Dermatoscopic evaluation of leprosy: A multi-centre cross-sectional study.

Background Leprosy is known to be a great mimicker. Its dermatoscopic evaluation may be of value in establishing diagnosis. Objective To study the dermatoscopic findings encountered across the leprosy spectrum. Methods This was a multi-centre cross-sectional study of leprosy patients, where after a thorough cutaneous and neurological evaluation, representative skin lesions from the study patients were photographed in standard settings, and the most representative skin lesions were chosen for dermatoscopic evaluation. Data was entered in a structured proforma and a descriptive analysis of dermatoscopic patterns was carried out. Results A total of 53 cases of ages between 14 and 80 years, ranging from tuberculoid to the lepromatous spectrum of disease, with active skin lesions in the form of patches and plaques were included. The spectrum of leprosy as per Ridley-Jopling classification at diagnosis was indeterminate in 1 (1.9%), tuberculoid in 1 (1.9%), borderline tuberculoid in 25 (21.5%), borderline lepromatous in 9 (17%), lepromatous in 14 (26.4%) and histoid in 3 (5.7%). Dermatoscopic features included distorted pigment network in 48 (90.6%), focal white areas in 40 (75.5%), reduced eccrine and follicular openings in 43 (81.1%), widened skin lines in 28 (52.8%), circle hairs in 15 (28.3%) and white shiny streaks in 17 (32.1%). Conclusion Dermatoscopy is a practical, non-invasive device to assess skin lesions of leprosy and provide cues to its diagnosis, spectral classification and differentiating it from other granulomatous disorders. However, dermatoscopy alone cannot reliably differentiate between the various types of leprosy and future large-scale studies are required. Limitations of the study The numbers for each subtype were variable and few in some spectrum of leprosy patients. A dermatoscopic-histologic correlation was not done.

Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.

Audiological Evaluation of Leprosy Patients in an Endemic Area of Central India: A Case-Control Pilot Study.

There are discrepancies in the literature about the specific influence of leprosy on auditory functions. In routine clinical practice regular hearing screening of leprosy patients is not done. Due to conflicting reports of auditory system involvement in the literature, we conducted this case control study to evaluate the need of regular hearing screening in leprosy patients. A complete otological examination of thirty leprosy patients was conducted. Thirty age and sex matched healthy individual attending ear, nose and throat outpatient department were enrolled as control. Ten cases (33.3%) out of the thirty leprosy patients were found to have high frequency (4 and 8 kHZ) sensorineural hearing loss. The results of this study suggest that leprosy patients require routine monitoring for auditory functions for early identifications of sensorineural hearing loss. As our study is a case-control study with small sample size, in future large prospective studies are required to evaluate the correlation of hearing loss with leprosy and to see the progression hearing loss. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04381-1.

Should prophylaxis against Pneumocystis jirovecii pneumonia be considered in selected patients with leprosy reactions?

Leprosy reactions often require prolonged high-dose steroids or immunosuppressive drugs, putting patients at risk of Pneumocystis jirovecii pneumonia (PJP). However, no PJP cases are reported, possibly due to dapsone treatment for leprosy. In patients with leprosy reactions not receiving dapsone because of toxicity or resistance and requiring long-term immunosuppression, PJP prophylaxis should be considered.

Analysis of interleukin 7 and platelet-derived growth factor-BB mRNA expression as potential markers in erythema nodosum leprosum.

Erythema nodosum leprosum (ENL) is an immunological complication of leprosy characterized by acute inflammation of the skin, nerves, and other organs. Identifying laboratory parameters is important for early diagnosis of leprosy reactions. Various cytokine biomarkers have been examined and only a few studies have reported on angiogenesis in leprosy. This study aims to understand the pathomechanism of ENL by examining IL-7 and platelet-derived growth factor (PDGF)-BB mRNA expression that can be the development and consideration of new effective therapies to prevent reactions, recurrences, and defects in leprosy. The study used a cross-sectional analytic design. Sampling was done by peripheral blood from the patient and measuring mRNA expression with specific primers RT-PCR. The expression of mRNA IL-7 and PDGF-BB was significantly different between multibasilar patients without reaction and with ENL reaction, where there was an increased expression in ENL patients. This could be used as the development of potential biomarkers in ENL and development of new therapeutic intervention pathways in ENL.

Backward logistic regression analysis of the determinants of the hand function among patients with leprosy: A cross-sectional study.

Introduction: The hands are the most common site of disability in leprosy. Hand dysfunction could result in difficulty performing activities of daily living. Therefore, hand function should be regularly assessed to ensure that any decrease in hand function could be diagnosed earlier. Methods: This study included 110 patients with leprosy from Likupang and Lembata, Indonesia. Hand function was assessed using the modified Jebsen test to measure hand function respective of the dominance. The grip and pinch strength were used as objective measures of clinical arm function. The World Health Organization (WHO) hand disability grade were used to determine the degree of impairment. Other factors such as age, sex and the type of leprosy were also considered. All factors were analysed using backward logistic regression. Results: Among the 110 participants, a decrease in the dominant (48.2%) and non-dominant (50.9%) hand functions were found. Pinch strength (OR: 3.39; 95% CI: 1.13-10.19) and age (OR: 4.91; 95% CI: 1.72-14.03) were significantly associated with hand function irrespective of the dominance. Conversely, the WHO hand disability grade (OR: 2.97; 95% CI: 1.10-8.04) and type of leprosy (OR: 0.34; 95% CI: 0.12-0.97) were significantly associated with only function of the dominant hand. Conclusion: There is a significant association of age and pinch strength with hand function regardless of the hand dominance. In contrast, the WHO hand disability grade and type of leprosy are significantly associated with the function of the dominant hand only.

Effectiveness of Sensitization Campaigns in Reducing Leprosy-Related Stigma in Rural Togo: Protocol for a Mixed Methods Cluster Randomized Controlled Trial.

BACKGROUND: In the global strategy to eliminate leprosy, there remains a need for early case detection to successfully interrupt transmissions. Poor knowledge about leprosy and leprosy-related stigma are key drivers of delayed diagnosis and treatment. Sensitization campaigns to inform and increase awareness among the general population are an integral part of many national neglected tropical disease programs. Despite their importance, the effectiveness of such campaigns has not been rigorously studied in the West African context. A multilingual rural setting with low health literacy in this region presents challenges to the potential impact of sensitization campaigns. OBJECTIVE: The primary objective of this study is to assess the causal effect of common practice community sensitization campaigns on leprosy-related knowledge and stigma at the community level and among community health volunteers. Additionally, we will test the potential of novel educational audio tools in the 15 most prominent local languages to overcome literacy and language barriers and amplify sensitization campaigns. METHODS: We will conduct a cluster randomized controlled trial using a sequential mixed methods approach in 60 rural communities across all regions of Togo, West Africa. The study features 2 intervention arms and 1 control arm, with intervention and control assignments made at the community level through randomization. Communities in intervention arm 1 will receive a sensitization campaign in line with the current Togolese national neglected tropical disease program. Communities in intervention arm 2 will receive the same sensitization campaign along with educational audio tools distributed to community households. The control arm will receive no intervention before data collection. Quantitative outcome measures on knowledge and stigma will be collected from a random sample of 1200 individuals. Knowledge will be assessed using the 9-item standardized Knowledge, Attitudes, and Practices Questionnaire. Stigma will be measured using the 7-item Social Distance Scale and the 15-item Explanatory Model Interview Catalogue Community Stigma Scale. We will estimate intention-to-treat effects at the individual level, comparing the outcomes of the intervention and control arms. In an accompanying qualitative component, we will conduct in-depth interviews with community members, community health volunteers, and health care workers in both treatment arms and the control arm to explore intervention and stigma-related experiences. RESULTS: This paper describes and discusses the protocol for a mixed methods cluster randomized controlled trial. Data collection is planned to be completed in June 2024, with ongoing data analysis. The first results are expected to be submitted for publication by the end of 2024. CONCLUSIONS: This trial will be among the first to test the causal effectiveness of community-based sensitization campaigns and audio tools to increase knowledge and reduce leprosy-related stigma. As such, the results will inform health policy makers, decision-makers, and public health practitioners designing sensitization campaigns in rural multilingual settings. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029355; https://drks.de/search/en/trial/DRKS00029355. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52106.

Unmasking the Hidden Burden: A Delayed Diagnosis of Leprosy Patients With Grade 2 Disability and Its Effects on the Healthcare System in Bangladesh.

Introduction Leprosy remains a significant cause of preventable disability worldwide. Early diagnosis and treatment of leprosy are critical not only to stop its spread but also to prevent physical and social complications and reduce the disease burden. Objectives The study aims to evaluate the factors that lead to a delayed leprosy diagnosis. Methods This study was conducted in the outpatient departments of Leprosy Control Institute and Hospital, Dhaka, Bangladesh, and at Medical College for Women and Hospital, Dhaka, Bangladesh, from March 2023 to June 2023. A total number of 252 male (148) and female (104) patients were selected with any sign of leprosy, including disability, age ranging from 15 to 74 years. Data was collected in a pre-designed structured questionnaire by the researchers. To assess the risk of independent exposures of Grade 2 leprosy disabilities, we used a logistic regression model. A chi-square test showed the association between significant effects and leprosy disabilities. A p-value of 0.05 was considered as significant. For statistical analysis, STATA version 15 (StataCorp LLC, College Station, Texas, USA) was used. Results The study participants exhibited a higher percentage of disability, with a rate of 25.8% for Grade 2 disabilities. In addition to this, males represented a more considerable proportion, 58.7%, than females among leprosy and disability patients across all levels of disability. In our study, lack of money and painless symptoms showed a significant association (p<0.001) with Grade 2 disability. Conclusion The study reveals that Grade 2 disabilities are more common in males and are particularly prevalent in lower socioeconomic groups.

The role of CXCL10 as a biomarker for immunological response among patients with leprosy: a systematic literature review.

Introduction: Involvement of a chemokine known as C-X-C motif chemokine ligand 10 or CXCL10 in the immunopathology of leprosy has emerged as a possible immunological marker for leprosy diagnosis and needed to be investigate further. The purpose of this systematic review is to assess CXCL10's potential utility as a leprosy diagnostic tool and evaluation of therapy. Methods: This systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. A thorough search was carried out to find relevant studies only in English and limited in humans published up until September 2023 using PubMed, Scopus, Science Direct, and Wiley Online Library database with keywords based on medical subject headings (MeSH) and no exclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized for quality assessment, while the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) was utilized for assessing the risk of bias. Additionally, a narrative synthesis was conducted to provide a comprehensive review of the results. Results: We collected a total of 115 studies using defined keywords and 82 studies were eliminated after titles and abstracts were screened. We assessed the eligibility of the remaining 26 reports in full text and excluded four studies due to inappropriate study design and two studies with incomplete outcome data. There were twenty included studies in total with total of 2.525 samples. The included studies received NOS quality evaluation scores ranging from 6 to 8. The majority of items in the risk bias assessment, using RoBANS, across all included studies yielded low scores. However, certain items related to the selection of participants and confounding variables showed variations. Most of studies indicate that CXCL10 may be a helpful immunological marker for leprosy diagnosis, particularly in leprosy reactions as stated in seven studies. The results are better when paired with other immunological markers. Its effectiveness in field-friendly diagnostic tools makes it one of the potential biomarkers used in diagnosing leprosy patients. Additionally, CXCL10 may be utilized to assess the efficacy of multidrug therapy (MDT) in leprosy patients as stated in three studies. Conclusion: The results presented in this systematic review supports the importance of CXCL10 in leprosy diagnosis, particularly in leprosy responses and in tracking the efficacy of MDT therapy. Using CXCL10 in clinical settings might help with leprosy early diagnosis. Yet the findings are heterogenous, thus more investigation is required to determine the roles of CXCL10 in leprosy while taking into account for additional confounding variables.

Serodiagnosis of paucibacillary and multibacillary leprosy using a recombinant chimeric protein composed of specific B-cell epitopes derived from Mycobacterium leprae proteins.

Leprosy diagnosis is difficult due to the clinical similarity with other infectious diseases, and laboratory tests presents problems related to sensitivity and/or specificity. In this study, we used bioinformatics to assess Mycobacterium leprae proteins and formulated a chimeric protein that was tested as a diagnostic marker for the disease. The amino acid sequences from ML0008, ML0126, ML0308, ML1057, ML2028, ML2038, ML2498 proteins were evaluated, and the B-cell epitopes QASVAYPATSYADFRAHNHWWNGP, SLQRSISPNSYNTARVDP and QLLGQTADVAGAAKSGPVQPMGDRGSVSPVGQ were considered M. leprae-specific and used to construct the gene encoding the recombinant antigen. The gene was constructed, the recombinant protein was expressed, purified and tested in ELISA using 252 sera, which contained samples from multibacillary (MB) or paucibacillary (PB) leprosy patients, from their household contacts and healthy individuals, as well as from patients with Chagas disease, visceral and tegumentary leishmaniases (VL/TL), malaria, tuberculosis, and HIV. Sensitivity (Se) and specificity (Sp) for MB and PB samples compared to sera from both healthy subjects and individuals with cross-reactive diseases were 100%. The Se value for MB and PB samples compared to sera from household contacts was 100%, but Sp was 64%. In conclusion, data suggest that this protein could be considered in future studies for leprosy diagnosis.

Adverse reactions induced by MDT/WHO (Rifampicin+Clofazimine+Dapsone) and ROM (Rifampicin+Ofloxacin+Minocycline) regimens used in the treatment of leprosy: a cohort study in a National Reference Center in Brazil.

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

Mitochondrial variants of complex I genes associated with leprosy clinical subtypes.

Leprosy is a chronic bacterial infection mainly caused by Mycobacterium leprae that primarily affects skin and peripheral nerves. Due to its ability to absorb carbon from the host cell, the bacillus became dependent on energy production, mainly through oxidative phosphorylation. In fact, variations in genes of Complex I of oxidative phosphorylation encoded by mtDNA have been associated with several diseases in humans, including bacterial infections, which are possible influencers in the host response to leprosy. Here, we investigated the presence of variants in the mtDNA genes encoding Complex I regarding leprosy, as well as the analysis of their pathogenicity in the studied cohort. We found an association of 74 mitochondrial variants with either of the polar forms, Pole T (Borderline Tuberculoid) or Pole L (Borderline Lepromatous and Lepromatous) of leprosy. Notably, six variants were exclusively found in both clinical poles of leprosy, including m.4158A>G and m.4248T>C in MT-ND1, m.13650C>A, m.13674T>C, m.12705C>T and m.13263A>G in MT-ND5, of which there are no previous reports in the global literature. Our observations reveal a substantial number of mutations among different groups of leprosy, highlighting a diverse range of consequences associated with mutations in genes across these groups. Furthermore, we suggest that the six specific variants exclusively identified in the case group could potentially play a crucial role in leprosy susceptibility and its clinical differentiation. These variants are believed to contribute to the instability and dysregulation of oxidative phosphorylation during the infection, further emphasizing their significance.

Neuromuscular Ultrasound in Polyneuropathies.

Neuromuscular ultrasound is a painless, radiation-free, high-resolution imaging technique for assessing the peripheral nervous system. It can accurately depict changes in the nerves and muscles of individuals with neuromuscular conditions, and it is therefore a robust diagnostic tool for the assessment of individuals with polyneuropathies. This review will outline the typical ultrasonographic changes found in a wide variety of polyneuropathies. In general, demyelinating conditions result in greater nerve enlargement than axonal conditions, and acquired conditions result in more patchy nerve enlargement compared to diffuse nerve enlargement in hereditary conditions. This review is data-driven, but more nuanced anecdotal findings are also described. The overall goal of this paper is to provide clinicians with an accessible review of the ultrasonographic approaches and findings in a wide variety of polyneuropathies.

Dermoscopic features of nails in Leprosy patients in a tertiary referral hospital in West Java, Indonesia.

INTRODUCTION: Leprosy is a chronic granulomatous infectious disease, mainly affecting the skin and peripheral nerves, caused by the obligate intracellular bacteria Mycobacterium leprae. The disease has been discussed in several review articles in recent research, but as far as we know, only a few have addressed the effects of leprosy on nails, especially those who examine the dermoscopic features of nails in leprosy patients. PURPOSES: We aimed to document nail changes in leprosy patients and identify any particular findings through dermoscopic examination. METHOD: This was an observational study conducted in the Dermatology and Venereology Clinic of Hasan Sadikin Hospital, West Java, Indonesia, from March 2023 through May 2023. All patients have established cases of leprosy, and the diagnosis is based on clinical and bacteriological examinations. Recruitment was done through total sampling. Dermoscopic examination of all fingernails and toenails was performed at 10x magnification using a handheld dermatoscope (Heine DELTA 20 T Dermatoscope) in polarized mode without the linkage fluid to document the dermoscopic features. RESULT: Of a total of 19 patients, 15 had nail changes due to leprosy. Out of 15 patients, 13 patients were male. Patients below 25 years old had more nail changes. Most of the patients had a duration of disease greater than two years. Both fingers and toes were involved in nine patients. In this study, the most common dermoscopic feature found was the longitudinal ridge. Other dermoscopic features found in this study were transverse lines, onycholysis, longitudinal melanonychia, leukonychia, subungual hemorrhage, subungual hyperkeratosis, anonychia, and onychorrexis. CONCLUSION: Nail changes are found in leprosy patients and have a wide variety of clinical appearances. A dermoscopy should be performed to assess nail changes in leprosy.

Challenging in leprosy relapse with antiphospholipid syndrome diagnosis: A case report.

Key Clinical Message: Infectious diseases like leprosy can cause antiphospholipid antibodies, leading to blood clots. Clinicians should consider this for patients with unusual thrombotic events and prior infectious disease history. Abstract: This case report details the diagnostic challenge of a 42-year-old man with a history of treated leprosy who presented with clinical features suggestive of antiphospholipid syndrome (APS). Vascular angiography revealed thrombosis, and serological tests were positive for APS antibodies. However, the patient subsequently developed symptoms, including thenar atrophy, paresthesia, and hypopigmented skin patches, which prompted further investigation. Electromyography detected sensorimotor polyneuropathy, while a nerve biopsy indicated a resurgence or chronic presence of leprosy. Despite initial APS management, the case evolved into a leprosy relapse confirmation after 20 years of remission, underscoring the diagnostic intricacies when concurrent autoimmune antibodies and infectious disease manifestations are present. This report emphasizes the importance of considering a broad differential diagnosis, including the potential for infectious disease relapse, in the presence of antiphospholipid antibodies. It illustrates the necessity of an interdisciplinary treatment approach in complex clinical scenarios.

Training and Active Case Detection to Prevent Leprosy: Effect on Knowledge, Attitude and Skills of Health Workers on Early Diagnosis of Leprosy in a Leprosy Hotspot District in Ethiopia.

BACKGROUND: Despite all of the efforts, leprosy continues to affect hundreds of thousands of people every year, including children, showing the ongoing transmission of the disease within the population. The transmission of leprosy can be interrupted through an integrated approach that includes active case-finding, contact tracing and capacity building of health workers. METHODS: A cross-sectional study design was used to assess the knowledge, attitudes and skills of health workers in the screening and diagnosis of leprosy. One hundred and eighty-one and eighty-eight health care workers participated in the pre-and post-assessment surveys, respectively. Data were collected through interviews and an observational checklist. Frequency tables and graphs were used to describe the study variables, and statistical significance between pre- and post-assessment surveys was declared at p-value < 0.5. RESULT: The percentages of healthcare workers with good knowledge, positive attitudes and skills were 61.2%, 55.6% and 51.7% in the pre-assessment survey and 77.3%, 56.3% and 75.0%, respectively, in the post-assessment survey. There was a significant improvement in the knowledge and skill scores of participants in the post-assessment survey (p < 0.01). During the campaign, 3780 index contacts were screened; 570 (15.1%) were diagnosed with skin diseases, and 17 new leprosy cases were diagnosed (case detection rate of 45 per 10,000 contacts). CONCLUSION: Training improved the knowledge and skills of healthcare workers, and a large number of skin diseases were detected through mass screening and active case findings. Providing training for frontline healthcare workers contributed to the detection of more cases and facilitated early detection of leprosy cases.