Non-melanoma skin cancer outcomes in kidney transplant recipients converted from calcineurin inhibitors to mTOR inhibitors: a systematic review.

Renal transplant recipients treated with calcineurin inhibitors (CNIs) are at a high risk of developing a skin cancer. Therefore, new therapeutic options such as inhibitors of the mammalian target of rapamycin (mTORi) have been studied to find treatment regimens decreasing the rate of skin cancers. This systematic review focuses on recent randomized controlled trials studying the impact of conversion from CNI to mTORi in renal transplant recipients on development of non-melanoma skin cancers (NMSC). Outcomes of analysed trials revealed that conversion from CNI to mTORi in post-transplant patients reduces the risk and delays the occurrence of NMSC. However, mTORi protective properties against NMSC are more effective in patients with a history of a single SCC compared with multiple SCCs. At the same time, conversion to mTORi is associated with more common discontinuations secondary to adverse events and also increased mortality. In conclusion, conversion to mTORi is protective against NMSC but given the high AE rates and therapy discontinuation there is a need to determine who would benefit from conversion and search for new treatment regimens including combination strategies with mTORi.

Demodicosis among immunocompromised patients: a review.

Introduction: Demodex mites (DM) are the most common ectoparasites of humans. Demodex folliculorum and Demodex brevis are the two species we are hosts for. Through the years there have been more data proving DM to be a pathogenic parasite. To this date it has not clear which groups of patients are clearly prone to develop demodicosis. Aim: To present a literature review in order to analyse and establish whether immunosuppressed patients are prone to develop demodicosis. Material and methods: Data were collected mostly from the PubMed database and through citation searching of the articles. Results: A total amount of 23 case reports and 13 original works were included. Out of them, 4 original works deny the correlation between demodicosis and immunosuppression whereas 9 original works suggest that correlation. Conclusions: Demodicosis seems to be correlated with immunosuppression, but it requires more study in the future.

Squamous cell carcinomas in organ transplant recipients. Comparison of histopathological and clinical features of squamous cell carcinoma in patients after organ transplantation to immunocompetent patients.

The occurrence of neoplasms is one of the most common complications and second most frequent cause of death in organ transplant recipients (OTRs). The most frequently occurring neoplasms are skin cancers, predominantly squamous cell carcinoma (SCC). However, the ratio between SCC and basal cell carcinoma (BCC) in OTRs differs in several studies depending on the follow-up time, country, environment and other factors. In this population SCC has a more aggressive course with the presence of metastases and tends to have multifocal growth. The clinical and histopathological picture of SCC in OTRs differs from that observed in immunocompetent patients, which implicates tumour treatment and prognosis. The clinical features and distinctness which pertain to SCC in post-transplantation patients are described in this paper.

Demodicosis as a Skin Complication in Organ Transplant Recipients: A Case Series.

BACKGROUND Patients after organ transplantation are, due to chronic immunosuppression, prone to have many cutaneous adverse events, both infections and neoplasms. Studies show that some groups of patients under chronic immunosuppression are prone to develop demodicosis. The significance of demodicosis in the population of organ transplant recipients has not been established yet. CASE REPORT We present 4 cases of patients with multiply dermatological complications of immunosuppression, in which one of them is demodicosis. The presented symptoms were itch, pustules, papules, and/or telangiectasias. Age of patients varied from 64 to 79 years old. Time between transplantation and diagnosis of demodicosis varied from 6 to 10 years. Other dermatological problems that appeared were basal cell carcinoma, actinic keratosis, and seborrheic keratosis. Patients showed complete resolution after treatment with topical ivermectin 10 mg/g and topical permethrin 50 mg/g. However, the medications were prolonged to 16 weeks in 1 case to reduce persistent papules and telangiectasias. The therapy did not cause any complications or disruptions in function of transplanted kidneys in any of reported patients. CONCLUSIONS Demodicosis may have a significant role in the group of infections that organ transplant recipients are prone to, and may co-exist with other dermatological diseases, including neoplasms. However, larger studies in the field are needed.

Skin cancer in children after organ transplantation.

Skin cancer is the second most common complication of organ transplantation in children. The frequency of skin cancer incidence after organ transplantation is different in paediatric and adult populations. The post-transplant lymphoproliferative disease is the most common group of malignancies after organ transplantation in paediatric population. The majority of researchers who examined children with kidney, liver, heart or lungs grafts observed that the risk of skin cancer was three times higher than in the general population whereas in adults even200 times higher. The occurrence of skin cancer in children after transplantation is extremely rare during childhood. The risk increases in early adulthood. Malignancies occurring after solid organ transplantation result from many different factors. These include the immunological condition of the child, dose and time of immunosuppression, and oncogenic viruses. The increased risk of skin cancer following paediatric transplantation requires prevention and adequate education of children and their parents. These involve avoiding sun exposure and protection such as sunscreens and protective clothing. The early detection of cancer in transplant recipients is very important. Prevention of cancer includes regular dermatological examination.

Evaluation of quantitative changes in regulatory T cells in peripheral blood of kidney transplant recipients with skin cancer after conversion to mTOR inhibitors.

INTRODUCTION: Immunosuppressive therapy, necessary for graft survival, has its clinical consequences with an increased risk of developing malignancies being one of them. It seems that the maintenance of a proper balance between cytotoxic and regulatory activity of the immune system may prevent graft rejection, and with a lower risk of cancer. AIM: To assess the quantitative changes in regulatory T cells (Tregs) in peripheral blood of kidney transplant recipients with post-transplantation skin neoplasm after conversion to mTOR inhibitors (mTORi) and to assess the incidence of secondary skin cancer in that group of patients. MATERIAL AND METHODS: Fourteen patients with post-transplant cutaneous malignancies converted to mTORi were included into the study. The control group consisted of eighteen patients maintained on immunosuppressive regimens without mTORi. The level of Tregs with a phenotype defined as CD4lowCD25high was measured before, and 6 months after, mTORi introduction. RESULTS: In all cases, 6 months after conversion, a significant decrease in the ratio of CD4+CD25+ to CD4lowCD25high from 6.52 to 4.29 was detected (p = 0.035). One patient converted to mTORi developed subsequent skin cancer, while in the control group, subsequent skin cancer was recognized in eight patients. Moreover, introducing mTORi significantly improved progression-free survival in this group of patients (p = 0.016). CONCLUSIONS: Introducing mTORi to the immunosuppressive regimen resulted in an increase in the number of regulatory cells without increasing the incidence of secondary skin cancer in the investigated group of patients.

[Carcinogenic viruses in etiopathogenesis of skin cancers in patients after organ transplantation]. / Wirusy onkogenne w etiopatogenezie nowotworów skóry u chorych po przeszczepieniach narzadów.

The latest literature report specifies multifactoral etiology of skin cancer in population of patients after organs transplats. Carcirogenic viruses are one of etiopathogenesis components. Viruses of a vital meaning for skin oncogenesis are called Human papillomavirus - HPV, Human herpesvirus 8 - HHV8 i Merkel cell polyomavirus - MCV. Report on connections exisisting between viruses HPV and skin cancers in the population of patients after organs transplants confirms clinical connection between viruses papillas and cancers centres occuring in similar locations and more frequent appearance of attributes characteristic for HPV infection within the limits of changes in the type of Squamous cell carcinoma (SCC). What's more, coexisting of viruses papillas and SCC is more often noticed in the population of organ recipients than in the population of healthy people. It is not confirmed yet that any specific correlation between subtypes of HPV and greater frequency of morbidity in skin cancers really exist. However, in the population of organ recipients infections of different types of HPV are found within the limits of cancers centres in the case of SCC (63%) as well as in basal cell carcinoma-BCC (55%). DNA of HPV was also fund in healthy parts of organ recipients skin (92-94%). HHV8 is also an oncogenic viruse that influences the development of lymphoma. Infection of that virus may cause ocuuring of Kaposi's sarkoma, which is one of the most frequent types of cancer appearing in population of patients treating by long-term immunosuppression in particular geographical zones. MCV, which belongs to the group called Polyomaviriade, owes a particular meaning in etiopathogenesis of Merkel cell carcinoma - MCC. It is a rare cancer derived from neuroendocrine cells of the basic layers of epidermie. For over 30 years it was supposed that correlation between viruses and skin cancers in population of organ recipient exist. Knowledge of the total viruses influence on skin cancers allows to widen the spectrum of anti-cancers prevention in the future.

[Risk factors for skin cancer development in patients after organ transplantation]. / Czynniki ryzyka rozwoju nowotworów zlosliwych skóry u chorych po przeszczepieniu narzadów.

Cancer has become the second most common cause of death in patients after organ transplantation. Among all cancers arising de novo after transplantation skin cancers are the most common, accounting for 95% of all skin neoplasms. Due to the significantly higher morbidity, aggressive, rapid progression of cancer and unfavorable prognosis, the population requires a specific oncological approach. Therefore, special attention should be paid to factors predisposing to the development of cancer, including skin cancer, in patients after organ transplantation. Some of these factors are well understood, while the role of others is still ambiguous. Among the etiological factors mentioned are those that are associated with the recipient. These include genetic factors such as male sex, fair skin and inability to be tanned, and compatibility of the HLA system, and non genetic factors such as patient age, chronic skin ulcers and scars, the type of transplanted organ, immunosuppression, and particularly the type and cumulative doses of drugs. In addition, the pathogenesis of cancer is influenced by environmental factors such as exposure to sunlight and therefore latitude, ionizing radiation, chemical carcinogens and viral infections. Knowledge of etiological factors and mechanisms of etiopathogenesis allow for indication and observation of patients with increased risk of cancer as well as faster healing in these patients.  

The sero-epidemiology of human papillomavirus among Caucasian transplant recipients in the UK.

BACKGROUND: Despite intensive study of high-risk mucosal human papillomaviruses (HPV), little is known of the epidemiology of cutaneous HPV. As part of a study of cutaneous squamous cell carcinoma and HPV among organ transplant recipients (OTR) from London and Oxford, we investigated the seroprevalence and risk factors for 34 HPV types (detected using Luminex technology) among 425 Caucasian OTR without skin cancer. RESULTS: Overall, 86% of participants were seropositive to at least one HPV: 41% to mucosal alpha types, 33% to cutaneous alpha types, 57% to alpha types, 56% to beta, 47% to gamma types and 45% to other types (nu, mu, HPV101 and 103). In both centres, the most common types were HPV6 (33% and 26% for London and Oxford respectively), HPV8 (24% and 18%), HPV15 (26% and 29%), HPV17 (25% and 21%), HPV38 (23% and 21%), HPV49 (19% and 21%), HPV4 (27% and 23%), HPV65 (30% and 25%), HPV95 (22% and 20%), HPV1 (33% and 24%) and HPV63 (28% and 17%). The seroprevalence of 8 HPV types differed significantly (P < 0.05) between London and Oxford. Those individuals seropositive to multiple types of one genus were more likely to be seroreactive to multiple types of another genus. As expected, antibodies against mucosal alphaHPV types were more frequent in younger patients and among women. Sunbed use and sunbathing was associated with seropositivity to multiple gammaHPV (P-trend = 0.007) and self-history of abnormal smear was related to seroactivity to multiple betaHPV (P = 0.01). Skin type and other self reported markers of exposure to ultraviolet radiation were not consistently associated with any HPV types. No other distinguishing epidemiological features of transplant recipients with antibodies against single or multiple HPV types were identified. CONCLUSION: Findings for mucosal HPV types were in line with results from previous studies. We observed differences in HPV seroprevalence between organ transplant recipients from two geographically close centres but no clear risk factor was found associated with cutaneous HPV seropositivity among organ transplant recipients. These findings have implications for interpretation of future seroepidemiology studies addressing the association between HPV and cutaneous SCC in OTR populations.

A case-control study of cutaneous squamous cell carcinoma among Caucasian organ transplant recipients: the role of antibodies against human papillomavirus and other risk factors.

A case-control study was conducted in 140 people with histology proven cutaneous squamous cell carcinoma (SCC) and 454 controls, nested within 2 cohorts of organ transplant recipients (OTR) recruited in London and Oxford between 2002 and 2006. All participants had a skin examination, completed a questionnaire and had serum tested for antibodies against the L1 antigen of 34 HPV types using Luminex technology. SCC was more common in men than women (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.1-2.8, p = 0.02) and in people with susceptibility to burn easily (OR = 3.0, 95%CI: 1.9-4.8; p < 0.001). The risk increased with increasing age (p-trend < 0.001), increasing time since transplant (p-trend < 0.001), increasing self-reported number of sunburns as a child (p-trend < 0.001) and with the presence of viral warts (p < 0.001). As expected, antibodies against HPV 16 were associated with a self-reported history of an abnormal cervical smear among women (OR 5.1, 95%CI: 2.6-10.2) and antibodies against HPV 6 were associated with a self-reported history of genital warts (OR 4.0, 95%CI: 2.2-7.2). However, no clear associations between any of the HPV types examined (including cutaneous betaHPVs) and SCC were identified. For example, the seroprevalence of HPV 5 was 15% among cases and 9% among controls (p = 0.09) and the seroprevalence of HPV 8 was 23% among cases and 21% among controls (p = 0.6). Nor was seropositivity to multiple types associated with SCC. These serological data do not provide evidence for a role for HPV in the aetiology of cutaneous SCC among OTR in two UK-based populations.