Clinical Reviews in Allergy & Immunology

, Volume 45, Issue 1, pp 47–62 | Cite as

Pathogenic Intracellular and Autoimmune Mechanisms in Urticaria and Angioedema

  • Katherine Altman
  • Christopher Chang


Urticaria and angioedema are common disorders. Chronic urticaria is defined as lasting longer than 6 weeks. Causes of chronic urticaria fall into the following categories: physical, allergic, hereditary, autoimmune, and idiopathic. Basophils and mast cells are the primary effector cells responsible for clinical symptoms and signs. These cells produce and secrete a variety of mediators including histamine, leukotrienes, prostaglandins, cytokines, chemokines, and other pro-inflammatory mediators. This leads to vasodilation, fluid exudation, increased vascular permeability, and accumulation of additional secondary inflammatory cells. Two mechanisms have been investigated as possibly contributing to the pathogenesis of chronic urticaria. One is the development of autoantibodies to FcεRI or IgE on mast cells and basophils. This appears to be responsible for 30–50 % of cases. The other is dysregulation of intracellular signaling pathways involving Syk, SHIP-1, or SHIP-2 in basophils and mast cells. The primary treatment for chronic urticaria is to treat the underlying pathology, if any can be identified. Otherwise, in idiopathic cases, H1 antihistamines, H2 antihistamines, antileukotrienes, and corticosteroids constitute the main pharmacologic treatment modalities. In severe and recalcitrant cases of chronic and autoimmune urticaria, immunosuppressive drugs have been used, most commonly cyclosporin. More recent experimental studies have also suggested that omalizumab, an anti-IgE therapy, may be of benefit. Currently, inhibitors of Syk are also being developed and tested in the laboratory and in animal models. As our understanding of the pathogenesis of idiopathic urticaria increases, development of additional drugs targeting these pathways may provide relief for the significant physical and psychological morbidity experienced by patients with this disorder.


Angioedema Autoimmune Basophil FcεRI Histamine IgE Leukotriene Mast cell Omalizumab Syk Urticaria 


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Allergy, Asthma and ImmunologyThomas Jefferson University, Nemours/AI duPont Hospital for ChildrenWilmingtonUSA
  2. 2.SeattleUSA

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