Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study.

BACKGROUND: Long-term treatment for atopic dermatitis (AD) using low-dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent exacerbations. OBJECTIVES: This 12-month, European, multicentre, randomized study investigated if proactive, twice-weekly application of 0.03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. PATIENTS AND METHODS: During the initial open-label period, 267 children with AD applied 0.03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of

A feasibility study using polychemotherapy (cisplatin + vindesine + dacarbazine) plus interferon-alpha or monochemotherapy with dacarbazine plus interferon-alpha in metastatic melanoma.

AIMS AND BACKGROUND: This trial evaluated the feasibility and tolerability of an immunochemotherapeutic approach that uses cisplatin, vindesine, and dacarbazine (DTIC), or only DTIC, in combination with interferon alpha-2a (IFN-alpha), in patients with metastatic melanoma, considering the significant toxicity of several different regimens used up to now. METHODS: Between May 1995 and September 1997, 51 melanoma patients (50 of whom were assessable) entered a multicentric trial and were randomized to receive cisplatin (30 mg/m2 daily for 3 days) + vindesine (2.5 mg/m2 only day 1) + DTIC (250 mg/m2 daily for 3 consecutive days) + IFN-alpha (3 MIU i.m. 3x/wk continuously) (CVD arm) versus DTIC (800 mg/m2 day 1) + IFN-alpha (3 MIU i.m. 3x/wk continuously) (DTIC arm). The chemotherapy was recycled every 21 days. Patient reevaluation was performed every two cycles, and the treatment was continued in case of objective response or stabilization of disease. RESULTS: We observed 3 complete responses, 2 partial responses and 5 stable diseases in the CVD arm, and 2 partial responses and 4 stabilizations of disease in the DTIC arm. CONCLUSIONS: We conclude that these chemotherapeutic regimens are well tolerated regimens with modest toxicity. Future trials will be conducted associating the CVD regimen with biological response modifiers (IFN, IL-2) in order to improve the results.

Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in patients with familial porphyria cutanea tarda (f-PCT).

In this work, we describe seven novel molecular defects in the uroporphyrinogen decarboxylase gene responsible for familial porphyria cutanea tarda in Italian subjects with reduced erythrocyte URO-D activity. Four of these molecular abnormalities (R142Q, L161Q, S219F, P235S) are missense mutations, one (Q206X) is a nonsense mutation, one (IVS8-1 G>C) is a splicing defect causing the exon 9 deletion and one (1107 G>A) is located in the 3' untranslated region of UROD gene. All the amino acid substitutions fall in conserved regions in several organisms suggesting an important role in catalysis or in the protein structure stabilization. Three of these mutations have been detected in more than one subject. These results suggest a molecular heterogeneity at the UROD locus in Italian PCT patients although recurrent mutations have been identified.

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 1,329 patients who received their first kidney (1,062 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 1,000 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 1,000 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.

p53, cyclin-D1, PCNA, AgNOR expression in squamous cell cancer of the lip: a multicenter study.

BACKGROUND: The development of squamous cell carcinoma of the lower lip is an interesting model of photocarcinogenesis because of the structural and topographic characteristics of the lips. The purpose of this study was to evaluate the expression of immunohistochemical markers on the lips of patients with lower lip squamous cell carcinoma (LLSCC), compared with a control population. METHODS: Of the 98 subjects involved in the study, 58 were suffering from squamous cell carcinoma of the lower lip. The remaining 40 acted as a control. The case studies were taken from six university and hospital dermatology and plastic surgery departments. Questionnaires were administered to assess the risk factors for LLSCC. The cases involving squamous cell carcinoma underwent surgical excision and punch biopsy specimens were obtained from 20 control patients. Tissues were prepared in 5-microm-thick sections to carry out the following immunohistochemical study: PCNA, p53, AgNOR, cyclin-D1, bcl-2. RESULTS: The lower lip was the predominant location of squamous cell carcinoma, with the following factors playing important roles: chronic sun exposure, history of smoking, alcohol use and familial risk of cutaneous tumors. The male/female ratio in our survey was 5:1. The p53 protein was positive in approximately 50% of SCC cases and in 20% of controls. This protein is mostly associated with chronically photoexposed skin areas. AgNOR positivity increased with the loss of cellular differentiation; a progressive increase in size and a poorly defined shape were evident in poorly differentiated carcinomas. CONCLUSIONS: The results of this multicenter study showed that there is a noticeable difference in the expression of PCNA, p53, cyclin-D1, and AgNOR in tissues from patients with LLSCC and controls.

Sunscreens and cutaneous malignant melanoma: an Italian case-control study.

The possible relation between use of sunscreens and the risk of cutaneous malignant melanoma (CMM) was investigated in a case-control study conducted in 27 Italian centres on 542 incident, histologically confirmed cases and 538 controls admitted for acute, other than neoplastic or dermatologic conditions. Compared with subjects reporting never sunscreen use, the multivariate odds ratios (OR), after allowance for age, sex, geographic area, education, skin, eye and hair colour, freckles, number of naevi, history of sunburns, tanning pattern and duration of sunny vacations, were 0.97 (95% confidence interval [CI] 0.69 to 1.35) for those reporting "sometimes" and 0.80 (95% CI 0.54 to 1.17) for those reporting "often " sunscreen use. With reference to type of product most frequently used, the ORs were 0.96 (95% CI 0.52 to 1.77) for minimal, 0.90 (95% CI 0.63 to 1.28) for moderate and 1.41 (95% CI 0.85 to 2. 35) for high sunburn protection factor. With reference to duration of use, the OR was 0.86 (95% CI 0.58 to 1.29) for use started since >/=20 years. None of the corresponding trends in risks were significant. The ORs for sunscreen use were similar across strata of major identified covariates and, if anything, tended to decline after multivariate analysis. The present findings confirm that sunscreen use, as currently adopted in Italy, is not appreciably related to subsequent CMM risk.

Fast, simple and highly sensitive double-rounded polymerase chain reaction assay to detect medically relevant fungi in dermatological specimens.

BACKGROUND: Early detection of fungal infection is essential for beginning of prompt and specific therapy. In this study we describe a rapid and sensitive procedure to detect, by polymerase chain reaction (PCR) assays, a wide range of medically important opportunistic and pathogenic fungi in dermal specimens from dermatomycoses-affected patients. MATERIALS AND METHODS: Three primer pairs, amplifying fragments of the highly conserved gene coding for small ribosomal RNA (18S rDNA) and the adjacent internal transcribed spacer (ITS) rDNA, previously published by others, were probed on DNA from pure cultures of medically relevant human and animal fungal species. In order to evaluate the specificity of the assay, amplifications of control DNAs from other eukaryotes and prokaryotes were also carried out, and they gave negative results. RESULTS: These primer sets, in single amplification or double-rounded PCR assays, allowed specific amplification when applied to a wide number of fungal DNA from human and animal tissue specimens, including dermatophytes (genera Trichophyton, Microsporum), several yeast species (Candida, Saccharomyces, Cryptococcus, Malassezia) and moulds (Aspergillus, Penicillium). The PCR assay was able to detect as little as 10 pg of fungal DNA, corresponding to approximately 25 fungal genomes per sample specimen. A small-scale DNA extraction method was also developed. This simple, time-saving and sensitive procedure was successfully applied to 40 human and veterinary specimens, and the diagnosis was confirmed with cultural techniques, being shown to work even in the presence of other lesions or contaminating organisms. CONCLUSIONS: This method allows early recognition of fungal pathogen cells in clinical samples as an alternative tool to conventional detection techniques.

Phakomatosis pigmentovascularis: A new case with renal angiomas and some considerations about the classification.

We report phakomatosis pigmentovascularis detected in a Caucasian child characterized by the presence of a nevus flammeus and nevus anemicus on the face, a telangiectatic linear nevus of the right leg, and a very extensive blue spot covering 60% of the body surface, with ocular melanosis. Multiple angiomatous lesions of the kidney are associated without alterations of the central nervous system (CNS). This association has not been reported before; it could be a further expression of the complex of developmental defects. Our case corresponds exactly to type IIb in the classification of phakomatosis pigmentovascularis proposed by Hasegawa. As this classification seems very extensive, the higher incidence of cases corresponding to the second subtype suggests that we should identify it by the term phakomatosis pigmentovascularis, while the others could be considered as only very uncommon variants.

Accuracy of epiluminescence microscopy among practical dermatologists: a study from the Emilia-Romagna region of Italy.

AIMS AND BACKGROUND: The accuracy of epiluminescence microscopy (ELM) for pigmented skin lesions (PSLs) is still unclear. The large scale utilization of the technique is generally discouraged. The present study was aimed at comparing the accuracy of ELM with that of clinical examination alone in a group of 20 practical dermatologists. METHODS AND STUDY DESIGN: Thirty digital clinical images of benign and malignant PSLs and their digital ELM counterparts were used. A set of cumulative accuracy measures reported in the combined clinical/ELM diagnosis was compared with that reported in the clinical diagnosis alone. RESULTS: The proportion of nonmelanocytic lesions (NMLs), melanocytic nevi, and melanomas correctly identified, the predictive value of such diagnoses, and the proportion of melanomas detected by referral for biopsy (irrespective of the diagnosis reported) increased significantly. The cases referred for biopsy despite a "benign" impression decreased significantly among NMLs. CONCLUSIONS: The observed tendency towards a greater accuracy suggests that even in the routine dermatology practice ELM has the potential to improve the clinical examination of PSLs.

A case of hypopigmented mycosis fungoides in a young Caucasian boy.

Hypopigmented mycosis fungoides is a variant of mycosis fungoides characterized by the presence of hypopigmented patches as the sole manifestation of the disease. It has been described almost always in young black or dark-skinned patients. The only white patient described was a 64-year-old woman who not only had hypopigmented lesions, but also nodular lesions with lymphadenopathy. We describe hypopigmented lesions arising in a white boy 12 years of age, born in northern Italy, without any foreign ancestors. The microscopic alterations, with epidermotropism, the immunologic markers, the negativity of T-cell receptor gene rearrangement, and the good response to PUVA therapy correspond to the main findings in black patients with this disease. Long-term follow-up of these patients is important to obtain better knowledge of the natural history of the disorder. Hypopigmented mycosis fungoides must now be included in the differential diagnosis of hypopigmented macular lesions not only in black or dark-skinned patients but also in white patients.

Number and distribution of melanocytic nevi in individuals with a history of childhood leukemia.

BACKGROUND: An increased number of melanocytic nevi at the termination of chemotherapy has been documented in children with hematologic malignancies. The persistence of the increased number of nevi over time and the relationship with personal (e.g. phenotype) and disease related variables remain to be explored. METHODS: One hundred Italian patients diagnosed as having acute lymphatic or myeloid leukemia, after 1975, were recruited and compared with a group of 100 control individuals drawn from friend of the enrolled patients. Information regarding lifetime sun exposure, phenotypic characteristics, and number of nevi was collected by experienced dermatologists. Counts of nevi were expressed both as totals and as counts per unit of body surface area ("density"). Multiple linear regression analysis was employed to control for potentially confounding factors when comparing patients and controls. RESULTS: The patients and controls were fairly comparable in terms of constitutional characteristics, but the patients had a significantly higher number and density of nevi > or = 2 mm or larger in diameter. In addition, patients had a greater number of large nevi ( > or = 6 mm in greatest dimension), and of nevi in unusual areas, such as the palms and soles. Differences in nevus density between patients and controls were notably maintained in the older age group ( > 12 years). None of the disease-related factors analyzed (e.g. treatment protocol and radiotherapy), appeared to be significantly correlated with nevus density. CONCLUSIONS: Patients with a history of childhood leukemia have a sustained increase in their nevus density. A fairly convincing body of evidence indicates that a large number of melanocytic nevi is the strongest risk factor for melanoma. Therefore, the utility of periodic skin examination of these should be considered.

Evaluation of the efficacy of oral cromolyn sodium or an oligoantigenic diet in children with atopic dermatitis: a multicenter study of 1085 patients.

One thousand eighty-five children with atopic dermatitis were enrolled in a multicenter study to evaluate the efficacy of 4 weeks of oral sodium cromoglycate or 4 weeks of a restricted diet. One thousand-eleven children (93%) concluded the study. At the end of the trial there was a significant improvement in skin lesions in the two groups: 61% of the patients in the sodium cromoglycate group and 69% in the restricted diet showed a significant improvement in atopic dermatitis. We concluded that, at least in our experimental design, both sodium cromoglycate and a restricted diet are equally effective in atopic dermatitis.

Sexually transmitted diseases and risk of HIV infection.

We have analyzed the association between sexually transmitted diseases (STD) and HIV infection, using data from a cross-sectional survey of subjects attending STD clinics in Northern Italy conducted since 1988. A total of 1,711 subjects (1,259 males, 452 females), who had referred themselves to three STD clinics in Northern Italy for suspected STD or STD treatment, were included for the study. Out of these, 145 subjects (113 males and 32 females) were HIV-positive. A total of 58 HIV-positive and 368 HIV-negative subjects reported a history of STD; the corresponding odds ratio (OR) was 2.3 (95% confidence interval (CI) 1.5-3.6) for subjects reporting a history of STD. Considering various STD in details, the estimated OR was 1.8 (95% CI 0.8-3.8) for a history of gonorrhoea and 1.5 (95% CI 0.8-2.7) of syphilis, and the OR was 1.8 (95% CI 1.0-3.2) and 2.2 (95% CI 1.3-3.8), respectively, for a positive TPHA and VDRL test. The results of the test for HbsAg were available in 50 HIV-positive and 1,028 HIV-negative subjects; the OR of HIV infection in subjects with HbSAg was 3.9 (95% CI 1.7-9.0). Presence of genital ulcers at clinical examination was not significantly associated with the risk of HIV infection (OR yes vs no genital ulcers 1.5, 95% CI 0.6-2.8).

Economic evaluation of an educational campaign for early diagnosis of cutaneous melanoma.

Public educational campaigns for the early diagnosis of cutaneous melanoma are considered an effective approach in the prevention of this disease, since they increase the number of cases detected early and consequently lengthen patients' life expectancy. We performed an economic evaluation of such a campaign in Bergamo, Italy, in order to quantify its costs and consequences. We used cost-effectiveness analysis to compare the costs and effects of the campaign with those of the 'do nothing' option. The analysis was performed from the perspective of the Italian National Health Service [the Servizio Sanitario Nazionale (SSN)]. Accordingly, only direct costs related to publicly financed healthcare services were considered. No indirect costs or benefits were considered because they are not relevant to the SSN. Incremental analysis was used to obtain results in terms of additional costs per life-year saved (LYS). Overall LYS were quantified by comparing the survival curves for 4 subgroups of patients with different lesional thicknesses at diagnosis ( < 0.76mm, 0.76 to 1.50mm, 1.51 to 3.00mm and > 3.00mm). All costs were estimated in 1993 Italian lire (L). Overall effectiveness amounted to 233.49 LYS. Using a 5% discount rate, the value of effectiveness was 171.3 LYS. The total cost of the educational campaign (i.e. the sum of the organisational and 'induced' costs minus the costs saved) was estimated at L817 million (approximate 1993 exchange rate $US1 = L1573), and L905 million after discounting at a rate of 5%. Thus, using discounted cost and effectiveness data, the cost of the educational campaign was L5.28 million per LYS.

Dietary factors and the risk of psoriasis. Results of an Italian case-control study.

We have conducted a case-control study to explore the relation between the consumption of selected foods and psoriasis. The out-patient services of nine teaching hospitals and five general hospitals in northern and southern Italy took part. Cases were newly diagnosed psoriatics with a history of skin problems of no more than 2 years. As controls, we selected subjects with newly diagnosed skin conditions, other than psoriasis, who were seen in the same out-patient clinics. Inclusion of cases and controls was limited to the age group 16-65 years. A total of 316 psoriatics and 366 controls were recruited. Anthropometric measures, including height and weight, were obtained. Diet was assessed by a semiquantitative food frequency questionnaire. Psoriasis appeared to be positively associated with body mass index (chi 2(1) trend 4.3, P < 0.05). Significant inverse relations with psoriasis were also observed for the intake of carrots (chi 2(1) trend 4.8, P < 0.05), tomatoes (chi 2(1) trend 26.3, P < 0.01), fresh fruit (chi 2(1) trend 11.7, P < 0.01) and index of beta-carotene intake (chi 2(1) trend 9.1, P < 0.01). Although largely explorative, these results provide some evidence for a potential role of diet in psoriasis.