Impact of body mass index on retention rates of anti-TNF-alfa drugs in daily practice for psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease which often requires life-long treatment. OBJECTIVE/AIM: Our objective was to assess the role of the body mass index (BMI) on the retention rates of anti-TNF-alfa therapies in patients with moderate to severe plaque psoriasis. MATERIAL AND METHODS: Retrospective observational study of psoriasis patients included in local databases of three public Italian hospitals. All patients, who received anti-TNF-alfa treatment in referral centers, were included. Only patients with at least 1-year follow-up were considered eligible. The outcome was the conservation of the treatment at 1 and 2 years of follow-up. RESULTS: 194 patients were enrolled. 307 treatment courses with a minimum follow-up of 12 months and 263 with a follow-up of 24 months were analyzed. The proportion of patients receiving the same treatment at months 12 and 24 was 67.43% and 42.21%, respectively. The proportion steadily decreased with increased values of BMI. CONCLUSIONS: The overall efficacy of TNF-alfa inhibitors diminishes with time. The BMI affects the long-term survival rate of anti-TNF-alfa in psoriatic patients. A high BMI can be considered a potential predictor of drug discontinuation.

Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features.

A rare variant of mycosis fungoides (MF) characterized by prominent involvement of the eccrine glands with syringometaplasia has been reported in the past as "syringolymphoid hyperplasia with alopecia," "syringotropic cutaneous T-cell lymphoma," "adnexotropic T-cell lymphoma," or "syringotropic MF." The clinicopathologic features of this variant are not well understood, and only a few case reports or small series have been published to date. We reviewed the clinicopathologic features of 14 patients with syringotropic MF (male:female=10:4; median age, 59 years; mean age, 57.8; age range, 33 to 83 y). Six patients had variably large, solitary patches or plaques, located on the thigh (n=3), arm, trunk, or eyebrow (1 each). The other 8 patients had multiple, mostly generalized lesions. A history of MF was known in 4 of these 8 patients. With the exception of 1 biopsy specimen that was too superficial and did include the eccrine secretory coils but not the eccrine glands, all cases showed prominent involvement of the eccrine glands. Variable degrees of syringometaplasia ranging from small to large epithelial complexes were present in all specimens. The eccrine glands and syringometaplastic structures were surrounded by dense lymphoid infiltrates with prominent epitheliotropism. Concomitant involvement of the epidermis and of the hair follicles was observed in 13 and 8 biopsies, respectively. This is the largest series of syringotropic MF, showing that this is a rare variant of the disease with peculiar clinicopathologic features. Dermatologists and dermatopathologists should be aware of this rare variant of MF to avoid delayed diagnosis and treatment.

Comano's (Trentino) thermal water interferes with tumour necrosis factor-alpha expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: yet other mechanisms of its anti-psoriatic action.

Thermal balneotherapy with Comano's spa water (CW; Trentino, Italy) is beneficial for psoriasis and other skin disorders but its operative mechanisms are largely unknown. Previously, we showed that CW interferes with the production and secretion of IL-6 and various VEGF-A isoforms and with CK-16 expression by cultured human psoriatic keratinocytes. In this study, confluent cultures of epidermal keratinocytes isolated from the lesional areas of 9 psoriatic patients were exposed for 11-13 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells), in order to assess the expression and secretion of TNF-alpha and IL-8 by such cells. The results gained by means of immunocytochemistry, Western immunoblotting (WB), and ELISA assays showed that CW exposure significantly down-regulated the intracellular levels of TNF-alpha, a key inducer of IL-8, IL-6, and other chemokines. However, no assayable TNF-alpha secretion occurred in keratinocyte-conditioned DW- and CW-DMEM samples. Moreover, the intracellular levels and secretion rates of IL-8 were also markedly reduced in the protein extracts and conditioned media of CW-DMEM-incubated keratinocytes. Notably, the most effective inhibition of IL-8 secretion was elicited by a 25% CW fraction in the DMEM. Altogether, our findings indicate that by attenuating at lesional skin sites the deregulated production and secretion of a cascade of several cytokines and chemokines (e.g. TNF- alpha, IL-8, IL-6, and various VEGF-A isoforms), and by offsetting the keratinocytes' abnormal differentiation program entailing CK-16 expression, CW balneotherapy may beneficially influence the clinical manifestations of psoriasis.

Comano's (Trentino) thermal water interferes with interleukin-6 production and secretion and with cytokeratin-16 expression by cultured human psoriatic keratinocytes: further potential mechanisms of its anti-psoriatic action.

Thermal balneotherapy with Comano's spa water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but its mechanisms of action are mostly unknown. Previously, we showed that CW can interfere with the expression and secretion of various VEGF-A isoforms by cultured human psoriatic epidermal keratinocytes. In this study, confluent cultures of IL-6-hypersecreting keratino-cytes isolated from 6 psoriatic patients were exposed for 11-15 days to DMEM, the chemicals of which had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by means of immunocytochemistry, Western immunoblotting, and ELISA assays, the intracellular levels and secretion rates of IL-6 were drastically curtailed in the CW-DMEM-incubated keratinocytes and in their cell-conditioned media. A nearly maximal inhibition of IL-6 release had already been induced by a CW fraction in the DMEM as low as 25%. CW exposure also promptly, intensely, and persistently down-regulated the expression of cytokeratin-16 (CK-16), a marker associated with keratinocyte psoriatic phenotype. Hence, CW balneotherapy may beneficially affect the clinical manifestations of psoriasis via an attenuation of the local deregulation of several cytokines/chemokines, including IL-6 and VEGF-A isoforms, and of a concurrent, abnormal cell differentiation program entailing the expression, amongst other proteins, of CK-16.

Comano's (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: a potential mechanism of its anti-psoriatic action.

Thermal balneotherapy with Comano spa's water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but the mechanism(s) of action of this hypotonic water are unknown. Since skin psoriatic manifestations are thought to be angiogenesis-dependent, we assessed CW's effects on the expression and release of VEGF-A protein isoforms by cultured human lesional keratinocytes isolated from skin biopsies performed in 9 patients. Confluent, psoriatic keratinocytes were exposed for 11 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by Western immunoblotting (WB), incubation in CW-DMEM elicited, with respect to DW-DMEM, an increase in intracellular and/or cell-bound L-VEGF-A189 and L-VEGF-A165 48 kDa protein isoforms with no concurrent change in L-VEGF-A121 and L-VEGF-A165 45 kDa proteins. Moreover, WB analysis of the secreted VEGF-A (sVEGF-A) proteins showed that the 20 and 15 kDa bands corresponding to different VEGF-A isoforms were directly and remarkably reduced in keratinocyte-conditioned CW-DMEM vs. DW-DMEM. Thus, CW interferes with VEGF-A isoform expression and secretion by the psoriatic keratinocytes. These effects would reduce all VEGF-A-mediated angiogenic, vessel permeabilising, and chemotactic effects, thereby at least in part explaining the beneficial actions of CW balneotherapy on the clinical manifestations of psoriasis.

Study of sunbathing in children: the preliminary evaluation of a prevention program.

AIMS AND BACKGROUND: Sunburn during childhood is associated with an increased risk for developing melanoma in an adult age. The aim of the present study was to define the validity of our educational program in order to teach the positive effects and risks of sun exposure during childhood. PATIENTS AND METHODS: We conducted a population-based, case-control study in primary schools of three towns in Northern Italy (Brescia, Bergamo and Trento) between 2001 and 2002. The study was carried out on 1945 pupils (aged 8-9 years) and included 1309 case children who received an educational program before the summer to increase awareness towards sun exposure and 636 control children who did not. Parents of case and control children were interviewed using a questionnaire about their children's skin characteristics, sun protective behavior and sunburns. The questionnaire was completed twice, before and after the summer, to verify the changes of sun exposure habits. RESULTS: A significant decrease in sunburns was demonstrated in the group of subjects who received the educational program, indicating the validity of our operative procedure (from 14.6% to 10%, P = 4 x 10(-4). CONCLUSIONS: Our educational melanoma program may be important to disseminate in a wider range of children a correct education on sun exposure during childhood.

Clinical validation of an automated system for supporting the early diagnosis of melanoma.

BACKGROUND: Early diagnosis and surgical excision is the most effective treatment of melanoma. Well-trained dermatologists reach a high level of diagnostic accuracy with good sensitivity and specificity. Their performances increase using some technical aids as digital epiluminescence microscopy. Several studies describe the development of computerized systems whose aim is supporting dermatologists in the early diagnosis of melanoma. In many cases, the performances of those systems were comparable to those of dermatologists. However, this cannot tell us whether a system is able to support dermatologists. Actually, the computerized system might correctly recognize the same lesions that the dermatologist does, without providing them any useful advice and therefore being useless in recognizing early malignant lesions. PURPOSE: We present a novel approach to enhance dermatologists' performances in the diagnosis of early melanoma. We provide results of our evaluation of a computerized system combined with dermatologists. METHODS: A Multiple-Classifier system was developed on a set of 152 cases and combined to a group of eight dermatologists to support them by improving their sensitivity. RESULTS: The eight dermatologists have average sensitivity and specificity values of 0.83 and 0.66, respectively. The Multiple-Classifier system performs as well as the eight dermatologists (sensitivity range: 0.75-0.86; specificity range: 0.64-0.89). The combination with the dermatologists shows an average improvement of 11% (P=0.022) of dermatologists' sensitivity. CONCLUSION: Our results suggest that an automated system can be effective in supporting dermatologists because it recognizes different malignant melanomas with respect to the dermatologists.

A multiple classifier system for early melanoma diagnosis.

Melanoma is the most dangerous skin cancer and early diagnosis is the key factor in its successful treatment. Well-trained dermatologists reach a diagnosis via visual inspection, and reach sensitivity and specificity levels of about 80%. Several computerised diagnostic systems were reported in the literature using different classification algorithms. In this paper, we will illustrate a novel approach by which a suitable combination of different classifiers is used in order to improve the diagnostic performances of single classifiers. We used three different kinds of classifiers, namely linear discriminant analysis (LDA), k-nearest neighbour (k-NN) and a decision tree, the inputs of which are 38 geometric and colorimetric features automatically extracted from digital images of skin lesions. Multiple classifiers were generated by combining the diagnostic outputs of single classifiers with appropriate voting schemata. This approach was evaluated on a set of 152 digital skin images. We compared the performances of multiple classifiers (2- and 3-classifier groups) between them and with respect to single ones (1-classifier group). We further compared the classifiers' performances with those of eight dermatologists. Classifiers' performances were measured in terms of distance from the ideal classifier. Compared with 1- and 2-classifier groups, performances of 3-classifier systems were significantly higher (P<0.0005 and P<0.001, respectively). No statistically significant differences were found between the 1- and 2-classifier groups (P=0.352). While the dermatologists group showed a level of performances significantly higher than the 1-classifier systems (P<0.020), no differences were found between the multiple classifier groups and the dermatologists groups, indicating comparable performances. This work suggests that a suitable combination of different kinds of classifiers can improve the performances of an automatic diagnostic system.