[en] Antihistaminic drugs have been used successfully for many years in the treatment of allergic diseases. Second-generation antihistamines have fewer sedating side effects than first-generation agents, and the number of newer drugs available for clinical use is growing. Various methods have been used to assess antihistaminic activity, the most popular of which is the epicutaneous histamine-induced wheal and flare. This test relies on the ability of epicutaneously injected histamine to bring about the wheal and flare, a neurovascular response that involves reflex vasodilation (flare) and local swelling caused by plasma extravasation (wheal). Antihistamines have been compared on the basis of their ability to block the histamine-induced wheal and flare in the skin. Results of these trials have been applied to predict the global antiallergic efficacy of various antihistamines. The review has examined the reliability of suppression of the histamine wheal and flare reaction in the skin to predict an antihistamine's clinical efficacy in two common allergic diseases seasonal allergic rhinitis and chronic idiopathic urticaria. Although histamine is one mediator in the allergic response in the skin and nasal mucosa, many other agents are important modulators of the allergic response. In addition, the major structural and functional differences that exist between the nasal mucosa and the skin affect the type of local response. These manifest themselves as differences between the responses to antigen and histamine challenge in the skin and the nose. The allergic responses in these tissues are not simply the consequence of one chemical but are the result of a cascade of interactions among various cells and mediators. The clinical manifestations of these complex interactions obviously cannot be fully replicated by injection of one chemical mediator, histamine, into the outer layer of the skin. Studies with antihistamines have shown that certain drugs, such as cetirizine, are more suppressive than others (loratadine, terfenadine) in controlling the histamine-induced wheal and flare reaction in the skin. When the clinical efficacy of these medications is compared in clinical trials in seasonal allergic rhinitis and chronic idiopathic urticaria, all are equally efficacious in controlling symptoms. Although the histamine-induced wheal and flare reaction can serve as a useful clinical pharmacologic test to assess dose-response relations for an antihistamine, its lack of correlation with clinical responses among antihistamines indicates that this model should not be used to predict or compare clinical efficacies of antihistamines in seasonal allergic rhinitis and chronic idiopathic urticaria.
Disciplines :
Immunology & infectious disease
Author, co-author :
Monroe, E. W.
Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Shalhoub, R. F.
Language :
English
Title :
Appraisal of the validity of histamine-induced wheal and flare to predict the clinical efficacy of antihistamines.
Bovet D, Staub A. Action protectice des ethers phenoliques au cours de l'intoxication histaminique. Cr Soc Biol (Paris) 1937;124:547-9.
Howarth F, Emanuel M, Holgate S. Astemizole, a potent histamine H-l receptor antagonist: effects in allergic rhinoconjunctivitis, on antigen and histamine induced skin wheal and relationship to serum levels. Br J Clin Pharmacol 1984;18:1-8.
deShazo RD, Levinson AI, Dvorak HF, Davis RW. The late phase skin reaction: evidence for activation of the coagulation system in an IgE-dependent reaction in man. J Immunol 1979;122:692-8.
Cockcroft S, Gomperts BD. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature 1985;314:534-6.
Anggard A, Lundberg JM, Lundblad L. Nasal autonomic innervation with special reference to peptidergic nerves. Eur J Respir Dis 1983;64(suppl):143.
Baroody F, Proud D, Kagey-Sobotka A, et al. The effects of H-l antihistamines on the early allergic response. Ann Allergy 1989;63:551-5.
Huston DP, Bressler RB. Urticaria and angioedema. Med Clin North Am 1992;76:805-40.
Kaplan AP. Urticaria and angioedema. In: Middleton E, Reed CE, Ellis EF, et al., eds. Allergy: Principles and Practice. Vol. II, 4th ed. St. Louis: C.V. Mosby Co., 1993:1553-80.
Roman IJ, Kassem N, Gural RP, Herron I. Suppression of histamine-induced wheal response by loratadine (SCH 29851) over 28 days in man. Ann Allergy 1986;57:253-6.
Small P. Comparison of cetirizine and loratadine in inhibiting both early and late cutaneous reactions [Abstract]. J Allergy Clin Immunol 1993;91:244.
VanRooy P, Janssens M. Comparison of trough effects of five non-sedating antihistamines on histamine-induced wheal and flare reactions [Abstract]. J Allergy Clin Immunol 1991;87:51.
Paul E, Löhr A, Bödeker RH. Wirkungsvergleich von antihistaminika am modell der durch histamin und kodein induzierten hautreaktion. Allergologie 1994;17:486-9.
Shall L, Thompson DA, Barkley ASJ, Millard LG. Comparative inhibition profiles of three non-sedating antihistamines assessed by an extended Lewis model. Clin Exp Allergy 1992;22:711-6.
Simons FER, McMillan JL, Simons KJ. A double-blind, single dose, crossover comparison of cetirizine, terfenadine, loratadine, astemizole and chlorpheniramine versus placebo: suppressive effects on histamine-induced wheals and flares during 24 hours in normal subjects. J Allergy Clin Immunol 1990;86:540-7.
Rosenzweig P, Ulliac N, Cabanis MJ. Comparative wheal and flare study of mizolastine vs terfenadine, cetirizine, loratadine and placebo in healthy volunteers [Abstract], Br J Clin Pharmacol 1994;37:116P.
Lever LR, Hill S, Marks R, Rosenberg R, Thompson D. Effects of cetirizine, loratadine and terfenadine on histamine wheal and flare reactions. Skin Pharmacol 1992;5:29-33.
Humphreys F, Hunter JAA. The effects of astemizole, cetirizine and loratadine on the time course of wheal and flare reactions to histamine, codeine and antigen. Br J Dermatol 1991;125:364-7.
Kontou-Fili K, Paleologos G, Herakleous M. Suppression of histamine-induced skin reactions by loratadine and cetirizine diHCl. Eur J Clin Pharmacol 1989;36:617-9.
Pechadre JC, Vernay D, Trolese JF, Bloom M, Dupont P, Rihoux JP. Comparison of the central and peripheral effects of cetirizine and terfenadine. Eur J Clin Pharmacol 1988;35:255-9.
Rihoux JP, Dupont P. Comparative study of the peripheral and central effects of terfenadine and cetirizine 2 HCl. Ann Allergy 1987;59:235-8.
Fadel R, Herpin-Richard N, Dufresne F, Rihoux JP. Pharmacological modulation by cetirizine and loratadine of antigen and histamine-induced skin wheals and flares, and late accumulation of eosinophils. J Int Med Res 1990;18:366-71.
Breneman D, Bergstresser P, Boggs P, et al. A multi-site comparative study of the efficacy and safety of cetirizine vs astemizole and placebo in the treatment of chronic idiopathic urticaria [Abstract]. J Allergy Clin Immunol 1992;89:249.
Belaich S, Bruttmann G, DeGreef H, et al. Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria. Ann Allergy 1990;64:191-4.
Grant JA, Bernstein DI, Buckley CE, et al. Double blind comparison of terfenadine, chlorpheniramine, and placebo in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1988;81:574-9.
Guerra L, Vincenzi C, Valeri F, Marchesi E, Tosti A, Comparison between loratadine and cetirizine in the treatment of chronic urticaria. Proceedings of the 2nd Congress of the European Academy of Dermatol and Venereol. Athens, October 10-13, 1991:206.
Alomar A, De La Cuadro J, Fernandez J. Cetirizine versus astemizole in the treatment of chronic idiopathic urticaria. J Int Med Res 1990;18:358-65.
Dockx P, Lambert J, Arendt C, Darte D. Double-blind placebocontrolled comparison of cetirizine and terfenadine in chronic idiopathic urticaria. Presented at the symposium "Cetirizine: a new era in allergotherapy." Brussels, March 27-30, 1988:23.
Go MJT, Wuite J, Arendt C, Bernheim J. Double-blind placebo controlled comparison of cetirizine and terfenadine in chronic idiopathic urticaria. Acta Therapeut 1989;15:77.
Kint A, Constandt L, Arendt C, Bernheim J. Comparative efficacy of cetirizine and terfenadine in the treatment of chronic idiopathic urticaria. Acta Therapeut 1989;15:66.
Guilett G, Sayag J, Leroy D, et al. Evalaution de l'efficacite et de la tolerance de la loratadine dans l'urticaire idiopathique chronique et la dermatite atopique. Abstr Dermatol 1992;138:1-4.
Marcher E, Eichelberg D. Terfenadine and cetirizine in chronic idiopathic urticaria. Allergologie. Proceedings of the 14th Congress of the European Academy of Allergology and Clinical Immunol [Abstract]. Berlin, 1989:91.
D'Ambrosio FP, Niosi G, Orlando F, Musarra A, et al. Double blind comparative study on cetirizine and terfenadine treatment of CIU [abstract]. Schweizerische Medizinische Wochenscrift 1991;121(suppl):11.
Mauracher EH, Riches DJ. Comparative trial of two non sedating antihistamines, loratadine vs astemizole, in Chinese patients with chronic urticaria. Immunol Allergy Pract 1992;14:223.
Davies BH, Mullins J, Couch HA. Prophylactic treatment in seasonal allergic rhinitis. A comparison of cetirizine (Zirtek) and terfenadine (Triludan). Clin Trials J 1989;26:100-7.
Bousquet J. Clinical activity and side effects of loratadine and astemizole in patients with seasonal allergic rhinitis. Proceedings of the 44th Annual Congress of the American College of Allergists. Boston, November 1987.
Kemp JP, Buckley CE, Gershwin ME, et al. Multicenter, double-blind, placebo-controlled trial of terfenadine in seasonal allergic rhinitis and conjunctivitis. Ann Allergy 1985;54:502-9.
Dockhorn RJ, Bergner A, Connell JT, et al. Safety and efficacy of loratadine (Sch-29851): a new non-sedating antihistamine in seasonal allergic rhinitis. Ann Allergy 1987;58:407-11.
De Carpio J, Kabbash L, Turenne Y, et al. Efficacy and safety of loratadine (10 mg once daily), terfenadine (60 mg twice daily), and placebo in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 1989;84:741-6.
Kemp JR, Bahna SL, Chervinsky P, et al. A comparison of loratadine, a new nonsedating antihistamine, with clemastine and placebo in patients with fall seasonal allergic rhinitis. Am J Rhinol 1987;1:151-4.
Siegal S, Ellis E, Kemp J, et al. Efficacy and safety of loratadine in the treatment of allergic rhinitis in children [abstract]. Allergy 1988;7(suppl):5.
Reed CE, Aaronson DW, Bahna SL, et al. Comparison of cetirizine and astemizole treatment of seasonal allergic rhinitis [abstract]. Ann Allergy 1991;66:104.
Horak F, Bruttmann G, Pedrali P, et al. A multicencre study of loratadine, terfenadine and placebo in patients with seasonal allergic rhinitis. Arzneimittel-Forschung. 1988;38:124-8.
Alexander M, Small P, Thomson D, et al. Efficacy and tolerability of cetirizine, loratadine and placebo in the treatment of seasonal allergic rhinitis: A Canadian multicenter study [Abstract]. J Allergy Clin Immunol 1994;93:163.
Buckley CE, Buchman E, Falliers CJ, et al. Terfenadine treatment of fall hay fever. Ann Allergy 1988;60:123-8.
Backhouse CI, Rosenberg R. Prophylaxis of whole season hay fever symptomatology: a comparison of terfenadine with chlorpheniramine. Br J Clin Pract 1987;41:995-9.
Backhouse CI, Brewster BS, Lockhart JDF, et al. Terfenadine in allergic rhinitis. A comparative trial of a new antihistamine versus chlorpheniramine and placebo. Practitioner 1982;226:347-51.
Oei HD. Double-blind comparison of loratadine (Sch 29851), astemizole, and placebo in hay fever with special regard to onset of action. Ann Allergy 1988;61:436-9.
Skassa-Brociek W, Bousquet J, Montes F, et al. Double-blind placebo-controlled study of loratadine, mequitazine, and placebo on the symptomatic treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 1988;81:725-30.
Brandon ML, Weiner M. Clinical investigation of terfenadine, a non-sedating antihistamine. Ann Allergy 1980;44:71-5.
Brostoff J, Lockhart JDF. Controlled trial of terfenadine and chlorpheniramine maleate in perennial rhinitis. Postgrad Med J 1982;58;422-3.
Grossman J, Ball R, Shulan D, et al. Cetirizine vs. terfenadine in the treatment of allergic seasonal rhinitis [abstract]. N Engl Regional Allergy Proc 1988;9:370.
Backhouse CI, Renton R, Fidler C, Rosenburg RM. Multicentre double-blind comparison of terfenadine and cetirizine in patients with seasonal allergic rhinitis. Br J Clin Pract 1990;44:88-91.
Haltom JR, Mitchell DQ, Jackson M, et al. Comparison of cetirizine and terfenadine in the treatment of seasonal allergic rhinitis [abstract]. Ann Allergy 1992;68:110.
Lockey RF, Findley S, Mitchell DQ, et al. Eifects of cetirizine versus terfenadine in seasonal allergic rhinitis. Ann Allergy 1993;10:311-5.
Caiaffa MF, Iudice A, Macchia L, et al. Multicenter double-blind comparative study of terfenadine and cetirizine in hay fever. J Investig Allergol Clinical Immunol 1992;2:162-6.
Harcup JW, Hawkes G, Saul PA. The efficacy and sedative profile of astemizole and cetirizine in the treatment of grass pollen hay fever in general practice. Br J Clin Pract 1993;47:131-5.
Herman D, Arnaud A, Dry J, et al. Clinical effectiveness and safety of loratadine vs. cetirizine in the treatment of seasonal allergic rhinitis [abstract]. Clin Exp Allergy 1990;20(suppl):56.
Olsen OT, Nuchel Peterson L, Hoi L, et al. Comparison of loratadine and terfenadine in allergic seasonal rhinoconjunctivitis with emphasis on nasal stuffiness and peak flow. Arzneimittel-Forschung 1992;42:1227-31.
Rijintes E, Ghys L, Rihoux JP. Astemizole and cetirizine in the treatment of seasonal allergic rhinitis: a comparative double-blind multicenter study. J Int Med Res 1990;18:219-24.
Tjwa M, Widjaja P, DelBono L, et al. Loratadine compared with cetirizine in patients with seasonal allergic rhinitis. Allergy 1992;47(suppl):174.
D'Amato G, Martucci P, De Palma R, Lobefalo G. Anything new in antihistamine therapy? Comparative study on cetirizine vs. terfenadine [abstract]. Clin Exp Allergy 1990;20(suppl):101.
Rossi O, Bertoni M. Efficacy of cetirizine in the treatment of seasonal allergic rhinoconjunctivitis [abstract]. Allergy Clin Immunol News 1991;(suppl):358.
Katelaris C. Comparative effects of loratadine and azatadine in the treatment of seasonal allergic rhinitis. Asian Pacific J Allergy Immunol 1990;8:103-7.
Persi L, Demoly P, Harris AG, Tisserand B. Michel FB, Bousquet J. Comparison between nasal provocation tests and skin tests in patients treated by loratadine (L) and cetirizine (C). J Allergy Clin Immunol. In press.