Psoriasis has major physical, psychological, and social impacts: its management should not be restricted by individual financial considerations in Western countries as these have well-structured ...health systems and social/insurance coverage. We investigated if the socioeconomic characteristics of patients were associated with severity of psoriasis and access to healthcare. In a cross-sectional study, we included 903 patients with psoriasis that were consulting for the first time. We showed that low educational level was associated with severity of disease in multivariate analyses. Moreover, patients of lower class and lower educational level, with severe psoriasis, had seen fewer physicians and had less frequently received a systemic treatment. Thus, physicians need to be vigilante of patients with a low socioeconomic status. Both low socioeconomic status and less access to dermatologists are associated with clinical severity of psoriasis at a first consultation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Merkel cell carcinoma is a rare neuroendocrine carcinoma of the skin mostly induced by Merkel cell polyomavirus integration. Cytokeratin 20 (CK20) positivity is currently used to distinguish Merkel ...cell carcinomas from other neuroendocrine carcinomas. However, this distinction may be challenging in CK20-negative cases and in cases without a primary skin tumor. The objectives of this study were first to evaluate the diagnostic accuracy of previously described markers for the diagnosis of Merkel cell carcinoma and second to validate these markers in the setting of difficult-to-diagnose Merkel cell carcinoma variants. In a preliminary set (n = 30), we assessed optimal immunohistochemical patterns (CK20, thyroid transcription factor 1 TTF-1, atonal homolog 1 ATOH1, neurofilament NF, special AT-rich sequence-binding protein 2 SATB2, paired box protein 5, terminal desoxynucleotidyl transferase, CD99, mucin 1, and Merkel cell polyomavirus-large T antigen) and Merkel cell polyomavirus load thresholds (real-time PCR). The diagnostic accuracy of each marker was then assessed in a validation set of 103 Merkel cell carcinomas (9 CK20-negative cases and 15 cases without a primary skin tumor) and 70 extracutaneous neuroendocrine carcinoma cases. The most discriminant markers for a diagnosis of Merkel cell carcinoma were SATB2, NF expression, and Merkel cell polyomavirus DNA detection (positive likelihood ratios: 36.6, 44.4, and 28.2, respectively). Regarding Merkel cell carcinoma variants, cases without a primary skin tumor retained a similar immunohistochemical profile and CK20-negative tumors displayed a different profile (decrease frequency of NF and SATB2 expression), but Merkel cell polyomavirus DNA remained detected (78% of cases by qPCR). Moreover, 8/9 (89%) CK20-negative Merkel cell carcinoma cases but only 3/61 (5%) CK20-negative extracutaneous neuroendocrine cases were positive for at least one of these markers. In conclusion, detection of SATB2 and NF expression and Merkel cell polyomavirus DNA helps distinguish between Merkel cell carcinoma classical and variant cases and extracutaneous neuroendocrine carcinomas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening ...side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids. Methods We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18–80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1:1) to receive either oral prednisone alone, 1·0 or 1·5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0·5 or 1·0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov , number NCT00784589. Findings Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38·4–71·7; p<0·0001. This difference corresponded to a relative risk of success of 2·61 (95% CI 1·71–3·99, p<0·0001), corresponding to 1·82 patients (95% CI 1·39–2·60) who would need to be treated with rituximab plus prednisone (rather than prednisone alone) for one additional success. No patient died during the study. More severe adverse events of grade 3–4 were reported in the prednisone-alone group (53 events in 29 patients; mean 1·20 SD 1·25) than in the rituximab plus prednisone group (27 events in 16 patients; mean 0·59 1·15; p=0·0021). The most common of these events in both groups were diabetes and endocrine disorder (11 21% with prednisone alone vs six 22% with rituximab plus prednisone), myopathy (ten 19% vs three 11%), and bone disorders (five 9% vs five 19%). Interpretation Data from our trial suggest that first-line use of rituximab plus short-term prednisone for patients with pemphigus is more effective than using prednisone alone, with fewer adverse events. Funding French Ministry of Health, French Society of Dermatology, Roche.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Whereas several studies have underlined the association between severe psoriasis and metabolic syndrome (MetS), the association of androgenetic alopecia (AGA) and MetS have yielded ...inconsistent results.
Objective
To investigate the relationship between AGA and the components of MetS in a population of psoriatic male patients.
Methods
A non-interventional, cross-sectional, multicenter study was conducted in France. A standardized questionnaire was completed, including information on components of MetS and other possible risk factors. MetSwas defined in this study as a combination of three or more of the four components of MetS:waist circumference, hyperlipidemia, diabetes mellitus and hypertension. In addition, a standardized simplified Norwood classification limited into 5 grades (0–4) was used.
Results
In a total of 1073 male patients, hypertension, high waist circumference, diabetes mellitus and hyperlipidemia were observed in 28%, 59%, 11%, and 31%, respectively. In age-adjusted multivariate analysis, severe AGA (grade 3–4
versus
grade 0) was associated with the presence of at least one component of MetS. By groups of age, a statistically significant association of severe AGA and MetS was demonstrated in patients over 59 years. SevereAGAwas also associated with a first degree familial history of major cardiovascular event in patients older than 59 years.
Conclusions
Our study, based on a simplified but stringent definition of MetS, confirmed the link between severe AGA and individual components of MetS in psoriatic patients. This argues for careful follow-up with regular screening in male psoriatic patients with severe AGA in order to early detect determinants of MetS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.
We sought to assess the effectiveness and safety of ...dupilumab in adults with AD in a real-life French multicenter retrospective cohort.
We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up.
We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10−9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10−9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10−6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs.
No control group, missing data.
This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In 2008, Feng et al. identified Merkel cell polyomavirus integration as the primary oncogenic event in ~80% of Merkel cell carcinoma cases. The remaining virus-negative Merkel cell carcinoma cases ...associated with a high mutational load are most likely caused by UV radiation. The current study aimed to compare the morphological and immunohistochemical features of 80 virus-positive and 21 virus-negative Merkel cell carcinoma cases. Microscopic evaluation revealed that elongated nuclei-similar to the spindle-shape variant of small cell lung cancer-were less frequent in Merkel cell polyomavirus-positive Merkel cell carcinoma compared to the virus-negative subset (p = 0.005). Moreover, virus-negative cases more frequently displayed a "large-cell neuroendocrine carcinoma" phenotype with larger cell size (p = 0.0026), abundant cytoplasm (p = 4×10
) and prominent nucleoli (p = 0.002). Analysis of immunohistochemical data revealed frequent positivity for thyroid transcription factor 1 and cytokeratin 7, either absence or overexpression of p53, as well as frequent lack of neurofilament expression in virus-negative cases. By contrast, cytokeratin 8, 18 and 20 and a CD99 with a dot pattern as well as high EMA expression were identified as characteristic features of virus-positive Merkel cell carcinoma. In particular, the CD99 dot-like expression pattern was strongly associated with presence of the Merkel cell polyomavirus in Merkel cell carcinoma (sensitivity = 81%, specificity = 90%, positive likelihood ratio = 8.08). To conclude, virus-positive and -negative Merkel cell carcinoma are characterized by distinct morphological and immunohistochemical features, which implies a significant difference in tumor biology and behavior. Importantly, we identified the CD99 staining pattern as a marker indicating the virus status of this skin cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
Psoriasis‐related pruritus is a frequent and underestimated symptom with a strong impact on quality of life, psychological condition and sleep. Our main objective was to document, in ...real‐life clinical practice, the perception of pruritus and the efficacy of a 4‐week topical treatment with a fixed‐dose combination of calcipotriol/betamethasone dipropionate (Cal/BD) foam on psoriasis‐related moderate‐to‐severe pruritus.
Methods
This was an exploratory prospective observational study in psoriasis patients with a pruritus visual analogic scale (VAS) score ≥ 3/10 cm. The primary endpoint was the proportion of responder patients defined as the self‐assessed improvement from baseline of pruritus of at least 2 VAS score points 48 h after the first topical administration. The quality of sleep was assessed on VAS and the quality of life was assessed using the Dermatology Life Quality Index (DLQI) on Day 28.
Results
A total of 81 patients were included by 34 dermatologists and 40 self‐questionnaires were evaluable for efficacy on Day 28. At inclusion, pruritus was self‐assessed as severe by 60.8% of patients, whereas physicians reported severe pruritus in 16.9% of patients. A proportion of 91.4% (95% confidence interval: 82–100) of patients were responders to pruritus relief 48 h after the first Cal/BD application. Relevant improvements in quality of sleep after 24 h (+2.9 ± 3.0) and in quality of life after 28 days (−9.0 ± 6.8) were reported.
Conclusion
This exploratory study provides further evidence that pruritus is an underestimated symptom, and it confirms the usefulness of the fixed‐dose combination of Cal/DB foam in relieving moderate‐to‐severe pruritus and improving the quality of life and sleep in patients with plaque psoriasis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for ...female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Paediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises ...the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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