Dermatologic manifestations of infections in immunocompromised patients

Thirty-one immunocompromised patients (22 renal allograft recipients, 5 patients receiving chronic corticosteroid therapy, and 4 patients undergoing chemotherapy for acute leukemia) with significant dermatologic infection, excluding typical cellulitis and herpesvirus infections, were retrospectively identified over a 12-year period. Of these 31 patients, 15 (48%) had infection restricted to their skin, 6 (19%) appeared to have primary cutaneous infection that spread hematogenously to other parts of the body, 2 (6%) had infections of adjoining nasal tissue that spread to contiguous skin, and 8 (26%) appeared to have disseminated systemic infection that spread to the skin. In six of the eight patients with apparent secondary skin involvement, the development of the cutaneous lesion was the first clinical indication of disseminated infection. Eleven immunocompromised patients (35%) with bacterial infection of the skin or subcutaneous tissue were identified. These patients could be divided into three categories: leukemic patients with bacteremic gram-negative infection metastasizing to the skin (3 cases), renal transplant recipients with recurrent staphylococcal infection on and around the elbow ("transplant elbow") or streptococcal sepsis from a site of cellulitis (5 cases), and immunocompromised patients with opportunistic bacterial infection due to Nocardia asteroides or atypical mycobacteria (3 cases). Seventeen immunocompromised patients (55%) with fungal infection of the skin or subcutaneous tissue were identified. These included 12 patients with opportunistic fungal infection (Cryptococcus neoformans, 4 cases; Aspergillus species, 3 cases; Paecilomyces, 2 cases; Rhizopus species, 2 cases; and Candida tropicalis, 1 case) and 5 patients with extensive, confluent cutaneous dermatophyte infections. One patient with protothecosis and two patients with extensive papillomavirus infection were identified. Of these latter two cases, one had his immunosuppression discontinued, with clearing of his extensive warts; the other had confluent warts of the face and neck that subsequently underwent malignant degeneration to squamous cell carcinoma while chronic immunosuppressive therapy was continued.(ABSTRACT TRUNCATED AT 400 WORDS)     

Systemic nocardiosis following allogeneic bone marrow transplantation

Abstract: Five cases of systemic Nocardia infection were diagnosed among 301 allogeneic bone marrow transplant recipients. A sixth case included in this report received her transplant at another institution. The cumulative annual incidence rate of this infection was 1.75%. All patients had been treated previously for acute graft-versus-host disease (GVHD). At the time of diagnosis of systemic Nocardia infection, a median of 198 (range 148–1121) days after transplantation, all patients had extensive chronic GVHD and were taking 2 to 3 immunosuppressive medications. Prior to diagnosis of Nocardia infection patients had experienced multiple opportunistic infections, including infections with Mycobacterium avium-intracellulare, Pneumocystis carinii , and cytomegalovirus antigenemia. Treatment with trimethoprim-sulfamethoxazole (TMP-SMX), ceftriaxone, or carbapenem antibiotics resulted in a median survival of 219 days from the time of diagnosis and an actuarial 1-year survival of 40%. All patients who received more than 2 weeks of therapy were cured of their infections. Notably, 5/6 patients in this cohort were unable to take TMP-SMX because of myelosuppression. In comparison with randomly selected control patients, the use of pentamidine for prevention of P. carinii infection was associated with a marginal increase in the risk of Nocardia infection. We postulate that the use of TMP-SMX may be of benefit in the prophylaxis of infections other than P. carinii in patients with chronic GVHD.     

Phaeohyphomycosis due to Alternaria species in transplant recipients

R.D. Boyce, P.J. Deziel, C.C. Otley, M.P. Wilhelm, A.J. Eid, N.L. Wengenack, R.R. Razonable. Phaeohyphomycosis due to Alternaria species in transplant recipients.
Transpl Infect Dis 2010: 12: 242–250. All rights reserved Abstract: Alternaria species are members of a heterogenous group of dematiaceous fungi that rarely cause opportunistic infections in transplant recipients. During a 20‐year period from 1989 to 2008, 8 solid organ transplant recipients (63% males; median age, 48 years) developed Alternaria species infections at the Mayo Clinic. All patients were highly immunocompromised as evidenced by their receipt of multiple transplants, treatment of acute and chronic allograft rejection, and occurrence of other opportunistic infections. All patients presented with non‐tender erythematous or violaceous skin papules, nodules, or pustules in exposed areas of the extremities. No case of visceral dissemination was observed. Itraconazole was the most common drug used for treatment, although voriconazole, posaconazole, and caspofungin could potentially be useful based on our limited clinical data and in vitro antifungal susceptibility testing. One patient was treated with voriconazole, while another patient who was refractory to itraconazole had rapid resolution of lesions after the addition of caspofungin. Attempts at antifungal therapy alone were unsuccessful; all patients eventually required surgical excision of lesions. In conclusion, Alternaria species are rare but increasingly recognized opportunistic infections among highly immunocompromised transplant recipients. Wide excisional surgery combined with prolonged systemic antifungal therapy and reduction in immunosuppressive regimens provided the best chance of cure. Although itraconazole remains the most common drug for treatment, this case series highlights the potential clinical utility of caspofungin, voriconazole, and posaconazole as alternative regimens.     

Hospitalizations for fungal infections after renal transplantation in the United States

Abstract: Fungal infections in renal transplant recipients have not been studied in a national population. Therefore, 33,420 renal transplant recipients in the United States Renal Data System from 1 July 1994 to 30 June 1997 were analyzed in a retrospective registry study of hospitalized fungal infections (FI). FI were most commonly associated with secondary diagnoses of esophagitis (68, 23.9%), pneumonia (57, 19.8%), meningitis (23, 7.6%), and urinary tract infection (29, 10.3%). Opportunistic organisms accounted for 95.4% of infections, led by candidiasis, aspergillosis, cryptococcosis, and zygomycosis. Most fungal infections (66%) had occurred by six months post-transplant, but only 22% by two months. In logistic regression analysis, end-stage renal disease due to diabetes, duration of pre-transplant dialysis, maintenance tacrolimus and allograft rejection were associated with FI. In Cox regression analysis, recipients with FI had a relative risk of mortality of 2.88 (95% CI=2.22–3.74) compared to all other recipients. Among FI, zygomycosis and aspergillosis were independently associated with both increased patient mortality and length of hospital stay. Most fungal infections in renal transplant recipients were opportunistic, occurred later than previously reported, and were associated with greatly decreased patient survival. Recipients with diabetes, prolonged pre-transplant dialysis, rejection, and tacrolimus immunosuppression should be considered high risk for FI.     

Risk factors for the development of invasive fungal infections in allogeneic blood and marrow transplant recipients

Abstract: Blood and marrow transplantation (BMT) is increasingly used to treat malignant and nonmalignant diseases. Despite significant advances in the management of transplant recipients, however, fungal infections remain important life-threatening complications of BMT. Over the past two decades, the incidence of fungal infections in this population has continued to rise. Several factors predispose BMT recipients to invasive fungal infections. These include but are not limited to use of intensive myeloablative chemotherapy and radiation therapy combined with prolonged granulocytopenia; development of acute and chronic graft-versus-host disease; administration of immunosuppressive therapy, particularly using corticosteroids; use of central venous catheters; and prolonged impairment of cell-mediated immunity secondary to the underlying disease and post-transplant immunodeficiency. Environmental factors also play a key part in the pathogenesis of fungal infections. Therefore, infection-control measures are critical to the prevention of such infections. In addition, although Candida and Aspergillus species are still the major culprits, other opportunistic fungi have emerged in recent years.     

Sirolimus-based immunosuppression for treatment of cutaneous warts in kidney transplant recipients

Dermatological complications, especially skin infections, are very common following organ transplantation, and result in a lot of distress in the recipient. Herpes zoster, herpes simplex, and human papillomavirus infections are common infections in kidney transplant recipients, and therapeutic management is usually disappointing in immunosuppression state. We report here 2 cases of kidney transplant recipients who developed diffuse human papillomavirus-induced cutaneous warts with no response to conventional treatments. According to similar reports in organ transplant recipients, we modified the immunosuppressive regimen by converting to sirolimus, which led to a rapid relief from cutaneous warts in both patients. This evidence along with other case reports suggest that conversion to sirolimus may be considered as an effective strategy in cases of giant or multiple viral warts in kidney and perhaps other transplant recipients.     

Simultaneous mold infections in an orthotopic heart transplant recipient

Abstract: Simultaneous mold infections in heart transplant recipients have not been previously reported. Here we describe early onset post‐transplant pulmonary aspergillosis and cutaneous zygomycosis in a 46‐year‐old heart transplant recipient who was also treated with basiliximab. Along with surgical debridement, medical treatment of his cutaneous abdominal wall zygomycosis at the former left ventricular assist device driveline site with liposomal amphotericin B and voriconazole also led to cure of his pulmonary aspergillosis.     

Primary cutaneous mucormycosis in a lung transplant recipient: case report and concise review of the literature

Abstract: Mucormycosis (zygomycosis) is an invasive, opportunistic fungal infection caused by organisms of the class Zygomycetes. Immunocompromised individuals, including both solid organ and hematopoietic stem cell transplant recipients, are preferentially affected. Among solid organ transplant (SOT) recipients, the sinuses, with or without involvement of the orbits and cerebrum, are the most common sites of disease, although the pulmonary allograft appears to be targeted following lung transplantation. Here, we describe the unique case of a lung transplant recipient who developed multifocal cutaneous mucormycosis without involvement of the pulmonary allograft, and review the published literature regarding incidence, treatment, and prognosis of primary cutaneous mucormycosis following SOT.     

Hypogammaglobulinemia after heart transplantation: impact of pre-emptive use of immunoglobulin replacement (CytoGam®) on infection and rejection outcomes

Hypogammaglobulinemia (HGG) in solid organ transplant (SOT) patients confers an increased risk of opportunistic infections and poorer outcomes. Severe HGG (IgG < 350 mg/dL) after heart transplantation may follow intensification of immunosuppressive therapy and the resultant increased risk of opportunistic infections, particularly cytomegalovirus (CMV) disease. Evaluation of the effects of replacement therapy using intravenous immunoglobulin (CMV-IGIV, CytoGam®) was conducted in cardiac transplant recipients and the data matched with a historical control group. Patients with severe HGG who received pre-emptive replacement therapy had significantly fewer opportunistic infections ( P < 0.001) and episodes of rejection (grade 3; P  = 0.03 and grade 2; P  = 0.04) compared with the control group.     

Incidence and management of mycobacterial infection in solid organ transplant recipients

Although advances in surgical technique, immunosuppressive regimens, and medical management have led to improved survival and quality of life after solid organ transplantation, infection continues to represent a major cause of morbidity and mortality in transplant recipients. Immunosuppressive therapy after transplantation compromises cell-mediated immunity in particular, leaving the patient at risk for opportunistic as well as routine community-acquired infections. Mycobacterial infection is a rare but important complication of solid organ transplantation, presenting significant risk to the patient and challenges in terms of treatment. The available literature consists predominantly of case reports and institutional experiences. This article examines both Mycobacterium tuberculosis and nontuberculous mycobacterial infection in the transplant setting.     

Adenovirus infections in adult recipients of blood and marrow transplants.

Adenoviruses are increasingly recognized pathogens that affect blood and marrow transplant (BMT) recipients. Experiences with 2889 adult BMT recipients were reviewed to study the incidence, clinical spectrum, risk factors for dissemination, response to therapy, and outcome of adenovirus infections. Eight-five patients (3%) were diagnosed by means of culture (n=85) or culture and histopathological examination (n=6). Nine patients had asymptomatic viruria, and 76 had symptomatic infections, which included upper respiratory tract infection (n=20), enteritis (n=18), hemorrhagic cystitis (n=10), pneumonia (n=15), and disseminated disease (n=13). The overall mortality rate was 26%. A higher mortality rate was observed among patients with pneumonia (73%) and disseminated disease (61%). Risk factors for dissemination included receipt of an allogeneic transplant, presence of graft-versus-host disease (GVHD), and receipt of concurrent immunosuppressive therapy. Intravenous ribavirin was not associated with an appreciable benefit among 12 patients who received this treatment. In conclusion, adenovirus infections are an important cause of morbidity and mortality in adult BMT recipients, particularly allogeneic transplant recipients with GVHD who are receiving immunosuppressive therapy. The need for an effective, nontoxic antiviral therapy is apparent.     

Neurologic complications after liver transplantation

Neurologic complications are relatively common after solid organ transplantation and affect 15%-30%of liver transplant recipients.Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections.Most common complications include seizures and encephalopathy,and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients.Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor,headaches and encephalopathy.Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement.Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system(CNS)infections,but viral and fungal CNS infections still affect 1%of liver transplant recipients,and the morbidity and mortality in the affected patients remain fairly high.Critical illness myopathy may also affect up to 7%of liver transplant recipients.Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation.Accurate diagnosis and timely intervention are essential to improve outcomes,while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting.     

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991–92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community‐acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre‐intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high‐risk solid organ transplant patients.     

Successful use of posaconazole to treat invasive cutaneous fungal infection in a liver transplant patient on sirolimus

Fungi are an important and common cause of cutaneous infections affecting solid organ transplant recipients. These infections can represent a primary site of infection with the potential for dissemination, or a manifestation of metastatic infection. The high morbidity and mortality associated with these infections necessitates urgent therapy with antifungal drugs; however, the interaction between these drugs and immunosuppressive therapies can be a major limitation because of drug toxicity. A case of soft tissue infection of the toe caused by Fusarium chlamydosporum and Candida guilliermondii in a liver transplant patient on sirolimus, who was successfully treated with the new antifungal agent posaconazole, is described. The pharmacokinetic interactions of sirolimus and the new triazoles, and their impact on treatment choices are briefly discussed.     

Phaeohyphomycosis due to Exophiala species: clinical spectrum of disease in humans.

Phaeohyphomycosis caused by Exophiala species is an unusual infection, but it has been reported with increasing frequency as immunosuppressive therapy has become more widespread and laboratory methods for diagnosis have improved. To our knowledge, the first case of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei in a cardiac transplant patient is presented, and previously reported cases of exophiala infection are reviewed. This patient was successfully managed with surgical excision of the lesion and combination therapy with amphotericin B and 5-fluorocytosine.     

Fungal sepsis.

Immunocompromise can result from trauma, burns, cancer, cancer chemotherapy, and immunosuppressive therapy. Immunocompromise increases the risk of invasive infection from opportunistic fungi. The key to successful management of these infections is early recognition, aggressive therapy, and when indicated, surgical therapy. This article describes the common opportunistic fungal infections aspergillosis, zygomycosis, and candidiasis, which may arise in surgical patients or which may require surgical intervention for diagnosis or therapy.     

Impact of current transplantation practices on the changing epidemiology of infections in transplant recipients

The spectrum of infections in transplant recipients has been substantially affected by novel immunosuppressive regimens and the use of antimicrobial agents. Epidemiology and presentation of traditional opportunistic pathogens has changed. Invasive aspergillosis and cytomegalovirus occur later in the post-transplant period. The incidence of infections that were previously encountered rarely--eg, BK virus nephropathy--has increased, the clinical course of hepatitis C virus recurrence has become more aggressive, the risk factors for invasive aspergillosis have changed, and non-aspergillus moulds are occurring more commonly in transplant recipients. Recognition of these trends as they unfold has significant implications for the clinical care of the transplant recipients, for providing insights into the pathogenesis, and for continually improving the approaches to the management of infections.     

Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency.

Epstein-Barr virus (EBV) lymphoproliferative disease is seen in patients with both congenital and acquired immunodeficiencies. Lymphoproliferative disease has been reported in 1 to 3% of renal transplant recipients. Most patients presented with solid tumor masses, rather than an infectious mononucleosis-like syndrome. About one third of cases had involvement of the renal allograft with tumor; the small intestine or central nervous system was also frequently affected. About half of the patients survived. The most frequent therapy used for survivors was decreasing the dose of immunosuppressive therapy and surgical resection of lymphoproliferative lesions. Compared with fatal cases, survivors more often had evidence of active EBV infection (primary or reactivated), received cyclosporine as the major immunosuppressive agent, had polyclonal lesions, and had B-cell hyperplasia rather than lymphoma. Lymphoproliferative disease has been described in 5 to 13% of heart transplant recipients. In our review, the cardiac allograft was not involved by disease in any patient; however, the lungs were involved in more than half of the cases. The soft tissues were frequent sites of lymphoproliferative disease. All patients had lymphoma or immunoblastic sarcoma on pathology and all had monoclonal lesions. While only 8% of patients survived, about half died from causes unrelated to lymphoproliferative disease. EBV lymphoproliferative disease has been reported in 9% of heart-lung transplant recipients. Most of the patients presented with pulmonary symptoms and the pulmonary allograft was involved in 80% of cases. The large and small intestine were frequently affected. About 60% of patients survived; survivors were treated with acyclovir and decreases in the dose of immunosuppressive drugs. Lymphoproliferative disease has been described in 2% of liver transplant recipients. In our review, the hepatic allograft was involved in one third of cases; the tonsils, kidneys, and small intestine were frequently affected. Half of the patients survived; survivors were most often treated with reduction in immunosuppressive therapy and surgical resection of lesions. Compared with fatal cases, survivors had fewer organs involved and fewer monoclonal lesions. Lymphoproliferative disease has been reported in 1 to 2% of bone marrow transplant recipients. Use of T-cell depleted bone marrow and infusion of anti-T-cell antibodies to prevent graft-versus-host disease increased the risk of EBV lymphoproliferative disease. In our review, the bone marrow was involved by lymphoproliferative disease in one third of cases; the liver, spleen, kidney, and lungs were frequently affected. About 16% of patients survived; 2 survivors were treated with infusions of monoclonal anti-B-cell antibodies and 1 received interferon alpha.(ABSTRACT TRUNCATED AT 400 WORDS)     

Risk factors profile and cardiovascular events in solid organ transplant recipients

By advances in surgical techniques, success in prevention and treatment of transplant-related infections, and introduction of new immunosuppressive drugs, the patient and graft survival rates in solid organ transplant recipients has steadily and remarkably improved. It has been shown that the longer the transplant patients survival rate, the more saturation with cardiovascular risk factors and the greater risk of cardiovascular mortality. Currently, cardiovascular disease is the primary cause of death after kidney transplantation and is among the three most common causes of death after heart and liver transplantation. Over the past decades, because of risk factor reduction, mortality from coronary artery disease has substantially decreased in the general population. Recent studies suggest that risk factors reduction also significantly decreases cardiovascular events and deaths in solid organ transplant recipients.     

Effect of thymoglobulin induction on HIV-infected renal transplant recipients: differences between HIV-positive and HIV-negative patients

The best immunosuppressive regimen in HIV-infected renal transplant recipients has not been established. Thymoglobulin has been associated with an increased risk of serious bacterial infections in HIV-negative patients and, for this reason, there is some concern over its use in the HIV-infected population. We describe three consecutive HIV-infected renal transplant recipients who received thymoglobulin as induction therapy, and we compared their progress with a cohort of 23 HIV-negative recipients. Median follow-up was 24 and 11 months, respectively. Nadir lymphocytopenia was observed at 1 week in both groups, and their absolute lymphocyte count recovery was similar. An early and deep (<30 cells/mm(3)) CD4(+) T cell lymphocytopenia was seen in two of the three HIV-infected patients. No opportunistic infections were diagnosed in HIV-positive patients. One HIV-positive patient had a bacterial infection and five HIV-negative patients had one or more bacterial infections. Thymoglobulin was safe in our three HIV-infected renal transplant recipients. Until those data are confirmed in larger studies, close monitoring is recommended during the thymoglobulin-induced CD4(+) T cell lymphocytopenia period.