Allergy, Histamine and Antihistamines

  • Martin K. ChurchEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 241)


This chapter concentrates on the role in allergic disease of histamine acting on H1-receptors. It is clear that allergy has its roots in the primary parasite rejection response in which mast cell-derived histamine creates an immediate hostile environment and eosinophils are recruited for killing. This pattern is seen in allergic rhinitis where the early events of mucus production and nasal itching are primarily histamine mediated whereas nasal blockage is secondary to eosinophil infiltration and activation. In asthma, the role of histamine is less clear. Urticaria is characterized by mast cell driven pruritic wheal and flare-type skin reactions that usually persist for less than 24 h. Although the events leading to mast cell degranulation have been unclear for many years, it is now becoming evident that urticaria has an autoimmune basis. Finally, the properties of first- and second-generation H1-antihistamines and their role in allergic is discussed.


Allergy Asthma H1-antihistamines Parasitology allergic rhinitis Urticaria 


  1. Agostini JV, Leo-Summers LS, Inouye SK (2001) Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. Arch Intern Med 161:2091–2097CrossRefPubMedGoogle Scholar
  2. Altrichter S, Peter HJ, Pisarevskaja D et al (2011) IgE mediated autoallergy against thyroid peroxidase – a novel pathomechanism of chronic spontaneous urticaria? PLoS One 6:e14794CrossRefPubMedPubMedCentralGoogle Scholar
  3. Baroody FM, Naclerio RM (2011) Nasal-ocular reflexes and their role in the management of allergic rhinoconjunctivitis with intranasal steroids. World Allergy Organ J 4:S1–S5CrossRefPubMedPubMedCentralGoogle Scholar
  4. Baroody FM, Foster KA, Markaryan A et al (2008) Nasal ocular reflexes and eye symptoms in patients with allergic rhinitis. Ann Allergy Asthma Immunol 100:194–199CrossRefPubMedGoogle Scholar
  5. Bar-Sela S, Reshef T, Mekori YA (1999) IgE antithyroid microsomal antibodies in a patient with chronic urticaria. J Allergy Clin Immunol 103:1216–1217CrossRefPubMedGoogle Scholar
  6. Callebaut I, Vandewalle E, Hox V et al (2012) Nasal corticosteroid treatment reduces substance P levels in tear fluid in allergic rhinoconjunctivitis. Ann Allergy Asthma Immunol 109:141–146CrossRefPubMedGoogle Scholar
  7. Church MK (2011) Safety and efficacy of bilastine: a new H(1)-antihistamine for the treatment of allergic rhinoconjunctivitis and urticaria. Expert Opin Drug Saf 10:779–793CrossRefPubMedGoogle Scholar
  8. Church MK, Mcgill JI (2002) Human ocular mast cells. Curr Opin Allergy Clin Immunol 2:419–422CrossRefPubMedGoogle Scholar
  9. Church MK, Collier HO, James GW (1972) The inhibition by dexamethasone and disodium cromoglycate of anaphylactic bronchoconstriction in the rat. Br J Pharmacol 46:56–65CrossRefPubMedPubMedCentralGoogle Scholar
  10. Church MK, Maurer M, Simons FE et al (2010) Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper. Allergy 65:459–466CrossRefPubMedGoogle Scholar
  11. Church DS, Church MK, Scadding GK (2016) Allergic rhinitis: impact, diagnosis, treatment and management. Clin Pharmacist 8:249–255Google Scholar
  12. Concha LB, Chang CC, Szema AM et al (2004) IgE antithyroid antibodies in patients with Hashimoto’s disease and chronic urticaria. Allergy Asthma Proc 25:293–296PubMedGoogle Scholar
  13. Conlon NP, Edgar JD (2014) Adherence to best practice guidelines in chronic spontaneous urticaria (CSU) improves patient outcome. Eur J Dermatol 24:385–386PubMedGoogle Scholar
  14. Coombs RRA, Gell PGH (1968) Classification of allergic reactions responsible for drug hypersensitivity reactions. In: Coombs RRA, Gell PGH (eds) Clinical aspects of immunology, 2nd edn. Davis, Philadelphia, PAGoogle Scholar
  15. Corren J, Manning BE, Thompson SF et al (2004) Rhinitis therapy and the prevention of hospital care for asthma: a case-control study. J Allergy Clin Immunol 113:415–419CrossRefPubMedGoogle Scholar
  16. Dunford PJ, O’donnell N, Riley JP et al (2006) The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. J Immunol 176:7062–7070CrossRefPubMedGoogle Scholar
  17. Farre M, Perez-Mana C, Papaseit E et al (2014) Bilastine vs. hydroxyzine: occupation of brain histamine H1-receptors evaluated by positron emission tomography in healthy volunteers. Br J Clin Pharmacol 78:970–980CrossRefPubMedPubMedCentralGoogle Scholar
  18. Graham JE, Rockwood K, Beattie BL et al (1997) Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 349:1793–1796CrossRefPubMedGoogle Scholar
  19. Grattan CE, Francis DM, Hide M et al (1991) Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria. Clin Exp Allergy 21:695–704CrossRefPubMedGoogle Scholar
  20. Gray SL, Anderson ML, Dublin S et al (2015) Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med 175:401–407CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gruber BL, Baeza ML, Marchese MJ et al (1988) Prevalence and functional role of anti-IgE autoantibodies in urticarial syndromes. J Invest Dermatol 90:213–217CrossRefPubMedGoogle Scholar
  22. Hatada Y, Kashiwakura J, Hayama K et al (2013) Significantly high levels of anti-dsDNA immunoglobulin E in sera and the ability of dsDNA to induce the degranulation of basophils from chronic urticaria patients. Int Arch Allergy Immunol 161(Suppl 2):154–158CrossRefPubMedGoogle Scholar
  23. Hide M, Francis DM, Grattan CE et al (1993) Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med 328:1599–1604CrossRefPubMedGoogle Scholar
  24. Hiraoka K, Tashiro M, Grobosch T et al (2015) Brain histamine H1 receptor occupancy measured by PET after oral administration of levocetirizine, a non-sedating antihistamine. Expert Opin Drug Saf 14:199–206CrossRefPubMedGoogle Scholar
  25. Hogg JC, Pare PD, Boucher RC et al (1979) The pathophysiology of asthma. Can Med Assoc J 121:409–414PubMedPubMedCentralGoogle Scholar
  26. Holloway JW, Arshad SH, Holgate ST (2010a) Using genetics to predict the natural history of asthma? J Allergy Clin Immunol 126:200–209 (quiz 210-1)CrossRefPubMedGoogle Scholar
  27. Holloway JW, Yang IA, Holgate ST (2010b) Genetics of allergic disease. J Allergy Clin Immunol 125:S81–S94CrossRefPubMedGoogle Scholar
  28. Kallos P, Kallos L (1984) Experimental asthma in guinea pigs revisited. Int Arch Allergy Appl Immunol 73:77–85CrossRefPubMedGoogle Scholar
  29. Kaplan AP (2004) Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol 114:465–474 (quiz 475)CrossRefPubMedGoogle Scholar
  30. Kaplan AP, Greaves M (2009) Pathogenesis of chronic urticaria. Clin Exp Allergy 39:777–787CrossRefPubMedGoogle Scholar
  31. Kay AB (1985) Eosinophils: role in asthma, allergy and parasite immunity. N Engl Reg Allergy Proc 6:341–345CrossRefPubMedGoogle Scholar
  32. Kolkhir P, Church MK, Weller K et al (2016) Autoimmune chronic spontaneous urticaria: what we know and what we don’t know. J Allergy Clin Immunol (in press)Google Scholar
  33. Maurer M, Altrichter S, Bieber T et al (2011a) Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase. J Allergy Clin Immunol 128(202–209):e5Google Scholar
  34. Maurer M, Weller K, Bindslev-Jensen C et al (2011b) Unmet clinical needs in chronic spontaneous urticaria. A GA(2)LEN task force report. Allergy 66:317–330CrossRefPubMedGoogle Scholar
  35. Maurer M, Church MK, Goncalo M et al (2015) Management and treatment of chronic urticaria (CU). J Eur Acad Dermatol Venereol 29(Suppl 3):16–32CrossRefPubMedGoogle Scholar
  36. Mcevoy LK, Smith ME, Fordyce M et al (2006) Characterizing impaired functional alertness from diphenhydramine in the elderly with performance and neurophysiologic measures. Sleep 29:957–966CrossRefPubMedGoogle Scholar
  37. Mcgill JI, Holgate ST, Church MK et al (1998) Allergic eye disease mechanisms. Br J Ophthalmol 82:1203–1214CrossRefPubMedPubMedCentralGoogle Scholar
  38. Metz M, Ohanyan T, Church MK et al (2014) Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: a retrospective clinical analysis. J Dermatol Sci 73:57–62CrossRefPubMedGoogle Scholar
  39. Miura M, Uno T (2010) Clinical pharmacokinetics of fexofenadine enantiomers. Expert Opin Drug Metab Toxicol 6:69–74CrossRefPubMedGoogle Scholar
  40. Murphy K, Travers P, Walport M (2008) Janeway’s immunobiology, 7th edn. Garland Science, AbingdonGoogle Scholar
  41. Patou J, De Smedt H, Van Cauwenberge P et al (2006) Pathophysiology of nasal obstruction and meta-analysis of early and late effects of levocetirizine. Clin Exp Allergy 36:972–981CrossRefPubMedGoogle Scholar
  42. Puxeddu I, Piliponsky AM, Bachelet I et al (2003) Mast cells in allergy and beyond. Int J Biochem Cell Biol 35:1601–1607CrossRefPubMedGoogle Scholar
  43. Rorsman H (1962) Basophilic leucopenia in different forms of urticaria. Acta Allergol 17:168–184CrossRefPubMedGoogle Scholar
  44. Scadding GK, Durham SR, Mirakian R et al (2008) BSACI guidelines for the management of allergic and non-allergic rhinitis. Clin Exp Allergy 38:19–42CrossRefPubMedGoogle Scholar
  45. Shindo H, Ishii K, Yanase Y et al (2012) Histamine release-neutralization assay for sera of patients with atopic dermatitis and/or cholinergic urticaria is useful to screen type I hypersensitivity against sweat antigens. Arch Dermatol Res 304:647–654CrossRefPubMedGoogle Scholar
  46. Thurmond RL (2015) The histamine H4 receptor: from orphan to the clinic. Front Pharmacol 6:65CrossRefPubMedPubMedCentralGoogle Scholar
  47. Verster JC, Volkerts ER (2004) Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic. Ann Allergy Asthma Immunol 92:294–303 (quiz 303-5, 355)CrossRefPubMedGoogle Scholar
  48. Vuurman EF, Van Veggel LM, Uiterwijk MM et al (1993) Seasonal allergic rhinitis and antihistamine effects on children’s learning. Ann Allergy 71:121–126PubMedGoogle Scholar
  49. Walker S, Khan-Wasti S, Fletcher M et al (2007) Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case-control study. J Allergy Clin Immunol 120:381–387CrossRefPubMedGoogle Scholar
  50. Weller K, Ziege C, Staubach P et al (2011) H1-antihistamine up-dosing in chronic spontaneous urticaria: patients’ perspective of effectiveness and side effects – a retrospective survey study. PLoS One 6:e23931CrossRefPubMedPubMedCentralGoogle Scholar
  51. Westergren VS, Wilson SJ, Penrose JF et al (2009) Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis. Clin Exp Allergy 39:820–828CrossRefPubMedGoogle Scholar
  52. Yanai K, Zhang D, Tashiro M et al (2011) Positron emission tomography evaluation of sedative properties of antihistamines. Expert Opin Drug Saf 10:613–622CrossRefPubMedGoogle Scholar
  53. Zuberbier T, Asero R, Bindslev-Jensen C et al (2009) EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy 64:1427–1443CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Allergie-Centrum-Charité, Department of Dermatology and AllergyCharité – Universitätsmedizin BerlinBerlinGermany

Personalised recommendations