Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study.

BACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97-2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0-2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.

A skincare combined with combination of adapalene and benzoyl peroxide provides a significant adjunctive efficacy and local tolerance benefit in adult women with mild acne.

INTRODUCTION: Acne in adult women is an increasing reason for dermatological consultations. OBJECTIVE: The aim of this study was to assess in adult women with mild acne the efficacy and tolerance of a daily adjunctive application of a skincare (Normaderm® , Laboratoires Vichy, France) to a fixed combination of adapalene/benzoyl peroxide daily or every other evening and a standard emollient. METHODS: Subjects were randomized to receive the fixed combination applied either every evening or every other evening and a daily application of the standard emollient and the test care or a once daily application of the fixed combination and the standard emollient alone. Clinical evaluations at Day 0, Day 45 and Day 90 included the count of acne lesions, assessment of clinical improvement and local tolerance. The quantitative lipid profile of the stratum corneum of the forehead was also determined. RESULTS: After 90 days of application, acne had improved in all 299 subjects with a statistically significant difference in favour of the test care regimens (P < 0.05). Moreover, skin quality, subject satisfaction, skin discomfort and sebum composition were in favour of these regimens. CONCLUSION: In conclusion, the tested skincare combined with a fixed adapalene and benzoyl peroxide combination provides a significant adjunctive efficacy and local tolerance benefit in adult women with mild acne.

The European Status Quo in legal recognition and patient-care services of occupational skin cancer.

BACKGROUND: Skin cancer is the most common malignancy in Caucasian populations worldwide and ultraviolet radiation (UVR) is known for being the number one carcinogen. As, especially in outdoor workers, UVR is an inevitable carcinogen, the prevention and management of UVR-related skin cancers in these at-risk populations represent a collective challenge for dermatologists and healthcare policymakers likewise. OBJECTIVE: To provide an overview on the current regulations on the acknowledgement and management of work-related skin cancer in 11 European countries. METHODS: Dermatologists from 11 countries networking within the EU Horizon 2020 COST Action TD1206 'StanDerm' contributed to a standardized survey regarding current national regulations, implemented for the recognition, prevention and management as well as possible compensation regulations in their individual country of residence. RESULTS: Ten of 11 participating countries in this survey reported the existence of an established programme available on certain occupational diseases; work-related skin diseases were only specifically recognized in eight countries. Seven of 11 countries recognize cutaneous squamous cell carcinoma in outdoor workers as 'occupational skin cancer'. Basal cell carcinoma (6 of 11), actinic keratosis (5 of 11), Bowen's disease (5 of 11) and malignant melanoma (5 of 11) are not as regularly approved as potentially 'work-induced'. Only a few of the countries included into this survey established a general documentation system (national registry) on occupational skin diseases. So far, representatives of only three countries of this survey referred to a specific established national programme for the prevention, management or compensation of occupational skin cancers acquired during work-related UVR exposure. CONCLUSION: This survey highlights the need for mandatory regulations on the prevention, management and potential compensation of work-related UV-induced skin cancer across Europe. Against the background of a joint European domestic market, equal standards of occupational safety across Europe should include binding regulations for the protection and management of work-related skin cancer. The design of a common regulation to meet the increasing incidence of skin cancers in outdoor workers should become part of the European agenda, ensuring equal working and living conditions in the member states.

Pain identifies squamous cell carcinoma in organ transplant recipients: the SCOPE-ITSCC PAIN study.

Organ transplant recipients (OTR) are at high risk for cutaneous squamous cell carcinomas (SCC). We aimed to define clinically meaningful patient-reported warning signals predicting the presence of invasive SCC.Patient-reported signs and symptoms of 812 consecutively biopsied skin lesions from 410 OTR were determined by questionnaire and physical examination and related to the subsequent biopsy-proven diagnoses. Receiver-operating characteristic (ROC) curve analyses were used as a measure of distinction between the predictive values of patient-reported warning signals and the occurrence of SCC. Pain was an independent predictive patient-reported warning signal for a biopsy-proven invasive SCC. The odds ratio from the fully adjusted model predicting SCC was 4.4(95% confidence interval: 2.4­8.2). Higher scores on the visual analog scale (VAS) for pain were associated witha greater likelihood for the presence of SCC compared to none or mild pain. The for scores on the VAS from 1to 3, 4 to 6 and 7 to 10 were 4.9 (2.2­10.5), 2.3 (0.96­5.5)and 16.5 (3.6­75.8), respectively. Pain is the most powerful patient-reported warning signal for invasive cutaneous SCC in OTR. Empowerment of patients by education could accelerate diagnosis and treatment of cutaneous SCC.

Prevalence of benign cutaneous disease among Oxford renal transplant recipients.

BACKGROUND: The burden of malignant and benign cutaneous disease among renal transplant recipients (RTR) is substantial. Little attention is given to non-malignant skin problems in the literature despite their potential impact on quality of life or on aesthetics - which may contribute to poor compliance with immunosuppressive medications post-transplantation. OBJECTIVES: The aim of this study was to examine prevalence of benign cutaneous disease in a group of RTRs and identify risk factors for individual cutaneous conditions. METHODS: All cutaneous findings were recorded in a single full body skin examination of 308 RTRs. Data on medical, transplant and medication history were obtained from questionnaire and medical records. Odds ratios were calculated to look at associations between benign cutaneous diseases and various potential risk factors after controlling for gender, age, time since transplantation and skin type. RESULTS: Cutaneous infections such as viral warts (38%), fungal infection (18%) and folliculitis (27%) were common and usually chronic. A range of pilosebaceous unit disorders were observed with hypertrichosis being strongly associated with ciclosporin (P<0.0001). Other iatrogenic cutaneous effects included gingival hyperplasia (27%) and purpura (41%). We identified seborrhoeic warts and skin tags in 55% and 33% respectively. Inflammatory dermatoses were rare (<2%) apart from seborrhoeic dermatitis (9.5%). DISCUSSION: In this first comprehensive study on prevalence of benign cutaneous diseases in a UK transplant population, a wide range of skin disorders was identified. It is therefore important that RTRs have access to dermatology services post-transplantation for appropriate management of benign cutaneous conditions as well as early detection of cutaneous malignancy and education regarding risks of sun exposure.

Association of seborrhoeic warts with skin cancer in renal transplant recipients.

BACKGROUND: Renal transplant recipients (RTR) have a well recognized increased risk of cutaneous malignancy. A clinical observation that RTR with skin cancer often had multiple seborrhoeic warts prompted an investigation in RTR into the relationship between seborrhoeic warts and skin cancer and an exploration into potential risk factors for seborrhoeic warts in this population, including infection with human papillomavirus (HPV). METHODS: This was a case control study involving 308 RTR. Clinical examinations identified seborrhoeic warts. Histological records reviewed to look for evidence of prior cutaneous malignancy. Seroprevalence of antibodies to 34 different HPV types tested using multiplex serology. Odds ratios (OR) calculated using unconditional logistic regression analysis to look for associations between skin cancer, HPV infection and seborrhoeic warts, controlling for potential confounding factors of gender, age and time since transplantation. RESULTS: Seborrhoeic warts were associated with non-melanoma skin cancer [OR = 3.7; 95% confidence intervals (CI) ranging from 1.6-8.9; P = 0.002] when confounding factors of gender, age and time since transplantation were controlled for. There was also an association between seborrhoeic warts and viral warts (OR = 3.0, CI: 1.6-5.4; P < 0.0001), but no association between seborrhoeic warts and infection with single or multiple HPV types. CONCLUSIONS: Seborrhoeic warts are associated with cutaneous malignancy, but not with any of the HPV types tested. The reasons for this association are unclear. RTR with multiple seborrhoeic warts may require more regular cutaneous examination to monitor for early signs of skin cancer.

Melanoma in organ transplant recipients: clinicopathological features and outcome in 100 cases.

Organ transplant recipients have a higher incidence of melanoma compared to the general population but the prognosis of this potentially fatal skin cancer in this group of patients has not yet been established. To address this, we undertook a multicenter retrospective analysis to assess outcome for 100 melanomas (91 posttransplant and 9 pretransplant) in 95 individuals. Data were collected in 14 specialist transplant dermatology clinics across Europe belonging to the Skin Care in Organ Transplant Patients, Europe (SCOPE) Network, and compared with age, sex, tumor thickness and ulceration status-matched controls from the American Joint Committee on Cancer (AJCC) melanoma database. Outcome for posttransplant melanoma was similar to that of the general population for T1 and T2 tumors (< or = 2 mm thickness); but was significantly worse for T3 and T4 tumors (> 2 mm thickness); all nine individuals with a pretransplant melanoma survived without disease recurrence following organ transplantation. These data have implications for both cutaneous surveillance in organ transplant recipients and management of transplant-associated melanoma.

Solid Organ Cancer and Melanoma in Kidney Transplant Recipients: TumorTx Base Preliminary Results.

BACKGROUND: Incidence of malignancy in transplant recipients is higher than in the general population. Malignancy is a major cause of mortality following solid organ transplantation and a major barrier to long-term survival for the kidney. The aim of this study was to estimate the incidence of solid organ malignancy (SOM) and melanoma in renal transplant recipients (RTR) transplanted at 2 representative transplant centers in Poland based on data from the Polish Tumor Registry. MATERIAL AND METHODS: We analyzed the medical data of 3069 patients who underwent kidney transplantation (KTx) between 1995 and 2015. RESULTS: In our study 112 SOM (3.6%) were diagnosed. The majority of patients were male (n = 71; 63.4%; P < .01). The mean age at KTx was 48.0 ± 13.1 years and the mean age at the time of cancer diagnosis was 55.9 ± 12.7 years. The average time of malignancy occurrence was 5.9 ± 5.0 years after KTx. SOM was the cause of death in 60 patients (53%). The most common were malignancies of gastrointestinal tract (25%), urinary tract tumors (23.2%), lung cancer (n = 18; 16%), and lymphoma (13.4%). We found an increase in the percentage of chronic glomerular nephropathy in the group of SOM (n = 56; 50%) compared with renal insufficiency of other etiologies. CONCLUSIONS: RTR in Poland are at a significant risk of malignancy development in a variety of organs, primarily urinary tract tumors and lymphoma. Cancers most frequently occurring in the general population such as lung and colorectal cancer are common in our RTR. On this basis an appropriate tumor screening schedule can be developed in individual countries.

Association Between HLA Type and Skin Cancer in Kidney Transplant Recipients.

BACKGROUND: Organ transplant recipients (OTRs) are more susceptible to various diseases, among them cancers. Nonmelanoma skin cancers (NMSC) represent the most common malignancies in OTRs in Europe. Due to the significantly higher morbidity, aggressive and rapid progression, and poor prognosis of NMSC in the OTR population, these patients require a special oncological approach. Intensive attention should therefore be paid to factors predisposing OTRs to the development of cancer. The aim of this study was to establish the role of genetic factors in the pathogenesis of skin cancer in kidney transplant recipients (KTRs). METHODS: This single-center study was performed in 39 KTRs with posttransplant NMSC. The frequency of particular types of HLA Class I (HLA-A and HLA-B) and Class II (HLA-DR) in each group were compared to establish the association between the HLA type and risk of skin cancer after renal transplantation. RESULTS: HLA-DR15 were more commonly detected in patients with MNSC than in the control group of KTRs (P = .014) There was also a positive correlation between HLA-B18 and skin squamous cell carcinoma. The antigen was more often recorded in KTRs with squamous cell carcinoma than in KTRs without NMSC (P = .03) and in the general population (P = .002). CONCLUSIONS: Patients who are positive for HLA-BR15 and HLA-B18 should be under special dermatologic surveillance due to the potentially high risk of skin cancer.

Impact of Skin Cancer Awareness on Prophylactic Behavior Among Renal Transplant Recipients.

BACKGROUND: Renal transplant recipients (RTRs) have a risk for skin cancer. The most important risk factor, and the only one that depends on patient behavior, is the exposure to ultraviolet light. The aim of this study was to assess the level of skin cancer awareness and its impact on preventative behavior among RTRs. METHODS: Questionnaires were applied to assess the awareness of increased risk of skin cancer and its influence on preventative behavior among RTRs. RESULTS: Of the RTRs, 51.6% considered themselves as a group of patients with a high risk of skin cancer. Only 11.5% (group A) were able to fully explain the whole reason of the need for sun protection usage. A partial explanation was provided by 40.1% of the patients (group B). The other 48.5% of the patients (group C) provided no explanation. Among the patients, 53.9% of surveyed RTRs never applied any sunscreen. Of RTRs, 22.5% claimed to always avoid direct exposure to sunlight. Most of the patients admitted to having outdoor hobbies (81% of group A, 60.3% of group B, 58% of group C). In addition, 36.2% of RTRs thought that they were more attractive if they were tanned. CONCLUSIONS: The awareness of being in a group of increased risk of skin cancer is still poor among RTRs. Skin cancer awareness does not correlate with usage of different forms of sun prevention. There is a great need for active education of Polish RTRs.

Associations of Selected Cytokines Levels in Organ Transplant Recipients Without and With Malignant Skin Neoplasms.

INTRODUCTION: Skin malignancies are the most prevalent neoplasms seen in organ transplant recipients (OTRs). Immunosuppressive treatment has been attributed to play a causative role in malignancy development. The aim of the study was to assess cytokine concentrations involved in cytotoxic and regulatory responses in patients after organ transplantation (Tx). We compared two OTR subgroups: those with malignant skin tumors and those without any known changes developed after Tx. MATERIALS AND METHODS: We enrolled 102 patients, 63: 3-360 (median: min-max) months after Tx, aged 54.3 ± 9.9 (mean ± SD) years (38.2% females). Seventeen patients were diagnosed with malignant skin neoplasms. The most frequent treatment schemes were cyclosporine A - mycophenolate mofetil - glucocorticosteroids (GS) (37.4%), mycophenolate mofetil-tacrolimus - GS (15.2%), and azathioprine-cyclosporine A-GS (14.1%). A 5-mL sample of venous blood was obtained from participants of two subgroups: those with malignant skin tumors and those without any known changes. The blood was tested for interleukin 2 (IL-2), interferon gamma, IL-10, and transforming growth factor beta concentrations (Multicytokine Flex Set, ELISA). The Kruskal-Wallis test was used to compare variables; P < .05 was considered valid. RESULTS: Age, gender distribution, and time from transplantation did not differ across the two subgroups. We found significantly lower blood concentrations of IL-2 and IL-10 in patients with post-transplantation skin cancers versus patients without any known skin changes (0 pgmL(-1) vs. 21.22 pgmL(-1), and 4.93 pgmL(-1) vs. 7.36 pgmL(-1), respectively). The differences between interferon gamma and transforming growth factor beta levels were insignificant across studied groups. CONCLUSIONS: Our findings suggest that immunosuppressive response assessed by cytokine IL-2 and IL-10 levels may be used in the risk stratification for the development of skin cancer in organ recipient patients.

Benign Cutaneous Disease Among Polish Renal Transplant Recipients.

BACKGROUND: Organ transplant recipients are an at-risk group for skin cancers and benign cutaneous diseases. Immunosuppression type, dosage, and treatment length dictates the frequency of benign lesions. MATERIAL AND METHODS: Two hundred twenty-three consecutive adult renal transplant recipients (RTRs) were enrolled and screened for benign skin lesions. During examination, swabs, skin scrapings, and nail clippings were collected from any suspected areas infection and any cutaneous lesions marked for quality and quantity on a special questionnaire. The aim was to examine the prevalence of benign cutaneous disease and risk factors. RESULTS: Fungal infections were the most common infections found (60%), most commonly in the oral cavity (40.8%). Viral warts occurred in 18.4%, being significantly more common in those transplanted over 5 years (P = .002). Hypertrichosis was the most common pilosebaceous disorder found (P ≤ .001). Other iatrogenic cutaneous effects included purpura (50.2%), xerosis (41.2%), and gingival hyperplasia (28.2%), the latter strongly associated with cyclosporine (P = .0005). Seborrhoeic warts (23.8%) were most common in patients older than 50 years (P < .001). One-third of subjects had skin tags (31%). DISCUSSION: This is the largest study of the prevalence and type of non-malignant cutaneous diseases in Polish RTRs. We see increasing numbers of patients with long-term side effects from immunosuppressive therapy, and treatment, gender, age, and time since transplantation should be considered with new skin lesions in everyday practice with RTRs. CONCLUSIONS: The study group had a high prevalence of benign cutaneous diseases and these should not be overlooked as they can cause aesthetic problems and reduced quality of life.

Kaposi Sarcoma in the Genital Area in a Kidney Transplant Patient: A Case Report and Literature Review.

BACKGROUND: Kaposi sarcoma (KS) is a cancer with an incidence in patients after transplantation (Tx) that is 500 times greater than that in the healthy population. The risk of KS increases significantly during therapy, especially when immunosuppressive therapy with cyclosporine A (CsA) is used. Most cases of KS develop during the first 2 years after transplantation. After a KS diagnosis, it is recommended to reduce the doses of immunosuppressive medications. Conversion of immunosuppressive treatment into mammalian target of rapamycin (m-TOR) inhibitors is strongly suggested. PATIENTS AND METHODS: We present the case of a 65-year-old man with end-stage renal disease (ESRD) of unknown etiology, who had kidney transplantation in 2008. Immunosuppressive protocol was based on CsA, mycophenolate mofetil (MMF) and prednisolone (PRE). In 2011, during the dermatological consultation, on the penis glans a purple stain of uneven surface was noted. Histology study revealed the presence of KS. The treatment was modified. The patient was converted from CsA to everolimus. Before converting, the creatinine concentration was 1.79 mg/dl and proteinuria less than 0.3 g/day. RESULTS: The change in the scheme of immunosuppresion from CsA to everolimus was performed to treat the Kaposi sarcoma. Gradually, within a year, the KS was cured. However, the graft function deteriorated, and the graft was lost in one-years' time. CONCLUSION: We present the first documented case of KS in the genital area of a kidney patient. The reduction in the strength of immunosuppression, and the introduction of an m-TOR inhibitor, may have contributed to the deterioration of kidney function, however it was substantial in the treatment of KS.

Skin Cancers as Contraindication to Organ Transplantation.

The period of preparing patients for organ transplantation is a suitable time for dermatologic screening and examination that guarantee early diagnosis and easier treatment of precancerous states and skin cancers. In most cases, diagnosis of skin cancer in the pretransplantation period is not a contraindication to transplantation. Knowledge of risk factors and etiopathogenesis of skin cancers after transplantation make it easier to point out patients with increased risk of skin carcinogenesis. Patients with skin phototype I-III (Fitzpatrick classification) and with high cumulative doses of ultraviolet radiation have an increased risk of skin cancers. Patients who had skin cancers in the past should be carefully examined, and the skin cancer histopathology should be analyzed in detail. These examinations have to be done from the clinical, surgical, and histopathologic aspects. It helps dermatologists to estimate the risk and predict the patient's health after a possible organ transplantation. Basal cell carcinoma and squamous cell carcinoma that are present before transplantation indicate the possibility of similar cancer occurrence after transplantation; however, they are not a contraindication to transplantation after treatment of the primary foci. The waiting period to transplantation in the case of melanoma in situ takes 2 years, but in more serious forms of melanoma this time is prolonged to ≥ 5-10 years. Different skin cancers have a 3-year asymptomatic period to renewed indication for transplantation.

Human papillomavirus-related verrucous carcinoma in a renal transplant patient after long-term immunosuppression: a case report.

BACKGROUND: Verrucous carcinoma is a slow-growing tumor with 3 main localizations: Oral cavity, ano-urogenital region, and plantar surface of the foot. On the sole it may rise adjacent to viral warts and very often is mistaken for the common verruca plantaris. Although both conditions-viral warts and cutaneous squamous cell carcinoma-are often diagnosed in immunosuppressed patients, in literature we have found only 3 case reports of verrucous carcinoma in organ transplant recipients. CASE REPORT: We present a case of 26-year-old man after deceased donor renal transplantation with plantar verrucous carcinoma successfully treated with excision and 5% imiquimod.

Sebaceous carcinoma in patients receiving long-term immunosuppresive treatment: case report and literature review.

BACKGROUND: Sebaceous carcinoma (SC) is a very rare and aggressive malignant skin cancer that appears to occur with a greater frequency in the clinical setting of chronic immunosuppression; however, it is not reported in the literature as frequently as is squamous cell carcinoma (SCC). We report 2 cases of SC in organ transplant patients from clinical and histopathological points of view. METHODS: A 48-year-old patient after 3 renal transplantations (1986, 1986, and 1998) was presented to the Dermatology Department in 1999 because of a papillomatous lesion along her right upper eyelid. The lesion was excised. Histopathologically, it was diagnosed as a SC. There was no lymphovascular invasion and no metastasis; therefore no other treatment was included. No symptoms of recurrent disease were present 14 years since diagnosis. An 87-year-old patient after a renal transplantation in 1989 was referred to dermatologist in 1993 because of the lesion on his right temple. The lesion was excised; histopathologically, it was diagnosed as SC. Because of metastatic disease, he had a course of radiotherapy to the right side of the neck. The immunosuppressive drugs azathioprine and cyclosporine A were reduced. The patient died of metastatic disease 1 year later (3 years since diagnosis). Both patients had very high cumulative UV exposition during their lifetimes, and many skin cancers were diagnosed, especially SCC. RESULTS: It is necessary to realize that this cancer occurs more frequently in organ transplant patients, and its correct diagnosis is an essential issue because it has significantly more aggressive behavior than does SCC. In the 2 presented patients, we observed very rapid progression of disease. Despite aggressive treatment and reduction of immunosuppressive drugs, the second patient died 3 years after diagnosis. CONCLUSIONS: Regular dermatological follow-up is required in the population of organ transplant patients to identify all skin tumors in the early stage.

Superficial fungal infections in renal transplant recipients.

BACKGROUND: Renal transplant recipients (RTRs) are predisposed to fungal infections because of long-term graft-preserving immunosuppressive therapy. METHODS: We prospectively enrolled 223 consecutive adult RTRs. Patients were transplanted at 1 of 2 transplant centers in Poland. The group consisted of 97 women (43%) and 126 men (57%). The control group consisted of 100 patients (39 women and 61 men) randomly selected from the outpatient dermatology clinic and from hospital personnel. All RTRs and the control group were screened for the presence of superficial fungal infections. All patients were examined by the same dermatologist. The oral mucosa and the entire body surface were fully examined. Mucosal swabs were obtained from all patients in both the examined and control groups. Skin scrapings and swabs were obtained from any clinically suspicious lesions. Nail clippings were collected in the case of any nail changes. RESULTS: Superficial fungal infections have been detected in 133 RTRs (60%)and 27 controls (27%; P = .00001). One hundred eight RTRs (62%) developed superficial fungal infections in the first year after transplantation (P < .008). The most common site for superficial fungal infections in the RTRs group was the oral cavity. Candida albicans was the most frequently isolated species in the oral cavity. CONCLUSIONS: Superficial fungal infections in RTRs are statistically more common among RTRs than in the general population. Whether the drug was used separately or administrated under immunosuppressive combinations had no influence on the occurrence of fungal infections. The final results showed no correlation between patient age and the occurrence of fungal infections. Dermatologists who care for transplant patients should be aware of the clinical course of fungal species in RTRs compared with the general population.