Gianpaolo Tessari

Anti–tumour necrosis factor-α therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study

Background  Chronic plaque psoriasis is associated with overweight or obesity. Anti–tumour necrosis factor‐α (anti‐TNF‐α) treatments are now frequently used in psoriasis management. TNF‐α is deeply involved in body weight homeostasis, which may be affected by TNF‐α–targeted therapy.

Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registry-based study.

Background. Organ transplant recipients are at an increased risk of nonmelanoma skin cancer.Few data concern heart transplantation and populations from southern Europe. Methods. A total of 1329 patients who received their first kidney (1062 subjects) or heart allograft (267 subjects) were included in a partly retrospective cohort study to evaluate the risk of skin cancer. The incidence rate per 1000 person-years and the cumulative incidence were computed. Standardized morbidity ratio was estimated by comparison with Italian cancer registry data. To analyze the role of potential prognostic factors, Cox’s regression method was used. Results. The overall incidence rate of nonmelanoma skin cancer was 10.0 cases per 1000 posttransplant person-years (95% confidence interval 8.2–11.7). This estimate was far higher than expected in the general population. The overall risk of developing skin cancer increased from a cumulative incidence of 5.8% after 5 posttransplant years to an incidence of 10.8% after 10 years of graft survival. In a Cox proportional hazard risk model, the most important factors that appeared to favor the development of skin cancer were age at transplantation and sex. After adjustment for age at transplantation and sex, no definite increased risk was documented among heart as compared with kindney transplant recipients. Conclusions. Our study confirms the increased risk of nonmelanoma skin cancer among organ transplant recipients in a southern European population.

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.

Randomized controlled trial comparing the effectiveness of 308‐nm excimer laser alone or in combination with topical hydrocortisone 17‐butyrate cream in the treatment of vitiligo of the face and neck

Background  Vitiligo is a pigmentary disorder which may have disfiguring consequences. Its treatment remains a challenge.

Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: a multicenter cohort study.

OBJECTIVE To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients. DESIGN Partially retrospective cohort study. SETTING Two Italian transplantation centers. PATIENTS The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients. MAIN OUTCOME MEASURES Cumulative incidences and risk factors of the first and subsequent NMSCs. RESULTS Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a second NMSC after a median follow-up after the first NMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC. CONCLUSIONS Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable.

Nonmelanoma Skin Cancer in Solid Organ Transplant Recipients: Update on Epidemiology, Risk Factors, and Management

BACKGROUND Nonmelanoma skin cancers (NMSC) are the most frequently observed cancers in solid organ transplant recipients (SOTR) and may have a significant disease burden. OBJECTIVE To provide an update regarding the epidemiology and management of NMSC in SOTR. RESULTS Ten‐year incidence rates range from 10% in Italy to 20% in Northern Europe to 70% in Australia. More than 50% of NMSC are located on sun‐exposed areas (head, dorsum of hands). Many risk factors have been identified, including age at transplantation, fair skin, type of immunosuppressive drugs, cumulative sun exposure, viral infections, and various genetic markers. Patients with a first NMSC have a 49 times higher risk of developing a subsequent NMSC. Skin self‐examination and photoprotection should be encouraged in all transplanted patients. Long‐term skin surveillance, early diagnosis and aggressive treatment of any suspicious lesion, reduction of immunosuppressive therapy, and conversion to m‐TOR inhibitors can be also effective measures for reduction of NMSC incidence. CONCLUSIONS NMSC is the most frequent cancer observed in SOTR. Early diagnosis, patient education, and modification of immunosuppression are effective measures for reduction of NMSC incidence.

Antibody responses to 26 skin human papillomavirus types in the Netherlands, Italy and Australia

Solar UV radiation is the main risk factor for cutaneous squamous cell carcinoma (SCC), but infections with skin human papillomavirus (HPV) types have also been linked to the development of SCC. Little is known about the natural history of these infections and whether the seroprevalence of skin HPV types is affected by ambient or individual levels of sun exposure. This study investigated this by analysing sera for antibodies to 26 skin HPV types from five phylogenetic genera obtained from 807 healthy individuals from the Netherlands, Italy and Australia, countries with strong differences in sunlight intensity. Overall HPV seroprevalence was similar across the three countries (50-57 % for beta-HPV types, 40-48 % for gamma-HPV types), and the most frequent beta-HPV and gamma-HPV types were the same in all countries. The highest seroprevalences for 24 of the 26 skin HPV types were observed in Italy (14 types) and Australia (ten types). Seroprevalence among men was generally higher than among women, and the male sex was significantly associated with both beta-HPV [odds ratio (OR) 2.81, 95 % confidence interval (CI) 1.64-4.82] and gamma-HPV (OR 2.42, 95 % CI 1.40-4.18) antibodies in Australia. The only measure of sun sensitivity or UV exposure significantly associated with skin HPV seroprevalence was found for weekend sun exposure in Australia and beta-HPV antibodies. It was concluded that type spectra and HPV seroprevalence are similar in countries with different sunlight intensity, and that levels of UV exposure do not play a strong role in the development of skin HPV antibodies in this study population.

Renal Transplantation and Skin Diseases: Review of the Literature and Results of a 5-Year Follow-Up of 285 Patients

We present a review of the current literature on skin diseases in renal transplant recipients (RTR) and the results of a 5-year follow-up of 285 patients. Many skin diseases are only an aesthetic and functional cause for interest, but HPV infections and skin cancers are significantly more frequent in RTR than in immunocompetent subjects and can affect a patients prognosis. For this reason, we feel dermatological surveillance of RTR is necessary for early diagnosis and treatment of all high-risk lesions.

Incidence of Primary and Second Cancers in Renal Transplant Recipients: A Multicenter Cohort Study

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty‐three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow‐up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age‐ and sex‐matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non‐Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten‐year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non‐Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0–10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2–2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers.

Association of functional gene variants in the regulatory regions of COX‐2 gene (PTGS2) with nonmelanoma skin cancer after organ transplantation

Summary Background  Overexpression of cyclooxygenase‐2 (COX‐2), resulting in excessive prostaglandin production, has been observed in human epidermal keratinocytes after ultraviolet B injury, in squamous cell skin carcinoma (SCC), in actinic keratoses, and in the early stages of carcinogenesis in a wide variety of tissues. The dysregulation of COX‐2 expression can in part be due to functional changes affecting regulatory elements in the promoter or 3′ untranslated region (UTR) of the gene. Two common polymorphisms (–765G→C, and –1195A→G) in the promoter region of the COX‐2 gene (now PTGS2), and one common polymorphism in the 3′ UTR (8473T→C) have been described, and reported as associated with various malignancies.