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.

Bioinformatic approach for repurposing immunomodulatory drugs for lepromatous leprosy.

Background: The lepromatous leprosy (LL) disease is caused by Mycobacterium leprae and Mycobacterium lepromatosis which is characterized by inadequate response to treatment, a propensity to drug resistance, and patient disability. We aimed to evaluate current immunomodulatory medicines and their target proteins collectively as a drug repurposing strategy to decipher novel uses for LL. Methods: A dataset of human genes associated with LL-immune response was retrieved from public health genomic databases including the Human Genome Epidemiology Navigator and DisGeNET. Retrieved genes were filtered and enriched to set a robust network (≥10, up to 21 edges) and analyzed in the Cytoscape program (v3.9). Drug associations were obtained in the NDEx Integrated Query (v1.3.1) coupled with drug databases such as ChEMBL, BioGRID, and DrugBank. These networks were analyzed in Cytoscape with the CyNDEx-2 plugin and STRING protein network database. Results: Pathways analyses resulted in 100 candidate drugs organized into pharmacological groups with similar targets and filtered on 54 different drugs. Gene-target network analysis showed that the main druggable targets associated with LL were tumoral necrosis factor-alpha, interleukin-1B, and interferon-gamma. Consistently, glucosamine, binimetinib, talmapimod, dilmapimod, andrographolide, and VX-702 might have a possible beneficial effect coupled with LL treatment. Conclusion: Based on our drug repurposing analysis, immunomodulatory drugs might have a promising potential to be explored further as therapeutic options or to alleviate symptoms in LL patients.

Childhood borderline lepromatous leprosy: a case report.

BACKGROUND: Leprosy in children is a strong indicator of the recent failure of leprosy control and disease transmission programs. For twenty-two years, leprosy has been declared `eliminated as a public health hazard,` yet new cases continue to emerge in endemic areas. The new case detection rate among the child population was recorded at 4.4 per million children. Because of their underdeveloped or neonatal immunity and exposure to intrafamilial contacts, children tend to be the most vulnerable population. CASE: We present a case of the borderline lepromatous type of leprosy in a 9-year-old Indonesian male patient with the chief complaint of three stiff fingers on his left hand that began four years ago and hypopigmented patches on the back and buttocks that began five years ago. In this case, there was a history of leprosy in his mother`s sister, who had died. Leprosy in the patient was suspected of possibly being transmitted from his mother`s sister who had intense contact with the patient. The results of bacteriological examination with Ziehl- Neelsen staining of tissue scrapings found acid-fast bacilli. He was treated with a multibacillary multidrug regimen for 12 months. Periodical observations after the patient received the treatment revealed no new spots on the patient`s skin, some of the previous hypopigmented patches seemed to fade, especially those on the back. CONCLUSIONS: In the absence of an effective vaccine, early diagnosis and treatment are critical in preventing disability and deformity and reducing the physical, psychosocial, and economic burden of the disease.

Histoid leprosy complicated by erythema nodosum leprosum mimicking connective tissue disease.

Erythema nodosum leprosum (ENL) is an immunological complication of leprosy seen in 50% of lepromatous and 10% of borderline lepromatous leprosy. It usually presents as a multisystem disease with papulo-nodular skin lesions and fever. Arthralgia or arthritis is a common initial presentation of erythema nodosum leprosum. Pure rheumatologic presentation of lepromatous leprosy complicated by erythema nodosum leprosum is extremely rare, mimics connective tissue disease and is treated with steroids.

Systematic Review of Hansen Disease Attributed to Mycobacterium lepromatosis.

In 2008, bacilli from 2 Hansen disease (leprosy) cases were identified as a new species, Mycobacterium lepromatosis. We conducted a systematic review of studies investigating M. lepromatosis as a cause of HD. Twenty-one case reports described 27 patients with PCR-confirmed M. lepromatosis infection (6 dual M. leprae/M. lepromatosis): 10 case-patients in the United States (7 originally from Mexico), 6 in Mexico, 3 in the Dominican Republic, 2 each in Singapore and Myanmar, and 1 each in Indonesia, Paraguay, Cuba, and Canada. Twelve specimen surveys reported 1,098 PCR-positive findings from 1,428 specimens, including M. lepromatosis in 44.9% (133/296) from Mexico, 3.8% (5/133) in Colombia, 12.5% (10/80) in Brazil, and 0.9% (2/224) from the Asia-Pacific region. Biases toward investigating M. lepromatosis as an agent in cases of diffuse lepromatous leprosy or from Mesoamerica precluded conclusions about clinicopathologic manifestations and geographic distribution. Current multidrug treatments seem effective for this infection.

Case Report: Lepromatous Leprosy Masquerading as Acute Suppurative Lymphadenitis.

Leprosy is a chronic cutaneous infection. It is usually characterized by thickened nerves and maculo-anesthetic patches. Leprosy often has an unusual presentation, which is a diagnostic challenge. In this case report, we present a case of an elderly male who presented with fever and chronic pus-draining axillary, cervical, and inguinal lymph nodes. He also had a weak left foot for the previous 5 months. During his hospital stay, he developed additional papular lesions over his extremities. We performed fine needle aspiration from the lymph nodes and skin biopsy, which were suggestive of lepromatous leprosy. We initiated him on antileprosy medication. On follow-up, he was responsive to therapy. Although skin and nerve involvement in leprosy is common, this case had an atypical presentation of discharging lymph nodes.

Case Report: Necrotizing Erythema Nodosum as a Manifestation of Lepromatous Leprosy Relapse 50 Years after the Initial Infection.

Leprosy is a chronic infection caused by Mycobacterium leprae and Mycobacterium lepromatosis that preferentially compromises peripheral nerve, skin, and mucous membranes. Colombia achieved the goal of leprosy elimination in 1997. However, in Urabá (Colombia), there has been an increase in leprosy cases beginning in 2020. This case report shows a leprosy relapse 5 decades after the initial infection debuted as a necrotizing erythema nodosum leprosum. Therefore, long-term follow-up of patients with risk factors for relapse is emphasized, especially those treated before the standard of multidrug therapy (dapsone, clofazimine, and rifampin). This case report stresses the importance the importance of clinical follow-up and surveillance of patients with these events of interest for the public health.

Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy.

BACKGROUND: The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES: To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS: We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS: Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS: Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.

A real-world study of low-dose thalidomide in severe erythema nodosum leprosum highlighting its mechanistic rationale in a resource-constrained target population.

BACKGROUND: Corticosteroids remain the main therapy in erythema nodosum leprosum (ENL), and long-term usage in chronic or recurrent ENL is a cause of significant morbidity and mortality. Thalidomide exerts dramatic effect in controlling ENL and helps reduce the dose of steroids, but the cost is a hindrance to its usage. METHODS: Patients of ENL (steroid naïve and steroid-dependent) were recruited over a 1-year period. An escalating dose of low-dose thalidomide with a reducing dose of prednisolone was titrated depending on the control of disease activity. The primary aim was to reduce the dose of steroids to the lowest effective dose, and the secondary aim was to stop. RESULTS: Sixteen patients of ENL were studied (mean duration of ENL 22.1 months, 15 severe ENL), and a majority (11/16, 68%) were on steroids with a mean duration of 11.27 months. All patients had steroid-related side effects (cushingoid habitus 81.8%, weight gain 54.5%, diabetes mellitus 9%, hyperlipidemia 18.18%, cataract 18.1%, osteoporosis 36.3%, striae 36.3%, acneiform eruptions 18.1%, and myopathy 9%). Steroids could be tapered in a majority of patients (n = 9) within 3 months (mean 2.44 months) with a low dose of thalidomide (25-150 mg/day, mean 78.3 mg) achieving a significant reduction in prednisolone dose (33.16 mg at baseline; 4.28 mg at 3 months, P < 0.05). Steroids could be stopped in 92% of patients by 3.03 months, and both drugs could be stopped in 80% of cases by 5.83 months. CONCLUSION: The rapid and effective control of ENL with low-dose thalidomide in our series is comparable to the historical efficacy of high-dose thalidomide regimens, making it an affordable therapy in resource-constrained settings and an excellent steroid-sparing agent. The rapid onset of disease control is likely attributable to its action via neutrophils.

Evaluation of the influence of genetic variants in Cereblon gene on the response to the treatment of erythema nodosum leprosum with thalidomide.

BACKGROUND: Erythema nodosum leprosum (ENL) is an acute and systemic inflammatory reaction of leprosy characterised by painful nodules and involvement of various organs. Thalidomide is an immunomodulatory and anti-inflammatory drug currently used to treat this condition. Cereblon (CRBN) protein is the primary target of thalidomide, and it has been pointed out as necessary for the efficacy of this drug in others therapeutics settings. OBJECTIVES: In this study, we aimed to evaluate the influence of CRBN gene variants on the dose of thalidomide as well as its adverse effects during treatment of ENL. METHODS: A total of 103 ENL patients in treatment with thalidomide were included in this study. DNA samples were obtained from saliva and molecular analysis of CRBN gene were performed to investigate the variants rs1620675, rs1672770 and rs4183. Different genotypes of CRBN variants were evaluated in relation to their influence on the dose of thalidomide and on the occurrence of adverse effects. FINDINGS: No association was found between CRBN variants and thalidomide dose variation. However, the genotypes of rs1672770 showed association with gastrointestinal effects (p = 0.040). Moreover, the haplotype DEL/C/T (rs4183/rs1672770/rs1620675) was also associated with gastrointestinal adverse effects (p = 0.015). MAIN CONCLUSIONS: Our results show that CRBN variants affect the treatment of ENH with thalidomide, especially on the adverse effects related to the drug.

Diagnosing and treating leprosy in a non-endemic setting in a national centre, London, United Kingdom 1995-2018.

BACKGROUND: Leprosy is rare in the United Kingdom (UK), but migration from endemic countries results in new cases being diagnosed each year. We documented the clinical presentation of leprosy in a non-endemic setting. METHODS: Demographic and clinical data on all new cases of leprosy managed in the Leprosy Clinic at the Hospital for Tropical Diseases, London between 1995 and 2018 were analysed. RESULTS: 157 individuals with a median age of 34 (range 13-85) years were included. 67.5% were male. Patients came from 34 different countries and most contracted leprosy before migrating to the UK. Eighty-two (51.6%) acquired the infection in India, Sri Lanka, Bangladesh, Nepal and Pakistan. 30 patients (19.1%) acquired leprosy in Africa, including 11 from Nigeria. Seven patients were born in Europe; three acquired their leprosy infection in Africa, three in South East Asia, and one in Europe. The mean interval between arrival in the UK and symptom onset was 5.87 years (SD 10.33), the longest time to diagnosis was 20 years. Borderline tuberculoid leprosy (n = 71, 42.0%), and lepromatous leprosy (n =, 53 33.1%) were the commonest Ridley Jopling types. Dermatologists were the specialists diagnosing leprosy most often. Individuals were treated with World Health Organization recommended drug regimens (rifampicin, dapsone and clofazimine). CONCLUSION: Leprosy is not a disease of travellers but develops after residence in an leprosy endemic area. The number of individuals from a leprosy endemic country reflect both the leprosy prevalence and the migration rates to the United Kingdom. There are challenges in diagnosing leprosy in non-endemic areas and clinicians need to recognise the symptoms and signs of leprosy.

Palatal perforation in a patient with borderline lepromatous leprosy: leprosy still not eradicated.

Leprosy was eliminated globally in 2000, but it continues to be endemic in developing countries like India, Brazil and Indonesia, with a prevalence of 0.57/10 000 persons in India (2020). At the end of the year 2020, the prevalence was 129 389, and oral manifestation of the leprosy is luncommon. We hereby report a case of a female patient in her late 30s who presented with palatal perforation. Following a thorough history taking and full body clinical examination, we arrived at a diagnosis of leprosy, and prompt treatment was initiated. Knowledge of cases like this becomes important as the oral lesion is said to form an essential source of leprosy dissemination in the community, and awareness about them becomes crucial, demanding immediate attention.

Thalidomide and steroid in the management of erythema nodosum leprosum.

OBJECTIVE: The objective of the study was to assess the efficacy and safety profiles of combined treatment of prednisolone with thalidomide (Gr-A) and prednisolone with clofazimine (Gr. B) in patients with erythema nodosum leprosum (ENL) or type 2 lepra reactions. MATERIALS AND METHODS: Efficacy of both regimens was assessed on the basis of clinical recovery of recurrent ENL measured by reaction severity score (RSS), Visual Analog Scale (VAS), and recurrence of type 2 lepra reaction. The causality assessment of adverse drug reactions was done using the WHO UMC causality assessment scale. RESULTS: The average age of patients with recurrent ENL was 42.8 years (male) and 51.8yrs (female) and had mean duration of leprosy and recurrent ENL 2.4 years and 2.09 years, respectively. 80% of nonrecurrence was observed in Gr-A versus 66% in Gr-B. Significant (P < 0.05) lower RSS and VAS was found in both the treatment groups as compared to pretreatment value. The reduction in RSS and VAS was statistically significant (P < 0.05) in Gr-A compared to Gr-B treatment. CONCLUSION: Thalidomide combination with steroid was found to be more efficacious than clofazimine combination with steroid in the treatment of ENL both the treatment regimens showed few tolerable side effects. Improved strategies for the treatment and management of these reactions need to be developed.