[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.

[Vitiligo, no longer a fatality in 2023].

Vitiligo is an acquired auto-inflammatory disorder characterized by a depigmentation. It is a polygenic disease developed in a context of allelic variations. Its pathophysiology is complex, associating intrinsic skin defects, exposome triggering factors and innate then adaptive auto-immune activation leading to the loss of melanocytes. The diagnosis is clinical. Nevertheless, Wood's lamp is mandatory to assess the lesions and their activity, especially in fair-skinned patients. The management of vitiligo is long and aims to halt the depigmentation process and to repigment the affected areas. This requires a combination of immunosuppressive topical or systemic treatment with ultraviolet rays from phototherapy or sun exposure.

Le vitiligo est une dépigmentation acquise bien limitée, d'origine auto-immune. Il s'agit d'une maladie polygénique survenant dans un contexte de variations alléliques prédisposant son apparition. Sa physiopathologie est complexe et associe des défauts intrinsèques de la peau, des facteurs déclenchants liés à l'exposome et une activation immunitaire innée, puis adaptative, conduisant à la perte des mélanocytes. Son diagnostic est clinique mais la lumière de Wood est indispensable pour apprécier les lésions et leur activité, notamment sur peau claire. La prise en charge du vitiligo est longue et a pour but d'interrompre la dépigmentation et de repigmenter les zones lésionnelles. Pour cela, il faut associer un traitement immunosuppresseur topique ou systémique à des rayons ultraviolets, soit naturels, soit de la photothérapie.

[Lipedema†: an unknown entity]. / Le lipœdème†: une entité méconnue.

Lipedema is an infrequently recognized disorder. It is characterized by bilateral painful enlargement of the legs due to abnormal depositions of subcutaneous fat, that can result in considerable disability. The diagnosis is established on the basis of medical history and clinical findings. Early diagnosis of this disorder is necessary to start adapted management and prevent progression and complications of the disease. Currently there is no curative treatment. The conservative treatment requires a multidimensional approach including manual lymph drainage, compression garments and management or prevention of obesity as well as other comorbidities. In some cases, surgery may be considered.

Le lipœdème est une pathologie méconnue et sous-diagnostiquée. Il se caractérise par une accumulation anormale et douloureuse de tissu adipeux sous-cutané aux membres inférieurs, pouvant induire une morbidité et un retentissement psychologique importants. Le diagnostic est clinique. Il doit être posé le plus tôt possible afin d'initier une prise en charge adaptée, et ainsi empêcher le développement de la maladie et de ses complications. Il n'existe pour l'heure pas de traitement curatif. La prise en charge doit être globale. Le traitement conservateur comprend des drainages lymphatiques manuels, une compression, une gestion ou une prévention de l'obésité ainsi que des éventuelles comorbidités. Dans certains cas, une chirurgie peut être envisagée en privilégiant une liposuccion par tumescence.

[Extracorporeal photopheresis]. / Photophérèse extracorporelle.

During the treatment of extracorporeal photopheresis (ECP), white blood cells are collected by apheresis and exposed to ultraviolet A after incubation with 8-methoxypsoralen. Although ECP was first developed for cutaneous T cell lymphoma, it has shown promising efficacy in a number of other serious conditions, like acute and chronic graft-versus-host disease, lung and cardiac transplant rejection and other autoimmune diseases. The ECP has been used for thirty years in some specialized centers but remains unknown to most of the physicians. The aim of this article is to review the practical aspects, the mode of action and the current indications of ECP.

La photophérèse extracorporelle (PEC) est une méthode thérapeutique qui consiste à irradier les leucocytes préalablement collectés par aphérèse et sensibilisés par le 8-méthoxypsoralène. Les bénéfices ont été démontrés, notamment pour le traitement des lymphomes cutanés T avancés, la maladie du greffon contre l'hôte (aiguë et chronique), le rejet de greffe d'organes solides comme le poumon et le cœur et certaines maladies autoimmunes. La PEC est pratiquée depuis trente ans dans certains centres universitaires spécialisés, mais reste pour l'heure méconnue des praticiens. L'objectif de cet article est de revoir les aspects pratiques, le mécanisme d'action et les principales indications de la PEC.

[Off-label indications of biological drugs in dermatology]. / Indications off-label des traitements biologiques en dermatologie.

Last years, the development of biological drugs substantially improved the outcome of many inflammatory diseases. In dermatology, this kind of therapy is essentially prescribed for the treatment of psoriasis, and include the anti-TNF, anti-IL-12/IL-23 and anti-IL-17. Despite these treatments have not yet been approved, they seemed to be efficient for the treatment of many other inflammatory dermatosis, like granulomatous diseases, neutrophilic diseases, hydradenitis suppurativa or pityriasis rubra pilaris.

[Dermatology: re-defining psoriasis]. / Dermatologie. Redéfinir Le psoriasis.

Psoriasis has long been regarded to be one entity, comprising both plaque-type and non plaque-type manifestations. Genetic studies now provide evidence that some pustular forms should be classified separately: a mutation in the gene encoding for the interleukin 36 receptor antagonist (IL36Ra) was f6und to be associated with generalized pustular psoriasis (GPP) in several Tunesian families. This finding was subsequently confirmed in different psoriasis cohorts around the world. Additionally, gain-of-function mutations in the gene for CARD 14 were identified. Clinical implications comprise a different approach to treat GPP through blocking interleukin 1beta.

Mixed Individual-Aggregate Data on All-Cause Mortality in Bullous Pemphigoid: A Meta-analysis.

Importance: The 1-year standardized mortality ratio (SMR) of bullous pemphigoid (BP) has been reported as 2.15 to 7.56 and lower in the US than in Europe. Objective: To estimate the worldwide 1-year SMR of BP. Data Sources: PubMed, Embase, Cochrane Library, Google Scholar, Lissa, and gray literature (eg, medRxiv) were screened for studies of BP published from inception to June 10, 2020, with review of reference lists. Study Selection: Retrospective and prospective studies reporting 1-year all-cause mortality rate in patients with BP and providing age statistics (eg, mean [SD]). Data Extraction and Synthesis: Two reviewers independently extracted the data. The 1-year SMR was computed in studies reporting 1-year mortality by combining information on age obtained from studies with aggregate data and individual data. Risk of representativity, misclassification, and attrition bias were assessed by a custom tool. Main Outcomes and Measures: The primary end point was the worldwide 1-year SMR. Secondary analysis included comparison of 1-year SMRs between continents in a meta-regression. Results: Three studies were performed in the US (n = 260), 1 in South America (n = 45), 16 in Asia (n = 1903), and 36 in Europe (n = 10 132) for a total of 56 unique studies and 12 340 unique patients included in the meta-analysis (mean [SD] age, 77.3 [12.7] years; 55.9% women). The mean (SD) patient age in the United States was 75.6 (13.7) years; in Asia, 73.8 (13.6) years; and in Europe, 78.1 (12.3) years. The worldwide 1-year SMR was estimated at 2.93 (95% CI, 2.59-3.28; I2 = 85.6%) for all 56 studies. The 1-year SMR in the US was 2.40 (95% CI, 0.89-3.90; I2 = 86.3%) for 3 studies; in Asia, 3.53 (95% CI, 2.85-4.20; I2 = 86.3%) for 16 studies; and in Europe, 2.77 (95% CI, 2.35-3.19; I2 = 86.3%) for 36 studies. After adjustment on the expected 1-year mortality rate, the European 1-year SMR did not differ significantly from the 1-year SMR in the United States (-0.48 vs Europe; 95% CI, -2.09 to 1.14; P = .56) and Asia (0.51 vs Europe; 95% CI, -0.56 to 1.58; P = .35). Risk of attrition bias was high (>10% censorship) in 16 studies (28.6%), low in 16 (28.6%), and unclear in 24 (42.9%). Only 4 studies (7.1%) had a sampling method guaranteeing the representativity of BP cases in a population. Conclusions and Relevance: Although heterogeneity was high and overall quality of follow-up was poor, this meta-analysis confirms the high mortality rate among patients with BP.

Sign of Leser-Trélat and Cutaneous T-Cell Lymphoma: A Rare Association.

Sign of Leser-Trélat is a rare paraneoplastic cutaneous manifestation, characterized by the sudden appearance and rapid increase in size and number of seborrheic keratoses, accompanied by pruritus. Edmund Leser and Ulysse Trélat described this sign in 1890. Since their first description, their conclusions have been considered controversial and some authors assert the absence of a causal link. It seems to be frequently associated with solid tumors and in particular gastrointestinal cancer. Here, we describe a new case associated with a cutaneous T-cell lymphoma and a partial response to extracorporeal photopheresis.

Multiple Eruptive Sebaceous Hyperplasia Secondary to Cyclosporin in a Patient with Bone Marrow Transplantation.

Many cutaneous complications have been described in patients treated with cyclosporin. Alterations of the pilosebaceous unit such as hypertrichosis are particularly frequent. However, the occurrence of sebaceous hyperplasia is exceptional. These lesions seem to be specific to cyclosporin rather than secondary to immunosuppression. Here, we report an exceptional case of eruptive and disseminated sebaceous hyperplasia arising in a bone marrow transplant recipient only a few months after starting immunosuppressive treatment with cyclosporin.

A rare case of primary cutaneous follicle centre lymphoma presenting as a giant tumour of the scalp and combined with JAK2V617F positive essential thrombocythaemia.

Primary cutaneous follicle centre lymphoma (PCFCL) is a rare cutaneous B cell lymphoma in middle-age adults with excellent prognosis. Here we present a case of a patient with a PCFCL in the form of a giant tumour of the scalp in combination with a myeloproliferative neoplasm, JAK2V617F positive essential thrombocythaemia. This case may be of interest because of the favourable outcome in spite of the large size of the PCFCL, the rare combination with essential thrombocythaemia and because it contributes to discussion on the role of JAK2 mutation in such patients.