Cardiovascular events associated with thalidomide and prednisone in leprosy type 2 reaction.

BACKGROUND: Thalidomide is the drug of choice for the treatment of type 2 leprosy reactions and is often associated with corticosteroids. The use of these drugs in multiple myeloma is associated with the risk of cardiovascular events, but there have been few studies assessing this risk in leprosy patients. OBJECTIVE: To evaluate the occurrence of cardiovascular events in patients with multibacillary leprosy and their correlation with the use of thalidomide and prednisone. METHODS: Analytical cross-sectional study of all patients diagnosed with multibacillary leprosy treated at the Dermatology Service between 2012 and 2022, using electronic medical records. Thromboembolic vascular events, both arterial and venous, including acute myocardial infarction, were considered. The main independent variable was the concomitant use of thalidomide and prednisone during follow-up. RESULTS: A total of 89 patients were included, of which 19 used thalidomide and prednisone concomitantly. There were five cardiovascular events (26.3%), three of which of deep venous thrombosis. The combined use of medications was associated with the events (PR=6.46 [3.92 to 10.65]; p<0.01). STUDY LIMITATIONS: Small number of events, single-center retrospective study. CONCLUSION: The hypothesis of an association between cardiovascular events and the concomitant use of thalidomide and prednisone is supported, but more robust prospective studies are required for a better assessment.

Multibacillary leprosy with an incubation period exceeding 50 years.

Leprosy is a chronic granulomatous infection predominantly involving the skin and peripheral nervous system. The condition is caused by infection with the obligate intracellular bacillus Mycobacterium leprae and the clinical phenotype is largely dependent on the host immune response to the organism. Transmission is suspected to occur via respiratory secretions with infection usually requiring prolonged periods of contact. The incubation period is highly variable with disease manifestations appearing up to several decades after the initial exposure. The disease can be broadly divided into 'paucibacillary' and 'multibacillary', and treatment with multidrug therapy including dapsone, clofazimine and rifampicin offers high rates of cure. Here, we report of a case of leprosy with a suspected incubation period in excess of 50 years following occupational exposure in rural Australia. To our knowledge, this incubation period is the longest reported to date.

Descrição do seguimento farmacoterapêutico de pacientes com hanseníase em município hiperendêmico do estado de Mato Grosso / Pharmacotherapy follow-up of patients with leprosy in a hyperendemic city in the state of Mato Grosso

Introdução: A hanseníase é uma doença crônica, infectocontagiosa e considerada um problema de saúde pública no Brasil. O objetivo deste estudo foi descrever o seguimento farmacoterapêutico de pacientes com diagnóstico de hanseníase. Métodos: Estudo descritivo, com pacientes com hanseníase multibacilar do município de Rondonópolis, Mato Grosso. O seguimento farmacoterapêutico foi realizado a partir de uma versão adaptada do Método Dáder. Para análise de dados aplicou-se a estatística descritiva e o teste Qui-quadrado de Pearson.Resultados: Uma frequência de 95,6% dos participantes apresentou problemas relacionados aos medicamentos, 59,1% apresentaram 3 ou mais problemas, os mais frequentes foram administração errada do medicamento e interação medicamento/nutriente. A inefetividade não quantitativa foi o resultado negativo associado ao medicamento mais evidenciado. Os indivíduos acompanhados em um serviço especializado apresentaram menor número de problemas relacionados aos medicamentos quando comparados àqueles da Estratégia Saúde da Família (p = 0,027).Conclusão: A maioria dos pacientes acompanhados apresentou problemas relacionados ao uso de medicamentos. O método Dáder possibilitou realizar o seguimento farmacoterapêutico de indivíduos com hanseníase.

Introduction: Leprosy is a chronic, infectious, and contagious disease considered a public health problem in Brazil. The objective of this study was to describe the pharmacotherapy follow-up of patients diagnosed with leprosy. Methods: We conducted a descriptive study of patients with multibacillary leprosy in the city of Rondonópolis, state of Mato Grosso, Brazil. Pharmacotherapy follow-up was conducted based on an adapted version of the Dáder method. Data were analyzed using descriptive statistics and Pearson's chi-square test. Results: Drug-related problems (DRP) were reported in 95.6% of patients, among whom 59.1% had 3 or more problems DRPs. The most common DRPs were incorrect drug administration and drug-nutrient interaction. Nonquantitative ineffectiveness was the most common drug-related negative outcome. Patients monitored in a leprosy treatment center had fewer DRPs than those monitored by a Family Health Strategy team (p = 0.027). Conclusion: Most patients had DRPs. The Dáder method allowed pharmacotherapy follow-up of patients with leprosy.

Histoid leprosy presenting as a large tumor

Abstract Histoid leprosy is a rare form of multibacillary leprosy, characterized by the presence of papules, plaques, or nodules whose appearance is keloid-like, skin colored, or erythematous. Fusiform cells are the main histopathological feature. Due to the fact that it can simulate other dermatological lesions, for example, dermatofibroma and neurofibroma, it constitutes a diagnostic challenge for clinicians and pathologists. It is a bacilliferous form of leprosy, and it plays an important role in disease transmission. A case of a patient with histoid leprosy living in the Northeast Region of Brazil is reported.

Histoid leprosy presenting as a large tumor.

Histoid leprosy is a rare form of multibacillary leprosy, characterized by the presence of papules, plaques, or nodules whose appearance is keloid-like, skin colored, or erythematous. Fusiform cells are the main histopathological feature. Due to the fact that it can simulate other dermatological lesions, for example, dermatofibroma and neurofibroma, it constitutes a diagnostic challenge for clinicians and pathologists. It is a bacilliferous form of leprosy, and it plays an important role in disease transmission. A case of a patient with histoid leprosy living in the Northeast Region of Brazil is reported.

Frequent testicular involvement in multibacillary leprosy.

OBJECTIVE: Testicular involvement or atrophy in leprosy is silent, unreported, and under-estimated. The aim of this study was to assess the frequency of testicular atrophy and its consequences through the examination of clinical manifestations, hormonal profile, and semen analysis in leprosy patients. METHODS: A descriptive observational study using a cross-sectional design and consecutive sampling method was conducted from May to July 2018. The study was conducted in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia and included 32 men affected by leprosy and five healthy men as a control group. All patients were subjected to history-taking, dermatological and genital examinations, assessment of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, and testicular ultrasonography examination. Semen analysis was performed for the 10 patients who consented. RESULTS: Testicular atrophy was observed in 93.75% of patients. Clinical manifestations of testicular atrophy were loss of libido (21.87%), female pubic hair pattern (9.38%), gynecomastia (6.25%), and secondary infertility (6.25%). Hormonal imbalance was seen in 16 patients, and all 10 patients who underwent semen analysis showed an abnormality. CONCLUSIONS: This study showed a high frequency of testicular atrophy, but the symptoms were only present in a few of patients. The assessment of testicular function should be recommended as a routine work-up for leprosy patients.

Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy.

INTRODUCTION: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. OBJECTIVES: To determine whether epidemiological, clinical and immunological factors played a role in the long-term persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. METHODS: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-ß2 glycoprotein I (anti-ß2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. RESULTS: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-ß2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. CONCLUSION: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

Effectiveness of the retreatment of patients with multibacillary leprosy and episodes of erythema nodosum leprosum and/or persistent neuritis: a single-center experience

Abstract: Background: Erythema nodosum leprosum may appear before, during or after treatment of leprosy and is one of the main factors for nerve damage in patients. When it occurs or continues to occur after treatment, it may indicate disease recurrence and a new treatment may be instituted again. Objective: To evaluate the retreatment of patients with multibacillary leprosy who underwent standard treatment with multidrug therapy, but developed or continued to present reactions of erythema nodosum leprosum and/or neuritis 3-5 years after its end. Method: For this objective, a new treatment was performed in 29 patients with multibacillary leprosy who maintained episodes of erythema nodosum and/or neuritis 3-5 years after conventional treatment. Results: In general, we observed that 27 (93.10%) had no more new episodes after a follow up period of eight months to five years. In five of these patients the reason for the retreatment was the occurrence of difficult-to-control neuritis, and that has ceased to occur in all of them. Study limitations: Small number of patients.. Conclusion: In the cases observed, retreatment was an effective measure to prevent the occurrence of erythema nodosum leprosum and/or persistent neuritis.

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

[Leprosy in children in the region of Thiès, Senegal: study determining whether or not it is a signal of recrudescence]. / La lèpre de l'enfant à Thiès/Sénégal: signal d'une recrudescence?

Leprosy is an infectious and transmissible disease. According to the WHO, the number of new cases of leprosy in children in Senegal has risen moderately since 2013. This study aimed to analyze the epidemiological, clinical, therapeutic and evolutionary features of leprosy in children in the geographical areas of two social rehabilitation villages in the region of Thiès. We conducted a retrospective study over a period of 3 years (2013-2015). All new cases of Hansen's disease aged 0 -15 years were included. Over the three year period, 39 children were included in the study, with a boy predominance (n=23, 59%). Among these children, 27 (66.7%) came from a social rehabilitation village for leprosy patients. One family member was affected by leprosy in 27 cases (69.2%). More than half of the children (23 cases, 58.9%) had multibacillary leprosy (lepromatous-lepromatous). All children underwent a 12-month treatment, at the end of which thirty-six (92.3%) children were healed. Leprosy is still present in Senegal despite the efforts made by the national programme to combat leprosy. In the light of these results, it is important to emphasize the role of active screening strategy targeted to children, which seems to have shown its effectiveness in the region. Early detection, contact tracing and early treatment are important factors in the reduction of the contagiousity of leprosy.

Bullous Erythema Nodosum Leprosum as the First Manifestation of Multibacillary Leprosy: A Rare Phenomenon.

Erythema nodosum leprosum (ENL) may uncommonly present before treatment in patients with multibacillary leprosy. Atypical manifestations are known in ENL and may be clinically misleading. Such wide variations in the clinical presentation of leprosy in reaction make histopathology an important tool for supporting clinical diagnosis. We report bullous ENL presenting as the first manifestation of leprosy in a 30-year-old Indian man diagnosed using histopathology.

Leprosy treatment during pregnancy and breastfeeding: A case report and brief review of literature.

Leprosy is a chronic disease which primarily affects the skin, mucous membranes and peripheral nerves due to Mycobacterium leprae. It is now infrequent in Europe and is rarely reported during pregnancy. Leprosy can be exacerbated during pregnancy, and without treatment it can permanently damage the skin, nerves, limbs and eyes. Therefore, it is important to treat leprosy during pregnancy. This article describes a patient with multibacillary lepromatous leprosy who was treated with multidrug therapy during pregnancy and breastfeeding. The patient delivered a healthy baby girl without perinatal complications, and the infant's growth and development were normal during the 1-year follow-up period. Multidrug therapy consisting of dapsone, rifampicine, and clofazimine is highly effective for people with leprosy and considered safe, both for the mother and the child. Antileprosy drugs are excreted into human milk but there is no report of adverse effects except for skin discoloration of the infant due to clofazimine. Multidrug therapy for leprosy patients should be continued unchanged during pregnancy and breastfeeding.

Type 2 leprosy reaction with Sweet's syndrome-like presentation

Abstract Leprosy is a chronic disease characterized by manifestations in the peripheral nerves and skin. The course of the disease may be interrupted by acute phenomena called reactions. This article reports a peculiar case of type 2 leprosy reaction with Sweet's syndrome-like features as the first clinical manifestation of leprosy, resulting in a delay in the diagnosis due to unusual clinical presentation. The patient had clinical and histopathological features reminiscent of Sweet's syndrome associated with clusters of vacuolated histiocytes containing acid-fast bacilli isolated or forming globi. Herein, it is discussed how to recognize type 2 leprosy reaction with Sweet's syndrome features, the differential diagnosis with type 1 leprosy reaction and the treatment options. When this kind of reaction is the first clinical presentation of leprosy, the correct diagnosis might be not suspected clinically, and established only with histopathologic evaluation.

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.

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.

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.

Correlation between Central Memory T Cell Expression and Proinflammatory Cytokine Production with Clinical Presentation of Multibacillary Leprosy Relapse.

BACKGROUND: Despite the efficacy of multidrug therapy, surviving Mycobacterium leprae causes relapse in some leprosy patients, and these patients present signs and symptoms of disease after healing. This study focused on the cellular immune response in relapsed multibacillary patients but also included non-relapsed multibacillary cured individuals, newly diagnosed and untreated multibacillary patients, paucibacillary patients just before the beginning of treatment, and voluntary healthy individuals for comparative analysis. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of CD86 expression in the blood-derived monocytes and dendritic cells of relapsed multibacillary patients, either ex vivo or after M. leprae antigen stimulation was observed by flow cytometry. In addition, no significant changes in Interferon-gamma (IFN-g) expression were observed in 5-day culture supernatants of relapsed patients in response to M. leprae, neither before nor after treatment, as measured by ELISA. However, these patients demonstrated a significant increase in central memory CD4+ and CD8+ M. leprae-specific T cells, as assessed by multiparametric flow cytometry. The increase in frequency of central memory T cells in relapsed patients strongly correlated with the bacillary index and the number of skin lesions observed in these subjects. Moreover, cytokine multiplex analysis demonstrated significant antigen-specific production of Interlukin-1beta (IL-1b), IL-6, and Tumour Necrosis Factor (TNF) in the relapsed group with extremely low IL-10 production, which resulted in a high TNF/IL-10 ratio. CONCLUSIONS/SIGNIFICANCE: Inhibition of CD86 expression may function to reduce effector T cell responses against the M. leprae antigen. Furthermore, the predominance of central memory T cells in association with the high TNF/IL-10 ratio and no observed IFN-g production may be related to the pathogenesis of relapse in multibacillary leprosy. Therefore, our findings may be a direct result of the clinical presentation, including a number of skin lesions and bacterial load, of relapsed patients. To our knowledge, this is the first study correlating immune response parameters with the clinical presentation of relapsed multibacillary patients.