Antihistamines in Dermatology

Along with antibiotics, antihistamines are the most widely used systemic drugs in dermatology. This is attributable to the major role played by histamine in common diseases such as urticaria and atopic eczema. Of the currently recognised four subtypes of G protein-coupled histamine receptors, only the H₁ and H₂ subtypes have been positively identified in human skin. Traditionally believed to be competitive antagonists of histamine, H₁ and H₂ antihistamines are now considered to behave as inverse agonists. By consensus, H₁ antihistamines are classified as ‘first generation’ (associated with troublesome side-effects including somnolence, anti-adrenergic and atropine-like actions) and ‘second-generation’ compounds (in which these side-effects are reduced or absent). The main indications for H₁ antihistamines in skin are suppression of pruritus in urticaria and atopic eczema, both of which are associated with increased mast cell numbers and tissue histamine levels. However the evidence basis for use in atopic eczema is ambiguous and controversial, even though these drugs are widely used in practice. Currently, significant side-effects are mainly confined to the first-generation compounds and are especially troublesome in the elderly. Psychomotor impairment may persist throughout the day following administration. Anti-cholinergic and anti-α-adrenergic blockade and cardiotoxicity (torsade de pointes) may also occur with first-generation antihistamines. Two early low-sedation second-generation antihistamines caused arrhythmias in a small number of patients but these compounds have now been withdrawn. Generally, the second-generation H₁ antihistamines are well tolerated.