Resumo Antecedentes A hanseníase pode ter o seu diagnóstico histopatológico dificultado quando bacilos álcool-ácido resistentes não são encontrados nas amostras de pele dos pacientes. Objetivo Demonstrar que uma análise morfológica detalhada de alterações histopatológicas dos nervos dérmicos pode aumentar a eficácia diagnóstica. Métodos Foram selecionadas amostras de pele de pacientes com uma a cinco lesões suspeitas de hanseníase. Os casos selecionados foram classificados conforme achados histopatológicos: hanseníase (HD, n = 13), casos inconclusivos (INC, n = 11), e outras doenças (OD, n = 11). Quantificamos as lesões dos nervos cutâneos por meio do índice de lesão de nervos (nerve lesion index, NLI, em inglês) e do índice quantitativo de axônios (axon quantitative index, AQI, em inglês) imunorreativos a PGP9.5 nos nervos cutâneos. Também medimos o envolvimento inflamatório dos anexos em amostras de pele como evidência indireta de hanseníase. Resultados Foram observadas no grupo HD medianas mais altas do NLI com relação a infiltrados inflamatórios endoneurais (HD = 0,5; INC = 0; OD = 0; p < 0,001) e mais alta frequência de acometimento inflamatório de anexos cutâneos (HD = 7; INC = 1; OD = 0). Entretanto, as amostras dos grupos INC e OD também mostraram comprometimento inflamatório e não inflamatório dos nervos cutâneos, com 2 ou mais tipos de alterações de nervos na mesma amostra (respectivamente: INC = 1 e 2; OD = 3 e 5). Não houve diferença significativa na quantidade de axônios endoneurais imunorreativos a PGP9.5 entre os grupos. Conclusão A análise morfológica detalhada dos nervos cutâneos em lesões suspeitas de hanseníase permitiu selecionar pacientes com lesões inespecíficas inflamatórias ou não inflamatórias nos nervos dérmicos nos grupos INC e OD, para que sejam monitorados clinicamente visando um possível diagnóstico futuro da doença. Esses pacientes INC e OD não podem ter o diagnóstico de HD definitivamente excluído, e a hanseníase pode coexistir com outra doença como uma comorbidade. álcoolácido álcool ácido diagnóstica histopatológicos HD, 13, 13 , 13) INC, (INC 11, 11 11) (OD 11. . nerve index inglês axon AQI PGP95 PGP PGP9 5 PGP9. 0,5 05 0 0,001 0001 001 7 0. 0) Entretanto respectivamente (respectivamente 5. 5) excluído comorbidade 0, 0,00 000 00 0,0

Abstract Background The diagnosis of Hansen disease (HD) can be difficult when acid-fast bacilli are not detected in the patient's skin sample. Objective To demonstrate that detailed morphological analysis of nonspecific inflammatory and/or noninflammatory alterations in dermal nerves as well as skin adnexa in leprosy-suspected biopsy samples could improve the efficacy of histopathological diagnosis. Methods Patients with one to five skin lesions were enrolled in the study and classified into three groups by skin histopathology findings: Hansen disease (HD, n = 13), other diseases (OD, n = 11), and inconclusive cases (INC, n = 11). We quantified dermal nerve damage via the nerve lesion index (NLI) and PGP9.5-immunoreactive axon quantitative index in dermal nerves (AQI). We also measured inflammatory involvement of adnexa in cutaneous samples as indirect evidence of HD. Results We observed a higher median endoneurial inflammatory infiltrate NLI (HD = 0.5; INC = 0; OD = 0; p < 0.001) and more frequent inflammatory involvement of skin adnexa in samples of the HD group compared with those of the INC and OD groups (HD = 7; INC = 1; OD = 0). However, samples from the INC and OD groups also showed inflammatory and noninflammatory damage of dermal nerves, with 2 or more kinds of alterations in nerves in the same sample (respectively: INC = in 1 and 2 samples; OD = in 3 and 5 respectively). The quantification of PGP9.5-immunoreactive axons in dermal nerves revealed no difference between the groups. Conclusion A detailed morphological analysis of cutaneous nerves in lesions with a suspicion of HD enabled us to select patients with nonspecific inflammatory or non-inflammatory lesions in the dermal nerves in the INC and OD groups, so they may be clinically monitored aiming at a possible future diagnosis of the disease. These INC and OD patients cannot have the HD diagnosis definitely excluded, and HD may coexist with another disease as a comorbidity. acidfast acid fast patient s andor leprosysuspected leprosy suspected findings HD, 13, 13 , 13) OD, (OD 11, 11 11) INC, (INC 11. . (NLI PGP9.5immunoreactive PGP95immunoreactive PGPimmunoreactive PGP9.5 immunoreactive PGP9 PGP AQI. AQI (AQI) 0.5 05 0 0.001 0001 001 7 0. 0) However respectively (respectively respectively. respectively) non excluded comorbidity 5immunoreactive PGP95 PGP9. (AQI 0.00 000 00 0.0

BACKGROUND Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. OBJECTIVES The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. METHODS Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori’s trichrome) and fibrosis was evaluated via semi-quantitative estimation. FINDINGS Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. MAIN CONCLUSIONS The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.

RESUMO OBJETIVO Descrever o processo de adaptação transcultural da “Explanatory Model Interview Catalogue – Stigma Scale” para pessoas afetadas por hanseníase no Brasil. MÉTODOS Após a autorização do autor da escala para seu uso no contexto nacional, deu-se início aos cinco passos do processo de adaptação transcultural: (1) tradução, (2) reunião de síntese, (3) retrotradução, (4) comitê de peritos e (5) pré-teste. A consistência interna da escala foi avaliada utilizando o coeficiente alfa de Cronbach. RESULTADOS Os 15 itens da versão original da escala foram traduzidos para a língua portuguesa do Brasil. A escala adaptada apresentou evidência de boa compreensão de seu conteúdo, atestada tanto por peritos como por membros da população alvo. Sua consistência interna foi de 0,64. CONCLUSÕES O instrumento adaptado apresenta consistência interna satisfatória. Pode ser útil em estudos futuros que intencionem viabilizar ampla análise situacional que sustente programas sólidos de saúde pública com enfoque na efetiva redução de estigma. Em estudo ulterior será avaliada a validade de constructo, critério e reprodutibilidade.

ABSTRACT OBJECTIVE Describe the process of cross-cultural adaptation of the “Explanatory Model Interview Catalog – Stigma Scale” for people affected by leprosy in Brazil. METHODS After being authorized by the author of the scale to use it in the national context, we initiated the five steps process of cross-cultural adaptation: (1) translation, (2) synthesis meeting, (3) back-translation, (4) committee of experts and (5) pre-test. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. RESULTS The 15 items of the scale’s original version were translated into Brazilian Portuguese. The adapted scale showed evidence of a good understanding of its content, attested both by experts and members of the target population. Its internal consistency was 0.64. CONCLUSIONS The adapted instrument shows satisfactory internal consistency. It may be useful in future studies that intend to provide broad situational analysis that supports solid public health programs with a focus on effective stigma reduction. In a later study, the construct’s validity, criterion, and reproducibility will be evaluated.

RESUMO OBJETIVO Descrever o processo de adaptação transcultural da “Explanatory Model Interview Catalogue – Stigma Scale” para pessoas afetadas por hanseníase no Brasil. MÉTODOS Após a autorização do autor da escala para seu uso no contexto nacional, deu-se início aos cinco passos do processo de adaptação transcultural: (1) tradução, (2) reunião de síntese, (3) retrotradução, (4) comitê de peritos e (5) pré-teste. A consistência interna da escala foi avaliada utilizando o coeficiente alfa de Cronbach. RESULTADOS Os 15 itens da versão original da escala foram traduzidos para a língua portuguesa do Brasil. A escala adaptada apresentou evidência de boa compreensão de seu conteúdo, atestada tanto por peritos como por membros da população alvo. Sua consistência interna foi de 0,64. CONCLUSÕES O instrumento adaptado apresenta consistência interna satisfatória. Pode ser útil em estudos futuros que intencionem viabilizar ampla análise situacional que sustente programas sólidos de saúde pública com enfoque na efetiva redução de estigma. Em estudo ulterior será avaliada a validade de constructo, critério e reprodutibilidade.

ABSTRACT OBJECTIVE Describe the process of cross-cultural adaptation of the “Explanatory Model Interview Catalog – Stigma Scale” for people affected by leprosy in Brazil. METHODS After being authorized by the author of the scale to use it in the national context, we initiated the five steps process of cross-cultural adaptation: (1) translation, (2) synthesis meeting, (3) back-translation, (4) committee of experts and (5) pre-test. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. RESULTS The 15 items of the scale’s original version were translated into Brazilian Portuguese. The adapted scale showed evidence of a good understanding of its content, attested both by experts and members of the target population. Its internal consistency was 0.64. CONCLUSIONS The adapted instrument shows satisfactory internal consistency. It may be useful in future studies that intend to provide broad situational analysis that supports solid public health programs with a focus on effective stigma reduction. In a later study, the construct’s validity, criterion, and reproducibility will be evaluated.

AbstractLeprosy is a neglected disease. We point up the need of recognizing the unusual clinical presentations of the disease in order to make early diagnosis and proper treatment possible, and break the transmission chain. The authors report a rare type of multibacillary leprosy: histoid leprosy and present images of numerous well-circumscribed indurated papules and nodules distributed throughout the entire body.

The diagnosis of single-lesion paucibacillary leprosy remains a challenge. Reviews by expert dermatopathologists and quantitative polymerase chain reaction (qPCR) results obtained from 66 single-plaque biopsy samples were compared. Histological findings were graded as high (HP), medium (MP) or low (LP) probability of leprosy or other dermatopathy (OD). Mycobacterium leprae-specific genes were detected using qPCR. The biopsies of 47 out of 57 clinically diagnosed patients who received multidrug therapy were classified as HP/MP, eight of which were qPCR negative. In the LP/OD (n = 19), two out of eight untreated patients showed positive qPCR results. In the absence of typical histopathological features, qPCR may be utilised to aid in final patient diagnosis, thus reducing overtreatment and delay in diagnosis.

A reação do tipo 1 ou reação reversa expressa-se clinicamente por uma exacerbação inflamatória das lesões de pele e de troncos nervosos, levando a alterações sensitivas e motoras. Ocorre nas formas não-polares da hanseníase, embora possa ocorrer numa pequena percentagem de pacientes LL tratados. As incapacidades físicas, deformidades e morbidade, ainda presentes na hanseníase, são causadas principalmente por esses episódios agudos. O reconhecimento dos estados reacionais é imperativo para uma abordagem precoce e manejo adequado, evitando a instalação de incapacidades que tanto estigmatizam a doença. Esta revisão tem como objetivo descrever aspectos clínicos, imunopatogênese, epidemiologia, características histopatológicas e terapêutica do estado reacional do tipo 1.

A type 1 reaction or reversal reaction is expressed clinically by inflammatory exacerbation of the skin lesions and nerve trunks, consequently leading to sensory and motor alterations. It occurs in non-polar forms of leprosy, although it can occur in a small percentage of sub-polar LL treated patients. Disabilities, deformities and morbidity, still present in leprosy, are mainly caused by these acute episodes. The recognition of reactional states is imperative for an early approach and efficient management, to avoid the emergence of disabilities that stigmatize the disease. This review aims to describe the clinical aspects, immunopathogenesis, epidemiology, histopathological features and therapeutics of type 1 reactions.

Contact surveillance is a valuable strategy for controlling leprosy. A dynamic cohort study of leprosy contacts was initiated in 1987 at Oswaldo Cruz Foundation. The objective of this work was to review the data on the major risk factors leading up to the infectious stage of the disease, estimate incidence rates of leprosy in the cohort and characterise the risk factors for the disease among the contacts under surveillance. The incidence rate of leprosy among contacts of leprosy patients was estimated at 0.01694 cases per person-year in the first five years of follow-up. The following factors were associated with acquiring the disease: (i) not receiving the BCG vaccine, (ii) a negative Mitsuda reaction and (iii) contact with a patient with a multibacillary clinical form of leprosy. The contacts of index patients who had high bacilloscopic index scores > 1 were at especially high risk of infection. The following factors were associated with infection, which was defined as a seropositive reaction for anti-phenolic glicolipid-1 IgM: (i) young age (< 20 years), (ii) a low measured Mitsuda reaction (< 5 mm) and (iii) contact with an index patient who had a high bacilloscopic index. BCG vaccination and re-vaccination were shown to be protective among household contacts. The main conclusions of this study indicate an urgent need for additional leprosy control strategies in areas with a high incidence of the disease.

The clinical course of leprosy is often interrupted by reactions, which are acute inflammatory episodes that can be classified as type I or type II. Type II reactions can present as cutaneous lesions that resemble erythema multiforme (EM). EM is classically associated with drug allergies or pre-existing viral infections. However, the differential diagnostic criteria of the diverse causative agents remain controversial. The aim of this study was to determine both the clinical relevance and the morphological and immunohistochemical characteristics of the EM-like lesions during the course of type II leprosy reactions. Twenty-seven skin biopsies were taken from typical EM-like lesions of multibacillary patients and reviewed; their histological features were correlated to their clinical aspects. Then, a computer-assisted morphometric analysis was performed to measure the extent of angiogenesis during these acute episodes. The histopathological and immunohistochemical analysis of the EM lesions revealed that they shared the same features that have been previously described for ENL, including immunopositivity in the identical cell-mediated immune markers. Our results point to leprosy as the cause of the EM-like lesions in our patients. Therefore, leprosy should be considered in the differential diagnosis of EM.

Contact surveillance is an important strategy to ensure effective early diagnosis and control of leprosy; passive detection may not be as efficient because it is directly tied to the ready availability of heath care services and health education campaigns. The aim of this study was to reinforce that contact surveillance is the most effective strategy for the control of leprosy. The analysed data were obtained from a cohort of contacts and cases diagnosed through a national referral service for leprosy. We analysed data from patients diagnosed between 1987-2010 at the Souza Araújo Ambulatory in Rio de Janeiro. Epidemiological characteristics of leprosy cases diagnosed through contact surveillance and characteristics of passively detected index cases were compared using a conditional logistic regression model. Cases diagnosed by contact surveillance were found earlier in the progression of the disease, resulting in less severe clinical presentations, lower levels of initial and final disability grades, lower initial and final bacterial indices and a lower prevalence of disease reaction. In this respect, contact surveillance proved to be an effective tertiary prevention strategy, indicating that active surveillance is especially important in areas of high endemicity, such as Brazil.

O objetivo deste trabalho foi comparar dados epidemiológicos de pacientes de hanseníase residentes em dois municípios com perfil socioeconômico e nível de endemicidade diferentes e que foram acompanhados em um mesmo centro de referência. Foi realizado um estudo descritivo dos dados de pacientes tratados no ambulatório Souza Araújo, 1986 a 2008, residentes nos municípios do Rio de Janeiro (n = 1353) e Duque de Caxias (n = 336). Entre os pacientes desta cidade, em comparação com os da outra, observou-se maior proporção de casos: com idade inferior a 15 anos, multibalicares, com maior índice baciloscópico (IB) inicial, e detectados através da vigilância de contatos. Os pacientes de Duque de Caxias apresentaram menor renda média e nível de escolaridade. Não foram observadas diferenças estatisticamente significativas quanto ao sexo, grau de incapacidade inicial, reação no diagnóstico, IB final, abandono e regularidade do tratamento. As diferenças encontradas entre os pacientes acompanhados em um mesmo centro de referência poderiam estar, em parte, relacionadas a diferenças contextuais existentes entre os municípios. Por outro lado, observou-se que a oferta de tratamento e acompanhamento podem minimizar o efeito que os fatores contextuais apresentam sobre os desfechos de saúde.

The scope of this study was to compare epidemiological data on leprosy patients living in two cities with different socioeconomic and endemic profiles that were monitored in a single center of reference. A descriptive study was made of data from patients in the Souza Araújo Outpatient facility treated in the period 1986-2008, who were resident in the cities of Rio de Janeiro = 1353) and Duque de Caxias (n = 336). Results: Among patients from Duque de Caxias, in comparison with patients from Rio de Janeiro, there was a higher proportion of cases: below the age of 15 years, multibacillary, higher initial bacilloscopic index (BI) and cases detected through surveillance of contacts. Patients in Duque de Caxias had lower average incomes and education levels. There were no statistically significant differences regarding gender, disability level, reaction in the diagnosis, final BI, bandonment and regularity of treatment. The differences found between the patients monitored in a single center of reference, could be partly related to contextual differences between the municipalities. On the other hand, it was observed that the provision of treatment and monitoring can minimize the effect of different contextual factors on health outcomes.

O objetivo deste trabalho foi comparar dados epidemiológicos de pacientes de hanseníase residentes em dois municípios com perfil socioeconômico e nível de endemicidade diferentes e que foram acompanhados em um mesmo centro de referência. Foi realizado um estudo descritivo dos dados de pacientes tratados no ambulatório Souza Araújo, 1986 a 2008, residentes nos municípios do Rio de Janeiro (n = 1353) e Duque de Caxias (n = 336). Entre os pacientes desta cidade, em comparação com os da outra, observou-se maior proporção de casos: com idade inferior a 15 anos, multibalicares, com maior índice baciloscópico (IB) inicial, e detectados através da vigilância de contatos. Os pacientes de Duque de Caxias apresentaram menor renda média e nível de escolaridade. Não foram observadas diferenças estatisticamente significativas quanto ao sexo, grau de incapacidade inicial, reação no diagnóstico, IB final, abandono e regularidade do tratamento. As diferenças encontradas entre os pacientes acompanhados em um mesmo centro de referência poderiam estar, em parte, relacionadas a diferenças contextuais existentes entre os municípios. Por outro lado, observou-se que a oferta de tratamento e acompanhamento podem minimizar o efeito que os fatores contextuais apresentam sobre os desfechos de saúde.

The scope of this study was to compare epidemiological data on leprosy patients living in two cities with different socioeconomic and endemic profiles that were monitored in a single center of reference. A descriptive study was made of data from patients in the Souza Araújo Outpatient facility treated in the period 1986-2008, who were resident in the cities of Rio de Janeiro = 1353) and Duque de Caxias (n = 336). Results: Among patients from Duque de Caxias, in comparison with patients from Rio de Janeiro, there was a higher proportion of cases: below the age of 15 years, multibacillary, higher initial bacilloscopic index (BI) and cases detected through surveillance of contacts. Patients in Duque de Caxias had lower average incomes and education levels. There were no statistically significant differences regarding gender, disability level, reaction in the diagnosis, final BI, bandonment and regularity of treatment. The differences found between the patients monitored in a single center of reference, could be partly related to contextual differences between the municipalities. On the other hand, it was observed that the provision of treatment and monitoring can minimize the effect of different contextual factors on health outcomes.

Foi realizado um estudo comparativo de dois grupos de pacientes definidos de acordo com o esquema terapêutico, a fim de se avaliarem os índices baciloscópicos: PQT/12 doses (Grupo 1: 128 pacientes) e PQT/24 doses (Grupo 2: 85 pacientes). Todos os pacientes foram avaliados no início do tratamento, aos 12 meses, e novamente aos 24 meses. Ao final dos 24 meses, observou-se uma redução das médias dos índices baciloscópicos, semelhantes nos dois grupos. Não houve diferença estatística na avaliação da freqüência de quadros reacionais nos dois esquemas terapêuticos.

A comparative study was performed on the initial and final bacillary indexes of 213 multibacillary leprosy patients who received 12 doses (Group 1: 128 patients) or 24 doses (Group 2: 85 patients) of multidrug therapy (MDT/WHO) to measure the effectiveness of the two regimens. All patients were evaluated at treatment baseline, 12 months, and 24 months. The reduction in bacillary levels and mean bacillary indexes at 24 months was similar in the two groups. No statistical difference in reaction rates was observed between the two treatment regimens.

Foi realizado um estudo comparativo de dois grupos de pacientes definidos de acordo com o esquema terapêutico, a fim de se avaliarem os índices baciloscópicos: PQT/12 doses (Grupo 1: 128 pacientes) e PQT/24 doses (Grupo 2: 85 pacientes). Todos os pacientes foram avaliados no início do tratamento, aos 12 meses, e novamente aos 24 meses. Ao final dos 24 meses, observou-se uma redução das médias dos índices baciloscópicos, semelhantes nos dois grupos. Não houve diferença estatística na avaliação da freqüência de quadros reacionais nos dois esquemas terapêuticos.

A comparative study was performed on the initial and final bacillary indexes of 213 multibacillary leprosy patients who received 12 doses (Group 1: 128 patients) or 24 doses (Group 2: 85 patients) of multidrug therapy (MDT/WHO) to measure the effectiveness of the two regimens. All patients were evaluated at treatment baseline, 12 months, and 24 months. The reduction in bacillary levels and mean bacillary indexes at 24 months was similar in the two groups. No statistical difference in reaction rates was observed between the two treatment regimens.

O reconhecimento clínico precoce dos episódios reacionais traz grandes benefícios para os pacientes com hanseníase, devido à possibilidade de intervenção terapêutica imediata e adequada, evitando o desenvolvimento de incapacidades que tanto estigmatizam e complicam a doença. Existem três formas de episódios reacionais: os tipos 1 e 2, e a neurite. Esta última pode aparecer isoladamente ou acompanhar as formas anteriores. Em alguns casos só são observadas as manifestações cutâneas e/ou neurológicas das reações, enquanto em outros, alterações sistêmicas podem acrescentar-se ao quadro. O tratamento utilizando a associação de medicamentos antiinflamatórios e imunossupressores parece ser o mais adequado para evitar as recorrências e os efeitos colaterais.

The early clinical recognition of reactional states brings great benefits to leprosy patients due to the possibility of appropriate and immediate therapeutic intervention, thus avoiding the development of disabilities that so much stigmatize and complicate the disease. There are three types of reactional episodes: types 1, 2 and neuritis. The latter may occur alone or together with the former forms. In some cases only neurological and/or skin manifestations are observed in the reactions; in others, patients present systemic alterations. The treatment with an association of immunosuppressors and anti-inflammatory drugs seems to be the most effective to avoid recurrences and side effects