Case Report: Borderline Lepromatous Leprosy Therapy Complicated by Type 1 Leprosy Reaction and Adverse Reactions with Dapsone and Clofazimine.

Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is often challenging, especially in nonendemic areas. Here, we report a case of borderline lepromatous leprosy accompanied by dapsone-induced (neutropenia, anemia, and methemoglobinemia) and clofazimine-induced (skin discoloration and ichthyosis) side effects and type 1 leprosy reactions during administration of the multidrug therapy. The patient completely recovered without developing any deformities or visual impairment. To ensure early diagnosis and a favorable outcome, clinicians should be aware of the diminished sensation of skin lesions as a key physical finding and manage the drug toxicities and leprosy reactions appropriately in patients on multidrug therapy.

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.

Comparison between lymecycline with multidrug therapy and standard multidrug regimen (WHO-MDT) in the treatment of multibacillary leprosy patients: a retrospective cohort study.

BACKGROUND: Hansen's disease or leprosy is a chronic, infectious disease that has locally and globally afflicted all populations. Despite standard treatment with multidrug therapy (WHO-MDT), the incidence of drug resistance has been an increasingly prevalent global problem in leprosy management. This study compared the effectiveness between lymecycline with WHO-MDT and standard WHO-MDT in leprosy treatment. METHODS: The research is a retrospective cohort study at a tertiary hospital from January 2011 to July 2021. Pre- and post-treatment bacillary index, presence of new lesions, nerve function impairment, and leprosy reactions were obtained through chart review. RESULTS: The results showed a significant difference in bacteriological index (BI) in both groups at the end of the treatment. However, a higher reduction in BI was noted for the lymecycline group. For the group that took WHO-MDT alone, BI decreased by 0.7 (P < 0.001) whereas patients who took lymecycline and WHO-MDT had a BI difference of 3 (P < 0.001) upon completion of treatment. A significant decrease in the recurrence of lesions (P = 0.006) and nerve function impairment (P = 0.038) was also noted in the lymecycline group whereas there was no significant difference in leprosy reactions between the two groups. CONCLUSION: Lymecycline 600 mg daily for 3 months can be used as an adjunct in cases of leprosy resistance and treatment failure among multibacillary patients. Lymecycline significantly reduced bacillary index, recurrence of skin lesions, and nerve function impairment through its possible immunomodulatory, antiapoptotic, and neuroprotective effects.

Seventy years of evidence on the efficacy and safety of drugs for treating leprosy: a network meta-analysis.

OBJECTIVE: The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations. METHOD: All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score. RESULTS: Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens. CONCLUSIONS: The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction. AVAILABILITY OF DATA AND MATERIALS: All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Efficacy of fixed duration multidrug therapy for the treatment of multibacillary leprosy: A prospective observational study from Northern India.

BACKGROUND: In endemic regions of several countries, the prevalence of leprosy has not come down to the level of elimination. On the contrary, new cases are being detected in large numbers. Clinically, it is frequently noted that despite completion of multibacillary multidrug therapy for 12 months, the lesions remain active, especially in cases with high bacteriological indices. AIM: The present study focused on finding out the viable number of Mycobacterium leprae during the 12-month regimen of multibacillary multidrug therapy, at six and 12 months intervals and, attempting to determine their role in disease transmission. METHODS: Seventy eight cases of multibacillary leprosy cases were recruited from leprosy patients registered at The Leprosy Mission hospitals at Shahdara (Delhi), Naini (Uttar Pradesh) and Champa (Chhattisgarh), respectively. Slit skin smears were collected from these patients which were transported to the laboratory for further processing. Ribonucleic acid was extracted by TRIzol method. Total Ribonucleic acid was used for real-time reverse transcription-polymerase chain reaction (two-step reactions). A standard sample with a known copy number was run along with unknown samples for a reverse transcription-polymerase chain reaction. Patients were further assessed for their clinical and molecular parameters during 6th month and 12th month of therapy. RESULTS: All 78 new cases showed the presence of a viable load of bacilli at the time of recruitment, but we were able to follow up only on 36 of these patients for one year. Among these, using three different genes, 20/36 for esxA, 22/36 for hsp18 and 24/36 for 16S rRNA cases showed viability of M. leprae at the time of completion of 12 months of multidrug therapy treatment. All these positive patients were histopathologically active and had bacillary indexes ranging between 3+ and 4+. Patients with a high copy number of the Mycobacterium leprae gene, even after completion of treatment as per WHO recommended fixed-dose multidrug therapy, indicated the presence of live bacilli. LIMITATIONS: Follow up for one year was difficult, especially in Delhi because of the migratory nature of the population. Patients who defaulted for scheduled sampling were not included in the study. CONCLUSION: The presence of a viable load of bacilli even after completion of therapy may be one of the reasons for relapse and continued transmission of leprosy in the community.

Gene expression patterns associated with multidrug therapy in multibacillary leprosy.

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

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.

Lucio's phenomenon: A systematic literature review of definition, clinical features, histopathogenesis and management.

Leprosy is a chronic disease with clinical presentations according to the immunologic spectrum. Lepromatous form is the most advanced, with the highest transmissibility and risk of causing disabilities. Lucio's phenomenon is a rare manifestation among lepromatous patients with a rapid and severe evolution and high mortality. It is difficult to differentiate from ulcerative/necrotic erythema nodosum leprosum and has no consensus on how it should be treated. This article is a qualitative review of the literature after the introduction of multidrug therapy, aiming to bring consensus related to the clinical, laboratory and histopathological diagnostic criteria of the disease and its management.

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.

Disability progression among leprosy patients released from treatment: a survival analysis.

BACKGROUND: Leprosy can be cured, but physical disability (PD) as a result of the infection can progress in the post-release from treatment phase. This study evaluated the likelihood of, and factors associated with, the progression of the PD grade post-release from treatment among leprosy patients treated in Cáceres-MT, Brazil in the period 2000 to 2017. METHODS: A retrospective cohort study and survival analysis were performed in the hyperendemic municipality of Cáceres in the state of Mato Grosso. The study population consisted of newly diagnosed leprosy patients released from treatment between January 1, 2000 and December 31, 2017. The main outcome was the progression of the PD grade with regard to probability and time; and the evaluated covariates included clinical, operational and demographic variables. The Cox proportional risk model was used to estimate the risk ratio (Hazard Ratios) of the covariates. Both an univariate and a multivariate analysis were implemented, with 95% confidence intervals. RESULTS: The mean time for progression of the PD grade was 162 months for PB and 151 months for MB leprosy patients. The survival curve showed that 15 years after the release from treatment, the probability of PD grade progression was 35%, with no difference between PB and MB or age groups. Leprosy reactions and registered medical complaints of any kind during treatment were identified as risk factors with Hazard Ratios of 1.6 and 1.8 respectively. CONCLUSIONS: People released from treatment as cured of leprosy are susceptible to worsening of the PD, especially those who have had complications during multi-drug therapy treatment. This indicates that leprosy patients should be periodically monitored, even after the successful completion of multidrug therapy.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Utility and limitations of serodiagnostic tests in monitoring the response to treatment of leprosy patients.

Simple measures that can facilitate early recognition of leprosy complications are still lacking. We therefore evaluated a lateral flow-based rapid diagnostic test and fast enzyme-linked immunosorbent assay measuring anti-LID-NDO antibody responses among leprosy cases in Cebu, Philippines. Responses were measured at diagnosis, then during and after the provision of standard multidrug therapy. Our data indicate that both platforms are highly sensitive tools for the primary diagnosis of, in particular, multibacillary leprosy. A gradual, quantifiable decline in both magnitude of response and percent positive responders was observed during and after treatment. As a group, patients that developed erythema nodosum leprosum (ENL) had a significantly higher response at diagnosis than patients that either developed reversal reactions or did not develop reactions. Although higher initial anti-NDO-LID responses were a risk factor for ENL, neither platform, however, could reliably predict the time of emergence of reactional episodes.

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.