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Pathomechanisms of Chronic Spontaneous Urticaria: What Is Known and Up to Date

  • Urticaria (P Staubach, Section Editor)
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Abstract

The pathomechanism of chronic spontaneous urticaria (CSU), defined by the recurrence of short-lived wheals for more than 6 weeks without apparent triggers, remained to be mysterious until 1986. In that year, skin reactivity to the injection of autologous serum was reported in about half of patients with CSU; that observation and the subsequent discovery of histamine-releasing autoantibodies against the high-affinity IgE receptor (FcεRI) and against IgE in patients with CSU were major breakthroughs in the pathogenesis of this disorder. A role for complement activation in autoantibody-dependent histamine release was subsequently demonstrated. CSU was hence considered as an autoimmune disorder due to histamine-releasing autoantibodies in a consistent proportion of cases. However, this model does not fit all cases and shows several inconsistencies. Recently, it was shown that sera from most CSU patients are able to degranulate also mast cells lacking FcεRI, suggesting the involvement of other as yet unknown mechanisms. New light on CSU pathogenesis was shed by the demonstration of coagulation activation and eosinophil involvement during active phases of the disease, paralleling urticaria severity. Finally, the efficacy of omalizumab (a recombinant humanized monoclonal IgG anti-IgE antibody) in the treatment of refractory CSU opened a new scenario in the pathophysiology of the disease. Indeed, omalizumab has multiple biological effects relevant in CSU pathogenesis, such as binding of free IgE, downregulation of mast cell function including expression of high affinity IgE receptors, and induction of eosinophil apoptosis.

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Conflict of Interest

R Asero, A Tedeschi, AV Marzano, and M Cugno all declare no conflicts of interest.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

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Authors and Affiliations

  1. Ambulatorio di Allergologia, Clinica San Carlo, Via Ospedale, 21, Paderno Dugnano, 20037, Milan, Italy

    Riccardo Asero

  2. U.O. Allergologia e Immunologia Clinica, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Alberto Tedeschi

  3. Unità Operativa di Dermatologia, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy

    Angelo V. Marzano

  4. Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

    Massimo Cugno

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Asero, R., Tedeschi, A., Marzano, A.V. et al. Pathomechanisms of Chronic Spontaneous Urticaria: What Is Known and Up to Date. Curr Derm Rep 3, 191–196 (2014). https://doi.org/10.1007/s13671-014-0088-8

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