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.

Rejection-triggered haemophagocytic syndrome in renal transplantation successfully treated with intravenous immunoglobulin.

Haemophagocytic syndrome (HPS) is a rare and potentially lethal condition characterized by pancytopoenia, fever, organomegaly and widespread proliferation of macrophages phagocytosing blood elements. Among the triggers of this syndrome, excessive immunosuppression in a context of acute rejection has been rarely reported, although it might be underdiagnosed. Here, we report the case of a kidney transplant recipient with allograft dysfunction due to chronic antibody-mediated rejection treated with antithymocyte globulin and plasmapheresis. The patient developed high fever, pancytopoenia, diarrhoea and respiratory symptoms with no apparent infectious or neoplastic cause, despite an extensive work-up. Haemophagocytosis was found in bone marrow examination, along with hyperferritinaemia and hypertriglyceridaemia. The clinical profile improved after treatment with intravenous immunoglobulin and reduction of the basal immunosuppression.

Treatment of coronary artery disease in hemodialysis patients evaluated for transplant-a registry study.

BACKGROUND: We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD). METHODS: We analyzed 519 patients with CKD (56+/-9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography. RESULTS: In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction > or =70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft-intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48-15.10; death: hazard ratio=3.39; % confidence interval 1.41-8.45). CONCLUSIONS: In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.