Summary Although other forms of allergic disease were described in antiquity, hay fever is surprisingly modern. Very rare descriptions can be traced back to Islamic texts of the 9th century and European texts of the 16th century. It was only in the early 19th century that the disease was carefully described and at that time was regarded as most unusual. By the end of the 19th century it had become commonplace in both Europe and North America. This paper attempts to chart the growth of hay fever through the medical literature of the 19th century. It is hoped that an understanding of the increase in prevalence between 1820 and 1900 may provide an insight for modern researchers and give some clues into possible reasons for the epidemic nature of the disease today.

The paper provides a historical overview of the discovery of both histamine and the H1 antihistamines. The context of these discoveries is provided in relation to the development of medicinal chemistry during the 19th century. Background is provided on the history of discovery of mechanisms of anaphylaxis and allergy and the immunology of hypersensitivity at the end of the 19th and early 20th century. The discovery of histamine and the antihistamines is then discussed in relation to the development of pharmacological receptor theory culminating in the discovery of the first antihistamines in the 1930s and their widespread clinical introduction in the 1940s.

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1 The efficacy of astemizole, a new, long acting, oral histamine HI-receptor antagonist was compared to placebo for the treatment of allergic rhinitis and conjunctivitis during the grass pollen season of 1982. Sixty-three patients with a positive skin prick test to grass pollen and current symptoms participated in an 8 week, double-blind, randomized study. 2 Astemizole, 10 mg, was significantly better than placebo in alleviating both nose (P < 0.05) and eye (P < 0.01) symptoms despite significantly greater use of the reserve medication, clemastine, by the placebo group (P < 0.003). 3 There was a lag period of 5 days after initiation of therapy before treatment benefit became manifest. Subdivision of nasal symptoms indicated significant improvement compared to placebo over the 8 weeks for sneezing (P < 0.05) and runny nose (P < 0.05) but not blocked nose. The absence of effect on nasal blockage was confirmed by parallel measurement of nasal calibre by body plethysmography. 4 The antihistaminic potency of astemizole was indicated by an 80% inhibition of the histamine induced skin weal response after 8 weeks therapy. A positive correlation was found between serum drug levels and % inhibition of histamine skin weal (r = 0.64, P < (.001).5 Astemizole was free from adverse sedative or anticholinergic effects but did cause a mean increase in weight of 1.3 kg (P < 0.01) after 8 weeks therapy, not found with placebo.

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