C. Masini

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.

Therapy with rituximab for autoimmune pemphigus: Results from a single-center observational study on 42 cases with long-term follow-up

BACKGROUND Rituximab induces depletion of B cells and has shown efficacy in antibody-mediated autoimmune disorders. In studies on small series of patients with pemphigus, rituximab administration results in significant improvement. However, differences in inclusion criteria, treatment protocols, and follow-up make it difficult to derive uniform conclusions. OBJECTIVES We sought to test the efficacy and tolerability of rituximab as adjuvant therapy to corticosteroids in the treatment of pemphigus. METHODS In all, 42 patients with pemphigus were treated with rituximab and followed up for up to 5 years. No additional immunosuppressive agents were used. Steroids were rapidly tapered. Outcomes were the proportion of patients who achieved a complete response on or off therapy, the rate of discontinuation of corticosteroid within 6 months, length of remission, time to relapses, and occurrence of adverse events. RESULTS In all, 36 of 42 patients (86%; 95% confidence interval 75%-96%) achieved a complete response on or off therapy and discontinued steroids within 6 months from induction therapy. Six patients had a complete response off therapy with an additional infusion of rituximab 6 months after initial treatment. Twenty patients experienced a total of 34 relapses; the time to relapse was 8 to 64 months. Every relapse was treated with rituximab (500 mg) without corticosteroids, which induced a new complete response. No serious adverse events were observed. LIMITATIONS Lack of a control group is a limitation. CONCLUSIONS Rituximab therapy induces prolonged clinical remission in patients with pemphigus. Coadministration of other immunosuppressive agents is not necessary. Relapses can be managed with additional infusions administered on demand.

Kaposi's sarcoma in renal-transplant recipients: experience at the Catholic University in Rome, 1988-1996.

BACKGROUND The incidence of Kaposis sarcoma (KS) in patients transplanted at the Organ Transplant Center of Catholic University in Rome appears to have increased in recent years. OBJECTIVE To describe the clinical characteristics of KS in a group of transplant recipients. METHODS Over 8 years, a total of 302 renal-transplant recipients were followed. When KS was suspected, histology and staging procedures were performed. RESULTS Ten cases of KS have been diagnosed (8 males, 2 females; age 46.4 +/- 9.4 years); 4 of them were on triple therapy. All the patients were HIV-1 seronegative. The onset of KS occurred 3 months to 4 years after transplantation (21.1 +/- 17.6 months). The disease was limited to the skin in 6 cases and involved internal organs in the remaining 4. Four patients experienced complete remission of the disease following reduction of the immunosuppressive therapy. CONCLUSION The high incidence of KS in this population (2.98%), as compared to that reported in other transplant patient groups, suggests that, besides viral infection, genetic predisposition may play a pathogenetic role. However, immunosuppression is the leading factor in transplant patients.

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.

Severe persistent pemphigoid gestationis: long-term remission with rituximab

SIR, Pemphigoid gestationis (PG) is a rare autoimmune blistering disease of late pregnancy and the early postpartum period caused by antibasement membrane zone (BMZ) autoantibodies. The incidence of PG is estimated at between 1 in 10 000 and 1 in 50 000 pregnancies. In most cases PG affects women in the sixth to ninth gestational month and usually resolve spontaneously within weeks to months after delivery; however, flares can occur at or immediately after delivery and very uncommonly the disease persists for months or even years postpartum. Corticosteroids are the mainstay of therapy, but administration of high doses for a long period of time has considerable risk of severe irreversible side-effects. Several immunosuppressive treatments have been used for persistent PG as steroid-sparing agents, with varying degrees of success, and these also have potential long-term side-effects. We report a 31-year-old woman who developed PG during her third pregnancy in June 2004. She had a history of transitory cutaneous rash that had appeared and spontaneously disappeared at the end of her second pregnancy. During the fifth month of her third pregnancy she developed diffuse pruritic urticarial plaques with small blisters in some areas, resistant to systemic corticosteroid therapy (prednisone up to 40 mg daily). A healthy male child was born by caesarean section at the end of the 32nd week. Two days after delivery the patient experienced a flare of the cutaneous eruption. She came to our attention after 5 months of unsuccessful corticosteroid therapy with prednisone up to 100 mg daily associated with azathioprine 50 mg daily. She showed intensely pruritic papules and plaques predominantly located on the abdomen and extremities, with blisters (Fig. 1). She also had moon face, obesity, iatrogenic diabetes and osteoporosis. Histopathology of skin lesions showed subepidermal blisters with focal basal cell necrosis and an inflammatory infiltrate largely composed of eosinophils. Direct immunofluorescence of perilesional skin revealed linear deposition of IgG and C3 along the BMZ, while indirect immunofluorescence on monkey oesophagus was negative. Enzyme-linked immunosorbent assay (ELISA) (Medical and Biological Laboratories, Nagoya, Japan) demonstrated circulating anti-BP180 antibodies at 147 IU mL (normal < 9). Treatment was started with prednisone 100 mg daily, azathioprine 150 mg daily and dapsone 125 mg daily for 3 months, with only partial response. Intravenous immunoglobulin therapy at a dose of 0.5 g kg daily for three consecutive days was therefore initiated in February 2005 and repeated for two further 3-day courses monthly, resulting in only temporary improvement. Finally, intravenous rituximab was started at the dose of 375 mg m weekly for four consecutive weeks in May 2005, with complete clearing of cutaneous lesions in the subsequent 4 months. Azathioprine was discontinued and prednisone was gradually tapered to 12.5 mg daily. Anti-BP180 antibodies (a)

HHV8 in renal transplant recipients

Abstract Human herpevirus 8 (HHV8) DNA sequences have been found in lesions from patients with Kaposis sarcoma (KS) in several forms including immunosuppressed transplant patients. We wanted to study the transmission of HHV8 in kidney transplant recipients and to assess the risk of development of KS related to the viral infection in this group of patients. We tested sera of 120 renal transplant recipients with serological assay for antibodies to HHV8 antigens before transplantation and then we tested sera of 66 patients of the same group after transplantation. Antibodies were detectable in 27.5 % of the patients before transplantation. In the seropositive population 15.1 % developed KS and in the negative group 1.1 %. Analysing 66 posttransplant sera we noticed that 24 % of the seronegative patients became positive after transplantation. Our data suggest that being positive for HHV8 before transplantation could be an important risk factor for the development of KS.

Antibodies against human herpesvirus 8 in subjects with non-venereal dermatological conditions

BACKGROUND Human herpesvirus 8 (HHV8) is considered as the infectious cofactor involved in the pathogenesis of Kaposis sarcoma (KS). Its seroprevalence and modes of transmission in the general population are still undetermined. OBJECTIVES We aimed to estimate the prevalence of HHV8 infection in a population at low risk for sexually transmitted diseases. METHODS We conducted a seroepidemiological survey on randomly selected individuals attending the dermatology department of a teaching hospital in Rome. Of 257 patients, 248 had their blood analysed for anti-HHV8 antibodies and 201 completed a standardized interview. Serological analysis was performed by an immunofluorescence assay able to detect antilytic antibodies. RESULTS We found an overall seroprevalence of 15.7% (95% confidence interval, CI 11.4-20.9%), similar in men and women (15.1% vs. 16.3%) and higher at older ages. Seropositivity was not related to sexual habits, while it was significantly associated with a history of hepatitis (seroprevalence 34.6%, adjusted odds ratio, OR 4.08, 95% CI 1.52-11.00) and with a diagnosis of non-melanoma skin cancer (42.9%, OR 4.20, 95% CI 1.26-14.02) or atypical naevi (35.3%, OR 6.21, 95% CI 1.85-20.86). CONCLUSIONS Our data suggest that a non-sexual mode of transmission of HHV8 infection is plausible in an Italian population at low risk for sexually transmitted diseases and that other factors, besides differences in prevalence of HHV8 infection, may be involved in the epidemiology of classical KS. The unexpectedly high seropositivity rates in subjects with non-melanoma skin cancer and atypical naevi should be viewed with caution and require confirmation.

Dyshidrosiform Palmoplantar Pemphigoid in a Young Man: Response to Dapsone

© 2010 The Authors. doi: 10.2340/00015555-0734 Journal Compilation

Antibodies against human herpesvirus 8 in subjects with non-venereal dermatological conditions: HHV8 IN NON-VENEREAL DERMATOSES

Background  Human herpesvirus 8 (HHV8) is considered as the infectious cofactor involved in the pathogenesis of Kaposis sarcoma (KS). Its seroprevalence and modes of transmission in the general population are still undetermined. Objectives We aimed to estimate the prevalence of HHV8 infection in a population at low risk for sexually transmitted diseases. Methods We conducted a seroepidemiological survey on randomly selected individuals attending the dermatology department of a teaching hospital in Rome. Of 257 patients, 248 had their blood analysed for anti‐HHV8 antibodies and 201 completed a standardized interview. Serological analysis was performed by an immunofluorescence assay able to detect antilytic antibodies. Results We found an overall seroprevalence of 15·7% (95% confidence interval, CI 11·4–20·9%), similar in men and women (15·1% vs. 16·3%) and higher at older ages. Seropositivity was not related to sexual habits, while it was significantly associated with a history of hepatitis (seroprevalence 34·6%, adjusted odds ratio, OR 4·08, 95% CI 1·52–11·00) and with a diagnosis of non‐melanoma skin cancer (42·9%, OR 4·20, 95% CI 1·26–14·02) or atypical naevi (35·3%, OR 6·21, 95% CI 1·85–20·86). Conclusions Our data suggest that a non‐sexual mode of transmission of HHV8 infection is plausible in an Italian population at low risk for sexually transmitted diseases and that other factors, besides differences in prevalence of HHV8 infection, may be involved in the epidemiology of classical KS. The unexpectedly high seropositivity rates in subjects with non‐melanoma skin cancer and atypical naevi should be viewed with caution and require confirmation.