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Torsten Zuberbier (editor) - Urticaria and Angioedema

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Torsten Zuberbier (editor) Urticaria and Angioedema

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Urticaria is one of the most common diseases in dermatology and allergy. Unlike many other diseases, the ? eeting nature of the wheals makes ? rst diagnosis by both patients and phy- cians in many cases easy. However, this only refers to the ordinary wheals. The disease itself is highly complex in nature, with variety of clinical manifestations ranging from pinpoi- sized wheals to extensive angiodema. Complexity is also seen in the diversity of possible eliciting factors, the many different clinical subtypes and the therapeutic responsiveness. Only in recent years has a better understanding of the diversity in the different subtypes led to new classi? cations and new evidence-based guidelines for diagnostics and mana- ment of the disease. While mast cells are in the center of most urticaria reactions, it is now clearly understood that the responsible mediators are not only limited to histamines. The current book appears in a series of books by Springer. In 1986, the ? rst monograph was edited by Professor Henz ne Chanewsky. Since then, two updates of the book have appeared in the German language with Professor Henz as ? rst editor and T. Zuberbier, J. Grabbe, and E. Monroe as the co-editors of the most recent English version, published in 1998. All these books have been written as a joint effort of Professor Henz together with her team at the Department of Dermatology at the Virchow Clinic, Humboldt University, Berlin.

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Torsten Zuberbier , Clive E. H. Grattan and Marcus Maurer (eds.) Urticaria and Angioedema 10.1007/978-3-540-79048-8_1 Springer-Verlag Berlin Heidelberg 2010
1. History of Urticaria
M Greaves 1
(1)
Cutaneous Allergy Clinic, St. Johns Institute of Dermatology, St. Thomas Hospital, London, SE1 7EH, UK
M Greaves
Email:
Core Messages
  • The beginning of the twentieth century ushered in the era of molecular medicine, eventually leading to unravelling of the molecular and immunological basis of urticaria.
  • The mast cell and its histamine content remain central to the pathophysiology of the pruritic wheal in most forms of urticaria, and the synthesis, storage,regulation of release of histamine as well as molecular characterisation of its receptors are becoming well understood.
  • The challenge of the past 50 years has been to understand the causation of the promiscuous activation of dermal and mucosal mast cells in idiopathic chronic urticaria and angioedema.
  • The discovery in the 1980s of autoreactivity in the serum of some patients with chronic urticaria (the autologous serum skin test) was a major step forward and prompted attempts to identify and characterise this activity.
  • The subsequent finding in chronic urticaria of specific complement-dependent autoantibodies, which release histamine and other mediators from mast cells and basophils via dimerisation of their high affinity IgE receptors, has stimulated intense interest in the multifactorial modes of activation of mast cells and basophils in this disorder.
  • Antihistamines, discovered in the 1940s, remain the cornerstone of treatment of most types of urticaria. Although recent derivative (second-generation) compounds manifest greatly refined properties, they are often only moderately effective.
  • New therapeutic approaches round the corner include bradykinin B2 antagonists (for angioedema) and the anti-IgE immunobiologic omalizumab
1.1 Introduction
The history of urticaria divides itself conveniently into the early, clinically descriptive, and later pathophysiological eras. Much has been written on the early history of urticaria as a clinical entity, from Hippocrates in the fourth century BC to Heberden and Willan at the end of the eighteenth century AD. For useful accounts of urticaria in early Western writings, the reader is referred to publications by Czarnetzki [] and the ESHDV Special Annual Lecture entitled The History of Urticaria and Angioedema delivered by the late Lennart Juhlin in 2000, a transcript of which is available online. However, in the last hundred years, a dramatic increase in the understanding of the cellular and molecular basis of some common forms of urticaria took place, the foundations for which were laid down by pioneers in the latter years of the nineteenth century and in the early and later twentieth century. This period is the focus of the present account, which attempts to reveal to the reader a historical perspective on how we got to where we are today in urticaria.
1.2 The Cellular and Molecular Basis of Urticaria: First Steps
Although the mast cell (mastzellen) was discovered by Paul Ehrlich in 1877 [].
It was Lewis who first delineated the potency of histamine as a mediator of whealing in human skin [].
1.3 The Enigma of Chronic Idiopathic Urticaria
The problem of how, in urticaria, the dermal mast cell is prompted to relieve itself of its burden of histamine and other mediators has puzzled investigators in the post Second World War era. The discovery and characterisation of the reaginic IgE immunoglobulin by Ishizaka [] between dermal mast cell-bound IgE and specific allergen leading to release of histamine and other mast cell-derived mediators. However, the aetiology and pathogen-esis of chronic idiopathic urticaria (CIU) remained obscure and even in the twenty-first century there remain numerous unanswered questions. Why do the dermal mast cells degranulate explosively in a seemingly random way with no evident triggering factor?
In the 1960s and 1970s, attempts were made, mainly in Europe, to popularise the role of common food additives, colouring agents and preservatives such as tartrazine, sodium benzoate, and antioxidants as aetiological agents in CIU. Protagonists of this theory included Juhlin, Doeglas and Warner [], remains controversial.
Foci of infections are always liable to be invoked to explain otherwise inexplicable relapses in any chronic diseases, and chronic urticaria is no exception. The literature contains numerous usually anecdotal accounts of patients with severe chronic and recalcitrant urticaria who made a dramatic recovery following removal of an infected gallbladder/ tooth, or treatment of an infected sinus or urinary tract. The 1980s saw the emergence of a new putative microbial culpritHelicobacter pylori. Because of its ubiquity, especially in European populations, it was frequently found in patients with CIU. When patients with Helicobacter were treated, some got better both from the infection and from the urticaria. Although carefully controlled studies have not substantiated an aetiological relationship between H pylori and urticaria despite its frequency in these patients [].
The notion that antibodies may be causative in CIU is an old one. As long ago as 1962, Rorsman, a Swedish dermatologist, reported the striking basopenia in chronic urticaria and remarked on its absence in physical urticarias. He also pointed out that In cases where the basopenia is marked it appears probable that antigenantibody reactions bring about degranulation of basophil leukocytes []. However, at this juncture there was no convincing evidence that any autoantibodies found in CIU were anything more than passive bystanders in the pathogenesis of this disorder.
Against this background, an important observation was made in 1986 by Grattan [] supported the view that these autoantibodies are the cause of the whealing in those patients that have them. Although autoimmune urticaria has yet to justify, in a strict sense, its designation as an autoimmune disease (there is no animal model), these advances have for the first time put the investigation and treatment of chronic urticaria on a sound scientific basis. Lack of a convenient specific and sensitive screening test for autoimmune urticaria remains the main drawback to further progress.
1.4 Treatment of Urticaria: Antihistamines
Fortunately, most patients with chronic urticaria, whatever the cause, can be effectively managed by H1 antihistamines. These were first characterised by Bovet and Staub [], they were small and in any case their use was largely superseded by the advent of second-generation antihistamines.
Second-generation H1 antihistamines, as defined by Simons [] has laid the foundation for emergence of a truly new third generation of anthistamines for clinicians and patients alike to look forward to.
Future developments in the diagnosis and management of urticaria have also been greatly encouraged by the recent establishment of European Guidelines for definition, classification, diagnosis and management of urticaria []. These should also give much needed help to clinicians faced with investigation and treatment of urticaria.
1.5 Take Home Pearls
  • The autologous serum skin test established that in patients with chronic idiopathic urticaria, the causation was endogenous rather than due to external factors such as food allergy or pseudoallergy, and focal infection.
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