Langerhans cells express the nonpolymorphic antigen-presenting molecule CD1a, positioning them as contributors to host immunity against Mycobacterium leprae in human leprosy. CD1a was originally shown to present non-canonical lipopeptide antigens such as dideoxymycobactin and chemically diverse hydrophobic ligands. Here, we generated CD4⁺ T cell lines from leprosy lesions that recognized M. leprae in a CD1a-restricted manner. Unexpectedly, antigen recognition was protease-sensitive, prompting biochemical purification that identified two microbial protein antigens: LppX, a 25-kDa lipoglycoprotein, and Ag85A, a 30-kDa secreted protein with no known lipid modification. Recombinant proteins activated the corresponding T cell lines in a CD1a-dependent manner. Epitope mapping identified 12-mer peptides that fully reconstituted antigenicity, were conserved between M. leprae and M. tuberculosis , and elicited robust, dose-dependent IFN-γ production and T cell proliferation, establishing that DNA-encoded, ribosomally translated peptides serve as CD1a-restricted cognate antigens. Biochemical analyses showed peptide binding to CD1a, supported by isoelectric focusing and surface plasmon resonance ( K D ∼75 μM for Ag85A). CD1a-peptide tetramers specifically stained cognate T cells, soluble CD1a was sufficient to present peptide antigen, and transfer of the LppX-specific TCR into naïve T cells restored antigen responsiveness. Using CD1a-peptide tetramers, we identified antigen-specific T cells enriched in patients undergoing reversal reactions compared with patients with lepromatous leprosy and healthy donors. The CD1a-restricted T cell lines secreted IFN-γ and IL-26, cytokines with established antimicrobial activity. Together, these findings demonstrate that CD1a can present canonical microbial peptides as part of a cell-mediated immune response in leprosy, extending the known spectrum of CD1a ligands. Because CD1a is nonpolymorphic and presents antigens to antimicrobial T cells, CD1a-peptide complexes may provide a broadly applicable platform for studying, detecting, and potentially targeting mycobacterial immunity.

Background: Hansen's disease (Leprosy), caused by Mycobacterium leprae, is a chronic granulomatous condition with varied clinical presentations reflecting the host's immune response. Clinical and histological classifications may differ, leading to diagnostic errors. Histopathology offers definitive information on granulomas, bacillary load, and tissue changes. Thus, clinico-histopathological correlation is crucial for accurate diagnosis and appropriate treatment. Objectives: To study the clinic-histopathological comparison in patients with Hansen's disease and evaluate the concordance between clinical and histopathological findings. Materials and Methods: This retrospective observational study analyzed records of patients with Hansen’s disease who underwent skin biopsy at a tertiary care center in Nepal during a two-year study period. Cases with complete clinical and histopathological data were included. Clinical and histopathological classifications were performed according to the Ridley-Jopling spectrum. H&E staining and Fite-Faraco stain for bacilli was done. Clinico-histopathological correlation was assessed by comparing clinical and histopathological diagnoses. Data were analyzed using SPSS, with categorical variables expressed as frequencies, percentages and means. Clinicopathological correlation between clinical and histopathological classification of leprosy was assessed using Cohen’s kappa statistic. Results: A total of 150 patients aged 11-85 years were included, with a mean age of 43.75 ± 15.89 years and male predominance. Clinically, lepromatous leprosy was most common, while histopathology most often showed tuberculoid leprosy. The overall agreement was moderate (κ = 0.48) and was statistically significant (p < 0.001). The observed agreement between the two methods was 57.3%.The agreement of tuberculoid leprosy was 76.66% and lepromatous leprosy 75.75%, while it was moderate in borderline tuberculoid (54.83%); and low in borderline (30%) and borderline lepromatous (33.33%). Substantial reclassification occurred particularly within the borderline spectrum, with BB being clinically overestimated and IL being underestimated. Conclusion: A combined clinic-histopathological approach is essential for accurate classification, especially in borderline cases. While clinical features provide an initial impression, histopathology remains the gold standard for confirmation. A combined approach enhances diagnostic precision, ensures appropriate therapy, and contributes to better patient outcomes.

Delayed diagnosis and poor treatment compliance remain key challenges in leprosy control: a case of lepromatous leprosy with type 2 reaction.

Lepromatous reaction mimicking a primary systemic vasculitis: Case report and literature review.

Background: Multibacillary leprosy management is frequently complicated by severe immunological reactions and adverse drug events. Erythema nodosum leprosum is an immune-complex-mediated complication, while dapsone hypersensitivity syndrome is an idiosyncratic, potentially life-threatening drug reaction. The concomitant presentation of these distinct entities, especially with bullous eruptions, creates a profound diagnostic and therapeutic dilemma. Case presentation: A 42-year-old male with a history of relapsed borderline lepromatous leprosy and rheumatoid arthritis presented with exquisitely painful erythematous nodules, high-grade fever, and bullous eruptions exactly 72 hours after the re-initiation of multidrug therapy. Physical examination recorded a Visual Analog Scale pain score of 9. Expanded histopathological evaluation confirmed a dual pathology: extensive dermal neutrophilic infiltration characteristic of Erythema Nodosum Leprosum, occurring alongside pronounced subepidermal blistering and marked eosinophilic exocytosis indicative of a dapsone-induced bullous eruption. Standard multidrug therapy was immediately discontinued. A modified regimen comprising rifampicin, clarithromycin, and carefully titrated immunosuppressants (methylprednisolone and azathioprine) was initiated. Conclusion: The substitution of dapsone with clarithromycin facilitated rapid clinical resolution of both the bullous eruptions and recurrent immune reactions. This case underscores the critical need for precise temporal tracking, individualized therapeutic modifications, and comprehensive histopathological evaluation in leprosy patients demonstrating complex, overlapping hypersensitivity syndromes.

Leprosy is a chronic infectious disease with diverse clinical manifestations. Skin lesions may present as erythema, nodules, ulcers, bullae, or verrucous hyperplasia. When skin lesions and neurological symptoms are atypical, misdiagnosis is common. When patients develop rare skin lesions resembling pretibial myxedema, clinicians often misdiagnose the condition as hyperthyroidism or mucin deposition disorders. Such misdiagnoses can delay appropriate treatment and may lead to serious complications. We report a 74-year-old male with progressive bilateral pretibial edema and multiple translucent nodular lesions for over six months, accompanied by intermittent high-grade fever. The skin lesions were repeatedly misinterpreted as pretibial myxedema despite the absence of Graves’ disease and the presence of only subclinical hypothyroidism. Repeated bacterial smears obtained from ulcer exudates were negative, which may have contributed to further delaying diagnosis. Histopathological examination of nodular lesions revealed diffuse infiltration of foamy histiocytes with a heavy acid-fast bacillary load, confirming multibacillary leprosy with type 2 lepra reaction (erythema nodosum leprosum). Treatment with rifampicin and clofazimine, combined with systemic corticosteroids, resulted in rapid clinical improvement. Pretibial myxedema-like lesions in this patient represented chronic edema and nodular changes associated with lepromatous leprosy rather than true pretibial myxedema. This case highlights a common diagnostic pitfall and underscores the importance of early histopathological evaluation and heightened clinical suspicion to prevent delayed diagnosis and irreversible complications. Not applicable.

Infiltrated and Nodular Ear Pinna in a Case of Lepromatous Leprosy.

Background: Lucio’s phenomenon is a rare and severe vasculonecrotic complication of diffuse lepromatous leprosy, characterized by extensive necrotic skin lesions due to massive endothelial bacillary proliferation. It typically occurs in untreated or inadequately treated patients. Case Presentation: We report the case of a 52-year-old male presenting with chronic, diffuse necrotic skin ulcers, a leonine facies, and peripheral neuropathy. History revealed macular hypopigmented lesions dating back 20 years. Skin smears showed a high bacillary index (5+). A diagnosis of Lucio’s phenomenon revealing advanced lepromatous leprosy was established. The patient was treated with WHO-recommended multibacillary multidrug therapy, resulting in significant clinical improvement. Conclusion: Lucio’s phenomenon represents a diagnostic and therapeutic emergency in multibacillary leprosy. Prompt recognition, rapid bacteriological confirmation, and early initiation of multidrug therapy are crucial to prevent severe functional and systemic complications

Lepromatous leprosy, more commonly seen in endemic areas, is a severe multi-bacillary granulomatous infection of the skin and peripheral nerves, which leads to facial disfigurement and digital auto-amputation. Although treatable with multidrug therapy, diagnosis and early intervention remains of paramount importance. The bacilli are strongly positive with Fite special stain, and to this day this stain remains most widely used especially in areas that do not have access to PCR testing. Herein, we describe a case where the M. leprae bacilli were Fite positive but also very strongly GMS positive. This case highlights the value of using multiple special stains in diagnosis of leprosy.

Nodular lepromatous leprosy (LL) classically presents with diffuse infiltration, nodules, and plaques. However, unusual morphologies may lead to diagnostic confusion, particularly with histoid Hansen’s disease. We report a rare presentation of nodular lepromatous leprosy manifesting as crateriform and ulcerated papules and plaques, clinically simulating histoid leprosy. Detailed clinical evaluation, histopathology, and slit-skin smear examination aided in establishing the correct diagnosis. This case highlights the importance of recognizing atypical cutaneous manifestations of leprosy to avoid misclassification and ensure appropriate management.

Leprosy can present with subtle or atypical symptoms, particularly involving the upper respiratory tract, which may lead to misdiagnosis. Allergic rhinitis is a common condition, and overlapping nasal symptoms may distract clinicians from considering Hansen’s disease. We report a 37-year-old male who was repeatedly treated for allergic rhinitis due to chronic nasal obstruction, episodic sneezing, and persistent watery rhinorrhea. Despite treatment with antihistamines, intranasal corticosteroids, and saline irrigation for five months, his symptoms did not improve. Further evaluation revealed a xerotic patch, ear lobe infiltration, and thickened peripheral nerves. Slit-skin smear from the ear lobe demonstrated abundant acid-fast bacilli, confirming the diagnosis of lepromatous leprosy. Multidrug therapy was initiated, resulting in marked symptomatic improvement. This case highlights that leprosy should be considered in patients with chronic or atypical rhinitis unresponsive to standard therapy, and that thorough cutaneous and neurological examination remains critical for early diagnosis.

Background Leprosy and tuberculosis (TB) share common characteristics, such as acid-fastness of causative bacteria, geographic endemicity, route of spread, large number of asymptomatic infections, and requirement of multiple drugs for long periods of time to prevent resistance and provide treatment. Being relatively common, co-infection with the two diseases should occur based on chance alone. However, coinfection is surprisingly rare, with less than 20 cases being reported in the last decade. Aim The purpose of this case series was to study the clinico-epidemiological profile of patients with leprosy and TB co-infection. Methods This prospective, descriptive, case series describes leprosy patients with a past or current diagnosis of TB who visited the leprosy clinic of a tertiary care hospital over 3 years. The demographic details of the patients, details about the type of leprosy, slit skin smear, lepra reaction, and use of corticosteroids were noted for all patients. The type of TB, chest X-ray findings, sputum positivity, Interferon gamma release assay (IGRA) test, and Mantoux test results were recorded. The gap between the two diagnoses, the first disease to be diagnosed, family history of either disease, and the presence of predisposing factors were noted. Results This case series describes a total of 20 patients with leprosy co-infected with TB. There were 11 (55%) males, and the mean age of patients was 32.7 years. Half of these patients had lepromatous leprosy, and a similar number had type 2 lepra reaction. Pulmonary TB was seen in 12 (60%) patients, and tubercular pleural effusion in two (10%) patients. Multidrug-resistant TB was seen in two patients, and only one patient had received the bacilli of Calmette-Guerin (BCG) vaccination. Of the two diseases, leprosy was diagnosed first in six (30%) patients, while it was TB in 12 (60%) patients, and two (10%) patients had a concomitant diagnosis. Limitations The small number of patients in this single-centre study from a tertiary care hospital may not be reflective of the general population. Conclusion Leprosy and TB co-infection may present several management issues involving diagnosis and treatment, including drug resistance to tubercular bacilli. Management guidelines for such coinfections are needed to facilitate treatment of such patients and prevent high mortality and morbidity associated with such coinfections. More studies are needed to correctly define the clinico-epidemiological parameters of patients with co-infection.

ABSTRACTLeprosy and tuberculosis (TB) are both chronic granulomatous infections caused by bacilli of the genus Mycobacterium. The simultaneous occurrence of cutaneous tuberculosis and leprosy is rare. We report a 56‐year‐old male presenting with painful erythematous nodules and plaques over the face and extremities for 1 week, along with asymptomatic right axillary lesions for 1 year. Examination revealed tender nodules and plaques with ulceration on the face and extremities, and firm, matted subcutaneous nodules with sinus tracts in the axilla. Sensory loss in a glove‐and‐stocking distribution and peripheral nerve enlargement were also noted. Slit‐skin smear demonstrated a Bacteriological Index of 6+, while histopathology of the axillary lesion showed caseous necrosis with epithelioid granulomas. The patient was diagnosed with lepromatous leprosy in type 2 lepra reaction with scrofuloderma and treated with modified multibacillary multidrug therapy, anti‐tubercular therapy, and corticosteroids, achieving a favorable clinical response. This case report aims to describe a rare co‐occurrence of leprosy and tuberculosis, highlighting the immunological interplay between the two conditions and the importance of comprehensive diagnostic evaluation and individualized management in endemic settings.

Dermal leishmaniasis, particularly postkala-azar dermal leishmaniasis (PKDL), is an uncommon entity that may closely mimic lepromatous leprosy in endemic regions. Both conditions present with chronic, symmetric nodular or plaque-like lesions, leading to frequent diagnostic confusion, especially when peripheral nerve thickening is absent. We report a 71-year-old male with a 15-year history of diffuse erythematous nodules and scaly plaques over the palms and dorsum of the feet, repeatedly managed as lepromatous leprosy without clinical improvement. The absence of peripheral nerve thickening and a negative slit-skin smear prompted further evaluation. Skin biopsy demonstrated macrophages packed with Leishmania donovani (LD) bodies, and polymerase chain reaction (PCR) targeting the ITS-1 gene confirmed LD. The patient was initiated on miltefosine 50 mg twice daily for 12 weeks (standard regimen). At 4-week follow-up, lesions showed approximately 30% flattening, and at 12 weeks, more than 60% regression was noted, without adverse effects. This rare case of a 71-year-old male with >15 years of misdiagnosis highlights that chronic diffuse nodular dermatosis without nerve involvement should prompt consideration of PKDL even in the absence of documented prior visceral leishmaniasis. Accurate diagnosis using histopathology and PCR prevents prolonged inappropriate therapy and reduces the risk of community transmission.

Introduction: Leprosy is a persistent infectious illness which still persists in certain pockets of high endemicity in India. Many of these patients end up with complications with deformities and reactions reporting to our tertiary healthcare center. Aims and Objectives: To analyze the clinical trends of Hansen’s disease over a decade in a tertiary healthcare center in Bengaluru. Materials and Methods: A retrospective record-based study was conducted on leprosy patients registered in our department of dermatology in Bengaluru over a decade, starting from April 2013 to November 2023. Results: A total of 311 cases were registered in the last decade, out of which 73.3% were immigrants. The highest number of cases was among those aged 20–29 years. Childhood leprosy cases constituted 4.1% of total cases. Males exceeded females by 273 (87.7%). The highest cases (16.39%) were noted in 2016 with 51 patients. Multibacillary leprosy constituted 287 (92.28%), among which lepromatous leprosy was the most common presentation. Deformities were seen in 219 (70.4%) patients, with Grade 1 deformity in 158 (50.8%) and claw hand being the most common Grade 2 deformity. There were 22 (7.07%) patients who experienced a reaction; type 2 reactions are more frequent than type 1 reactions. Conclusion: Over the years, our tertiary health center has seen a consistent number of leprosy cases. However, a significant drop in cases was noted in 2020–2021, probably owing to the pandemic and lockdown restrictions. Strikingly, 73% of our patients were immigrants, hailing from West Bengal, Bihar, Orissa, and Andhra Pradesh. This indicates the need for policy makers to focus on the areas of active transmission in the era of eradication of leprosy.

Hansen's disease or leprosy is a chronic infectious disease caused by Mycobacterium leprae. As old as man himself, those who suffer from it continue to be marginalized and stigmatized as they were thousands of years ago. The World Health Organization (WHO), has developed a program aimed at preventing, diagnosing in a timely manner and treating it appropriately. In many cases, patients with leprosy are diagnosed late, accompanied by irreversible disabilities. For this reason, it is appropriate to present a clinical case of lepromatous leprosy, with late diagnosis and grade 2 disability, who was treated in de Dermatology Service of the Dr. Leon Cuervo Rubio teaching clinical surgical hospital in Pinar del Rio, due to skin lesions, with loss of sensitivity and bone resorption, of 5 years of evolution. A bacilloscopy was indicated which confirmed the diagnosis of lepromatous leprosy, so combined polychemotherapy was started, although he is still under treatment. It is vitally important to continue training the Basic Health Team to be able to make early diagnoses of leprosy at the primary care level, thus avoiding the appearance of disabilities.

Introduction: Hansens disease is a chronic infectious disease caused by Mycobacterium leprae bacilli, primarily affecting the skin and peripheral nerves. Despite treatment with multidrug therapy (MDT), it remains a public health concern in many countries, particularly in South-East Asia. Early detection is essential to prevent the diseases spread and disability. Due to the multiple morphologies, it may be difficult to accurately diagnose certain cases based solely on clinical signs; therefore, histopathology is crucial for definitive diagnosis. Objectives: To evaluate the clinical and histopathological correlation with their concordance rates thereby highlighting the role of histopathology in diagnosis and management, especially in borderline leprosy (Hansens disease) cases. Methods: A retrospective study was conducted at Malla Reddy Institute of Medical Sciences from October 2023 to March 2025. Fifty-two skin biopsies from clinically suspected leprosy cases were studied using Haematoxylin Eosin and Fite-Faraco staining. Cases were classified histologically along with bacteriological index as per the Ridley-Jopling system. Concordance between clinical and histological diagnosis was statistically analysed. Results: Out of 52 cases, 61.5 were males, females contributing to 38.4. The most affected age group was 2130 years (46). Histopathological types included Lepromatous Leprosy (LL) (42.3), Borderline Lepromatous (BL) (21), and Borderline Tuberculoid (BT) (15.3). Overall concordance between clinical and histopathological classification was analysed statistically with highest agreement observed in TT (96.2) and BT (94.2) with a greater number of multibacillary cases showing acid-fast bacilli on Fite-Faraco staining. Conclusion: Accurate diagnosis using Ridley-Jopling classification integrates clinical, histological, and immunological findings which plays a pivotal role for effective management.

Lepromatous leprosy (LL) represents the anergic pole of the leprosy spectrum and may rarely mimic histoid leprosy (HL). A 45-year-old man presented with multiple shiny umbilicated papules and nodules over normal skin resembling HL. Slit-skin smear revealed numerous solid-staining bacilli (BI 5+), and histopathology showed diffuse foamy macrophages without spindle cells, confirming LL. The patient responded to multibacillary multidrug therapy. This case emphasizes the clinical overlap between LL and HL and the importance of bacteriological and histopathological evaluation for accurate diagnosis and management to prevent misclassification and ensure effective treatment.

Background: Erythema nodosum leprosum (ENL) is a severe, immune-complex mediated complication of lepromatous leprosy that can manifest before, during, or after multidrug therapy (MDT). While the primary etiology involves the release of Mycobacterium leprae antigens, the chronicity of ENL is frequently driven by secondary, often occult, triggers. Focal infections, particularly of odontogenic origin, are frequently overlooked in standard dermatological assessments, leading to refractory clinical courses. Case presentation: We report the case of a 32-year-old male with a history of borderline lepromatous (BL) leprosy who had achieved release from treatment (RFT). The patient presented with severe, chronic, and recurrent ENL characterized by painful erythematous nodules, high-grade fever, and acute neuritis, occurring more than one year post-RFT. Laboratory evaluation revealed significant inflammatory markers, including a C-Reactive Protein level of 172.7 mg/L and leukocytosis. Crucially, intraoral examination identified neglected chronic dental caries (gangrene radix) and generalized periodontal inflammation. Despite medical advice, the patient refused dental intervention. The reactional state was managed with a combination of intravenous methylprednisolone and high-dose oral clofazimine. While cutaneous symptoms improved, the persistence of the focal infection poses a substantial risk for further recurrence. Conclusion: This case highlights the critical and often underestimated role of odontogenic focal infections as perpetuating factors in chronic ENL. It underscores the necessity for a multidisciplinary approach integrating dentistry and dermatology. We propose that recalcitrant ENL in post-RFT patients should trigger mandatory screening for occult dental infections to disrupt the cycle of systemic inflammation.

Although the prevalence of leprosy has significantly decreased in India, it has been still not eradicated, therefore necessitating ongoing efforts to raise awareness for its control. To determine the diagnostic utility of slit skin smear (SSS) and Fite-Faraco stain (FFS) techniques on histopathology of skin and nerve biopsies for the diagnosis of leprosy in a tertiary care center. The present cross-sectional study was carried out on patients clinically suspected to have leprosy consulting in a tertiary care center in Gujarat, India, from January 2022 to December 2024. Statistical analysis was done by using Statistical Package for Social Sciences (SPSS) version 21.0. Continuous variables were presented as mean and categorical variables as numbers and percentages (%). Comparative analysis between various parameters of test effectiveness by using FFS and SSS methods was done. The age of leprosy cases ranged from 18 to 60 years, with a mean age of 35.2 years. Male to female ratio was 5.5 to 1. Histopathologically lepromatous leprosy (61.6%) and multibacillary type based on World Health Organisation (WHO) classification (77%) were the most common forms of leprosy. When comparing the efficacy of SSS and FFS techniques on tissue sections, FFS was found to be more effective than SSS. Sufficient knowledge and clinical expertise, along with effective diagnostic techniques, prompt symptom reporting and heightened social awareness to mitigate the stigma associated with the condition from the patient's perspective, can collectively advance the nation towards the goal of leprosy eradication.