Case Report: Type 2 Leprosy Reaction Mimicking Sweet Syndrome: A Case Report and Literature Review.

Type 2 leprosy reaction is a type of acute inflammation that predominantly affects borderline lepromatous leprosy and lepromatous leprosy patients and occurs before, during, or after therapy. The atypical variant, which resembles Sweet syndrome, could easily lead to misdiagnosis. Here, we report a case of a 52-year-old man who presented with type 2 leprosy reaction that mimicked Sweet syndrome. In addition, we review published cases and summarize their features to raise awareness of this atypical variant to enable improved diagnosis and management.

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.

Reverse Koebner phenomenon in erythema nodosum leprosum.

BACKGROUND: Erythema nodosum leprosum (ENL) is an immunologically mediated phenomenon complicating the course of leprosy. Reverse Koebner phenomenon is the term used to describe the sparing of previously injured or diseased skin by new skin lesions of the disease. METHODS: A middle-aged woman with a known case of lepromatous leprosy for the past year presented with an eruption of reddish painful nodules over her body. The lesions were found to characteristically spare the sites of previous scars. RESULTS: This sparing phenomenon of previous scar sites has been termed reverse Koebner phenomenon, a site of the body that offers greater resistance than the rest of the body to the onset of the disease, seen in various diseases, but it has never been described in ENL. CONCLUSION: This sparing of scar sites in ENL can be attributed to reverse Koebner phenomenon.

Overview and Current Advances in Dapsone Hypersensitivity Syndrome.

PURPOSE OF REVIEW: As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent. RECENT FINDINGS: In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome.

COVID-19 vaccination and leprosy-A UK hospital-based retrospective cohort study.

BACKGROUND: Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised. Vaccines for SARS-CoV-2 may provoke a T cell response. The latter poses a theoretical risk of provoking an immunological response to latent Mycobacterium leprae infection leading to clinical disease or in those with clinical disease triggering a leprosy reaction. BCG vaccination is associated with the development of leprosy in a small proportion of healthy contacts of people with leprosy within twelve weeks of administration. BCG causes a Th1 immune response. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort study to determine the SARS-CoV-2 vaccination status of individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any had developed leprosy or experienced a new leprosy reaction within twelve weeks of receiving a dose of a SARS-CoV-2 vaccine. The electronic patient records were used to retrieve data. Fifty-two individuals with leprosy attended the clinic in 2021 of which five people were newly diagnosed with leprosy. Thirty-seven (71%) were male and the median age was 48.5 years old (Range 27-85 years). Eight (15.4%) individuals were taking multi-drug therapy (MDT) and eight (15.4%) had completed MDT within three years of the study. Twenty-two (41.5%) individuals were prescribed a systemic immunosuppressant drug during 2021. Ten (18.9%) individuals have one or more risk factors for severe COVID-19. The SARS-CoV-2 vaccination status of fifty (96%) were recorded of which forty-nine were vaccinated (98%). One individual had declined vaccination. One individual was diagnosed with borderline tuberculoid (BT) leprosy having developed red skin lesions with reduced sensation (which increased in size and number) and thickened peripheral nerves one week after a second dose of BNT162b2 vaccine. Another individual who had completed MDT more than three years earlier developed red plaques and tender thickened nerves consistent with a leprosy Type 1 reaction eight weeks after a single dose of BNT162b2 vaccine (having received two doses of CoronaVac vaccine three months earlier). CONCLUSIONS/SIGNIFICANCE: The development of BT leprosy and a Type 1 reaction in another individual shortly after a dose of BNT162b2 vaccine may be associated with vaccine mediated T cell responses. The benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events but data from leprosy endemic countries may provide further information about potential adverse effects of augmented T cell responses in individuals with leprosy or latent M. leprae infection.

Case Report: Chemoradiation with Paclitaxel and Carboplatin Unveiling Leprosy Type 1 Downgrading Reaction.

Type 1 lepra reaction (T1R) is a major complication seen in nonpolar forms of leprosy and leads to significant morbidity. The classification of T1R as up and downgrading, based on previously defined histopathological criteria (by Ridley), has therapeutic and prognostic implications. The trigger factors for these reactions are poorly described, especially in case of downgrading T1R and we describe a case of leprosy reaction that was possibly triggered by chemoradiation and elucidate the possible mechanism.

Clinical and epidemiological trends in childhood leprosy: A 20-year retrospective analysis from a tertiary care hospital in Jammu, North India.

Background Slightly more than half the total number of childhood leprosy cases worldwide are from India. Aim To analyze the clinical and epidemiological trends of childhood leprosy over 20 years in a tertiary care hospital. Methods We retrieved the medical records of all children less than 15 years of age registered in the leprosy clinic between April 1998 and March 2018. We tabulated and analyzed data pertaining to demographic details along with clinical findings such as cutaneous lesions, nerves involved, sensory loss, deformities, reactions, smear status, histopathology and treatment. Results Out of total 1548 leprosy cases registered during the study period, 55 (3.55%) cases of childhood leprosy were diagnosed. Thirty five (63.6%) children were in the age group of 11-15 years and 83.7% were migrants from other states. Thirteen (23.6%) children reported contact with a diagnosed case of leprosy, mainly in close contacts. Fifty three (96.4%) children presented with cutaneous lesions while 2 (3.6%) had pure neural involvement. Borderline tuberculoid leprosy was the most common clinical presentation in 27 (49.1%) followed by borderline lepromatous leprosy in 11 (18%). Thickened peripheral nerve trunks were detected in 42 (76.4%), most commonly the ulnar nerve. Reactional episodes occurred in 12 (21.8%) cases (Type 1 reaction, 10 (18.2%); Type 2 reaction, 2 (3.6%)). Grade 2 disability was detected in 4 (7.3%). Multidrug therapy was started in all patients, multibacillary (MB) regimen in 42 (76.3%) patients and paucibacillary (PB) regimen in 13 (23.7%). Twenty five (45.4%) children defaulted from the treatment. On comparing the data of 2008-18 with that of the previous decade (1998-2007), there was a higher proportion of migrant cases as compared to local cases (3:1-11:1) and MB cases as compared to PB cases (2:1-6:1). The proportion of treatment defaulters declined from 60% to 36%. Limitations Relapse rate could not be calculated due to inadequate follow-up period. As it is a hospital-based retrospective study with no active surveys, these findings may not reflect trends in the community. Conclusion Childhood leprosy continues to be a significant problem. There is a clear need to strengthen early detection, treatment and regular follow-up of these cases in both high and low endemic settings.

IL-21 plays an important role in modulating "Th17-Treg" cell axis in leprosy Type 1 reactions.

Leprosy type 1 reaction (T1R) is a cell-mediated inflammatory reaction which involves skin and peripheral nerves in leprosy. Lesions with T1R have higher production of IL-17 cytokine from CD4+ T cells along with lower TGF-ß producing FOXP3+ CD4+ Tregs. IL-21 is an important cytokine that promotes the development and stability of Th17 cells in an autocrine manner. It can play an important role in the pathogenesis of T1R in leprosy. However, the mechanism by which IL-21 influences the pathogenic progress of leprosy T1R remains poorly understood. In the present study, we evaluated the expression of IL-21 cytokine in skin lesions of both non-reactional (NR) and T1R via immuno-histochemistry and quantitative PCR (qPCR). Further, expression of various genes (IL-17A, IL-17F, TGF-ß, FOXP3, RORC and IL-21) was also measured by qPCR in cultured cells. We also analyzed the secretion of various cytokines such as of IL-21, IL-17A/F and TGF-ß in the culture supernatants by ELISA. In addition, differentiation of Th17 and Treg cells were studied in PBMC cultures after stimulation with Mycobacterium leprae sonicated antigens and rIL-21 for 48 hrs and the phenotypes of Th17 and Tregs were determined by flowcytometric analysis. Our results clearly indicate that IL-21+T cells were significantly higher in both peripheral blood and skin lesions of T1R as compared to NR patients. Moreover, we observed that recombinant IL-21 cytokine inhibited TGF-ß producing Treg cells differentiation along with up-regulating Th17 cells under in-vitro conditions. The gene expression of IL-21 was significantly negatively correlated with Treg and positively correlated with Th17 cell markers in T1R patients. Our results suggested that IL-21 promotes T1R mediated inflammation via modulating the balance of Th17 and Treg cell populations.

Autochthonous leprosy in Europe: a case report and literature review.

Leprosy is currently uncommon in Europe: the diagnosed cases are almost all imported from endemic areas. We report on an autochthonous case of borderline lepromatous leprosy in a 71-year-old Portuguese woman. The case was complicated by a reversal reaction and then by erythema nodosum leprosum. A literature review identified 18 reported cases of European autochthonous leprosy since 2000; all but one were observed in Mediterranean countries. Therefore, active clusters of leprosy persist in Europe, particularly in Spain, Greece, Portugal, and Italy.

Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects.

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.

Nerve abscess in Hansen's disease as part of immune reconstitution inflammatory syndrome: a case report.

Immune reconstitution inflammatory syndrome is an inflammatory reaction in HIV-infected patients after initiation of antiretroviral therapy resulting from restored immunity to specific infectious or non-infectious antigens. A 36-year-old male patient on highly active antiretroviral therapy of six months duration, presented with reddish, tender lesions over medial aspect of arm and a single, anaesthetic patch. Tender fluctuant swellings were seen on the medial aspect of left forearm. A few of them had ruptured spontaneously discharging pus. A skin biopsy from the anaesthetic patch showed caseating epitheloid granulomas. A diagnosis of Hansen's disease borderline tuberculoid in type 1 reversal reaction, with formation of nerve abscess due to Immune Reconstitution Inflammatory Syndrome was made. The patient was started on multibacillary multidrug therapy as per WHO guidelines and highly active antiretroviral therapy was continued.

Vitiligo on black skin: epidemiological and clinical aspects in dermatology, Cotonou (Benin).

BACKGROUND: Vitiligo is unsightly on darkly pigmented skin and leads important stigmatization because of the mix-up with leprosy. PATIENTS AND METHODS: We analyzed retrospectively the epidemiological and clinical patterns of vitiligo on darkly pigmented skin between 1988 and 2008 in the Department of Dermatology in Cotonou (Benin). The diagnosis was made based on the clinical characteristics of vitiligo. RESULTS: Two hundred and forty-six patients were seen, representing 0.9% of new consultations. The gender ratio was 1 : 1, and the mean age of patients was 25.9 years. The mean duration of the lesions was 30.9 months. Among the 246 patients, an associated pathology was found in 26% of cases. These included atopy (23.2%), diabetes (1.6%), thyroid disease (0.8%), and alopecia (0.4%). A family history of vitiligo was present in 1.2% of cases. The sites of the lesions were in descending order of frequency: head (60.6%), lower limbs (40.2%), upper limbs (33.3%), trunk (22.4%), genitals (13.0%), and neck (8.9%). On the head, the most common sites affected were the lips (65.1%), cheek (20.8%), and ears (16.8%). According to the different clinical forms, vitiligo was achromic (76%), speckled (12.6%), and trichromic (11.4%). Vitiligo vulgaris was the commonest form of the disease (52.4%), followed by localized vitiligo (36.2%), segmental vitiligo (9.8%), and vitiligo universalis (1.6%). Triggering factors were identified in 4.5% of patients. CONCLUSION: Our survey shows that the patterns of vitiligo are similar to that reported from other African countries with a few distinguishing particularities.

Variables affecting interpretation of skin prick test results.

BACKGROUND: Both performer- and device-dependent variabilities have been reported in sizes of wheal responses to skin prick tests. OBJECTIVE: We aimed to evaluate whether or not variabilities in sizes of wheal responses influence the final interpretation of skin prick tests; in other words, the decision on whether or not there is an allergy to a given antigen. METHODS: Skin prick tests with positive and negative controls and extracts of Dermatophagoides farinae and Dermatophagoides pteronyssinus were done for 69 patients by two different persons, using two different puncturing devices- disposable 22-gauge hypodermic needles and metal lancets. RESULTS: Among four different skin prick tests, the average coefficients of variation in sizes of wheal responses were near to or higher than 20% for all of them. On the other hand, in the final interpretation of results, kappa values indicated substantial or almost perfect agreements between these tests. However, the frequency of establishing allergy to the house dust mites widely ranged in these tests (20.8-35.8% for D. farinae and 20.8-28.3% for D. pteronyssinus). LIMITATIONS: The conduction of the study in a single center and the comparisons of results of only two performers. CONCLUSION: We feel that variabilities in sizes of wheal responses of skin prick test can influence its categorical results.

Complex Type 2 Reactions in Three Patients with Hansen's Disease from a Southern United States Clinic.

In non-endemic countries, leprosy, or Hansen's disease (HD), remains rare and is often underrecognized. Consequently, the literature is currently lacking in clinical descriptions of leprosy complications in the United States. Immune-mediated inflammatory states known as reactions are common complications of HD. Type 1 reactions are typical of borderline cases and occur in 30% of patients and present as swelling and inflammation of existing skin lesions, neuritis, and nerve dysfunction. Type 2 reactions are systemic events that occur at the lepromatous end of the disease spectrum, and typical symptoms include fever, arthralgias, neuritis, and classic painful erythematous skin nodules known as erythema nodosum leprosum. We report three patients with lepromatous leprosy seen at a U.S. HD clinic with complicated type 2 reactions. The differences in presentations and clinical courses highlight the complexity of the disease and the need for increased awareness of unique manifestations of lepromatous leprosy in non-endemic areas.