Recommendations for risk minimization when using Janus kinase inhibitors for the treatment of chronic inflammatory skin diseases.

In accordance with article 20 of Regulation (EC) No 726/2004, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has re-evaluated the safety of Janus kinase inhibitors for the treatment of inflammatory diseases and formulated safety information deviating from the previous indications in the respective summary of product characteristics of the products concerned. These refer to the consideration of a possibly increased risk of venous thromboembolic or severe cardiovascular events, an increased infection rate and an increase in the prevalence of skin cancer across drugs and indications. Therefore, in patients with independent risk factors (age 65 years and older, smokers or former smokers, patients with oral contraception or hormone replacement therapy and other risk factors), it is recommended to use Janus kinase inhibitors therapeutically only if there are no suitable treatment alternatives. To facilitate a pragmatic and thorough detection of high-risk patients in everyday clinical practice, an interdisciplinary checklist was developed that is suitable as a working tool from the perspective of the dermatologist.

[Therapeutic peculiarities in diseases of the nipple skin]. / Therapeutische Besonderheiten bei Erkrankungen der Mamillenhaut.

The nipple region is characterized by special anatomical conditions and from a dermatological perspective can be divided into breast skin, skin of the areola and the skin of the nipple. In a clinical context the nipples are often altered during lactation by mechanical alteration, changes in the environment with maceration by the milk flow and by microbial pathogens. In addition, there is a risk of developing puerperal mastitis. Outside of pregnancy and lactation, eczema diseases are occasionally found on the mammary skin, often with atopic disposition (atopic nipple eczema) or as irritant contact eczema ("joggers nipple"). More rarely, allergic contact eczema is observed from preservatives in topical preparations or metals (piercings). Also, in the context of a scabies infestation involvement of the nipples, especially in women, is regularly observed. Of great clinical importance are rare preinvasive lesions of breast cancer or Paget's disease of the mamilla of the extramammary type. Due to the special anatomical conditions, it is obvious that specific penetration conditions are also derived from the application of topical substances. Experimental studies on human skin ex vivo suggest that depending on the molecular weight and solubility of the drug as well as the vehicle system used, a significant increase in cutaneous bioavailability, especially on the nipple itself through the transpapillary diffusion pathway, may occur. This should be considered in particular in the topical application of drugs with known potential of dose-dependent side effects (e.g. glucocorticoids); however, there is still no clinical evidence for this.