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Late-onset adverse events (AEs) of anti-programmed cell death 1 (anti-PD1) antibodies have not been systematically described.The purpose was to evaluate late-onset AEs in melanoma patients treated with anti-PD1 administered for at least 2 years in a real-life setting.Patients were screened from MelBase, a French multicentric biobank dedicated to the prospective follow up of unresectable stage III or IV melanoma. The study included 119 patients who received anti-PD1 during at least 2 years from January 2013 to November 2019. Median follow up was 41.7 months (range, 25.2-57.5 months). Fifty-three patients received nivolumab and 66 patients received pembrolizumab.AEs occurred in 99 patients (83%) with a median time of 13.3 months (range, 0-53.9 months), including severe AEs (grade 3 or 4) in 30 patients (30%). Late-onset AEs, mostly grades 1 or 2, occurred in 51 (43%) patients and led to 5 (4%) hospitalizations, of which 4 were severe. Factors associated with late-onset AEs in multivariate analysis were early-onset AEs (within the first 2 years of treatment) and treatment duration (P = .02 and P = .03, respectively).Our data demonstrate the possibility of late-onset AEs occurring after 2 years of anti-PD1 therapy. Late-onset AEs appear frequently and were mostly mild or moderate. Early-onset AEs and prolonged anti-PD1 treatment may increase the risk of late-onset AEs.

Background Despite a solid rationale, the usefulness of antioxidants in treating vitiligo has not been clearly demonstrated. Combining superoxide dismutase (SOD) with a wheat gliadin biopolymer protects it during the passage through the gastrointestinal tract. Objective To evaluate the efficacy of gliadin‐protected SOD (GP‐SOD), associated with narrowband ultraviolet B(NB‐UVB), for treating vitiligo. Methods We conducted a 24‐week monocentric interventional prospective randomized placebo‐controlled trial in the tertiary center for vitiligo care in the department of Dermatology of Nice University hospital, Nice, France. Subjects with non‐segmental vitiligo affecting more than 5% of the total body surface were included. The subjects received gliadin‐protected SOD (GP‐SOD; 1 g/day for 12 weeks followed by 0.5 g/day for 12 weeks) or placebo in combination with twice‐weekly sessions of NB‐UVB. The primary endpoint was the total repigmentation rate at 24 weeks, compared with baseline, as assessed by investigator‐assessed Vitiligo Extent Score (VES) on standardized pictures. Results A total of 50 patients were included. After 24 weeks, a greater improvement in VES was observed in the GP‐SOD group (19.85%; SE 4.63, P

Immune checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, up to 60% of treated patients do not respond to ICI and/or develop immune-related adverse events (irAEs). Currently, robust and reliable biomarker to predict response and/or occurrence of irAEs to ICI are missing. Herein, we wanted to explore whether germline variants (SNPs) could predict the clinical outcomes of melanoma patients treated with ICIs. We performed a whole exome sequencing using gDNA isolated from blood, from a discovery cohort of 57 patients with metastatic melanoma. The top associations were then tested in a validation cohort of 57 patients. Our work suggests that individual germline genetic variants have no or weak impact on the response to ICIs. Only, variants in IL1RL1 have a significant impact in treatment response. The role of IL1RL1 in the immune response against melanoma and as a theranostic marker warrants further investigations.

This case report describes a 78-year old woman with a stage IIA BRAF wild-type melanoma on the left leg who experienced a grade 2 vitiligo, a marked skin thickening, and painful swelling of the limbs.

International audience; Background: Targeted therapies such as BRAF and MEK inhibitors and immunotherapies have been made available to treat melanoma.Objectives: To provide an overview of the management of the French Stage III melanoma population after complete lymph node resection prior to new adjuvant therapies.Materials and methods: A subgroup data analysis.Results: Data from 1,835 patients were analysed (15.58% Stage IIIA, 39.24% Stage IIIB, 43.92% Stage IIIC and 1.25% Stage IIID). Superficial spreading melanoma was the most frequent (70.98% in Stage IIIA for whom mutation analysis was performed; BRAF mutation was identified in up to 62% Stage IIIA patients). Sentinel lymph node biopsy was performed in 88.46% of Stage IIIA patients, 42.36% of Stage IIIB, 53.97% of Stage IIIC and 34.78% of Stage IIID. Up to 80% of Stage IIIA patients had no adjuvant treatment follow-up. Ulceration (p = 0.004; RR: 2.98; 95% CI: 1.4-6.3) and age at diagnosis (p = 0.0002; RR: 1.04; 95% CI: 1.02-1.06) were significant predictive factors for survival. Adjuvant interferon-α was administered in up to 13.04% of Stage IIID patients.Conclusion: Only a small number of Stage III melanoma patients were treated with interferon-α in adjuvant settings. New adjuvant therapies are currently having an effect on clinical practice in France, increasing survival and decreasing cost.

Immune checkpoint inhibitors (ICIs) have dramatically changed the prognosis of advanced melanoma patients, but also exposed them to immune-related adverse events (irAEs).1 Furthermore, with the combination ipilimumab (IPI) plus nivolumab (NIVO) some rare irAEs, such as myositis and neuromuscular diseases, are increasingly emerging.2 Similar manifestations have been reported during coronavirus disease 2019 (COVID-19)3 and more rarely with the vaccination.4 Because cancer patients exhibit severe and fatal forms of the COVID-19 disease, vaccination is recommended.

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Importance Since 2011, many patients with metastatic melanoma have been treated with ipilimumab therapy and have developed severe immune-related adverse events (AEs). Because several immune therapies are now available to treat metastatic melanoma, a better knowledge of mechanisms and recurrence risks of immune-related AEs is needed before reintroduction of immunotherapies. Objectives To evaluate the risk of a recurrence of immune toxic effects associated with anti–programmed cell death 1 antibody (anti–PD-1) therapy after discontinuation of ipilimumab monotherapy because of severe AEs. Design, Settings, and Participants This cohort study conducted at 19 French melanoma referral centers included patients with metastatic melanoma who experienced severe immune-related AEs after ipilimumab therapy and then were treated with anti–PD-1 therapy between February 1, 2013, and December 31, 2016. The study cutoff was June 1, 2017. Statistical analysis was performed from June 1, 2016, to August 31, 2017. Exposures Monotherapy with at least 1 cycle of ipilimumab that was associated with a grade 3 or 4 immune-related AE and subsequent treatment with at least 1 cycle of an anti–PD-1 (nivolumab or pembrolizumab) therapy. Main Outcomes and Measures The primary outcome was the rate of immune-related AEs associated with anti–PD-1 therapy. Secondary outcomes were characteristics of ipilimumab-related and anti–PD-1 immune–related AEs and overall response rate and overall survival associated with anti–PD-1 therapy. Results Of 56 patients with metastatic melanoma included in the study, all of whom experienced severe immune-related AEs after ipilimumab therapy (31 [55%] male; mean [SD] age, 64 [14.9] years), 20 (36%) experienced at least 1 immune-related AE associated with pembrolizumab (6 of 20 [30%]) or nivolumab (14 of 20 [70%]) therapy. A total of 12 patients (21%) experienced grade 3 or 4 immune-related AEs, and among these patients, 4 (33%) presented with the same immune-related AE as with ipilimumab therapy. Severe immune-related AEs were resolved with use of systemic corticosteroids (7 [58%]) and/or anti–tumor necrosis factor (1 [8%]), and no grade 5 toxic effects were reported. Five patients discontinued anti–PD-1 therapy because of immune-related AEs. The overall response rate was 43%, with a median overall survival of 21 months (interquartile range, 18 to ongoing). Conclusions and Relevance The findings suggest that anti–PD-1 therapy may be associated with reduced risk of toxic effects and improved survival among patients who have experienced severe toxic effects after ipilimumab therapy.

The potential role of CLEC12B, a gene predominantly expressed by skin melanocytes discovered through transcriptomic analysis, in melanoma is unknown. In this study, we show that CLEC12B expression is lower in melanoma and melanoma metastases than in melanocytes and benign melanocytic lesions and that its decrease correlates with poor prognosis. We further show that CLEC12B recruits SHP2 phosphatase through its immunoreceptor tyrosine-based inhibition motif domain, inactivates signal transducer and activator of transcription 1/3/5, increases p53/p21/p27 expression/activity, and modulates melanoma cell proliferation. The growth of human melanoma cells overexpressing CLEC12B in nude mice after subcutaneous injection is significantly decreased compared with that in the vehicle control group and is associated with decreased signal transducer and activator of transcription 3 phosphorylation and increased p53 levels in the tumors. Reducing the level of CLEC12B had the opposite effect. We show that CLEC12B represses the activation of the signal transducer and activator of transcription pathway and negatively regulates the cell cycle, providing a proliferative asset to melanoma cells.

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Introduction L’association de calcipotriol et de betamethasone sous forme de mousse a montre une meilleure efficacite sur le psoriasis que la betamethasone en monotherapie. Il existe tres peu de donnees sur l’evolution de l’infiltrat inflammatoire T CD8+ mais aussi des Natural Killer (NK) sous traitement topique dans le psoriasis. L’objectif de cette etude etait d’etudier l’evolution des populations T CD8+ et NK avant et apres differents traitements topiques. Materiel et methodes Trente patients (3 groupes de 10) ont ete inclus dans une etude comparative intra-individuelle. Les criteres d’inclusion etaient un psoriasis leger a modere sur les deux genoux ou les deux coudes permettant de tester d’un cote la combinaison calcipotriol + betamethasone en mousse et de l’autre une mousse placebo, de la betamethasone en pommade et du propionate de clobetasol en pommade. Des biopsies ont ete effectuees sur chaque zone test avant et apres 4 semaines de traitement. La quantite de lymphocytes T CD8 (CD8+) et de NK (CD56+ GranzymeB +) dans les coupes de peau a ete determinee par immunofluorescence. L’evaluation clinique se faisait a l’aide du target PASI (tPASI). L’evaluation clinique et histologique s’est faite en insu du traitement recu. Resultats L’evolution du tPASI entre S0 et S4 etait de 7,0 a 1,4 pour le calcipotriol-betamethasone en mousse, de 7,4 a 2,5 pour le clobetasol, de 6,8 a 2,7 pour la betamethasone et de 6,9 a 4,4 pour la mousse placebo. Les LT CD8 et les NK sont presents en plus grande quantite dans les peaux lesionnelles que non lesionnelles. Apres 4 semaines de traitement, tous les traitements (mais pas le placebo) ont induit une diminution significative des LT CD8+ dans le derme. Cette diminution etait aussi observee pour les LT CD8+ epidermiques mais elle n’etait statistiquement significative qu’avec le traitement combine. La quantite de NK est egalement augmentee dans la peau lesionnelle et diminue avec les 3 traitements, sans cependant que cela soit statistiquement significatif. Discussion Nos resultats confirment l’augmentation de l’infiltrat LT CD8+ et NK dans les peaux de psoriasis. Ils montrent surtout une diminution de ces infiltrats sous traitements locaux. La population LT CD8+ apparait cependant plus rapidement sensible au traitement que les NK. L’infiltrat inflammatoire cutane lymphocytaire CD8 apparait comme un bon marqueur de la reponse au traitement local dans le psoriasis. La combinaison calcipotriol-betamethasone semble avoir un effet plus important que les steroides seuls sur la diminution de LT CD8 dans la peau psoriasique.

Introduction L’obesite est un facteur de risque de nombreux cancers et peut conferer un pronostic plus pejoratif. Ces donnees restent debattues en ce qui concerne le melanome. Le concept du « paradoxe de l’obesite » a recemment emerge et plusieurs etudes, dont celle de McQuade JL et al., qui avancent qu’un IMC eleve serait associe a un taux de survie superieur chez les patients traites par immunotherapie et therapie ciblee pour un melanome metastatique. Nous avons etudie l’association entre l’IMC et la survie sans progression (SSP) ainsi que la survie globale (SG) chez les patients atteints de melanome metastatique sous traitement systemique. Materiel et methodes Cette etude retrospective a ete menee a partir de la cohorte prospective francaise MelBase. Les patients atteints de melanome metastatique traites en premiere ligne par immunotherapie, therapie ciblee et chimiotherapie etaient inclus. L’IMC etait defini selon les criteres de l’OMS. Les patients maigres (IMC Resultats Un total de 1214 patients ont ete inclus. La majorite etait traitee par immunotherapie, puis par therapie ciblee. Les patients obeses representaient 22 % de la cohorte. La mediane de suivi etait de 13,5 mois. Les patients en surpoids ou obeses ne presentaient pas de beneficie de SSP (p = 0,88) ni de SG (p = 0,25) par rapport aux patients avec un IMC normal. L’analyse univariee et multivariee, stratifiees sur l’âge, le sexe, et certains parametres pronostiques (LDH, nombre de metastases) ne trouvaient par de difference de survie pour les patients en surpoids ou obeses. Discussion Il s’agit de la seconde plus grande cohorte sur le sujet, qui, a l’inverse de celle publiee par Mc Quade et al., ne trouve pas d’association ni positive ni negative entre IMC et SSP/SG chez les patients traites pour un melanome metastatique, quel que soit le traitement. Parce que l’IMC ne reflete pas dans son integralite la composition corporelle (pas de distinction entre masse maigre/masse grasse), il s’agit d’une approche inadaptee, comme l’atteste d’ailleurs l’heterogeneite des resultats et l’absence de reproductibilite entre les etudes. Nous mettons en garde sur l’utilisation de l’IMC comme marqueur predictif de la survie chez les patients traites pour un melanome metastatique.

Resume Introduction Les lymphœdemes primaires sont lies a des anomalies constitutionnelles du systeme lymphatique. Les formes secondaires surviennent apres des lesions du systeme lymphatique, essentiellement apres des traitements de cancers ou par compression extrinseque, notamment ganglionnaire. Il existe aussi de multiples autres causes, dont la filariose qui reste toutefois exceptionnelle en France. Observation Un homme de 52 ans, en excellent etat general, consultait pour une augmentation de volume du membre inferieur gauche apparue deux mois plus tot. L’aspect clinique etait celui d’un lymphœdeme ferme, ne prenant pas le godet, avec presence d’un signe de Stemmer, associe a une hydrocele homolaterale, sans adenopathie loco-regionale palpable. Le bilan initial approfondi, biologique et par imagerie, etait sans particularite. Une lymphoscintigraphie revelait une hypofixation du membre inferieur gauche. La symptomatologie ne cessait de s’aggraver, avec majoration et bilateralisation du lymphœdeme. Deux mois plus tard, on notait l’apparition d’adenopathies axillaires en rapport avec des metastases d’une linite gastrique. Malgre deux lignes de chimiotherapie, le patient decedait huit mois plus tard des suites d’une evolution poly-metastatique. Discussion Notre observation est originale du fait de l’absence de mecanisme compressif a l’origine du lymphœdeme, signe revelateur d’un cancer gastrique. En l’absence de processus compressif, le mecanisme pourrait etre la presence de micro-metastases endo-lymphatiques. Un lymphœdeme acquis des membres inferieurs doit etre reconnu comme un possible signe precurseur et precoce de cancer, en particulier de carcinome gastrique, et doit mener a des explorations approfondies.

Introduction La decouverte de la voie Th17 a permis une avancee therapeutique majeure dans le psoriasis, avec l’enregistrement de 3 biotherapies ciblant l’IL-17. Les effets secondaires cutanes decrits lors des phases III–IV etaient essentiellement des candidoses. La constatation, depuis la commercialisation, d’eruptions psoriasiformes ou eczematiformes nous a conduit a effectuer un recueil large des eruptions non infectieuses sous anti-IL17 pour mieux les caracteriser. Materiel et methodes Etude retrospective, puis prospective du 01/01 au 01/10/18 menee au sein du GRPso. Etaient inclus les patients ayant presente une eruption non infectieuse apparue apres introduction d’un anti-IL17 pour un psoriasis, hors etude industrielle. Les donnees etaient recueillies par questionnaire. Resultats Quarante-sept cas etaient inclus (15 centres). La forme clinique principale etait le psoriasis en plaques (80,8 %) avec 23 % de rhumatisme psoriasique associe. L’âge moyen lors de l’eruption etait de 48,3 ans. Les antiIL17 etaient le secukinumab (n = 31;66 %), l’ixekizumab (n = 13;28 %), non precise (n = 3). Les reactions cutanees etaient classees en 4 categories: – eczematiforme: 24 cas, avec un delai d’apparition moyen de 29 semaines (1,5–156). L’histologie etait de type eczema dans 7 cas/8, – psoriasiforme: 9 cas, differents de l’atteinte psoriasique initiale (inverse, palmo-plantaire), delai d’apparition moyen de 20.5 semaines (1–49). L’histologie confirmait le psoriasis dans 2 cas/2, – reactions d’hypersensibilite: 8 cas, dont 7 angio-oedemes au site d’injection, – divers: 9 cas, 2 vascularites, 1 lichen plan, 1 lichen folliculaire (ces 4 derniers confirmes a l’histologie), 1 acne, 1 folliculite non infectieuse, 1 Verneuil, 1 vulvite aspecifique et 1 dermite seborrheique. Certains patients avaient plusieurs types de lesions. L’arret du traitement etait necessaire dans 72 % des cas, avec relai dans 28 cas (60 %) par une autre molecule. Discussion Nous rapportons ici une serie descriptive originale d’eruptions sous anti-IL17. L’IL17 assure un role central dans l’immunite cutaneo-muqueuse par le recrutement des PNN et l’augmentation de production des peptides antimicrobiens. En ciblant l’IL17, cette protection contre les agressions de la surface epitheliale est amoindrie, comme observe dans la dermatite atopique. Ceci pourrait expliquer les reactions eczematiformes observees au cours de l’etude. Les reactions psoriasiformes pourraient s’apparenter aux reactions paradoxales survenant sous anti-TNF, le blocage de la voie IL17 bloquant aussi la production du TNF. Conclusion A l’instar des anti-TNF, des reactions cutanees inflammatoires parfois severes peuvent survenir sous anti-IL17, necessitant souvent leur arret. L’etude plus approfondie des mecanismes cellulaires et moleculaires impliques dans ces manifestations dysimmunitaires apparait necessaire pour mieux comprendre les interactions entre la voie IL17 et les autres voies d’inflammation.

Introduction La maladie de Hailey–Hailey est une maladie autosomique dominante, secondaire a une mutation d’un transporteur de calcium, caracterisee par un trouble de l’adhesion keratinocytaire avec acantholyse. Nous rapportons trois cas particulierement severes et traites par de la naltrexone a faible dose. Observations Une patiente de 69 ans presentait une maladie de Hailey–Hailey severe atteignant les plis sous-mammaires et inguinaux evoluant depuis de nombreuses annees. Plusieurs lignes therapeutiques s’etaient revelees inefficaces dont le laser CO2 ablatif et l’ixekizumab. La seconde patiente, âgee de 79 ans, presentait une atteinte severe similaire en echec de traitements par toxine botulique, laser CO2 ablatif et ixekizumab. La troisieme patiente âgee de 53 ans presentait une atteinte severe des plis et cutanee en echec de methotrexate, laser erbium, apremilast, secukinumab, ixekizumab. Les trois patientes avaient une atteinte diffuse avec un fort retentissement sur leur qualite de vie. Un traitement par chlorhydrate de naltrexone a ete entrepris a une dose de 3 mg par jour en solution buvable. Apres 1 mois, les trois patientes notaient une nette amelioration de leur qualite de vie avec une diminution des lesions cutanees superieure a 70 %. Aucune poussee inflammatoire et aucun effet secondaire n’ont ete notes depuis le debut du traitement. Cette efficacite est maintenue apres 3 mois de recul pour deux patientes et apres 6 semaines pour la derniere. Discussion Les traitements utilises dans la maladie de Hailey–Hailey sont nombreux mais leur efficacite reste souvent partielle ou temporaire dans les formes severes. Des publications recentes rapportent des cas d’efficacite de la naltrexone faible dose. La naltrexone est un antagoniste aux opioides utilise a forte dose comme antagoniste competitif dans les sevrages de toxicomanie. A faible dose, il existe un effet paradoxal avec augmentation du nombre de recepteurs aux opioides a la surface des keratinocytes et donc augmentation des effets lies a leur activation. On observe un effet antalgique, une meilleure cicatrisation du fait d’une augmentation de la migration et de la proliferation keratinocytaires et une modification de l’homeostasie du calcium qui joue un role dans l’adhesion keratinocytaire. A doses faibles, la tolerance est excellente et les effets indesirables sont presque inexistants. Conclusion Nous rapportons ici trois cas d’efficacite de la naltrexone faible dose dans la maladie de Hailey–Hailey. Ce medicament peut etre envisage du fait de son rapport benefice–risque favorable dans les formes severes avec retentissement sur la qualite de vie. Un nombre plus important de cas et un suivi prolonge apparaissent toutefois indispensables pour determiner le reel interet de cette approche.

IMPORTANCE: Hailey-Hailey disease (HHD) is a rare, autosomal-dominant acantholytic dermatosis characterized clinically by development of recurrent blisters and erosions in friction areas. Despite progression in our understanding of the molecular genetics of HHD, therapy remains suboptimal and there is no known cure. OBJECTIVE: To determine whether the novel phosphodiesterase-4 inhibitor apremilast is effective in the treatment of HHD. DESIGN, SETTING, AND PARTICIPANTS: Clinical case series of 4 patients with severe, treatment-resistant HHD at an outpatient clinic in the Department of Dermatology of Nice University Hospital, Nice, France. The patients were treated with apremilast; after the initial titration, the dose was 30 mg, twice daily. MAIN OUTCOMES AND MEASURES: Objective clinical response was assessed by the treating dermatologist using the physician global assessment score; recorded adverse effects were monitored throughout the treatment at intervals of 2 to 3 months. RESULTS: Three women and 1 man, with a mean age of 56 years, were treated and followed up for 6 to 10 months. Family history of the disease was noted in 3 (75%) of the cases. The lesions affected the axillary regions (75%), submammary regions (75%), inguinal regions (100%), and back and neck areas (50%). An improvement in the symptoms was reported by all of the patients after a treatment period of 1 month. After 6 months, the improvement of HHD lesions was reported as moderate to almost cleared among the patients. However, 2 patients developed some flares after 6 to 10 months of treatment and stopped apremilast therapy. One of the patients developed uncontrolled diffuse lesions and apremilast was reintroduced, resulting in partial control of her disease. CONCLUSIONS AND RELEVANCE: Apremilast appears to offer a low-risk therapeutic alternative or adjunct in resistant and severe forms of HHD. A prospective controlled trial with long-term follow-up is required to confirm these preliminary observations.

Introduction Le carcinome a cellules de Merkel (CCM) est une tumeur neuroendocrine cutanee primitive rare. Son incidence est en hausse et son pronostic severe. Peu de donnees nationales sont disponibles. Notre objectif est de faire une mise a jour des donnees francaises concernant les cas de CCM dans le reseau CARADERM. Materiel et methodes Il s’agit d’une etude prospective et retrospective epidemiologique multicentrique. Nous avons extrait tous les cas de CCM du reseau CARADERM inclus du 01/01/2015 au 30/04/2020. Resultats Nous avons analyse 875 cas. Il existait une predominance masculine (55 %) avec un âge median au moment du diagnostic de 78 ans. Vingt-huit pour cent des patients avaient eu au moins un cancer extra-cutane, 27,5 % des patients un autre cancer cutane. 16,6 % des patients etaient immunodeprimes. Parmi les CCM, 38,5 % etaient localises sur la tete et le cou. La taille mediane du primitif etait de 21 mm. Aucun primitif cutane n’etait identifie dans 8 % des cas, il existait alors une atteinte ganglionnaire dans 100 % des cas, associee a une atteinte viscerale dans 28,6 % des cas. Le ganglion sentinelle etait realise chez 49 % des patients pour qui il etait indique. Sa realisation etait moins frequente dans les CCM de la tete et du cou (p Discussion Notre cohorte est la plus importante en France et continue de croitre. Nos resultats sont coherents avec les donnees de la litterature. CARADERM est un outil precieux pour recueillir des donnees nationales de pratique en vraie vie sur cette tumeur rare, qui pourront etre utiles pour generer des etudes, identifier les ecarts par rapport aux referentiels et ameliorer la prise en charge.

The risk of relapse after successful repigmentation in vitiligo is estimated to 40% within the first year. It has been shown in atopic dermatitis that continuous low-level use of topical corticosteroids and calcineurin inhibitors in previously affected skin can prevent new flares. We hypothesized that a twice-weekly application of 0.1% tacrolimus ointment might be effective for maintaining repigmentation in therapeutically repigmented lesions of vitiligo patients. After randomization, sixteen patients with 31 patches were assigned to the placebo group and 19 patients with 41 patches were assigned to the tacrolimus group. In the intention-to-treat analysis, 48.4% of lesions showed depigmentation in the placebo group, whereas 26.8% did in the tacrolimus group (P=0.059). The intention-to-treat results did not remain significant after adjustment for within-patient clustering, odds ratio (OR) 2.55; 95% confidence interval (CI; 0.65–9.97); P=0.1765. The per-protocol analysis (n=56) showed that 40% of lesions had some depigmentation in the placebo group, whereas only 9.7% did in the tacrolimus group (P=0.0075). The per-protocol results remained significant after adjustment for within-patient clustering: OR 6.22; 95% CI (1.48–26.12); P=0.0299. Our study shows that twice-weekly application of 0.1% tacrolimus ointment is effective in preventing the depigmentation of vitiligo patches that have been previously successfully repigmented.

Topical or intralesional corticosteroids are referred to as gold standard treatments for keloids. Recent studies showed that ablative fractional laser (AFL) treatment facilitates delivery of topical drug deeply into the skin by creating vertical channels. The objective of the present study was to assess the ablative erbium laser in fractionated mode, combined with topical high potent corticosteroid cream for treating resistant keloid scars. We conducted a retrospective study in the laser center of the Department of Dermatology (University Hospital of Nice, France), from January 2010 to June 2012, on patients with keloids who were resistant to a first-line of treatment. A 2940-nm ablative fractional erbium laser was used. Topical betamethasone cream was applied twice a day under occlusion with transparent film dressings. A total of 23 patients with 70 keloids were treated from January 2010 to June 2012. The median percentage of improvement was 50% (range -43 to 84). The mean follow-up was 8 months (range 3-18), and a recurrence was observed for eight lesions (22%). Although this observation warrants a prospective comparative evaluation, it supports the interest of the laser-assisted delivery of steroids for treating keloids scars.

circadian clocks regulate a wide range of functions of human body organs, including the skin. Studies have shown that the key genes responsible for the differentiation and the proliferation of skin cells are regulated according to a circadian rhythm[1, 2]. This ascertainment might have some therapeutic consequences. Indeed, topical steroids are usually prescribed once daily but the time of application is not based on any scientific data. We hypothesized that the efficacy of topical corticosteroids in psoriasis might be influenced by the time of their application. This article is protected by copyright. All rights reserved.

e21051 Background: Ingenol mebutate gel is indicated for the treatment of actinic keratoses. In vitro, it has been shown that ingenol mebutate can induce the apoptosis of melanoma cells, but robust clinical data are missing with only few case reports reported.The objectives of the current study was to assess the efficacy and safety of ingenol mebutate for the treatment of lentigo maligna (LM). Methods: We conducted a prospective, multicentre, and single-arm phase 2 trial (NCT02723721), from June 2016 to November 2017. This trial was planned according to Simon’s optimal two-stage design for a total sample size of 23 subjects. Adults with LM of the head were included. Ingenol mebutate gel 150 µg/g was applied daily for 3 consecutive days (one cycle). For patients having no remission or only partial remission at 2 months, a second cycle was done. Patients were evaluated 2 months after the (re)treatment and then every 3 months for 36 months if a complete response (CR) was obtained. The primary endpoint was the CR, defined as the complete clearing of the LM evaluated at 2 months clinically and histologically. Results: Twelve patients with a median age of 73 years were recruited. Only 2 achieved a CR; one patient relapsed during the first year following the treatment. Forty-seven adverse events related to ingenol mebutate were declared. Most were grade 3-4 (66%), but all were resolved without any sequelae. The mean maximum local skin reaction score was 12 (min: 3 – max: 22). These results should be interpreted with caution, because this study has limitations, such as the lack of a comparative arm and the heterogeneity of LM (size and localization). Conclusions: To our knowledge, we report the first prospective study evaluating the efficacy and safety of IM in patients with LM of the head. Unfortunately ingenol mebutate is not an effective treatment of LM in this indication at the concentration of 150 µg/g. Its use with a more intense regimen (more cycles and/or highest concentration (500 µg/g)) is also limited by a poor safety profile. Clinical trial information: NCT 02723721.

Background Limited information is available regarding factors associated with long-term drug survival of infliximab for psoriasis in real life. Objectives The main aim pf this study was to identify predictors of long-term (>12 months) drug survival among patients treated with infliximab for psoriasis in a real-world clinical setting. Methods Retrospectively collected data, relating to disease, patient characteristics and treatment procedures, in a multicentre observational cohort of patients with moderate-to-severe plaque psoriasis treated with infliximab at eight university hospitals, 120 of whom maintained a response to infliximab for more than 12 months, were compared with prospectively collected data in the same centres from 54 patients who experienced secondary loss of response within a 12-month period. Results Mean duration of drug survival of infliximab in patients with long-term drug survival was 41.12 months ± 20.64 SD vs. 8.5 months ± 2.43 SD in patients with a secondary loss of response. Multivariate analysis identified greater disease severity at treatment onset (PASI score >12) (OR = 5.18, 95% CI: 1.60–16.77, P = 0.006), high levels of initial psoriasis clearance (PASI-90 reduction or equivalent) (OR = 18.50, 95% CI: 4.56–74.45, P = 0.0001) and combination with methotrexate (OR = 13.15, 95% CI: 1.46–118.79, P = 0.022) as independent predictors of long-term drug survival and sustained efficacy of infliximab. Conclusion Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials.

Background Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non-plaque psoriasis. Objectives To prepare for evidence-based recommendations concerning the practical use of CyA in psoriasis, we performed a systematic review to better define treatment strategy, risk of kidney toxicity and evidence for use in non-plaque psoriasis. Methods A systematic search was performed on PubMed, Cochrane and Embase databases, using the key-words ‘psoriasis’, ‘CyA’, ‘nephrotoxicity’ during the period from 1980 to June 2010. Results The initial literature search identified 428 articles. The final selection included 16 randomized controlled trials (RCT) for treatment strategy, 25 articles (histological studies and RCT) for risk of kidney toxicity and 10 articles (RCT, prospective studies and case series) for use in non-plaque psoriasis. Higher doses of CyA of 5 mg/kg produced Psoriasis Area Severity Index (PASI) 75 response in between 50 and 97% of patients, whereas lower doses of 2.5 mg/kg yielded PASI 75 in between 28 and 85%. CyA could maintain remission at doses of at least 3 mg/kg/day. Low calory diet in obese patients was shown to improve CyA efficacy. More than 50% of the patients treated with CyA may have an increase in serum creatinin value over 30% of baseline if treatment is prolonged for 2 years. CyA at a dose of 2.5 mg/kg/day was effective for 89% of patients with palmoplantar pustulosis. More than 50% of the patients with erythrodermic psoriasis obtained a significant improvement at doses between 3 and 5 mg/kg/day at 2–4 months. CyA was more effective than etretinate on nail psoriasis. Conclusion Oral CyA is indicated for patients with plaque psoriasis, pustular psoriasis or erythrodermic psoriasis. The starting dose of 5 mg/kg is associated with a higher degree of clearance. The benefit-risk appears to be better for patients without risk factors for nephrotoxicity: non-obese patients without hypertension and aged below 60. Although CyA is ideally suited for crisis intervention, continuous maintenance treatment with CyA may be envisaged in some patients provided serum creatinin is regularly monitored and the cumulative treatment duration is preferably limited to 2 years or less.

Background There is a high level of heterogeneity regarding the practical use of conventional systemic treatment in psoriasis. Objectives The aim of this study was to develop evidence-based recommendations for the use of traditional systemic treatments in psoriasis in daily clinical practice: methotrexate (MTX), cyclosporin and retinoids. Methods A scientific committee selected clinically relevant questions concerning the use of MTX, cyclosporin and retinoids in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2010, including 66 dermatologists. Recommendations for daily use of psoriasis systemic treatments were made during interactive workshops where the evidence was reviewed. Agreement among participants and the impact of the recommendations on clinical practice were systematically assessed using voting procedure in a plenary session. Results A total of 2800 references were identified, among which 122 articles were included in the systematic reviews. Three key recommendations on the use of MTX in psoriasis were formulated, including optimal dosage and route, use of folic acid, risk factors for liver fibrosis and monitoring of hepatotoxicity. The recommendations for cyclosporin in psoriasis focused on the modalities of cyclosporin prescription: dosage, scheme of treatment, optimal duration of treatment, renal toxicity monitoring and evidence for use of cyclosporin in non-plaque psoriasis (erythrodermic, pustular and ungueal). Recommendations were also made concerning the efficacy and safety of retinoids (mainly acitretin) in plaque and non-plaque psoriasis. Conclusions These recommendations for the use of traditional systemic therapies in psoriasis are evidence based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the agreement of physicians who were not involved in generating the recommendations.

Background/Aim To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. Objective To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. Methods A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. Results Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. Conclusions Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15–25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity.

Background There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes. Objective To systematically review the available literature on: (i) modalities of administration and prescription of oral retinoids as single agent or combined therapy for the treatment of plaque-type psoriasis (PV), nail psoriasis and localized and generalized pustular psoriasis : initial and optimal dosage; (ii) skeletal toxicity of retinoid for the treatment of psoriasis. Methods A systematic literature search was carried out in MEDLINE, EMBASE, and Cochrane Library databases from 1975 to 2010 searching for randomized controlled trials and observational studies evaluating 1) various dosages of retinoid in psoriasis and 2) skeletal toxicity of retinoid in psoriasis. Articles were limited to human subjects and English/French languages. Results Efficacy of retinoids in psoriasis. Among 1348 identified references, 44 published studies were included. Starting daily dosages between 10 and 25 mg and stepwise escalation were associated with higher clinical efficacy and lower incidence of adverse events in comparison with higher doses and regimens rapidly reaching optimal dose. Retinoids as single agent therapy appeared to show limited efficacy in PV, while the good clinical efficacy reported in pustular forms should be cautiously considered, given the spontaneously remitting course of the disease. Combining retinoids with phototherapy appeared to be highly effective in patients with PV. Potential skeletal toxicity of retinoids. 15 published studies out of 105 identified references were included. There is no strong evidence of an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids. Conclusion Acitretin appears to provide better efficacy in pustular psoriasis than in PV as a single agent treatment. There is no evidence for skeletal toxicity of retinoids in the setting of psoriasis, and accordingly monitoring this risk through X-ray is not warranted.

Introduction Les anti-PD1 ont ameliore le pronostic des patients atteints de melanome avance. Ces immunotherapies sont associees a des effets secondaires immunologiques. Nous rapportons, a notre connaissance, le premier cas de sarcoidose pulmonaire induite par le nivolumab. Observations Un homme de 56 ans, sans antecedents, avait en 2012 un curage ganglionnaire axillaire droit (7N+/27) revelateur d’un melanome de l’epaule gauche (SSM, Breslow 0,2 mm sans ulceration ni mitose). Huit mois apres, apparaissaient des metastases hepatiques, pulmonaires et ganglionnaires mediastinales (biopsie des ganglions mediastinaux) et un traitement par vemurafenib plus placebo/cobimetinib etait debute (BRAF [+], etude CoBRIM). En juin 2015, 4 lesions cerebrales survenaient et le nivolumab etait introduit en plus d’une radiotherapie stereotaxique cerebrale. Le patient etait alors en parfait etat general. Une semaine apres la 2e perfusion, il developpait une dyspnee stade I, sans fievre, un syndrome sec oculaire associe a un œdeme de la face et une parotidomegalie. Le scanner retrouvait des opacites en verre depoli et des micronodules autour de la scissure principale (Fig. 1). Les ganglions mediastinaux et les metastases pulmonaires connus etaient stables. Le PET-SCAN retrouvait une hyperfixation des glandes parotides. Les EFR et la gazometrie etaient normales. La bronchoscopie avec lavage bronchiolo-alveolaire retrouvait 32 % de lymphocytes avec un ratio CD4:CD8+ augmente a 4,2 (norme : 0,9–2,5) sans cellules malignes. Les investigations microbiologiques revenaient negatives. Les biopsies bronchiques retrouvaient un granulome epithelioide gigantocellulaire sans necrose caseeuse. La calcemie et l’ECA etaient normales. Sur ces donnees et les proprietes immunologiques du nivolumab, le diagnostic de sarcoidose pulmonaire grade 1 secondaire au nivolumab etait retenu. L’evolution clinique et radiologique (Fig. 2) etait favorable apres 1 mois de corticotherapie et apres avoir decale la 3e perfusion d’une semaine. Cependant, l’evaluation tumorale d’octobre 2015 montrait une progression cerebrale de la maladie et le patient decedait un mois plus tard. Discussion Plusieurs cas de sarcoidose ont ete rapportes au cours de l’histoire naturelle du melanome ou lors de son traitement. Recemment, 2 cas ont ete rapportes avec le pembrolizumab au cours d’un sarcome avance. Nous rapportons, a notre connaissance, le premier cas de sarcoidose pulmonaire induite par nivolumab. L’aspect radiologique et la confirmation histologique de ganglions mediastinaux metastatiques suggerent fortement que les lesions pulmonaires, presentes avant le debut du nivolumab, etaient aussi d’origine metastatique. Conclusion Avec l’utilisation croissante des anti-PD1, il est important d’alerter le clinicien sur le risque de reaction sarcoidosique secondaire et de prendre en consideration le risque potentiel d’exacerbation d’une sarcoidose chez des patients atteints et pour qui une telle immunotherapie serait envisagee.

Introduction Plus de 50 % des melanomes presentent une mutation du gene BRAF ou NRAS. Les inhibiteurs de BRAF ont permis d’ameliorer la survie globale des patients traites pour un melanome metastatique. La detection de ces mutations repose sur des techniques de sequencage de l’ADN. Les objectifs de ce travail sont d’evaluer la faisabilite et les performances analytiques du systeme Biocartis Idylla™ (processus automatise couplant l’extraction, le sequencage et l’analyse de l’ADN), pour la caracterisation des mutations BRAF et NRAS tissulaire et plasmatique chez des patients atteints de melanome en phase metastatique. Materiel et methodes Le statut mutationnel a ete etudie chez 20 patients (10 patients mutes BRAF, 5 patients mutes NRAS, 5 patients non mutes) suivis pour un melanome metastatique, a la fois sur coupe tissulaire (copeaux de paraffine) et sur l’ADN plasmatique avant et apres traitement (cible ou systemique). Les analyses ont ete realisees avec les kits tissu Idylla™ BRAF Mutation Test (CE-IVD) ; BRAF-NRAS-EGFR Mutation Assay (RUO) et plasma ctBRAF ; ctNRAS Mutation Assay (RUO). Les resultats ont ete compares aux deux techniques de reference accreditees ISO 15189 et realisees dans le laboratoire : le pyrosequencage (kits CE-IVD - Therascreen BRAF et NRAS Qiagen, Hilden, Germany) et l’immunohistochimie BRAFV600E (clone VE1, Ventana, Tucson, AZ). Resultats Le genotypage par le systeme Idylla est simple d’utilisation et rapide (environ 90 min). Les resultats de l’analyse tissulaire BRAF et NRAS sont concordants avec le pyrosequencage [85 % (k = 0,69) et 93 % (k = 0,81) respectivement] et l’immunohistochimie BRAFV600E [77 % (k = 0,49)]. L’analyse plasmatique montre qu’une mutation de BRAF ou de NRAS etait detectable chez 80 % (13/15) des patients avant traitement et 13 % (2/15) patients apres traitement. Ces deux derniers patients sont en progression selon les criteres Recist. La mutation etait donc indetectable apres traitement chez 13/15 patients, ce qui semble etre associe a une bonne reponse therapeutique initiale (p = 0,09). Discussion Certains resultats discordants sur l’analyse tissulaire sont en cours de verification (par analyse par PCR digitale) et pourraient etre lies a une plus grande sensibilite de la technique Idylla permettant de detecter jusqu’a 1 % d’allele mute versus 5 % pour le pyrosequencage. Conclusion La technique Idylla™ est tres specifique et tres sensible pour la detection des mutations sur les genes BRAF et NRAS sur tissu et ADN plasmatique et est une bonne alternative aux methodes conventionnelles de sequencage. L’analyse « en-temps reel » et la facilite de mise en œuvre technique en font un systeme compatible avec une utilisation « en routine » pour le suivi et le monitoring de la maladie residuelle des patients atteints de melanomes metastatiques apres traitement.

Introduction Le lymphœdeme est une affection du systeme lymphatique, primaire en rapport avec une hypoplasie lymphatique congenitale, ou secondaire le plus souvent a une infection parasitaire, une chirurgie ou un cancer par compression extrinseque. Nous rapportons un cas de lymphœdeme acquis du membre inferieur revelant un cancer gastrique sans compression extrinseque. Observations Un homme de 52 ans, sans antecedent, consultait pour un œdeme du membre inferieur gauche, apparu 2 mois apres une chirurgie de volvulus de Meckel. L’anamnese ne revelait aucun autre evenement loco-regional. Le patient etait asymptomatique en bon etat general. L’aspect clinique etait celui d’un lymphœdeme avec signe de Stemmer positif, associe a une hydrocele, sans adenopathies palpables. Le bilan sanguin etait normal (notamment serologie filariose, Quantiferon ® , marqueurs tumoraux). Un scanner abdominal montrait des ganglions mesenteriques interpretes comme secondaire a la chirurgie, non compressifs et une infiltration sous-cutanee du membre inferieur gauche. Le doppler arterio-veineux et la FDG-PET etaient strictement normaux. Une lymphoscintigraphie isotopique revelait une absence de circulation lymphatique du membre inferieur gauche. Malgre des mesures symptomatiques, le tableau ne cessait de s’aggraver avec majoration et bilateralisation du lymphœdeme. Deux mois plus tard apparaissaient des adenopathies axillaires fermes. Une biopsie ganglionnaire revelait une infiltration par des cellules en bague a chaton marquees a l’anti-cytokeratine signant une origine digestive. Une fibroscopie gastrique montrait une infiltration de la muqueuse secondaire a un adenocarcinome de type linite gastrique. Discussion Le lymphœdeme acquis de cause tumorale est le plus souvent secondaire a un curage ganglionnaire ou a une compression extrinseque. Cette observation originale par le fait que le lymphœdeme est revelateur d’un cancer gastrique, l’est encore plus car le mecanisme est non compressif. Seize cas similaires ont ete rapportes, parmi lesquels, comme chez notre patient, le lymphœdeme precedait le diagnostic de cancer de plusieurs mois. Le cancer gastrique a cellules en bague a chaton est present dans la moitie des cas. L’atteinte clinique dans notre cas pourrait s’expliquer par des micrometastases non compressives du systeme lymphatique comme cela a ete decrit dans un article rapportant un lymphœdeme des organes genitaux. Dans ce cas, la biopsie cutanee scrotale a permis de poser le diagnostic en montrant des vaisseaux lymphatiques envahis par des cellules tumorales gastriques. Notre patient a refuse un tel prelevement. Conclusion Un lymphœdeme acquis du membre inferieur peut etre un signe precurseur precoce de cancer gastrique et doit mener a des explorations exhaustives. En l’absence de cause compressive, un envahissement lymphatique doit etre evoque.

Introduction L’hidrosadenite suppuree (HS) est une dermatose inflammatoire chronique impactant considerablement sur la qualite de vie. Il existe plusieurs traitements, notamment les anti-TNF-α comme l’adalimumab (ADA) et l’infliximab (IFX) dont l’efficacite reste toutefois aleatoire. L’identification de marqueurs predictifs de la reponse a ces biologiques apparait donc d’un grand interet. Materiel et methodes Le serum des parametres suivants etait recueilli, chez des patients atteints d’HS modere a severe (Hurley stade 2–3 depuis au moins 6 mois), a la semaine 0 (S0), S2, S8, S14 : TNF-α, interleukine (IL)-1β, IL-6 et CRP-us. Le critere principal d’efficacite etait le PGA. L’activite de la maladie et la gravite etaient evaluees par le score Hurley, la douleur par l’EVA et la qualite de vie par l’echelle DLQI. L’objectif de cette etude, pilote monocentrique prospective, etait de determiner si le profil inflammatoire de ces patients pouvait etre predictif de la reponse a l’IFX. Resultats Treize patients etaient inclus, aucun effet secondaire n’etait observe excepte un psoriasis pustuleux paradoxal. Une reponse objective etait observee pour 9 patients. Deux patients, non repondeurs, etaient sous-doses avec un residuel d’IFX Discussion Ces premiers resultats suggerent que les niveaux initiaux de CRP-us et surtout d’IL-6 sont des marqueurs potentiels de reponse a l’IFX dans l’HS. Des etudes prospectives realisees avec l’ADA ont montre la necessite d’utiliser une dose 2 fois plus elevee que dans le psoriasis. Dans notre etude, la dose d’IFX etait de 5 mg/kg comme dans le psoriasis. Aussi, il est necessaire d’etre prudent avant d’extrapoler ces resultats avec l’ADA 40 mg/semaine comme il est recommande pour l’HS. Conclusion L’IL-6 et la CRP-us sont des marqueurs predictifs potentiels de reponse a l’IFX dans l’HS. Des etudes menees, sur de plus grandes cohortes de patients randomises et traites par ADA, sont necessaires pour confirmer nos resultats dans l’optique d’epargner aux patients des traitements inutiles et pour reduire les couts de sante.

Introduction La maladie de Hailey-Hailey, ou pemphigus benin chronique familial, est une genodermatose autosomique dominante rare caracterisee par une atteinte vesiculeuse, erosive et fissuraire douloureuse des plis. Des anomalies de signalisation intracellulaire sont dues aux mutations du gene ATP2C1 , codant pour une pompe a calcium appelee SPCA1 et qui conduisent a une acantholyse intra-epidermique responsable des manifestations cliniques de la maladie. Les UV, la sudation et le frottement et la surinfection sont des facteurs aggravants frequents mais les medicaments sont tres rarement responsables d’une exacerbation des symptomes. Seuls quelques cas d’aggravation ont ete rapportes apres prise de lithium. Le mecanisme suspecte serait une diminution de l’expression des ATPases de calcium SERCA2 et SPCA1 ou une modification de l’homeostasie cellulaire du calcium. Observations Nous rapportons le cas d’une femme de 52 ans ayant une maladie de Hailey-Hailey controlee par des applications episodiques de dermocorticoides depuis 30 ans. En 2011, des poussees severes et recidivantes etaient notees quelques semaines apres l’introduction d’un traitement par topiramate pour une migraine. La severite des symptomes necessitait 3 hospitalisations en 2 ans. Apres 2 ans, une amelioration de la migraine conduisait a l’arret du topiramate. Une amelioration tres sensible de son Hailey-Hailey etait alors notee. En 2015, le topiramate etait a nouveau introduit (50 mg/j) et dans les 3 semaines, la patiente presentait une nouvelle aggravation de sa maladie. Dans les 3 mois suivants, elle avait des poussees severes et recurrentes repondant tres difficilement aux applications quotidiennes de dermocorticoides. Devant la forte suspicion de son imputabilite, le topiramate etait alors arrete. Une amelioration sensible etait observee dans les 15 jours suivant son arret. Avec 10 mois de recul, sa maladie reste aujourd’hui peu evolutive avec uniquement de rares poussees de faible intensite et rapidement corticosensibles. Discussion A notre connaissance, il s’agit du premier cas rapporte d’aggravation de la maladie de Hailey-Hailey par le topiramate. Ce dernier est un medicament antiepileptique indique dans le traitement prophylactique de la migraine. Parmi ses multiples mecanismes d’action, il inhibe les canaux calciques de type-L et reduit les signaux secondaires calcium-dependant. Dans le cas de notre patiente, l’aggravation rapide des poussees apres l’instauration de topiramate et l’amelioration spontanee a son arret et ce, a 2 reprises, suggerent fortement son imputabilite dans l’exacerbation des lesions de Hailey-Hailey. Nous pensons que le topiramate peut aggraver la maladie de Hailey-Hailey par ses effets sur les canaux calciques et la quantite intracellulaire de calcium qui ont un role important dans la pathogenie de cette maladie. Conclusion Le topiramate apparait donc comme un medicament pouvant aggraver les manifestations de la maladie de Hailey-Hailey.