Solid organ transplant and subsequent graft survival have increased worldwide, while immunosuppression has prevented rejection with increasing success. Side effects of cutaneous infection and... Show moreSolid organ transplant and subsequent graft survival have increased worldwide, while immunosuppression has prevented rejection with increasing success. Side effects of cutaneous infection and neoplasm, however, affect the majority of solid organ transplant recipients (OTRs). Squamous cell carcinoma of the skin (SCC) is the most common neoplasm overall following organ transplant with a risk that is 60-100 times greater than for the immunocompetent population. This review focuses on questions of ongoing debate about SCC formation in OTRs such as viral carcinogenesis, systemic photoprotection, photosensitization by drugs, the impact of immunosuppressive drugs and inflammation as a driver of carcinogenesis. Show less
Koning, M.N.C. de; Schegget, J. ter; Eekhof, J.A.H.; Kamp, M.; Kleter, B.; Gussekloo, J.; ... ; Quint, W.G.V. 2010
A large number of human papillomavirus (HPV) types, distributed over five papillomavirus genera, are detectable in the skin. HPV types belonging to the alpha, gamma, and mu genera have been... Show moreA large number of human papillomavirus (HPV) types, distributed over five papillomavirus genera, are detectable in the skin. HPV types belonging to the alpha, gamma, and mu genera have been detected in cutaneous warts. A state-of-the-art HPV genotyping assay for these cutaneous wart-associated HPV types does not exist although warts constitute a highly prevalent skin condition, especially in children (33%) and organ transplant recipients (45%). Cutaneous warts are again the focus of attention as their clinical relevance rises with the increasing number of chronically immunosuppressed patients. The objective of this study was to develop and evaluate a DNA-based genotyping system for all known cutaneous wart-related HPV types using PCR and Luminex xMAP technology. The broad-spectrum PCR amplified DNA of all known wart-associated HPV types from the genera alpha (HPVs 2, 3, 7, 10, 27, 28, 29, 40, 43, 57, 77, 91, and 94), gamma (HPVs 4, 65, 95, 48, 50, 60, and 88), mu (HPVs 1 and 63), and nu (HPV41). The probes were evaluated using plasmid HPV DNA and a panel of 45 previously characterized cutaneous wart biopsy specimens showing high specificity. HPV was also identified in 96% of 100 swabs from nongenital cutaneous warts. HPV types 1, 2, 27, and 57 were the most prevalent HPV types detected in 89% of the swabs. In conclusion, this Luminex-based genotyping system identifies all known cutaneous wart HPV types including phylogenetically related types, is highly HPV type specific, and is suitable for large-scale epidemiological studies. Show less
Background. The risk of skin cancer is highly increased in kidney-transplant recipients (KTR), but the risk of subsequent skin cancers is less well studied. The aim of this study was to estimate... Show moreBackground. The risk of skin cancer is highly increased in kidney-transplant recipients (KTR), but the risk of subsequent skin cancers is less well studied. The aim of this study was to estimate the cumulative incidence of subsequent squamous- and basal-cell carcinomas (BCCs) and to analyze potential risk factors. Methods. All histologically confirmed skin cancers between 1966 and 2006 were included in the study and counted. Cumulative incidences of subsequent squamous- and BCCs were calculated using Kaplan-Meier survival analyses. For the analyses of risk factors, we used Cox proportional hazard analyses. Results. A total of 239 (13%) of 1906 KTR developed skin cancer of whom 222 were diagnosed in our hospital. Altogether 167 (75%) of these 222 patients developed multiple skin cancers. The cumulative incidence of a second skin cancer increased from 32%, I year, to 59%, 3 years, and 72%, 5 years after the first skin cancer. KTR who started with squamous-cell carcinoma (SCC) mainly developed SCC and recipients who started with BCC mainly developed BCC as second skin cancer. Immunosuppression with azathioprine in combination with prednisone was associated with a significantly increased risk of subsequent SCCs but not with subsequent BCCs. Conclusion. Skin cancer multiplicity is common in KTR. Patients with a first skin cancer are at increased risk for more skin cancers and need to be carefully checked for subsequent skin cancers. Show less
Koning, M.N.C. de; Schegget, J. ter; Eekhof, J.A.H.; Kamp, M.; Kleter, B.; Gussekloo, J.; ... ; Quint, W.G.V. 2010
A large number of HPV types, distributed over five papillomavirus genera, is detectable in the skin. HPV types belonging to the alpha, gamma and mu genus have been detected in cutaneous warts. A... Show moreA large number of HPV types, distributed over five papillomavirus genera, is detectable in the skin. HPV types belonging to the alpha, gamma and mu genus have been detected in cutaneous warts. A state-of-the-art HPV genotyping assay for these cutaneous wart-associated HPV types does not exist, although warts constitute a highly prevalent skin condition especially in children (33%) and organ transplant recipients (45%). Cutaneous warts are again the focus of attention as their clinical relevance rises with the increasing number of chronically immunosuppressed patients. The objective of this study was to develop and evaluate a DNA based genotyping system for all known cutaneous wart-related HPV types using PCR and Luminex xMAP technology. The broad spectrum PCR amplified DNA of all known wart-associated HPV types from the alpha- (HPV2, 3, 7, 10, 27, 28, 29, 40, 43, 57, 77, 91 and 94), gamma- (4, 65, 95, 48, 50, 60 and 88), mu- (HPV1 and 63) and nu-genus (HPV41). The probes were evaluated using plasmid HPV DNA and a panel of 45 previously characterised cutaneous wart biopsies showing high specificity. HPV has also been identified in 96% of 100 swabs from non-genital cutaneous warts. HPV types 1, 2, 27 and 57 were the most prevalent HPV types detected in 89% of the swabs. In conclusion, this Luminex based genotyping system identifies all known cutaneous wart HPV types including phylogenetically related types, is highly HPV-type specific and is suitable for large-scale epidemiological studies. Show less
Background Several new therapeutic options for psoriasis have been tested in clinical trials in recent years. Choice of comparator, study duration and outcome measures are critical for interpreting... Show moreBackground Several new therapeutic options for psoriasis have been tested in clinical trials in recent years. Choice of comparator, study duration and outcome measures are critical for interpreting application of trial results to clinical practice. Objectives We examined whether these trial aspects have changed substantially in recent years in comparison with the past. Methods A systematic search and evaluation of all randomized controlled trials (RCTs) for psoriasis published from January 2001 up to December 2006 in 14 leading medical and dermatological journals, compared with those published from 1977 to 2000. Results There were 140 RCTs of psoriasis in the period 2001-2006 and 249 in the period 1977-2000. The proportion of placebo-controlled studies increased from 44.6% to 69.3%. The median study duration increased from 7 weeks to 12 weeks. The proportion of studies adopting the Psoriasis Area and Severity Index score as an outcome increased from 30.6% to 57.7%, while the number of studies incorporating a quality of life measure increased from only one (0.4%) to 12 studies (7.7%). The proportion of studies sponsored by pharmaceutical companies increased from 61.0% to 73.7%. Conclusions Despite the increased number of new options, the number of head-to-head comparative trials has decreased and most trials focus on short-term effects, probably reflecting the increased influence of industrial sponsorship on the research agenda. Show less
Background Skin diseases are frequently observed in organ-transplant recipients (OTRs). Objectives To count the registered skin diseases in all 2136 OTRs who had been transplanted in a single... Show moreBackground Skin diseases are frequently observed in organ-transplant recipients (OTRs). Objectives To count the registered skin diseases in all 2136 OTRs who had been transplanted in a single centre between 1966 and 2006 and to calculate their relative contribution in relation to the number of years after transplantation. Methods All registered skin diseases which were entered into a computerized system between 1994 and 2006 at the Leiden University Medical Centre were counted and their relative contributions were calculated. Results Between 1994 and 2006, 2408 skin diseases were registered in 801 of 1768 OTRs who were at risk during this specific time period. The most commonly recorded diagnoses were skin infections (24.0%) followed by benign skin tumours (23.3%) and malignant skin lesions (18.2%). The relative contributions of infectious and inflammatory disorders decreased with time after transplantation, whereas the contribution of squamous cell carcinomas strongly increased with time. Conclusions This study gives a systematic overview of the high burden of skin diseases in OTRs. The relative distributions of skin diseases importantly changed with time after transplantation, with squamous cell carcinoma contributing most to the increasing burden of skin diseases with increasing time after transplantation. Show less
