Stefano Piaserico

Prevalence of metabolic syndrome in patients with psoriasis: a hospital‐based case–control study

Background  Psoriasis is a chronic inflammatory disease associated with an increased cardiovascular risk. Metabolic syndrome is a significant predictor of cardiovascular events.

Immune and Nonimmune Predictors of Cardiac Allograft Vasculopathy Onset and Severity: Multivariate Risk Factor Analysis and Role of Immunosuppression

We studied 361 patients, to evaluate risk factors for cardiac allograft vasculopathy (CAV) onset and severity/diffusion in heart transplantation (HT). Rejection scores (RS) on endomyocardial biopsy were calculated (first year and whole follow‐up). CAV onset was defined as any lesion seen at yearly angiography. A CAV severity/diffusion index was calculated for each patient summing up the scores of all lesions. Cox multivariate analysis included: donor age, sex, and weight; recipient sex, age, pre‐HT diagnosis, hypertension, diabetes and hyperlipidemia post‐HT; number of treated rejections and RS; and immunosuppressive dosage at 3, 6, and 12 months. CAV frequency was 2% at 1 year, 22% at 5 and 39% at 10 years. Risk factors for CAV onset were older donor age [p < 0.0001, relative risk (RR) = 9.9], male donor (p < 0.001, RR = 3.2), high RS for severe (≥ 3A) grades (p < 0.02, RR = 2.01), high cyclosporine at 3 months (p < 0.02, RR = 1.9). Risk factors for CAV severity/diffusion were higher donor weight (p < 0.01, RR = 7.5), high prednisone dosage at 1 year (p < 0.0001, RR = 21.1), and coronary disease pre‐HT (p < 0.002, RR = 9.7). High RS was an independent predictor for CAV onset, not severity/diffusion. This suggests an immune basis for CAV onset and nonimmune modulation for progression. High RS for severe grades may provide a predictor for patients at risk.

Skin cancer in heart transplant recipients: frequency and risk factor analysis

BACKGROUND The frequency of skin cancer is increased among organ transplant recipients, but the predisposing risk factors are controversial. It is also unclear whether heart transplant patients face an increased risk compared to recipients of other organs, e.g. kidney transplants. METHODS We performed univariate and multivariate analysis of risk factors for skin cancer in 252 heart transplants and in a control series of 228 kidney transplants followed up at a single center. An extensive dermatologic examination was carried out; baseline features, type of immunosuppression, number of 3A rejection episodes, extent of sunlight exposure and skin type were recorded. Multivariate analysis (Cox regression) included: age at transplantation, sex, skin type (Fitzpatricks criteria), presence of solar keratosis, presence of warts, type of organ, sunlight exposure. RESULTS During follow up skin cancer was more common among heart transplants (40, 16 %) than in kidney transplants (16, 7%, p = 0.004). The cumulative incidence of skin cancer by life table analysis increased from 16% after 5 years to 33% after 10 years in heart transplant patients and from 6% to 17% in kidney transplants (p 10000 hours (relative risk = 2.8), but not organ type were significant risk factors. CONCLUSION Age at transplant, skin type and sunlight exposure, but not type of organ and type of immunosuppressive regimen, are associated with increased risk of skin cancer in heart transplantation.

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.

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.

Eruptive melanocytic nevi in patients with renal allografts: report of 10 cases with dermoscopic findings.

Eruptive nevi have been reported after renal allograft transplantation, particularly in children and adolescents, and immunosuppression has been suggested to favor both benign and malignant melanocyte proliferation. In this study, we describe the dermoscopic features of eruptive melanocytic nevi in 10 children, adolescents, and young adults with renal allografts in whom multiple melanocytic nevi developed during a short period after transplantation. Dermoscopy of the eruptive pigmented lesions revealed a peripheral rim of brown globules. This rim of peripheral globules was present in 80% of the patients with eruptive nevi and in most of the lesions of the same patient. The other standard dermoscopic criteria for melanocytic nevi were normal. In our study, we confirm previous reports concerning the development of eruptive nevi in children and adolescents receiving immunosuppressive therapies. In particular, we showed by dermoscopy the presence of a characteristic symmetrical rim of peripheral brown globules. This finding is consistent with the hypothesis that a symmetrical peripheral rim of globules may indicate rapid enlargement of melanocytic lesions. Moreover, we have identified a new group of patients characterized by this dermoscopic feature. These patients are children, adolescents, and young adults with renal allografts receiving immunosuppressive therapy and it is plausible that this dermoscopic characteristic may be found in eruptive nevi developed in association with immunosuppression from any cause.

Practical approach to the use of daylight photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: a European consensus†

Daylight‐mediated photodynamic therapy has been shown to be an effective therapy for actinic keratoses (AKs) and a simple and tolerable treatment procedure in three randomized Scandinavian studies and two recent Phase III randomized controlled studies in Australia and Europe.

European Dermatology Forum Guidelines on topical photodynamic therapy

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines.

Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue?

Introduction: Immunogenicity of antitumor necrosis factor-alpha (TNFα) agents has been proven to play a significant role in the variability of clinical responses among patients with chronic inflammatory diseases. However, its clinical impact on the outcome of patients with psoriasis and psoriatic arthritis receiving anti-TNFα treatment is not yet fully clear. Despite the high rates of efficacy of anti-TNFα agents in psoriasis, a substantial proportion of patients remain who experience a primary or secondary failure or significant side effects, which are potentially ascribable to immunogenicity. Areas covered: Topics include immunologic response elicited by anti-TNFα agents, the impact of immunogenicity on treatment response to anti-TNFα and the role played by immunogenicity in the lack of efficacy of anti-TNFα agents (infliximab, adalimumab and etanercept) in psoriasis. Expert opinion: Based on data available in the literature and the clinical experience of the authors, this article suggests the optimal approach to drug monitoring and antidrug antibody assay and the most effective use of biologic immunotherapies in this setting. Immunogenicity should be taken into account in the adoption of therapeutic choices in psoriatic patients, such as anti-TNFα agent intensification, or switching to another anti-TNFα agent or a drug with a different mechanism of action.

Immunosuppression and melanocyte proliferation.

Melanocytes are pigmented cells derived from the neural crest; their proliferation is restrained by immune system. The eruption of nevi after an immunosuppressive condition is a peculiar phenomenon indicating that the immune system may play a major role in limiting proliferation of melanocytes. In this review, we analyze the role of immunosuppressive regimens on melanocyte proliferation. In particular, we discuss the eruptive nevi phenomenon, which is determined by the inability of the immune system to inhibit melanocyte proliferation. These clinical observations indicate that the immune system has a pivotal role in restraining melanocyte proliferation. However, although the role of the immune system in the development of nonmelanoma skin cancer has been shown clearly in several studies involving organ transplant patients, the role of immunosuppression in melanoma genesis has not yet been established. Further investigations are required to establish the real immunogenicity of melanoma, particularly in the light of the dichotomy between the eruptive nevi phenomenon in immunosuppressed patients and the low incidence of melanoma in transplanted patients.