This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell–driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert‐guided and evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.

These recommendations for the definition, diagnosis and management of chronic inducible urticaria (CIndU) extend, revise and update our previous consensus report on physical urticarias and cholinergic urticaria (Allergy, 2009). The aim of these recommendations is to improve the diagnosis and management of patients with CIndU. Our recommendations acknowledge the latest changes in our understanding of CIndU, and the available therapeutic options, as well as the development of novel diagnostic tools.

The regression phase of the hair cycle (catagen) is an apoptosis‐driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor β1 (TGF‐β1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF‐β1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF‐β1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF‐β1 null mice and age‐matched wild‐type littermates, and assessed the effects of TGF‐β1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF‐β1 —/— mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF‐β1 — /— mice displayed more Ki‐67‐positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF‐β1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratino‐cytes was reduced and the number of TUNEL + cells was increased in the TGF‐β1‐treated mice compared to controls. Double visualization of TGF‐β type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF‐β1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TGF‐βRII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).—Foitzik, K., Lindner, G., Mueller‐Roever, S., Maurer, M., Botchkareva, N., Botchkarev, V., Handjiski, B., Metz, M., Hibino, T., Soma, T., Dotto, G. P., Paus, R. Control of murine hair follicle regression (catagen) by TGF‐β1 in vivo. FASEB J. 14, 752–760 (2000)