Abstract: A 61-year-old Italian man, who underwent a renal transplantation 8 years ago, receiving azathioprine, prednisone, and cyclosporine for immunosuppressive therapy, presented with a large reddish indurated plaque with a central ulcer, which was slowly enlarged, on the right knee. From the diseased tissue biopsy, a dematiaceous fungus matching Alternaria alternata in all essential characters was isolated in pure culture. This is an uncommon fungal complication in a kidney transplant patient. A detailed morphological description of the isolate is provided as well as review of the literature.
Abstract: 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. OBJECTIVES: To determine if common known polymorphisms in the regulatory region of the COX-2 gene (PTGS2) can be associated with nonmelanoma skin cancer (NMSC) predisposition after organ transplantation, to evaluate if cancer risks are associated with specific COX-2 gene (PTGS2) haplotypes containing these polymorphisms, and to identify possible new genetic polymorphisms in the proximal 5' or 3' regulatory regions of the gene associated with disease. METHODS: The frequency of the three polymorphisms was determined in 240 Northern Italian transplant recipient patients (107 cases and 133 controls) with polymerase chain reaction-restriction fragment length polymorphism analysis. The proximal 5' and 3' regulatory regions of the gene were screened by heteroduplex analysis. RESULTS: Stratification by age at transplant and type of tumours [SCC or basal cell carcinoma (BCC)] demonstrated that allele -765C represented a protective factor in BCC cases undergoing transplantation before 50 years of age (CC + CG vs. GG, Fisher exact test P = 0.003). One rare polymorphism, -62C-->G, was detected in the 5' flanking region. The allele frequency of -62G was 0.019, and no difference in genotype between cases and controls was observed. No other variants were found, suggesting that sequence variations in these regions are not likely to contribute to NMSC risk in this population. Haplotype analysis showed that the haplotype containing all major alleles represents a protective factor in patients with SCC undergoing transplantation after 50 years of age [P = 0.009; OR = 0.37 (0.18-0.79)] and that variant -1195A-->G may represent a risk factor in this subgroup of patients [P = 0.01; OR = 4.77 (1.47-16.41)]. Haplotype analysis in patients with BCC revealed that variant -765C might be a protective factor in patients undergoing transplantation before 50 years of age. Variant 8473T-->C, located in the 3' UTR region of the gene, showed no association with NMSC risk after transplantation. CONCLUSIONS: COX-2 common variants -765G-->C and -1195A-->G appear to be associated with risk of NMSC, although in different ways in the SCC and BCC subgroups, indicating that environmental and genetic risk factors may play different roles in the outcome leading to these two phenotypes.
Abstract: A history of sunburns in early life nearly doubles the risk of developing malignant melanoma in adulthood. From 2001 to 2004, we conducted a cluster-randomized trial of an educational intervention to reduce sunburn rates (primary outcome) and improve sun-protection behavior (secondary outcome) in schoolchildren. A total of 122 Italian primary schools (grades 2 and 3) were randomized to receive, or not, an intervention consisting of an educational curriculum at school, conducted by trained teachers, which included the projection of a short video and the distribution of booklets to children and their parents. Behavior while in the sun was assessed at baseline and 14-16 months after baseline. In a subgroup (44% of the total sample), melanocytic nevi were also counted. Of the 11,230 children enrolled, 8,611 completed the study. A total of 1,547 children (14%) reported a history of sunburns at baseline. At follow-up, no difference in sunburn episodes was documented between the study groups (odds ratio 0.97, 95% confidence interval 0.84-1.13) and similar sun-protection habits were reported. No significant impact of the proposed educational program was documented at 1-year follow-up. Innovative strategies need to be developed to increase the effectiveness of future educational interventions in this area.
Abstract: This study examines the association of keratotic skin lesions with the development of skin cancer in 915 solid organ-transplant recipients in five European countries. In a hospital-based case-control study, cases with squamous- and basal-cell carcinoma were compared with controls without skin cancer. Questionnaires, scrutiny of medical charts, and skin examination were delivered according to a standardized protocol. Keratotic skin lesions and viral warts were counted on different body sites. Keratotic skin lesions were strongly associated with an increased risk of squamous-cell carcinoma, with adjusted odds ratios of 4.1 (2.4;7.0) and 12.1 (6.1;24) for 1-49 and 50 and more keratotic skin lesions compared with no lesions, respectively. Keratotic skin lesions were also associated with basal-cell carcinoma with adjusted odds ratios of 2.9 (1.7;4.9) and 4.0 (1.7;9.2) for 1-49 and 50 and more lesions, respectively. Lighter skin types and painful sunburns were also significantly associated with an increased risk of squamous- and basal-cell carcinoma. Keratotic skin lesions are strongly associated with skin cancer and are, thus, an important clinical criterion for identifying those organ-transplant recipients at an increased risk of skin cancers who should be offered more intensive skin surveillance.
Abstract: Scanty information is available on the relation between nevus count on specific anatomic areas and the total body surface, particularly in children. The authors analyzed this issue by using data from a uniquely large study conducted in 1997 on 3,406 schoolchildren (1,746 boys and 1,660 girls) aged 13-14 years in 13 cities from northern, central, and southern Italy. Children were examined by trained dermatologists who counted melanocytic nevi (>or=2 mm in diameter) on 19 different anatomic sites. Overall, the mean number of nevi was 17.3 (18.6 in boys and 15.8 in girls). The adjusted correlation coefficients (r) with number of nevi on the whole body were 0.74 for head and neck, 0.83 for anterior and 0.84 for posterior trunk, and 0.88 for upper and 0.80 for lower limbs. With reference to single anatomic sites, the best predictor of total nevus count was the lateral arms (r=0.80), overall and in strata of sex and pigmentary characteristics. This large study provides definite evidence that examining the upper limbs only, particularly the lateral arms, is a practical and suitable tool for predicting total nevus count in children.
Abstract: BACKGROUND: Few studies on the prevalence and incidence of many skin conditions in the general population are available because it is difficult to submit to dermatologic examination large samples of seemingly healthy population. OBJECTIVE: The aim of this study was to estimate the prevalence of several skin conditions among a sample that is deemed to be representative of the general population of young men living in southern Italy. PATIENTS/METHODS: Potential conscripts resident in the coastal regions of southern Italy and called at the age of 18 to the Draft's Council Medical Unit in Taranto underwent a clinical and instrumental examination to evaluate their psycho-physical fitness to compulsory service in Italian Navy. From January 1998 to April 2004 a dermo-epidemiologic project named EpiEnlist (EPIdemiology in ENLISTed Men) project was carried out by the Department of Dermatology of the Italian Navy Hospital in Taranto under the auspices of the Italian Group for Epidemiological Research in Dermatology. All the subjects showing skin lesions evocative of neurofibromatosis (NF), congenital melanocytic nevus (CMN), Becker nevus (BN), and vitiligo were referred to the Department of Dermatology of the Italian Navy Hospital for confirming the diagnosis. The confirmed cases were recorded in a predefined patient's card, containing the main anamnestic, clinical, instrumental, and laboratory data. RESULTS: Because the recording of the various conditions started and ended in different times, the total number of examined subjects varied. NF type 1 was diagnosed in 6 of 34 740 subjects [prevalence 1:5735 or 0.017%; 95% confidence interval (95% CI), 0.0008-0.0037], CMN in 157 of 23 354 (prevalence 1:148 or 0.67%; 95% CI, 0.57-0.79). BN was observed in 70 of 27 954 young men (prevalence 1:399 or 0.25%; 95% CI, 0.15-0.35), and its mean age of appearance was 11.9 years (minimum 5-maximum 17). In 41 subjects (58.6%), the age of appearance was over 10 years. Vitiligo was recorded in 60 of 34 740 persons (prevalence 1:579 or 0.17%; 95% CI, 0.13-0.22). In 40 subjects with vitiligo, the blood test was done: in 40% of these circulating autoantibodies, mainly anti-thyroid (25.6%) and anti-smooth muscle (17.3%) autoantibodies were detected, but only in 5% of cases, a thyroid disease was diagnosed, and no other sign of autoimmune diseases was observed. CONCLUSIONS: The epidemiological data of the skin conditions considered in the present study can be considered roughly in agreement with those reported in the available surveys. Because they were obtained in a large sample of Italian young males from the general population, they can be useful for therapeutic and preventive interventions by the public health organizations.
Abstract: Background Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile, nonfollicular pustules usually arising on an oedematous erythema often accompanied by leucocytosis and fever. It is usually attributed to drugs. Objectives To evaluate the risk for different drugs of causing AGEP. Patients and methods A multinational case-control study (EuroSCAR) conducted to evaluate the risk for different drugs of causing severe cutaneous adverse reactions; the study included 97 validated community cases of AGEP and 1009 controls. Results Strongly associated drugs, i.e. drugs with a lower bound of the 95% confidence interval (CI) of the odds ratio (OR) > 5 were pristinamycin (CI 26-infinity), ampicillin/amoxicillin (CI 10-infinity), quinolones (CI 8.5-infinity), (hydroxy)chloroquine (CI 8-infinity), anti-infective sulphonamides (CI 7.1-infinity), terbinafine (CI 7.1-infinity) and diltiazem (CI 5.0-infinity). No significant risk was found for infections and a personal or family history of psoriasis (CI 0.7-2.2). Conclusions Medications associated with AGEP differ from those associated with Stevens-Johnson syndrome or toxic epidermal necrolysis. Different timing patterns from drug intake to reaction onset were observed for different drugs. Infections, although possible triggers, played no prominent role in causing AGEP and there was no evidence that AGEP is a variant of pustular psoriasis.
Abstract: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse reactions (SCAR) related to a variety of medications. They have a significant public health impact because of high mortality and morbidity. A multinational case-control study conducted in Europe between 1997 and 2001 evaluated the risk of medications to induce SCAR. Cases were actively detected through a hospital network covering more than 100 million inhabitants. Three hospitalized patients per case matched on age, gender, and date of interview were enrolled as controls. After validation by an expert committee blinded to exposures, 379 SCAR cases and 1,505 controls were included. Among drugs recently introduced into the market, strong associations were documented for nevirapine (relative risk (RR)>22) and lamotrigine (RR>14), and weaker associations for sertraline (RR=11 [2.7-46]), pantoprazole (RR=18 [3.9-85]), and tramadol (RR=20 [4.4-93]). Strong associations were confirmed for anti-infective sulfonamides, allopurinol, carbamazapine, phenobarbital, phenytoin, and oxicam-NSAIDs , with some changes in relative numbers of exposed cases. Thus, many cases were still related to a few "old" drugs with a known high risk. Risk was restricted to the first few weeks of drug intake. The use of such drugs as first-line therapies should be considered carefully, especially when safer alternative treatments exist. A number of widely used drugs did not show any risk for SJS and TEN.Journal of Investigative Dermatology advance online publication, 6 September 2007; doi:10.1038/sj.jid.5701033.
Abstract: BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions. OBJECTIVES: We sought to update knowledge on the causes of SJS or TEN with a focus on the rate of allopurinol-associated cases and to identify risk factors for allopurinol-associated SJS or TEN. METHODS: We conducted a multinational case-control study. RESULTS: In all, 379 patients with severe cutaneous adverse reactions validated as SJS or TEN and 1505 matched hospitalized control subjects were enrolled. Allopurinol was the drug most frequently associated with SJS or TEN, with 66 exposed patients (17.4%) and 28 exposed control subjects (1.9%) (adjusted odds ratio = 18, 95% confidence interval: 11-32). Allopurinol use was greater than in a previous case-control European study. Daily doses equal to or greater than 200 mg were associated with a higher risk (adjusted odds ratio = 36, 95% confidence interval: 17-76) than lower doses (adjusted odds ratio = 3.0, 95% confidence interval: 1.1-8.4). The risk was restricted to short-term use (</=8 weeks). The use of comedications did not increase the risk. LIMITATIONS: Nonsystematic recording of the indications for allopurinol use was a limitation. CONCLUSIONS: Results of this multinational study (EuroSCAR) revealed that allopurinol is the drug most commonly associated with SJS or TEN. The incidence of allopurinol-associated SJS or TEN has increased possibly because of increased use and dosages of this drug.
