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The occurrence or the worsening of cutaneous T-cell lymphoma (CTCL) during or after a treatment with dupilumab has recently been reported in a limited number of patients including a small series of 7 patients, of whom 4 had been previously diagnosed with atopic dermatitis (AD).1 We hereby describe a previously unreported observation of systemic CD30+ lymphoproliferation occurring during treatment with dupilumab, adding to the literature of new-onset cutaneous lymphomas associated with dupilumab therapy.

Dupilumab is a therapeutic antibody targeting IL-4 and IL-13 receptor subunit alpha used for the treatment of atopic dermatitis (AD) patients. Cases of psoriasis-like reactions induced under dupilumab treatment (DI-Pso) for AD were recently reported. To understand the pathogenesis of DI-Pso, we performed gene expression profiling studies on skin biopsies of DI-Pso (n=7) compared with plaque psoriasis (PSO), AD and healthy controls (HC) (n=4 each). Differential gene expression was performed using enrichment and gene ontology analysis. Gene expression was validated by qPCR and protein levels assessed by immunohistochemistry. Transcriptomic and protein analysis of DI-Pso compared with HC, PSO and AD skins revealed an activation of Th17/IL-23 pathways associated with a significant expression of IL-36, surrogate marker of pustular psoriasis (PP). By contrast, Th2 representative genes' expression were strongly decreased in DI-Pso across comparison. Matching analysis with public data of PP skin corroborated that DI-Pso and PP upstream regulators overlap, greater than with PSO. Furthermore, DI-Pso showed strongly decreased expression of many barrier skin genes compared with HC, PSO and AD. Our data indicate that pathogenesis of DI-Pso relied on a shift of skin immune responses from a Th2 to an IL-36 and Th17 polarization and on intensified skin barrier alterations.

Human immunoglobulins are used for treating diverse inflammatory and autoimmune disorders. Eczema is an adverse event reported but poorly described.To describe the clinical presentation, severity, outcome, and therapeutic management of immunoglobulin-associated eczema.This retrospective and descriptive study included a query of the French national pharmacovigilance database, together with a national call for cases among dermatologists.We included 322 patients. Eczema occurred preferentially in men (78.9%) and in patients treated for neurological pathologies (76%). The clinical presentation consisted mainly of dyshidrosis (32.7%) and dry palmoplantar eczema (32.6%); 5% of cases exhibited erythroderma. Sixty-two percent of the eczema flares occurred after the first immunoglobulin course. Eczema was observed with 13 intravenous or subcutaneous immunoglobulin types and recurred in 84% of patients who maintained the same treatment and in 68% who switched the immunoglobulin type. After immunoglobulin discontinuation, 30% of patients still had persistent eczema.Retrospective study, with possible missing data or memory bias.Immunoglobulin-associated eczema occurred with all immunoglobulin types, preferentially in patients with neurologic diseases who required prolonged immunoglobulin treatment. Recurrence was frequent, even after switching the immunoglobulin type, which can lead to a challenging therapeutic situation when immunoglobulin maintenance is required.

Background and Objectives: Bullous pemphigoid (BP) clinical profile may have evolved during the last 2 decades. A retrospective, single-centre analysis investigated a possible shift of clinical presentation of the disease over time regarding both lesions’ clinical pattern and locations and more particularly an increased frequency of characteristics considered as less classical regarding the usual clinical description of BP. Patients and Methods: Initial clinical data from all BP patients treated between January 2001 and April 2017 in a reference centre were collected and compared between four 4-year successive chronological subsets (G1 to G4). Results: 213/312 patients retained for final analysis (68.3%) displayed at least one initial non-classical characteristic, mainly head and neck, palmo-plantar, and/or mucosal involvement. Chronological analysis confirmed a significant increase over time of the percentage of patients displaying such features (G1 57.9% vs. G4 73.7%, p = 0.041). Conclusion: Changes in BP clinical pattern may have occurred over the last two decades with the progressive emergence of forms with a number of less classical features. No significant clinical difference was observed between patients receiving or not DPP4 inhibitors at the time of diagnosis.

International audience; Acquired angioedema with C1-inhibitor deficiency is a rare and peculiar entity belonging to the spectrum of bradykinin angioedemas. It usually occurs in subjects over 60 years old, and is mostly associated with a B-cell lymphoid hemopathy or a monoclonal gammopathy.The diagnosis relies on at least one angioedema episode, lasting more than 24 h, and on the decrease of functional C1-inhibitor. Low C1q is observed in 90% of patients, and an anti C1-inhibitor antibody is found in 50% of patients.The treatment of severe attacks relies on icatibant or C1-inhibitor perfusions. Long term prophylaxis in patients with frequent attacks requires treatment of the associated hemopathy if so. In case of idiopathic angioedema, tranexamic acid and danazol may be used, provided that there is-no thrombophilia; as well as rituximab as second-line treatment. Inhibitors of kallikrein still need to be evaluated in this therapeutic indication.; Les angiœdèmes par déficit acquis en C1-inhibiteur représentent une entité rare au sein des angiœdèmes bradykiniques. Ils diffèrent des formes héréditaires essentiellement par le terrain, car ils surviennent chez des sujets âgés de 60 ans en moyenne, et sont, le plus souvent, associés à une hémopathie lymphoïde B de bas grade ou à une gammapathie monoclonale.Leur diagnostic repose sur la survenue d'au moins un épisode d'angiœdème durant plus de 24 heures et sur la diminution de C1-inhibiteur fonctionnel. Une baisse du C1q est présente dans 90 % des cas et un anticorps anti C1-inhibiteur chez 50 % des patients.Le traitement des crises sévères repose sur l'icatibant ou l'administration de C1-inhibiteur. Le traitement préventif, indiqué en cas de crises fréquentes, nécessite le traitement de l'hémopathie identifiée. En l'absence de pathologie associée, l'acide tranexamique ou le danazol sont des options à envisager en l'absence de facteur de risque de thrombose, et le rituximab peut être proposé en cas d'échec. La place des inhibiteurs de la kallicréine sera à définir dans cette indication.

International audience; Hemophagocytic lymphohistiocytosis (HLH) has been only rarely reported in patients with BRAF-mutated advanced melanoma treated with targeted therapies and never with first-line dabrafenib/trametinib combination thus far. Two patients treated with first-line dabrafenib and trametinib combination therapy for metastatic melanoma presented with sudden occurrence of fever, cytopenia, rhabdomyolysis, hepatic cytolysis, hypertriglyceridemia and very high ferritin levels after few weeks of treatment, associated with concomitant epstein-barr virus (EBV) reactivation in one patient. In both cases, drug-induced HLH was primarily considered owing to a high H-score and the absence of other etiology. Patients rapidly improved after treatment discontinuation associated with oral steroids in one patient and did not relapse after subsequent treatment resumption with a concurrent anti-BRAF/anti-MEK combination. In metastatic melanoma HLH may occur either spontaneously in the absence of any treatment as a paraneoplastic condition, related to an intercurrent infection or drug-induced mainly with various immunotherapy or with dabrafenib and trametinib following immunotherapy. However, such observations are scarce and these are the first cases of HLH occurring during first-line treatment with dabrafenib and trametinib in advanced melanoma to our knowledge. Pathomechanisms remain to be elucidated since triggering factors may encompass the treatment itself but also other significant actors including viral reactivation along with the underlying disease. The liability of treatment should be considered in cases of HLH occurring in patients with advanced melanoma successfully treated with a combined targeted therapy. A rechallenge with a concurrent anti-BRAF/anti-MEK can be proposed in this setting.

Lenalidomide (LND), a synthetic thalidomide analog mainly used in haematological malignancies has proved efficient and well-tolerated in small case series of refractory Cutaneous Lupus Erythematosus (CLE). A retrospective survey of CLE patients treated with low-dose LND in three institutional Departments of Dermatology was conducted to further assess the benefit/risk ratio of this molecule in this setting (Institutional Review Board for ethical issues of University Hospital of Montpellier 2018_IRB-MTP_11-01). Primary endpoints were best overall response (BOR) obtained with initial dosage or after dose adjustment and time to achieve BOR.

International audience

Optimal doses of total skin electron beam therapy for mycosis fungoides remain to be established. Clinical efficiency and adverse effects of middle-dose (25 Gy) vs. low-dose (10-12 Gy) total skin electron beam therapy were retrospectively compared in a series of 14 and 12 mycosis fungoides, respectively. Overall skin response rate was 96.2% (92.9% middle-dose and 100% low-dose; not significant (NS)). Overall complete and partial skin response rates were 57.7% (42.9% middle-dose and 75% low-dose; NS) and 38.5% (50% middle-dose and 25% low-dose; NS), respectively. All responding patients relapsed after an overall median time of 5 months (7 months middle-dose vs. 4 months low-dose; p = 0.164, NS). Tolerance was equally fair in both groups, with only grade 1 and 2 adverse events observed in 100% vs. 66.7% of patients in middle-dose and low-dose groups (NS). Although no significant difference was observed, middle-dose protocol may be recommended owing to a longer relapse-free survival for a similar tolerance.

Background Essure is an effective method for hysteroscopic sterilization. Reports of adverse effects, the underlying mechanisms of which are unknown, have increased in recent years. Objective The aim of the study was to determine whether there is a relationship between adverse events attributed to Essure and nickel sensitization. Methods Patients presenting alleged adverse reactions to Essure were referred for nickel patch testing before removal. Data regarding medical history of nickel sensitization and symptoms attributed to Essure were collected. Dimethylglyoxime spot tests were performed on the explanted Essure. There was a follow-up at 3 months to evaluate whether there is improvement of the symptoms after Essure removal. Conclusions Nickel sensitization via the classic delayed hypersensitivity pathway did not seem to be responsible for adverse events attributed to Essure. Among systemic symptoms reported, extracutaneous symptoms had the highest prevalence. Systemic contact dermatitis to nickel could not be ruled out in one case.

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International audience; Research Letter

Treatment of benign familial pemphigus or Hailey-Hailey disease (HHD), a rare inherited condition associated with a significant impairment of quality of life, is often challenging and disappointing with frequent relapses and infectious complications. Topical photodynamic therapy (PDT) may offer new perspectives in this difficult setting.Eight patients with long-lasting HHD lesions refractory to multiple treatments were treated on at least one involved site with PDT using methyl-amino levulinate with a standardized protocol of three sessions of irradiation separated by 3-week intervals.A complete or partial clearing was achieved in all treated areas, and the result was satisfactorily maintained in all cases after a follow-up period ranging from 3 to 36 months. Results were of higher quality in non-inguinal areas. Tolerance was overall acceptable with local pain during and shortly after irradiation being the main limiting factor.Our series, although limited in size, emphasizes the interest of PDT in this difficult condition even though results may be incomplete. Treatment-related pain can be adequately managed by prior analgesics, cooling with sprayed water and local tumescent anesthesia. Overall, PDT appears as a relevant option in refractory HHD management with a favorable benefit/risk ratio.

Introduction L’hypereosinophilie (HE, taux d’eosinophiles sanguins (Eos) ≥ 1500/mm3) sous dupilumab dans la dermatite atopique (DA) semble plus importante dans notre etude de vraie vie menee par le GREAT (Groupe de Recherche sur l’Eczema ATopique) en 2019 que dans les essais cliniques. Toutefois, tres peu de donnees sont disponibles concernant la cinetique et l’impact clinique de cette HE. Materiel et methodes Nous avons conduit au sein du GREAT une etude retrospective incluant tous les patients avec DA moderee a severe et presentant une HE sous dupilumab, quel que soit le taux d’Eos avant traitement et la date de declaration de l’HE apres debut du dupilumab. Nous avons collecte les donnees demographiques, date d’introduction du dupilumab, score IGA (Investigator Global Assessment), taux d’Eos avant et pendant le traitement et l’impact clinique de ces eosinophiles. Resultats Sur 653 patients traites entre mars 2017 et mars 2020, 59 presentaient une HE sous dupilumab (prevalence de 9 %). 50/59 (85 %) presentaient des Eos entre 500–1500/mm3 avant traitement, et 4 une HE prealable. L’HE apparaissait rapidement apres introduction du dupilumab (delai moyen de 2,5 mois). Sur 15 patients chez lesquels le dupilumab etait arrete, l’HE etait le motif d’arret chez 10. Aucun ne presentait d’atteinte d’organe en lien avec l’HE. Les donnees evolutives disponibles a 6 mois montraient une persistance de l’HE chez 12/15 (80 %) patients ayant poursuivi le traitement, contre 5/8 (62,5 %) dans le groupe avec arret du dupilumab. Les donnees a plus long terme montraient une tendance vers la normalisation du taux d’Eos chez les patients pour lesquels des donnees etaient disponibles. Discussion La majorite des patients avec HE sous dupilumab presentait dans notre etude un taux d’Eos augmente avant traitement (500–1500/mm3), comme cela a ete rapporte dans l’asthme. Une augmentation rapide du taux d’Eos sous dupilumab etait observee mais le mecanisme physiopathologique n’est pas completement elucide. Il a ete montre que le blocage de l’IL-4 et de l’IL-13 par le dupilumab entraine une diminution rapide de la production d’eotaxine-3, chimiokine a l’origine de la migration des eosinophiles dans les tissus. Les eosinophiles se trouveraient donc « bloques » dans le sang, et ce jusqu’a regulation des taux de cytokines, expliquant ainsi le caractere transitoire de l’HE. A la difference de ce qui a ete decrit chez quelques patients dans les essais du dupilumab dans l’asthme, aucune atteinte d’organe severe en lien avec l’HE n’a ete rapportee dans notre etude. Ces donnees rassurantes nous incitent a ne pas arreter systematiquement le dupilumab lorsqu’il est responsable d’HE. Toutefois, en l’absence d’etudes prospectives et mecanistiques dediees, il est recommande de surveiller le taux d’Eos avant et au moins pendant les premieres semaines du traitement.

International audience

Les anticorps monoclonaux thérapeutiques en dermatologie ont d’abord été utilisés pour la prise en charge du psoriasis, puis, plus récemment, de l’urticaire chronique spontanée et de la dermatite atopique. Trois exemples seront abordés dans cette revue: le dupilumab, l’omalizumab et le lanadélumab. Leur mode d’action spécifique résulte d’une meilleure compréhension des mécanismes inflammatoires de ces maladies chroniques qui partageaient autrefois des traitements topiques ou systémiques plus ou moins ciblés. Leur utilisation onéreuse doit cependant être raisonnée par la mise en perspective de l’épidémiologie, de l’évaluation précise de la sévérité, de l’optimisation des traitements de première ligne, et de la balance bénéfices/risques.

International audience; The efficacy and safety of dupilumab, a humanized monoclonal antibody targeting the α subunit of the interleukin (IL)-4 and IL-13 receptors, has been assessed in adults with moderate-to-severe atopic dermatitis (AD).1,2 Injection site reactions, nasopharyngitis, conjunctivitis, and transient increases in eosinophil counts from baseline were higher in the dupilumab groups than in the placebo groups in pivotal studies.1,2 A recent study by Zhu et al3 reported new regional dermatoses in 17 patients with AD treated with dupilumab, with facial area involvement in 14 cases, whereas Blauvelt et al4 reported an equal improvement of AD with dupilumab on different anatomic regions in a post hoc analysis of data extracted from 4 phase 3 clinical trials.

International audience; BackgroundDupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.ObjectiveWe sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort.MethodsWe included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up.ResultsWe included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10−9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10−9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10−6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs.LimitationsNo control group, missing data.ConclusionThis real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.

International audience; Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease characterized by AE resistant to antihistamines and a chronic course. We report five new cases of InH-AAE (two women and three men) with a rapid and dramatic response to the anti-immunoglobulin-E antibody omalizumab. In our literature review, we found 13 other relevant cases with a good response to this treatment. Overall, in 6 out of 18 patients, the doses of omalizumab required to prevent recurrences of attacks were higher than the licensed dose for chronic urticaria. No significant adverse effects have been reported.

Introduction Les conseils discordants des professionnels de sante pendant le parcours de soin des patients souffrant d’eczema atopique generent de la confusion et diminuent l’adhesion au traitement. Les pharmaciens sont le dernier maillon de la chaine de soins avant le domicile. Le Groupe d’education therapeutique de la SFD (GET) en partenariat avec la Fondation Eczema a mis en place le programme de formation POP Training (pour « Parcours Officinal du Patient »), reposant sur du e-learning dedie aux pharmaciens d’officine. L’objectif de ce travail etait d’evaluer l’impact de ce programme de formation sur les connaissances des pharmaciens d’officine et leur personnel. Materiel et methodes Les pharmaciens s’inscrivaient pour suivre 6 modules d’une heure et demie sur une plateforme pedagogique en ligne, developpee par la Fondation Eczema. Le programme couvrait la physiopathologie, la corticophobie, les traitements locaux, la motivation pour un maintien des traitements dans la duree et l’approche educative. Le resultat des quiz evaluant les connaissances avant et apres chaque module a ete evalue statistiquement. Resultats Sur les 1630 inscrits, 336 pharmaciens ont suivi le module 1 et 195 ont termine l’ensemble des 6 modules. Les notes obtenues aux quiz ont montre une amelioration des connaissances d’environ 2,5 points/20, sur l’ensemble des modules. Neanmoins, les pharmaciens, les preparateurs et les etudiants n’avaient pas les memes niveaux de progression. Discussion Chaque module de POP TRAINING a cible des thematiques specifiques. Les equipes officinales avaient une bonne connaissance des traitements locaux (module 3), qui sont de leur domaine d’expertise. Cependant, la formation a apporte des connaissances supplementaires, puisque la moyenne apres le module etait augmentee. Le niveau de connaissance en education therapeutique du patient (ETP) etait egalement eleve avant le module 5, 40 h de formation d’ETP etant integrees au cursus universitaire des pharmaciens. Toutefois, on note une amelioration a l’issue du module. L’etat des connaissances sur la corticophobie et l’approche psychologique pour garder les patients motives, ont montre des niveaux de connaissance plus faibles en debut des modules 2 et 4. Ces resultats soulignent les points forts et les points faibles des connaissances des pharmaciens sur le terrain. Le programme POP Training a permis une amelioration des connaissances des pharmaciens pour la prise en charge des patients souffrant d’eczema atopique. Il permet d’asseoir leur role dans ce parcours de soin, avec un alignement des discours entres les differents acteurs de soins.

La dermatose inflammatoire peri-orificielle, erosive, fissuraire, surinfectee au cours d’un traitement par anti-TNFα pour une maladie inflammatoire chronique intestinale (MICI) est encore mal decrite. Les cas inclus presentaient des lesions cutanees peri-orificielles ± des plis ou du scalp, avec recueil des donnees histopathologiques et bacteriologiques des lesions et des gites orificiels, des scores d’activite de la MICI, du statut nutritionnel. Ces donnees etaient egalement recueillies chez des temoins. Par des biopuces a ADN, la caracterisation moleculaire des S. aureus des lesions et des gites orificiels etait comparee. Resultats Vingt huit patients et 42 temoins etaient inclus. 67,9 % des cas presentaient une rhinite crouteuse, 57,1 % une eruption pustuleuse perineale, 42,9 % des fissures retro-auriculaires. Un S. aureus communautaire etait present dans 75 % des cas. Les cas etaient davantage colonises a S. aureus que les temoins (82.1 % versus 36,6 %), majoritairement avec le meme clone dans les lesions (OR 7,97[2,51–25,35], p Conclusion L’interet d’un traitement anti-staphylococcique et d’une supplementation des carences vitaminiques dans cette dermatose inflammatoire devrait etre evalue.

International audience; Le risque de cancers cutanés induits par des médicaments photosensibilisants est connu. Le rôle de l’hydrochlorothiazide a été soulevé par plusieurs études épidémiologiques récentes. Une revue systématique des études cas-témoins ou de cohortes prospectives montre qu’il existe un surrisque de carcinomes épidermoïdes dans la majorité des études même si certains facteurs de confusion comme le tabac n’ont pas été pris en compte. Les données sont plus contradictoires pour les carcinomes basocellulaires et les mélanomes. Ces résultats ne remettent pas en cause le rapport bénéfice/risque de cette molécule, mais peuvent inciter à des mesures de prévention renforcées chez les malades pour lesquels une prescription d’hydrochlorothiazide est proposée : identifier les patients à risque de carcinomes cutanés, éviter si possible de prescrire cette molécule chez les patients immunodéprimés ou ayant un carcinome, effectuer un examen cutané régulier chez les malades recevant ce traitement au long cours.

Introduction Les savons et emollients au lait d’ânesse (LA) sont plebiscites dans differents medias rappelant les celebres bains de Cleopâtre. Observations La patiente 1 (p1, 19 ans) sans allergie alimentaire, avec une dermatite atopique ancienne, signalait une eruption urticarienne generalisee avec malaise sans dyspnee lors de la 1re utilisation d’un savon, aggraves par l’application d’un emollient. La patiente 2 (p2, 47 ans), avec une urticaire chronique sous omalizumab et desloratadine depuis 1 an, des allergies alimentaires multiples type LTP, rapportait une urticaire generalisee avec angiœdeme du visage, malaise hypotensif et dyspnee sibilante au 3e jour d’application d’un nouvel emollient. Les cosmetiques incrimines contenaient du LA. Les 2 patientes rapportaient l’utilisation anterieure toleree de cosmetiques au LA sans (p2) ou avec un grand intervalle libre (p1). La declaration en cosmetovigilance etait realisee. Les prick-tests etaient positifs pour le LA frais ( Fig. 1 ). La p2 tolerait le lait de vache mais ni de chevre ni de brebis. Le SDS-PAGE du LA puis l’immunoblot IgE avec le serum des patientes, le LA et le lysozyme de LA purifie montraient un profil de sensibilisation a ce dernier ( Fig. 2 ). Discussion Seuls 5 cas de reactions d’HS immediate au LA ont ete decrits lors de l’application de cosmetiques ou de l’inhalation de lyophilisats en contexte professionnel ou de l’ingestion de LA. Dans ces derniers cas, l’utilisation de cosmetiques avait precede l’ingestion parfois de plusieurs annees, renforcant ainsi la theorie de sensibilisation par voie percutanee. Le long delai entre les applications de la petite enfance et a 19 ans de la patiente 1 fait suspecter une grande remanence de la sensibilisation malgre une eviction complete. L’utilisation prealablement bien toleree de cosmetiques par la patiente 2 evoque une rupture de tolerance (liee a une concentration en LA du nouvel emollient a 40 % vs les 5 a 15 % habituels ?). Chez 2 autres patientes en 2018 etait trouve un profil de sensibilisation identique contre le lysozyme du LA, aux proprietes conservatrices recherchees dans l’elaboration des cosmetiques. Les 5 cas decrits survenaient chez des atopiques : responsabilite du defaut de barriere cutanee ? biais d’utilisation plus assidue de cosmetiques dits « naturels » ? Ces cas rappellent les anaphylaxies decrites avec les cosmetiques contenant des proteines de soja ou d’isolats de ble, ayant fait l’objet d’une suppression apres de nombreuses declarations de cosmetovigilance. Enfin, l’utilisation concomitante d’huiles essentielles pour masquer l’odeur du LA complete le tableau de cosmetiques a risque de sensibilisation. Conclusion Ces 2 nouveaux cas alertent sur les dangers de l’utilisation de proteines sensibilisantes dans les cosmetiques, en particulier le LA, en particulier chez l’atopique, et rappellent l’utilite des declarations en cosmetovigilance.

The mortality rate for malignant melanoma is higher in elderly patients aged 75 years or more, with over 25% of melanomas being diagnosed in this population. This poorer prognosis might perhaps be improved by emerging targeted therapies and immunotherapy, although these agents must be prescribed with care in this rather fragile population. The purpose of our review of the literature concerning phase-2 and -3 published trials of these innovative molecules was to examine their optimal use in elderly patients presenting metastatic malignant melanoma. Most of the trials examined included elderly patients and some were analyzed by age sub-groups. In conclusion, elderly patients with ECOG 0/1 status can be given ipilimumab or vemurafenib as first-line therapy depending on tumoral BRaf mutation status. The benefit of combined targeted therapies does not seem to apply consistently in elderly patients and their use must be discussed. Further specific data must be collected in elderly patients concerning anti-PD1 molecules. For more fragile patients, risk scales or scores should enable more accurate use of innovative therapies in metastatic melanoma. Moreover, physicians must be aware of the common drug interactions with targeted therapies, since elderly patients are often taking several concomitant drugs.

BACKGROUND: Identification of myositis-specific autoantibodies (MSAs) for dermatomyositis (DM) could allow the characterization of an antibody-associated clinical phenotype. OBJECTIVE: We sought to define the clinical phenotype of DM and the risk of cancer, interstitial lung disease (ILD) and calcinosis based on MSA. METHODS: A 3.5-year multicentre prospective study of adult DM patients was conducted to determine the clinical phenotype associated with MSAs and the presence of cancer, ILD and calcinosis. RESULTS: MSAs were detected in 47.1% of 117 included patients. Patients with antimelanoma differentiation-associated protein-5 antibodies (13.7%) had significantly more palmar violaceous macules/papules [odds ratio (OR) 9.9], mechanic's hands (OR 8), cutaneous necrosis (OR 3.2), articular involvement (OR 15.2) and a higher risk of ILD (OR 25.3). Patients with antitranscriptional intermediary factor-1 antibodies (11.1%), antinuclear matrix protein-2 antibodies (6.8%) and antiaminoacyl-transfer RNA synthetase (5.1%) had, respectively, significantly more poikiloderma (OR 5.9), calcinosis (OR 9.8) and articular involvement (OR 15.2). Cutaneous necrosis was the only clinical manifestation significantly associated with cancer (OR 3.1). CONCLUSION: Recognition of the adult DM phenotype associated with MSAs would allow more accurate appraisal of the risk of cancer, ILD and calcinosis.

International audience; A 31-year-old woman was investigated for multiple, slightly erythematous or flesh-coloured, firm, asymptomatic papu-les, a few mm in diameter, located exclusively on the chin and the lower part of both cheeks (Fig. 1a). These elements had gradually emerged over the 2 previous years and were initially considered and treated unsuccessfully as retentional acne. Physical examination was otherwise unremarkable and the general status of the patient was excellent. Histo-logical examination of a papule displayed a multi-nodular lymphocytic infiltrate of moderate density involving the upper and medium dermis that was well-limited laterally (Fig. 1b). Standard laboratory investigations and routine serologies, including serological diagnosis of Borrelia, were normal or negative. Computed tomography (CT) scan of the chest, abdomen and pelvis was unremarkable. What is your diagnosis? See next page for answer. Fig. 1. Clinical and histological features. (a) Multiple, small-sized papules of the lower part of the face with chronic evolution. (b) multi-nodular dermal infiltrate of moderate density involving the upper and medium dermis with reactive germinal centre-like structures (Haematoxylin-eosin ×5).

International audience; The aim of this 10-year monocentric prospective study was to determine a cut-off value of Fas/CD95 expression by peripheral blood CD4+ T lymphocytes in discriminating patients with mycosis fungoides from controls with cutaneous benign lymphocytic conditions. CD95 expression in peripheral blood CD4+ T lymphocytes was measured using flow cytometry in 330 patients referred for diagnosis: 104 with mycosis fungoides and 226 with eczema, psoriasis, drug reaction, etc. The sensitivity and specificity of different thresholds of CD95 expression were calculated regarding the final diagnosis of patients with mycosis fungoides or controls. CD95 expression higher than 30% reached a specificity of 91% in ruling out a diagnosis of mycosis fungoides, although overall CD95 expression was not significantly different from that of controls (p = 0.309) and sensitivity was very low (5%). Thus, peripheral CD95 expression higher than 30% could be used among the exclusion criteria in a multicomponent score for mycosis fungoides diagnosis.

Introduction Les inhibiteurs de l’enzyme de conversion (IEC) et les sartans induisent des angiœdemes (AE) par defaut de catabolisme enzymatique bradykinique chez 0,1 a 2,2 % des patients traites (10 % de reaction croisee IEC/sartans). Un AE aux IEC/sartans (AE-IEC) est evoque devant tout AE chez un patient sous IEC/sartans ou en ayant pris dans les 6 mois precedents, avec un taux de C1-inhibiteur normal, les contre-indiquant a vie. Des recidives d’AE-IEC malgre l’arret de l’IEC sont decrites (50 % des cas apres arret de l’IEC, surtout le 1er mois). Devant toute persistance/recidive des AE plus de 6 mois apres l’arret des IEC, le diagnostic d’urticaire chronique (UC) sous forme d’AE histaminiques isoles doit etre evoque. La presence d’urticaire superficielle associee est un argument diagnostique, les AE histaminiques isoles ou inauguraux sont decrits (respectivement 10 et 40 % des UC). L’UC ne contre-indique pas la reprise de l’IEC/sartan. Aucun marqueur biologique ne permet actuellement de differencier les AE sous IEC dans le cadre d’une UC et les AE-IEC. Leur pronostic et traitement sont tres differents. L’objectif principal de cette etude etait d’evaluer l’imputabilite des IEC/sartans dans une population de patients presentant des AE sous IEC/sartans et d’identifier d’eventuels facteurs predictifs d’AE-IEC. Patients et methodes Etude retrospective monocentrique incluant tous les patients sous IEC/sartan consultant pour AE isoles entre 2007 et 2017, a C1-inhibiteur normal, avec recueil de donnees cliniques a M0 et M6 ou plus. Les donnees epidemio-cliniques etaient comparees entre les groupes AE-IEC et UC avec les tests de Fisher et de Student. Resultats Soixante-dix patients ont ete inclus entre 2007 et 2017, 56 (80 %) sous IEC et 14 (20 %) sous sartans, dont 44,3 % de femmes, d’âge moyen de 69 ans. Le traitement etait arrete chez 65 (91,4 %) patients et une UC diagnostiquee chez les 5 patients l’ayant poursuivi. Trente-deux (45,7 %) patients ont rechute apres 5,1 semaines en moyenne. Une urticaire superficielle secondaire est survenue chez 14 (20 %) patients. Une UC etait diagnostiquee a posteriori chez 33 (47,1 %) patients versus 34 (48,6 %) AE-IEC, 3 patients ont ete perdus de vue (4,3 %). Parmi les donnees suivantes : âge (p = 0,15), sexe (p = 0,09), terrain atopique personnel (p = 0,79), dysthyroidie auto-immune (p = 1), delai de survenue apres introduction du traitement (p = 0,15), duree des AE (p = 0,75), presence d’une atteinte endobuccale (p = 0,239) ou d’une toux aux IEC (p = 0,49), seul l’antecedent d’urticaire etait predictif du diagnostic final d’UC (p = 0,023). Conclusion Tous les patients consultant pour AE isole(s) survenu(s) sous IEC/sartan devraient etre revus apres 6 mois d’arret pour proposer une re-introduction de traitement cardio/nephroprotecteur en cas de diagnostic final d’UC. Seul l’antecedent d’urticaire a ete retrouve comme facteur predictif d’UC dans cette etude retrospective.

International audience

International audience; Cold contact urticaria (CCU) is a physical urticaria, also called inducible urticaria, which is triggered by exposure of the skin to cold air, surfaces or fluids. Clinical manifestations of CCU range from mild, localized whealing to life-threatening anaphylactic shock. CCU is mostly idiopathic (primary), but in rare cases it is secondary to infectious disease, with or without cryoproteins. We report here, for the first time, 4 cases of CCU that developed following vaccination, which suggests a link between these events.

The diagnosis of actinic keratosis is generally established by clinical examination. However, actinic keratosis can progress into an invasive squamous cell carcinoma, therefore biopsy and histological examination may be needed. The risk of progression into an invasive carcinoma is not well established; it varies in the literature between 0.025% and 20% for a given lesion. Some clinical aspects suggest transformation into an invasive carcinoma; they include inflammation, induration, size > 1 cm, rapid enlargement of the lesion, bleeding or ulceration, and should prompt the clinician to perform a skin biopsy. In case of resistance after a well-driven treatment, a biopsy may be necessary. Finally, in cases of atypical clinical aspect, a biopsy may be useful in order to obtain a correct diagnosis.

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Summary Background The interest of long-term superpotent topical steroids (STS) in bullous pemphigoid (BP) has been supported by randomized controlled trials. However, inadequate compliance, poor cutaneous tolerance and nursing difficulties are potential drawbacks. Open-label studies on limited series of patients suggested that low-dose methotrexate (MTX) may be useful, permitting long-term maintenance of a clinical remission obtained by initial, short-term STS. Objectives Open, clinical records-based retrospective analysis of a multicentre series of patients receiving a combined regimen of initial, short-term STS and MTX followed by long-term MTX alone. The primary objective was evaluation of the clinical efficiency of this strategy based on initial clinical remission and subsequent clinical maintenance. The secondary objective was evaluation of the tolerance (type and rating of adverse events) of this combined regimen. Methods Seventy patients with BP (mean age 82·7 years) were included. Treatment consisted of an initial combination of STS and MTX for a mean duration of 12·3 weeks followed by long-term MTX alone for a mean duration of 8·48 months with a mean and median MTX dosage of 10 mg per week. Results One hundred per cent of the patients showed an initial, complete clinical remission after a mean time interval of 21·9 days. The overall rate of long-term disease control was 76%, whereas 24% of patients experienced at least one relapse during subsequent treatment with MTX alone. Drug-related adverse effects were mainly haematological and gastrointestinal and resulted in treatment discontinuation in 11 patients (16%). Six patients (9%) died during the follow-up period with one death (1%) most likely to be related to treatment. Conclusions Long-term low-dose MTX combined with short-term STS may result in protracted control of BP in carefully selected patients. These results should prompt randomized controlled trials comparing this treatment with the more usual regimen of long-term STS alone.

Background The additional benefit of 18FDG-Positron Emission Tomography-Computed Tomography (FDG PET-CT) compared with conventional imaging is still a controversial issue in MCC. Objectives This study was designed to evaluate the ability of FDG PET-CT to detect secondary lesions clinically inconspicuous and not shown by conventional imaging. Methods Clinical records of 15 MCC patients were retrospectively reviewed to investigate the specific interest of FDG PET-CT compared with X-computed tomography (CT). The main endpoint was the ability of FDG PET-CT to detect secondary lesions and the possible resulting changes in disease staging and management compared with pre-FDG PET-CT data including clinical examination, sentinel lymph node biopsy (SLNB), and diagnostic CT. Results FDG PET-CT was relevant with a single false negative result and led to significant changes in disease staging and management in 46% of patients compared with clinical examination alone. However, additional secondary lesions not detected by CT were evidenced during follow-up in a single patient with an already known metastatic disease, data which did not result in any change in staging and treatment. Sensitivity, specificity, positive predictive value and negative predictive value were respectively 0.66, 1, 1 and 0.8 for SLNB, 0.89, 1, 1 and 0.93 for CT and 0.89, 1, 1 and 0.93 for FDG PET-CT. No additional neoplasm was detected by FDG PET-CT. Conclusion Although FDG PET-CT is of questionable value in MCC management when used in parallel with CT, it may be considered as a valuable option as a single whole-body survey procedure.

Introduction L’urticaire au froid (UF) est une urticaire chronique inductible au potentiel letal par noyade. Son diagnostic repose sur l’histoire clinique et la positivite d’un test de provocation, qui peut etre negatif dans jusqu’a 20 % des cas, caracterisant les UF « atypiques ». Materiel et methodes Etude retrospective monocentrique incluant tous les patients consultant pour une UF entre 2004 et 2017. Resultats Cent trente-cinq patients etaient inclus : 67 % de femmes, avec un âge moyen de 30 ans au debut des symptomes ; 45 % etaient atopiques. Les facteurs declenchant principaux des crises etaient la baignade, l’air froid, le contact avec un objet froid et les ingestats froids (respectivement 85 %, 85 %, 28 % et 30 %), ainsi qu’un differentiel de temperature dans 19 % des cas. L’UF presentait un stade de severite de type 1 (urticaire limitee), 2 (urticaire diffuse sans malaise) et 3 (urticaire diffuse avec malaise ou signes de choc) dans 36 %, 42 % et 22 % des cas respectivement, avec 2 chocs anaphylactoides. Des signes extra-cutanes (douleurs abdominales, arthralgies) etaient presents au moment des crises dans 16 % des cas et 22 % des patients rapportaient des signes cutanes lies au froid (livedo, engelures, phenomene de Raynaud ou acrosyndrome). Le test au glacon etait positif chez 77 % des patients, avec un temps de pose superieur a 5 minutes chez 23 patients. Huit patients avaient une cryoglobulinemie et/ou une cryofibrinogenemie mais aucun d’entre eux n’avait de signe cutane lie au froid. Le seul facteur associe a la severite etait un temps de positivation du test au glacon Discussion Les donnees de cette etude sont comparables a celles de la litterature en termes d’epidemiologie et de circonstances declenchantes, ainsi que de frequence faible des cryoprotidemies et des dysthyroidies. La predominance des formes diffuses est en accord avec les donnees issues de regions littorales semblables. Le taux de faux negatifs du test au glacon est eleve (17 %), lie a un temps de pose probablement trop court. Le risque de reaction severe est inversement proportionnel au delai de positivation du test. Les donnees concernant les signes cutanes lies au froid et le declenchement par un differentiel de temperature ne sont pas toujours disponibles. Les ingestats froids semblent plutot plus frequents dans notre serie. En cas d’angiœdeme oropharynge isole aux ingestats froids, l’UF devrait etre consideree comme une forme severe (type 3) et non uniquement localisee (type 1). Les traitements hors autorisation de mise sur le marche (AMM) par antihistaminiques a posologie augmentee, de meme que l’addition eventuelle d’omalizumab hors AMM, semblent efficaces. Conclusion Le risque de reaction severe etant eleve, les tests de provocation devraient etre optimises pour faciliter le diagnostic, le bilan biologique necessaire mieux precise de meme que les recommandations de prise en charge. L’omalizumab semble prometteur pour les formes resistantes.

We report here the first case of a misleading association of Clostridium difficile infection (CDI) with ipilimumab-related immune diarrhea in a patient with unresectable stage III melanoma.After an unsuccessful first-line chemotherapy with dacarbazine (1000 mg/m2 every three weeks) for a subcutaneous and nodal relapse of a stage IIb melanoma of the right lower limb (Breslow index 3.75 mm, Clark level IV), treated by surgical excision 11 months previously and incomplete adjuvant treatment with alpha [...]

Resume Introduction Le lymphome cutane T epidermotrope CD8+ « agressif » est une entite rare faisant partie du groupe des lymphomes cutanes a phenotype T cytotoxique et/ou NK et qui se differencie nettement du mycosis fongoide qu’il soit CD4+ ou CD8+ par ses lesions tumorales d’emblee rapidement evolutives, la presence de necroses keratinocytaires, un immunophenotype T cytotoxique et un pronostic defavorable. Observation Un homme de 33 ans atteint d’une myotonie de Steinert etait adresse pour des lesions tumorales ulcerees d’evolution rapide dans un contexte d’alteration marquee de l’etat general. Les donnees cliniques, histologiques et immunohistologiques permettaient de conclure a un lymphome cutane epidermotrope CD8+ « agressif ». Le traitement par CHOP etait efficace malgre une tolerance cardiaque moyenne liee a la myotonie mais l’evolution se faisait vers une recidive cutanee puis vers un deces par infection pulmonaire apres reprise de la chimiotherapie. Discussion Le traitement du lymphome cutane epidermotrope CD8+ « agressif » n’est pas codifie. Il fait appel en general a une chimiotherapie systemique de type CHOP mais la recidive est la regle avec une mediane de survie ne depassant pas 34 mois. Chez le malade presente, la presence d’une myopathie induisait une difficulte supplementaire en raison de la toxicite cardiaque du traitement cytostatique rendant difficile une intensification et conduisant a une modification de protocole.