B.J. Vermeer

Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study.

PURPOSE The purpose of this study was to investigate the effect of acitretin on the development of keratotic skin lesions, and on squamous cell carcinomas and basal cell carcinomas in a group of renal transplant recipients. PATIENTS AND METHODS Forty-four renal transplant recipients with more than 10 keratotic skin lesions on the hands and forearms were enrolled onto a randomized, double-blind, placebo-controlled trial to test the possible skin cancer-preventing effect of a 6-month treatment with acitretin 30 mg/d. RESULTS No deterioration in renal function occurred in any of the 38 assessable patients treated. During the 6-month treatment period, two of 19 patients (11%) in the acitretin group reported a total of two new squamous cell carcinomas, compared with nine of 19 patients (47%) in the placebo group who developed a total of 18 new carcinomas (chi 2 = 6.27, P = .01). The relative decrease in the number of keratotic skin lesions in the acitretin group was 13.4%, as compared with a relative increase in the placebo group of 28.2% (difference, 41.6%; 95% confidence interval, 11.5 to 71.7). Most patients treated with acitretin had mild mucocutaneous side effects, but these were easily manageable. Some patients experienced mild hair loss. With the exception of three patients, no increase in serum cholesterol or triglyceride above pretreatment levels was observed, and liver function remained unchanged in all patients. CONCLUSION Acitretin 30 mg/d over 6 months had significantly more effect than placebo in the prevention of squamous cell carcinomas and reduced the occurrence of keratotic skin lesions in a group of renal transplant recipients with severe lesions. This effect was most pronounced in patients with a history of squamous cell carcinomas and basal cell carcinomas.

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.

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.

Adjuvant high-dose intravenous gammaglobulin in the treatment of pemphigus and bullous pemphigoid: experience in six patients

At present, initial high‐dose prednisone is the treatment of choice for patients with pemphigus and bullous pemphigoid. To reduce the risks associated with long‐term corticosteroid treatment, other immunosuppressants are often given as steroid‐sparing agents. Occasionally, the dose of steroids cannot be reduced. In this study, we report six patients with pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid, in whom the daily corticosteroid dose could only be tapered to acceptable, effective, maintenance levels following treatment with high‐dose intravenous gammaglobulin.

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.

Resurfacing the back of the hand as treatment and prevention of multiple skin cancers in kidney transplant recipients

BACKGROUND Skin cancer is a serious problem in renal transplant recipients. In some patients numerous skin cancers develop on the back of the hand. Instead of repeated excisions, a more radical procedure may be necessary. For these patients a new surgical therapy is available: resurfacing the back of the hand. OBJECTIVE Our purpose was to clinically evaluate this new procedure. METHODS Eleven kidney transplant recipients who underwent resurfacing of the back of the hand were analyzed in a retrospective follow-up study. With this surgical procedure the skin of the entire dorsum of the hand is excised and split-skin grafts harvested from thigh and buttock skin are then placed. Information was gathered from the medical records and questionnaires, and by physical examination. RESULTS The mean follow-up time was 4.7 years. No recurrences of skin cancer were observed in the transplanted skin. The cosmetic appearance was acceptable, and there were few side effects. CONCLUSION Resurfacing the back of the hand can be a successful treatment for carefully selected patients with multiple skin cancers on the back of the hand and can be used prophylactically in patients with severely actinically damaged skin.

PUVA keratosis: A clinical and histopathologic entity associated with an increased risk of nonmelanoma skin cancer

BACKGROUND Various types of hyperkeratotic lesions can be observed in patients with psoriasis treated with PUVA. Clinically it can be difficult to classify them and to differentiate benign from malignant hyperkeratotic lesions. Recently, we introduced the term PUVA keratosis, which we regard as a distinct entity. OBJECTIVE The purpose of the study was to describe in more detail the clinical and histopathologic features of PUVA keratoses and to investigate a possible relation with nonmelanoma skin cancer. METHODS A group of 13 psoriasis patients with PUVA keratoses was studied and compared with 247 psoriasis patients without these keratoses, who had also received long-term therapy with PUVA. RESULTS The presence of PUVA keratoses was associated with an increased risk of nonmelanoma skin cancer. The estimated relative risk for skin cancer in patients with PUVA keratoses, adjusted for age, sex, and UVA dose, as compared with psoriasis patients without these keratoses, who had also received long-term PUVA treatment, was 6.5 (95% confidence interval, 1.3 to 32.1). Squamous cell carcinomas contributed the most to this increased risk. CONCLUSION PUVA keratoses are associated with an increased risk of nonmelanoma skin cancer. Therefore careful clinical follow-up of psoriasis patients with PUVA keratoses is necessary, and cessation of PUVA treatment should be considered.

A Female Patient with the Rothmund-Thomson Syndrome Associated with Anhidrosis and Severe Infections of the Respiratory Tract

The Rothmund-Thomson syndrome is a rare syndrome which is believed to be inherited in an autosomal pattern. Poikiloderma of the face and extremities is a characteristic feature. Besides this, less common aspects have been reported like alopecia, cataracts, short stature, musculoskeletal/bone defects or small hands, hypogonadism, abnormal teeth, dysplastic nails, anhidrosis and a high incidence of cutaneous and non-cutaneous malignancies. We present a patient with the Rothmund-Thomson syndrome together with anhidrosis and multiple infections of the upper and lower respiratory tract. Investigation of immunological function revealed a low total number of T lymphocytes with a slightly depressed reactivity. Immunoglobulins were markedly increased.

Ultraviolet exposure and the development of banal and atypical naevi--a cross-sectional study on Curaçao and in The Netherlands.

The atypical naevus is both a risk factor for and a precursor lesion of melanoma. Sunlight is known to be an important aetiological factor for melanoma. Whether solar exposure is also involved in the initiation of (atypical) naevi is an issue of current interest. We performed a cross-sectional study among 270 inhabitants in the cloudy Netherlands and 282 white Dutch immigrants of the tropical island Curacao to investigate whether solar exposure plays a role in the development of atypical naevi. All participants were interviewed and underwent total skin examination; banal melanocytic naevi and atypical naevi were counted. There was no significant difference in the mean number of melanocytic naevi ≥ 2 mm or ≥5 mm between Curacao and the Netherlands. Furthermore, there was no significant difference in the mean crude and age standardized prevalence of atypical naevi between the Netherlands and Curacao. In both groups individuals with atypical naevi had significantly more total naevi. Concerning the role of sun exposure in the development of naevi in the Netherlands, we found that the total naevus count had a significant association with cumulative sun exposure before the age of 12 as well as with two or more painful sunburns before the age of 12. In Curacao these relationships were not observed. In contrast, however, on Curacao the presence of atypical naevi showed an association (odds ratio=2.6, 95% confidence interval 1.1-6.0) with the highest level of cumulative sun exposure and with painful sunburns before the age of 12 (odds ratio=2.6, 95% confidence interval 1.2-5.5). In the Dutch group these associations were not significant. We hypothesize that in the development of banal naevi there is an association between the total number of naevi and sun exposure only at low exposure levels; however, after overstepping a critical threshold a further association between melanocytic naevi and sun exposure is lacking. Sunlight exposure before the age of 12 plays a complex role: only very high exposure levels seem to contribute to the development of atypical naevi.

Prevention of Skin Cancer During Acitretin Therapy in Renal-Transplant Recipients; a Placebo-Controlled Study

Forty-four renal-transplant recipients were enrolled in a randomised, doubleblind, placebo-controlled trial to test the possible skin-cancer-preventing effect of a six-month treatment with acitretin 30 mg daily. No deterioration in renal function occurred in any of the 38 evaluable patients treated. During the six-month treatment period 2 out of 19 patients (11%) in the acitretin group reported all together 2 new squamous cell carcinomas compared with 9 out of 19 patients (47%) in the placebo group who developed all together 18 new carcinomas: 15 squamous cell carcinomas, 1 Bowen’s disease and 2 basal cell carcinomas (chi-square 6.27, p = 0.01). Interestingly, the effect of acitretin in preventing new skin cancers could largely be attributed to the group of 19 patients with a history of skin cancer. Most patients treated with acitretin had mild mucocutaneous side effects, but these were well manageable. Some patients experienced mild hair loss. With the exception of three patients no increase in serum cholesterol or triglyceride above pre-treatment levels was observed, and liver function remained unchanged in all patients. Acitretin 30 mg daily during six months had significantly more effect than placebo to prevent squamous cell carcinomas in a group of renal-transplant recipients who suffered severely from these lesions. This effect was most pronounced in patients with a history of skin cancer.