TNF Inhibitors in Dermatology: From Thalidomide to Biologics

Inflammatory skin diseases represent an important part of dermatological pathology. Recent advances in the understanding of inflammatory processes have identified various cytokines, and in particular Tumor necrosis factor (TNF) as a potent and central proinflammatory cytokine involved in many conditions, including rheumatic, gastrointestinal tract, and skin diseases. Therefore, inhibition of TNF has become a major therapeutic target in the treatment of inflammatory disorders. Thalidomide is one of the first TNF inhibitors that have been used. It was initially prescribed by chance and pragmatically by dermatologists in inflammatory diseases such as erythema nodosum leprosum, lupus and severe aphtosis, but its identification as an inhibitor of TNF is more recent. The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the emergence of 3 new anti-TNF alpha drugs. These so-called biologics are two monoclonal antibodies (infliximab and adalimumab) and one fusion protein composed of a soluble TNF alpha receptor (etanercept) specifically directed against TNF. The first clinical data are very impressive, but new and unexpected side effects have progressively been described. These powerful drugs are increasingly prescribed, and the aim of this work is to summarize the recent knowledge on the old (thalidomide) and new (biologics) TNF inhibitors in dermatological diseases

[What's new in internal medicine?]

This article focuses on current trends in various autoimmune diseases of interest for the dermatologist. In the antiphospholipid syndrome, many news: better characterization of the severe disease, involvement of the mTOR pathway in the vasculopathy-induced renal disease, and diversification of the therapeutic approaches: use of mTOR inhibitors and several biologics, new various antiplatelet and anticoagulants. In dermatomyositis, new autoantibodies are better characterized with a good correlation with clinical disease; the results of a large study on genetic predisposition to the disease are available. There are also some therapeutic innovations in systemic sclerosis: benefit of rituximab that seems well tolerated, the results of a large controlled European study about aggressive immunoablative chemotherapy followed by autologous stem cells have just been published, intralesional stem cells injections in the fingers of sclerodactylic patients. Finally, news in celiac disease that is constantly increasing and whose mild forms often have cutaneous manifestations, leading to diagnosis

Pityriasis rubra pilaire

Pityriasis rubra pilaris is a rare heterogeneous dermatosis associating three clinical signs to different degrees: follicular corneal papules, reddish-orange palmoplantar keratoderma and erythematosquamous lesions that may in some cases be very extensive, interspersed with patches of healthy skin. The aetiology is unclear, and in most cases, the trigger factors consist of trauma or infection, probably in subjects with an existing predisposition. In other cases, the condition is associated with immunological disorders or, in familial cases, genetic keratinisation abnormalities similar to ichthyosis. Given the widely varying signs, several classifications have been proposed, based on clinical criteria and outcomes. The outcome varies in accordance with the clinical forms involved. Therapeutic approaches are poorly qualified and there have been no clinical trials due to the rarity of the disease. However, the best results appear to have been obtained using oral retinoids, with second-line therapy comprising methotrexate and cyclosporine. The landscape of therapeutic strategy seems to be changing with the advent of new anti-tumour necrosis factor and anti-interleukin-12/23 antibodies

Pityriasis rubra pilaire : une dermatose mal connue

Pityriasis rubra pilaris is a rare heterogeneous disorder characterized by follicular keratosis, perifollicular erythema and palmoplantar hyperkeratosis. The aetiology is still unknown. In the majority of cases some triggering factors are found such as trauma or bacterial infection, possibly on a predisposed condition. In other cases, some immunological disorders are associated, and in familial cases a genetic disorder of keratinization has been suggested. The evolution is variable according to the clinical type. The treatment is not well defined, and there is a lack of clinical trials. The best results however are obtained with oral retinoids, methotrexate or ciclosporine as alternative therapy. New TNF inhibitors and anti-IL-12/23 showed a good result and could be have interest in the future

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

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 « en flammèche » 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