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

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.

Analytic epidemiology in psoriasis.

The cause of psoriasis has only recently been subject to structured epidemiologic research approach. This is reflected in the scarcity of quantitative knowledge about etiologic factors for psoriasis other than genetics. A schematic model suggests that susceptibility to develop psoriatic lesions includes both genetic and extragenetic predisposing factors. Expression in terms of visible lesions is modulated by precipitating or trigger factors. Unlike many chronic diseases, psoriasis spontaneously waxes and wanes. When assessing factors that trigger the onset of the disease, one must also consider factors that lead to recurrence or exacerbation. Cohort and case-control studies are the main methodologic options for risk assessment. Combination of these techniques and the merging of an epidemiologic approach with basic biologic research are suggested routes to valuable results in this area.

A unique cytoplasmic structure in papular histiocytoma.

Intracytoplasmic granules with a unique and highly complex ultrastructure, have been observed within the cellular infiltrate of the lesions of two patients with papular histiocytosis. Examination of serial sections has enabled construction of a three-dimensional model of these granules, which appear to be composed of an elaborate arrangement of membranes and vesicles. Two hypotheses (endocytosis and exocytosis) are proposed for the mode of formation of these unique cytoplasmic structures.

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.

Risk factors for HIV infection in adults attending sexually transmitted disease clinics in Italy.

We assessed prevalence and risk factors for human immunodeficiency virus (HIV) infection in 637 patients (506 men, 131 women; median age 30 years, range 17-64) attending between September 1988 and July 1989 for the first time two sexually transmitted disease (STD) clinics in Northern Italy, for suspected or STD treatment. A total of 44 subjects (6.9%, 95% confidence interval, (Cl): 4.9-8.9) were seropositive for HIV antibodies. The prevalence of HIV infection decreased with age, from 9% in patients aged 24 years or less to 3% in those aged 45 years or more (chi 21 trend 4.97, p less than 0.05). Women tended to have a lower prevalence of infection than men (5.3% versus 7.3%) but this was not statistically significant. Compared with men reporting no homosexual intercourse, HIV infection risk was about 50% higher in those reporting bisexual intercourse (age- and sex-adjusted odds ratio (OR) 1.5,95% Cl: 0.6-3.6) and about fourfold in those reporting only homosexual intercourse (OR 3.8, 95% Cl: 1.7-8.5). No clear trend in risk was observed with number of sexual partners both in men and in women. Intravenous drug users had an increased risk of HIV infection; compared with non-users, the OR was 5.6 (95% Cl: 3.0-10.5) in users, and the point estimates increased with frequency of use, from 3.3 (95% Cl: 0.8-11.5) in occasional users to 6.4 (95% Cl: 3.2-12.8) in regular users. The risk of HIV infection was 2.2 (95% Cl: 1.1-4.3) in patients reporting a history of STD, and 1.6 (95% Cl: 0.8-3.3) in those reporting syphilis.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Effects of phlebotomy on urinary porphyrin pattern and liver histology in patients with porphyria cutanea tarda.

Urinary porphyrin profiles and liver histology have been investigated in a group of adult alcoholics with porphyria cutanea tarda (PCT) before and after one year phlebotomy. Both parameters were evaluated during the same period in a group of patients who did not undergo specific therapy for PCT. All patients were advised to abstain from alcohol. At the end of the one year observation period there was a significant fall of urinary total porphyrins and in the uro/coproporphyrin ratio in treated patients compared to basal values whereas no changes were found in controls. Liver biopsy findings revealed a significant reduction of hepatic fatty degeneration and siderosis with no changes in inflammatory infiltrates and fibrosis in treated patients, so the progression of liver disease was similar to controls. These results show that clinical and biochemical remission of PCT can occur independently of the evolution of the concomitant liver disease.

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.

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 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.

[Vulvar pruriginous squamous papillomatosis]. / Papillomatosi squamosa pruriginosa vulvare.

Pruritic vulvar squamous papillomatosis (PVSP) is a recently described clinical entity whose aetiologic agent has been reported to be the human papilloma virus. We have seen 9 patients with PVSP. We believe that our clinical and histological data, along with the results of the in situ hybridizations stress out the evidence of a viral aetiology in the PVSP.

[Pigmentation abnormalities in the course of topical immunotherapy of alopecia areata]. / Anomalie pigmentaire in corso di immunoterapia topica per l'alopecia areata.

Pigmentation troubles have been associated in the past years with contact dermatitis and patch-testing. Contact allergy and increase of pigmentation has been associated with Tinopal; on the other hand contact allergy and depigmentation have been associated with many substances such as DNCB, squaric acid dibutylester (SADBE), carbyne, alstroemeria. Leukoderma can also be produced by irritant compound such as phenols, catechols and mercaptoamines. During 1978 and 1984 we have treated 132 patients suffering from alopecia areata with DNCB or SADBE: 51 patients have been treated by DNCB and 81 by SADBE. During the treatment 10 patients developed a leukoderma vitiligo-like localized to the areas of topical application of the allergens and to the flare-up site; one patient had an increase of pigmentation. Lesions vitiligo-like appeared 10-15 weeks after the onset of treatment. Among the patients who developed leukoderma, 4 had a personal history of vitiligo. The possible pathogenetic mechanisms are discussed.

[Von Willebrand factor multimers in systemic scleroderma]. / I multimeri del fattore di von Willebrand nella sclerodermia sistemica.

In scleroderma endothelial cell damage plays an early and pivotal role in the pathogenesis of sclerotic lesions. In our study we determined whether or not plasma from 11 consecutive patients with scleroderma contained a subset of larger than normal (supranormal) multimers of von Willebrand factor which are potent inducers of platelet aggregation and adhesion. Supranormal multimers were found in all patients, but in none of the normal controls. Supranormal multimers may contribute to the pathogenesis of systemic sclerosis by inducing platelet aggregation and enhancing adhesion to subendothelium.