Cutaneous ulceration as a presenting feature of type 1 lepra reaction: A case report.

Reactions in leprosy represent sudden shift in the immunological response and are seen in 11-25% of affected patients. It can be seen before, during or after the completion of multidrug therapy (MDT).1 Two types of reactions are recognized; Type 1 reaction (T1R), seen in borderline leprosy, affecting mainly skin and nerves; type 2 reaction (T2R) or erythema nodosum leprosum (ENL), seen in lepromatous leprosy, characterized by systemic features in addition to cutaneous lesions. Trophic ulcers and ulcerating ENL are well known entities while cutaneous ulceration in T1R is extremely rare; we describe an immune-competent woman with cutaneous ulceration as a presenting feature to highlight the need to recognize this entity at the earliest opportunity.

Unusual non-trophic ulcerations in leprosy: A case series of 17 patients.

Non-neuropathic ulcers in leprosy patients are infrequently seen, and atypical presentations are prone to misdiagnosis. We evaluated diagnosed cases of leprosy between January 2017 and January 2020 for the presence of cutaneous ulceration, Ridley-Jopling subtype of leprosy, reactions and histologic features of these ulcerations. Treatment was given as WHO recommended multi-bacillary multi-drug therapy. We found 17/386 leprosy patients with non-neuropathic ulcers. We describe three causes - spontaneous cutaneous ulceration in lepromatous leprosy (one nodular and one diffuse), lepra reactions (five patients with type 1; nine with type 2, further categorised into ulcerated Sweet syndrome-like who also had pseudoepitheliomatous hyperplasia, pustulo-necrotic and necrotic erythema nodosum leprosum) and Lucio phenomenon (one patient). Our series draws attention towards the different faces of non-neuropathic ulcers in leprosy, including some atypical and novel presentations.

Persistent Infection Versus Type 2 Immunological Reaction in Lepromatous Leprosy.

The distinction between persistent infection and immunologic reactions in leprosy is often difficult but critically important since their management is different. We present the case of a 51-year-old Vietnamese female who presented in 2015 with areas of erythema and skin infiltration on face and chest, as well as edema on her hands and feet. Skin biopsy was consistent with lepromatous leprosy. She was treated with rifampin, clarithromycin, and levofloxacin for 2 years. Her lower extremity edema was attributed to type 2 immunological reaction for which she was started on prednisone and methotrexate, but she was lost to follow-up for 19 months. She presented with new skin lesions and pain on her extremities. New biopsies revealed an intense neutrophilic infiltrate in the dermis and acid-fast bacilli focally within cutaneous nerve twigs. As compared with the initial biopsy, the inflammatory infiltrates were diminished and the bacilli had a degenerating appearance. These findings were consistent with type 2 immunological reaction. The patient was treated with thalidomide with improvement in the appearance of the skin lesions. A follow-up biopsy showed lack of neutrophilic infiltrates and decreased number of bacilli. This case illustrates the importance of differentiating between persistent infection and immunologic reactions in leprosy. Clinicians should be aware of these complications. A high index of suspicion and accurate interpretation of skin biopsy results are essential for appropriate diagnosis.

Differential Expression of IFN-γ, IL-10, TLR1, and TLR2 and Their Potential Effects on Downgrading Leprosy Reaction and Erythema Nodosum Leprosum.

Leprosy reactions are acute immunological events that occur during the evolution of chronic infectious disease causing neural damage and disabilities. A study using blood samples of 17 leprosy reaction patients and 17 reaction-free was carried out by means of associations between antigens, receptors, and expression of cytokines, using path analysis providing new insights into the immunological mechanisms involved in triggering leprosy reactions. Toll-like receptors (TLR) such as TLR1 and TLR2, presented balanced expression in the reaction-free multibacillary (MB) group (TLR1: 1.01 ± 0.23, TLR2: 1.22 ± 0.18; p = 0.267). On the other hand, downgrading type 1 reaction (T1R) (TLR1: 1.24 ± 0.17, TLR2: 2.88 ± 0.37; p = 0.002) and erythema nodosum leprosum (ENL) (TLR1: 1.93 ± 0.17, TLR2: 2.81 ± 0.15; p = 0.004) revealed an unbalance in relation to the expression of these receptors. When the path analysis was approached, it was noted that interleukin 10 (IL-10) expression showed a dependence relation with phenolic glycolipid I (PGL-I) in downgrading T1R (direct effect = 0.503 > residual effect = 0.364), whereas in ENL, such relationship occurred with lipoarabinomannan (LAM) (direct effect = 0.778 > residual effect = 0.280). On the contrary, in the reaction-free leprosy group, interferon-gamma (IFN-γ) levels were dependent on the association between TLR2 and TLR1 (0.8735). The high TLR2 expression associated with IL-10 levels, in the leprosy reaction groups, may be hypothetically related to the formation of TLR2/2 homodimers and/or TLR2/6 heterodimers linked to evasion mechanisms in downgrading reactions and pathophysiology of ENL.

The effects of prednisolone treatment on serological responses and lipid profiles in Ethiopian leprosy patients with Erythema Nodosum Leprosum reactions.

BACKGROUND: Erythema nodosum leprosum (ENL) is a systemic inflammatory complication occurring mainly in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL). Prednisolone is widely used for treatment of ENL reactions. However, it has been reported that prolonged treatment with prednisolone increases the risk for prednisolone-induced complications such as osteoporosis, diabetes, cataract and arteriosclerosis. It has been speculated that perhaps these complications result from lipid profile alterations by prednisolone. The effects of extended prednisolone treatment on lipid profiles in ENL patients have not been studied in leprosy patients with ENL reactions. Therefore, in this study we conducted a case-control study to investigate the changes in lipid profiles and serological responses in Ethiopian patients with ENL reaction after prednisolone treatment. METHODS: A prospective matched case-control study was employed to recruit 30 patients with ENL and 30 non-reactional LL patient controls at ALERT Hospital, Ethiopia. Blood samples were obtained from each patient with ENL reaction before and after prednisolone treatment as well as from LL controls. The serological host responses to PGL-1, LAM and Ag85 M. leprae antigens were measured by ELISA. Total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured by spectrophotometric method. RESULTS: The host antibody response to M. leprae PGL-1, LAM and Ag85 antigens were significantly reduced in patients with ENL reactions compared to LL controls after treatment. Comparison between patients with acute and chronic ENL showed that host-response to PGL-1 was significantly reduced in chronic ENL after prednisolone treatment. Untreated patients with ENL reactions had low lipid concentration compared to LL controls. However, after treatment, both groups had comparable lipid profiles except for LDL, which was significantly higher in patients with ENL reaction. Comparison within the ENL group before and after treatment showed that prednisolone significantly increased LDL and HDL levels in ENL patients and this was more prominent in chronic ENL than in acute patients with ENL. CONCLUSION: The significantly increased prednisolone-induced LDL and TG levels, particularly in patients with chronic ENL reactions, is a concern in the use of prednisolone for extended periods in ENL patients. The findings highlight the importance of monitoring lipid profiles during treatment of patients to minimize the long-term risk of prednisolone-induced complications.

T-cell regulation in Erythema Nodosum Leprosum.

Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T-cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL.

Treatment of severe refractory erythema nodosum leprosum with tumor necrosis factor inhibitor Etanercept.

Erythema nodosum leprosum (ENL) is a common complication of lepromatous leprosy. Some patients unresponsive to conventional, first-line therapeutics develop recurrent, recalcitrant ENL. Here, we report a case of severe refractory ENL that was successfully treated with Etanercept. Biologics may be considered as therapeutic alternatives in management of severe, recalcitrant ENL.

Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia.

BACKGROUND: Erythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL. METHODS AND RESULTS: Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin. CONCLUSIONS: This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients' assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid-sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale.

Elastophagocytosis and Elastolysis in Leprosy.

Elastophagocytosis is the engulfment of the elastic fibres by the histiocytes, multinucleated giant cells, or both. The cutaneous lesions showing elastophagocytosis are annular elastolytic giant cell granuloma, actinic keratoses, persistent insect-bite reactions, elastosis perforans serpiginosa, foreign body granuloma. Occasionally, it may occur in infectious diseases like leprosy, granulomatous syphilis, North-American blastomycosis, bacterial folliculitis, and cutaneous leishmaniasis. We report a case of lepromatous leprosy with necrotic erythema nodosum leprosum with secondary anetoderma. Histopathology from the atrophic macule of anetoderma revealed periappendageal, perineural infiltration, elastophagocytosis and reduction in elastic fibres.

Unusual Presentation of Necrotic Erythema Nodosum Leprosum on Scalp: A Case Report.

Lepra reactions are acute episodes occurring during the disease process of leprosy and are of 2 types: type 1 or reversal reaction and type 2 reaction or erythema odosumleprosum (ENL). In the episodes of lepra reaction several parts are affected including face and extremities like oral cavity. In the present case report we reported a rare case of lepromatous leprosy with necrotic ENL involving scalp apart from the usual sites. A 58 year old married male presented to us with complaints of spontaneous onset, recurrent eruption of multiple reddish raised painful lesions. Biopsy from the infiltrated skin over the back showed atrophic epidermis, free Grenz zone, diffuse and periadnexal macrophage granulomas with predominant mononuclear infiltrate, appandageal atrophy, fibrosis around the neural structures and leukocytoclastic vasculitis. Fites stain showed strong positivity for M. leprae. His routine blood investigations showed anemia (Hb = 7.8 gm%), neutrophil leukocytosis (TLC = 17,600, DLC = P66L28M4E2) and raised ESR (80 mm in the first hour). These bullous and necrotic lesions in leprosy may be a manifestation of severe type II reactions in patients with very high bacillary load.

Resident rounds part III: case report: a papulo- nodular eruption with systemic signs and symptoms.

This is a typical presentation of erythema nodosum leprosum in a patient with lepromatous leprosy who recently migrated from Micronesia. The clinical presentation, pathology findings, pathogenesis, and therapeutic options are reviewed here.

Recognizing and managing the immunologic reactions in leprosy.

Immunologic reactions are an important aspect of leprosy that significantly impacts the course of the disease and the associated disability. Reversal reaction (type 1), erythema nodosum leprosum (type 2), and Lucio phenomenon are the 3 leprosy reactions, and they are most commonly seen in patients with the lepromatous and borderline categories of the disease. Because these forms of leprosy are the most common types seen in the United States, it is particularly important for physicians to be able to recognize and treat them. The reactions may occur before, during, or after treatment with multidrug therapy. Reversal reactions are the most common cause of nerve damage in leprosy, and erythema nodosum leprosum may also lead to neuritis. Although there have not been enough studies to confirm the most effective management regimens, treatment of reversal reaction and Lucio phenomenon with prednisone and of erythema nodosum leprosum with thalidomide and/or prednisone may help improve symptoms and prevent further disability.

[Effectiveness of thalidomide for erythema nodosum leprosum (ENL): retrospective study of 20 Japanese cases in National Sanatrium Oku-Komyoen].

Thalidomide is a TNF-alpha inhibitor and has been administrated for erythema nodosum leprosum (ENL, Type II leprosy reaction) which is one of leprosy reactions and can cause serious illness to patients oflepromatous pole among the immune spectrum. Twenty live cases (at May, 2011) were identified to whom thalidomide had been administrated since 1978 for their ENL reactions. Data were collected from their clinical records in order to evaluate the usage and effectiveness of thalidomide in National Sanatorium Oku-Komyoen, Okayama, Setouchi-city, Japan. Individual data includes bacillary index (BI), total dose, average daily dose, maximum daily dose, minimum daily dose, methods of thalidomide administration and change of symptoms of ENL. Results: No adverse effect was found among 20 cases. Average daily dose of 20 cases was 19 mg. Regarding to the maximum daily dose, in 3 cases (15%) more than 100 mg, in 3 cases (15%) 50 mg, and in 14 cases (70%) less than 40 mg was administrated. Dose was gradually tapered in most cases. From clinical records, thalidomide was found effective for ENL in 19 cases and clinicians concerned were trying to adjust the proper dose of the drug carefully depending on the current symptoms, because there was no guideline of thalidomide administration for ENL. This data suggests that even less than 50-100 mg as the initial daily dose was still effective, though 50-100 mg daily dose is recommended in the current guideline of Japan (2011) and more dose had been administrated in USA and India.

Using methotrexate to treat patients with ENL unresponsive to steroids and clofazimine: a report on 9 patients.

UNLABELLED: Erythema nodosum leprosum (ENL) is a chronic recurrent systemic complication of multi-bacillary leprosy frequently associated with the development of neuritis, iritis, orchitis, arthritis and dactylitis. It is well managed by thalidomide, but thalidomide is not available in Bangladesh. The World Health Organization recommends high doses of clofazimine and prednisolone. About 19% of patients do not respond completely to this regimen or experience relapse when reducing steroid dosage. OBJECTIVE: We undertook this study to determine whether oral prednisolone combined with methotrexate was an effective and safe treatment regimen for individuals with ENL resistant to clofazimine and prednisolone. METHODOLOGY: Between September, 2006-June, 2011, we treated nine resistant ENL patients with a combination of prednisolone and methotrexate for 24-36 months with a mean duration of 30 months. RESULT: We observed improvement leading to persistent remission of ENL in all our patients. Adverse effects were mild weight gain, weight gain with facial swelling, folliculitis and extensive Pityriasis versicolor infection in one patient and crusted scabies in another. CONCLUSION: A combination of prednisolone and methotrexate was safe and effective in managing ENL not controlled by clofazimine and prednisolone.

[Leprosy reactions in a Colombian national reference centre]. / Reacciones por lepra en un centro de referencia nacional en Colombia.

INTRODUCTION: Colombia is the country in America with the highest proportion of new cases leprosy with severe disability. To decrease such disability it is necessary to control these reactions, the main cause of nerve damage in leprosy. OBJECTIVE: To describe the clinical and epidemiological characteristics and the treatment of patients with type 1 and 2 leprosy reactions who consulted the Centro Dermatológico Federico Lleras Acosta. MATERIALS AND METHODS: It is a descriptive study which included patients with clinical diagnoses of type 1 and 2 reactions who were seen in the center between 2003 and 2009. The town of origin of the patients, their age, clinical features and treatments were analysed. RESULTS: We studied 96 reactions in 87 patients, 35 type 1 and 61 type 2 reactions; 75% of the patients came from the departments of Tolima, Cundinamarca, Santander and Boyacá; 77% of type 1 reaction occurred before the beginning of multidrug therapy for leprosy. The reactions that started after stopping the multidrug therapy were considered as a leprosy relapse. CONCLUSIONS: Correct identification of type 1 reaction by the general practitioner will allow the diagnosis of leprosy in a large percentage of patients. The type 1 reaction that begins after stopping the leprosy multidrug therapy may be a manifestation of a relapse of the disease.

Reacciones por lepra en un centro de referencia nacional en Colombia / Leprosy reactions in a Colombian national reference centre

Introducción. Colombia es el país de América con mayor proporción de casos nuevos de lepra con discapacidad grave. Para disminuir tal discapacidad se requiere el control de las reacciones, principal causa del daño neural en esta enfermedad. Objetivo. Describir las características clínicas y epidemiológicas y el tratamiento de los pacientes con reacciones de tipo 1 y 2 que consultaron al Centro Dermatológico Federico Lleras Acosta. Materiales y métodos. Se trata de un estudio descriptivo que incluyó la población de pacientes con diagnóstico clínico de reacciones de tipo 1 y de tipo 2 por lepra, que acudieron al centro entre los años 2003 y 2009. Resultados. Se estudiaron 96 reacciones, 35 del tipo 1 y 61 del tipo 2. El 75 % de los pacientes provenía de los departamentos de Tolima, Cundinamarca, Santander y Boyacá. El 56 % de las reacciones de tipo 1 se presentaron antes de iniciar la poliquimioterapia para la lepra; el dermatólogo tratante consideró que las reacciones que se presentaron después de suspender la poliquimioterapia eran recaídas. El 94 % de las reacciones de tipo 1 se trataron con corticoides orales. El 97 % de los pacientes con reacciones de tipo 2 presentaron eritema nudoso, y todos se trataron con talidomida. Conclusiones.La clínica de la reacción de tipo 1 puede orientar al diagnóstico de la lepra en un paciente sin el antecedente de esta enfermedad (56 %). La reacción de tipo 1 que se inicia después de suspender la poliquimioterapia para la lepra, podría ser una manifestación de recaída de la enfermedad. La reacción de tipo 2 es más frecuente en hombres, con una relación hombre a mujer de 4:1. El 97 % de los pacientes con reacción de tipo 2 presentó eritema nudoso.

Introduction: Colombia is the country in America with the highest proportion of new cases leprosy with severe disability. To decrease such disability it is necessary to control these reactions, the main cause of nerve damage in leprosy. Objective: To describe the clinical and epidemiological characteristics and the treatment of patients with type 1 and 2 leprosy reactions who consulted the Centro Dermatológico Federico Lleras Acosta. Materials and methods: It is a descriptive study which included patients with clinical diagnoses of type 1 and 2 reactions who were seen in the center between 2003 and 2009. The town of origin of the patients, their age, clinical features and treatments were analysed. Results: We studied 96 reactions in 87 patients, 35 type 1 and 61 type 2 reactions; 75% of the patients came from the departments of Tolima, Cundinamarca, Santander and Boyacá; 77% of type 1 reaction occurred before the beginning of multidrug therapy for leprosy. The reactions that started after stopping the multidrug therapy were considered as a leprosy relapse. Conclusions: Correct identification of type 1 reaction by the general practitioner will allow the diagnosis of leprosy in a large percentage of patients. The type 1 reaction that begins after stopping the leprosy multidrug therapy may be a manifestation of a relapse of the disease.

[Leprosy and the testis]. / La lepra y el testículo.

INTRODUCTION: Damage of testicles is frequent in lepromatous leprosy and worsened by the presence of erythema nodosum leprosum. Objective. A patient is presented who developed lepromatous leprosy and erythema nodosum leprosum with major testicular compromise. MATERIAL AND METHODS: The 28-year-old male patient had lepromatous leprosy since age 22. During a polychemotherapy treatment for the lepromatous leprosy, he presented chronic erythema nodosum leprosum that affected both testicles; he did not respond to the conventional treatment. A left orchidectomy was performed to treat the persistent pain. RESULTS: The extracted testis evidenced the following: tubular atrophy, extensive fibrosis, cumulus of foamy macrophages without rods, focal Leydig cell hyperplasia, linfocitary and granulomatous arteritis and endarteritis of small and medium size vessels. These changes were also observed in the epididymis. Two years after the polychemoterapy and the orchidectomy, the patient exhibited azoospermy, normal total testosterone, slightly diminished free testosterone and elevated levels of luteinizing hormone and follicle-stimulating hormone. No loss of libido or sexual activity was reported. General concepts of erythema nodosum leprosum were reviewed, as well as the pathologic changes produced by leprosy in the testis. CONCLUSION: Lepromatous leprosy may lead to hypogonadism. This condition is recommended for inclusion in leprosy diagnostic programs in order to detect and treat the consequences of the possible hypogonadism.