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Immune factors such as interferon‑ɣ and interleukin 4 belong to the group of cytokines that are dependent on type I/II receptors for their signal transmission. Upon activation, these receptors transmit their signal to the cell nucleus and, thus, modulate gene transcription via a signaling cascade consisting of Janus kinases (JAK). This family of four kinases (JAK 1, JAK 2, JAK 3, and tyrosine kinase 2 (TYK2)) subsequently activate members of the signal transducer and activator of transcription (STAT). This finding turned the JAK/STAT signaling pathway into a pharmacological target for the treatment of inflammatory diseases in which cytokines using type I/II receptors play a pathogenic role. In 2018, the European Medicines Agency (EMA) approved tofacitinib for the treatment of psoriatic arthritis. This was the first approval of a JAK/STAT pathway inhibitor for patients treated by dermatologists and rheumatologists. Since then, several new JAK inhibitors have been approved for dermatologic diseases such as atopic dermatitis, alopecia areata, vitiligo, and plaque-type psoriasis. In addition, JAK inhibitors are being investigated for the treatment of many other skin diseases. Thus, systemic JAK inhibitors complete the spectrum of immunotherapeutics with a broader immunological approach compared to monoclonal antibodies. The low molecular weight of JAK inhibitors enables the preparation of these drugs for both systemic and topical administration. Their utilization could represent a valuable alternative to topical steroids. The safety profile of JAK inhibitors must be taken into account. Possible long-term effects may become apparent in the next few years. This article describes both approved JAK inhibitors and relevant new JAK inhibitors that are promising candidates for approval as therapeutics in dermatology., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Chronic inflammatory skin diseases are of great social and medical importance and require effective drug therapy. Phosphodiesterase 4 (PDE4) inhibitors represent a possible therapeutic option by regulating inflammatory processes. PDEs cause the release of proinflammatory cytokines by interfering with signaling pathways. The PDE4 inhibitors apremilast (treatment of psoriasis and Behçet's disease), roflumilast (treatment of chronic obstructive pulmonary disease), and crisaborole (treatment of atopic dermatitis) are currently approved in Europe., Psoriasis: Apremilast is used for second-line treatment of plaque psoriasis and psoriatic arthritis and has a favorable side effect profile. Topical PDE4 inhibitors are currently being researched and have not yet been approved by the European Medicines Agency (EMA)., Atopic Dermatitis: The topical PDE4 inhibitor crisaborole was approved by the EMA in 2020 as a topical treatment alternative to glucocorticoids and calcineurin inhibitors. Although the substance has shown good tolerability in studies and also alleviates the accompanying itching, it did not find its way onto the German market. BEHçET'S DISEASE: Apremilast is approved for the treatment of Behçet's disease in adults with refractory, severe oral ulcers., Outlook: Case studies have also demonstrated the efficacy of systemic PDE4 inhibition in other skin diseases (including blistering autoimmune dermatoses, lichen planus, and acantholytic genodermatoses). The substances are also being researched and used to treat extracutaneous inflammatory diseases., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The importance of topically applied pharmaceuticals, especially for the treatment of dermatological diseases, is still essential. Thanks to detailed knowledge of the organisation and function of the physicochemical barrier of the skin, new galenic concepts have increasingly been developed to market maturity in recent years. Colloidal drug carrier systems in particular, but also targeted physicochemical modifications of matrices are used to optimise the cutaneous bioavailability of topically applied drugs. In addition, new molecules are increasingly becoming available for the development of these preparations or drugs known from systemic therapy are being formulated into topicals. Against this background, dermatopharmacology is also developing more and more into a highly specialised science in this area, which is producing innovative concepts for the therapy of special indications. In addition to the classic small-molecule drugs, biotechnological molecules are increasingly finding their way into application, so that a modern age of dermatopharmacology has dawned, which will open up previously unimagined possibilities for topical therapy now and in the coming years., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

For the treatment of moderate to severe atopic dermatitis (AD), two groups of modern systemic therapies with a total of five drugs are currently approved in Germany: biologics (dupilumab, tralokinumab) and "small molecules" (abrocitinib, baricitinib, upadacitinib). The growing armamentarium of therapy options, especially with more than one drug per substance group, makes it challenging for practitioners to select the appropriate treatment for the individual patient. In this review article, the preconditions and requirements of each drug group as well as the corresponding substances are presented comparatively. On the one hand, direct therapeutic effects on the severity of the disease are considered and, on the other hand, the spectrum of potential adverse drug reactions are discussed. In particular, short- and long-term effects, the safety profile and the patient's concomitant diseases represent key factors for shared decision-making with regard to select the optimum personalized therapy option., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

In 1997 rituximab, a genetically engineered chimeric monoclonal antibody (mAb) targeting CD20 expressed on B cells was approved for treatment of non-Hodgkin's lymphoma. Since then, pharmacological improvements combined with increased knowledge on the immunopathogenesis of diseases led to the development of specific mAb targeting different antigens (e.g., interleukins or transmembrane receptors). This approach reshaped the therapeutic methodology in many fields, including dermatology. Nowadays, the treatment of frequent and possibly impairing inflammatory disorders such as psoriasis, atopic dermatitis or hidradenitis suppurativa have different mAbs approved for both adult and pediatric patients. This class of drugs often shows a more favorable outcome and a better safety profile than routine immunosuppressants, such as steroids and steroid-sparing substances. For many years mAbs also represented a pillar of oncological treatment for severe diseases such as malignant melanoma or Merkel cell carcinoma. This review summarizes the current knowledge on already approved and promising new mAbs for the treatment of inflammatory and oncological skin diseases., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Psoriasis is a chronic inflammatory systemic disease that requires optimal long-term management due to its high prevalence in the population and the numerous comorbidities that severely impair quality of life. A variety of treatment options are now available. In addition to objective skin findings and a specific location such as nails or genital area, the presence of psoriatic arthritis and other comorbidities as well as the disease burden of the affected person play a decisive role in individualized treatment decision-making. Good communication with the patient is fundamental to understand the individual needs and expectations of the patient. Shared decision-making can positively influence adherence and thus also the clinical outcome and patient satisfaction. In addition, interdisciplinary collaboration is crucial and often necessary for a comprehensive therapy strategy., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Janus kinase inhibitors (JAKi) represent an immunomodulatory targeted therapy in various dermatoses. Throughout the past few years, JAKi have been approved for atopic dermatitis (AD), psoriasis vulgaris (PSO), alopecia areata (AA), and vitiligo. Further indications are currently under investigation. In this article the various systenic and topical JAKi used in dermatology are being presented regarding their efficacy and safety profile. A specific focus will be set on handling with safety issues including screening and control measures during treatment with JAKi. In addition, future use of JAKi in various dermatological diseases for which nowadays only insufficient therapy options are available is being discussed., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief., Objective: Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given., Material and Methods: Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented., Results: In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T‑helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC)., Conclusion: A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Due to its high prevalence and associated socioeconomic consequences, hand eczema is a burden for those affected and for society. The various hand eczema subtypes must be differentiated from each other through structured anamnesis and diagnostics in order to initiate cause-related preventive measures in addition to symptomatic therapy. There are new developments in the diagnosis, prevention, and treatment of hand eczema. The diagnostic possibilities are being expanded through molecular methods. Modern topical and systemic therapies offer promising treatment options for patients with atopic but also chronic hand eczema regardless of the underlying etiology., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)