Evaluation of nerve growth factor serum level for early detection of leprosy disability.

INTRODUCTION: this research aimed to analyze nerve growth factor (NGF) contents as diagnostic tools for early disability in leprosy patients and the cut-off point value. METHODS: research samples consisted of 79 leprosy patients with disability grade 0 or 1 who met the clinically approved inclusion criteria. The age of patients ranged from 14 to 50 years. For both sample groups, blood serum was collected to determine NGF concentration. NGF level was analyzed by enzyme-linked immunosorbent assay (ELISA) according to the manual guide of the kit insert from Cussabio®. Statistical analysis used SPSS 17 software for Windows. A comparison was performed with the Student's t-test and the NGF concentration cut-off point was determined using a receiver operating characteristic (ROC) curve. RESULTS: the research result demonstrated that NGF concentration in multibacillary leprosy with disability grade 0 was higher than in grade 1. Leprosy with disability grade 0 had an NGF content reaching 100.46 pg/mL, while those with grade 1 had a lower concentration of NGF at 30.56 pg/mL. The higher disability grade indicated a lower NGF concentration in the blood serum. Based on the ROC analysis result, the NGF cut-off was shown to be 81.43 pg/mL. This result indicated that low NGF in nerve and skin lesions of leprosy patients contributes to early peripheral nerve malfunction due to Mycobacterium leprae infection. CONCLUSION: these results prove that NGF can be used as a marker of early disability in leprosy, with the cut-off value at 81.43 pg/mL.

Clinical and Neurophysiological Features of Leprosy Patients with Neuropathic Pain.

Neural pain is a frequent symptom in leprosy disease. There is a paucity of data regarding neural pain diagnostics resulting in common prescriptive errors when neuritis is confused with neuropathic or mixed nociceptive-neuropathic pain. The present study identified important demographic, clinical, and neurophysiological features of 42 leprosy neuropathy patients presenting neuropathic pain (NP). During routine evaluations, patients were selected asking if they had ever experienced neural pain. Data analyses of their pain characteristics, clinical examination results, and both the Douleur Neuropathique 4 Questionnaire and Hamilton Depression Scale scores were used to classify these patients. The most common word they used to describe the sensation of pain for 25 (60%) of these patients was "burning." In the early stages of the disease and before leprosy diagnosis, 19 (45%) had already complained about NP and leprosy treatment was unable to prevent its occurrence in 15 (36%). Leprosy reactions, considered NP risk factors, occurred in 32 (76%) cases. Knowledge of typical NP characteristics could be used to develop more effective therapeutic approaches for a notoriously difficult-to-treat pain condition.

Heart rate variability in multibacillar leprosy: Linear and nonlinear analysis.

OBJECTIVE: To evaluate the heart rate variability (HRV) in patients with multibacillary leprosy using dynamic linear and nonlinear analysis. MATERIAL AND METHODS: Twenty-one leprosy patients (mean age: 39.14 ±10.58 years) and 21 healthy subjects (mean age: 36.24 ± 12.64 years) completed the sample. Heart rate variability recording was performed by a Polar RS800 CX heart monitor during a period of 15 min in the supine position and 15 min in a sitting position. Analysis of HRV was performed by frequency domain from high frequency (HF) and low frequency (LF) spectral indexes in absolute and normalized units. The nonlinear analysis of HRV was calculated using symbolic analysis (0V%, 1V%, 2LV% and 2UV% indexes), Shannon entropy (SE) and normalized complexity index (NCI). RESULTS: Linear analysis: both groups showed higher HF values (p < 0.05) and smaller LF values (p < 0.05) in supine than in sitting position. The leprosy patients showed higher LF values (p < 0.05) and smaller HF values (p < 0.05) compared to the controls on supine position. Symbolic analysis: leprosy patients had higher 0V% values (p < 0.05), smaller 2LV% values (p < 0.05) and 2UV % values compared to healthy subjects on both positions. The 1V % had higher values (p < 0.05) for leprosy patients than for controls in the sitting position. The control subjects had smaller 0V % values (p < 0.05), and higher 2UV % values (p < 0.05) in the supine position compared to the sitting position. Leprosy patients had higher 2UV index values (p < 0.05) in the supine position compared to the sitting position. In the complexity analysis, leprosy patients had smaller SE and NCI values (p < 0.05) than the control in the supine position. There was no difference between the SE and NCI values of leprosy and the control subjects in the sitting position. The control subjects had higher SE and NCI values (p < 0.05) in the supine position than in the sitting position. CONCLUSION: Leprosy patients had higher sympathetic modulation and smaller vagal modulation than controls, indicating less HRV and cardiac modulation with lower complexity. The control group displayed significant HRV differences in response to position changes while leprosy patients had fewer HRV differences after the same postural change. An analysis of HRV with linear and non-linear dynamics proved to be a reliable method and promising for the investigation of autonomic dysfunction in patients with multibacillary leprosy.

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.

Placas eritematosas hipoestésicas en paciente procedente de Brasil, un nuevo caso de lepra importada / Hypoaesthesic erythematous plaques in patients from Brazil, a new case of leprosy imported

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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.

Comparison between Different Methods of Monofilament Test in Multibacillary Leprosy.

BACKGROUND: Leprosy or Hansen's disease predominantly affects skin and peripheral nerves; therefore, can cause visible deformities from sensory and motor impairment. Early detection of sensory deficit has been of great benefit in a vigorous preventive role. OBJECTIVE: To compare the result of sensory evaluation in multibacillary leprosy (AB) patients using Semmes-Weinstein monofilament (SWM) and conventional monofilament technique used in Thailand and to observe the course of neuritis detected during the study period MATERIAL AND METHOD: MB patients from Hansen's clinic at the Department of Dermatology, Siriraj Hospital, and Leprosy clinic at Raj Pracha Samasai Institute were evaluated for sensory impairment using monofilament test by both SWM and conventional technique for two consecutive follow-up visits. The patients'demographic data, clinical and laboratory findings, and course of disease were recorded RESULTS: Seventy MB patients were enrolled Two-third of the patients were male (71.4%) and a mean (SD) age was 43 (15.75) years with a range of 19 to 85-years-old. The results from SWM and conventional Thai technique were not statistically different for ulnar median, and posterior tibial nerve distribution excluding heel area (p = 1.00). Twenty-eight (40%) patients who mentioned of numbness at either palms or soles had impaired sensation detected by SWMtechnique (p = 0.014). CONCLUSION: Using SWMwith less tested points can minimize the time spent on sensory evaluation in MB patients; hence, we encourage the application of the present SWM technique to shorten the time in each follow-up visit and to improve the follow-up practice for better services of leprosy patients in Thailand.

Facial sensory loss in multi-bacillary leprosy patients.

Sensation over the face was estimated using the Semmes-Weinstein's monofilament (target force 0-05 gms) in a cohort of multi-bacillary (MB) patients whose clinical and ocular characteristics were available at the time of leprosy diagnosis. Among the 190 MB patients examined, 56 (30%) had areas of sensory impairment somewhere on the face and 43 (23%) had sensory deficit over the lids and/or the malar area. Lagophthalmos (adjusted OR 8.96, 95% CI 0.96-83.50), Type 1 reaction (aOR 2.47, 95% CI 1.11-5-52), history of reactions (aOR 6.36, 95% CI 2.40-16.85) and glove and stocking anaesthesia (aOR 3.49, 95% CI 1-40-8.70) were associated with impaired facial sensation. Hypoesthesia restricted to areas over the lids and/or malar area showed a stronger association with lagophthalmos (aOR 17.5, 95% CI 1.98-154.36). Loss of facial sensation appears to be associated with lagophthalmos in MB patients.

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.

Effect of corticosteroid usage combined with multidrug therapy on nerve damage assessed using nerve conduction studies: a prospective cohort study of 365 untreated multibacillary leprosy patients.

The purpose of this study is to determine the extent of nerve involvement and to study the effect of corticosteroids combined with multidrug therapy on nerve damage in leprosy patients using sensory and motor nerve conduction studies. A cohort of 365 untreated multibacillary leprosy patients were prospectively studied using sensory and motor nerve conduction studies on upper and lower limb nerves. They were subgrouped as those to be treated with 12-week regimen of corticosteroids for reaction and/or neuritis or silent neuropathy of <6 months duration along with 12-month multidrug therapy (group A), and those with no reaction were treated with multidrug therapy only (group B). Analysis was performed using SPSS version 10.0. Significance of association was tested using chi(2) test. At registration, abnormality by nerve conduction studies was seen in 92% of patients and majority (65%) showing involvement of more than five sensory and motor nerves. Sensory nerve abnormalities were higher (52%) than motor (37%) (P < 0.001). Affection of sensory and motor nerves was higher in group A (P < 0.001). Notably, 40% nerves in group B also showed impairment at 0 month. This implies that almost all patients showed abnormal nerve conduction studies at onset regardless of reaction, proving nerve damage is more widespread than envisaged. At 18 months, overall percentile deterioration (23%) of nerves was higher than improvement (9%) (P < 0.001) indicating that corticosteroids combined with multidrug therapy failed to significantly improve the nerve status. Sensory nerve (57%) affection was significantly higher than motor (46%) (P < 0.001). Moreover, percentile deterioration of sensory nerves was higher in group A (P < 0.001) implying corticosteroids is not very efficacious in the prevention or reversal of nerve damage. Electrophysiological tests provide valuable information for detecting nerve function impairment and evaluating appropriate therapeutic regimens.

Hansen lepromatoso reaccional en un paciente pediátrico / No disponible

La lepra entre los niños es más frecuente de lo que se solía pensarse, sobre todo en lugares tropicales y subtropicales, como nuestro país. El hecho de que los síntomas iniciales de la lepra son muchas veces mal diagnosticados por pacientes y médicos, hace que el diagnóstico se establezca tardíamente, motivo por el cual el pediatra y dermatólogo deberían pensar en esta enfermedad para realizar de esta manera un diagnóstico precoz con el tratamiento específico. Se presenta el caso clínico de un niño de 13 años de edad con una forma multibacilar de lepra considerada poco frecuente en niños (AU)

Childhood leprosy is very frequent specially in tropical and subtropical areas, like our country. The fact is that initial symtoms are underestimated in routine examination and the diagnosis can pass unnoticed. The pediatricians and dermatologists should consider this disease to make an early diagnosis and to give the specific treatment . We present the case of a 13 year old child with multibacillar form of hansen’s disease, considered not usual in children (AU)

Lepra leucomelanodérmica / Leukomelanodermic leprosy

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