Bacterial load in the nose and its correlation to the immune response in leprosy patients.

INTRODUCTION: Leprosy, whose etiologic agent is M. leprae, has its clinical manifestations correlated with distinct immunologic forms. The mechanism of infectivity and dissemination of the disease are not completely known, although the nasal mucosa is supposed to have an important role in pathogenesis. OBJECTIVE: To correlate the clinical and bacteriological parameters with that of nasal biopsy and immunological tests, such as lepromin and ML-Flow results, in untreated leprosy patients. MATERIAL AND METHOD: Two hundred and twenty-two patients were evaluated, clinically classified and subjected to skin smear, nasal biopsy, ML-Flow, and Mitsuda test. RESULTS: 689% of the cases were borderline cases. Nasal biopsy revealed 91.4% positivity in those who had specific antibodies against M. leprae on blood sample. Lepromatous leprosy cases were 100% positive on ML-flow test, had a large involvement in the nasal mucosa (91%), positive skin smears (100%) and negative Mitsuda test. Nasal bacillary index showed a good correlation with ML-Flow and had similar results when compared to skin smear. The tests agreement was good, revealing that nasal biopsy can be reliable in the diagnosis of multibacillary clinical forms and in the evaluation of the immunological status of leprosy patients. CONCLUSION: The presence of disseminated bacilli in the nasal mucosa was similar to skin involvement, when correlated with Mitsuda test and ML-Flow. As a result, the role of nasal bacillary index may play an important role in the clinical and immunologic characterization of leprosy patients.

Congenital granular cell lesion: clinical, microscopic and immunohistochemical aspects in a case of multiple lesions.

Congenital granular cell lesion of the newborn, also known as congenital epulis, is a rare benign oral cavity tumor presenting at birth. Usually, it appears as a solitary mass arising in the mouth and originates from the anterior alveolar ridge. The objective of the present article is to report a case of congenital granular cell lesion in an 8-day-old female newborn. The patient presented four intraoral pedunculated lesions. Diagnosis, treatment, microscopic and immunohistochemical characteristics are also discussed.

Infectious diseases in paediatric pathology: experience from a developing country.

Infectious and parasitic diseases have always challenged man. Although many of them are typically seen in some areas of the world and can be adequately managed by just improving socioeconomic status and sanitary conditions, they are still quite prevalent and may sometimes be seen outside their original geographical areas. Human migration due to different reasons, tourism, blood transfusion and solid organ transplantation has created new concerns for health professionals all over the world. If not for diagnostic purposes, at least these tropical and infectious diseases should be largely known because their epidemiology, pathogenesis, host/parasite interaction, inflammatory and reparative responses are quite interesting and teach us about human biology. Curiosity is inherent to pathology practice and so we are compelled to look for things other than tumours or degenerative diseases. This review focuses on infectious and parasitic diseases found in a developing country and brings up-to-date information on diseases caused by viruses (dengue, yellow fever), bacteria (typhoid fever, leprosy), parasites (Chagas' disease, cutaneous and visceral leishmaniasis, amoebiasis, Capillaria hepatica, schistosomiasis, cysticercosis) and caused by fungi (paracoccidioidomycosis, cryptococcosis, histoplasmosis) that may be useful for pathologists when facing somewhat strange cases from developing countries.

Localized cutaneous leishmaniasis of the plantar region: a 40-year outcome.

We report the case of a 78-year-old male Brazilian farmer, who presented with an extensive ulcer on the right foot that had an erythematous and raised border. This ulcer involved most of the right plantar region and had persisted for more than 40 years. Satellite erythematous papules and tumor-like growths were also seen on the right ankle. Extracutaneous involvement was not found. Light microscopy showed epithelial hyperplasia and diffuse histiocyte infiltration with intense plasmocytosis. Cultures for fungi and Leishmania were negative. The polymerase chain reaction with specific primers for Leishmania was performed using DNA extracted from the lesions; it showed an amplification of 120 pB. The patient had an excellent response after two 20-day cycles of intra-venous N-methylglucamine antimonate (15 mg/Kg/day). Leishmaniasis should be highly considered in the differential diagnosis of chronic ulcers in endemic areas.

Emergency in leprosy: involvement of the larynx.

We present eight patients with larynx involvement in leprosy. Seven were classified as lepromatous and one was borderline leprosy in reversal reaction. One patient required an emergency tracheostomy and one had an almost complete uppe airway obstruction.

Exuberant verrucous carcinoma arising from a burn scar.

Verrucous carcinoma (VC) is an unusual, well-differentiated, and low-grade type of squamous cell carcinoma, characterized by slow growth, low metastatic spread, local invasion, and little dysplasia. It occurs predominantly on the genitals, in the oropharynx, or in the palmoplantar region, being less frequent at other sites; however, it can occur on any part of the body. Many factors have been associated with its pathogenesis, including the presence of previous skin lesions, such as varicose, decubitus, traumatic, or neuropathic plantar ulcers. VC arising from a burn scar is rare. We report the case of a patient who developed exuberant VC on his knee many years after having burn injuries at that site.

Diagnosis of mycosis fungoides: a comparative immunohistochemical study of T-cell markers using a novel anti-CD7 antibody.

Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma. In its early stage it may mimic benign dermatoses both on a clinical and histologic basis. MF usually expresses CD3 and CD4 (T-cell) markers. CD7 is expressed on about 90% of CD4 T cells and is often deficient on malignant T cells. Thus, CD7 may be useful in evaluating the nature of dermal lymphoid infiltrates. The aim of this study was to evaluate the usefulness of immunohistochemical detection of T-cell markers on paraffin-embedded sections, CD3 and CD7 (clone CBC.37), in the differential diagnosis of MF and benign dermatoses. Forty-two patients with diffuse dermal T-lymphocytic infiltrates were selected. Previous clinicopathologic correlation and follow-up had established the diagnosis of MF in 31 patients and benign dermatoses in 11. The mean value of stained cells in MF was 86.45% for CD3 and 53.09% for CD7 (P<0.001); in benign dermatoses it was 79.09% for CD3 and 73.63% for CD7 (P=0.669). CD7 immunolabeling was significantly lower in the MF group (P=0.048). A semiquantitative evaluation revealed a considerable loss of CD7 immunolabeling in comparison with CD3 in patients with MF. The authors conclude that CD7 study may represent a valuable tool in the distinction between inflammation and neoplasia in T-lymphoproliferative skin disorders.

Detection of Mycobacterium leprae in nasal mucosa biopsies by the polymerase chain reaction.

Several discoveries about leprosy indicate that Mycobacterium leprae transmission mainly occurs by inhalation, and the nose is major port of entry and exit. The present study evaluated the clinical application of PCR for detection of M. leprae DNA in nasal mucosa biopsies in untreated leprosy patients (52) and their contacts (99) from the State Reference Center in Sanitary Dermatology and Leprosy, Uberlandia, MG, Brazil. PCR detection of a 372-base pair DNA fragment from M. leprae was accomplished in 36 (69.2%) patients, from which 34 (91.9%) of them were multibacillaries. Furthermore, PCR was positive in 3 (16.7%) of 18 slit-skin smear negative, 4 (25.0%) of 16 skin lesion BI negative, 8 (33.3%) of 24 nasal mucosa BI negative patients, and 10 of 99 contacts (10.1%). The presence of bacilli in 10.1% of the contacts may potentially reflect an occult leprosy, and these patients must be accompanied, followed by a chemoprophylaxy treatment. Considering all PCR results against clinical and BI classification of patients and controls, we have found a sensitivity of 69.2%, a specificity of 89.9%, and an accuracy of 82.8%. It has been demonstrated here through PCR of nasal biopsies that the bacillus invades the mucosa, passing through the nasal inferior turbinate to reach peripheral blood. Therefore, the molecular investigation of invasive nasal biopsies by PCR tests has proven to be useful in defining patients of higher risk of transmission and risk-group contacts, which is an important step to reach the World Health Organization objective towards the elimination of leprosy as a public health problem.

Larva migrans in the oral mucosa: report of two cases.

Cutaneous Larva migrans is a very common disease in tropical regions. In the oral mucosa, the infection occurs in the same way as in the skin, but it is rarer. This report describes two cases of Larva migrans in the oral mucosa. The first case was in a 27-year-old woman who presented an erythematous plaque located on the buccal mucosa, extending to a posterior direction, following a linear pattern, to other areas of the mouth. After incisional biopsy of the anterior-most portion of the lesion, morphological details obtained in multiple examined sections suggested Necator or Ancylostoma braziliense larvae as the cause of infection. The second case was in a 35-year-old male who presented a fusiform erythematous plaque in the palatal mucosa. This area was removed and submitted to microscopic examination under a presumptive diagnosis of "parasite migratory stomatitis". The histological characteristics were suggestive of a larva pathway. In both cases the lesion disappeared after biopsy and the patients were symptom-free.

Granulomatous reactivation during the course of a leprosy infection: reaction or relapse.

BACKGROUND: Leprosy is a chronic granulomatous infectious disease and is still endemic in many parts of the world. It causes disabilities which are the consequence of nerve damage. This damage is in most cases the result of immunological reactions. OBJECTIVES: To investigate the differences between a type 1 leprosy (reversal) reaction and relapse on using histopathology. METHODS: The histopathological changes in 167 biopsies from 66 leprosy patients were studied. The patients were selected when their sequential biopsies demonstrated either different patterns or maintained the same pattern of granulomatous reaction over more than two years during or after the treatment of leprosy. RESULTS: In 57 of the patients studied, a reactivation was seen which coincided with a decrease in the bacteriological index (BI), suggesting that this reactivation (reversal reaction or type 1 leprosy reaction) coincides with an effective capacity for bacteriological clearance. In nine patients, an increase of the bacteriologic index (IB) or persistence of solid bacilli occurred during the reactivation, indicating proliferative activity, suggestive of a relapse. The histopathological aspects of the granulomas were similar in both groups. CONCLUSION: Bacterioscopy provided the only means to differentiate a reversal reaction from a relapse in patients with granulomatous reactivation. The type 1 leprosy reaction may be considered as a part effective immune reconstitution (reversal, upgrading reaction) or as a mere hypersensitivity reaction (downgrading reaction) in a relapse.

Granulomatous Reactivation during the Course of a Leprosy Infection: Reaction or Relapse

Leprosy is a chronic granulomatous infectious disease and is still endemic in many parts of the world. It causes disabilities which are the consequence of nerve damage. This damage is in most cases the result of immunological reactions...

Monostotic fibrous dysplasia: a 23-year follow-up of a patient with spontaneous bone remodeling.

Fibrous dysplasia is a benign fibro-osseous disease that affects one or more bones. Although its etiology has been defined, the mechanism of spontaneous resolution is still unclear. There is strong evidence indicating the occurrence of stabilization when bone maturation is completed. Deformities that lead to esthetic and functional disorders are observed in almost all cases. Plastic surgery is often recommended when the maxilla and mandible are involved. In the case of mild deformities, careful follow-up during skeletal growth is recommended. We describe here the 23-year follow-up of a patient with monostotic fibrous dysplasia whose disease had stabilized by 13 years of follow-up.

Sporadic and multiple neurofibromas in the head and neck region: a retrospective study of 33 years.

The neurofibroma occurs as isolated or multiple lesions frequently associated with neurofibromatosis type 1 (NF-1). The aim of this study was to analyze the clinical and histopathological features of neurofibromas, particularly the plexiform variant, in the skin and oral mucosa, discussing their pathogenesis as well as clinical management of isolated lesion unassociated with NF1. The clinicopathologic features of 66 neurofibromas in the head and neck region diagnosed at the pathology laboratories of the Bauru Dentistry School and Lauro de Souza Lima Research Institute from 1970 to 2003 were reviewed. The clinical data, therapy, and follow-up information were obtained from the medical records. The results showed a high frequency of cutaneous lesions (81.8%) occurring mainly in females older than 40 years. Isolated neurofibromas were found in 51.2% of patients, and multiple lesions were often associated with the NF-1. The histopathological analysis demonstrated that diffused neurofibromas occur more frequently than the plexiform type. However, one case of plexiform neurofibroma was detected in the oral mucosa as an isolated lesion non-associated with the NF-1. The indolent clinical behavior of isolated neurofibromas in the head and neck region and the absence of NF-1 association reinforce that sporadic lesion could be hyperplastic or hamartomatous rather than neoplastic in nature.

Malignant fibrous histiocytoma (undifferentiated high-grade pleomorphic sarcoma) occurring in tuberous sclerosis: a case report.

Tuberous sclerosis is an autosomal dominant genetic disorder that is characterized by the early development of hamartomas, malformations, and congenital tumors of the nervous system, skin, kidneys, lungs, and heart. Variable clinical expressivity has been reported and more than one gene can be responsible for the disorder. Benign neoplasias accompanying the syndrome are common but malignant neoplasias are rare, being generally mesenchymal and possibly affecting the jaws. We report here a clinical case of a malignant fibrous histiocytoma (undifferentiated high-grade pleomorphic sarcoma) of the mandible in a patient with tuberous sclerosis.

Larva migrans in the oral mucosa: report of two cases

Cutaneous Larva migrans is a very common disease in tropical regions. In the oral mucosa, the infection occurs in the same way as in the skin, but it is rarer. This report describes two cases of Larva migrans in the oral mucosa. The first case was in a 27-year-old woman who presented an erythematous plaque located on the buccal mucosa, extending to a posterior direction, following a linear pattern, to other areas of the mouth. After incisional biopsy of the anterior-most portion of the lesion, morphological details obtained in multiple examined sections suggested Necator or Ancylostoma braziliense larvae as the cause of infection. The second case was in a 35-year-old male who presented a fusiform erythematous plaque in the palatal mucosa. This area was removed and submitted to microscopic examination under a presumptive diagnosis of "parasite migratory stomatitis". The histological characteristics were suggestive of a larva pathway. In both cases the lesion disappeared after biopsy and the patients were symptom-free.

Larva migrans cutânea é uma doença muito comum em regiões tropicais. Na mucosa oral, a infecção ocorre da mesma forma como na pele, mas é raro. Este relato descreve dois casos de Larva migrans na mucosa oral. O primeiro caso foi de uma mulher de 27 anos de idade, que apresentou uma placa eritematosa localizada na mucosa julgal, estendendo-se posteriormente, em conformação linear, para outras áreas da boca. Após biópsia incisional da porção mais anterior da lesão, detalhes morfológicos obtidos em múltiplos cortes examinados sugeriram Necator ou larvas de Ancylostoma braziliense como a causa da infecção. O segundo caso foi de um homem de 35 anos de idade que apresentou uma placa fusiformes eritematosas na mucosa palatina. Esta área foi removida e submetida a exame microscópico, com diagnóstico presuntivo de "estomatite migratória por parasita". As características histológicas foram sugestivas de trajeto de larva. Em ambos os casos a lesão desapareceu após a biópsia e os pacientes estavam assintomáticos.

Recidiva de hanseníase após 24 doses de poliquimioterapia multibacilar / Relapse in leprosy after 24 months o who multidrug therapy

The WHO multidrug therapy has changed the leprosy scenario since its implementation, with a low relapse rate. However, it is still a challenge the duration of treatment for effective cure in patients with high bacillary load. We report in this article a relapse in a patient 9 years after he had finished the therapy. It is also discussed the diagnostic criteria for leprosy relapse and the possibility that some patients require a longer treatment than the usually preconized.

Estudo terapêutico comparando a associação de rifampicina, ofloxacina e minociclina com a associação rifampicina, clofazimina e dapsona em pacientes com hanseníase multibacilar / Therapeutic study comparing the association rifampin, ofloxacinand minocycline, with the association rifampin, clofazimine anddapsone in multibacillary leprosy patients

Foram comparados dois esquemas terapêuticos em pacientes com hanseníase multibacilar. O grupo controle com 14 pacientes recebeu o tratamento convencional.O grupo teste com 12 pacientes recebeu a associação de rifampicina 600 mg, ofloxacina 400 mg,e minociclina 100 mg, uma vez por mês, durante dois anos. Na avaliação inicial foram realizados exames clínicos, baciloscópicos e histológicos. A baciloscopia e a biópsia foram repetidas no final do primeiro e segundo ano de tratamento. As avaliações clínicas realizadas mensalmente. Todos pacientes apresentavam lesões cutâneas, que os caracterizavam como virchovianos ou peri-virchovianos. No grupo controle, o índice baciloscópico antes do tratamento variou de 2 a 4,8 e no grupo teste de 1,6 a 4,8. Histologicamente apresentavam quadro de hanseníase virchoviana ativa, exceto um paciente do grupo teste. Ao final do primeiro ano de tratamento estavam todos clinicamente melhorados,o índice baciloscópico diminuído e quadro histológico regressivo. Essa tendência se mantinha e ao final do segundo ano todos estavam clinicamente, baciloscopicamente e histologicamente ainda melhores. Análise estatística mostrou não haver diferença significante entre os grupos, sendo os esquemas equivalentes. No grupo controle todos apresentaram pigmentação cutânea devido a clofazimina. Os resultados deste estudo demonstraram que o esquema com rifampicina, ofloxacinae minociclina, teve eficácia e segurança equivalente a poliquimioterapia convencional para multibacilar. Além disso, não causa pigmentação cutânea, pode ser totalmente supervisionado, podendo ser utilizado como esquema alternativo

Two therapeutic schemes in multibacillary leprosy patients were compared. The control group with 14 patients received the conventional treatment (MDT-MB). The test group with 12 patients, received the association rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg (ROM), administrated under supervision once a month, during two years. Initial evaluations include clinical, bacilloscopic and histological exams. The bacilloscopy and the biopsy were repeated at the end of first and second year of treatment. Clinical evaluations were performed monthly. All patients presented skin lesions characteristic of the lepromatous type. In the control group, the bacterial index (BI) before treatment ranged from 2 to 4.8 and in the test group it ranged from 1.6 to 4.8. Histological picture resembled active lepromatous leprosy, except one patient from the test group. At the end of the first year of treatment all patients showed clinical improvement, decreased BI and regressive histological picture. This tendency was maintained and at a final evaluation at the end of the second year all patients showed improvement on clinical, bacilloscopic and histological evaluations. Statistical analysis showed no significant differences between the groups, therefore, the two schemes were similar. In the control group all patients presented skin pigmentation after clofazimine intake. The results demonstrated that monthly administration of ROM is as efficacious and safe as MDT-MB. Besides, it doesn’t cause skin pigmentation, it can be given under supervision and can be used as alternative scheme.

Reação reversa com vasculites granulomatosas e lesões cutâneas necrosantes e ulcerativas / Reversal reaction with granulomatous vasculities and necrotizing cutaneous lesions

Um indivíduo com 49 anos de idade recebe o diagnóstico de Hanseníase Virchoviana sub-polar. Ele referiu, durante os prévios 11 anos, sintomas, principalmente neurológicos, característicos de hanseníase, mas este diagnóstico não foi definido nos serviços médicos que freqüentou. Após 6 meses de poliquimioterapia passou a apresentar neurites que foram tratadas como reação tipo 2. Em um último episódio apresentou febre, mal estar, mialgias e lesões necróticas e ulcerativas nos membros, nádegas, dorso, pavilhão auricular esquerdo. O aspecto clínico destas lesões era semelhante as lesões observadas no fenômeno de Lúcio e no Eritema nodoso necrosante. As biópsias mostram alterações da microvasculatura superficial, necrose epidérmica e dérmica, similares a estas reações, mas as alterações básicas são vasculites granulomatosas no derma profundo e tecido celular sub-cutâneo. Estes aspectos clínicos e histopatológicos são interpretados e discutidos como reação tipo 1 (reação reversa) com envolvimento vascular predominante.

Hanseniase: episodio reacional tuberculoide desencadeado preconcemente apos instalaçao de poliquimioterapia, em individuo inicialmente diagnosticado como multibacilar / Leprosy: tuberculoid reactional episode developed early after multidrugtherapy was initiated in patient initially diagnosed as multibacillary

Um homem de cor parda, 66 anos de idade, refere ha 10 anos disturbio de sensibilidade na regiao dorsal do halux direito, e ha 6 meses placa eritematosa no braço direito co diagnostico histopatologico de hanseniase multibacilar. Quinze dias apos instalaçao de poliquimioterapia, a lesao inicial se tumefaz, ulcera e aparecem novas lesoes eritemato-edematosas disserminadas na pele. A biopsia de uma dessas novas lesoes demonstra hanseniase reacionla na faixatuberculoide com baciloscopia de 3+/6. O aparecimento da lesao inicial coincidiu com diagnostico recente de diabetes mellitus, e durante o episodio reacional o paciente apresentou mal-estado geral, febre e leve ictiricia Os autores discutem a patogenese destes eventos, surgerindo uma fase previa de degradaçao (downgrading) devido a progressiva proliferaçao bacilar, com consequente inibiçao da imunidade celular pela açao dos antigenos capsulares produzidos pela fraçao de bacilos integros e viaveis...

Hanseníase tuberculóide em paciente com Aids / Tuberculoid leprosy in aids patient

Relata-se o caso de uma criança de oito anos, portadora de Aids, que desenvolveu hanseníase tuberculóide antes do início da terapia anti-retroviral. Apresentava lesões ulceradas nos membros, Mitsuda de 8,5mm, hipoestesia em perna esquerda, e o diagnóstico de hanseníase foi definido pela imuno-histoquímica antiproteína S-100, que mostrou fragmentos de ramos nervosos no interior dos granulomas. A incidência da hanseníase não aumentou com o advento da Aids, e não há modificações na apresentação clínica ou na resposta terapêutica nos casos de hanseníase associados à Aids. Também não se observou neste caso o desenvolvimento da reação tipo 1 como resultado da reconstituição imunológica devido ao tratamento anti-retroviral.

The authors present a 8 year-old child with AIDS who developed tuberculoid leprosy prior the beginning of the anti-retroviral treatment. The pacient presented ulcered lesions in arms and legs, the Mitsuda reaction was 8,5 mm, there was hypostesia of the left leg and the leprosy diagnosis was reached mainly supported by the anti-S100 protein immunohistochemistry staining that showed fragments of nerve branches inside granulomas. The incidence of leprosy has not increased because of AIDS. There havenÆt been changes in the clinical presentation and in the response to therapy in cases of leprosy associated with AIDS. We havenÆt also observed development of type 1 reaction in this patient resulting from restoring of the immune response after the anti-retroviral treatment.