clínicas que podem ocorrer, um exame da pele completa é necessária -neural em todas as crianças, apresentando lesões cutâneas sugestivas e fonte infecciosa suspeita. Conclusões: A presença de máculas hipocrômicas e nervos neurites periféricas bilaterais e simétricas anestésicos: auricular ulnar e a história da família presença da doença e da lepra histologia provavelmente contribuiu para o diagnóstico de lepromatous macular.
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Se realizó un estudio observacional, descriptivo y transversal de 14 pacientes con lepra, diagnosticados y atendidos en la consulta de Dermatología del Hospital Nacional Guido Valadares, en Dili, Timor Oriental, de julio a diciembre del 2015, con vistas a caracterizarles y describir algunos aspectos clínicos y epidemiológicos de la enfermedad. En la serie se obtuvo una mayor frecuencia de pacientes en el grupo etario de 26 a 35 años y del sexo masculino, la forma clínica predominante fue la multibacilar y el tiempo de evolución de los síntomas hasta que fuera establecido el diagnóstico fue de menos de un año. Igualmente, en la mayoría existieron reacciones agudas, principalmente de tipo II o eritema nudoso leproso, y diferentes grados de discapacidad.
An observational, descriptive and cross-sectional study of 14 patients with leprosy, diagnosed and assisted in the Dermatology Service of Guido Valadares National Hospital, in Dili, Timor Lester was carried out from July to December, 2015, with the aim of characterizing them and to describe some clinical and epidemiological aspects of the disease. In the series a higher frequency of patient was obtained in the age group 26 to 35 years and of the male sex, the predominant clinical form was the multibacilar and the time of clinical course of the symptoms up to reaching the diagnosis was shorter than a year. Equally, in most of them acute reactions were presented, mainly of type II or from the erythema leprosy group, and different degrees of inability.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Hanseníase Dimorfa , Hanseníase Virchowiana , Hanseníase , Mycobacterium lepraemurium , Epidemiologia Descritiva , Estudos Transversais , Pessoas com Deficiência , Estudo ObservacionalRESUMO
RESUMEN En este estudio del caso, los autores discuten la presentación de un varón de 56 años, con lepra lepromatosa multibacilar, localizado en un hospital del distrito de Trujillo. La biopsia de una de las lesiones, demostró infiltraciones difusas por macrófagos espumosos en toda su extensión; con la tinción de Ziehl - Neelsen se encuentran: bacilos ácido-alcohol resistentes sueltos o empaquetados en grupos, con índice bacilar: 6. La condición se manejó inicialmente en la comunidad como un "pénfigo ampolloso", sugiriendo que las barreras locales actualmente impiden la detección de la lepra en este sistema de atención primaria, en desarrollo. La lepra es una enfermedad multisistémica y el paciente demostró alteraciones neurológicas periféricas evidentes. Promover el conocimiento de estas manifestaciones sistémicas, evitará un retraso en el diagnóstico, a su vez disminuirá las complicaciones y eludirá la morbilidad a largo plazo. Los esfuerzos para optimizar los sistemas de detección, gestión, educación pública y profesional son esenciales, para impulsar la erradicación en estas poblaciones en riesgo.
SUMMARY In this case study, the authors discuss the presentation of a 56-year-old male in a hospital in the Trujillo district with lepromatous multibacillary leprosy. The biopsy of one of the lesions showed diffuse infiltrations by foamy macrophages in all its extension, with the stain of Ziehl - Neelsen bacilli acid resistant alcohol loose or packaged in groups, the bacilar index: 6. The condition was initially managed in the community as a "bullous pemphigus" that suggests that local barriers currently prevent the detection of leprosy in this developing primary care system. Leprosy is a multisystem disease and the patient demonstrated evident peripheral neurological alterations. Promoting the knowledge of these systemic manifestations will avoid a delay in the diagnosis, in turn will reduce complications and avoid long-term morbidity. Efforts to optimize detection systems, management and public and professional education are essential to promote eradication in these populations at risk.
RESUMO
Leprosy is a chronic disease caused by Mycobacterium leprae that affects the skin and peripheral nerves. It may present as one of two distinct poles: the self-limiting tuberculoid leprosy and the highly infectious lepromatous leprosy (LL) characterized by M. leprae-specific absence of cellular immune response. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) enhance the bactericide activities of macrophages after interaction with its receptor, CD74. Importantly, MIF also possesses chemoattractant properties, and it is a key factor in situ for the activation of macrophages and in blood to promote leukocytes migration. MIF-mediated activation of macrophages is a key process for the elimination of pathogens such as Mycobacterium tuberculosis; however, its participation for the clearance of M. leprae is unclear. The aim of this study was to evaluate the serum levels of MIF as well as MIF and CD74 expression in skin lesions of LL and compare it with healthy skin (HSk) taken from subjects attending to dermatological consult. Samples of serum and skin biopsies were taken from 39 LL patients and compared with 36 serum samples of healthy subjects (HS) and 10 biopsies of HSk. Serum samples were analyzed by ELISA and skin biopsies by immunohistochemistry (IHC). IHC smears were observed in 12 100× microscopic fields, in which percentage of stained cells and staining intensity were evaluated. Both variables were used to calculate a semi-quantitative expression score that ranged from 0 to 3+. We found no differences in MIF levels between LL patients and HS in sera. In addition, MIF was observed in over 75% of cells with high intensity in the skin of patients and HSk. Although we found no differences in MIF expression between the groups, a CD74 score statistically higher was found in LL skin than HSk (p < 0.001); this was the result of a higher percentage of cells positive for CD74 (p < 0.001). As a conclusion, we found that CD74-positive cells are intensely recruited to the skin with LL lesions. In this manner, MIF signaling may be enhanced in the skin of LL patients due to increased expression of its receptor, but further studies are required.
Assuntos
Antígenos de Diferenciação de Linfócitos B/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Oxirredutases Intramoleculares/sangue , Hanseníase Virchowiana/imunologia , Fatores Inibidores da Migração de Macrófagos/sangue , Pele/imunologia , Adulto , Antígenos de Diferenciação de Linfócitos B/metabolismo , Biópsia , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imunidade Celular , Oxirredutases Intramoleculares/imunologia , Oxirredutases Intramoleculares/metabolismo , Hanseníase Virchowiana/sangue , Hanseníase Virchowiana/patologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/citologia , Pele/patologiaRESUMO
La lepra histioide de Wade, es una forma clínico-histopatológica especial de lepra multibacilar, caracterizada por la presencia de tubérculos (lesiones papulosas o nodulares) correspondientes a lepromas formados por histiocitos de morfología fusiforme. La misma es una variante infrecuente de lepra lepromatosa, que se desarrolla generalmente como recaída, en pacientes que recibieron monoterapia con dapsona, aunque se reportó su presentación de novo. En el presente trabajo, se comunica el caso clínico de una paciente de sexo femenino de 45 años de edad, con diagnóstico tardío de lepra histioide. Además, se examinan las características principales de esta forma particular de expresión de la lepra, sus diferencias con la forma clásica de presentación, los diagnósticos diferenciales que deben considerarse y la importancia de tener a esta patología entre las sospechas diagnósticas, para comenzar el tratamiento adecuado y evitar su propagación.
Wade's hystioid leprosy is a special clinical-pathological form of multibacillary leprosy, characterized by papular and nodular lepromas that consist of spindle histiocytes. It is a variant of lepromatous leprosy. Most of the cases have been related to dapsone resistance in the context of longterm monotherapy. De novo cases, not associated with previous anti-leprosy treatment, have been less frequently reported. This article presents the case of 45 years old female, with late diagnosis of histoid leprosy. There will be explained the main features of this particular form of leprosy, its differences with the classic presentation, the differential diagnoses to be considered, and the importance of having this pathology among diagnostic suspicions to begin adecuate treatment.