Risk factors for early-onset basal cell carcinomas and the trend towards their female predominance.

BACKGROUND: A dramatic rise in the incidence rates of basal cell carcinoma (BCC) in young women has been reported. OBJECTIVES: We investigate potential risk factors (RF) for sporadic BCC in young patients and the current distribution of such RF in the general population of Catalonia, comparing the differences among men and women. PATIENTS AND METHODS: A case-control study was performed, 69 BCCs diagnosed in patients ≤ 45 years of age vs. 69 healthy controls. Afterward, 1,078 participants from the general population completed an RF questionnaire. RESULTS: Repeated sunburns were more frequent in instances of early-onset BCC in covered skin than in sun-exposed skin (P  =  0.029). In the general population, 39.1 % of participants reported sunbed use (50.1 % in women, 10.9 % in men). Sunbed use was the only relevant RF more predominant in women than men, favoring the trend to female predominance of BCCs above other RF. Additionally, we found a significant trend in young participants for reduced sunbed use (P < 0.001), although they had the same percentage of repeated sunburns. Repeated sunburns are the most relevant RF for early-onset BCCs that can be targeted in prevention campaigns. CONCLUSIONS: We should be aware of the more relevant RF for early-onset BCCs and their distribution among the general population to address preventive campaigns.

IL-15 and IL-23 synergize to trigger Th17 response by CLA+ T cells in psoriasis.

IL-15 has emerged as a potentially relevant target in the IL-17 response in psoriasis. However, its mechanism is poorly characterized in humans. IL-15 and IL-23 are constitutively expressed in the psoriatic lesion. Also, IL-15 is considered a susceptibility-associated gene in psoriasis, as are IL-23R, and HLACW6. Here, we studied the effect of IL-15 and IL-23 stimulation on the cytokine response of CLA+/CLA- T cells from 9 psoriasis patients and 3 healthy control subjects. To this end, CLA + and CLA- T cells from blood samples were cultured with epidermal cells from skin biopsies and treated with IL-15 and IL-23. After five days of culture, cytokines in supernatant were measured by ELISA or fluorescent bead-based immunoassay. There was a statistically significant increase in IL-17F and IL-17A production (P < .001) in cocultures of psoriasis skin-homing CLA + T cells with epidermal cells when stimulated with IL-15 and IL-23, but this effect was not observed in the cells of healthy controls. Interestingly, this response was reduced by around 50 to 80% by blocking HLA class I and II molecules. Our results point to the synergic action of IL-15 and IL-23 selectively for CLA + cells in psoriasis, leading to the induction of Th17 cell-related cytokines.

Patients with Moderate to Severe Psoriasis Associate with Higher Risk of Depression and Anxiety Symptoms: Results of a Multivariate Study of 300 Spanish Individuals with Psoriasis.

Psoriasis is a chronic skin disease associated with considerable physical and psychological comorbidities. Stress and emotional disturbances have been implicated in both triggering the onset and exacerbation of psoriasis. In order to determine the level of perceived stress and mood alterations in patients with psoriasis and their association with disease severity, 300 individuals completed diverse validated questionnaires assessing stress and psychological mood. Evaluation of perception of disease was also measured. A significant association between psoriasis severity and mood, emotional disturbances and an impact on assessments of the quality of life were observed. Particularly, Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale and Hospital Anxiety and Depression Scale for Depression detected a significant risk for depression in relation to the disease severity. The association between depression features, anxiety and perceived stress with psoriasis severity is important and can influence the appropriate management of psoriasis.

Streptococcus pyogenes-induced cutaneous lymphocyte antigen-positive T cell-dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis.

BACKGROUND: Guttate psoriasis (GP) is characterized by acute onset of small, rounded psoriatic lesions. Although this particular phenotype of psoriasis is usually associated with streptococcal throat infections and mainly occurs in HLA-Cw6(+) patients, the specific immunologic response to this innate stimulus that causes these skin lesions is poorly understood. OBJECTIVE: This study aims to elucidate how key cellular elements of patients with GP respond to Streptococcus pyogenes and whether this initial immune response is favored by the genetic and environmental background of these patients. METHODS: Circulating memory T cells and autologous epidermal cells from samples from either patients with GP (n = 14) or healthy control subjects (n = 6) were cocultured ex vivo in the presence of an S pyogenes extract. Levels of the psoriasis-associated cytokines IL-17A, IL-17F, IFN-γ, TNF-α, IL-6, and IL-8 were determined. The expression of several genes with increased (DEFB4, S100A7, LCN2, IL36G, IL8, CXCL9, CXCL10, and CXCL11) or decreased (FLG and LOR) transcripts in psoriatic lesions was examined in keratinocytes treated with coculture supernatants. RESULTS: When skin-homing effector memory cutaneous lymphocyte antigen-positive T cells were used in cocultures, a TH17-dominant response was observed, as reflected by the higher amounts of IL-17A and IL-17F than IFN-γ. Moreover, a higher TH17 response was observed in cells isolated from patients with flares associated with a streptococcal tonsillitis and with the HLA-Cw6 allele (cohort 1). In addition, in normal keratinocytes the supernatants from these cocultures induced an increase in IL-17-associated genes, such as DEFB4, S100A7, LCN2, IL36G, and IL8 but a decrease in FLG and LOR, thereby confirming the role of activated TH17 cells. CONCLUSION: This study reveals a dominant TH17 response of cutaneous lymphocyte antigen-positive T cells activated by epidermal cells and S pyogenes in patients with GP.

Circulating CLA+ T lymphocytes as peripheral cell biomarkers in T-cell-mediated skin diseases.

T lymphocytes expressing the CLA antigen constitute a subset of effector memory lymphocytes that are functionally involved in T-cell-mediated cutaneous diseases. Skin-seeking lymphocytes recirculate between inflamed skin and blood during cutaneous inflammation. Many studies in different T-cell-mediated inflammatory cutaneous diseases have clearly related their pathologic mechanisms to CLA+ T cells. Based on common features of these cells in different cutaneous disorders mediated by T cells, we propose that circulating CLA+T cells could constitute very useful peripheral cellular biomarkers for T-cell-mediated skin diseases.

Inguinal syndrome secondary to Prevotella bivia after accidental bite in orogenital sex.

The authors report a case of an inguinal bubo in a young man caused by an anaerobe, Prevotella bivia, which was acquired during oral sexual intercourse. As far as the authors know, this is the first reported case of a sexually transmitted infection by Prevotella. Prevotella spp. inhabit the oral cavity and are highly prevalent in bacterial vaginosis, a polymicrobial syndrome resulting from replacement of the normal vaginal Lactobacillus spp. flora by high concentrations of anaerobic microorganisms such as Prevotella spp., Mobiluncus spp., Gardnerella vaginalis and other uncultivated anaerobes.

Microbe-Dependent Induction of IL-9 by CLA+ T Cells in Psoriasis and Relationship with IL-17A.

IL-9 is present in psoriatic lesions and is produced by lymphocytes. However, it is not known whether this cytokine is induced by relevant pathogenic triggers of psoriasis, such as Streptococcus pyogenes. Here we addressed the production of IL-9 in response to various pathogens in a psoriatic ex vivo model. Extracts of S. pyogenes and Candida albicans triggered the production of IL-9 and also IL-17A and IFN-γ. This induction was dependent on the interaction between CLA+ T cells and epidermal cells. Neutralization of IL-9 reduced S. pyogenes-induced IL-17A production by CLA+ T cells but had no effect on IFN-γ production. Also, IL-9 increased the survival of circulating psoriatic CLA+ T cells. Co-cultures from patients with guttate or plaque psoriasis with S. pyogenes produced similar amounts of IL-9. High cytokine responses in streptococcal-driven guttate patients paralleled peaks in Psoriasis Area Severity Index and anti-streptolysin O levels. Our results confirm that IL-9 promotes inflammation in psoriasis by up-regulating IL-17A production and support the clinical association of the immune response by streptococcal-sensitized CLA+ T cells with this cytokine, especially in guttate psoriasis.