Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases.

After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This "polarization" of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes. Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy.

Reacciones lepromatosas en pacientes adultos y pediátricos en un centro de referencia. Programa Nacional de Lepra, Paraguay / Lepromatous reactions in adults and pediatric outpatients in a reference center. National Lepra Program, Paraguay

Introducción la lepra, llamada también enfermedad de Hansen, es una afección de la piel y de los nervios periféricos, infectocontagiosa, causada por Mycobacterium leprae. Las reacciones lepromatosas se presentan aún con tratamiento y son expresiones de respuesta inmunitaria. Conocerlas es importante a fin de facilitar el abordaje. Objetivo determinar la frecuencia y tipo de reacciones lepromatosas en pacientes con diagnóstico de lepra que acuden al centro de referencia de Enfermedad de Hansen en el Hospital Distrital de San Lorenzo, de enero 2013 a diciembre 2015. Metodología observacional, descriptivo, retrospectivo de corte transverso. Resultados se incluyeron 217 pacientes, 72% presentaban lepra MB y 63% era de sexo masculino. La prevalencia de reacción lepromatosa fue 44%, siendo más frecuentes las de tipo 2 (65%). Se presentó reacción lepromatosa como debut de la enfermedad en 27 %. Treinta y tres pacientes presentaron de tres a doce episodios de reacción lepromatosa. El tratamiento fue talidomida y corticoides. Conclusiones la prevalencia de leprorreacciones fue cercana al 50%, predominando las de tipo 2. El tratamiento utilizado fue talidomida y/o corticoides dependiendo del tipo de reacción lepromatosa.

Introduction leprosy, wich is cause by Mycobacterium leprae, also known as Hansen's Disease, affects skin and peripheral nerves. Lepromatous reactions (LRs) are expressions of an immune reaction and remain as a major persistent problem. LRs are present even with appropriated treatment. Emphasis must be made in early diagnosis and prevention of the catastrophic consequences of LRs. Objective to determine the frequency and type of lepromatous reactions in leprosy patients with leprosy attending to reference center of Hansen´s Disease in the District Center Hospital in San Lorenzo, from January 2013 to December 2015. Methodology observational, retrospective cross sectional study. Results 217 patients were included, 72% with multibacillary leprosy. 63% were male. Lepromatous reactions were found in 44%, been more frequent Type II reaction, in 65% of cases. LRs as oset disease occurred in 27%. 33 patients presented from 3 to 12 episodes of lepromatous reaction. The number of LRs episodes per patient were 3 to 12. Thalidomide was used as treatment in Erithema Nodosum Leprosum (ENL) and corticosteroids for the other types de LRs. Conclusions prevalence of PRs were 50%, been more frecuent the type II. Reaction the treatment used was Thalidomide and/or corticosteroids depending on the type of lepromatosus reaction.

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

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.

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.

Perfil de citocinas séricas en la Lepra y su correlación con el perfil clínico-histopatológico / No disponible

Objetivos: Analizar las citocinas y sus niveles séricos en los pacientes de lepra para correlacionarlo con el perfil clínico-histopatológico y evaluar el efecto de la multiterapia estándar sobre el perfil citocínico sérico. Metodología: Se realizaron inmunoensayos (ELISA) séricos para determinar la TNF-α, IFN-γ, IL-1β e IL-10 en 61 nuevos casos de lepra antes de iniciar la terapia y durante los episodios reaccionales. De ellos, los ensayos para citocinas pudieroncompletarse en 17 casos al finalizar la multiterapia. Resultados: Los niveles de todas las citocinas analizadas estaban significativamente elevadas en los casos comparados con controles (P < 0·05). Los niveles de TNF-α e IFN-γ estaban significativamente elevados en los paucibacilares, mientras que todas las citocinas analizadas lo estaban en los casos multibacilares con los incrementos en IL- 1β e IL-10 siendo incluso estadísticamente significativos (P < 0·001). No se detectaron diferencias significativas entre los tipos TT y BT y los BB, BL y LL. Todas las citocinas estudiadas estaban incrementadas en las fases reaccionales en comparación con las no reaccionales. Al comparar la reacción Tipo 2 (T2R) y la reacción Tipo 1 (T1R), los niveles de IFN-γ, IL-1β e IL-10 eran más elevadas en casos T2R, pero solo en el caso de IL-10 era estadísticamente significativa (P = 0·05), mientras que la TNF-α era mayor en los casos T1R. Los niveles séricos post-tratamiento de las citocinas era significativamente menor (P < 0·05) que los niveles pretratamiento y resultó comparable a los valores de los controles. Entre los casos paucibacilares, todas las citocinas disminuyeron a los 6 meses de tratamiento con la multiterapia estándar. En los multibacilares, los niveles promedio de las citocinas disminuyeron al año de finalizar la multiterapia, excepto IFN-γ. Conclusión: el análisis de las citocinas séricas puede desempeñar un papel significativo en la clasificación de las distintas formas de lepra y puede utilizarse para controlar la multiterapia (AU)

Objectives: To analyse the serum levels of cytokines in leprosy patients, to correlate them with clinico-histopathological profile, and to study the effect of standard multidrug therapy on serum cytokine levels. Design: Serum immunoassays of TNF-α, IFN-γ, IL-1β and IL-10 were performed by ELISA in 61 newly diagnosed cases of leprosy before starting therapy and during reactional episodes. Of these, cytokine assays could be performed in 17 cases after completion of therapy. Results: Levels of all the studied cytokines were significantly raised in casescompared to controls (P < 0·05). Levels of TNF-α and IFN-γ were significantly raised in paucibacillary cases whereas all the studied cytokines were raised in multibacillary cases with rise in IL-1β and IL-10 being statistically significant (P < 0·001). No significant difference was however noted between TT and BT type; and BB, BL and LL types. All the studied cytokines were raised in reactional cases as compared to non-reactional cases. Comparing Type 2 reaction (T2R) and Type 1 reaction (T1R) cases, levels of IFN-γ, IL-1β and IL-10 were higher in T2R cases but only IL-10 was found to be statistically significant (P = 0·05) while TNF-α was higher in T1R cases. Post therapy serum levels of all the studied cytokines were significantly lower than pretherapy levels (P = 0·05) and were comparable to controls. Among the paucibacillary cases, levels of all the cytokines were seen to decrease after 6 months of standard multidrug therapy. In the multibacillary cases, mean levels of the cytokines were found to decrease after 1 year of therapy except IFN-γ. Conclusion: Serum cytokine estimation may have a significant role in classifying various forms of leprosy and can be used to monitor therapy (AU)

Nerve conduction studies in paucibacillary and multibacillary leprosy: a comparative evaluation.

Involvement of peripheral nerves in patients with leprosy results in sensory, motor and autonomic dysfunctions along with deformities and disability. Pattern of nerve involvement is different for different forms of leprosy. In this study, we evaluated and compared the nerve conduction parameters of paucibacillary leprosy with that of multibacillary leprosy. In this study, 40 consecutive patients of leprosy (19 cases of paucibacillary and 21 cases of multibacillary leprosy) were included. Nerve conduction studies were performed according to the standard procedure described in the manual of the machine. We observed that patients with multibacillary leprosy had significantly more severe changes in nerve conduction parameters as compared to that of paucibacillary leprosy. In paucibacillary leprosy, the dominant pattern of nerve involvement was that of mononeuropathy, however, in 6 paucibacillary cases the nerve involvement was in form of mononeuritis multiplex. Electrophysiological assessment also revealed involvement of clinically uninvolved nerves. Nerve conduction parameters were suggestive of mixed axonal as well as demyelination of the peripheral nerves.

Leprosy: down but not out.

Leprosy is a chronic disabling disease and there are areas of high endemicity in India. Case findings and management strategies suffer a setback when disease manifestations are not picked up in time by health-care providers. This article attempts to estimate the annual incidents of leprosy and to study the confounding factors which may potentially cause delays in diagnosis in an office-based, tertiary health-care setting.