Cutaneous tuberculosis: epidemiological, clinical, diagnostic and therapeutic update

Abstract Tuberculosis is certainly one of the diseases considered to be ancient on planet Earth. The etiological agent of tuberculosis is Mycobacterium tuberculosis. This terrible bacterial infection still results in severe socioeconomic consequences to date, and its complete eradication represents a great challenge. It constitutes one of the most important public health problems in developing countries. According to the World Health Organization, this infection results in more than 4,000 deaths daily worldwide, with 10.4 million being affected annually and 1.5 million deaths from TB every year. With the emergence of the HIV/AIDS pandemic, the disease became the main cause of morbidity and mortality in patients infected with the human immunodeficiency virus. Cutaneous tuberculosis is a rare infection that represents 1% to 1.5% of extrapulmonary tuberculosis, whose etiological agents are Mycobacterium tuberculosis, Mycobacterium bovis, and the attenuated form of the bacillus Calmette-Guérin (BCG vaccine). Cutaneous tuberculosis can be exogenous; endogenous: caused by contiguity or autoinoculation and by hematogenous spread; induced by the Calmette-Guérin bacillus and manifest as a tuberculid. The diagnosis of the infection is carried out through the direct test, culture, histopathology, tuberculin skin test, polymerase chain reaction, interferon-gamma release assay, and genotyping. Drugs used comprise isoniazid, rifampicin, pyrazinamide and ethambutol.x

Cutaneous tuberculosis: epidemiological, clinical, diagnostic and therapeutic update.

Tuberculosis is certainly one of the diseases considered to be ancient on planet Earth. The etiological agent of tuberculosis is Mycobacterium tuberculosis. This terrible bacterial infection still results in severe socioeconomic consequences to date, and its complete eradication represents a great challenge. It constitutes one of the most important public health problems in developing countries. According to the World Health Organization, this infection results in more than 4,000 deaths daily worldwide, with 10.4 million being affected annually and 1.5 million deaths from TB every year. With the emergence of the HIV/AIDS pandemic, the disease became the main cause of morbidity and mortality in patients infected with the human immunodeficiency virus. Cutaneous tuberculosis is a rare infection that represents 1% to 1.5% of extrapulmonary tuberculosis, whose etiological agents are Mycobacterium tuberculosis, Mycobacterium bovis, and the attenuated form of the bacillus Calmette-Guérin (BCG vaccine). Cutaneous tuberculosis can be exogenous; endogenous: caused by contiguity or autoinoculation and by hematogenous spread; induced by the Calmette-Guérin bacillus and manifest as a tuberculid. The diagnosis of the infection is carried out through the direct test, culture, histopathology, tuberculin skin test, polymerase chain reaction, interferon-gamma release assay, and genotyping. Drugs used comprise isoniazid, rifampicin, pyrazinamide and ethambutol.

Use of the brief Confusion Assessment Method in a veteran palliative care population: A pilot validation study.

OBJECTIVE: Many patients with advanced serious illness or at the end of life experience delirium, a potentially reversible form of acute brain dysfunction, which may impair ability to participate in medical decision-making and to engage with their loved ones. Screening for delirium provides an opportunity to address modifiable causes. Unfortunately, delirium remains underrecognized. The main objective of this pilot was to validate the brief Confusion Assessment Method (bCAM), a two-minute delirium-screening tool, in a veteran palliative care sample. METHOD: This was a pilot prospective, observational study that included hospitalized patients evaluated by the palliative care service at a single Veterans' Administration Medical Center. The bCAM was compared against the reference standard, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Both assessments were blinded and conducted within 30 minutes of each other. RESULT: We enrolled 36 patients who were a median of 67 years (interquartile range 63-73). The primary reasons for admission to the hospital were sepsis or severe infection (33%), severe cardiac disease (including heart failure, cardiogenic shock, and myocardial infarction) (17%), or gastrointestinal/liver disease (17%). The bCAM performed well against the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, for detecting delirium, with a sensitivity (95% confidence interval) of 0.80 (0.4, 0.96) and specificity of 0.87 (0.67, 0.96). SIGNIFICANCE OF RESULTS: Delirium was present in 27% of patients enrolled and never recognized by the palliative care service in routine clinical care. The bCAM provided good sensitivity and specificity in a pilot of palliative care patients, providing a method for nonpsychiatrically trained personnel to detect delirium.

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.

Acral lichen sclerosus et atrophicus--case report.

Lichen sclerosus et atrophicus is a chronic disorder of the skin and mucosal surfaces, most commonly affecting the female genitalia. Few cases of lichen sclerosus et atrophicus confined to the feet and/or hands have been reported. We report a case of lichen sclerosus et atrophicus involving first the extremities and then the perigenital area.

Líquen escleroso e atrófico acral: relato de caso / Acral lichen sclerosus et atrophicus: case report

O líquen escleroso e atrófico é uma doença crônica da pele e mucosas, que, usualmente, afeta a área genital de mulheres. Poucos casos de líquen escleroso e atrófico, confinados nos pés e/ou mãos, têm sido relatados. Relatamos um caso de líquen escleroso e atrófico envolvendo as extremidades e,posteriormente, a área perigenital.

Lichen sclerosus et atrophicus is a chronic disorder of the skin and mucosal surfaces, most commonly affecting the female genitalia. Few cases of lichen sclerosus et atrophicus confined to the feet and/or hands have been reported. We report a case of lichen sclerosus et atrophicus involving first the extremities and then the perigenital area.

Hemangiomas extensos da infância tratados com propranolol: relato de dois caso / Propranolol for extensive hemangiomas of infancy: two case reports

Hemangiomas são os tumores benignos mais frequentes da infância, apresentando como história natural crescimento rápido, seguido de uma fase de regressão que culmina com o desaparecimento parcial ou total da lesão. Opções terapêuticas devem ser avaliadas para casos extensos. Os glicocorticoides sistêmicos são a terapia de escolha; contudo, há relatos de que o propranolol oferece resultados melhores e mais rápidos. Este trabalho descreve dois casos de hemangioma infantil de grande volume associados à limitação funcional e desfiguração estética com significativa resposta ao propranolol, droga esta que surge como uma proposta terapêutica oferecendo resultados satisfatórios e mantidos, com poucos efeitos colaterais.

Hemangiomas are the most common benign tumors of childhood. They show rapid growth, followed by a regression phase that culminates in the partial or total disappearance of the lesion. Therapeutic options should be evaluated for extensive cases. Systemic glucocorticoids are the therapy of choice; however, there are reports that propranolol offers better and faster results. We report two cases of large volume infantile hemangioma associated with functional limitation and aesthetic disfigurement, treated successfully with propranolol, a drug that comes as a therapeutic option providing satisfactory and maintained results, with few side effects.

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

Epidermólise bolhosa distrófica pruriginosa: relato de caso / Epidermolysis bullosa pruriginosa: case report

A epidermólise bolhosa distrófica pruriginosa é doença genética rara cujo padrão de herança ainda não está bem estabelecido na literatura. O defeito genético, que envolve a codificação do colágeno tipo VII, está localizado no braço curto do cromossomo 3, ocorrendo mutação no gene COL7A1. Apresenta-se o caso de um paciente do sexo masculino que referia prurido nas pernas há cerca de 15 anos, cujo diagnóstico foi firmado com base nos exames dermatológico e imuno-histopatológico. Devido à raridade dessa condição patológica, realiza-se breve revisão do tema.

Epidermolysis bullosa pruriginosa is a rare genetic disease that the pattern of inheritance still remains not established in the literature. The genetic defect, that disturbes the type VII collagen encoding, is located on the short arm of chromosome 3, with mutation in gene COL7A1. We report a male patient that was affected by itching on the legs for about 15 years, and the diagnostic was made based on clinicopathological features. Due to low frequency of this disease, we performed a brief review about this topic.

Linchen Aureus: relato de dois caso com apresentações distintas / Linchen Aureus: report of two cases showing different clinical features

Linchen aureus é uma variedade de púrpura pigmentar crônica caracterizada por pápulas e placas liquenóides, com tonalidades de cor que variam do amarelo-ouro ao marrom escuro e uma disposição em geral unilateral nos membros inferiores. São apresentados dois casos da doença exibindo aspectos histopatológicos considerados clássicos, porém divergentes na forma de expressão clínica, com destaque para uma rara disposição segmentar-zosteriforme observado em um deles

Liquen plano penfigóide: relato de caso / Lichen planus pemphigoides: case report

O termo liquen plano penfigóide reporta-se a uma condição morbida que associa eflorescências típicas de liquen plano com lesões vesicobolhosas, estas surgindo tanto em áreas liquenóides como sobre pele aparentemente sã. Considerando semelhanças existentes entre o componente vesicobolhoso da doença e o penfigóide bolhoso, ambos apresentando bolhas subepidérmicas, fluorescência linear na zona de membrana basal e autoanticorpos dirigidos contra um antígeno de 180 kD, alguns autores especulam ser o liquen plano penfigóide uma superposição de liquen plano com penfigóide bolhoso. Apresenta-se um caso observado em paciente adulto, do sexo masculino, cujas manifestações cutâneas, aspectos histopatológicos e de imunofluorêscia direta, além de uma resposta rápida e completa à corticoterapia sistêmica foram considerados critérios suficientes para o diagnóstico

Micose de Lobo simulando forma gomosa: um caso raro / Lobomycosis simulating gummatous form: a rare case

Apresenta-se um caso extremamente raro da micose de Jorge Lobo em que as lesöes nodulares evoluíam com as características das gomas, sem a compatibilidade histopatológica com esse quadro. As lesöes se dispunham ao longo da rede linfática do braço direito, simulando esporotricose. Um dos autores (DS), aliás já havia descrito essa forma nodular gomosa típica, porém em tais casos, o resultado histopatológico confirmou a estrutura das gomas, com necrose e riqueza de parasitos no interior de macrófagos. No presente caso, a estrutura encontrada era bem diferente, sem necrose