Ensayo

Clinical pearls

What the first 10,000 patients with chronic urticaria have
taught me: A personal journey
Allen P. Kaplan, MD

Charleston, SC

Key words: Urticaria, angioedema, histamine, antihistamine,
corticosteroids, cyclosporine, anti-IgE receptor

Chronic urticaria remains one of the disorders treated by
allergists with which there is (and has been throughout my
lifetime)associated myths regarding the cause of the disorder and
its treatment that are extremely difficult to dispel. In this brief
article I would like to address some of these beliefs, review the
literature where it exists, point out where there are gaps in our
understanding, and convey some of my own conclusions that will,
hopefully, become hypotheses for future investigation. Table I
lists the beliefsthat I think are false and potentially detrimental
to the care of patients. I will expand on each of these.
I became board certified in allergy and clinical immunology in
1974, and that was a period in which chronic urticaria was
seriously considered by many to be an emotional disorder.1,2 The
idea remains prominent within the public at large, leading to questions asked by many new patients,such as ‘‘Is it my nerves?’’ Factitious urticaria is another term for dermatographism, which
implies that the skin reaction is not real or that the patient self-inflicts the rash and has only himself or herself to blame. It does not
acknowledge the severe pruritus associated with a functional skin
abnormality (yet to be defined) of cutaneous mast cells as the underlying problem. Angioneuroticedema is now just angioedema
as we move away from a psychic cause of these things. The discovery of C1 esterase inhibitor deficiency as the defect in hereditary angio(neurotic)edema was particularly helpful.
Foods and food additives as a putative cause of chronic
urticaria date almost as far back as ‘‘nerves’’ as a cause. I will
mention one in particular. James and Warin3 described exacerbations ofurticaria after challenge with food yeasts and Candida albicans extracts; 69% of patients with a positive skin prick test
response to C albicans had a positive challenge result to food
yeast, and a ‘‘large percentage’’ responded to a low-yeast diet.
At the National Institutes of Health (1978-1987), some of our first
observations disproved this thesis by limiting foods to a diet of
From theDepartment of Medicine, Medical University of South Carolina, and the
National Allergy, Asthma, and Urticaria Centers of Charleston.
Disclosure of potential conflict of interest: A. P. Kaplan has received honoraria from
Sanofi-Aventis, GlaxoSmithKline, and Novartis/Genentech; has received consulting
fees from Lev Pharmaceutical; and has received research support from Lev Pharmaceutical andNovartis.
Received for publication August 5, 2008; revised October 23, 2008; accepted for
publication October 24, 2008.
Available online December 11, 2008.
Reprint requests: Allen P. Kaplan, MD, Department of Medicine, Division of Pulmonary
Critical Care Medicine and Allergy and Clinical Immunology, Medical University of
South Carolina, Charleston, SC-29425. E-mail: kaplana@musc.edu.
J AllergyClin Immunol 2009;123:713-7.
0091-6749/$36.00
Ó 2009 American Academy of Allergy, Asthma & Immunology
doi:10.1016/j.jaci.2008.10.050

rice, lamb, and water for 5 days and recording the effect on the
person’s urticaria. The study was neither controlled nor blinded.
Nevertheless, no one improved, and after the first 20 patients,
we stopped. I assumed that chronic urticaria was not caused byfood allergy or by uncharacterized reactions to food additives
and have never become suspicious that this could be incorrect.
By 1980, it was concluded that food additives precipitate hives
in 2000 of 6600 patients with chronic urticaria, and one author
added that reactions in asthmatic subjects are even higher.4 As
the decades passed, the reader will note that IgE-mediated food
allergy is no...