The challenges of chronic urticaria part 1: Epidemiology, immunopathogenesis, comorbidities, quality of life, and management

Abstract

This is Part 1 of an updated follow-up review of a World Allergy Organization (WAO) position paper published in 2012 on the diagnosis and treatment of urticaria and angioedema. Since 2012, there have been advances in the understanding of the pathogenesis of chronic urticaria, and greater experience with the use of biologics, such as omalizumab, in patients with severe refractory disease. For these reasons, the WAO decided to initiate an update targeted to general practitioners around the world, incorporating the most recent information on epidemiology, immunopathogenesis, comorbidities, quality of life, clinical case presentations, and the management of chronic spontaneous and chronic inducible urticaria, including urticaria in special situations such as childhood and pregnancy. A special task force of WAO experts was invited to write the different sections of the manuscript, and the final document was approved by the WAO Board of Directors. This paper is not intended to be a substitute for current national and international guidelines on the management of urticaria and angioedema but to provide an updated, simplified guidance for physicians around the world who manage patients with this common ailment.

Keywords: Angioedema; Chronic inducible urticaria; Chronic spontaneous urticaria; Omalizumab Treatment; Urticaria.

Fig. 1

Urticaria classification

Fig. 2

Urticaria can be divided into 3 clinical phenotypes on the basis of its duration (less or more than 6 weeks) and in the presence or absence of inducing factors (inducible vs spontaneous). The known stimuli can be a physical agent like temperature, pressure, U/V light, or others as water, chemical irritants or exercise. The unknown stimuli can be related to autoimmunity or autoallergic mechanisms. b. Mast cell activation can be elicited by internal dysregulation and/or external stimuli activation via membrane receptors. Abbreviations. Syk: spleen tyrosine kinase; SHIP = Src homology 2 (SH2)-containing inositol phosphatases; Ag: antigen or allergen (both); C5aR: receptor for C5a; PAR: protease-activated receptor; PGD2: prostaglandin D2; CRTh2: chemoattractant receptor homologous molecule expressed on TH2 cells; IL-4: interleukin 4; IL-4Ra: interleukin 4 receptor alpha chain; Subst P: substance P; MBP: major basic protein; MRGPRX2: mas-related G-protein coupled receptor X2; Eos: eosinophils; PAMPs: pathogen-associated molecular patterns; DAMPs: damage-associated molecular patterns; TLRs: toll-like receptors; FceRIa: type I Fc epsilon receptor alpha chain; TPO: thyroid peroxidase; IL-24: interleukin-24

Fig. 3

Potential targets for the treatment of chronic urticaria with biotherapeutic agents

Fig. 4

Potential biomarkers for chronic spontaneous urticaria

Fig. 5

Biomarkers as predictors of response in chronic spontaneous urticaria