Functional decline among bullous pemphigoid patients: A retrospective monocentric cohort study.

BACKGROUND: Bullous pemphigoid (BP) affects older patients with numerous comorbidities. The impact of BP on patient autonomy remains poorly understood. OBJECTIVES: To assess the frequency and factors associated with functional decline (FD) in BP. METHODS: In this retrospective monocentric study, we selected patients aged ≥75 years with BP diagnosed between 1 January 2015 and 31 December 2021 and followed for more than 3 months. We assessed activity limitation at diagnosis and included patients with no or mild activity limitation. We described FD and its associated factors at 6 weeks and 3 months. FD was qualified as moderate or severe. Age, comorbidities (CIRS-G score), BP characteristics at diagnosis (including palms and soles involvement) and hospitalization were collected. Factors associated with FD were investigated through univariate and multivariate logistic regression models. Worsening of previous comorbidities or new comorbidities at Week 6 were collected. RESULTS: One hundred and thirty-one patients were included (mean age 85 years), 75 (57.3%) had no activity limitation, and 56 (42.7%) a mild activity limitation at baseline. At Week 6, FD was observed in 44 (33.6%) patients, including 23 out of 75 (30.7%) with no activity limitation and 21 out of 56 (37.5%) with mild activity limitation at baseline. FD was moderate in 20 cases (45.5%) and severe in 24 (54.5%) and persisted at Month 3 in 37 (84%) patients. By multivariate analysis, factors associated with FD were a CIRS-G score >7, palms and soles involvement and anti-BP180 antibodies level. Fifty (38.2%) patients experienced a worsening of their pre-existing comorbidities or a new one. CONCLUSION: FD is often observed in patients with BP, especially in those with severe symptoms, palms and soles involvement and comorbidities. A comprehensive, multidisciplinary approach involving geriatric assessments should be adopted to manage these patients.

Impact of the first wave of the COVID-19 pandemic on the treatment of psoriasis with systemic therapies in France: Results from the PSOBIOTEQ cohort.

BACKGROUND: The nature of the COVID-19 pandemic led to concerns among patients and physicians about the potential impact of immunosuppressive treatments for chronic diseases such as psoriasis on the risk of severe COVID-19. OBJECTIVES: To describe treatment modifications and determine the incidence of COVID-19 infection among psoriasis patients during the first wave of the pandemic, and identify the factors associated with these events. METHODS: Data from PSOBIOTEQ cohort relating to the first COVID-19 wave in France (March to June, 2020), as well as a patient-centred COVID-19 questionnaire, were used to evaluate the impact of lockdown on changes (discontinuations, delays or reductions) in systemic therapies, and to determine the incidence of COVID-19 cases among these patients. Logistic regression models were used to assess associated factors. RESULTS: Among the 1751 respondents (89.3%), 282 patients (16.9%) changed their systemic treatment for psoriasis, with 46.0% of these changes being initiated by the patients themselves. Patients were more likely to experience psoriasis flare-ups during the first wave if they changed their treatment during this period (58.7% vs 14.4%; P < 0.0001). Changes to systemic therapies were less frequent among patients with cardiovascular diseases (P < 0.001), and those aged ≥ 65 years (P = 0.02). Overall, 45 patients (2.9%) reported having COVID-19, and eight (17.8%) required hospitalization. Risk factors for COVID-19 infection were close contact with a positive case (P < 0.001) and living in a region with a high incidence of COVID-19 (P < 0.001). Factors associated with a lower risk of COVID-19 were avoiding seeing a physician (P = 0.002), systematically wearing a mask during outings (P = 0.011) and being a current smoker (P = 0.046). CONCLUSIONS: Discontinuation of systemic psoriasis treatments during the first COVID-19 wave (16.9%) - mainly decided by patients themselves (46.0%) - was associated with a higher incidence of disease flares (58.7% vs 14.4%). This observation and factors associated with a higher risk of COVID-19 highlight the need to maintain and adapt patient-physician communication during health crises according to patient profiles, with the aim of avoiding unnecessary treatment discontinuations and ensuring that patients are informed about the risk of infection and the importance of complying with hygiene rules.

Psoriasis-related treatment exposure and hospitalization or in-hospital mortality due to COVID-19 during the first and second wave of the pandemic: cohort study of 1 326 312 patients in France.

BACKGROUND: Data on treatment exposures for psoriasis and poor COVID-19 outcomes are limited. OBJECTIVES: To assess the risk of hospitalization or in-hospital mortality due to COVID-19 by treatment exposure in patients with psoriasis. METHODS: All adults with psoriasis registered in the French national health-insurance (Système National des Données de Santé, SNDS) database between 2008 and 2019 were eligible. Two study periods were considered: 15 February to 30 June 2020 and 1 October 2020 to 31 January 2021, the first and second waves of the COVID-19 pandemic in France, respectively. Patients were classified according to their baseline treatment: biologics, nonbiologics, topicals or no treatment. The primary endpoint was hospitalization for COVID-19 using Cox models with inverse probability of treatment weighting. The secondary endpoint was in-hospital mortality due to COVID-19. RESULTS: We identified 1 326 312 patients with psoriasis (mean age 59 years; males, 48%). During the first study period, 3871 patients were hospitalized for COVID-19 and 759 (20%) died; during the second period 3603 were hospitalized for COVID-19 and 686 (19%) died. In the propensity score-weighted Cox models, risk of hospitalization for COVID-19 was associated with exposure to topicals or nonbiologics [hazard ratio (95% confidence interval): 1·11 (1·04-1·20) and 1·27 (1·09-1·48), respectively] during the first period, and with all exposure types, during the second period. None of the exposure types was associated with in-hospital mortality due to COVID-19. CONCLUSIONS: Systemic treatments for psoriasis (including biologics) were not associated with increased risk of in-hospital mortality due to COVID-19. These results support maintaining systemic treatment for psoriasis during the pandemic.

Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients.

BACKGROUND: Neurofibromatosis 1 (NF1) is one of the most common inherited disorders characterized by mutations in the tumour suppressor gene NF1. Its clinical manifestations are highly variable and unpredictable. A specific NF1 mutation does not predict the severity or complications of the disease. OBJECTIVE: The objective of this study was to build an empirical classification scheme without any a priori hypotheses to identify the underlying NF1 subtypes that best explain the observed heterogeneity. METHODS: We performed latent class analysis (LCA) of 1351 consecutive NF1 patients aged >17 years seen between 2002 and 2014. Data and phenotypic features were collected prospectively on a standardized form. RESULTS: The median age was 36.8 (17-81) years. A three-class model showed the best fit: 706 (52%) belonged to the LC1 'Cutaneous neurofibromas' class having preferentially cutaneous neurofibromas (99%), plexiform neurofibromas (63%) and blue-red macules (29%); 593 (44%) belonged to the LC2 'Subcutaneous neurofibromas' class characterized by the presence of at least 10 subcutaneous neurofibromas (21%) and a familial form (77%) and 52 (4%) belonged to the LC3 'Dysmorphic phenotype' class characterized by dysmorphic features (78%) and learning difficulties (87%). Patients in LC1 had a higher likelihood of developing scoliosis (RR = 1.7, 95% confidence interval (CI) [1.2-2.4]). Patients in LC2 were more likely to be men (RR = 1.4, 95% CI [1.1-1.7]). Patients in LC3 were at higher risk of having an optic pathway glioma (RR = 4.8, 95% CI [1.9-11.8]) and epilepsy (RR = 4.5, 95% CI [1.8-11.6]). CONCLUSION: Our findings invite the performance of a larger cohort study to test whether the various latent classes reflect different underlying genetic modifiers of these phenotypic traits.

Palmoplantar pustulosis and acrodermatitis continua of Hallopeau: demographic and clinical comparative study in a large multicentre cohort.

BACKGROUND: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. OBJECTIVES: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. METHODS: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. RESULTS: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). CONCLUSION: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.

Switches between biologics in patients with moderate-to-severe psoriasis: results from the French cohort PSOBIOTEQ.

BACKGROUND: Biologics are the cornerstone of treatment of patients with moderate-to-severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. OBJECTIVES: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. METHODS: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate-to-severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra-class - i.e. within the same therapeutic class - vs. inter-class) in patients switching from a TNF-alpha inhibitor using multivariate logistic regression. RESULTS: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF-alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL-17 inhibitor. Patients switching from a first-line TNF-alpha inhibitor before 2016 were more likely to switch to another TNF-alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF-alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. CONCLUSION: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL-17 inhibitors.

CITY-PSO: Prescribing behaviour of French private-practice dermatologists in psoriasis management: An observational, multicentre, cross-sectional study.

BACKGROUND: Information regarding the prescribing behaviour of French private-practice dermatologists (PPDs) is scarce. OBJECTIVES: First, to describe the population of PPDs involved in psoriasis management. Second, to describe the population of adult patients treated for psoriasis and their management. METHODS: We published a call for participation targeting PPDs; we first asked respondents to complete a form regarding their prescribing behaviour, and then to include consecutive patients consulting for psoriasis during a one-month study period and to collect patient data. RESULTS: The 94 participating PPDs included 1022 patients of mean age 52.9±17.9 years. The average body mass index was 28, and 25% had vascular comorbidities. Two thirds of patients had chronic psoriasis, for which 45% had consulted at least 5 times. Psoriasis was mostly with plaques (70.8%) and 11.4% of patients had psoriatic arthritis. The average body surface area (BSA) affected was 10.1%. Among the 679 patients without initial systemic treatment, 159 were started on systemic treatment. The main agents initiated were phototherapy (n=63), methotrexate (n=40), acitretin (n=30) and apremilast (n=20). In multivariate analysis, a higher BSA [Odds Ratio (OR) 1.10, 95% Confidence Interval (CI): 1.07-1.13; P<10-4] and Dermatology Life Quality Index (DLQI) [OR 1.09, 95% CI: 1.03-1.15; P=0.04] were associated with prescription of systemic therapy at the end of the consultation. CONCLUSION: The main limitation of our study was that participating PPDs were strongly involved in psoriasis management, which accounts for the high proportion of moderate-to-severe psoriasis and prescription of systemic treatments. Such committed PPDs and the development of psoriasis networks are key factors for improving the quality of care provided to psoriasis patients.

Meta-analysis results do not reflect the real safety of biologics in psoriasis.

BACKGROUND: In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference. OBJECTIVES: This systematic review and meta-analysis aimed to explore this possibility. METHODS: Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495). RESULTS: We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events. CONCLUSIONS: On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.

Interventions for chronic palmoplantar pustulosis: abridged Cochrane systematic review and GRADE assessments.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease in which sterile and relapsing pustules appear on the palms and soles. OBJECTIVES: To assess the effects of interventions for chronic PPP to induce and maintain complete remission. METHODS: We searched for randomized controlled trials (RCTs), including people with PPP or chronic palmoplantar pustular psoriasis, in the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and eight trials registers up to July 2020. Study selection, data extraction and risk-of-bias assessment were carried out independently by two review authors. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. RESULTS: We included 37 RCTs (1663 participants, 76% women, mean age 50 years). Mean treatment duration was 11 weeks. Topical vitamin D derivative may be more effective than placebo in achieving clearance [risk ratio (RR) 7·83, 95% confidence interval (CI) 1·85-33·12; low-certainty evidence from two trials]. Concerning biological therapies, there was little or no difference between etanercept and placebo in achieving clearance (low-certainty evidence from one trial), ustekinumab is less effective than placebo in reducing severity (low-certainty evidence from one trial), and guselkumab (RR 2·88, 95% CI 1·24-6·69) and secukinumab (RR 1·55, 95% CI 1·02-2·35) are probably better in reducing disease severity (moderate-certainty evidence from two and one trial(s), respectively) but may cause more serious adverse events than placebo. CONCLUSIONS: Evidence is lacking for or against major chronic PPP treatments. Risk of bias and imprecision limit our confidence in the results.

Epidemiologic study in a real-world analysis of patients with treatment for psoriasis in the French national health insurance database.

BACKGROUND: Psoriasis is one of the most frequent chronic inflammatory dermatoses in the world. Data on the prevalence of psoriasis in adults differ depending on the study. OBJECTIVE: To estimate the prevalence of patients with treatment for psoriasis in France and to identify and characterize patients receiving systemic treatments. METHODS: This was a French, nationwide cohort study based on health administrative data from the French national health insurance scheme linked to the national hospital discharge database (SNDS-PMSI). All adults with psoriasis registered in the SNDS between 1 January 2008 and 31 December 2016 were eligible for inclusion. All patients with a new prescription for a systemic treatment for psoriasis were included. RESULTS: A total of 874 549 patients were identified as having psoriasis (mean ± SD age 53.8 ± 17 years; 52.4% males); 112 969 (13%) had filled at least one prescription for a systemic medication used to treat psoriasis. The prevalence of patients with treatment for psoriasis was estimated at 1.3%. Overall, 73 168 and 16 545 were new users of conventional systemic treatments and biologics, respectively. The most frequent comorbidities associated with psoriasis were hypertension, dyslipidaemia, diabetes and chronic obstructive pulmonary disease. CONCLUSION: The prevalence of psoriasis we found was lower than in other studies. It was probably underestimated because we identified only patients with treatment for psoriasis. Our results concerning comorbidities associated with psoriasis patients requiring systemic treatment were similar to those from other published studies using other data sources, highlighting our ability to catch moderate-to-severe psoriasis. This study highlights the usefulness and reliability of the use of insurance databases in studies, because they allow for a better application to the general population.

Persistence of apremilast in moderate-to-severe psoriasis: a real-world analysis of 14 147 apremilast- and methotrexate-naive patients in the French National Health Insurance database.

BACKGROUND: Real-world data on the persistence of apremilast vs. methotrexate are inconclusive. OBJECTIVES: To assess and compare the long-term persistence of apremilast and methotrexate in a large cohort of patients with psoriasis. METHODS: All adult patients with psoriasis registered in the French national health insurance database ('Système National des Données de Santé') between 2009 and 2017 were eligible for inclusion. The study population comprised apremilast- and methotrexate-naive patients, defined as those with a first prescription of apremilast or methotrexate. Levels of persistence were compared using a Cox model with propensity-score matching that included potential confounders (notably age, sex, psoriatic arthritis, comorbidities and previous exposure to topical and systemic treatments). RESULTS: In this nationwide population-based cohort, 14 147 adult patients with psoriasis (mean age 52·3 years, 55·2% male) were found to be naive to both apremilast and methotrexate. After propensity-score matching, two subgroups of 4805 patients with similar baseline characteristics were included, of whom 3207 apremilast-treated patients and 2736 methotrexate-treated patients discontinued their treatment. Kaplan-Meier survival propensity-score analyses revealed a discontinuation rate of 69% for apremilast and 59% for methotrexate in the first year of treatment. Apremilast-treated patients had a higher risk of discontinuation than methotrexate-treated patients when considering the study population as a whole (hazard ratio 1·28, 95% confidence interval 1·23-1·34) or in a propensity-score-matched analysis (hazard ratio 1·34, 95% confidence interval 1·27-1·41; P < 0·001). CONCLUSIONS: Our real-world data suggest that in the first year of treatment, the discontinuation rate was significantly higher for apremilast-treated patients than for methotrexate-treated patients, regardless of the previous therapeutic lines received. What's already known about this topic? Psoriasis is a common chronic, relapse-remitting, inflammatory skin disease associated with severe psychosocial impact. Apremilast, a phosphodiesterase 4 inhibitor, is one of the most recently commercialized psoriasis drugs. Little is known about the long-term clinical effectiveness of apremilast. What does this study add? The discontinuation rate at 1 year for apremilast was 69%, compared with 58% for methotrexate, in a nationwide population-based cohort including 14 147 nonselected adult patients with psoriasis. Patients in the apremilast cohort had a higher risk of discontinuation than patients in the methotrexate cohort using propensity-score matching, including potentially relevant individual risk factors such as age, sex, comorbidities and psoriatic arthritis, and regardless of the previous therapeutic lines received. In daily practice, physicians should take these results into account when choosing between methotrexate and apremilast as a first-line systemic therapy.

Pathogen identification by shotgun metagenomics of patients with necrotizing soft-tissue infections.

BACKGROUND: Necrotizing soft-tissue infections (NSTIs) are life threatening, requiring broad-spectrum antibiotics. Their aetiological diagnosis can be limited by poor performance of cultures and administration of antibiotics before surgery. OBJECTIVES: We aimed (i) to compare 16S-targeted metagenomics (TM) and unbiased semiquantitative panmicroorganism DNA- and RNA-based shotgun metagenomics (SM) with cultures, (ii) to identify patients who would best benefit from metagenomics approaches and (iii) to detect the microbial pathogens in surrounding non-necrotic 'healthy' tissues by SM-based methods. METHODS: A prospective observational study was performed to assess the analytical performance of standard cultures, TM and SM on tissues from 34 patients with NSTIs. Pathogen identification obtained with these three methods was compared. RESULTS: Thirty-four necrotic and 10 healthy tissues were collected from 34 patients. The performance of TM was inferior to that of the other methods (P < 0·05), whereas SM performed better than standard culture, although the result was not statistically significant (P = 0·08). SM was significantly more sensitive than TM for the detection of all bacteria (P = 0·02) and more sensitive than standard culture for the detection of anaerobic bacteria (P < 0·01). There was a strong correlation (r = 0·71, Spearman correlation coefficient) between the semiquantitative abundance of bacteria in the culture and the bacteria-to-human sequence ratio in SM. Low amounts of bacterial DNA were found in healthy tissues, suggesting a bacterial continuum between macroscopically 'healthy' and necrotic tissue. CONCLUSIONS: SM showed a significantly better ability to detect a broader range of pathogens than TM and identify strict anaerobes than standard culture. Patients with diabetes with NSTIs appeared to benefit most from SM. Finally, our results suggest a bacterial continuum between macroscopically 'healthy' non-necrotic areas and necrotic tissues. What's already known about this topic? Necrotizing soft-tissue infections (NSTIs) are characterized by rapidly progressive necrosis of subcutaneous tissues and high mortality, despite surgical debridement combined with broad-spectrum antibiotics. The spectrum of potentially involved pathogens is very large, and identification is often limited by the poor performance of standard cultures, which may be impaired by previous antibiotic intake. Metagenomics-based approaches show promise for better identification of the pathogens that cause these infections, but they have not been evaluated in this medical context. What does this study add? Shotgun metagenomics (SM) showed higher sensitivity than 16S rRNA gene sequencing and a better ability than culture to detect anaerobic bacteria. As a result, a significant proportion of infections with bacteria, such as Pasteurella multocida or Clostridium perfringens, were detected only by SM. SM bacterial quantification enabled better detection of low amounts of bacterial DNA from macroscopically 'healthy' tissue, suggesting a subclinical infectious extension. What is the translational message? The high analytical performance of SM shown in this study should allow its future implementation for the diagnosis of necrotizing fasciitis, complementing or replacing routine methods. The large amount of data, including additional information on antimicrobial resistance, virulence profiles and metabolic adaptation of the pathogens, will improve microbiological documentation. Our results will improve our understanding of infectious pathophysiology in the future, leading to potentially better medical care.

Individual- and hospital-level factors associated with epidermal necrolysis mortality: a nationwide multilevel study, France, 2012-2016.

BACKGROUND: Epidermal necrolysis (EN) is a rare and life-threatening condition. OBJECTIVES: To assess whether admitting hospital characteristics and interhospital transfer are associated with mortality due to EN. METHODS: We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted during 2012-2016 with a code for EN in the International Classification of Diseases, 10th Revision, were eligible. We extracted data on the patients (age, sex, intensive care unit admission, comorbidities) and hospitals (private proprietary vs. public, nonteaching or teaching; and number of admissions for EN as a proxy for experience). Multivariable analysis was used to identify independent predictors of in-hospital mortality with mixed logistic regression. RESULTS: We identified 991 patients (467 male; mean age 52·7 ± 23 years). They were admitted to 300 different hospitals, including teaching hospitals (25% of hospitals) for around half of the patients. Overall, 597 patients (60%) had a diagnosis of Stevens-Johnson syndrome (SJS), 171 (17%) had SJS/toxic epidermal necrolysis (TEN) overlap and 223 (23%) had TEN. In total, 109 (11%) patients died: nine (2%) with SJS, 26 (15%) with SJS/TEN overlap and 74 (33%) with TEN. The in-hospital mortality rate was lower in centres with vs. without substantial EN experience - odds ratio for one supplemental EN admission in a department 0·5 (95% confidence interval 0·3-1·0); P = 0·05 - even after adjusting for potentially relevant individual risk factors. We found no significant association between mortality and interhospital transfer. CONCLUSIONS: Our findings highlight increased survival of patients with EN in centres with a high volume of EN procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition. What's already known about this topic? Epidermal necrolysis (EN) is a rare and life-threatening condition. At the individual level, risk factors for in-hospital mortality have been identified. Few studies have examined the association between hospital characteristics and EN mortality, with special attention to referral hospitals. What does this study add? Short-term mortality rates were lower for patients in centres with EN experience than in centres without EN experience, after adjusting for known risk factors. We found no association between interhospital transfer and survival. If confirmed in other settings, these findings support the early transfer of patients with suspected or diagnosed EN to centres with experience, where a multidisciplinary approach can be implemented by experienced healthcare professionals, to maximize short-term survival.

Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

Efficacy and satisfaction of surgical treatment for hidradenitis suppurativa.

BACKGROUND: Surgery is a radical treatment for hidradenitis suppurativa (HS) and may be considered as the only one potentially curative. OBJECTIVES: To characterize HS recurrence in patients after surgery and assess the risk factors of recurrence. METHODS: We conducted a monocentric retrospective cohort study. All consecutive patients who had surgery (January 1, 2012 to March 31, 2017) were included. We estimated the rate of recurrence of HS lesions after surgery (<1 cm from the scar), and recurrence-associated factors were analysed by univariate then multivariate logistic regression, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 75 patients [median age 31.4 years (range 16-71); 36 females], corresponding to 115 interventions were included. The Hurley score at surgery was III for 70 (60%) patients. In total, 61/115 (53%) interventions involved wide excision and 50 (43%) limited local excision. The localizations were axillary folds (n = 46; 40%), buttocks (n = 15, 13%), genital area (n = 13; 11%), perineal area (n = 12; 10%) and inguinal folds (n = 18; 16%). We observed 11 (10%) complications and 40 (35%) recurrences. On multivariate analysis, probability of recurrence was associated with only one-stage surgical closure [OR 3.2 (95% CI 1.4-7.3), P = 0.005]. Overall, 44 (52%) patients were completely satisfied and 22 (26%) partially satisfied, and most (81%) considered the surgery the best treatment. CONCLUSIONS: Hidradenitis suppurativa recurrence in our study was 35% and associated with one-stage surgical closures, but two-thirds of patients were satisfied with surgical treatment and would recommend surgery.

Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau.

BACKGROUND: Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. OBJECTIVES: To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. METHODS: A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]. CONCLUSIONS: We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.

Users of biologics in clinical practice: would they be eligible for phase III clinical studies? Cohort Study in the French Psoriasis Registry PSOBIOTEQ.

BACKGROUND: Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. METHODS: In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab - REVEAL, ustekinumab - PHOENIX, brodalumab - AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. RESULTS: A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non-plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9-9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non-eligible patients [0.78 (95% CI 0.62-0.97) (P = 0.03)]. CONCLUSION: The majority of patients treated with biologics in the PsoBioTeq real-life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events.

Persistence of treatment with biologics for patients with psoriasis: a real-world analysis of 16 545 biologic-naïve patients from the French National Health Insurance database (SNIIRAM).

BACKGROUND: Long-term clinical effectiveness of biologics in psoriasis is needed. OBJECTIVES: We aimed to assess the long-term persistence of biologics used to treat psoriasis in a real-life setting. METHODS: All adults with psoriasis having been registered in the French National Health Insurance database (SNIIRAM) between 2008 and 2016 were eligible for inclusion. Psoriasis was defined as the fulfilment of at least two prescriptions for topical formulations of a vitamin D derivative within a 2-year period. The study population comprised biologic-naïve patients, i.e. those with a first prescription of etanercept, infliximab, adalimumab or ustekinumab. Persistence of treatment with a biologic was defined as the time interval between initiation and discontinuation. RESULTS: In this nationwide population-based cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naïve (mean age 48·6 years; males 57·3%, mean follow-up 3·6 years). The mean ± SD length of follow-up for biologic-naïve patients was 3·6 ± 2·4 years. There were 9988 treatment discontinuations. Kaplan-Meier survival analyses revealed a persistence rate of 61·9% for the first, 33·3% for the third and 22·6% for the fifth year. Ustekinumab had a higher persistence rate than the other biologics. This finding should be interpreted with caution, in view of differences in administration between the biologics. About 85% of patients, having discontinued their first biologic, resumed systemic treatment of some type in the following year (biologics in 85% of cases). CONCLUSIONS: Our data suggest that biologics are less effective than physicians have been led to believe in a real-life, nonselected population. Further, long-term disease control requires several courses of different biologics.

GENIPSO: a French prospective study assessing instantaneous prevalence, clinical features and impact on quality of life of genital psoriasis among patients consulting for psoriasis.

BACKGROUND: Genital psoriasis is often under-recognized. OBJECTIVES: To assess the instantaneous prevalence of genital psoriasis and describe its clinical features, association with a particular subtype of psoriasis and its impact on general and sexual quality of life (QoL). METHODS: GENIPSO is a prospective study conducted by private and hospital-based dermatologists. This study featured the consecutive inclusion of patients consulting for extragenital psoriasis. The clinical features of psoriasis and genital psoriasis were recorded and QoL and sexual health questionnaires were distributed to patients. RESULTS: Overall, 335 of 776 patients (43·2%) included in the study had genital involvement. All were aware that they had genital lesions but only 135 patients (40%) declared that they had been previously examined. Genital lesions were associated with male sex, severity of psoriasis, age of onset > 20 years, inverse psoriasis and involvement of scalp, nail and external auditory canal, but were not associated with obesity, psoriatic arthritis and active sex life. Itching was the main symptom. Genital psoriasis was associated with impairment of QoL and sexual health according to the Dermatology Life Quality Index and the Female Sexual Function Index. CONCLUSIONS: Genital psoriasis has a high prevalence in patients consulting for extragenital psoriasis, which affects QoL, and should be taken into account by dermatologists in order to optimize global care.

Post-traumatic stress disorder in Stevens-Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. A prospective study of 31 patients.

BACKGROUND: Epidermal necrolysis is a rare and severe cutaneous adverse reaction to drugs with long-term somatic consequences and potentially underrecognized psychological complications. OBJECTIVES: To assess the prevalence and risk factors of post-traumatic stress disorder (PTSD) in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing psychiatric evaluation. METHODS: In this prospective study, we included adult patients admitted at the acute phase of SJS/TEN to our dermatology department from June 2009 to February 2013. The main objective was to assess the prevalence of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist score > 44. Secondary objectives were to investigate risk factors of PTSD in the medical history of patients and characteristics of the disease at the acute phase by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and Peritraumatic Distress Inventory (PDI) and the degree of impairment on the Sheehan Disability Scale. RESULTS: We initially included 32 of 80 patients admitted during the study period. At 6 months, seven of 30 still followed up had a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%) patients had a hydroxyzine prescription at the acute phase. The main risk factors associated with PTSD at 6 months were psychological results at the acute phase. CONCLUSIONS: Despite frequent prescription of hydroxyzine at the acute phase, almost one-quarter of patients with SJS/TEN had PTSD at 6 months. A systematic psychiatric evaluation should be offered regularly for at least 1 year after the acute disease phase.