Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

BACKGROUND: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. CASE PRESENTATION: A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. CONCLUSIONS: Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.

Meaning of leprosy for people who have experienced treatment during the sulfonic and multidrug therapy periods / Significado da hanseníase para pessoas que viveram o tratamento no período sulfônico e da poliquimioterapia / Significado de la lepra para personas que experimentaron el tratamiento en el período sulfónico y de poliquimioterapia

AbstractObjective: to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods.Method: qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy.Results: the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy.Conclusion: the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous.

ResumoObjetivo:analisar significados da hanseníase para as pessoas que foram tratadas no período sulfônico e no período da poliquimioterapia.Método:estudo de natureza qualitativa fundamentado na abordagem histórico-cultural de Vigotski, a qual orientou a construção e análise dos dados. Foram incluídos oito entrevistados que já tiveram hanseníase e que realizaram tratamento no período sulfônico e da poliquimioterapia, sendo participantes do Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Resultados:os significados foram organizados em três núcleos de significação: manchas no corpo: alguma coisa está fora de ordem; lepra ou hanseníase? e hanseníase a partir da inserção no Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Conclusão:os significados de hanseníase para pessoas tratadas nos dois períodos apontam para a construção complexa dos mesmos, indicando diferenças e semelhanças nos dois períodos. Os profissionais de saúde podem contribuir para a mudança de significados, pois esses são socialmente construídos e as transformações são contínuas.

ResumenObjetivo:analizar los significados de la lepra para las personas que fueron tratadas en el período sulfónico y en el período de poliquimioterapia.Método:estudio de naturaleza cualitativa fundamentado en el abordaje histórico cultural de Vygotsky, el cual orientó la construcción y análisis de los datos. Fueron incluidos ocho entrevistados que ya tuvieron lepra y que realizaron tratamiento en el período sulfónico y de poliquimioterapia, siendo participantes del Movimiento de Reintegración de Personas Afectadas por la Lepra.Resultados:los significados fueron organizados en tres núcleos de significación: manchas en el cuerpo: alguna cosa está fuera de orden; ¿Lepra o enfermedad de Hansen?; y lepra a partir de la inserción en el Movimiento de Reintegración de Personas Afectadas por la Lepra. Conclusión: los significados de la lepra para las personas tratadas en los dos períodos apuntan para la construcción compleja de los mismos, indicando diferencias y semejanzas en los dos períodos. Los profesionales de la salud pueden contribuir para el cambio de significados, ya que estos son socialmente construidos y las transformaciones son continuas.

[Multibacillary leprosy in a renal recipient patient: a case report]. / Hanseníase multibacilar em paciente transplantado renal: relato de caso.

Leprosy is still a public health concern in Brazil, where more than 30,000 new cases are detected every year. There are few reports of this mycobacteriosis in immunosuppressed patients, despite the increasing number of solid organ transplantation and the use of post-transplant drugs in this country. The authors describe a case of multibacillary leprosy in a renal transplant recipient, detected 12 years after the procedure, and discuss the therapy, adverse effects and management of leprosy reactions in patients immunosuppressed by drugs.

Hanseníase multibacilar em paciente transplantado renal: relato de caso / Multibacillary leprosy in a renal recipient patient: a case report

O Brasil é um país onde a hanseníase ainda é um problema de saúde pública, apresentando mais de 30.000 novos casos por ano nos últimos anos. Apesar do crescente número de transplante de órgãos sólidos realizados no país, sobretudo o transplante renal, não são frequentes os relatos dessa micobacteriose em pacientes imunossuprimidos pelas medicações póstransplante. Os autores relatam um caso de hanseníase multibacilar manifestada 12 anos depois do transplante renal, acompanhado desde o diagnóstico, durante a poliquimioterapia, tratamento e seguimento do eritema nodoso hansênico.

Leprosy is still a public health concern in Brazil, where more than 30,000 new cases are detected every year. There are few reports of this mycobacteriosis in imunossupressed pacients, despite the increasing number of solid organ transplantation and the use of post-transplant drugs in this country. The autors describe a case of multibacillary leprosy in a renal transplant recipient, detected 12 years after the procedure, and discuss the therapy, adverse effects and management of leprosy reactions in pacients imunosupressed by drugs.

Lepromatous leprosy in a kidney transplant recipient: a case report.

Leprosy is a chronic granulomatous disease of the skin and peripheral nerves caused by Mycobacterium leprae. Among mycobacterial infections, leprosy is rare in renal transplant recipients. Here, we report the manifestations of lepromatous leprosy in a 41-year-old renal transplant recipient. Before the renal transplant, the patient had recurrent bullous lesions on his extremities with no systemic complaints. He was on an immunosuppressive regimen that included prednisolone (1 mg/kg/d), cyclosporine (6 mg/kg), and mycophenolate mofetil (2000 mg/d), and had 2 serologically confirmed acute episodes of cytomegalovirus infection that responded favorably to intravenous ganciclovir. The density of his bullous skin lesions decreased after renal transplant. During his regular posttransplant visits, we noticed a decrease in his eyebrow hairs on their lateral margins bilaterally. Later, he developed generalized, symmetric, erythematous papules. With a positive acid-fast bacilli with Fite staining, the results of a skin biopsy showed diffuse foamy histiocyte infiltration in the dermis. These findings are compatible with lepromatous leprosy. After antileprosy therapy, no deterioration of renal allograft function or lepra reactions was noted in a 4-month follow-up. Clinicians should consider leprosy in the differential diagnosis of skin lesions in immunocompromised hosts, and in particular, solid organ transplant recipients in endemic areas.

Leprosy in a renal transplant recipient: review of the literature.

A 52-year-old male underwent living-related renal transplantation. He received prednisolone, azathioprine, and cyclosporine as immunosuppression protocol. Eleven years after transplantation, he developed pyrexia with multiple nodular lesions on his limbs, trunk, and face. Skin biopsy and smears showed the presence of numerous acid-fast bacilli with 5% sulfuric acid indicative of Mycobacterium leprae. He was initiated on multidrug therapy (MDT) including dapsone, clofazimine, and rifampicin. After 2 years of MDT, he developed new multiple erythematous, tender subcutaneous nodules in crops over his face and upper limbs. Skin biopsies and histopathological examination confirmed the diagnosis of type 2 lepra reaction or erythema nodosa leprosum. He was managed with an increase in the dose of prednisolone and thalidomide. He was continued on MDT.

Skin lesions in renal transplant recipients: a single center analysis.

BACKGROUND: The chronic use of immunosuppressants in renal transplant recipients (RTRs) predisposes them to a variety of skin manifestations. Studies on skin lesions in RTRs from India have been limited. AIM: To study the prevalence and clinical spectrum of skin diseases in RTR in patients attending the Nephrology clinic of a tertiary care hospital in South India. METHODS: Between October 2002 and June 2003, 365 RTRs were evaluated for skin lesions, including 280 examined after renal transplant (group A) and 85 examined once before and then monthly after transplant for a period of 6 months (group B). RESULTS: A total of 1163 skin lesions were examined in 346 RTRs (94.7%) including lesions of aesthetic interest (LAI) [62.3%] followed by infections [27.3%]. All LAI were drug-related manifestations, making it the most common skin lesion, while fungal (58.7%) and viral (29.3%) infections constituted majority of lesions caused by infection. Lesions related to neoplasms were relatively uncommon (2.1%) and all lesions were benign. Miscellaneous lesions constituted 8.3% of skin lesions, which included vaccine-induced necrobiotic granulomas at the site of Hepatitis B vaccination and acquired perforating dermatoses. CONCLUSION: Skin lesions among RTRs from India consist predominantly of drug-related LAI and infections and are different from the West in view of the paucity of neoplastic lesions.

Leprosy in a renal transplant recipient: a case report and literature review.

Leprosy is rarely seen in organ transplant patients; only ten cases of leprosy in organ transplant recipients have been reported. We herein report a Taiwanese renal transplant recipient concomitantly infected with borderline lepromatous leprosy. A 68-year-old male received renal transplantation at Guilin, China, in 2000, and then received immunosuppressive therapy with prednisolone, tacrolimus, and mycophenolate. Three years after transplantation, multiple erythematous tender nodules and plaques over the face and lower limbs developed. Biopsies and histopathological examination confirmed the diagnosis of leprosy. We treated the patient with a multidrug regimen including dapsone, clofazimine, and rifampine since November of 2003 with a good response. Unfortunately, he suffered from a cluster of complications after an accidental fall, finally leading to septic shock and death five months later. In summary, we report a rare case of new-onset leprosy after renal transplantation in Taiwan and suggest leprosy should be listed in the differential diagnosis of unusual skin manifestations in organ transplant patients.

Trasplante renal y lepra / Renal trasplantation and leprosy

Presentamos un paciente varon de 62 años que diez años despues de ser sometido a un trasplante renal contrajo lepra dimorfa lepromatosa. A los ocho meses de recibir la terapeutica multidroga de la Organizacion Mundial de la Salud desarrollo un cuadro de deterioro agudo de la funcion del riñon trasplantado relacionado con la administracion de rifampicina. El paciente evoluciono en forma favorable con la suspension del farmaco y continuo tratamiento para su enfermedad de Hansen con un esquema alternativo con buena evolucion. Destacamos la dificultad terapeutica del paciente trasplantado con lepra y la necesidad de un estricto control nefrologico durante el tratamiento. El compromiso renal por rifampicina es raro; su incidencia aumenta cuando el farmaco es administrado en forma intermitente

Trasplante renal y lepra / Renal trasplantation and leprosy

Presentamos un paciente varon de 62 años que diez años despues de ser sometido a un trasplante renal contrajo lepra dimorfa lepromatosa. A los ocho meses de recibir la terapeutica multidroga de la Organizacion Mundial de la Salud desarrollo un cuadro de deterioro agudo de la funcion del riñon trasplantado relacionado con la administracion de rifampicina. El paciente evoluciono en forma favorable con la suspension del farmaco y continuo tratamiento para su enfermedad de Hansen con un esquema alternativo con buena evolucion. Destacamos la dificultad terapeutica del paciente trasplantado con lepra y la necesidad de un estricto control nefrologico durante el tratamiento. El compromiso renal por rifampicina es raro; su incidencia aumenta cuando el farmaco es administrado en forma intermitente (AU)