These guidelines were developed by the psoriasis research group of the French Society of Dermatology with the aim of providing updated decision‐making algorithms for the systemic treatment of adult ...patients with moderate‐to‐severe psoriasis. Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in the generation of the algorithms. We have proposed two new algorithms to assess therapeutic responses, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.
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Objective
Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune‐related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been ...excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer.
Methods
A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response.
Results
The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty‐four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression‐free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression‐free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation.
Conclusion
Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.
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Bullous pemphigoid is the most frequent autoimmune bullous skin disease and affects subjects who are about 80 years old.
The risk factors are neurological degenerative diseases, poor Karnovski's ...status and some drugs (aldactone and neuroleptics).
Typically, the disease consists of itching eczematous or urticarial sheets, surmounted by blisters. The blisters heal without scars. Mouth and head are rarely involved.
The diagnostic is made by histological examination . It shows a subepidermal blister with some degree of dermal infiltrate with lymphocytes and eosinophils. Direct immunofluorescence reveals a linear pattern of IgG deposition along the basal membrane, which signs the diagnosis. Indirect immunofluorescence detecting anti-basal membrane antibodies is of poor diagnostic value. New tests detecting BPAg 2 antibodies by enzyme-linked immunosorbant assay (ELISA) seems to be good markers for disease activity and prognosis.
Recommended treatment is topical corticosteroids (clobetasol propionate cream) for several months. It has been showed to be more effective and less dangerous than oral corticotherapy in severe forms of bullous pemphigoid. Corticosteroid sparing agents like methotrexate or mycophenolate mofetil are sometimes used because of cutaneous or systemic side effect of strong and protracted topical corticosteroid therapy.
The management of these patients shall be done by specialized and coordinated staff in order to bring the best care.
La pemphigoïde bulleuse est la plus fréquente des dermatoses bulleuses auto-immunes de l’adulte. Elle atteint le sujet âgé en moyenne de 80 ans.
Les affections neurologiques, l’état grabataire et certains médicaments sont des facteurs de risque.
Le diagnostic repose sur la sémiologie de l’éruption constituée de bulles tendues sur des plaques érythémateuses prurigineuses, sans atteinte du visage, ni de la muqueuse buccale et avec une guérison sans cicatrice dystrophique dans la plupart des cas. Les formes atypiques eczématiformes ou urticariennes chroniques sont fréquentes et doivent faire chercher le diagnostic après 70 ans.
Le mécanisme est auto-immun avec un rôle direct d’auto-anticorps dirigés contre des protéines de structure de la jonction dermo-épidermique responsables de l’ancrage de l’épiderme sur le derme (hémidesmosomes). Deux antigènes cibles ont été identifiés : BPAg 1 (230
kD) et BPAg 2 (180
kD).
Le diagnostic est affirmé sur la biopsie cutanée avec mise en évidence d’une bulle sous-épidermique à toit respecté en coloration standard, et sur la présence d’anticorps de classe IgG fixés de façon linéaire sur la jonction dermo-épidermique révélés par une technique d’immunofluorescence directe.
La présence d’auto-anticorps sériques (anticorps antimembrane basale) détectés par immunofluorescence indirecte n’a qu’une valeur diagnostique et pronostique faible. Cette technique tend à être remplacée par la recherche d’anticorps dirigés contre une protéine cible (BPAg 2) par
enzyme-linked immunosorbant assay (ELISA), sensible, spécifique et corrélée à l’évolution.
Le traitement de référence est une dermocorticothérapie forte (propionate de clobétasol). Il a montré être aussi efficace qu’une corticothérapie systémique avec une diminution de la morbimortalité. En cas d’échec ou de contre-indication, on propose un immunosuppresseur type méthotrexate ou mycophénolate mofétil, pour lesquels des études sont nécessaires avant qu’ils ne soient validés.
La prise en charge de ces patients est difficile et nécessite des équipes spécialisées et formées pour adapter au mieux les soins locaux et le choix du traitement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mycosis fungoides (MF) is a low-grade cutaneous lymphoma accounting for more than half of primary cutaneous T-cell lymphomas (CTCLs). Due to the rarity of CTCL, randomized studies are lacking, and ...treatment is based mainly on the recent published European Organisation for Research and Treatment of Cancer guidelines. Basically, early-stage MF is treated with skin-directed treatments, whereas advanced-stage MF requires more aggressive therapies. Among the skin-directed therapies, nitrogen mustard has been used for more than 50 years. A gel formulation was developed recently, showing a slight decrease in efficacy, counterbalanced by better tolerance (essentially due to a decrease in delayed hypersensitivity reactions). This review aims to summarize the current management of MF and the role of chlormethine gel in the treatment of the disease.
Introduction
Despite the existence of multiple assessment scores for psoriasis severity, skin disease with limited skin lesions but significant impairment of quality of life can be difficult to ...classify, leading to under- or overtreatment. Our objective was to obtain consensus on clinical criteria to classify psoriasis severity in French clinical practice, with a focus on moderate disease, using a modified Delphi method.
Methods
A steering committee (SC) formulated a 22-item questionnaire to classify moderate psoriasis. An independent panel of French dermatologists indicated their level of agreement for each item using a 9-point Likert scale (round 1). Items without a strong consensus were modified and included in round 2. For each item, strong consensus was defined as at least 75% of scores ≥ 7 and median score ≥ 8; good consensus was defined as at least 75% of scores ≥ 7 or median score ≥ 8.
Results
Of 80 dermatologists who agreed to participate, 47 (59%) responded in round 1. All participants from round 1 responded in round 2. Fifteen (68%) items achieved strong consensus and four (18%) achieved good consensus. For psoriasis severity, several clinical dimensions assessed both by the physician (location, symptoms, temporality, previous treatments) and the patient (perception, physical and psychological impairment) obtained consensus. The following were considered sufficient to confirm that psoriasis is at least at a moderate stage: limited involvement but with an impact on patient/family quality of life; involvement of a special area; presence of uncontrolled symptoms (scaling, bleeding, pruritus, insomnia); accumulation of mild intensity symptoms; presence of burdensome onychodystrophy; failure of well-applied topical treatments. There was strong consensus that recognition of moderate psoriasis should lead to reassessment of topical treatments.
Conclusion
Our modified Delphi panel suggests detailed criteria to help physicians classify patients with psoriasis which is at least at a moderate stage, which could, in turn, improve treatment in these patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE: Calcific uremic arteriolopathy (CUA), a rare, potentially fatal, disease with calcium deposits in skin, mostly affects patients with end-stage renal disease who are receiving dialysis. ...Chemical composition and structure of CUA calcifications have been poorly described. OBJECTIVES: To describe the localization and morphologic features and determine the precise chemical composition of CUA-related calcium deposits in skin, and identify any mortality-associated factors. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter cohort study was conducted at 7 French hospitals including consecutive adults diagnosed with CUA between January 1, 2006, and January 1, 2017, confirmed according to Hayashi clinical and histologic criteria. Patients with normal renal function were excluded. For comparison, 5 skin samples from patients with arteriolosclerosis and 5 others from the negative margins of skin-carcinoma resection specimens were also analyzed. MAIN OUTCOMES AND MEASURES: Localization and morphologic features of the CUA-related cutaneous calcium deposits were assessed with optical microscopy and field-emission–scanning electron microscopy, and the chemical compositions of those deposits were evaluated with μ Fourier transform infrared spectroscopy, Raman spectroscopy, and energy dispersive radiographs. RESULTS: Thirty-six patients (median range age, 64 33-89 years; 26 72% female) were included, and 29 cutaneous biopsies were analyzed. Calcific uremic arteriolopathy and arteriolosclerosis skin calcifications were composed of pure calcium–phosphate apatite. Calcific uremic arteriolopathy vascular calcifications were always circumferential, found in small to medium-sized vessels, with interstitial deposits in 22 (76%) of the samples. A thrombosis, most often in noncalcified capillary lumens in the superficial dermis, was seen in 5 samples from patients with CUA. Except for calcium deposits, the vessel structure of patients with CUA appeared normal, unlike thickened arteriolosclerotic vessel walls. Twelve (33%) patients died of CUA. CONCLUSIONS AND RELEVANCE: Calcific uremic arteriolopathy–related skin calcifications were exclusively composed of pure calcium–phosphate apatite, localized circumferentially in small to medium-sized vessels and often associated with interstitial deposits, suggesting its pathogenesis differs from that of arteriolosclerosis. Although the chemical compositions of CUA and arteriolosclerosis calcifications were similar, the vessels’ appearances and deposit localizations differed, suggesting different pathogenetic mechanisms.
Merkel cell carcinoma (MCC) is an aggressive skin cancer for which Merkel cell polyomavirus integration and expression of viral oncogenes small T and Large T have been identified as major oncogenic ...determinants. Recently, a component of the PRC2 complex, the histone methyltransferase enhancer of zeste homolog 2 (EZH2) that induces H3K27 trimethylation as a repressive mark has been proposed as a potential therapeutic target in MCC. Because divergent results have been reported for the levels of EZH2 and trimethylation of lysine 27 on histone 3, we analyzed these factors in a large MCC cohort to identify the molecular determinants of EZH2 activity in MCC and to establish MCC cell lines' sensitivity to EZH2 inhibitors. Immunohistochemical expression of EZH2 was observed in 92% of MCC tumors (156 of 170), with higher expression levels in virus-positive than virus-negative tumors (P = 0.026). For the latter, we showed overexpression of EZHIP, a negative regulator of the PRC2 complex. In vitro, ectopic expression of the large T antigen in fibroblasts led to the induction of EZH2 expression, whereas the knockdown of T antigens in MCC cell lines resulted in decreased EZH2 expression. EZH2 inhibition led to selective cytotoxicity on virus-positive MCC cell lines. This study highlights the distinct mechanisms of EZH2 induction between virus-negative and -positive MCC.
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Introduction
Cyclosporine and methotrexate are the two preferred first‐line immunosuppressive treatments in atopic dermatitis. The aim of this study was to compare the treatment profiles of ...methotrexate and cyclosporine in daily practice as the first‐line immunosuppressive treatment in atopic dermatitis, using two survival analyses, ‘drug survival’ (time on the drug) and ‘postdrug survival’ (time between two drugs).
Methods
Retrospective study including patients with moderate‐to‐severe atopic dermatitis treated with methotrexate or cyclosporine as the first‐line immunosuppressive treatment. The reasons for discontinuation of treatment were collected as follows: controlled disease, treatment failure, side event pregnancy and non‐compliance. ‘Drug survival’ and ‘postdrug survival’ analyses were performed using the Kaplan–Meier method and predictive factors were analysed using uni‐ and multivariate Cox regression analyses.
Results
Fifty‐six patients, among whom 25 patients treated with cyclosporine and 31 with methotrexate (median age: 34 ± 15 years), were included between 2007 and 2016. Reasons for discontinuation were not significantly different between ‘controlled disease’ and other reasons (P = 0.11). The median ‘drug survival’ was significantly longer for methotrexate (23 months) than for cyclosporine (8 months) (P < 0.0001). Six months from baseline, 93% of patients treated with methotrexate were still being treated vs 63% among patients treated with cyclosporine. The median of ‘postdrug survival’ was significantly longer for methotrexate (12 months) than for cyclosporine (2 months). Only treatment with CYC was a predictive factor for decreased ‘drug survival’ and ‘postdrug survival’.
Conclusion
This is the first direct comparison between methotrexate and cyclosporine as first‐line immunosuppressive treatments for moderate‐to‐severe atopic dermatitis in daily practice. We evidenced two different treatment profiles: the duration of methotrexate administration is longer than that of cyclosporine. ‘Postdrug survival’ could be a new tool to assess the maintenance of effect of a drug after withdrawal in atopic dermatitis, and more broadly in chronic skin disease.
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