Macrophage immunophenotypes in Jorge Lobo's disease and lepromatous leprosy- A comparative study.

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.

Bioinformatic approach for repurposing immunomodulatory drugs for lepromatous leprosy.

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.

Evidencing leprosy neuronal inflammation by 18-Fluoro-deoxy-glucose.

BACKGROUND: Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations. METHODS: Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six. RESULTS: Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves. CONCLUSIONS: 18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.

Case Report: Lepromatous Leprosy Masquerading as Acute Suppurative Lymphadenitis.

Leprosy is a chronic cutaneous infection. It is usually characterized by thickened nerves and maculo-anesthetic patches. Leprosy often has an unusual presentation, which is a diagnostic challenge. In this case report, we present a case of an elderly male who presented with fever and chronic pus-draining axillary, cervical, and inguinal lymph nodes. He also had a weak left foot for the previous 5 months. During his hospital stay, he developed additional papular lesions over his extremities. We performed fine needle aspiration from the lymph nodes and skin biopsy, which were suggestive of lepromatous leprosy. We initiated him on antileprosy medication. On follow-up, he was responsive to therapy. Although skin and nerve involvement in leprosy is common, this case had an atypical presentation of discharging lymph nodes.

Boletim epidemiológico: frequência de contatos não examinados de casos novos de hanseníase virchowiana e dimorfa com baciloscopia positiva - Goiás, 2017 a 2021 / Epidemiological bulletin: frequency of unexamined contacts of new cases of Virchowian and borderline leprosy with positive bacilloscopy - Goiás, 2017 to 2021

A hanseníase é uma doença infecciosa crônica, causada pelo Mycobacterium leprae, um bacilo com tropismo pela pele e pelos nervos periféricos, com potencial de provocar deformidades físicas e incapacidades. O período de incubação da doença é longo, de 2 a 7 anos, podendo chegar a 20 anos ou mais. Este estudo consiste em uma análise retrospectiva, quantitativa, descritiva, das fichas de notificação do Sistema de Informação de Agravos de Notificação - SINAN dos pacientes com diagnóstico de hanseníase (CID A30), nos anos de 2017 a 2021 e os Boletins de acompanhamento das referidas fichas

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a bacillus with tropism for the skin and peripheral nerves, with the potential to cause physical deformities and disabilities. The incubation period of the disease is long, from 2 to 7 years, and can reach 20 years or more. This study consists of a retrospective, quantitative, descriptive analysis of the notification of the Notifiable Diseases Information System - SINAN of patients diagnosed with leprosy (ICD A30), in the years 2017 to 2021 and the follow-up Bulletins of the referred forms

Ancient DNA confirmation of lepromatous leprosy in a skeleton with concurrent osteosarcoma, excavated from the leprosarium of St. Mary Magdalen in Winchester, Hants., UK.

To establish a biological profile and disease aetiologies for one of four burials recovered during a Time Team dig at the St. Mary Magdalen leprosarium, Winchester, UK in AD 2000. Osteological techniques were applied to estimate age at death, biological sex, stature and pathology. Visual assessment of the material was supplemented by radiographic examination. Evidence for leprosy DNA was sought using ancient DNA (aDNA) analysis. The remains are those of a male individual excavated from a west-east aligned grave. The skeleton shows signs of two pathologies. Remodelling of the rhino-maxillary area and degenerative changes to small bones of the feet and reactive bone on the distal lower limbs suggest a multibacillary form of leprosy, whereas the right tibia and fibula show the presence of a primary neoplasm identified as an osteosarcoma. The aDNA study confirmed presence of Mycobacterium leprae in several skeletal elements, and the strain was genotyped to the 3I lineage, one of two main SNP types present in mediaeval Britain and ancestral to extant strains in America. This is a rare documentation of leprosy in association with a primary neoplasm.

Fenómeno de Lucio como forma de presentación de enfermedad de Hansen / Lucio's phenomenon as a presentation of Hansen disease / Fenômeno de Lucio como forma de apresentação da hanseníase

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.

Fenómeno de Lucio. A propósito de un caso / Lucio´s phenomenon. About a case

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.

Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function.

BACKGROUND: The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions. METHODS: A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells. RESULTS: 30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells. CONCLUSION: The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25+ depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25+ cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.

Challenges related to the cases of lepromatous leprosy: a report of two cases.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae with various clinical symptoms. Even though the incidence of leprosy has diminished in Saudi Arabia, it still has not been eliminated. We present two cases of leprosy from India residing in Saudi Arabia that were successfully managed with multidrug therapy. The first patient was a 33-year-old man with a history of enlarging erythematous patch and nose deformity on his face and upper and lower extremities started two years ago. The second patient was a 25-year-old man who presented with multiple hyperpigmented plaques on the upper and lower extremities in the last two years. The patient was firstly misdiagnosed and treated as tinea corporis without improvement. In both patients, the histological study from cutaneous lesions confirmed lepromatous leprosy. This report aimed to introduce the manifestations of leprosy, emphasizing the nose's involvement in the first case and the misdiagnosis of leprosy in the second case.

Different cell death mechanisms are involved in leprosy pathogenesis.

Leprosy is a chronic granulomatous disease that remains a serious public health problem in developing countries. According to the Madrid classification, leprosy presents in four clinical forms: two immunologically unstable forms (indeterminate and borderline) and two stable polar forms (tuberculoid and lepromatous). In leprosy, the relationship of cell death to clinical disease outcome remains unclear. Therefore, we investigated the extent of autophagy and different cell death mechanisms-such as apoptosis, necroptosis, and pyroptosis-in cutaneous lesions of patients with leprosy, as well as the role of these mechanisms in clinical disease progression. This cross-sectional analytical study included 30 patients with a confirmed diagnosis of leprosy, with 10 patients in each of the following groups: lepromatous (LL), tuberculoid (TT), and indeterminate (II) leprosy groups. For histopathological analysis, skin samples were subjected to haematoxylin-eosin staining and immunostaining for apoptotic and necroptotic markers. The results indicated that FasL expression was much higher in the LL form than in the TT and II forms. Similar results (higher expression in the LL form than in the TT and II forms) were observed for caspase 8, RIP1, and RIP3 expressions. MLKL, BAX, and caspase 3 expression levels were highest in the LL form, especially in globular foamy macrophages. Beclin-1 expression was highest in the TT form but was low in LL and II forms. Caspase 1 expression was highest in the LL form, followed by that in the TT and II forms. In conclusion, our study elucidates the role of different cell death mechanisms in the pathophysiology of various forms of leprosy and suggests measures that may be used to control the host response to infection and disease progression.

Lepromatous leprosy with dermatofibroma features: colonization or morphological variant of histoid leprosy with epidermal induction?

BACKGROUND: Leprosy is one of the main health problems in developing countries. It can show many different clinical presentations. CASE REPORT: A 37-yr-old woman with multiple reddish-brown papules on the lower and upper limbs, including the palms. The initial clinical impression was pityriasis lichenoides chronica. Biopsies were taken. The specimen from the left shin showed classical histological features of lepromatous leprosy. The specimen from the left thigh was similar to lipidized dermatofibroma showing epidermal hyperplasia with basal layer hyperpigmentation, a narrow Grenz zone, and spindle xanthomatous cells among dermal fibers. Fite-Faraco staining revealed many bacilli. DISCUSSION: No matter the clinical presentation, in the presence of lipidized macrophages, Fite-Faraco staining (an inexpensive method available worldwide) should be performed to rule out leprosy, even in nonendemic areas or associated with a tumor.

Chronic recalcitrant erythema nodosum leprosum: therapeutic dilemma and role of mycobacterium indicus pranii vaccine

Abstract Erythema nodosum leprosum is a severe immune reaction that complicates the usual course of multibacillary leprosy. There is increased activation of T-cells in erythema nodosum leprosum. Treatment modalities available to date for the management are systemic steroids, thalidomide, methotrexate, cyclophosphamide, azathioprine, minocycline, and apremilast but none of them is promising and safe. Mycobacterium indicus pranii is an atypical mycobacterium possessing strong immunomodulatory properties. The vaccine for this mycobacterium has been shown to have both immunotherapeutic and immunoprophylactic effects in multibacillary leprosy patients. We report a case of chronic recalcitrant erythema nodosum Leprosum which responded to Mycobacterium indicus pranii vaccine without any adverse effects, thereby suggesting its role as a novel therapeutic option in this reaction.

Erythema nodosum leprosum (type 2 reaction) in a patient with neurofibromatosis type 1.

Being a region endemic for leprosy, clinical practitioners in India often encounter myriad manifestations and diverse complications of the disease. However, the masking of the obvious clinical presentations due to the coexistence of a closely resembling unrelated disorder, a 'mimicker', would indeed pose a serious diagnostic predicament unless a high degree of clinical suspicion is maintained. Leprosy, also known as Hansen's disease is a chronic infectious disease caused by Mycobacterium leprae complex that involves the skin and peripheral nerves. Neurofibromatosis type 1 (NF1) also known as von Recklinghausen's disease is an autosomal dominant genetic disorder that presents with skin changes and benign peripheral nerve sheath tumours called neurofibromas. Here, we present the case of a 35-year-old man with NF1 who presented with type 2 lepra reaction (erythema nodosum leprosum, ENL) and the skin biopsy unmasked ENL nodule among the group of NF1 nodules.

Histoid leprosy presenting as a large tumor

Abstract Histoid leprosy is a rare form of multibacillary leprosy, characterized by the presence of papules, plaques, or nodules whose appearance is keloid-like, skin colored, or erythematous. Fusiform cells are the main histopathological feature. Due to the fact that it can simulate other dermatological lesions, for example, dermatofibroma and neurofibroma, it constitutes a diagnostic challenge for clinicians and pathologists. It is a bacilliferous form of leprosy, and it plays an important role in disease transmission. A case of a patient with histoid leprosy living in the Northeast Region of Brazil is reported.

Eritema nodoso hansênico com apresentação vesiculosa simulando infecção herpética: um relato de caso / Erythema nodosum leprosum with vesicular presentation simulating herpetic infection: a case report

Contexto: As reações hansênicas são episódios inflamatórios agudos imunomediados que podem ocorrer em indivíduos com hanseníase. Lesões atípicas de eritema nodoso hansênico (ENH) são raras e podem se apresentar como pústulas, bolhas, necrose, úlceras e, eventualmente, podem simular outras doenças como a síndrome de Sweet e eritema multiforme. Descrição do caso: Paciente do sexo masculino, 24 anos de idade, com diagnóstico prévio de hanseníase virchowiana e realização de tratamento adequado, com término da poliquimioterapia quatro anos antes de comparecer ao nosso serviço quando foi avaliado, apresentando pequenas vesículas translúcidas agrupadas sobre uma base eritematosa e áreas com crostas necróticas, simulando lesões herpéticas, na porção superior das costas, parte inferior do pescoço e haste do pênis. O exame histopatológico da biópsia cutânea foi sugestivo de reação tipo 2 e o tratamento com talidomida foi satisfatório. Discussão: As reações na hanseníase representam episódios de hipersensibilidade aguda a antígenos de Mycobacterium leprae e podem se desenvolver antes, durante ou após o término do tratamento. Acredita-se que o ENH, ou reações do tipo 2, ocorram devido à deposição de imunocomplexos em múltiplos órgãos em pacientes que apresentam a forma multibacilar. Conclusões: As reações hansênicas são desafios no manejo da hanseníase, especialmente pelo fato de a maioria das sequelas permanentes ser secundária a esses episódios inflamatórios agudos. O conhecimento das possíveis apresentações atípicas das reações hansênicas é fundamental para o diagnóstico precoce e o tratamento adequado, a fim de prevenir morbidade grave relacionada à hanseníase.