Infections In Organ Transplant Recipients Research Articles

Modulatory immune responses in fungal infection associated with organ transplant - advancements, management, and challenges.

Organ transplantation stands as a pivotal achievement in modern medicine, offering hope to individuals with end-stage organ diseases. Advancements in immunology led to improved organ transplant survival through the development of immunosuppressants, but this heightened susceptibility to fungal infections with nonspecific symptoms in recipients. This review aims to establish an intricate balance between immune responses and fungal infections in organ transplant recipients. It explores the fundamental immune mechanisms, recent advances in immune response dynamics, and strategies for immune modulation, encompassing responses to fungal infections, immunomodulatory approaches, diagnostics, treatment challenges, and management. Early diagnosis of fungal infections in transplant patients is emphasized with the understanding that innate immune responses could potentially reduce immunosuppression and promise efficient and safe immuno-modulating treatments. Advances in fungal research and genetic influences on immune-fungal interactions are underscored, as well as the potential of single-cell technologies integrated with machine learning for biomarker discovery. This review provides a snapshot of the complex interplay between immune responses and fungal infections in organ transplantation and underscores key research directions.

Mathematical Model Predicting the Kinetics of Intracellular LCMV Replication

The lymphocytic choriomeningitis virus (LCMV) is a non-cytopathic virus broadly used in fundamental immunology as a mouse model for acute and chronic virus infections. LCMV remains a cause of meningitis in humans, in particular the fatal LCMV infection in organ transplant recipients, which highlights the pathogenic potential and clinical significance of this neglected human pathogen. Paradoxically, the kinetics of the LCMV intracellular life cycle has not been investigated in detail. In this study, we formulate and calibrate a mathematical model predicting the kinetics of biochemical processes, including the transcription, translation, and degradation of molecular components of LCMV underlying its replication in infected cells. The model is used to study the sensitivity of the virus growth, providing a clear ranking of intracellular virus replication processes with respect to their contribution to net viral production. The stochastic formulation of the model enables the quantification of the variability characteristics in viral production, probability of productive infection and secretion of protein-deficient viral particles. As it is recognized that antiviral therapeutic options in human LCMV infection are currently limited, our results suggest potential targets for antiviral therapies. The model provides a currently missing building module for developing multi-scale mathematical models of LCMV infection in mice.

Cytomegalovirus Infection in Organ Transplant Recipients: Diagnosis, Prevention and Treatment

The most common infectious complication after first month of solid organ transplants is cytomegalovirus (CMV). Both direct such as viral syndrome, hepatitis, pneumonitis, colitis, etc. and indirect consequences such as rejection, infections by other microorganisms and graft dysfunction, are carried on by the virus. Latent infection, active infection, viral syndrome, and invasive disease are the four types of infection that can emerge due to transmission from the transplanted organ, reactivation of latent infection, or after a primary infection in seronegative individuals. Typically, this syndrome appears 30 to 90 days following transplantation. Several antiviral medications, including acyclovir, valacyclovir, ganciclovir, and valganciclovir, are being used for CMV prophylaxis and therapy. Furthermore, these antiviral medications are toxic and have serious adverse effects, including drug resistance, leukopenia, thrombocytopenia, renal failure, and neuropsychiatric symptoms. We attempted to discuss CMV risk factors, laboratory diagnosis, prevention, treatment and therapeutic in this review study with regard to organ transplantation.

The association between Parvovirus B19 infection and persistent anaemia in renal transplant recipients

BackgroundThe immunosuppressive drug therapy makes post-transplant recipients are at risk of developing both primary viral diseases and reactivation of persistent viruses. There are published case reports and studies on Parvovirus B19 infection in organ transplant recipients which have led to persistent anaemia secondary to lengthy suppression of erythropoiesis. ObjectiveTo assess the association between persistent unexplained anaemia and Parvovirus B19 infection amongst renal transplant recipients MethodsA matched case-control study was conducted in five government transplant centres in Sri Lanka by recruiting 42 cases and 42 controls prospectively. Cases were defined as adult renal transplant recipients with moderate to severe persistent unexplained anaemia. Quantitative PCR assay was performed for the quantification of Parvovirus B19 DNA in plasma of cases and controls and positive samples were further tested for the presence of IgG antibodies against Parvovirus B19. ResultsPost-transplant unexplained persistent anaemia was identified in 5.6% (95% CI: 4.21–7.42%) of the screened population. Parvovirus B19 infection was detected in one patient amongst 42 cases (2.2%), and no controls had confirmed Parvovirus B19 infection. The odds ratio for the association between persistent anaemia (outcome) and Parvovirus B19 infection (exposure) was 3.0723 (95% CI: 0.1216–77.5982) for persistent anaemia and parvoviraemia. (P-value: 0.4957). ConclusionThe finding of 5.6% of post-transplant unexplained persistent anaemia amongst RTRs demonstrates its importance as a significant modifiable morbidity factor in the modern renal transplant era. The association between Parvovirus B19 infection and persistent anaemia in Sri Lankan renal transplant recipients was not demonstrated by this study.

Pneumocystis jirovecii pneumonia in liver transplant recipients in an era of routine prophylaxis.

Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis.MethodsWe included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects.ResultsWe included 343 liver transplant recipients with 1153 person‐years of follow‐up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow‐up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9–148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5–53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died.ConclusionsPCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high‐dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted.

Rare and Unusual Follow-up Sequelae of Coronavirus Disease 2019: Splenic Mucormycosis in a Renal Transplant Recipient

BackgroundCoronavirus disease 2019 (COVID-19) is associated with adverse outcomes in transplantation communities. Mucormycosis, although a rare infection, has been classically linked to organ transplantation and is associated with exceptionally high morbidity and mortality rates. In this pandemic era, the double infection of mucormycosis and COVID-19 is a lethal combination but is rarely described in the literature on organ transplantation.Case presentationThis article presents the case of a young kidney transplant recipient with diabetes who acquired severe COVID-19, followed by disseminated mucormycosis. The patient was a health care worker who developed severe COVID-19, for which he received remdesivir, anticoagulation, and dexamethasone. No immunomodulatory therapy was used. His maximum oxygen support was bilevel positive airway pressure ventilation. His sugar levels were frequently deranged during the stay. He developed secondary sepsis with Klebsiella, followed by nonhealing lung consolidation. He later developed pleural effusion and splenic abscess, which was detected incidentally. He underwent an emergency splenectomy, the culture of which yielded mucormycosis. Liposomal amphotericin B 5 mg/kg was administered. The patient deteriorated, and a repeat laparotomy yielded gastric perforation, with pus culture showing mucormycosis. The patient died after a long hospital stay.ConclusionsThe diagnosis and management of this dual infection during the pandemic is extremely challenging. In this case, the unusual location of mucormycosis complicating COVID-19 calls for a meticulous approach to opportunistic fungal infections in organ transplant recipients who are positive for COVID-19, especially in those patients with diabetes.

Human pegivirus 1 infection in lung transplant recipients: Prevalence, clinical relevance and kinetics of viral replication under immunosuppressive therapy

Human pegivirus 1 (HPgV1) may cause persistent infections in immunocompetent and immunosuppressed individuals. Its clinical relevance, however, has not been determined. Previous studies have described a higher prevalence of HPgV1 infection in organ transplant recipients compared to healthy controls, but its occurrence in lung transplant recipients (LTRs) and its association with immunosuppressive therapy has not been assessed.The aim of this study was to evaluate the prevalence and clinical significance of HPgV1 infection in LTRs, and to compare HPgV1 loads and kinetics to Torque Teno Virus (TTV) kinetics, which reflects the level of immunosuppression.From each of 110 LTRs, five consecutive plasma samples were collected within the first year after transplantation and tested for HPgV1 RNA and TTV DNA loads by quantitative PCR. Data were related to demographic data and clinical parameters followed up for 3 years post transplantation.HPgV1 prevalence in LTRs was 18,2%. HPgV1 detection was significantly associated with younger age, but not with graft rejections or other microbial infections. The viral replication level remained unaffected by immunosuppressive therapy. This was in contrast to TTV loads which increased after initiation of immunosuppressive therapy, independent of the patients' HPgV1 infection status.In contrast to TTV, HPgV1 kinetics do not reflect the level of immunosuppression after lung transplantation, and there is no correlation between the replication of both persistent viruses in the post transplantation follow up. Thus the individual virus host interactions seem to differ substantially and require further investigation.

S2505 Aspergillus Fumigatus Vertebral Osteomyelitis With Intracardiac and Renal Aspergillomas in a Liver Transplant Recipient: A Clinical Vignette

INTRODUCTION: Immunosuppressed patients are at risk of fungal infections associated with high morbidity and mortality. Invasive aspergillosis (IA) leading to vertebral osteomyelitis, intracardiac and renal aspergillomas in the post-transplant setting is a rare infectious complication. CASE DESCRIPTION/METHODS: A 64-year-old former prison nurse, with a history of alcohol dependence and COPD, presented to our university medical center with fulminant hepatitis A requiring urgent orthotopic liver transplantation (OLT). Intra-operatively, she was noted to have focal ischemic colitis of the cecum and proximal ascending colon with mucosal necrosis, necessitating a right hemicolectomy and primary ileocolostomy. She received induction immunosuppression with basiliximab, followed by maintenance tacrolimus and mycophenolate mofetil. Post-operatively, she received antimicrobial and antifungal prophylaxis and was discharged to a rehab unit on post-op day 11. Her post-OLT course was further complicated by failure to thrive and de novo cytomegalovirus (CMV) viremia at 2 months (CMV D+/R−). > 90 days post OLT she developed fevers and lower back pain. MRI of the spine demonstrated lumbar discitis/osteomyelitis and abdominal CT scan showed a right renal nodule. Biopsies of the L-spine and right kidney revealed septated fungi and tissue cultures were positive for Aspergillus fumigatus. Immunosuppression was stopped and she was treated with amphotericin B, but later switched to isavuconazole and anidulafungin. Despite aggressive medical therapy, she continued to deteriorate clinically, and a TEE and CT chest revealed multi-chamber intracardiac and left ventricular free wall involvement by IA that had progressed. The prognosis was felt to be extremely poor, and she later died in hospice, 5 months post-OLT. DISCUSSION: IA has been recognized as one of the most highly lethal opportunistic fungal infections in organ transplant recipients. In this unique case, late-onset IA (>90 days post-OLT) manifested with vertebral, intracardiac, and renal involvement. Her risk factors included immunosuppression, hemodialysis, and CMV infection. Early initial treatment of IA involves immunosuppression minimization and systemic antifungal therapy using a combination of an azole with or without echinocandin. Surgical resection of an aspergilloma may be indicated prior to starting medical therapy. However, despite aggressive therapy, there is generally <35% survival from IA in this high-risk population.Figure 1.: CT chest showing intracardiac masses in the left atrium (white arrow; left image). CT abdomen showing a right renal nodule that was biopsied (white arrow; right image).

Bacillary Angiomatosis in Renal Transplant Recipient: A Case Report

IntroductionBacillary angiomatosis (BA) is a rare, opportunistic infectious disease caused by the aerobic Gram-negative bacilli Bartonella henselae or Bartonella quintana. The main reservoir for those microbes are cats. The disease mostly affects immunocompromised patients with human immunodeficiency virus infection, after organ transplantation, undergoing corticosteroid and methotrexate therapy or with oncological history. Case reportWe represent the case of a 65-year-old man who reported to the Department of Dermatology with a high fever and numerous nodular skin lesions on the 5th month of kidney transplantation. At that time, his immunosuppressive therapy consisted of tacrolimus 6 mg/day, mycophenolate mofetil 2 g/day, and prednisone 5 mg/day. Laboratory tests revealed an increased leukocyte count and elevated values of acute-phase proteins, but blood cultures were negative.Skin biopsy was performed and BA was diagnosed. The patient was given oral doxycycline 100 mg twice a day. During antibiotic therapy, his body temperature normalized and skin lesions began to resolve. The patient continued the above treatment for the next 3 months with good tolerance, and no relapse occurred in 1 year. ConclusionBA should be listed among possible opportunistic infections in organ transplant recipients.

Molecular characterization of fungi causing colonization and infection in organ transplant recipients: A one-year prospective study.

Background and Purpose:Organ transplant recipients are vulnerable to fungal infections. The aim of this study was to determine the prevalence of fungal colonization and infections among patients who underwent various transplantations and molecularly characterize the etiological agents.Materials and Methods:This study was conducted on candidates for transplantation in Imam Khomeini Hospital, Tehran, Iran, from April 2017 to April 2018. All patients were monitored for fungal colonization or infections before and after transplantation. Isolated fungi were identified using molecular methods.Results:A total of 125 patients, including 86 males and 39 females, with the mean age of 52.2 years participated in the study (age range: 15-75 years). Out of 125 patients, 84 (67.2%) cases had fungal colonization that appeared pre- and post-transplantation in 21 and 63 cases, respectively (alone or concurrent with another infection in 55 and 29 cases, respectively). In addition, a total of 39 episodes of fungal infections were diagnosed in 36 (28.8%) recipients (alone or concurrent with colonization in 7 and 29 cases, respectively). Out of the 39 fungal infections, 9 cases appeared pre-transplantation, while the other 30 cases occurred post-transplantation. However, no fungal colonization or infection was observed in 34 (27.2%) patients. Oral candidiasis (n=20) was the most common type of infection, followed by funguria (n=7), onychomycosis (n=5), candidemia (n=3), rhinocerebral mucormycosis (n=1), cutaneous mucormycosis (n=1), cutaneous aspergillosis (n=1), and peritonitis (n=1). Six yeast species were recovered from colonization cases with the dominance of Candida albicans both before and after transplantation. The observed fungal infections were caused by 11 distinct species, including the members of Candida (i.e., C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei), Aspergillus (i.e., A. oryzae and A. candidus), Rhizopus (i.e., R. oryzae and R. microsporus), Trichosporon asahii, and Trichophyton interdigitale. The results also indicated that the development of a fungal infection post-transplantation was associated with fungal colonization (r=0.0184; P=0.043). Conclusion:Based on the results, fungal colonization was a common finding in transplant recipients at Imam Khomeini Hospital. However, the incidence of fungal infections was comparable with those of other centers. As the oral cavity was the most common site of colonization and infection, it might be beneficial to take further care about the oral health of patients using effective mouthwash.

Cytomegalovirus renal infection: Rare manifestation of a common post-transplant viral infection-A case series.

Cytomegalovirus is the most common viral infection in organ transplant recipients that usually affects the brain, lungs, liver, and gastrointestinal tract. Renal involvement of Cytomegalovirus (CMV) is otherwise rare. We present six cases of biopsy-proven CMV renal infection. Five out of the six patients had detectable CMV viremia. Kidney biopsy revealed glomerulopathy in four cases and tubulointerstitial involvement in two cases. All patients exhibited decline in renal function at the onset of infection. Four out of six patients had improvement of renal function following treatment of CMV disease. To date, this is the largest case series of purebiopsy-proven CMV renal infection described in a single center.

Human papillomavirus infection in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These guidelines from the American Society of Transplantation Infectious Diseases Community of Practice update the epidemiology and management of human papillomavirus (HPV) infections in organ transplant recipients. HPV is one of the most common sexually transmitted infections and is associated with cancers of the anogenital region. Increasing evidence suggests an association with head and neck cancers as well. Solid organ transplant recipients have a higher risk of HPV infection than the general population. Infection manifests as premalignant lesions, warts, or cancer of the cervix, penis, vulva, scrotum, and anal canal. Most are asymptomatic initially, so diagnosis can be difficult without screening. A vaccine is available though not effective in preventing all cancer-causing strains. Organ transplant recipients should be screened for HPV-associated cancers and appropriate therapy initiated in a timely manner. Further studies are warranted to delineate the most effective screening methods and therapeutic modalities, including whether changes in immunosuppression are effective in attenuating disease.

Herpes Simplex Virus-1 qPCR in the Diagnosis of Lower Respiratory Tract Infections in Organ Transplant Recipients and Critically Ill Patients.

To determine a quantitative herpes simplex virus (HSV) DNA threshold in lower respiratory tract specimens that correlates with positive viral culture and clinical outcomes. Bronchoalveolar lavage and bronchial wash samples from 53 HSV culture-positive and 61 culture-negative matched controls were tested using HSV-1 and HSV-2 quantitative polymerase chain reaction (qPCR). Median viral culture turnaround time was 21.8 days and 9.9 days for culture-negative and culture-positive specimens, respectively. Using an HSV-1 viral load threshold of 1.62 × 103 copies/mL, there was 93% agreement with viral culture. An HSV-1 viral load ≥1.3 × 104 copies/mL was associated with worse clinical outcome compared to a viral load <1.3 × 104 copies/mL (hazard ratio [HR] = 4.27, P = .017), and there was a trend of worse outcome compared to patients with undetectable HSV-1 DNA (HR = 1.60, P = .056). qPCR has clinical utility for rapid accurate identification of HSV-1 in lower respiratory tract specimens.

Dermatological infections in organ transplant recipients: a retrospective study on 222 patients

Dermatological infections in organ transplant recipients: a retrospective study on 222 patients

Hepatitis E viral infection in solid organ transplant patients.

The purpose of this chapter is to review the literature published in the past 10 years with focus to the best literatures published since 2015 regarding chronic hepatitis E virus (HEV) infection in patients who received solid organ transplantation. Diagnosis of this disease relies primarily on identification of HEV RNA in serum and more recently in stool as way of predicting relapse and guide therapy duration. Current management focuses primarily on primary prevention and supportive care, because additional research is needed to identify efficacious pharmacologic therapy, though use of ribavirin has shown promise in case series in treatment of some genotypes. Infection with HEV is a rare but significant infection in organ transplant recipients. Though initially thought to be a primarily self-limiting infection, cases of chronic and persistent infection are increasing, being recognized both in developing and developed nations as a cause of cirrhosis, and, in some cases, of fulminant hepatic failure. Clinical manifestations of this infection, including evidence of hepatocellular liver injury, are mostly indistinguishable from alternative diagnoses.

Seroprevalence and Molecular Evaluation of Toxoplasmosis in Patients Undergoing Chemotherapy for Malignancies in the Bushehr Province, Southwest Iran.

BackgroundToxoplasmosis is a life-threatening infection in organ transplant recipients, people receiving corticosteroid or radiation therapy, people with malignancies, and AIDS patients.ObjectivesThe current study aimed to determine the prevalence of toxoplasmosis in patients receiving chemotherapy for malignancies in the Bushehr province of southwest Iran.MethodsBlood samples were taken from 86 patients who were continuously referred to the chemotherapy center in Bushehr province and evaluated by ELISA to determine anti-Toxoplasma IgG and IgM antibodies. Moreover, a blood buffy coat of each sample was assessed by polymerase chain reaction (PCR), targeting a 529 bp gene of T. gondii. PCR products of the positive samples were sequenced to determine the genotype of the parasite.ResultsAnti-Toxoplasma IgG antibodies were detected in the sera of 21 (24.4%) cases. All of the patients were negative for anti-Toxoplasma IgM antibodies. No statistically significant correlation was found between seropositivity to Toxoplasma and duration of chemotherapy or having contact with cats. PCR detected a 529 bp band of T. gondii in the buffy coats of two out of 86 (2.3%) cases. The sequence analysis demonstrated that both cases were 95% identical to type III (VEG strain) of T. gondii.ConclusionsFindings of this study demonstrated the presence of type III T. gondii in the buffy coats of patients undergoing chemotherapy. Given that toxoplasmosis is a life-threatening infection in immunocompromised patients, these patients should be screened for toxoplasmosis before and during chemotherapy to prevent acute toxoplasmosis.

Strategies to prevent BK virus infection in kidney transplant recipients.

Despite improvements in posttransplant care, BK virus (BKV) remains one of the most challenging posttransplant infections in kidney transplant recipients with high rates of allograft failure. In the absence of well tolerated and efficacious viral specific therapeutics, treatment is primarily focused on reduction of immunosuppression, which poses a risk of rejection and fails to lead to viral clearance in a number of patients. Recent work has turned toward preventive therapies analogous to those used for other infections like cytomegalovirus. These efforts have focused on the use of quinolone antibiotic prophylaxis to prevent BKV infection and pretransplant vaccination to boost humoral and cellular immunity. Despite promising in-vitro and observational data, quinolone antibiotic prophylaxis has not been effective in preventing BKV infection in prospective studies. However, prophylaxis with newer less toxic viral specific agents such as brincidofovir - the lipid oral formulation of cidofovir - may yet prove effective. Strategies focused on eliciting a humoral immune response to recombinant virus-like particles or using adoptive transfer of BKV-specific T cells have also shown significant potential to prevent BKV infection in organ transplant recipients.

Comparison of Staphylococcal Flora in Denture Plaque and the Surface of the Pharyngeal Mucous Membrane in Kidney Transplant Recipients

BackgroundBiofilm occurring on removable prostheses is a reservoir of bacterial flora, consisting of both physiological and pathogenic multidrug-resistant microorganisms. Patients undergoing dialysis and organ transplantation are particularly prone to bacterial infections, which can have its source in denture plaque. This study was a comparison of the composition of staphylococcal flora within the surface of the pharyngeal mucous membrane as well as denture plaque in kidney transplant recipients. MethodsThe study included 44 subjects with removable prostheses who reported for a kidney transplant procedure. Swab samples were collected from prostheses and the pharyngeal wall. Isolated strains were identified and investigated for drug resistance. ResultsA total of 72 strains of Staphylococcus were isolated from the denture plaque and 53 from the pharynx. In the pharynx, the following species prevailed: Staphylococcus epidermidis, Staphylococcus warneri, and Staphylococcus aureus. The following species prevailed in denture plaque: S epidermidis, S aureus, and Staphylococcus haemolyticus. Among the pharyngeal strains, antibiotic resistance most commonly referred to natural penicillin (77%), constitutive macrolide-lincosamide-streptogramin B resistance (28%), and tetracycline (26.4%). In case of denture plaque, the highest percentage of strains demonstrated resistance to natural penicillin (60%), fosfomycin (32%), and cefoxitin (25%). In 10 subjects (48%), Staphylococcus-induced infections occurred in the first year after transplantation, 5 of which had the same bacterial strain as cultured previously from dentures. ConclusionsThe denture biofilm and surface of the pharynx differ in terms of bacterial composition and bacterial drug resistance profiles. Denture plaque constitutes a considerable reservoir of staphylococcal flora, which can be a potential source of infection in organ transplant recipients.

Sepsis in the severely immunocompromised patient.

The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients.

Voriconazole-Associated Cutaneous Malignancy: A Literature Review on Photocarcinogenesis in Organ Transplant Recipients

This article synthesizes the current data regarding the implication of voriconazole in the development of skin cancer in organ transplant recipients (OTRs) and offers suggestions for additional research. According to Organ Procurement and Transplantation Network data, 28 051 solid organ transplants were performed in 2012. Due to advancements in immunosuppression and management of infectious diseases, survival of OTRs has substantially increased. Voriconazole is a widely prescribed antifungal medication used for prophylaxis and for treatment of invasive fungal infections in OTRs. Case reports describing skin cancer associated with voriconazole exposure emerged shortly after US Food and Drug Administration approval of the drug, and it is now established that voriconazole is an independent risk factor for the development of cutaneous malignancy in lung transplant recipients. The mechanism of voriconazole-induced skin cancer is still unknown and may involve its primary metabolite, voriconazole N-oxide. Here we discuss the current data and potential mechanisms of voriconazole-associated photosensitivity and carcinogenesis and identify areas that require further research.