Copyright © Blackwell Publishing, Inc., 2005
Blackwell Publishing, Ltd.
Antihistamines and their role as antipruritics
MICHAEL O’DONOGHUE & MICHAEL D. THARP
Department of Dermatology, Rush University Medical Center, Chicago, Illinois
ABSTRACT:Antihistamines that bind to the histamine 1 receptor (H1) serve as important therapeutic agents to counter the effects of histamine in the skin. Two generations of antihistamines exist; however, second-generation agents are more advantageous because they cause less sedation, have a longer half life and are more selective for the H1 receptor. While H1 antihistamines have proven to be effective atreversing the pruritus and cutaneous lesions of chronic urticaria, their ability to treat pruritus associated with other cutaneous and systemic diseases is unproven. KEYWORDS: antihistamines, atopic dermatitis, urticaria, wheal-and-ﬂare reaction
Histamine was ﬁrst identiﬁed by Sir Henry Dale in 1910, and in the ensuing 10–15 years became recognized as an important mediator ofimmediate allergic reactions (1,2). Histamine receptors were discovered in 1937, and by 1942 the ﬁrst (ﬁrst generation) antihistamines were developed. More recently, second-generation antihistamines have become available for clinical use and offer advantages over ﬁrst-generation agents (1–5). Histamine is derived from L-histidine by the enzymatic activity of histidine decarboxylase. In the skin, mosthistamine arises from dermal mast cells; however, circulating basophils also produce this amine. Histamine mediates it effects in tissues by binding to four receptor subtypes (H1–H4); however, H1 and H2 receptors are preferentially expressed in the skin (4,6). The afﬁnity of histamine for the H1 receptor is approximately 10 times that for the H2 receptor; thus, histamineinduced cutaneousvasodilatation, edema, and pruritus occur predominantly through binding to H1 receptors (3). Likewise, the wheal-and-ﬂare
Address correspondence and reprint requests to: Michael D. Tharp, MD, Department of Dermatology, Rush University Medical Center, 707 S. Wood St., Annex Bldg., Rm. 220, Chicago, IL 60612, or email: email@example.com.
reaction caused by histamine occur primarily through the bindingto H1 receptors in postcapillary venules (7). Pruritus or itch is transmitted by dedicated afferent C-type nerve ﬁbers in the skin, which are distinct from polymodal neurons associated with pain (8). These unique itch neurons are characterized by their slow conduction velocities, extensive terminal branching, and prolonged responses to histamine stimulation (9). In the skin, histamine stimulatesC-type ﬁbers, ultimately leading to the perception of itch in the central nervous system (CNS) (8,9). Positron emission tomography (PET) studies have shown that histamine-induced itch activates multiple sites in the brain, including the supplementary motor area. These observations lend support to the conclusion that there is no single CNS itch center and that the perception of itch is linked tothe need to scratch (9). Histamine-induced itch can be eliminated with ﬁeld stimulation in which superﬁcial cutaneous nerves are activated electrically. Field stimulation inhibits itch produced by histamine as much as scratching eliminates the itch sensation. Nilsson et al. have demonstrated that cutaneous ﬁeld stimulation signiﬁcantly decreases the perception of histamine-induced pruritus withoutaffecting the wheal-and-ﬂare reaction, suggesting that its mechanism of action is independent of histamine receptors. It is believed that ﬁeld stimulation
O’Donoghue & Tharp
activates myelinated A neurons that in turn inhibit neural circuits in the gray matter of the spinal cord leading to itch suppression (8–10). The topical application of capsaicin also inhibits histamine-induced...