Psoriasis is a chronic inflammatory skin disorder effectively treated by blocking IL-17RA, a receptor chain used by several IL-17 family members, including IL-17E. Although IL-17A is critically involved in the pathogenesis of psoriasis, the contribution of IL-17E remains unknown. Here we show that IL-17E(+) cells are more abundant than IL-17A(+) cells in lesional psoriatic skin. IL-17E synthesis is increased in keratinocytes within psoriatic plaques, and macrophages having a mixed M1/M2 phenotype represent an important proportion of the IL-17E(+) cells infiltrating the dermis. Mechanistically, macrophages do not synthetize but rather take up IL-17E via receptor-mediated clathrin-dependent endocytosis. Furthermore, monocyte-derived macrophages in vitro polarized in M2, but not M1, express the IL-17E receptor and respond to IL-17E by preferentially producing inflammatory cytokines and chemokines involved in neutrophil recruitment. Remarkably, IL-17E expression in lesional psoriatic skin correlates with the number of neutrophils while being inversely proportional to the number of infiltrating T cells. These data provide strong evidence for a proinflammatory role of keratinocyte-derived IL-17E in psoriasis, possibly via macrophage activation.

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Numerous guidelines and recommendations exist for the treatment of psoriasis in various populations. One important population is patients with psoriatic arthritis (PsA) who have symptoms of both joint and skin disease. In patients with both facets of psoriatic disease, skin and joints must be treated separately, but also simultaneously. As several systemic therapies are approved for either one or both, the concept of treating both facets with the same drug is feasible. This review summarizes evidence from studies in patients with PsA on the efficacy of these drugs on psoriatic skin disease in these patients.

BackgroundAnkylosing spondylitis (AS) is a chronic rheumatic condition that has a negative impact on health-related quality of life (HRQoL). Secukinumab (SEC), a fully human anti-IL-17A monoclonal antibody, has been shown to effectively control AS symptoms and improve HRQoL.ObjectivesTo evaluate the impact of SEC on HRQoL, assessed by the Short Form-36 Health Survey (SF-36), in pts with active AS stratified by time since first diagnosis (<2 or ≥2 yrs).MethodsPts were randomized to placebo (PBO) or SEC in MEASURE 1 (10 mg/kg intravenously followed by 150 or 75 mg SC), MEASURE 2 (150 or 75 mg SC) and MEASURE 4 (150 mg SC with/without SC loading). At Wk 16 or Wk 24, depending on ASAS 20 response, pts on PBO were re-randomized to SEC. Mixed-models for repeated measures were used to evaluate changes in SF-36 from baseline (BL) to Wk 16; observed data are presented at Wk 52. The proportion of pts reporting improvements meeting/exceeding the minimal clinically important differences (MCID) for SF-36 physical (PCS responders) and mental component summary (MCS responders), and individual SF-36 domains was also assessed. Missing data were recorded as non-response and Fisher’s exact test was used to compare the proportion of responders between groups at Wk 16. Only pooled data for pts receiving the licensed dose of SEC (150 mg) are shown.ResultsOverall 739 patients were included, with 427 and 312 in the SEC 150 mg and PBO groups, respectively. Of those, 37% and 36% of the SEC and PBO groups, respectively, were classified as <2 yrs since first AS diagnosis (Overall: 37%). The mean time since AS diagnosis was similar for the PBO and SEC treatment groups in both the <2 yrs (approx. 0.80 yrs) and the ≥2 yrs subgroups (approx.11 yrs). The least squares mean (LSM) changes in PCS from BL to Wk 16 were increased with SEC 150 mg compared with PBO, in both <2 yrs (PBO: 2.11; 150 mg: 6.44, p<0.0001) and ≥2 yrs since diagnosis (PBO: 3.03; 150 mg: 5.82, p<0.0001) groups. Significant increases were also reported in LSM changes in MCS scores from BL to Wk 16 with SEC 150 mg in patients <2 yrs since diagnosis (PBO: 2.10; 150 mg: 5.53, p<0.01), but not in the ≥2 yrs group. Analysis of individual SF-36 domain scores showed improvements with SEC vs PBO in the overall population and in both time since diagnosis subgroups, except Role-Emotional and Mental Health in the ≥2 yrs group (Figure). At Wk 16, the proportions of PCS responders were significantly higher with SEC 150 mg vs PBO, regardless of time since diagnosis (<2 yrs: PBO = 50.0%, SEC = 73.6%, p<0.01; ≥2 yrs: PBO = 45.0%, SEC = 69.8%, p<0.0001). MCS responses were not significantly different with SEC vs PBO in either subgroup. Overall, improvements in SF-36 scores and clinically meaningful MCID responses with SEC were more prominent in the <2 yrs since diagnosis compared with the ≥2 yrs group. Improvements in PCS, MCS, individual SF-36 domains and overall MCID responses were sustained to Wk 52 with SEC 150 mg.ConclusionTreatment with SEC 150 mg resulted in significant, clinically meaning...

Rare or opportunistic fungal infections are mostly described in immunosuppressed patients. We present a case of a cutaneous phaeohyphomycosis that developed on the dorsal foot in an immunosuppressed woman suffering from AIDS, caused by a novel Phialemoniopsis species. It clinically presented as an indurated violaceous plaque, surmounted by nodules exuding a sero-purulent discharge. A filamentous fungus was isolated from pus and cutaneous biopsy. ITS and LSU sequences phylogenetically resolved the fungus as an unknown species of Phialemoniopsis, which is an unresolved family within Sordariomycetes. In this study we describe the new species as Phialemoniopsis limonesiae, which clusters on a single branch clearly separated from its closest phylogenetic neighbours. This new strain showed low MIC to itraconazole, voriconazole and posaconazole.

Significant differences, distinguishing NAMs from DNMs, were detected particularly when considering both baseline signs and follow-up changes. Earlier identification of NAMs and their subsequent improved histological characterization will help define the subgroup of high-risk patients, for whom comprehensive image monitoring may be beneficial.

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