J.N. Bouwes Bavinck

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.

Sunlight, keratotic skin lesions and skin cancer in renal transplant recipients

In a retrospective follow‐up study, 36 renal transplant recipients with, and 101 without, skin cancer, who had received their first transplant before January 1981 and who were still alive with a functioning graft on 1 August 1989, were assessed to determine the risk of non‐melanoma skin cancer in relation to exposure to sunlight during childhood and adolescence. The contribution of the number of keratotic skin lesions to the skin cancer risk was also assessed.

Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis

Summary  Background Therapy with fumaric acid esters (FAE) has been shown to be safe and effective in patients with severe psoriasis in several clinical studies with limited follow‐up periods. In view of the chronic character of psoriasis, long‐term safety aspects are of major importance in determining the suitability of a drug during prolonged periods of treatment.

A case-control study of betapapillomavirus infection and cutaneous squamous cell carcinoma in organ transplant recipients

We examined the association between betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (>94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline‐significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in organ transplant recipients. Confirmation of a betaPV profile predictive of risk for SCC may pave the way for clinically relevant pretransplant HPV screening and the development of preventive and therapeutic HPV vaccination.

Detection of epidermodysplasia verruciformis-like human papillomavirus types in malignant and premalignant skin lesions of renal transplant recipients

To evaluate the putative role of human papillomaviruses (HPV) in the development of skin cancer in renal transplant recipients, a series of skin biopsies from premalignant and malignant skin lesions was analysed using the polymerase chain reaction. Four different consensus primer pairs were used. HPV DNA was detected in five of 24 cases of squamous cell carcinoma, in one of three cases of Bowens disease, in none of four basal cell carcinomas, in two of seven cases of actinic keratosis and in one of five cases of keratoacanthoma. Typing by direct sequencing of the amplified HPV DNA was possible in seven of nine cases, and revealed epidermodysplasia verruciformis (EV)‐associated HPV types, or HPV types related to EV‐associated types. Hence, HPV DNA could be detected in a significant proportion of (pre)malignant skin tumours in renal transplant recipients. The finding that some of the detected HPV types were as yet uncharacterized EV‐related types, suggests that HPV DNA could be present in a higher percentage of lesions, and might be detected with refinement of the techniques.

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.

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 (≤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.

The presence of antibodies against virus‐like particles of epidermodysplasia verruciformis‐associated humanpapillomavirus type 8 in patients with actinic keratoses

Epidermodysplasia verruciformis‐associated human papillomaviruses (EV‐HPVs) are possibly involved in the development of actinic keratoses and may play a part in the pathogenesis of squamous cell carcinoma (SCC) of the skin, as the DNA of these viruses is frequently detected in biopsies of such lesions. Properly designed epidemiological studies, using serological tests to investigate the role of infection with EV‐HPVs in cutaneous oncogenesis, are still rare. An IgG‐specific enzyme‐linked immunosorbent assay using virus‐like particles composed of the major capsid protein L1 of the EV‐specific HPV 8 (HPV 8 VLPs) was developed and used to test the seroprevalence of HPV 8 in 114 inhabitants of a tropical island, of whom 13 had developed SCC, and 19 had developed basal cell carcinoma. Gender, age, eye and hair colour, sun exposure and number of actinic keratoses were recorded for all individuals. The presence of antibodies against HPV 8 VLPs was associated with the development of large numbers of actinic keratoses. After adjusting for gender, age, eye and hair colour, and sun exposure, the odds ratio to develop 37 (the median in this dataset) or more actinic keratoses in the presence of antibodies against HPV 8 VLPs was 2·3 (95% confidence interval: 1·0; 5·3). Similarly, after adjustment for the same factors, the presence of these antibodies was associated with SCC with an odds ratio of 3·1 (0·74; 13·3), but the small number of individuals with SCC does not permit any definite conclusions. The presence of these antibodies did not appear to be associated with basal cell carcinoma as, after adjustment for the same factors, the odds ratio was 0·73 (0·23; 2·4). This study provides serological evidence that infection with EV‐HPVs may play a part in the pathogenesis of actinic keratoses. The role of EV‐HPVs in the development of SCC, however, remains to be elucidated.

Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands.

Background  Information on the prevalence of bacterial cellulitis (BC) and erysipelas (ER) of the leg (BCERL) is sparse and dependent on the definitions used. There is no information available on the number of hospitalized and non‐hospitalized patients with BCERL, and related treatment costs.

Viral oncogenesis and its role in nonmelanoma skin cancer.

In recent years, the contribution of viruses to cutaneous oncogenesis has steadily gained recognition. The archetype is human herpesvirus 8, which is well established as the causative agent in Kaposi sarcoma. Other viruses believed to play a role in nonmelanoma skin cancer include human papillomavirus and the recently described Merkel cell polyomavirus. We review the mechanisms by which these three viruses interact with the host cell, ultraviolet radiation and immunosuppression to result in carcinogenesis.