Antihistamines and Itch

Abstract

Histamine is one of the best-characterized pruritogens in humans. It is known to play a role in pruritus associated with urticaria as well as ocular and nasal allergic reactions. Histamine mediates its effect via four receptors. Antihistamines that block the activation of the histamine H₁receptor, H₁R, have been shown to be effective therapeutics for the treatment of pruritus associated with urticaria, allergic rhinitis, and allergic conjunctivitis. However, their efficacy in other pruritic diseases such as atopic dermatitis and psoriasis is limited. The other histamine receptors may also play a role in pruritus, with the exception of the histamine H₂receptor, H₂R. Preclinical evidence indicates that local antagonism of the histamine H₃receptor, H₃R, can induce scratching perhaps via blocking inhibitory neuronal signals. The histamine H₄receptor, H₄R, has received a significant amount of attention as to its role in mediating pruritic signals. Indeed, it has now been shown that a selective H₄R antagonist can inhibit histamine-induced itch in humans. This clinical result, in conjunction with efficacy in various preclinical pruritus models, points to the therapeutic potential of H₄R antagonists for the treatment of pruritus not controlled by antihistamines that target the H₁R.

Substance P activates Mas-related G protein–coupled receptors to induce itch

“…The limited efficacy of antihistamines in most pruritic conditions 20,21 highlights the importance of histamine-independent mechanisms of itch. Mrgprs are among the most important mediators of histamine-independent itch.…”

Levocetirizine for the treatment of itch in psoriasis patients: An open‐label pilot study in a real‐world setting

“…In contrast, the role of histamine in psoriasis-related itch is controversial. It is widely accepted that histamine is not a key mediator in psoriasis (Reich & Szepietowski, 2007;Reich & Szepietowski, 2014;Thurmond, Kazerouni, Chaplan, & Greenspan, 2015). However, there is evidence that histamine could be of relevance in psoriatic itch.…”

“…As the effect of antihistamines on itch in psoriasis patients has not been investigated in a prospective real-world setting yet (Thurmond et al, 2015), we examined the short-term effects of levocetirizine, second-generation antihistamine 1 receptor (H1) antihistamine, on psoriasis-related itch and itch-related quality of life in an open-label setting. We selected this nonsedating histamine as we hypothesized that antihistamines might have a direct antipruritic effect in psoriasis.…”

Spinal Functions of B-Type Natriuretic Peptide, Gastrin-Releasing Peptide, and Their Cognate Receptors for Regulating Itch in Mice

“…Generally, ligand-receptor signaling plays a fundamental role in the generation of itch. For instance, keratinocyte-derived histamine, which binds to the transmembrane H 1 receptor, is a well known pruritogen and had been considered as a possible target for clinical therapies (Thurmond et al, 2015). However, antihistamines are not effective in alleviating itch derived from most dermatoses, systemic diseases, and opioid administration (Biro et al, 2005;Yosipovitch and Bernhard, 2013;van Zuuren et al, 2014).…”