Search

Cutaneous lichen planus is a highly pruritic dermatosis with an unmet need in its management. The aim of this study was to evaluate the short-term effect and tolerance of high doses of clobetasol propionate 0.05% in cutaneous lichen planus. We conducted a single-center retrospective cohort study from 2017 to 2021. All adults treated with high-dose (5 g/day) clobetasol propionate 0.05% for cutaneous lichen planus were included. Patients with less than 10% affected body surface area at initial presentation or who received concomitant systemic therapy were excluded. The primary endpoint was the rate of complete remission by week 16. Secondary endpoints included maximum daily and median cumulative doses, reduction in pruritus and occurrence of adverse events. Fifty-seven patients, 60% female, with a mean age of 48 years (min-max,18-83) were included. Cutaneous lichen planus had been present for a median duration of 2 months at initial presentation (min-max, 1-4) and involved a median body surface area of 27%. Pruritus was reported by 55/57 (96%) patients. At week 16, 41/57 (72%) patients had achieved complete remission without treatment modification, among whom 25/41 (61%) had achieved it at week 6. The median daily and cumulative doses were, respectively, 20 g/day (IQR, 10-20) and 560 g (IQR, 320-925). Three patients experienced mild adverse events. No statistical association was demonstrated between the duration of the disease before treatment initiation and clinical response. In conclusion, high-dose clobetasol propionate 0.05% seems to be an effective, well-tolerated, and easy-to-implement treatment for cutaneous lichen planus.

The incidence of necrotising soft-tissue infections has increased during recent decades such that most physicians might see at least one case of these potentially life-threatening infections in their career. Despite advances in care, necrotising soft-tissue infections are still associated with high morbidity and mortality, underlining a need for continued education of the medical community. In particular, failure to suspect necrotising soft-tissue infections, fuelled by poor awareness of the disease, promotes delays to first surgical debridement, amplifying disease severity and adverse outcomes. This Review will focus on practical approaches to management of necrotising soft-tissue infections including prompt recognition, initiation of specific management, exploratory surgery, and aftercare. Increased alertness and awareness for these infections should improve time to diagnosis and early referral to specialised centres, with improvement in the prognosis of necrotising soft-tissue infections.

Background Compared to other life-threatening infection survivors, long-term health-related quality of life (QOL) of patients surviving necrotizing soft-tissue infections (NSTI) and its determinants are little known. In this monocentric prospective cohort including NSTI survivors admitted between 2014 and 2017, QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36), the Hospital Anxiety and Depression (HAD), the activity of daily living (ADL), instrumental ADL (IADL) scales and the Impact of Event Scale-Revised (IES-R). The primary outcome measure was the SF-36 physical component summary (PCS). NSTI patients were compared according to intensive care unit (ICU) admission status. ICU survivors were matched on SAPS II with non-NSTI related septic shock survivors. Results Forty-nine NSTI survivors were phone-interviewed and included in the study. Median PCS was decreased compared to the reference population [− 0.97 (− 2.27; − 0.08) SD]. Previous cardiac disease was the only variable associated with PCS alteration [multivariate regression coefficient: − 8.86 (− 17.64; − 0.07), p = 0.048]. Of NSTI survivors, 15.2% had a HAD-D score ≥ 5 and 61.2% an IES-R score ≥ 33. ICU admission was not associated with lower PCS [35.21 (25.49–46.54) versus (vs) 41.82 (24.12–51.01), p = 0.516], but with higher IES-R score [14 (7.5–34) vs 7 (3–18), p = 0.035] and a higher proportion of HAD-D score ≥ 5 (28.6 vs 4.0%, p = 0.036). Compared to non-NSTI septic shock-matched controls, NSTI patients had similar PCS [33.81 (24.58; − 44.39) vs 44.87 (26.71; − 56.01), p = 0.706] but higher HAD-D [3.5 (1–7) vs 3 (1.5–6), p = 0.048] and IES-R scores [18 (8–35) vs 8 (3–19), p = 0.049]. Conclusions Long-term QOL in NSTI survivors is severely impaired, similarly to that of non-NSTI septic shock patients for physical compartments, but with more frequent depressive and/or post-traumatic stress disorders. Only ICU admission and previous cardiac disease were predictive of QOL impairment.

UNSTRUCTURED N/A

During the first COVID-19 pandemic wave, dermatologists were urged to postpone non-urgent and outpatient visits,1 to limit COVID-19 spreading. Teledermatology (TD) integration, through live-and-interactive (LI) video consultation or store-and-forward (SF) expertise, was raised as a potential substitute to maintain continuity of care.2,3 The aim of this study was to determine whether TD implementation during the pandemic could (or not) compensate for the outpatient activity predicted in the absence of COVID-19 pandemic. It was conducted in a dermatology department of a tertiary center, providing SF TD since 2016, notably for skin emergencies.

Background Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head to head, which is why we chose to conduct a network meta-analysis. Objectives To compare the efficacy and safety of conventional systemic agents (acitretin, ciclosporin, fumaric acid esters, methotrexate), small molecules (apremilast, tofacitinib, ponesimod), anti-TNF alpha (etanercept, infliximab, adalimumab, certolizumab), anti-IL12/23 (ustekinumab), anti-IL17 (secukinumab, ixekizumab, brodalumab), anti-IL23 (guselkumab, tildrakizumab), and other biologics (alefacept, itolizumab) for patients with moderate to severe psoriasis and to provide a ranking of these treatments according to their efficacy and safety. Search methods We searched the following databases to December 2016: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registers and the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports. We checked the reference lists of included and excluded studies for further references to relevant RCTs. We searched the trial results databases of a number of pharmaceutical companies and handsearched the conference proceedings of a number of dermatology meetings. Selection criteria Randomised controlled trials (RCTs) of systemic and biological treatments in adults (over 18 years of age) with moderate to severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate to severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. Data collection and analysis Three groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the Psoriasis Area and Severity Index score (PASI) 90) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE; we evaluated evidence as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. Main results We included 109 studies in our review (39,882 randomised participants, 68% men, all recruited from a hospital). The overall average age was 44 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo controlled (67%), 23% were head-to-head studies, and 10% were multi-armed studies with both an active comparator and placebo. We have assessed all treatments listed in the objectives (19 in total). In all, 86 trials were multicentric trials (two to 231 centres). All of the trials included in this review were limited to the induction phase (assessment at less than 24 weeks after randomisation); in fact, all trials included in the network meta-analysis were measured between 12 and 16 weeks after randomisation. We assessed the majority of studies (48/109) as being at high risk of bias; 38 were assessed as at an unclear risk, and 23, low risk. Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90. In terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. Small molecules were associated with a higher chance of reaching PASI 90 compared to conventional systemic agents. At drug level, in terms of reaching PASI 90, all of the anti-IL17 agents and guselkumab (an anti-IL23 drug) were significantly more effective than the anti-TNF alpha agents infliximab, adalimumab, and etanercept, but not certolizumab. Ustekinumab was superior to etanercept. No clear difference was shown between infliximab, adalimumab, and etanercept. Only one trial assessed the efficacy of infliximab in this network; thus, these results have to be interpreted with caution. Tofacitinib was significantly superior to methotrexate, and no clear difference was shown between any of the other small molecules versus conventional treatments. Network meta-analysis also showed that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab outperformed other drugs when compared to placebo in terms of reaching PASI 90: the most effective drug was ixekizumab (risk ratio (RR) 32.45, 95% confidence interval (CI) 23.61 to 44.60; Surface Under the Cumulative Ranking (SUCRA) = 94.3; high-certainty evidence), followed by secukinumab (RR 26.55, 95% CI 20.32 to 34.69; SUCRA = 86.5; high-certainty evidence), brodalumab (RR 25.45, 95% CI 18.74 to 34.57; SUCRA = 84.3; moderate-certainty evidence), guselkumab (RR 21.03, 95% CI 14.56 to 30.38; SUCRA = 77; moderate-certainty evidence), certolizumab (RR 24.58, 95% CI 3.46 to 174.73; SUCRA = 75.7; moderate-certainty evidence), and ustekinumab (RR 19.91, 95% CI 15.11 to 26.23; SUCRA = 72.6; high-certainty evidence). We found no significant difference between all of the interventions and the placebo regarding the risk of serious adverse effects (SAEs): the relative ranking strongly suggested that methotrexate was associated with the best safety profile regarding all of the SAEs (RR 0.23, 95% CI 0.05 to 0.99; SUCRA = 90.7; moderate-certainty evidence), followed by ciclosporin (RR 0.23, 95% CI 0.01 to 5.10; SUCRA = 78.2; very low-certainty evidence), certolizumab (RR 0.49, 95% CI 0.10 to 2.36; SUCRA = 70.9; moderate-certainty evidence), infliximab (RR 0.56, 95% CI 0.10 to 3.00; SUCRA = 64.4; very low-certainty evidence), alefacept (RR 0.72, 95% CI 0.34 to 1.55; SUCRA = 62.6; low-certainty evidence), and fumaric acid esters (RR 0.77, 95% CI 0.30 to 1.99; SUCRA = 57.7; very low-certainty evidence). Major adverse cardiac events, serious infections, or malignancies were reported in both the placebo and intervention groups. Nevertheless, the SAEs analyses were based on a very low number of events with low to very low certainty for just over half of the treatment estimates in total, moderate for the others. Thus, the results have to be considered with caution. Considering both efficacy (PASI 90 outcome) and acceptability (SAEs outcome), highly effective treatments also had more SAEs compared to the other treatments, and ustekinumab, infliximab, and certolizumab appeared to have the better trade-off between efficacy and acceptability. Regarding the other efficacy outcomes, PASI 75 and Physician Global Assessment (PGA) 0/1, the results were very similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for a third of the interventions. Authors' conclusions Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well. In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naive patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

Introduction Le nombre de traitements systemiques (TS) disponibles dans l’indication psoriasis modere a severe a augmente de facon considerable durant les 20 dernieres annees. La meta-analyse en reseau (MAR) est une methode statistique permettant de comparer des traitements n’ayant pas ete compares dans des essais (ECR) face-face et de classer les traitements en fonction de leur efficacite et tolerance. L’objectif de cette revue systematique (RS) avec MAR etait de comparer l’efficacite et la tolerance des TS chez l’adulte dans le psoriasis modere a severe. Sont presentes les resultats de la mise a jour la plus recente. Materiel et methodes Les bases bibliographiques CENTRAL, MEDLINE, Embase et les resumes de congres, les registres d’essais ont ete consultes jusqu’en septembre 2020. Les criteres d’inclusion etaient : ECR comparant un TS chez des adultes atteints de psoriasis modere a severe (Pso), par rapport a un PBO ou entre eux. La selection des ECR, l’extraction des donnees, l’evaluation du risque de biais ont ete effectuees independamment par 2 auteurs. Les criteres de jugement (CJ) principaux etaient: la proportion de participants atteignant le PASI 90 et la proportion de participants presentant des evenements indesirables graves (EIG) entre 8 et 24 semaines. Resultats Un total de 158 ECR ont ete inclus (57 831 patients, d’âge moyen de 45 ans, 68 % d’hommes, avec un score initial moyen PASI de 20) dans la revue systematique et 130 ECR (50 081 patients) dans la MAR comparant 20 TS ou PBO. Le risque de biais etait considere comme faible pour 80 ECR/158. Les patients sous infliximab, ixekizumab, secukinumab, brodalumab, risankizumab et guselkumab atteignaient significativement plus le PASI90 comparativement aux patients sous ustekinumab ou sous l’un des 3 autres anti-TNF: adalimumab, certolizumab, et etanercept. L’ustekinumab et adalimumab etaient significativement plus efficaces pour l’obtention du PASI 90 que l’etanercept; l’ustekinumab etait egalement plus efficace que le certolizumab. Aucune difference n’etait constatee entre l’ustekinumab et l’adalimumab. L’efficacite clinique de ces 7 TS par rapport au PBO a ete est detaillee. Aucune difference significative entre les TS et le PBO a ete trouvee concernant le risque d’EIG. Discussion Cette RS/MA permet de donner de facon actualisee en continu les donnees d’efficacite et de tolerance relatives des TS. Ces donnees sont importantes dans la prise de decision medicale et pour les auteurs de recommandations. Les limites de cette etude sont le manque de donnees d’efficacite et de tolerance a long terme necessaires dans le cadre d’une maladie chronique.

Introduction La necrolyse epidermique (NE, incluant les syndromes de Stevens-Johnson, SJS et Lyell) est d’origine medicamenteuse dans 85 % des cas. Ses profils de gravite et d’evolution differents pourraient faire intervenir d’autres facteurs que ceux du SCORTEN, score predictif de mortalite en phase aigue. Afin de preciser les differents groupes clinico-biologiques de NE et de les correler au pronostic, nous avons conduit une analyse non supervisee. Materiel et methodes Cette etude retrospective monocentrique a inclus les patients hospitalises pour NE entre le 01/01/2015 et le 31/12/2020. Une analyse non supervisee etait realisee, combinant une classification hierarchique sur composantes principales. Les variables incluses dans le modele etaient les donnees cliniques et biologiques a l’admission (âge, surface cutanee decollee decollable (SDD), bicarbonates, uree, creatininemie, neutrophiles, lymphocytes, LDH, albumine, CRP, phosphates). Les criteres de jugement etaient : mortalite, SDD maximale, infections, bacteriemies, besoin en ventilation mecanique. Resultats Cent treize patients etaient inclus (76 F, âge median 46 ans (IQR 35–60)). Trois classes etaient identifiees, deux (n = 40 et 60) chez des patients jeunes, et une (n = 13) chez des sujets nettement plus âges. La comparaison des classes 1 et 2 montrait dans la classe 1 une nette predominance feminine (87 vs 60 %, p = 0,033), un âge plus jeune de 10 ans (36 vs 46 ans, p = 0,031) et moins de cancer (3 vs 17 %, p = 0,055). La classe 2 avait une SDD initiale plus importante (30 vs 3 %, p Discussion En dehors de patients âges, au pronostic sombre comme attendu, notre etude montre deux profils distincts de NE chez des patients plus jeunes : d’une part des SJS peu graves, chez des femmes jeunes, et d’autre part des syndromes de Lyell chez des patients 10 ans plus âges. L’âge, la SDD initiale > 10 % et le cancer sont des facteurs pronostiques deja connus, mais nous identifions des anomalies biologiques non decrites a ce jour comme associees au moins bon pronostic (neutropenie, lymphopenie, LDH elevees, hypoalbuminemie, hypophosphatemie). Des analyses multivariees permettront de comprendre la part respective de ces facteurs. Les mecanismes physiopathologiques conduisant a une progression de la NE et donc a un pronostic plus sombre une fois la reaction installee sont a decouvrir.

Introduction Le recours dermatologique par télédermatologie (TD) vs. consultation présentielle a été encouragé pendant la pandémie COVID-19. L’objectif de ce travail est d’évaluer l’effet de la pandémie COVID-19 sur le nombre de télé-expertises (TLX) pour cancer cutané (CC) au sein d’un réseau de TD durant les 2 vagues COVID-19 en France. Matériel et méthodes L’étude a été menée dans un réseau de TD qui permet des TLX entre professionnels de santé et dermatologues. Afin d’évaluer l’impact du COVID sur le nombre de TLX pour CC, nous avons recueilli et comparé le nombre des TLX des 2 premiers mois des 1re (mars et avril 2020) et 2e (octobre et novembre 2020) vagues françaises du COVID-19 à la même période en 2019. Les variables extraites étaient la provenance [institutions (hôpitaux et EHPAD) vs. médecins généralistes (MG)] et les diagnostics [CC vs. autres] des patients. Résultats 1re vague : Le nombre total des TLX était de 583 en 2019 vs. 629 en 2020. La proportion des TLX pour CC a diminué significativement, quelle que soit la provenance des patients (Institutions ou MG), 7 % en 2019 (41/583) vs. 1,6 % en 2020 (10/629) (p

Introduction En permettant l’acces a l’expertise dermatologique, la teledermatologie (TD) facilite la prise en charge des patients atteints de maladies rares eloignes des centres de reference (CR). L’objectif de notre etude etait d’analyser les demandes d’avis pour suspicion de necrolyse epidermique (NE, syndromes de Stevens-Johnson, SJS, et de Lyell) adresses par TD a un CR et la prise en charge qui en a decoule. Materiel et methodes Cette etude retrospective monocentrique a inclus toutes les demandes consecutives d’avis de TD adressees pour suspicion de NE entre 2016 (mise en place de la TD dans notre CR) et 2020. Les dossiers avec donnees manquantes (i.e. photographies) ont ete exclus. Les demandes ont ete analysees avec une grille incluant les donnees necessaires au diagnostic de NE sur photo (atteinte muqueuse, decollement) et a l’evaluation de la severite (items du SCORTEN, lactates, signes respiratoires), la provenance des patients, et la prise en charge decidee. La qualite des avis etait definie par le nombre d’echanges et la qualite des photographies transmises (echelle de Likert 1, mauvaise qualite-4, tres bonne qualite). Resultats Parmi les 81 demandes d’avis incluses, une NE a ete confirmee dans 52 cas (64 %), un diagnostic differentiel pose dans 29 cas (36 %), et 34 patients (43 %) ont ete transferes, dont 28 NE. Les medecins demandeurs etaient essentiellement hospitaliers (97 %) dont 26 % de reanimateurs. Le nombre median d’echanges de mails pour obtenir les informations sur la gravite du patient etait de 3 [1–5]. Concernant la qualite des photos le score median etait de 3 [2–5]. Il n’y avait pas de difference d’âge des patients transferes ou non (50 et 57 ans respectivement, p = 0,21). Le nombre d’echanges n’etait pas different pour les patients avec diagnostic NE ou non. La provenance geographique des avis concernant les patients transferes etait: notre region dans 23 cas (68 %), une autre dans 10 (29 %) et non renseignee dans 1 cas (3 %). Un protocole de prise en charge etait transmis pour les NE confirmees non transferees. Discussion Notre etude montre qu’un transfert est decide pour pres de la moitie des patients avec suspicion de NE, et ce quel que soit le diagnostic final pose. Pour 2/3 des cas, le diagnostic de NE a ete confirme. La qualite des photos doit etre amelioree afin de mieux apprecier l’etendue des lesions. Le nombre d’echanges de mails necessaire a l’obtention de l’ensemble des informations et notamment a l’evaluation de la gravite (SCORTEN et surface corporelle decollee) est eleve. Ainsi, une meilleure sensibilisation des medecins aux signes de gravite et une « check-list » des donnees clinico-biologiques essentielles a fournir sont necessaires pour guider au mieux le diagnostic, la decision de transfert (en reanimation ou en dermatologie) et la prise en charge des patients. Pour ceux qui ne sont pas transferes, la TD assure aussi un role de conseil et de suivi au sein d’un reseau de soin.

Introduction Le lichen plan cutane (LPC) est une dermatose inflammatoire affichante et prurigineuse alterant la qualite de vie des patients. Regulierement resolutive en 9 a 12 mois, l’efficacite des traitements est incertaine et la prise en charge mal codifiee. Le but de cette etude etait d’evaluer l’interet a court terme de fortes doses de propionate de clobetasol 0,05 %. Materiel et methodes Cohorte historique monocentrique, (accord IRB) de 2017 a 2021 ayant inclus tous les patients de plus de 18 ans suivis dans le service de dermatologie d’un hopital universitaire pour un LPC traite par propionate de clobetasol 0,05 % a des doses > 5 g/jour. Les patients presentant une surface corporelle atteinte (SCA) initiale inferieure a 5 % ou recevant un traitement systemique concomitant etaient exclus. Le critere de jugement principal etait le taux de remission complete avant 16 semaines de traitement, defini par une SCA Resultats Cinquante-deux patients, 62 % de femmes, d’un âge median de 49 ans [18–83], ont ete inclus. La poussee de LPC, confirmee par l’examen histologique chez 47/52, evoluait depuis une duree mediane de 3 mois (EI 1,1–4,8) et concernait une SCA mediane de 26,5 % (EI 15–40). Tous les patients sauf un rapportaient un prurit. La quantite mediane de propionate de clobetasol 0,05 % journaliere etait de 20 g [5–30], pour une duree mediane de 3 semaines (EI 2–4). A 16 semaines : 37/52 patients, soit 71,2 % (IC 95 % = [56,9 %–82,9 %]), etaient en reponse complete sans modification ou ajout de traitement, dont 50 % dans les 6 premieres semaines. Le prurit avait disparu chez 32 patients, soit 61,5 % (IC 95 % = [47,0 %–74,7 %]), et aucun evenement indesirable n’a ete signale. Enfin, aucune association statistique n’a ete demontree entre la duree de la poussee avant la mise sous traitement et la reponse clinique. Discussion Cette etude met en evidence une reponse complete a 16 semaines chez 71 % des patients ayant un LPC. La principale limite de cette etude est sa nature retrospective pour une maladie dont la resolution spontanee est la regle. Neanmoins, la reponse obtenue des 1 mois et demi pour la moitie des patients et la courte duree d’evolution du LPC a l’inclusion sont en faveur d’un role du traitement plutot que de l’evolution naturelle de la maladie. La balance benefice/risque de ce schema therapeutique semble interessant comparativement aux autres traitements disponibles (corticosteroides, methotrexate, acitretine, phototherapie) dont le niveau de preuve d’efficacite est egalement faible. Ces resultats plaident pour la realisation d’une etude prospective multicentrique.

International audience; Background: Scleromyxedema (SME) is a rare mucinosis associated with monoclonal gammopathy. Several biochemical peculiarities of monoclonal immunoglobulins (Ig) in SME patients were reported in case reports or short series, such as IgGλ over-representation, cationic migration, and partial deletion. Methods: Monoclonal immunoglobulins (Ig) from the serum of 12 consecutive patients diagnosed with scleromyxedema (SME) were analyzed using electrophoretic and immunoblotting techniques. Results: All monoclonal Ig from 12 SME were of IgG1 subclass, with an overrepresentation of the lambda-type light chain and a cationic mobility on standard zone electrophoresis, as compared with 21 cases of monoclonal gammopathy of undetermined significance (MGUS) of IgG1 subclass. Reactivity with specific monoclonal antibodies demonstrated no evident deletion of the heavy chain constant domains, which was also confirmed by analysis of Ig heavy chain molecular weight on a purified monoclonal component from one case. Conclusions: Significant isotype restriction of both heavy and light chains, and peculiar biochemical properties suggest that monoclonal Ig might be involved in pathophysiological events of SME.

Background There is no consensus on the treatment of drug reaction with eosinophilia and systemic symptoms (DRESS). At our center, systemic steroids (SS) are used for severe cases while topical steroids (TS) are used for mild and moderate forms. Objectives To investigate the short-term outcome for patients with DRESS receiving SS as first-line therapy before being transferred to our department and then switched to TS after admission. Methods A retrospective monocenter study in DRESS patients (RegiSCAR score ≥ 4) transferred to our dermatology department from a different setting between 07/2012 and 06/2018 and who had received SS before being transferred. Epidemiological, clinical and laboratory data were collected, as well as details of treatment modalities and outcome. Results Twenty patients were included. On admission to our department, 4 were assessed as having severe DRESS and continued on SS, while 16 were assessed as mild/moderate DRESS and were switched to TS. Among these 16 patients, the outcome on TS was favorable for 12 and quickly unfavorable for 4, who had to be switched back to SS. Retrospective analysis of the initial data (before transfer) showed that these 4 patients had previously had a greater number of severity criteria than the other 12. Conclusion Caution is needed not only when deciding to initiate SS in DRESS but also on withdrawal of these drugs. Our series suggests that when SS are used as first-line therapy in DRESS patients with initial severity criteria, they should not be withdrawn quickly for a switch to TS, even where progression appears favorable, due to the risk of relapse.

Novel approaches for adjunctive therapy are urgently needed for complicated infections and patients with compromised immunity. Necrotizing fasciitis (NF) is a destructive skin and soft tissue infection. Despite treatment with systemic antibiotics and radical debridement of necrotic tissue, lethality remains high. The key iron regulatory hormone hepcidin was originally identified as a cationic antimicrobial peptide (AMP), but its putative expression and role in the skin, a major site of AMP production, have never been investigated. We report here that hepcidin production is induced in the skin of patients with group A Streptococcus (GAS) NF. In a GAS-induced NF model, mice lacking hepcidin in keratinocytes failed to restrict systemic spread of infection from an initial tissue focus. Unexpectedly, this effect was due to its ability to promote production of the CXCL1 chemokine by keratinocytes, resulting in neutrophil recruitment. Unlike CXCL1, hepcidin is resistant to degradation by major GAS proteases and could therefore serve as a reservoir to maintain steady-state levels of CXCL1 in infected tissue. Finally, injection of synthetic hepcidin at the site of infection can limit or completely prevent systemic spread of GAS infection, suggesting that hepcidin agonists could have a therapeutic role in NF.

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.

Introduction Le maintien de la continuité des soins dermatologiques pendant la pandémie COVID-19 a contraint les dermatologues à utiliser téléconsultation (TC) et télé-expertise (TLX). L’objectif de ce travail était d’estimer si l’implantation de la télédermatologie (TD) pendant la pandémie pourrait (ou non) compenser l’activité ambulatoire prédite en l’absence du COVID-19. Matériel et méthodes Entre janvier 2019 et décembre 2020 l’activité présentielle, soit le nombre mensuel de consultations dermatologiques programmées (CDP) et de consultations non programmées d’urgences dermatologiques (UD) ainsi que le nombre de TC et TLX ont été recueillis au sein d’un service hospitalo-universitaire de dermatologie. Pour chacune des activités, un modèle ARIMA (modèle autorégressif et moyenne mobile) a été appliqué afin de prédire l’évolution d’une série temporelle complète (représentation de phénomènes variant dans le temps et prédiction de valeurs futures en fonction de valeurs précédentes). Pour confirmer que ces modifications étaient liées à la pandémie COVID 19, un modèle d’inférence causale a été effectué. Résultats L’impact de la pandémie COVID 19 et des confinements sur l’activité d’un service de dermatologie est illustré dans la Figure 1 et le tableau 1. Pendant le premier confinement, on observe une nette diminution de l’activité présentielle : pour les UD, le modèle ARIMA et d’inférence causale montrent respectivement une baisse de 4472 et 4635 consultations entre mars et octobre 2020 (p

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.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused by bacteria. Associated rates of mortality and morbidity are high, with the former estimated at around 23%, and disability, sequelae, and limb loss occurring in 15% of patients. Standard management includes intravenous empiric antimicrobial therapy, early surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies such as intravenous immunoglobulin (IVIG). OBJECTIVES: To assess the effects of medical and surgical treatments for necrotizing soft tissue infections (NSTIs) in adults in hospital settings. SEARCH METHODS: We searched the following databases up to April 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers, pharmaceutical company trial results databases, and the US Food and Drug Administration and the European Medicines Agency websites. We checked the reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs conducted in hospital settings, that evaluated any medical or surgical treatment for adults with NSTI were eligible for inclusion. Eligible medical treatments included 1) comparisons between different antimicrobials or with placebo; 2) adjuvant therapies such as intravenous immunoglobulin (IGIV) therapy compared with placebo; no treatment; or other adjuvant therapies. Eligible surgical treatments included surgical debridement compared with amputation, immediate versus delayed intervention, or comparisons of number of interventions. RCTs of hyperbaric oxygen (HBO) therapy for NSTI were ineligible because HBO is the focus of another Cochrane Review. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome measures were 1) mortality within 30 days, and 2) proportion of participants who experience a serious adverse event. Secondary outcomes were 1) survival time, and 2) assessment of long‐term morbidity. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included three trials randomising 197 participants (62% men) who had a mean age of 55 years. One trial compared two antibiotic treatments, and two trials compared adjuvant therapies with placebo. In all trials, participants concomitantly received standard interventions, such as intravenous empiric antimicrobial therapy, surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies. All trials were at risk of attrition bias and one trial was not blinded. Moxifloxacin versus amoxicillin‐clavulanate One trial included 54 participants who had a NSTI; it compared a third‐generation quinolone, moxifloxacin, at a dose of 400 mg given once daily, against a penicillin, amoxicillin‐clavulanate, at a dose of 3 g given three times daily for at least three days, followed by 1.5 g three times daily. Duration of treatment varied from 7 to 21 days. We are uncertain of the effects of these treatments on mortality within 30 days (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.39 to 23.07) and serious adverse events at 28 days (RR 0.63, 95% CI 0.30 to 1.31) because the quality of the evidence is very low. AB103 versus placebo One trial of 43 randomised participants compared two doses, 0.5 mg/kg and 0.25 mg/kg, of an adjuvant drug, a CD28 antagonist receptor (AB103), with placebo. Treatment was given via infusion pump for 10 minutes before, after, or during surgery within six hours after the diagnosis of NSTI. We are uncertain of the effects of AB103 on mortality rate within 30 days (RR of 0.34, 95% CI 0.05 to 2.16) and serious adverse events measured at 28 days (RR 1.49, 95% CI 0.52 to 4.27) because the quality of the evidence is very low. Intravenous immunoglobulin (IVIG) versus placebo One trial of 100 randomised participants assessed IVIG as an adjuvant drug, given at a dose of 25 g/day, compared with placebo, given for three consecutive days. There may be no clear difference between IVIG and placebo in terms of mortality within 30 days (RR 1.17, 95% CI 0.42 to 3.23) (low‐certainty evidence), nor serious adverse events experienced in the intensive care unit (ICU) (RR 0.73 CI 95% 0.32 to 1.65) (low‐certainty evidence). Serious adverse events were only described in one RCT (the IVIG versus placebo trial) and included acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents. Only one trial reported assessment of long‐term morbidity, but the outcome was not defined in the way we prespecified in our protocol. The trial used the Short Form Health Survey (SF36). Data on survival time were provided upon request for the trials comparing amoxicillin‐clavulanate versus moxifloxacin and IVIG versus placebo. However, even with data provided, it was not possible to perform survival analysis. AUTHORS' CONCLUSIONS: We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30‐day mortality or serious adverse events due to the very low quality of the evidence. The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real‐life population. Management of NSTI participants (critically‐ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo‐controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long‐term functional outcomes, e.g. quality of life (in the chronic phase).

International audience; Importance Nigella sativa oil (NSO) is widely used for cosmetic and culinary purposes. Cases of severe acute contact dermatitis due to NSO are poorly described, with no histologic description.Objectives To describe the clinical and histologic features of severe acute contact dermatitis due to NSO and investigate the components responsible for such eruptions.Design, Setting, and Participants A case series study of 3 patients with contact dermatitis admitted to the dermatology department between August 21, 2009, and February 19, 2017, was conducted. All patients had been referred to the dermatology department for acute contact dermatitis due to NSO and had patch tests performed.Main Outcomes and Measures Clinical and histologic features of the cutaneous eruptions, length of hospital stay, chemical analysis of NSO, and results of patch tests.Results Three patients (3 women; median age, 27 years [range, 20-47 years]) were included in the case series. All patients had polymorphic skin lesions spreading beyond the area of NSO application: typical and atypical targets, patches with central blisters, erythematous or purpuric plaques with a positive Nikolsky sign mimicking Stevens-Johnson syndrome, or toxic epidermal necrolysis. Two patients had pustules. They had severe impairment, with more than 15% skin detachment and fever. The results of skin biopsies showed epidermal apoptosis characterized by vacuolar alteration of the basal layer, keratinocyte apoptosis, and a moderate perivascular infiltrate of lymphocytes in the dermis. The results of patch tests using the patients’ NSO were all positive. The results of gas chromatography combined with mass spectrometry performed on the NSO of 1 patient identified several constituent substances, mainly terpenes, thymoquinone, linoleic acid, and fatty acids.Conclusions and Relevance These cases suggest that acute contact dermatitis due to NSO may induce topically triggered epidermal apoptosis, previously described as the concept of acute syndrome of apoptotic pan epidermolysis. Thymoquinone and p-cymene may be the main agents involved in the pathophysiologic characteristics of this acute contact dermatitis. Clinicians should be aware of such severe reactions to NSO and report these cases to pharmacovigilance authorities.

Cyclosporine has shown promising results for mortality in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. However, available studies included only a small number of patients and did not include a validated and homogenous control group. We present the results from a retrospective monocentric study including 174 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis during 2005–2016. Among them, 95 received cyclosporine (3 mg/kg/day) plus supportive care, and 79 received supportive care only. Both a traditional exposed/unexposed method and a propensity score-matching method were used to compare the progression of skin detachment between day 0 and day 5, the proportion of patients with cutaneous re-epithelialization starting on day 5 or mucosal re-epithelialization on day 10, the duration of progression, and the number of deaths between the two groups. None of these outcomes significantly favored cyclosporine, either by the exposed/unexposed method or the propensity score method. Acute renal failure affected more patients receiving cyclosporine (P = 0.05). Overall, the results of this epidemiological study did not show a beneficial effect of cyclosporine in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. They are discordant with those previously published. The large number of patients and the use of a propensity score method provide valuable insights. The main limitation of the study is the lack of randomization.

Plexiform neurofibromas (PNs) are common and potentially debilitating complications of neurofibromatosis 1 (NF1). These benign nerve-sheath tumors are associated with significant pain and morbidity because they compress vital structures. The mammalian target of rapamycin (mTOR) pathway is a major mediator involved in tumor growth in NF1. We present 3 cases of patients with NF1, aged 8, 16, and 17 years, followed for inoperable and symptomatic PNs; patients received sirolimus for life-threatening and painful neurofibromas after multidisciplinary consultation. Epidemiologic, clinical, and radiologic data were retrospectively collected. The volume of PNs did not differ between baseline and 12-month follow-up and pain was alleviated, with withdrawal of analgesics in 2 cases at 6 months, and significantly decreased for the third case. Sirolimus for inoperable symptomatic PNs in patients with NF1 permitted stabilization of mass and produced unpredictable and important alleviation of pain in all cases with good tolerance. This treatment was proposed in extreme cases, in absence of therapeutic alternatives, after multidisciplinary consensus. The mTOR pathway may be both a major mediator of NF1 tumor growth and regulator of nociceptor sensitivity. mTOR inhibitors clinically used as anticancer and immunosuppressant drugs could be a potential treatment of chronic pain.