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...

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.

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.

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.

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.

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.

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.

Manifestações de padrão tuberculóide reacional na hanseníase dimorfa: estudo histoquímico e imuno-histoquímico comparativo, em biópsias cutâneas, entre reações tipo 1 ocorridas antes e durante a poliquimioterapia / Manifestations of reactional tuberculoid pattern in borderline leprosy: comparative, histochemical and immunohistochemical study, in skin biopsies, between type 1 reactions ocurred before and during multidrugtherapy

FUNDAMENTOS: Na hanseníase dimorfa é comum a ocorrência de reações tipo 1 antes, durante ou depois da poliquimioterapia (PQT). Trabalhos recentes sugerem que a reação tipo 1 seria um desequilíbrio imunológico entre citocinas pró-inflamatórias e antiinflamatórias. OBJETIVOS: Compreender melhor a fisiopatologia das reações tipo 1. MÉTODOS: Estudaram-se biópsias cutâneas de 10 indivíduos com hanseníase dimorfa-tuberculóide reacional não tratada (DTR) e 10 dimorfos em reação reversa após o início da PQT (DRR), comparando-se os parâmetros morfológicos e imunológicos por meio de colorações HE e Faraco-Fite, e técnicas imuno-histoquímicas (CD4, CD8, CD20, CD79a, CD57, iNOS, IL-10, LAM e BCG). RESULTADOS: Houve, nos DRR, mais macrófagos multivacuolados, maior marcação nos macrófagos para a enzima óxido nítrico sintase induzível (iNOS) e menos linfócitos T CD8+ (p<0,05). Afora a presença de bacilos típicos nos DTR e sua ausência nos DRR, não houve diferenças na baciloscopia ou na marcação para antígenos micobacterianos (LAM e BCG) entre os grupos. O número de células IL-10+ foi similar nos dois grupos, porém houve correlação negativa entre essa citocina e a proporção CD4/CD8 apenas nos pacientes DRR (p<0,05). Houve tendência à redução do infiltrado específico e ao maior número de células NK nos DRR. CONCLUSÃO: Na presença de muitos bacilos viáveis em um paciente sem imunidade celular plena, haveria tendência à piora imunológica (downgrading). A PQT, ao reduzir a carga bacilar, melhoraria a imunidade celular (upgrading), com posterior desvio da imunidade adquirida para a inespecífica (resposta Th3), evoluindo para a cura.

BACKGROUND: Type 1 reactions are common in borderline leprosy, and can occur before, during or after multidrugtherapy (MDT). Recent papers suggest that these reactions could be a result of an imbalance between proinflammatory and anti-inflammatory citokines. OBJECTIVE: To understand better the physiopathology of type 1 reactions. METHODS: We studied skin biopsies from 10 non-treated patients with reactional borderline tuberculoid leprosy (BTR) and 10 from borderline leprosy with reversal reactions after the beginning of MDT (BRR), to compare morphological and immunological parameters by routine staining (H-E and Faraco-Fite) and immunohistochemical technics (CD4, CD8, CD20, CD79a, CD57, iNOS, IL-10, LAM and BCG). RESULTS: We found, in BRR group, stronger staining for iNOS into macrofages, fewer CD8+ T cells and more multivacuolated macrofages than BTR group (p<0,05). Despite the presence of viable bacilli in BTR and its absence in BRR, there weren't differences in baciloscopy and staining for mycobacterial antigens (LAM and BCG) between the groups. The number of IL-10+ cells was similar in both groups, but there was a negative correlation between this cytokine and the CD4:CD8 ratio only in BRR group (p<0,05). It was seen a tendency for a decreased specific infiltrate and increased number of NK cells in BRR group. CONCLUSIONS: The presence of many viable bacilli in a patient with partial cellular immunity could worse the immunological status (downgrading). Once started MDT, the reduction bacilli charge would improve cellular immunity (upgrading), with latter shift to innate immunity (Th3 response), evolving to cure.

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.