Factors associated with the seroprevalence of 26 cutaneous and two genital human papillomavirus types in organ transplant patients.

Viral skin infections are commonly present in organ transplant recipients (OTR). In this study, we aimed to identify factors associated with human papillomavirus (HPV) infections in OTR. Patients with solid-organ transplants were recruited from the outpatient nephrology and dermatology clinics in five European countries. Only patients with no current or past skin cancer were included in this analysis. Serum samples were analysed for antibodies to the L1 proteins of 26 cutaneous and two genital HPV types from five phylogenetic genera (α, ß, γ, µ and ν). The most consistent association was found between recreational sun exposure and the seroprevalence of all tested genera, except α. The antibody presence of any ß type was higher among people who had been transplanted at least 23 years prior to participation than in those who had been transplanted for less than 7 years. The prevalence of two γ-HPV types (60 and 65) and three ß-HPV types (15, 38 and 49) was associated with time since transplantation. The presence of a high number of warts was associated with the presence of any µ-PV or ν-PV types, and having greater than 50 keratotic skin lesions was almost significantly associated with the presence of antibodies to two or more γ-PV. Discrepancies in the results of the present study, as well as in previous reports, may depend on different methodologies and on geographical variations. Our results also indicate that further research with more standardized methods is needed to clarify the role of cutaneous HPV in OTR.

Early and late effects of the immunosuppressants rapamycin and mycophenolate mofetil on UV carcinogenesis.

Increased skin cancer risk in organ transplant recipients has been experimentally emulated with enhanced UV carcinogenesis from administering conventional immunosuppressants. However, newer generation immunosuppressive drugs, rapamycin (Rapa) and mycophenolate mofetil (MMF), have been shown to impair angiogenesis and outgrowth of tumor implants. To ascertain the overall effect on UV carcinogenesis, Rapa and MMF were admixed into the food pellets of hairless SKH1 mice receiving daily sub-sunburn UV dosages. With immunosuppressive blood levels neither of the drugs affected onset of tumors (<2 mm), but in contrast to MMF, Rapa significantly increased latency of large tumors (>or=4 mm, medians of 190 vs 125 days) and reduced their multiplicity (1.6 vs 4.5 tumors per mouse at 200 days). Interestingly, tumors (>2 mm) from the Rapa-fed group showed a reduction in UV-signature p53 mutations (39% vs 90%) in favor of mutations from putative base oxidation. This shift in mutation spectrum was not essentially linked to the reduction in large tumors because it was absent in large tumors similarly reduced in number when feeding Rapa in combination with MMF, possibly owing to an antioxidant effect of MMF. Significantly fewer tumor cells were Vegf-positive in the Rapa-fed groups, but a correspondingly reduced expression of Hif1alpha target genes (Vegf, Ldha, Glut1, Pdk1) that would indicate altered glucose metabolism with increased oxidative stress was not found. Remarkably, we observed no effect of the immunosuppressants on UV-induced tumor onset, and with impaired tumor outgrowth Rapa could therefore strongly reduce skin carcinoma morbidity and mortality rates in organ transplant recipients.

Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR).

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile, nonfollicular pustules usually arising on an oedematous erythema often accompanied by leucocytosis and fever. It is usually attributed to drugs. OBJECTIVES: To evaluate the risk for different drugs of causing AGEP. PATIENTS AND METHODS: A multinational case-control study (EuroSCAR) conducted to evaluate the risk for different drugs of causing severe cutaneous adverse reactions; the study included 97 validated community cases of AGEP and 1009 controls. Results Strongly associated drugs, i.e. drugs with a lower bound of the 95% confidence interval (CI) of the odds ratio (OR) > 5 were pristinamycin (CI 26-infinity), ampicillin/amoxicillin (CI 10-infinity), quinolones (CI 8.5-infinity), (hydroxy)chloroquine (CI 8-infinity), anti-infective sulphonamides (CI 7.1-infinity), terbinafine (CI 7.1-infinity) and diltiazem (CI 5.0-infinity). No significant risk was found for infections and a personal or family history of psoriasis (CI 0.7-2.2). CONCLUSIONS: Medications associated with AGEP differ from those associated with Stevens-Johnson syndrome or toxic epidermal necrolysis. Different timing patterns from drug intake to reaction onset were observed for different drugs. Infections, although possible triggers, played no prominent role in causing AGEP and there was no evidence that AGEP is a variant of pustular psoriasis.

The occurrence of residual or recurrent squamous cell carcinomas in organ transplant recipients after curettage and electrodesiccation.

BACKGROUND: Organ transplant recipients frequently develop multiple squamous cell carcinomas (SCCs). Surgical excision and Mohs micrographic surgery are frequently used treatments for these carcinomas; however, curettage and electrodesiccation are a useful alternative in these patients. OBJECTIVES: To evaluate the efficacy of curettage and electrodesiccation for the treatment of appropriately selected low-risk SCCs in organ transplant recipients at different sites. METHODS: Between April 1989 and December 2004, 211 SCCs in 48 organ transplant recipients were treated by curettage and electrodesiccation. Only histologically confirmed SCCs were considered in this study. The charts of these patients were retrospectively reviewed and checked for the rate of residual or recurrent SCCs. The occurrence of residual or recurrent SCCs at different locations after treatment of SCCs with curettage and electrodesiccation was estimated with Kaplan-Meier survival analysis. RESULTS: The mean follow-up time after curettage and electrodesiccation of the individual SCCs was 50 months (median 41; range 3-186). In total, 13 residual or recurrent SCCs were observed in 10 patients. The overall rate of residual or recurrent SCCs was 6%, with 7% for SCCs on the dorsum of the hands or fingers, 11% for SCCs on the head and neck, 0% for the forearms, and 5% for the remaining nonsun-exposed areas (shoulder, legs). No major clinical or cosmetic adverse events were registered after treatment. CONCLUSIONS: In organ transplant recipients with many SCCs curettage and electrodesiccation can be a safe therapy for appropriately selected low-risk SCCs, with an acceptable cure rate.

Overview of studies of treatments for hand eczema-the EDEN hand eczema survey.

BACKGROUND: Hand eczema is a major cause of morbidity and lost earnings. Many interventions ranging from topical steroids to oral ciclosporin are used, but their evidence base and the best methods to assess their efficacy are uncertain. OBJECTIVES: As part of a long-term project to improve standards of design and reporting in hand eczema trials, we sought to describe the prevalent study designs and comment on the quality of reporting of such studies. METHODS AND DATA SOURCES: Electronic databases (Cochrane, Medline, Embase, Pascal, Jicst-Eplus, Amed) were searched from January 1977 to April 2003 using all possible variants of the terms hand and eczema/dermatitis. In addition, four general medical and 17 specialist dermatology journals were hand-searched by pairs of researchers for all possible therapeutic studies. STUDY SELECTION: Studies were eligible for inclusion if they dealt with hand eczema as diagnosed by a physician irrespective of the aetiology, and if they described the results of a study of a therapeutic intervention in humans. Single case reports and reviews were excluded, but case series and nonrandomized studies were considered alongside randomized studies. Data selection For each study, two researchers independently assessed the type of study, outcome measures, enrolment criteria, randomization, masking of interventions and how losses to follow-up were dealt with. MAIN OUTCOME MEASURES: Proportion of studies according to type of intervention and study type. Proportion of randomized controlled trials (RCTs) that adequately reported eligibility criteria, randomization generation and concealment, masking and intention-to-treat analysis. RESULTS: A total of 90 studies reported in 87 papers dealt with 11 different classes of interventions. Around 80% of the studies dealt with just four interventions: ultraviolet light, topical steroids, radiation and systemic immunosuppressives. Of the 90 studies, 44 were case series, 15 were nonrandomized controlled trials, and the remaining 31 were RCTs. Of the 31 RCTs, 16 were parallel (one with cross-over design) and 15 self-controlled. Only 11 of the RCTs adequately reported eligibility criteria. The randomization method was described in 10, and there was adequate concealment of allocation in eight. Masking the treatment allocation from both the study assessors and patients was done in 11 RCTs, and intention-to-treat analysis was reported in four. Only 13 RCTs were 4 months or longer in duration. No study reported a rationale for the sample size, and in only one study had the outcome variable been validated. CONCLUSIONS: Most 'trials' in hand eczema are not RCTs. Internally controlled (left/right) studies were common. Based on the poor overall quality of reporting, most RCTs of hand eczema trials are not adequate to guide clinical practice. Future trials of hand eczema should be randomized, using a parallel group or self-controlled design. Research is needed to develop validated and clinically relevant outcome measures. Most of the remaining issues relating to poor quality of existing evidence can be relatively easily dealt with by following the CONSORT guidelines.