Image Morphometric Analysis of B Cells and Plasma Cells in Erythema Nodosum Leprosum With Clinicopathological Correlation.

ABSTRACT: Erythema nodosum leprosum (ENL) occurs as an immunological complication of multibacillary leprosy (MBL). The pathogenesis of ENL is long considered to be a T-cell-mediated process. The role of B cells and plasma cells in ENL is not well described in the literature. Therefore, we investigated the B-cell and plasma cell infiltrates in the skin biopsies of biopsy-proven cases of ENL by immunohistochemistry and image morphometry and compared the result with paucibacillary leprosy and MBL. Moreover, we sought a correlation of the B-cell and plasma cell infiltrates with different clinical, hematological, histopathological, and bacteriological parameters as well as the T-cell subsets in the skin biopsies. Our study highlighted a significant reduction in the number of B cells from paucibacillary leprosy to MBL to ENL, although there was no significant variation in the plasma cell infiltrate. The plasma cell infiltrate correlated with absolute neutrophilia in the blood and the presence of eosinophils in the ENL lesions. Both B cells and plasma cells positively correlated with CD4-positive T-helper cells and the CD8-positive cytotoxic T cells. Besides, the B cells also correlated positively with the CD3-positive pan T cells in the biopsy and negatively correlated with the T-regulatory:T-cell ratio. Our results suggested the role of B cells and plasma cells even at the tissue level in the pathobiogenesis of ENL.

Appropriately Selected Nerve in Suspected Leprous Neuropathy Yields High Positive Results for Mycobacterium leprae DNA by Polymerase Chain Reaction Method.

Identification of Mycobacterium leprae DNA by polymerase chain reaction (PCR) is a reliable and an affordable method to confirm leprosy. DNA from 87 nerve samples (61 from paraffin blocks and 26 fresh samples) was extracted. Mycobacterium leprae DNA was amplified by PCR from 80/87 (92%) specimens. Patients were seen over a period of 11 years (2007-2019), and leprosy was diagnosed based on clinical and characteristic histopathology findings. The clinical diagnostic possibilities were as follows: leprous neuropathy in 73/80 (91.3%), mononeuritis multiplex of unknown etiology in four (5.0%), vasculitic neuropathy in two (2.5%), and distal symmetric sensory motor neuropathy in one (1.3%). The biopsied nerves were as follows: superficial radial = 34 (42.6%), dorsal cutaneous branch of ulnar = 19 (23.8%), sural = 18 (22.5%), and superficial peroneal = 9 (11.3%), and corresponding neurological deficits were recorded in 77 (96.3%) cases. The histopathological diagnoses in total group were as follows: (borderline tuberculoid (BT) = 52, tuberculoid (TT) = 8, borderline lepromatous (BL) = 8, borderline borderline (BB) = 3, nonspecific inflammation = 3, healed/fibrosed = 4, and axonopathy = 2). Acid fast bacilli (AFB) was demonstrated in 11 (13.7%) samples. For comparison, 31 clinically and histopathologically defined non-leprous disease control nerves (inherited neuropathy = 20, vasculitis = 8, and nutritional neuropathy = 3) subjected to PCR were negative for M. leprae DNA. In most instances, there are multiple thickened peripheral nerves in suspected cases of leprosy, but neurological deficits pertaining to the thickened nerve are not as widespread. The current findings emphasize the importance of selecting the most appropriate nerve for biopsy to obtain a positive PCR result. We infer that clinical, histopathological, and PCR tests complement each other to help achieve a definitive diagnosis of leprosy particularly in pure neuritic leprosy and in leprous neuropathy with negative skin smears/biopsy.

Clinical and histopathological features of paucibacillary leprosy before and after multidrug therapy: a prospective study.

BACKGROUND: Leprosy often heals with residual skin lesions after completion of treatment. WHO recommends fixed duration multidrug therapy (MDT) irrespective of whether lesions clear or persist after treatment. Patients with residual lesions are often unsatisfied and may undergo repeat biopsy and re-treatment. This study was conducted to compare the clinicohistopathological features in paucibacillary leprosy before and after MDT from September 2012 to February 2014. METHODS: Sixty-one untreated cases of paucibacillary leprosy were investigated and given standard WHO paucibacillary-MDT for 6 months. Scoring of clinical activity was done; histopathological activity was graded according to granuloma fraction. Forty-four patients who completed the treatment were subjected to post-treatment biopsy. Clinical response to therapy was graded as active, resolving and inactive and histopathological changes were compared in all patients. RESULTS: Among the 44 patients, the lesions were inactive, resolving and active in 39% (17/44), 39% (17/44) and 23% (10/44) of patients respectively. Histologically, disease was inactive, resolving and active in 30% (13/44), 9% (4/44) and 61% (27/44). But histomorphological features suggesting regression: loose granulomas (59%, 26/44); lymphocyte predominance (66%, 29/44); vacuolar change in epithelioid cell cytoplasm (59%, 26/44), were statistically significant in post-treatment compared to pre-treatment. CONCLUSIONS: Although histological resolution is slower than clinical resolution, qualitative histomorphological changes in correlation with clinical inactivity can offer a fair suggestion to the clinician to terminate therapy.

Leprosy among children under 15 years of age: literature review

Abstract Leprosy is a chronic infectious disease caused by Mycobacterium leprae, representing a public health issue in some countries. Though more prevalent in adults, the detection of new cases in children under 15 years of age reveals an active circulation of bacillus, continued transmission and lack of disease control by the health system, as well as aiding in the monitoring of the endemic. Among patients under 15 years of age, the most affected age group is children between 10 and 14 years of age, although cases of patients of younger than 1 year of age have also been reported. Household contacts are the primary source of infection, given that caretakers, such as babysitters and others, must be considered in this scenario. Paucibacillary forms of the disease prevailed, especially borderline-tuberculoid leprosy, with a single lesion in exposed areas of the body representing the main clinical manifestation. Reactional states: Lepra reactions are rare, although some authors have reported high frequencies of this phenomenon, the most frequent of which is Type 1 Lepra Reaction. Peripheral nerve involvement has been described at alarming rates in some studies, which increases the chance of deformities, a serious problem, especially if one considers the age of these patients. The protective effect of BCG vaccination was found in some studies, but no consensus has been reached among different authors. Children must receive the same multidrug therapy regimen and the doses should, ideally, be calculated based on the child´s weight. Adverse reactions to this therapy are rare within this age group. This article aims to review epidemiological, clinical, and therapeutic aspects of leprosy in patients under 15 years of age.

Leukemia cutis in a patient of relapsed leprosy- Coincidence or predisposition?

Leprosy, a disease of skin and peripheral nerves has varied manifestations which principally affect the immune status of the host. Leukemic skin infiltrations in patients with leukemia are referred to as leukemia cutis. It can be seen in all types of leukemia, especially in patients with acute myelomonocytic leukemia (AML). In majority of cases, the cutaneous lesions are nonspecific manifestations associated with an impaired immune system.1 Though various malignancies have been documented with leprosy, no case of borderline-tuberculoid (BT) Hansen's disease with coexisting leukemia cutis has ever been reported in literature to the best of our knowledge.

Description of leprosy classification at baseline among patients enrolled at the uniform multidrug therapy clinical trial for leprosy patients in Brazil.

The uniform multidrug therapy clinical trial, Brazil (U-MDT/CT-BR), database was used to describe and report the performance of available tools to classify 830 leprosy patients as paucibacillary (PB) and multibacillary (MB) at baseline. In a modified Ridley and Jopling (R&J) classification, considering clinical features, histopathological results of skin biopsies and the slit-skin smear bacterial load results were used as the gold standard method for classification. Anti-phenolic glycolipid-I (PGL-I) serology by ML Flow test, the slit skin smear bacterial load, and the number of skin lesions were evaluated. Considering the R&J classification system as gold standard, ML Flow tests correctly allocated 70% patients in the PB group and 87% in the MB group. The classification based on counting the number of skin lesions correctly allocated 46% PB patients and 99% MB leprosy cases. Slit skin smears properly classified 91% and 97% of PB and MB patients, respectively. Based on U-MDT/CT-BR results, classification of leprosy patients for treatment purposes is unnecessary because it does not impact clinical and laboratories outcomes. In this context, the identification of new biomarkers to detect patients at a higher risk to develop leprosy reactions or relapse remains an important research challenge.

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.

Understanding the type 1 reactional state for early diagnosis and treatment: a way to avoid disability in leprosy / Compreender melhor o estado reacional tipo 1 para o diagnostico e tratamento precoces: uma forma de se evitar as incapacidades na hanseniase

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.

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.

Reacciones por lepra en un centro de referencia nacional en Colombia / Leprosy reactions in a Colombian national reference centre

Introducción. Colombia es el país de América con mayor proporción de casos nuevos de lepra con discapacidad grave. Para disminuir tal discapacidad se requiere el control de las reacciones, principal causa del daño neural en esta enfermedad. Objetivo. Describir las características clínicas y epidemiológicas y el tratamiento de los pacientes con reacciones de tipo 1 y 2 que consultaron al Centro Dermatológico Federico Lleras Acosta. Materiales y métodos. Se trata de un estudio descriptivo que incluyó la población de pacientes con diagnóstico clínico de reacciones de tipo 1 y de tipo 2 por lepra, que acudieron al centro entre los años 2003 y 2009. Resultados. Se estudiaron 96 reacciones, 35 del tipo 1 y 61 del tipo 2. El 75 % de los pacientes provenía de los departamentos de Tolima, Cundinamarca, Santander y Boyacá. El 56 % de las reacciones de tipo 1 se presentaron antes de iniciar la poliquimioterapia para la lepra; el dermatólogo tratante consideró que las reacciones que se presentaron después de suspender la poliquimioterapia eran recaídas. El 94 % de las reacciones de tipo 1 se trataron con corticoides orales. El 97 % de los pacientes con reacciones de tipo 2 presentaron eritema nudoso, y todos se trataron con talidomida. Conclusiones.La clínica de la reacción de tipo 1 puede orientar al diagnóstico de la lepra en un paciente sin el antecedente de esta enfermedad (56 %). La reacción de tipo 1 que se inicia después de suspender la poliquimioterapia para la lepra, podría ser una manifestación de recaída de la enfermedad. La reacción de tipo 2 es más frecuente en hombres, con una relación hombre a mujer de 4:1. El 97 % de los pacientes con reacción de tipo 2 presentó eritema nudoso.

Introduction: Colombia is the country in America with the highest proportion of new cases leprosy with severe disability. To decrease such disability it is necessary to control these reactions, the main cause of nerve damage in leprosy. Objective: To describe the clinical and epidemiological characteristics and the treatment of patients with type 1 and 2 leprosy reactions who consulted the Centro Dermatológico Federico Lleras Acosta. Materials and methods: It is a descriptive study which included patients with clinical diagnoses of type 1 and 2 reactions who were seen in the center between 2003 and 2009. The town of origin of the patients, their age, clinical features and treatments were analysed. Results: We studied 96 reactions in 87 patients, 35 type 1 and 61 type 2 reactions; 75% of the patients came from the departments of Tolima, Cundinamarca, Santander and Boyacá; 77% of type 1 reaction occurred before the beginning of multidrug therapy for leprosy. The reactions that started after stopping the multidrug therapy were considered as a leprosy relapse. Conclusions: Correct identification of type 1 reaction by the general practitioner will allow the diagnosis of leprosy in a large percentage of patients. The type 1 reaction that begins after stopping the leprosy multidrug therapy may be a manifestation of a relapse of the disease.

Revalidation of various clinical criteria for the classification of leprosy--a clinic-pathological study.

UNLABELLED: WHO guidelines classify leprosy patients clinically into PB and MB group based on the number of skin lesions (NSL) with > or = 6 skin lesions as a criterion for MB leprosy. Other clinical criteria for classification are based on the number of body areas affected (NBAA) and on size of the largest skin lesions (SLSL). They are also fairly simple and easily practicable in the field. OBJECTIVES: The objective of this study is to explore whether sensitivity and specificity of the WHO classification can be improved by addition of clinical criteria based on NBAA and SLSL to WHO classification. STUDY DESIGN: Among 100 newly diagnosed untreated leprosy patients classified into PB and MB group according to WHO classification, the NSL and NBAA were recorded and the size (longest diameter) of largest skin lesion was measured in centimeters. The Receiver Operator Characteristic (ROC) curves were plotted for each parameter to find the best cut off point (with highest sensitivity and specificity). RESULTS: The sensitivity and specificity of the WHO classification tested, using slit-skin smear (SSS) and skin biopsy results as the gold standard, was found to be 63% and 85% respectively. The ROC curve for NSL found the best cut off of three and more lesions for MB group (sensitivity 90% & specificity 80%). Similarly, ROC curves for NBAA and SLSL found the best cut off points for classification into MB group to be two or more (sensitivity 90% & specificity 75%) and 5 cm or more (sensitivity 87% and specificity 65%) respectively. On combining all these criteria together sensitivity was increased to 98.5% with no significant change in specificity, which was 77.5%. CONCLUSION: The study concluded that the sensitivity of the present clinical classification can be further improved by addition of two other clinical criteria.

Changes in the size and number of skin lesions in PB leprosy on treatment and follow-up.

BACKGROUND: The increase in size of existing skin lesions and appearance of new skin lesions are considered important signs of clinical activity both in untreated and treated leprosy. To confirm such activity, the number and size of lesions need to be recorded methodically prior to therapy and on follow-up, especially in PB leprosy where clinical signs alone define the reactivation of the disease. However, no systematic follow-up studies are available on changes in size and number of skin lesions in PB leprosy before and after therapy. OBJECTIVES: To measure changes in the number and size of skin lesions in PB leprosy patients before starting MDT PB and after 18 months follow-up in order to evaluate their relevance in assessing clinical improvement and identifying possible relapses. DESIGN: In 32 untreated leprosy patients with 1-5 skin lesions, the number of skin lesions were recorded on body charts and their size measured using a grid chart method to arrive at total area of involvement in each patient prior to starting MDT PB and after 18 months. Skin smears and skin biopsies were performed at entry and follow-up to assist the clinical evaluation. RESULTS: Twenty three patients had single skin lesion (SSL), followed by three each with two and three skin lesions respectively, two with four and one with five skin lesions. The area of involvement ranged from six to 1686 sq cm. Few patients with SSL had higher areas of involvement than those who had multiple skin lesions. On follow-up at 18 months, in 14 (44%) patients skin lesions were not measurable, while in 18 (56%) they were measurable, with eight (25%) patients showing no change, three (9%) showing decrease and seven (22%) showing increase in area of involvement. Of the seven patients showing increase, in three it was due to the spread of existing skin lesions alone, in one it was due to a new skin lesion alone and in three due to the spread of existing skin lesions and the appearance of new skin lesions. New skin lesions were multiple (> 3) in two patients. T1R was observed in three out of four patients with new skin lesions, and this was persistent at 18 months in one patient. When histopathology at the entry and 18 month follow-up was compared, in one patient with persistent T1R with appearance of multiple new skin lesions, there was increase in GF from 10 to 40% with histological features of T1R and a BI of granuloma of 1+. CONCLUSIONS: In 32 treated patients of PB leprosy on 18 month follow-up for changes in size and number of skin lesions, of six patients showing increase in area of involvement of existing skin lesions, 3 (50%) developed new skin lesions, indicating persistent disease activity. The new lesions which were associated with T1R increased the total number of skin lesions to > 5 in two of these patients requiring a change of drug regimen from PB to MB MDT, with one of them fulfilling clinical and histopathological criteria for relapse of leprosy. Hence, although new lesions are known to occur as part of T1R in PB patients, they are events of great significance which need to be assessed in a methodical manner for their influence on classification and therapy of leprosy.

Características epidemiológicas e clínicas das reações hansênicas em indivíduos paucibacilares e multibacilares, atendidos em dois centros de referência para hanseníase, na Cidade de Recife, Estado de Pernambuco / Characteristics of leprosy reactions in paucibacillary and multibacillary individuals attended at two reference centers in Recife, Pernambuco

INTRODUÇÃO: As reações são frequentes e importantes no contexto da hanseníase, representando uma significativa parcela de pacientes com incapacidades e submetidos ao retratamento da hanseníase. A caracterização clínico-epidemiológica dos padrões reacionais é primordial para o manejo dos pacientes. O objetivo desse trabalho é descrever as características epidemiológicas e clínicas das reações hansênicas em indivíduos paucibacilares e multibacilares. MÉTODOS: Estudo transversal onde foram avaliados 201 pacientes com história de quadro reacional, atendidos em dois centros de referência para tratamento da hanseníase. Variáveis como baciloscopia inicial, sexo, idade, fototipo, procedência, forma clínica, tipo de tratamento e de reação, índice baciloscópico final e período de surgimento da reação em relação ao tratamento foram avaliados. A análise estatística foi realizada usando-se frequências simples. Para cálculo dos fatores de risco para as formas multibacilares, foram realizadas análises univariada e multivariada. RESULTADOS: Sexo masculino, idade entre 30-44 anos, fototipo V, a forma clínica borderline, tratamento regular, reação tipo I, neurite, presença de 10 a 20 nódulos e surgimento da reação hansênica durante o tratamento foram os achados mais frequentes. CONCLUSÕES: Predominaram os indivíduos do sexo masculino que se associaram a um maior risco de desenvolvimento da forma multibacilar. As reações hansênicas foram mais frequentes durante o tratamento, os pacientes multibacilares foram mais propensos ao retratamento da hanseníase e aqueles com reações tipo I e II, apresentaram maior frequência de neurite, linfadenopatia, artrite e irite do que aqueles com reação isolada.

INTRODUCTION: Significant reactions frequently occur among leprosy cases, and thus a significant proportion of leprosy patients present disabilities and undergo leprosy retreatment. Clinical-epidemiological characterization of reaction patterns is essential for managing such patients. Objective to describe the epidemiological and clinical characteristics of leprosy reactions among paucibacillary and multibacillary individuals. METHODS: In this cross-sectional study, 201 patients with histories of reactions who were attended at two reference centers for leprosy treatment were evaluated. Variables such as initial bacilloscopy, sex, age, skin phototype, origin, clinical presentation, type of treatment, type of reaction, final bacilloscopy index and time of reaction onset in relation to the treatment were evaluated. Statistical analysis was performed using simple frequencies. To calculate risk factors for multibacillary forms, univariate and multivariate analyses were performed. RESULTS: Male sex, age between 30 and 44 years, phototype V, borderline clinical form, regular treatment, type I reaction, neuritis, presence of 10 to 20 nodules and onset of the leprosy reaction during the treatment were the most frequent findings. CONCLUSIONS: Male patients predominated and were associated with greater risk of developing the multibacillary forms. Leprosy reactions occurred most frequently during the treatment. Multibacillary patients were more likely to need leprosy retreatment, and those with type I and type II reactions presented greater frequency of neuritis, lymphadenopathy, arthritis and iritis than did those with isolated reactions.