[Dermatology. New uses for JAK inhibitors in dermatology: a panacea, but at what price?] / Dermatologie. Nouvelles utilisations des inhibiteurs de JAK en dermatologie : panacée mais à quel prix ?

Janus kinase inhibitors (JAKi) are small molecules which prevent the phosphorylation of JAKs, thereby blocking the intracellular phosphorylation cascade required for the transcription of several cytokines. In addition to approved indications that have been extensively studied, including atopic dermatitis, alopecia areata, vitiligo and psoriasis, JAKi are also proposed off-label, included topically, in several dermatological conditions where standard treatments are often disappointing, such as hidradenitis suppurativa (HS), extensive morphea, cutaneous sarcoidosis and lichen planus. On the other hand, the wide mechanism of action on cytokine blockade implies a safety profile that requires a case-by-case assessment of the risk/benefit ratio before their introduction.

Les inhibiteurs de Janus kinases (JAKi) sont de petites molécules empêchant la phosphorylation des JAK et bloquant ainsi la cascade de phosphorylation intracellulaire nécessaire à la transcription de plusieurs cytokines. Au-delà des indications approuvées ayant fait sujets de larges études, dont la dermatite atopique, la pelade, le vitiligo et le psoriasis, les JAKi sont aussi proposés off-label y compris en formulation topique dans plusieurs pathologies dermatologiques où les traitements habituellement utilisés sont souvent décevants : maladie de Verneuil, morphées étendues, sarcoïdose cutanée, lichen plan. En revanche, le mécanisme d'action assez large sur le blocage cytokinique implique un profil de sécurité nécessitant une évaluation cas pour cas du ratio risques/bénéfices avant leur introduction.

[Dupilumab: beyond atopic dermatitis, off-label use in dermatology]. / Dupilumab : au-delà de la dermatite atopique, les principales utilisations hors indication en dermatologie.

Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL-4 receptor inhibiting the signaling of interleukin-4 and interleukin-13, two major cytokines in type 2 inflammatory diseases such as atopic dermatitis, asthma and nasosinusal polyposis. Since its approval for atopic dermatitis in 2017, the molecule has occasionally been used off-label in several dermatological conditions where standard treatments are often disappointing.Furthermore, what emerges from the data currently in the literature is a favourable safety profile with few, reversible side effects.

Le dupilumab est un anticorps monoclonal recombinant humain de type IgG4 qui inhibe la signalisation de l'interleukine-4 et l'interleukine-13, deux cytokines majeures impliquées dans les pathologies inflammatoires de type 2 telles que la dermatite atopique, l'asthme et la polypose naso-sinusienne. À côté d'une bonne efficacité dans ces pathologies, on retient un bon profil de sécurité avec peu d'effets secondaires, généralement assez bénins et réversibles. Depuis son approbation pour la dermatite atopique en 2017, cette molécule a été utilisée hors indication dans plusieurs pathologies dermatologiques où les traitements habituellement utilisés peuvent être insuffisants ou mal tolérés.

Fractional Photothermolysis for Treatment of a Residual Discoid Lupus Erythematosus Lesion: A Case Report.

Cutaneous discoid lupus erythematosus (CDLE) is a chronic inflammatory skin disease often resulting in permanent scarring of the affected area. Fractional photothermolysis (FP) is a well-known inducer of tissue regeneration by wounding the skin in a fractional pattern, hence inducing a well defined, wound healing response. It has been used clinically to treat atrophic as well as hypertrophic scars and also fibrotic diseases like morphea since more than a decade. We report a case of a young female patient treated with three sessions of ablative FP for stable atrophic scars due to CDLE affection of the upper left and right cheeks. After the last treatment, no side effects were observed. At the 13-month follow-up visit, the treated atrophic scars showed satisfying improvement for the patient. Skin texture, relief, color, and overall cosmetic appearance were all rated as improved by three independent dermatologists. No signs of unwanted side effects were observed at any time point. This case report should be followed up with a larger case series or ideally a prospective randomized clinical trial to better establish FP as a safe and effective tool to treat reminiscent scars after CDLE.

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Management of dupilumab-associated ocular surface diseases in atopic dermatitis patients.

Atopic dermatitis is a chronic inflammatory skin disease characterised by eczematous skin lesions and intense pruritus. It is often associated with other atopic diseases such as allergic rhinitis and conjunctivitis, bronchial asthma and eosinophilic oesophagitis. Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis in Switzerland. Dupilumab targets the interleukin (IL)-4/IL-13 receptor and thus inhibits the signalling of IL-4 and IL-13, two key mediators of type 2 inflammation, resulting in an improvement of clinical signs and symptoms of atopic dermatitis. Patients with atopic dermatitis present more often with ocular surface diseases (OSDs), such as allergic conjunctivitis, blepharitis and keratitis as well as infectious conjunctivitis and keratoconus compared with the general population. Upon dupilumab therapy, increased rates of ocular surface diseases have been reported in clinical trials. Interestingly, dupilumab-associated (da) OSD is restricted to atopic dermatitis patients and has not been observed in asthma and chronic rhinosinusitis trials. Fortunately, most cases of dupilumab-associated OSD are mild-to-moderate and transient. Thus, ocular surface disease presents a particular adverse event of treatment with dupilumab in dermatology. This article aims at providing a practical guide for physicians, with a special focus on dermatologists, allergists and ophthalmologists in Switzerland, to the diagnosis and management of dupilumab-associated OSD in atopic dermatitis patients.For this purpose, an expert group of dermatologists and ophthalmologists from university and cantonal hospitals in Switzerland reviewed data on ocular surface diseases published in clinical trial and real-life reports of dupilumab therapy, published case reports and case series on the management of dupilumab-associated OSD, as well as recent recommendations provided by experts of national and international boards. Based on the observations of dupilumab-associated OSD and practical experiences in identifying and treating OSD, an algorithm has been developed that is specific to the needs in Switzerland. Considering concomitant ocular diseases and differential diagnoses, the clinical presentation of dupilumab-associated OSD and its response to therapeutic measures, a stepwise approach is recommended. Mild dupilumab-associated OSD can be managed by dermatologists and allergists, whereas patients with moderate-to-severe OSD requiring corticosteroid or calcineurin inhibitor therapy should necessarily be referred to an ophthalmologist. The effects of preventive measures, such as artificial tears, are uncertain. The recommendations provided here should guarantee a prompt and effective treatment of OSD for patients under dupilumab therapy in order to prevent that an otherwise potent therapy has to be ceased because of ocular adverse events.

[A non-infectious cellulitis to know: Wells' syndrome]. / Cellulite non infectieuse à connaître: le syndrome de Wells.

Wells' syndrome is a rare inflammatory eosinophilic dermatosis. It typically appears as a sudden-onset of one or multiple inflammatory plaques associated with a pruritus. General symptoms are rare. There is often blood eosinophilia and a marked dermal eosinophilic infiltrate with flame figures on skin biopsy. Numerous trigger factors and associated diseases are described. The etiology is unclear. Most experts believe it to be a type IV hypersensitivity reaction in predisposed individuals with an imbalance TH1/TH2 cells. Circulating TH2 cells may be implicated by producing IL- 5 which stimulates eosinophils' degranulation. The aim of this article is to review the diagnostic and therapeutic options of this pathology knowing that the main differential diagnosis is cellulitis of infectious origin.

Le syndrome de Wells est une dermatose éosinophilique rare qui se présente sous forme de plaques inflammatoires d'apparition brutale, souvent prurigineuses, généralement sans signes généraux. Une hyperéosinophilie sanguine est souvent présente et, en histopathologie, un infiltrat éosinophilique avec des images «â€…en flammèche ¼ est retrouvé. Il existe de nombreux facteurs déclenchants et maladies associées. La physiopathologie est inconnue, certains auteurs parlent d'une hypersensibilité retardée (réaction de type IV) sur un terrain prédisposé avec un déséquilibre TH1/TH2 et des cellules TH2 sécrétant de l'interleukine-5, qui stimulerait la dégranulation des éosinophiles. Le but de cet article est de faire le point sur cette pathologie rare, le principal diagnostic différentiel étant une cellulite d'origine infectieuse.

Topical Treatment of Psoriasis Vulgaris: The Swiss Treatment Pathway.

Topical treatment is crucial for the successful management of plaque psoriasis. Topicals are used either as a stand-alone therapy for mild psoriasis or else in combination with UV or systemic treatment for moderate-to-severe disease. For the choice of a suitable topical treatment, the formulation matters and not just the active substances. This expert opinion paper was developed via a non-structured consensus process by Swiss dermatologists in hospitals and private practices to illustrate the current treatment options to general practitioners and dermatologists in Switzerland. Defining treatment goals together with the patient is crucial and increases treatment adherence. Patients' personal preferences and pre-existing experiences should be considered and their satisfaction with treatment and outcome regularly assessed. During the induction phase of "classical" mild-to-moderate psoriasis, the fixed combination of topical calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g once daily is frequently used for 4-8 weeks. During the maintenance phase, a twice weekly (proactive) management has proved to reduce the risk of relapse. Of the fixed combinations, Cal/BD aerosol foam is the most effective formulation. However, the individual choice of formulation should be based on a patient's preference and the location of the psoriatic plaques. Tailored recommendations are given for the topical management of specific areas (scalp, facial, intertriginous/genital, or palmoplantar lesions), certain symptoms (hyperkeratotic or hyperinflammatory forms) as well as during pregnancy or a period of breastfeeding. As concomitant basic therapy, several emollients are recommended. If topical treatment alone does not appear to be sufficient, the regimen should be escalated according to the Swiss S1-guideline for the systemic treatment of psoriasis.

Skin Cancer Development in Solid Organ Transplant Recipients in Switzerland (Swiss Transplant Cohort Study).

IMPORTANCE: Skin cancer, in particular squamous cell carcinoma, is the most frequent malignancy among solid organ transplant recipients with a higher incidence compared to the general population. OBJECTIVE: To determine the skin cancer incidence in organ transplant recipients in Switzerland and to assess the impact of immunosuppressants and other risk factors. DESIGN: Prospective cohort study of solid organ transplant recipients in Switzerland enrolled in the Swiss Transplant Cohort Study from 2008 to 2013. PARTICIPANTS: 2,192 solid organ transplant recipients. MATERIALS AND METHODS: Occurrence of first and subsequent squamous cell carcinoma, basal cell carcinoma, melanoma and other skin cancers after transplantation extracted from the Swiss Transplant Cohort Study database and validated by medical record review. Incidence rates were calculated for skin cancer overall and subgroups. The effect of risk factors on the occurrence of first skin cancer and recurrent skin cancer was calculated by the Cox proportional hazard model. RESULTS: In 2,192 organ transplant recipients, 136 (6.2%) developed 335 cases of skin cancer during a median follow-up of 32.4 months, with squamous cell carcinoma as the most frequent one. 79.4% of skin cancer patients were male. Risk factors for first and recurrent skin cancer were age at transplantation, male sex, skin cancer before transplantation and previous transplantation. For a first skin cancer, the number of immunosuppressive drugs was a risk factor as well. CONCLUSIONS AND RELEVANCE: Skin cancer following solid organ transplantation in Switzerland is greatly increased with risk factors: age at transplantation, male sex, skin cancer before transplantation, previous transplantation and number of immunosuppressive drugs.