Cutaneous infections from viral sources in solid organ transplant recipients

IntroductionSolid organ transplant recipients (SOTRs) are susceptible to various dermatological complications caused by long-term immunosuppressive therapy. Of these complications, viral infections are noteworthy because of their high prevalence and the potential morbidity associated with viral carcinogenesis.ObjectivesTo evaluate the occurrence of cutaneous viral infections in SOTRs and their correlation with clinical features, transplant type, and the length and intensity of immunosuppressive therapy.MethodsThis retrospective cohort study included SOTRs followed up at the Department of Dermatology in a tertiary hospital. The outcomes analyzed were the occurrence of cutaneous viral infections, including human papillomavirus (HPV) infection, herpes simplex, herpes zoster, molluscum contagiosum, Merkel cell carcinoma, Kaposi's sarcoma, and cytomegalovirus, and the occurrence of HPV-related neoplasms. Clinical variables, such as length and intensity of immunosuppression, type of transplanted organ, and comorbidities, were analyzed as possible risk factors for cutaneous viral infections in SOTRs.ResultsA total of 528 SOTRs were included in this study, among which 53.8% had one or more viral infections. Of these, 10% developed a virus-associated malignancy (HPV-associated carcinoma, Merkel cell carcinoma, or Kaposi's sarcoma). The higher risk of viral infections among SOTRs was associated with cyclosporine intake (1.40-fold higher risk) and younger age at transplantation. The use of an immunosuppressive regimen, including additional drugs, was associated with a higher risk of genital HPV infection (1.50-fold higher risk for each incremental drug).ConclusionsThe occurrence of cutaneous viral infections in SOTRs is directly associated with the duration and intensity of immunosuppressive therapy. Patients at higher risk were those taking drugs with a stronger impact on cellular immunity and/or those on an immunosuppressive regimen comprising various drugs.     

Fungal infections in liver transplant recipients

Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.     

Fungal infections in liver transplant recipients

A retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections. Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients. Twelve of the 13 episodes developed during the first 2 postoperative months. None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious nonfungal infection) correlated significantly with the episodes in our patients. However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P<0.001). Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P=0.01). Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor). Infections involving such patients are combined with a very high mortality (57%). We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients. In each case treatment led to full recovery.

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Pilzinfektionen nach Lebertransplantation

Zusammenfassung Um Inzidenz, Risikofaktoren, klinischen Verlauf und Prognose von Pilzinfektionen nach Lebertransplantation zu klären, wurden die Verläufe von 462 Patienten retrospektiv untersucht, die zwischen Oktober 1988 und Februar 1994 konsekutiv transplantiert wurden. Bei 13 unserer Patienten (2,8%) beobachteten wir Infektionen mit Aspergillus (6mal), Candida (5mal), Mucor (1mal) und Cryptococcus (1mal) Dabei trat die Infektion bei 12 der 13 Patienten bereits während der ersten 2 postoperativen Monate auf. Von den von anderen Autoren beschriebenen potentiellen Risikofaktoren (Alter, Abstoßungsbehandlung, Dialyse, maschinelle Beatmung, Graftversagen, lange Operationszeit, Retransplantation, schwere Allgemeininfektion) korrelierte bei unseren Patienten keine einzige mit den Infektionen. Allerdings war die Inzidenz der Pilzinfektionen bei Patienten, die 3 oder mehr dieser Risikofaktoren zeigten, signifikant erhöht (p<0,001). Ferner traten 6 von 7 exogenen Infektionen (Aspergillus, Mucor) vor dem Umzug unserer Transplantationsstation aus dem 1. Stock eines alten, efeubewachsenen Ziegelbaus in den 7. Stock eines Neubaus im Juli 1991 auf (p=0,01). Dies zeigt, daß die Exposition die Inzidenz von Pilzinfektionen nach Lebertransplantation wesentlich beeinflußt. Daraus folgt, daß insbesondere schwer kompromittierte Patienten einer strengen Expositionsprophylaxe unterzogen wurden müssen, um Infektionen mit Aspelgillus/Mucor zu vermeiden, die bei unseren Patienten eine Letalität von 57% aufwiesen. Bei 5 Patienten beobachteten wir Candidainfektionen als pathologisches Überwuchern der oralen Standortflora in Trachea und/oder Speiseröhre, die unter Therapie ausnahmslos ausheilten.

     

Fungal infections in solid organ transplantation: An update on diagnosis and treatment

Invasive fungal infections constitute an important cause of morbidity and mortality in solid organ transplantation recipients. Since solid organ transplantation is an effective therapy for many patients with end-stage organ failure, prevention and treatment of fungal infections are of vital importance. Diagnosis and management of these infections, however, remain difficult due to the variety of clinical symptoms in addition to the lack of accurate diagnostic methods. The use of fungal biomarkers can lead to an increased diagnostic accuracy, resulting in improved clinical outcomes. The evidence for optimal prophylactic approaches remains inconclusive, which results in considerable variation in the administration of prophylaxis. The implementation of a standard protocol for prophylaxis remains difficult as previous treatment regimens, which can alter the distribution of different pathogens, affect the outcome of antifungal susceptibility testing. Furthermore, the increasing use of antifungals also contributes to incremental costs and the risk of development of drug resistance. This review will highlight risk factors, clinical manifestations and timing of fungal infections and will focus predominately on the current evidence for diagnosis and management of fungal infections.     

Fungal infections in transplant recipients receiving alemtuzumab

Recently, we have used an anti-T-cell agent, alemtuzumab, as induction or conversion therapy to achieve a calcineurin (CNI) and steroid-free immunosuppressive regimen. We identified recipients who developed systemic fungal infections after the initiation of alemtuzumab and looked at their outcomes. The study population consisted of all pancreas transplant recipients who received alemtuzumab. Only invasive fungal infections were included in the analysis (eg, fungemia, meningitis, or pneumonia; fungal urinary tract infections were excluded). The organism was confirmed by culture, histopathology, or latex antigen test. Between February 2003 and February 2004, a total of 121 pancreas transplant recipients received alemtuzumab-56 as part of induction, and 65 as part of conversion. Of these, 8 (6.6%) developed an invasive fungal infection; 2 (3.6%) recipients as part of induction therapy and 6 (9.2%) as part of conversion therapy. Mean recipient age was 42.1 years. The mean length of time from alemtuzumab administration (first dose) to the diagnosis of the fungal infection was 115.9 days (range 5 to 318). The organisms identified initially were: Cryptococcus, Histoplasma, Aspergillus, and Candida. Overall, 3 (38%) of the eight patients died during ongoing treatment of their fungal infection: two from sepsis, one due to myocardial infarction. The other five recipients were treated successfully and have functioning grafts. The initial therapeutic agents used included: amphotericin B/liposomal AMB (n = 6), voriconazole (n = 3), capsofungin (n = 2), and fluconazole (n = 1). The use of alemtuzumab as induction or conversion therapy in pancreas transplant recipients may predispose patients to the development of systemic fungal infections. It would be important to determine what the most appropriate prophylaxis regimen would be for these patients.     

Fungal infections in renal transplant recipients.

Infection continues to be a major source of morbidity and the major source of mortality in renal transplant recipients who are susceptible to opportunistic infections. We recently reviewed all renal transplant recipients who had fungi cultured during a three year period. C. albicans and T. glabrata were cultured most frequently. Deep fungal infections occurred in many patients and were frequently observed late in the course of bacterial and viral infections. Ten patients had fungemia, and primary fungal pneumonia occurred in eight patients. Three patients had fungal infection of the central nervous system. Three of eight patients with fungal pneumonia and eight of ten patients with fungemia died as a result of their fungus infections. These patients frequently had poor renal function and were receiving high steroid doses or had recently been treated for kidney rejection. One patient with fungal pneumonia and six patients with fungemia had the fungus cultured from a superficial site. Several patients developed fungal infections late in the course of viral or bacterial infections. Amphotericin-B and 5-fluorocytosine remain the mainstays of antifungal therapy.     

Posttransplant anemia in solid organ recipients

Posttransplantation anemia (PTA) is a prevalent sequela of solid organ transplantation and a potential independent risk factor for cardiovascular morbidity and mortality in kidney transplant recipients. There are multiple causes of PTA, some of which are associated with early phase anemia (<6 months), whereas others more often induce anemia in the late posttransplant phase (>6 months). Although impaired kidney function contributes to PTA, it is only one of many factors that result in anemia in transplant recipients. Other causes include iron deficiency, medications, infections, acute rejection, inflammation, and erythropoietin deficiency. Unlike in the predialysis chronic kidney disease population, the impact of anemia after kidney transplantation outcomes is unknown. This is in large part due to the absence of controlled trials that address whether correction of anemia improves allograft function or patient morbidity and mortality. Current guidelines recommend evaluation for hemoglobin level of less than 12 g/dL and treatment when the value falls less than 11 g/dL and a target of 11 to 12 g/dL. Additional treatments may entail removing the cause of the anemia, nutritional supplementation, and/or an erythrocyte stimulating agent.     

Hypertension in solid organ transplant recipients

Hypertension (HT) is one of the most frequent complications of solid organ transplantation; about 70-90% of this population have high blood pressure or require antihypertensive therapy. Abnormal blood pressure is a potent non-immunological risk factor directly related to patient and graft survival. The etiology of hypertension after orthotopic heart transplantation is multifactorial and varies depending on the time following transplantation. In the early period after transplantation, hypertension is generally related to intravascular volume expansion and persistently increased systemic vascular resistance. Other factors predominant in kidney allograft recipients include: donor age, donor familial history of hypertension, transplant renal artery stenosis, graft function, the recurrence or de novo appearance of glomerulonephritis in transplanted kidney, and post-biopsy arteriovenous fistula. In liver and heart transplantation, hypertension is mainly due to impaired kidney function, with all its consequences. Another contributing factor is immunosuppressive regimen based on calcineurin inhibitors and steroids. The management of post-transplant hypertension usually requests non-pharmacological and pharmacological treatment. In this review, the pathogenesis and treatment of post-transplant hypertension in solid organ transplantation is presented.     

Incidence of fungal infections in a solid organ recipients dedicated intensive care unit

Invasive fungal infections are a significant cause of morbidity and mortality for patients undergoing solid organ transplantation. Our aim was to evaluate the incidence of invasive fungal infections in solid organ recipients within a dedicated intensive care unit (ICU). MATERIALS AND METHODS: From May 2002 to May 2005, 278 patients undergoing solid organ transplantation (105 liver, 142 kidney, 20 lung, 2 combined liver-kidney, 9 combined pancreas-kidney) were admitted to our posttransplant intensive care unit. We retrospectively analyzed data obtained from the ICU stay. Fungal infection was defined by positivity of normally sterile biological samples and by elevated positivity of normally non sterile biological samples. We did not consider superficial fungal infections and asymptomatic colonizations. RESULTS: Forty-six patients (16.5%) developed a fungal infection; at least one mycotic agent was isolated from each patient. Candida albicans was the most common pathogen, isolated from 71 % of infected patients (33 of 46). Infected patients showed a mortality rate of 35%, while that for non infected recipients was 3.5%. Total length of ICU stay was the most significant risk factor among infected patients (30.26 days vs 5.04 days P < .0001). Mean time between transplantation and first positive samples was 6.17 days (SD 8.88). CONCLUSION: Fungal infections in solid organ transplant patients are a major issue because of their associated morbidity and mortality. Candida albicans was the most common pathogen and total length of ICU stay was the most important risk factor.     

Zygomycosis and other rare filamentous fungal infections in solid organ transplant recipients.

Fungi cause severe infections in solid organ transplant (SOT) recipients. Recently, a shift towards non-Aspergillus filamentous fungal infections (nAFFI) was noticed. In a series of 2878 SOTs (kidney, pancreas, islets, liver, heart, lung, and bowel) performed between January 1995 and December 2006 at the Innsbruck medical university, eleven cases of nAFFI were diagnosed. The encountered species included Zygomyzetes (n = 8), and Alternaria alternate, Pseudallescheria boydii, Trichoderma spp. (one each); there were three liver and three heart, one intestinal, pancreas, lung, bilateral forearm and renal recipient each. Five patients died from nAFFI (zygomycosis: 4, Pseudallerichia boydii: 1); four were diagnosed postmortem. In five cases infection was surgically treated in combination with antifungals. Risk factors for nAFFI were renal failure (73%) and intensified immunosuppression (73%); two cases were associated with post-transplant lymphoproliferative disorder, one with graft versus host disease. An increase in the incidence of nAFFI was observed parallel to introduction of caspofungin and voriconazole (three cases until 12/2003, seven cases thereafter). NAFFI are increasingly found in SOT recipients. If diagnosed in time, the outcome seems acceptable. Intensified immunosuppression and exposure to antifungals not active against zygomycetes may be risk factors. Surgical therapy may play an important role in these infections.     

Genitourinary malignancies in solid organ transplant recipients

Malignancy is a recognized complication of transplantation. Genitourinary cancers are the second most common tumors in transplant recipients with prostate cancer and renal cell carcinoma the most common. Unlike the more common skin malignancies, genitourinary tumors have a significant impact on both graft and patient survival. Surgical and radiation treatments need to consider the location of heterotopic transplants and administration of chemotherapy may need alteration in light of immunosuppression being used. The major genitourinary malignancies and their management will be reviewed in this article with emphasis on the concerns that arise in a transplant recipient.