The cytotoxic T cells may contribute to the in situ immune response in Jorge Lobo's Disease human lesions.

Jorge Lobo's Disease (JLD) is a cutaneous chronic granulomatous disease caused by the pathogenic fungus Lacazia loboi. It is characterized by a granulomatous reaction with multinucleated giant cells and high number of fungal cells. In order to contribute to the comprehension of immune mechanisms in JLD human lesions, we studied the cytotoxic immune response, focusing on TCD8+ and NK cells, and granzyme B. Forty skin biopsies of lower limbs were selected and an immunohistochemistry protocol was developed to detect CD8+ T cells, NK cells and Granzyme B. In order to compare the cellular populations, we also performed a protocol to visualize TCD4+ cells. Immunolabeled cells were quantified in nine randomized fields in the dermis. Lesions were characterized by inflammatory infiltrate of macrophages, lymphocytes, epithelioid and multinucleated giant cells with intense number of fungal forms. There was a prevalence of CD8 over CD4 cells, followed by NK cells. Our results suggest that in JLD the cytotoxic immune response could represent another important mechanism to control Lacazia loboi infection. We may suggest that, although CD4+ T cells are essential for host defense in JLD, CD8+ T cells could play a role in the elimination of the fungus.

Th17 and regulatory T cells contribute to the in situ immune response in skin lesions of Jorge Lobo's disease.

Jorge Lobo's disease (JLD) is a chronic granulomatous mycosis described in various Latin American countries. The main objective of the present study was to investigate the possible role of Th17 and Foxp3+ Treg cells in the pathogenesis of Jorge Lobo's disease. Human skin biopsies were submitted to an immunohistochemistry protocol to detect Foxp3, interleukin (IL)-1beta, CD25, IL-6, IL-17, and IL-23. The epidermis presented acanthosis, hyperkeratosis, and frequent presence of fungi. The dermis presented inflammatory infiltrate comprising macrophages, lymphocytes, epithelioid and multinucleated cells, and an intense number of fungi. Foxp3+ Treg cells and IL-17+ cells were visualized in lymphocytes in the inflammatory infiltrate. IL-1, IL-2R (CD25), IL-6, and IL-23 were visualized in the dermis, intermingled with fungal cells, permeating or participating of the granuloma. Following IL-17, the most prominent cytokine was IL-6. IL-23 and cells expressing CD25 were present in fewer number. The comparative analysis between IL-17 and Foxp3 demonstrated a statistically significant increased number of IL-17+ cells. Th17 cells play a role in the immune response of JLD. IL-1beta and IL-6 added to the previously described increased number of TGF-beta would stimulate such pattern of response. Th17 cells could be present as an effort to modulate the local immune response; however, high levels of a Th17 profile could overcome the role of Treg cells. The unbalance between Treg/Th17 cells seems to corroborate with the less effective immune response against the fungus.

Jorge Lobo's disease: immunohistochemical characterization of dendritic cells in cutaneous lesions.

BACKGROUND: Jorge Lobo's disease (JLD) is a cutaneous chronic mycosis caused by Lacazia loboi. We studied Factor XIIIa + dermal dendrocytes (FXIIIa + DD), Langerhans cells (LC) through the expression of langerin and the expression of S100 protein. METHODS: A total of 41 biopsies and 10 normal skins (control) were developed with a polymer-based immunohistochemical method. RESULTS: Lesions presented infiltrate comprising macrophages, some asteroid corpuscles, lymphocytes, multinucleated giant cells and a large number of fungi. LCs presented short dendrites and were scarcely distributed. Dermal langerin + cells were detected in nine JLD lesions. FXIIIa + DD were hypertrophic, visualized in the inflammatory infiltrate of JLD lesions. Cells S100+ were present in JLD and control group with a similar number of cells. A total of 14 specimens did not express FXIIIa, and this considerable number probably contributed to the statistical similarity with the control group. CONCLUSIONS: The results indicate that LCs are present in the immune response against Lacazia loboi. Some dermal langerin + cells could be another subset of dendritic cells. Our data indicate changes of LCs in JLD cutaneous lesions and present, for the first time, results that show langerin + cells in the dermis and corroborate previous observations on the participation of FXIIIa + DD in the in situ immune response in JLD.

Plasmacytoid dendritic cells in cutaneous lesions of patients with chromoblastomycosis, lacaziosis, and paracoccidioidomycosis: a comparative analysis.

Plasmacytoid dendritic cells (pDCs) are characterized by expression of CD123 and BDCA-2 (Blood Dendritic Cell Antigen 2) (CD303) molecules, which are important in innate and adaptive immunity. Chromoblastomycosis (CBM), lacaziosis or Jorge Lobo's disease (JLD), and paracoccidioidomycosis (PCM), are noteworthy in Latin America due to the large number of reported cases. The severity of lesions is mainly determined by the host's immune status and in situ responses. The dendritic cells studied in these fungal diseases are of myeloid origin, such as Langerhans cells and dermal dendrocytes; to our knowledge, there are no data for pDCs. Forty-three biopsies from patients with CBM, 42 from those with JLD and 46 diagnosed with PCM, were evaluated by immunohistochemistry. Plasmacytoid cells immunostained with anti-CD123 and anti-CD303 were detected in 16 cases of CBM; in those stained with anti-CD123, 24 specimens were obtained from PCM. We did not detect the presence of pDCs in any specimen using either antibody in JLD. We believe that, albeit a secondary immune response in PCM and CBM, pDCs could act as a secondary source of important cytokines. The BDCA-2 (CD303) is a c-type lectin receptor involved in cell adhesion, capture, and processing of antigens. Through the expression of the c-lectin receptor, there could be an interaction with fungi, similar to other receptors of this type, namely, CD207 in PCM and CD205 and CD209 in other fungal infections. In JLD, the absence of expression of CD123 and CD303 seems to indicate that pDCs are not involved in the immune response.

Jorge Lobo's disease with restricted labial presentation.

Jorge Lobo's Disease (JLD) is a chronic granulomatous cutaneous mycosis caused by Lacazia loboi. The most typical lesions are keloid-like growths preferentially located on limbs and ears. To the best of the authors' knowledge, only one labial case has previously been reported. We describe the case of a man who presented with a left-sided papulonodular lesion of 10 years' duration on the vermillion border of the upper lip. A successful surgical resection of the lesion was performed and there was no recurrence in eight years of follow-up.

Doença de Jorge Lobo de localização labial exclusiva / Jorge Lobo's disease with restricted labial presentation

Doença de Jorge Lobo (DJL) é infecção granulomatosa cutânea crônica produzida pelo fungo Lacazia loboi, cujas lesões mais típicas têm aspecto queloidiano, com localizações preferenciais em membros e orelhas. As lesões restringem-se à pele, havendo apenas uma referência, do conhecimento dos autores, à localização em semimucosa labial. Apresenta-se caso de doença de Jorge Lobo em paciente masculino, com lesão papulonodular no vermelhão do lábio superior, à esquerda, de dez anos de evolução, exitosamente submetida a tratamento cirúrgico, sem recidiva após oito anos.

Jorge Lobo's Disease (JLD) is a chronic granulomatous cutaneous mycosis caused by Lacazia loboi. The most typical lesions are keloid-like growths preferentially located on limbs and ears. To the best of the authors' knowledge, only one labial case has previously been reported. We describe the case of a man who presented with a left-sided papulonodular lesion of 10 years' duration on the vermillion border of the upper lip. A successful surgical resection of the lesion was performed and there was no recurrence in eight years of follow-up.

Coinfecção hanseníase-leishmaniose / Confection leprosy-leishmaniasis

Relatar dificuldades diagnósticas face à ocorrência simultânea, num mesmo paciente,de duas enfermidades infecciosas com aspectos clínicos semelhantes. Relato de caso: homemde 21 anos, há nove meses apresentando placas eritematovioláceas infiltradas na face, dorso e pédireito. A histopatologia de uma lesão do dorso evidenciou quadro de dermatite granulomatosa,com pesquisa de bacilos álcool-ácido resistentes negativa à coloração de Fite-Faraco. Umdiagnóstico de hanseníase dimorfo-tuberculoide foi realizado e o paciente submetido àpoliquimioterapia multibacilar. As lesões do pé direito evoluíram com ulceração e pesquisadireta positiva para formas amastigotas de Leishmania spp; entretanto, um exame imunohistoquímicodo material emblocado da biópsia anterior, do dorso, mostrou resultado negativocom anticorpo antileishmania, Considerações finais: A conclusão diagnóstica de coinfecçãohanseníase-leishmaniose tegumentar para o caso apresentado, somente foi possível graças àcorrelação clínico-patológica e realização de provas histoquímicas e imuno-histoquímicas.

To report diagnostic difficulties that may arise when a simultaneous occurrence oftwo infectious diseases presenting similar clinical features takes place in a single patient. Casereport: a 21-year-old male presented with violaceous, infiltrated plaques on his face, dorsumand right foot. A granulomatous dermatitis was diagnosed histologically in a biopsy taken fromthe dorsum, with no demonstrable acid-fast organisms on Fite-Faraco stain. A diagnosis ofbordeline-tuberculoid leprosy was concluded, and the patient was given multibacillarypolychemotherapy. The lesions on the right foot became ulcerated, and positive smears forLeishmania spp amastigotes were obtained. However, immunohistochemistry failed todemonstrate leishmania antigens in recuts of the paraffin-embedded material from the originaldorsal biopsy. Final considerations: the diagnosis of leprosy-leishmaniasis coinfection to thiscase has been possible only after clinical-pathological correlation as well as histochemical andimmunohistochemical procedures were carried out