Therapy of visceral leishmaniasis in renal transplant recipients intolerant to pentavalent antimonials

Visceral leishmaniasis should be suspected in renal transplant recipients in whom a fever develops of unknown origin. A 53-year-old renal transplant recipient developed pyrexia, hepatosplenomegaly, and pancytopenia 4 years after transplantation. Antileishmaniasis serology was negative, and the diagnosis was confirmed through bone marrow examination. Treatment with glucantine (N-methylglucamine antimoniate) led to acute pancreatitis, and treatment with ketoconazole plus allopurinol for 21 days was effective to eradicate Leishmania donovani.     

Non-typhoid Salmonella septicemia and visceral leishmaniasis in a renal transplant patient

BACKGROUND: We report on a renal transplant patient with recurrent attacks of fever, in which Salmonella septicemia as well as visceral leishmaniasis were diagnosed. PATIENT: The patient was a 62-year-old man with diabetic nephropathy and a living related kidney transplantation. RESULTS: Nearly 2 years after the transplantation, the patient developed recurrent attacks of fever, which were initially diagnosed as non-typhoid salmonellosis and improved after treatment. Three months later, he had relapses of fever. As the patient developed pancytopenia, a bone marrow aspiration was done, showing Leishmania parasites. The patient responded well to treatment with sodium stibogluconate. CONCLUSIONS: A high index of suspicion, together with better diagnostic assays to detect visceral leishmaniasis, is warranted in the diagnostic work-up of any fever of unknown origin in immunocompromised patients, especially in endemic areas.     

Toxoplasmosis-associated hemophagocytic syndrome in renal transplantation

Toxoplasmosis is an infrequent, often difficult to diagnose and potentially lethal disease in kidney transplant recipients. Among reported cases, a few were associated with hemophagocytic syndrome (HPS), a rare condition characterized by widespread proliferation of macrophages phagocytizing blood elements, accompanied by fever and pancytopenia. We report here the case of a patient who received a Toxoplasma gondii positive kidney allograft and developed invasive toxoplasmosis 10 days after surgery, with high fever, skin rash, arthralgias, and renal failure, followed by pneumonia, anemia, thrombocytopenia, liver dysfunction, and encephalitis. Mislead by the absence of Toxoplasma on blood smears, alveolar fluid, renal graft biopsy, and negative brain computed tomography, confusion with serum sickness, and simultaneous herpetic infection, we failed to make the right diagnosis and the patient died with septic shock 11 days later. An HPS was revealed by a late bone marrow analysis. This may well be the fourth case ever reported of toxoplasmosis-associated HPS in renal transplant recipients.     

Azathioprine-lnduced Megaloblastic Anemia with Pancytopenia 22 Years after Living-Related Renal Transplantation

Macrocytosis and megaloblastic changes in the bone marrow are frequently seen in renal transplant recipients treated with azathioprine(Az). However, severe anemia is a rare side effect of Az. We recently observed a case of severe megaloblastic anemia with pancytopenia in a renal transplant recipient who had been receiving Az therapy for 22 years. The patient was a 46-year-old woman who had been administered Az and prednisolone at a dose of approximately 1.7mg/kg and 0.17 mg/kg daily, respectively. A bone marrow aspiration revealed megaloblastic anemia with the depletion of myeloid cells and megakaryocytes. She did not have vitamin B₁₂ or folate deficiency. Therefore, FK506 (tacrolimus), a macrolide produced by Streptomyces tsukubaensis, which acts directly on T cells and is known to have less myelosuppression than Az, was substituted for Az. Although the leukopenia improved, the anemia and thrombocytopenia did not improve in the short term. She developed dyspnea and severe subcutaneous bleeding of the right lower extremity due to knee contusions. Hemodialysis was started to treat her uremic state. Although it was impossible to evaluate the long-term effects of FK506 therapy for the pancytopenia in our case, the conversion from Az to a less myelosuppressive drug, such as FK506, should be considered in renal transplant recipients with severe myelosuppression caused by long-term Az treatment.     

两性霉素B脂质体梯形方案成功治疗复发性黑热病一例

目的通过对黑热病复发患者两性霉素B脂质体（L-AmB）治疗病例进行回顾性总结，为临床诊疗提供依据。 方法回顾性分析患者的临床资料、诊疗经过和实验室指标。 结果患者，男性、60岁。6个月前因发热、血常规示血红蛋白、白细胞计数及血小板计数减低、脾脏肿大等经骨髓检测确诊黑热病，予足量锑剂治疗好转。仅间隔5个月，再次出现上述症状，复查骨髓提示黑热病复发，经L-AmB个体化梯形方案给药并小剂量维持（第1日10 mg，约0.15 mg·kg^-1·d^-1；第2日起按照10 mg/d逐日递增，至40 mg/d，约0.6 mg·kg^-1·d^-1小剂量维持，直至达指南推荐剂量）治疗好转，随访3个月无复发。 结论L-AmB梯形方案给药并小剂量维持可实现黑热病的病原学治愈。     

Haemophagocytic syndrome after liver transplantation in adults

The haemophagocytic syndrome is defined as a proliferation of phagocytic macrophages in the bone marrow, lymph nodes and spleen. Clinically, it is characterised by fever and pancytopenia. We present here a case of haemophagocytic syndrome after liver transplantation in a 63-year-old man who had undergone transplantation for autoimmune hepatitis. One month after liver transplantation, he developed ascites, fever and progressive pancytopenia. Bone marrow biopsy showed proliferation of non-neoplastic histiocytes, demonstrating phagocytosis of haemopoietic cells. No infectious or neoplasm-associated disease was found. Several kinds of treatment were attempted, but the course was fatal. The haemophagocytic syndrome is uncommon after liver transplantation, but this diagnosis has to be kept in mind in cases of pancytopenia of unknown origin.     

Hemophagocytic syndrome as an unusual form of presentation of tuberculosis in a hemodialysis patient: case report and review of the literature

We present an unusual manifestation of tuberculosis in a patient on hemodialysis. A 73-year-old woman was admitted to our hospital with a picture of fever, dyspnea and weight loss. She had chronic renal failure and had started periodic hemodialysis 5 years before. Fifteen days after admission, she began with pancytopenia, abnormal liver function and coagulopathy. A bone marrow aspiration was made 1 week later showing macrophage elements with phagocytic activity. Eight weeks later, bone marrow culture in Lowenstein media confirmed the presence of tuberculosis. After the beginning of antituberculosis therapy, the laboratory disturbances disappeared and the clinical situation improved. We think that fever of unknown origin and pancytopenia in patients on maintenance hemodialysis must lead to an early bone marrow biopsy or aspiration since after the diagnosis a specific therapy can cure the disease.     

Sinus disease in the bone marrow transplant population: Incidence, risk factors,and complications

BACKGROUND: Fever associated with sinus disease in the immunocompromised bone marrow transplant recipient requires prompt evaluation and therapy. Very little is known about the incidence, risk factors, and sequelae of nonsurgically treated sinus disease in this population. METHODS: A retrospective review of 107 consecutive allogeneic and autologous bone marrow transplant recipients from August 1987 to July 1989 was performed to determine (1) the overall incidence of sinus disease; (2) factors that influence the development of sinus disease; and (3) the sequelae of sinus disease treated nonsurgically. RESULTS: Overall 33 (31%) of 107 bone marrow transplant recipients had sinus disease defined as a radiographic abnormality with clinical symptoms. Eleven (10%) of 107 recipients had preexisting sinus disease. Sinus disease developed in 22 (21%) of 107 recipients after bone marrow transplantation. Sinus abnormalities were significantly higher among allografted bone marrow transplant recipients than among autografted recipients (p = 0.027). The diagnosis, stage of disease, cytoreductive regimen, or graft-vs.-host disease were not different between recipients in whom sinus disease did and did not develop. There were no deaths as a result of sinus complications. CONCLUSIONS: Sinus disease developed in 21% of the studied population after bone marrow transplantation. Allogeneic recipients had a higher incidence of sinus disease than autologous recipients. There were no deaths attributed to sinus complications. All sinus disease in this bone marrow transplant population was treated medically. No patient required surgical intervention either before or after bone marrow transplantation. (OTOLARYNGOL HEAD NECK SURG 1995;113:705-11.)     

Disseminated Histoplasmosis Associated with Hemophagocytic Lymphohistiocytosis in Kidney Transplant Recipients

Transplant patients are susceptible to infectious complications due to chronic immunosuppression. We present two cases of persistent fever, weight loss and pancytopenia in kidney transplant recipients (originally concerning for posttransplant lymphoproliferative disease) that were later diagnosed with disseminated histoplasmosis on bone marrow and lymph node biopsy. In both patients, pancytopenia was due to hemophagocytic lymphohistiocytosis (HLH) which has rarely been described in association with histoplasmosis and not previously reported in kidney transplant recipients with this fungal infection. The diagnosis of histoplasmosis can be complex due to nonspecific symptomatology, delays in isolating histoplasma by fungal culture and false‐negative antibody titers in immunocompromised patients. A review of the literature including the clinical features of histoplasmosis in immunosuppressed patients (prevalence, current diagnostic testing and treatment options) as well as the association of HLH in immunocompromised states are discussed.     

Visceral Leishmaniasis: A Case Report of a Challenging Diagnosis After Orthotopic Liver Transplantation

Leishmaniasis is a disease caused by a protozoan and transmitted by sandfly species in several emerging countries. Visceral leishmaniasis is a serious complication, especially in immunosuppressed patients, and is uncommon after liver transplantation. We report the case of a 48-year-old female patient who underwent liver transplantation owing to polycystic liver disease. Six months after the procedure, she was hospitalized with diarrhea, acute kidney failure, and leukopenia. She had been off steroids for 3 months and was taking mycophenolate and tacrolimus. She had already been treated for cytomegalovirus, which was negative on admission. During hospitalization, fever, splenomegaly, ascites, and pancytopenia appeared. Serology for Leishmania by indirect immunofluorescence was negative. Then, bone biopsy and molecular testing for Leishmania diagnosed it as visceral leishmaniasis. Amphotericin therapy was initiated with resolution of fever after 4 days of treatment and gradual recovery from pancytopenia. This case highlights the challenge of early diagnosis of visceral leishmaniasis in liver transplant recipients with diarrhea and leukopenia, which can be caused by immunosuppression or more prevalent viral diseases. Late onset of fever, splenomegaly, and a first negative serologic test also made early diagnosis difficult. The aim of the report is to emphasize the suspicion of visceral leishmaniasis in symptomatic patients from emerging countries and to question the benefit of including protozoan screening in liver transplant donors and recipients in endemic areas.     

Visceral Leishmaniasis in renal transplant recipients: is it still a challenge to the nephrologist?

A case of visceral Leishmaniasis in a renal transplant recipient is reported because of its peculiar clinical presentation: the presence of most clinical signs of the disease, such as high-grade fever, marked leucopenia, and splenomegaly, but persistent negativity of serology and of bone marrow smear. Forty days after the first bone marrow biopsy, the diagnosis was made possible by a second biopsy, and the treatment was started with antimonial compounds, which led to complete remission of symptoms. A relapse was observed 1 month after discontinuation of therapy, successfully treated with a new cycle of the same drug and allopurinol. The diagnosis of Leishmaniasis must always be considered in immunosuppressed transplant recipients with fever and leucopenia of unknown origin, even when serology and bone marrow smear are negative.     

Leishmaniasis in solid organ and hematopoietic stem cell transplant recipients

Leishmaniasis occurs in <1% of solid organ and hematopoietic stem cell transplant recipients in endemic countries in which transplants are performed. Visceral leishmaniasis (VL) makes up the bulk of reported cases. The onset generally occurs months after transplantation and the mode of acquisition is often impossible to determine, but de novo vector‐borne infection and reactivation of inapparent infection are thought to be the principal means. The potential role of clinically inapparent donor infection is uncertain and screening is not currently recommended, nor is it recommended for recipients from endemic areas, some of whom may have detectable circulating protozoan nucleic acid. While transplant recipients with VL often present with the non‐specific findings of fever and cytopenia, the additional presence of hepatosplenomegaly in patients from endemic areas should lead to a directed diagnostic evaluation with bone marrow examination and PCR testing of marrow and peripheral blood having a high yield. Management may often be complicated by the presence of concomitant infections. A lipid formulation of amphotericin B is the preferred treatment, especially for VL, but the relapse rate in transplant recipients is approximately 25%. PCR monitoring of blood for either secondary prophylaxis or preemptive therapy requires further study.     

Unresponsiveness to a kidney graft after a fully matched allogenic bone marrow transplantation combined with low-dose tacrolimus therapy: a case report

We present the case of a patient with past medical history of acute mieloblastic leukemia treated with a related, fully match alogenic bone marrow transplantation (BMT). He presented after BMT treatment graft versus host disease (GVHD) and thrombotic thrombocytopenic purpura. He also developed end-stage renal disease that required renal replacement therapy. A preemptive kidney transplant was performed. The haematopoiesis were in complete chimera and the patient developed tolerance to the kidney graft, requiring only minimal immunossupression because of his GVHD.     

Fatal hemophagocytic syndrome after living-related liver transplantation: a report of two cases.

BACKGROUND: Hemophagocytic syndrome (HPS) is a serious hematological disorder caused by activated T lymphocytes in immunologically compromised patients. There is no report of HPS in liver transplant recipients. METHODS: Among 135 patients who underwent living-related liver transplantation between June 1990 and October 2000, HPS developed in two pediatric patients (1.5%) on the 15th and 134th postoperative day, respectively. The courses of these patients were evaluated. RESULTS: The cause of HPS was unknown in patient 1 and suspected to be Epstein-Barr virus infection in patient 2. The course of patient 2 was also complicated by posttransplant lymphoproliferative disorder. Both patients had high fever, pancytopenia, coagulopathy, and marked elevation of serum-soluble interleukin 2 receptor, serum ferritin, and urine beta2-microglobulin levels. The diagnosis was established based on clinical findings, laboratory data, and bone marrow biopsy. Both patients died in an acute course despite intensive care. CONCLUSIONS: HPS should be recognized as a severe hematological complication in liver transplant patients. Prompt institution of adequate treatment is necessary to prevent fatality.     

Graft-versus-Host Disease Presenting With Pancytopenia After En Bloc Multiorgan Transplantation: Case Report and Literature Review

Graft-versus-host disease (GVHD) is a dreaded complication of bone marrow and solid organ transplantation. Commonly affected organs include skin, liver, and the gastrointestinal tract, with bone marrow and renal involvement occurring more rarely. GVHD is less commonly seen with solid organ transplants. Fewer than 100 cases of GVHD have been reported in the literature following liver transplantation. We report a case of a 53-year-old woman who required a multiorgan transplant after a complicated postoperative course following paraduodenal hernia repair. She developed isolated pancytopenia approximately 4 months after receiving an en bloc transplant involving the liver, kidney, small bowel, and pancreas. No evidence of skin, gastrointestinal, or hepatic involvement was discovered. HLA typing of the peripheral blood revealed that 28% of patient peripheral blood was composed of donor lymphocytes. Bone marrow biopsy showed a markedly hypocellular marrow with 23% donor lymphocytes and 80% of the T-cell population from the donor as well. The patient began treatment for GVHD, including high-dose steroids, basiliximab, and rituximab. Unfortunately, she developed overwhelming sepsis and subsequently died. This case describes an instance of GVHD manifested by isolated pancytopenia after en bloc transplantation of multiple solid organs. GVHD is a rare, but serious complication of solid organ transplantation that can result in death. Although isolated bone marrow involvement is uncommon, it must be considered early to avoid a delay in diagnosis. This case also highlights an association of GVHD with multiorgan transplants, although this is incompletely characterized in the current literature.     

Hemophagocytic syndrome after liver transplantation: Report of two cases

We report two cases of hemophagocytic syndrome (HPS), a rare but fatal complication after living-donor liver transplantation (LDLT). Despite their recovery from pancytopenia following treatment with steroid pulse therapy, granulocyte stimulating factor, and intravenous γ-globulin, both patients died. The outcomes reported in cases published in English are devastating, with only 4 survivors among the total 14 patients including ours. Pancytopenia is frequently recognized postoperatively in liver transplant recipients, although its cause is difficult to establish. When pancytopenia accompanying persistent high fever is recognized in LDLT recipients, HPS should be suspected and bone marrow aspiration performed as promptly as possible because of the poor prognosis of this syndrome. There is still no optimal treatment for HPS after liver transplantation.     

Amelioration of anemia after kidney transplantation in severe secondary oxalosis

INTRODUCTION: In small bowel disease such as M. Crohn, the intestinal absorption of oxalate is increased. Severe calcium oxalate deposition in multiple organs as consequence of enteric hyperoxaluria may lead to severe organ dysfunction and chronic renal failure. The management of hemodialyzed patients with short bowel syndrome may be associated with vascular access problems and oxalate infiltration of the bone marrow leading to pancytopenia. Although the risk of recurrence of the disease is very high after renal transplantation, it may be the ultimate therapeutic alternative in secondary hyperoxaluria. CASE: Here, we report a patient with enteric oxalosis due to Crohn's disease. He developed end-stage renal disease, erythropoietin-resistant anemia, oxalate infiltration of the bone marrow and severe vascular access problems. Following high-urgency kidney transplantation, daily hemodiafiltration of 3 hours was performed for 2 weeks to increase oxalate clearance. Despite tubular and interstitial deposition of oxalate in the renal transplant, the patient did not require further hemodialysis and the hematocrit levels normalized. DISCUSSION: Early treatment of hyperoxaluria due to short bowel syndrome is essential to prevent renal impairment. Declining renal function leads to a further increase in oxalate accumulation and consecutive oxalate deposition in the bone marrow or in the vascular wall. If alternative treatments such as special diet or daily hemodialysis are insufficient, kidney transplantation may be a therapeutic alternative in severe cases of enteric oxalosis despite a possible recurrence of the disease.     

Intermediate term results of total lymphoid irradiation for the treatment of non-specific graft dysfunction after heart transplantation.

BACKGROUND: A proportion of heart transplant recipients develop poor graft function in the absence of cellular infiltrate in endomyocardial biopsies or transplant associated coronary artery disease. The condition has a poor prognosis and its aetiology is poorly understood. We report encouraging intermediate term results with total lymphoid irradiation (TLI) in the management of this condition. METHODS: Eleven adult cardiac transplant recipients who developed severe allograft dysfunction (NYHA class-4) at a median period of 4 months after orthotopic heart transplantation were successfully treated with TLI. Endomyocardial biopsies and coronary angiography were normal in each patient and biventricular failure developed in spite of immunosuppression with Cyclosporin-A, Azathioprine, oral Prednisolone, Cyclophosphamide and intravenous Methylprednisolone therapy. Total lymphoid irradiation was given with standard Mantle and inverted Y-fields over ten treatments to achieve a cumulative dose of 8 Gy. RESULTS: Each patient had a significant improvement in clinical response and in ventricular performance within 2 months of commencing TLI. Nine patients are currently well (four NHYA class-1, five NHYA class-2) at 4-48 (median 26) months following TLI. Two patients died; one from bacterial septicaemia and one as a consequence of chronic renal failure. Three patients developed opportunistic infection which was successfully treated with appropriate antimicrobial agents. An Ebstein-Barr virus associated lymphoproliferative disorder occurred in one patient and was successfully treated by reduction in immunosuppression and high dose Acyclovir. Two patients developed transient bone marrow suppression. CONCLUSION: The intermediate term results of TLI in the management of poor graft function in cardiac transplant recipients with normal endomyocardial biopsies and coronary angiography are encouraging. Although complications of opportunistic infection, bone marrow suppression and lymphoproliferative disorder occurred, treatment was successful in each case.     

Post-transplant lymphoproliferative disorders: clinicopathological analysis of 43 cases in a single center, 1990-2009

Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous set of complications of organ transplantation associated with poor patient prognosis. We analyzed the clinicopathological features of PTLDs in 43 adult and pediatric recipients of solid organ or bone marrow transplantation at a large transplant service in the Republic of Korea between 1990 and 2009. Of 4545 solid organ and 747 bone marrow transplant recipients, 37 (0.81%) and 6 (0.8%), respectively, developed heterogeneous types of PTLDs. The cumulative incidences of PTLDs during this period were 1.79% (4/223) for heart transplant recipients, 0.78% (17/2192) for kidney transplant recipients, and 0.77% (16/2067) for liver transplant recipients. The patterns of disease onset, histology, and patient survival were associated with the types of organs transplanted. There is a trend for shorter overall survival (OS) in recipients with early-onset PTLDs and monomorphic PTLD histology, while kidney transplant recipients showed favorable OS. This study may be the first comprehensive analysis of the characteristics of PTLDs in Korean patients.     

Visceral Leishmaniasis in Renal Transplant Recipients: Report of 2 Cases

Visceral leishmaniasis is a disease caused by the protozoan Leishmania and is transmitted by Lutzomyia longipalpis (sand fly). It is an endemic parasitic infection in numerous areas around the Mediterranean basin. Though immunocompetent patients may not develop the disease, in transplant recipients the use of corticoids and intensified immunosuppressants to prevent graft rejection may accelerate the disease, causing severe damage to the liver, spleen, and hematopoietic system. We report 2 cases of visceral leishmaniasis with an atypical presentation in transplant recipients. The first patient, who had a kidney transplant, was treated successfully with liposomal amphotericin B, and the second patient, a combined kidney-pancreas transplant recipient, suffered a relapse 3 years after treatment. Visceral leishmaniasis should be considered in the differential diagnosis of pancytopenia or unexplained fever occurring after organ transplantation in patients living in endemic areas or returning from endemic countries.