Inhibition of the histamine‐induced weal and flare response: a valid surrogate measure for antihistamine clinical efficacy?

Abstract

Histamine plays a central role in allergic responses. Inhibition of the weal and flare response to histamine is a traditional pharmacodynamic tool to measure the activity of H(1)-receptor antagonists. The time course and duration of cutaneous weal and flare inhibition are often used as surrogate measures of clinical efficacy. Pharmacodynamic differences among antihistamines are often interpreted to indicate differences in clinical efficacy. A systematic review of literature from 1980 to 2006 regarding the histamine induced weal and flare was undertaken. Search terms included 'histamine', 'skin test', 'weal', 'flare', and 'antihistamine'; retrieved articles were searched for relevant studies not identified initially. Data from human studies on the inhibition of the weal and flare by second-generation antihistamines were extracted and assessed. A literature search from 1980 to 2006 was undertaken for comparative studies of second-generation antihistamines in the clinical settings of allergic rhinitis (AR) and chronic idiopathic urticaria; data extracted from these studies underwent systematic review. Differences were noted among second-generation antihistamines in terms of their ability to inhibit the histamine-induced weal and flare. Corresponding differences in terms of clinical efficacy in AR and chronic urticaria were not identified following a systematic review. The reasons for the disconnect between pharmacodynamic effects and clinical efficacy may include differences between the route and concentration of histamine, the involvement of mediators other than histamine in the allergic response, and the short time course of pharmacodynamic studies. The histamine-induced weal and flare response is a pharmacodynamic test that should not be used to compare the clinical efficacy of different antihistamines, and is not an adequate alternative to clinical end-point assessments in AR or chronic idiopathic urticaria.

BSACI guideline for the management of chronic urticaria and angioedema

“…The efficacy of the various antihistamines using suppression of the weal and flare response does not correlate with clinical urticarial responses and hence should not be solely used to predict or compare clinical responses in CU [78][79][80].…”

Prediction of the Efficacy of Antihistamines in Chronic Spontaneous Urticaria Based on Initial Suppression of the Histamine- Induced Wheal

“…Devillier et al [19] concluded that measuring suppression of the wheal and flare reaction by antihistamines does not correlate with clinical efficacy based on multiple intervening factors, including-but not limited to-dose, metabolism, and effects of other mediators on the course of chronic urticaria. Kalogeromitros et al [20] observed that environmental and metabolic factors such as menstrual cycle could affect test reactivity [20].…”

“…However, there is no agreement on the usefulness of SPT as a surrogate measure of clinical efficacy. Devillier et al [19] searched the literature from 1980 to 2006 and concluded that histamine SPT or intradermal testing should not be used to compare the clinical efficacy of antihistamines in allergic rhinitis or chronic urticaria. On the other hand, in a more recent study published in 2012, Church and Maurer [10] concluded that the wheal and flare response appears to be the best tool for evaluation of the effectiveness of antihistamines in clinical practice.…”

Escin Inhibits Type I Allergic Dermatitis in a Novel Porcine Model

“…Wheal formation after allergen exposure is caused by a combination of low-level endogenous histamine and additional stimuli. A much higher concentration of externally applied histamine is required to provoke the same allergic reaction [36]. In the absence of known specific allergens in the pig, a direct comparison of allergen, histamine, and compound 48/80 is not feasible.…”