Allergy-Hormone Links Shilpa Bhupatrai Shah
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HistoryCHAPTER 1

The concept of “allergy” was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after he noted that some of his patients were hypersensitive to normally innocuous entities such as dust, pollen, or certain foods. Pirquet called this phenomenon “allergy” from the Greek words allos meaning “other” and ergon meaning “reaction”.1,2 Historically, all forms of hypersensitivity were classified as allergies, and all were thought to be caused by an improper activation of the immune system.
Later, it became clear that several different disease mechanisms were implicated, with the common link to a disordered activation of the immune system. In 1963, Philip Gell and Robin Coombs designed a new classification scheme that described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity.3
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Fig 1.1: Clemens von Pirquet
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Fig 1.2: Philip Gell
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Fig 1.3: Robin Coombs
Many disorders have been associated with the phases of the menstrual cycle, including acne, asthma, hereditary angiedema, apthous ulcers, Behcet's syndrome, porphyria, epilepsy, myasthenia gravis, allergic rhinitis and migraines.413 Autoimmune progesterone dermatitis14 describes an allergic reaction to progesterone that can lead to severe dermatitis and anaphylaxis. Geber15 described the first documented case of cyclic urticaria associated with the menstrual cycle in 1921. He suggested a terminology of hormone allergy after demonstrating a flare in the disease by administering the patient's own premenstrual serum.4 As early as 1935, Riebe7,8 first, and then, in 1945 and 1947, Zondek and Bromberg16,17 advanced the concept of allergy to ovarian hormones. They performed skin tests on a healthy population and on patients with endocrine disturbances and found positive skin tests to endocrine test materials only in individuals with endocrine abnormalities. Furthermore, they were able to passively transfer this reaction to healthy individuals using sera from patients with hormone sensitivity. This positive skin reaction indicated that the serum contained specific antibodies to hormones.16 While all these observations and experimental findings supported the theory of hypersensitivity to hormones, only 22 and 35 years later, steroid-binding globulin,18 and 17-hydroxyprogesterone-binding immunoglobulin16 2were identified in the serum of a woman with periodic rashes.19 This patient suffered from primary infertility and a history of recurrent oral and perennial rashes that appeared just prior to the midcycle rise in basal body temperature and subsided with the onset of menses. Sera obtained during the follicular and luteal phases of her cycle were found to contain a progestin-binding component having properties of IgG.19 In these cases the hormone-producing gland (corpus luteum) would most likely be attacked and perhaps this actually happened, explaining the infertility. Rashes are the symptom of this hormone allergy reaction. Other clinical entities have been associated with hormone variations. Miller20 and Mabray et al.21 treated headache, joint pain, backache, breast pain and hot flashes utilizing allergy management with progesterone as an antigen. A review of menstrual related migraines suggests connections between menstrual cycles and frequency and severity of migraines.6 Between 33 percent and 52 percent of asthmatic women experience premenstrual increases in asthma symptoms.812 Another 22 percent report increasing asthma symptoms during menses.11 These women experience higher rates of hospitalization each year. Nearly 50 percent of women admitted to the hospital for asthma have been perimenstrual.13 This can be related to effects of hormones and hormone allergies, on the sensitivity of bronchial smooth muscle to leukotrienes, histamine, adrenaline, acetylcholine or other mediators.
  1. Bendiner E. Baron von Pirquet. The aristocrat who discovered and defined allergy. Hospital Practice 1981;16(10): 137, 141, 144.
  1. Rapaport HG. Clemens von Pirquet and allergy. Annals of allergy 1973; 31(10): 467–75.
  1. Gell PGH, Coombs RRA, (eds). Clinical Aspects of Immunology. 1st edition. Blackwell;  Oxford, England:  1963.
  1. Geber J. Desensitization in the treatment of menstrual intoxication and other allergic symptoms. Br J Dermatol 1930;51:265–8.
  1. Riebel FA. Allergic coryza at menstruation from ovarian hormone. Ann Intern Med 1935;9:91–92.
  1. McGregor EA, Hackshaw A. Prevalence of migraine on each day of the natural menstrual cycle. Neurology 2004;63:351–3.
  1. Haggerty CL, Ness RB, Kelsey S, Waterer GW. The impact of estrogen and progesterone on asthma. Ann Allergy Asthma Immunol 2003;90:284–91.
  1. Rees L. An aetiological study of premenstrual asthma. J Psychosom Res 1963; 7:191–7.
  1. Eliasson O, Scherzer HH, DeGraff AC. Morbidity in asthma in relation to the menstrual cycle. J Allergy Clin Immunol 1986;77:87–94.
  1. Gibbs CJ, Coutts II, Lock R, Finnegan OC, White RJ. Premenstrual exacerbation of asthma. Thorax 1984;39:833–6.
  1. Wulfson NL, Politzer WM. Bronchial asthma during menses and pregnancy. S Afr Med J 1964;38:173.
  1. Chandler MH, Schuldheisz S, Phillips BA, Muse KN. Premenstrual asthma: the effect of estrogen on symptoms, pulmonary function, and β2-receptors. Pharmacotherapy 1997;17:224–34.
  1. Skobeloff EM, Spivey WH, Silverman R, Eskin BA, Harchelroad F, Alessi TV. The effect of the menstrual cycle on asthma presentations in the emergency department. Arch Intern Med 1996;156:1837–40.
  1. Snyder JL, Krishaswamy G. Autoimmune progesterone dermatitis and its manifestation as anaphylaxis: a case report and literature review. Ann Allergy Asthma Immunol 2003;90:469–77.
  1. Geber H. Einege Daten zur Pathologie der Urticaria menstrationalis. Dermat Z 1921;32:143.
  1. Zondek B, Bromberg YM. Endocrine allergy. J Allergy 1945;16:1–16.
  1. Zondek B, Bromberg YM. Endocrine allergy: clinical reactions of allergy to endogenous hormones and their treatment. J Obstet Gynaecol Br Emp 1947; 54:1–19.
  1. Westphal U. Assay and properties of corticosteroid-binding globulin and other steroid-binding serum proteins. Meth Enzymol 1969;15:761.
  1. Cheesman KL, Gaynor LV, Chatterton RT, Radvany RM. Identification of a 17-hydroxyprogesteronebinding immunoglobulin in the serum of a woman with periodic rashes. J Clin Endocrinol Metab 1982;55:597–9.
  1. Miller JB. Relief of premenstrual symptoms, dysmenorrheal, and contraceptive tablet intolerance. J Med Assoc State Ala 1974;44:57.
  1. Mabray CR, Burditt ML, Martin TL, Jaynes CR, Hayes JR. Treatment of common gynecologic–endocrinologic symptoms by allergy management procedures. Obstet Gynecol 1982;59:560–4.