Allergy through 20 Centuries Bergmann K-C, Ring J (eds): History of Allergy. Chem Immunol Allergy. Basel, Karger, 2014, vol 100, pp 46–52 DOI: 10.1159/000358500
Terminology of Allergic Phenomena Johannes Ring Department of Dermatology and Allergy Biederstein, Christine Kuehne Center for Allergy Research and Education (CK-CARE), Technical University of Munich, Munich, Germany
Over the last 2,000 years a variety of terms have been used for the description of phenomena possibly related to allergy. Many have been forgotten, while some of them have remained. In Greco-Roman literature the term ‘idiosyncrasy’ was used to describe an individual characterization of a health condition, possibly comparable to ‘constitution’. The same term was also used to describe individual reaction patterns, and the term ‘antipathy’ was used in a similar sense. ‘Hypersensitivity’ originated from the German word ‘Überempfindlichkeit’ and was first used in a medical sense by Emil von Behring when he described untoward reactions to his antitoxin containing serum therapy. ‘Anaphylaxis’ was coined by Richet and Portier to describe the new phenomenon of a life-threatening general pathogenic reaction after repeated injection of antigen. In 1906, Clemens von Pirquet introduced the term ‘allergy’ in order to bring more clarity to the confusing debate regarding protective and harmful immunity. In order to characterize the familial occurrence of hypersensitivity reactions such as asthma, hay fever and others, the American allergists A.F. Coca and R.A. Cooke in-
troduced the term ‘atopy’. Contrary to anaphylaxis, which was experimentally induced, this type of ‘hypersensitiveness’ occurred spontaneously. The nature of the pathogenic factor was called the ‘atopic reagin’ and was found to be transferable with serum by Prausnitz and Küstner. After the detection of immunoglobulin (Ig) E as the carrier of this type of hypersensitivity, the term ‘atopy’ gained a new sense, since IgE is a characteristic – yet not exclusive – parameter of the so-called atopic diseases. Clinically similar diseases such as asthma, rhinoconjunctivitis or eczema can be found in the absence of IgE, and are then called ‘intrinsic’ variants of the same disease. © 2014 S. Karger AG, Basel
It is impossible to write a history of allergy without discussing terminology. This is because many and contrasting terms were and are used for the description of a variety of clinical conditions. Over the centuries or millennia it was not the development of new diseases – as shown in the opening two chapters of this volume – and neither was it the occurrence of new elicitors (pollen or indoor allergens), but rather Downloaded by: UCONN Storrs 198.143.38.1 - 7/6/2015 7:39:33 PM
Abstract
Idiosyncrasy The earliest term we can find in the context of descriptions of possible allergic phenomena in medical history might be the term ‘idiosyncrasy’, which was used in Hippocratic medicine and was better described probably, for the first time, by Ptolemaios (885–960 AD) [5, vol. 1, p. 8; 6, 7]. This term described the uniqueness or individuality of a single human being and was based on the Hippocratic concept of the four humors, which have to be in the correct mixture within the individual. Earlier sources possibly described the term ‘symmixis’, which was used by the philosopher Anaxagoras [8]. Today, the term ‘idiosyncrasy’ could probably be best translated as ‘constitution’. The word is derived from the Greek ‘synkerannimi’, meaning ‘mix’, and ‘idios’, meaning ‘own’ or ‘itself’. Occasionally the expression also describes the specific reaction patterns of an individual. In some sources, besides or instead of idiosyncrasy, the terms ‘idiosystasy’, ‘idiaesthesy’ or ‘idiosynkrisy’ are found [5, vol. 1, p. 12]: Quite often (susceptible) people are suffering with regard to their body from idiosynkrasy, e.g. certain foods or drinks as for example after heavy intake of wine. [9]
Terminology of Allergic Phenomena
Galen uses the term in a pharmacological sense when he describes unexpected drug effects which cannot be explained by the effect of the substance, but rather by the property of a certain patient [5, vol. 1, p. 13]:
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And someone who did not know this drug, prepared it in a weaker form and in a finer powder, and thus it did not have any effect with regard to the stool but a rather stronger effect with regard to the urine. He reported this observation because he was surprised and he wanted to find the true cause. He himself thought that a certain idiosyncrasy of the respective patient was the cause of the phenomenon and he called it like that. [10]
In a variety of texts of antiquity, idiosyncrasy is used to explain various phenotypes or differences between races and skin colors, as well as different tolerability of foods or luxury foods [8]. The same author used this term in the description of a special tolerance regarding poisons, in cases where certain persons were tolerating otherwise fatal or lethal poisons without any adverse reactions, or when it described different degrees of susceptibility to pain in different individuals or population groups. Later, the term was used for psychological phenomena or philosophical conditions. For example, Immanuel Kant [11] (1724–1804) spoke about this in the sense of ‘hobby’ or ‘crank’: Idiosyncrasy … wanted to be popular term which does not find acceptance with wise people … but rather behaves like a cricket in the head and is chirping without to be heard by anybody else.
In a letter from November 24, 1812, to a lady serving the Empress of Austria, Johann Wolfgang von Goethe (1749–1832) used the word ‘idiosyncrasy’ to describe his distaste of writing letters [5, vol. 1, p. 21; 12, vol. 9, p. 677]. The same Goethe also used the term in a medical sense when he described a strange disease with complaints in the throat and the esophagus which could not be explained by the physicians and which he suspected to be caused by his activity in etching and erasing copperplates [5, vol. 1, p. 28]. I felt quite well in this time after my work, although during these days I was attacked by an evil which I had never known before. The throat was quite sore and especially the part which is called uvula was inflamed.
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a new understanding of a pathophysiologic mechanism on the basis of an altered and thereby pathogenic immune response which was new. That was the intention of Clemens von Pirquet when he created the term ‘allergy’ in his short essay in the Münchner Medizinische Wochenschrift of 24 July 1906 [1]. This term itself is neither the beginning nor the end of the history of allergy terminology, it has itself changed in meaning over the decades, including in the 20th century. In the following we want to briefly discuss some of the most important terms used in the description of allergic phenomena in the past. From time to time regional and international organizations have tried to standardize terminology and give clear-cut definitions [2–4]. Not all these endeavors were successful. With increasing knowledge new concepts arose and new interpretations and names developed.
I could only swallow with great pain and the doctors did not know what to do. They tortured me with gargling and brushing yet without relieving me from this pain. Finally I realized intuitively that when I was etching not carefully and especially when I did it more often and with passion, I acquired this evil and it came back repeatedly. Now the doctors agreed and saw the plausibility and finally when I stopped the etching and erasing – especially because my experiments were not at all good – … I found the easier consolation the sooner I was liberated from this unpleasant evil. [12, vol. 10, p. 382]
In the sense of ‘constitution’, the term idiosyncrasy was also sometimes replaced by the following other terms: ‘idiopathy’ (Galenos), ‘diathesis’ (in Latin ‘dispositio’), ‘schisis’ (posture of body and appearance; in Latin ‘habitus’), and ‘physis’ (in Latin ‘natura’). The term ‘diathesis’ will be discussed together with ‘atopy’, below.
Other authors used the term ‘idiosyncrasy’ in order to describe compulsory neurotic conditions, like an acute desire to urinate when listening to lute music or singultus after coitus [5, vol. 1, p. 27; 13]. By such widely differing meanings the term became more and more diluted, leading Wolf Eissner [14] (1877–1848) to feel it should be preserved for allergic reactions:
It is surprising that the term ‘hypersensitivity’, which today is the main term for the various immunologically or non-immunologically mediated reactions against environmental substances, was only discovered in the 19th century for medical use. It was Emil von Behring (1854–1917) who used it in the year 1893 in order to describe untoward reactions to his serum therapy [5, vol. 1, p. 45; 18, 19]:
A large number of idiosyncrasies can now be explained as hypersensitivity against the application of foreign protein, especially occurring after previous injections of the respective protein when a hypersensitivity against this substance has developed.
Let us understand the result of the milk and serum tests: so maybe at a first glance it looks paradoxical that an animal which in its blood and also in the secretions contains considerable amounts of tetanus antitoxin should develop less resistance against the tetanus poison than it had at a time, when it had not developed antitoxin in its organism. [20]
Antipathy Over the centuries another term – today mostly used in a psychological context – was ‘antipathy’, which also described incompatibility symptoms against certain substances or against colors. Occasionally classic allergic conditions were also described as sequels of antipathy, such as by Johann Samuel Eggers from Halle in the year 1730, who classified cases of rose fever under ‘antipathy’ [5, vol. 1, p. 41; 17].
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Von Behring and his co-worker Wladimiroff used the term ‘paradoxical reaction’ for a phenomenon when organisms, which should actually be protected by immunization, reacted pathogenically. The phenomenon itself was not new; Robert Koch had already noted – and von Behring [21] also mentioned this – that stronger skin reactions could be observed after repeated injections of tuberculin. Clemens von Pirquet and Béla Schick also used the term in the sense of the later introduced term ‘allergy’ when they wrote an article entitled ‘Überempfindlichkeit und beschleunigte Reaktionen’ (‘Hypersensitivity and accelerated reactions’) [22]. There they described increased second-set reactions by an increased reaction of the organism to a second injection of antigen in the form of hypersensitivity. Coca and Cooke used the German term as ‘hypersensitiveness’ in English, and later as ‘hypersensitivity’ when they described a special form of this hypersensitiveness as ‘atopy’ [23]. Today, hypersensitivity is used in order to describe a ‘reaction exceeding the normal’.
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In modern allergology the term was used to distinguish certain genetically defined non-allergic hypersensitivity reactions, for instance together with enzyme defects like the favism or lathyrism, when intoxication symptoms occur after the application of chickpeas. Today, idiosyncrasy is used in Anglo-Saxon literature in order to describe non-immunologic hypersensitivity reactions, the symptoms of which differ in quality from the pharmacological effect of the substance, e.g. aspirin idiosyncrasy [15, 16].
Hypersensitivity
Anaphylaxis The birth of the term ‘anaphylaxis’ has been described and commented on often in allergy history, and rightly so: it shows the importance of giving names to a newly discovered phenomenon. This will be discussed in detail in the chapter by Ring et al. [this vol., pp. 54–61]. Here we only reflect the terms used in context with the discovery of Richet and Portier [24, 25] in the 20th century and beyond. Richet used the term to describe potentially lifethreatening generalized reactions after repeated injection of protein. As an adjective, ‘anaphylactic’ was very well accepted. Von Behring, who had seen such reactions and called them ‘paradoxical’ or ‘hypersensitivity’, now called reactions without preceding antigen injections which showed a clinically similar symptomatology ‘anaphylactoid’: These processes which are symptomatic for anaphylactic (anatoxic) poisoning, in their origin yet markedly differ and occur not in an organism which is hypersensitive or sensitized, I want to call ‘anapyhlactoid’. [21]
Later, several authors tried to differentiate nonimmunologic reactions with the symptoms of anaphylaxis by calling them ‘anaphylactoid’ [26]; other terms used include ‘allergoid’, ‘allergy-like’ or ‘pseudo-allergic’ [27]. The new definition of the World Allergy Organization (WAO) is based on the clinical symptomatology and defines anaphylaxis as ‘acute generalized potentially life-threatening reaction with varying symptomatology’ [4]. It is independent from the pathomechanism; there is an immunologic (allergic) anaphylaxis and a non-immunologic anaphylaxis. With this all other terms, such as anaphylactoid, are superfluous [28]. Several authors tried to improve the etymologically incorrect term ‘anaphylaxis’ by calling it ‘paraphylaxis’ [29–31] or ‘aristophylaxy’ (Karl Momsen) when there is natural sensitization [32]. However, these ideas were not acknowledged by the public.
Terminology of Allergic Phenomena
After a large dose of antigen a phase of tolerance was sometimes observed and was called ‘sceptophylaxis’ (‘sceptos’ means ‘acute thunderstorm’). Alexandre Besredka used the term ‘antianaphylaxis’ for a state of tolerance after desensitization [33]. In modern pharmacology, the term ‘tachyphylaxis’ is still used to describe a phenomenon where the effect of a substance is weakened after its repeated application [34]. Elicitors of these reactions were called ‘anaphylactogen’ or ‘anaphylactin’. In the decades after the term was born, ‘anaphylaxis’ conquered the world; many authors used it equally with allergy or to describe all kinds of hypersensitivity. The term became so popular that some authors felt they should warn of the ‘myth of anaphylaxis’ or the danger of an ‘anaphylactomania’ [35]. Today, ‘anaphylaxis’ is a clearly defined term which describes a subgroup of hypersensitivity reactions which may be allergic but also non-immunologic in nature.
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Allergy When in 1906 Clemens von Pirquet wrote his famous essay of one and a half pages, he used an artificial new creation which he justifies as follows: We need a new general not-prejudicing word for the change in condition which exists in an organism after knowing some organic living or dead poison … For this general condition of altered reactivity I propose the term ‘allergy’. ‘Allos’ means the deviation of an original condition, of a behavior of normality, like allorhythmy, allotropy, … The new names do not alter the existing special nomenclature. The well-defined terms like antitoxins, cytolysins, hemolysins, precipitins, agglutinins, coagulins are not affected. Hypersensitivity is a new field in which only recently the formation of terms takes place under painful adaptation to old names. From this feeling and in order to bring clarity in this formation of terms I propose the new terms and hope that by making the external forms more simple, the investigation of the interesting processes in this field will be facilitated for the co-workers. [1]
This proposal was based on the clinical situation which he had observed in his studies on serum sickness together with Béla Schick. The term did not contain bacteriological or immunological mecha-
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This does not necessarily have immunological implications [4, 16]; the term can also be used for psychological phenomena or increased pain sensitivity.
Allergy is an acquired qualitatively altered capacity of living tissue to react induced by a specific allergen. [2]
Besides this term others were developed, such as ‘parallergy’ or ‘metallergy’, which aimed to describe that during the development of hypersensitivity against one antigen, increased reactions to another non-related antigen can be observed [36, 37]. The inherent dilemma of one common definition for clinical symptoms and basic pathomechanisms at the same time continues. Often the fact that these are different categories which are not necessarily connected is not considered. Four aspects remain until today: (1) altered reactivity (mostly increased); (2) specificity; (3) involvement of the immune system, and (4) a pathogenic effect. Therefore, in agreement with most authors, ‘allergy’ can today be defined as follows: Allergy is a specific alteration of the immune response leading to a pathogenic hypersensitivity. [16]
The nomenclature task force of the WAO made the following definition: Allergy is an immunologically mediated specific hypersensitivity. [4]
Terms like ‘neuroallergy’, ‘psychoallergy’ or ‘panallergy’ should be mentioned, although they did not become established [5]. Other authors tried to describe the phenomenon as ‘pathobiosis’ [38] and ‘allobiosis’, or, in the example of the surgeon August Bier, ‘metakinesis’ [5, vol. 1, p. 91; 39, p. 11]. In the description of allergy-related diseases various names were created, like the term ‘allergoses’,
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further divided into ‘rhinallergoses’, ‘ophthallergoses’, ‘bronchiallergoses’, ‘enterallergoses’, ‘dermallergoses’, etc. Erich Hoffmann subsumed allergic occupational diseases in the term ‘ergasidermatoses’ (in Greek ‘ergasia’, meaning ‘occupation’) [40]. The tendency of an individual to develop allergic reactions was called allergic diathesis by Kämmerer [41]. This leads us directly to the term ‘atopy’.
Atopy While the immense progress of early allergology was mainly due to experimental investigations (e.g. anaphylaxis) or immunological studies following active of passive vaccinations, the mere clinical observation was not so important. It was well known that diseases like hay fever and asthma, and also the skin disease called ‘neurodermite’ by Brocq and Jacquet [42], often occurred in one and the same patient, but even more often in various family members. This familial disposition – in contrast to the artificially induced situation of anaphylaxis – was adopted by the American allergists Arthur Fernandez Coca (1875–1955) and Robert Anderson Cooke (1880– 1960), and was newly defined. They were modest with regard to their linguistic etymologic competence and consulted the Graeco-philologist Edward Perry (1856–1938) from the Columbia University of New York. Perry proposed the term ‘atopy’, which he created from the Greek word ‘atopos’ (meaning ‘unusual, strange, not in the right place’). Coca and Cooke [23] proposed this term in an article in 1923 in a series on ‘Phenomena of hypersensitiveness’, and intended to describe patients who suffered either from seasonal allergic rhinitis, bronchial asthma or other allergic phenomena: The individuals as a group possess a peculiar capacity to become sensitive to certain proteins to which the environment and habits of life frequently expose them. [43, p. 122]
Since there were no precipitating antibodies in hay fever patients, which were well-known from serum sickness, other relevant agents were suspected which were named ‘atopic reagins’ and were transferrable by serum, as shown by Prausnitz and Küstner [44] in 1921.
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nisms [22]. From the philological viewpoint, the word is not strictly correct since the melting of ‘ο’ (omicron) and ‘ε’ (epsilon) in Greek would lead to ‘ου’. In his meaning, von Pirquet’s altered reactivity also included deviations from the norm to the lesser, i.e. weakened reactions. This has been lost over time. After many discussions in international nomenclature committees, the following was decided at the 3rd International Congress for Allergology in 1958 in Paris:
Atopy is the tendency to produce immunoglobulin E antibodies against environmental substances leading to clinical symptoms. [4]
The other definition from the Handbook of Atopic Eczema is: Atopy is the familial tendency to develop certain diseases (asthma, rhinoconjunctivitis, eczema) on the basis of a hypersensitivity of skin and mucus membranes against environmental substances associated with increased IgE production and/or altered non-specific reactivity. [45]
This latter definition originates from the clinical symptom observed by the physician, before he or she is able to measure IgE in the serum. Today one might connect this altered reactivity probably to epithelial barrier dysfunction. Both definitions differ essentially insofar as in the first (WAO), increased IgE levels must be present per definition in order to call a disease ‘atopic’. However, it is a general clinical experience that exactly the
References
Terminology of Allergic Phenomena
same clinical diseases, namely rhinoconjunctivitis, bronchial asthma and eczema, can occur with and without elevated IgE levels. This may be due to a lack of methodology for measuring IgE antibodies against specific allergens not yet known. However, it is more likely that the disease itself can exist as hypersensitivity of the skin and mucus membranes without a necessary involvement of IgE antibodies. Therefore, the concept for asthma with an ‘intrinsic’ versus ‘extrinsic’ form is also valid for rhinoconjunctivitis where the nonIgE-associated form is often called ‘vasomotor’. Wüthrich [46] transferred this concept to atopic eczema and postulated an extrinsic and intrinsic variant of atopic eczema. The problem of the term ‘intrinsic’ is its negative nature – it can only be diagnosed by exclusion of detectable immune reactions. This weakens the defining potency. As soon as there was a positive marker of the intrinsic variant, this dilemma would be solved. For allergy practice it is important to measure IgE antibodies. Only when they are detectable should specific therapeutic regimens, such as avoidance recommendation or allergen-specific immunotherapy, be commenced.
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Conclusion The knowledge and the discussion of terminology is no child’s play, nor is it for sophisticated selfpurpose [47, 48]. Underlying each term there is a more or less well thought out concept regarding the understanding of a disease or a pathomechanism, and their practical consequences for diagnosis and therapy. Therefore, it is important to clearly define what one is talking about!
1 von Pirquet C: Allergie. Münch Med Wochenschr 1906;53:1457. 2 International Association of Allergology and Clinical Immunology (IAACI): Definitions of ‘allergy’ and ‘allergen’. Ann Allergy 1958;16:680. 3 Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela
T, Kowalski ML, Mygind N, Ring J, van Cauwenberge P, van Hage-Hamsten M, Wuthrich B; EAACI (the European Academy of Allergology and Clinical Immunology) Nomenclature Task Force: A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001:56:813-824.
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For certain forms of food hypersensitivity where Coca could not see positive skin tests, as well as certain forms of drug hypersensitivity, he proposed the term ‘idioblapsis’ (‘idios’ meaning ‘own, itself’ and ‘blaptein’ meaning ‘damage’), equally following the advice of the Graeco-philologist Kurt von Fritz [5, vol. 1, p. 101]. This term did not succeed, whereas ‘atopy’ was well accepted and gained increasing importance, especially after the detection of the nature of reaginic antibodies such as immunoglobulin (Ig) E [see the chapter by Johansson, this vol., pp.150– 154). Yet also here, as was the case with the term ‘allergy’, the discussion between immunological-experimental investigators and clinicians continued, meaning there are at least two similar but not identical definitions for ‘atopy’, one originating from the tendency to form IgE, the other from the clinical situation (WAO definition):
4 Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, Motala C, Ortega Martell JA, Platts-Mills TA, Rng J, Thien F, Van Cauwenberge P, Williams HC: Revised nomenclauture for allergy for global use: report of the Nomenclauture Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004;113:832–836. 5 Schadewaldt H: Geschichte der Allergie. Munich, Dustri, 1979/1980, vol 1. 6 Nielsen CB: History and present status of tissue anaphylaxis. Stanf Med Bull 1961;19: 120. 7 Ptolemaios: Tetrabiblos; in Doll F, Boer AE (eds): Opera quae exstant omnia. Leipzig, 1957, vol 3.1. 8 Sextus Empiricus: Pyrrhoniarum hypotyposeon; in Bury RG (ed): Opera Graece et Latine (first ed Leipzig 1718: Opera). London, Loeb Classical Library 1, 1933, vol 1. 9 Dioskorides: Pedanii Dioscorides Anazerbei libri; in Kühn CG (ed): Medicorum Graecorum Opera. Leipzig, 1829, vol 25-1, p 184/ Leipzig, 1830, vol 26-2, p 4. 10 Galenos: Opera (Kühn CG ed). Leipzig, 1821–1833. Corpus Medicorum Graecorum. (Mewaldt J et al/Koch UK et al eds). Leipzig, 1914/1923, vol 5.4.2/5.9.1. Oeuvres anatomiques, physiologiques et médicales (von Daremberg C ed). Paris, 1854, vol 1, p 549. 11 Kant I: Anthropologie in pragmatischer Hinsicht; in Schbert F (ed): Sämtliche Werke. Leipzig, vol 7.2. 12 von Goethe JW: Gesammelte Werke Artemis Ausgabe. Zürich, 1949, vol 9, p 677/vol 10, p 382. 13 Baumgarten-Crusius M: Periodologie oder die Lehre von den periodischen Veränderungen im Leben des gesunden und kranken Menschen (Gruber JGG ed). Halle, 1831, vol 344, p 296 ff. 14 Woff-Eisner A: Das Heufieber, sein Wesen und seine Behandlung. Munich, 1906. 15 Middleton H, Ellis F, Reed C (eds): Allergy: Principles and Practice. St Louis, Mosby, 2008. 16 Ring J: Allergy in Practice. Berlin, Springer, 2005. 17 Eggers HS (Präses: M. Alberti): De sensibilitate personali. Med Inaug Diss, HalleMagdeburg, 1730, p 23.
18 von Behring E: Über Idiosynkrasie, Anaphylaxie, Toxin-Überempfindlichkeit, Disposition und Diathese. Schmidts Jb Ges Med 1914;319:113. 19 von Behring E: Experimentelle Analyse und Theorie der anaphylaktischen und apotoxischen Vergiftung. Dtsch Med Wochenschr 1914;40:1749. 20 Wladimiroff A: Über die antitoxinerzeugende und immunisierende Wirkung des Tetanusgiftes bei Thieren. Hyg Infekt Kr 1893;15:405. 21 von Behring E: Über Idiosynkrasie, Anaphylaxie, Toxin-Überempfindlichkeit, Disposition and Diathese. Schmidts Jb Ges Med 1914; 319: 113/Gesammelte Abhandlungen, NF No 23. Bonn, 1915, p 175 ff. 22 von Pirquet C, Schick B: Überempfindlichkeit und beschleunigte Reaktion. Münch Med Wochenschr 1906;53:66. 23 Coca AF, Cooke RA: On the classification of the phenomena of hypersensitiveness. J Immunol 1923;8:163. 24 Richet C: De l’anaphylaxie ou sensibilité croissante des organismes à des doses successives de poison. Arch Fisiol 1903/1904;1: 129. 25 Portier P, Richet C: De l’action anaphylactique de certains vénins. CR Soc Biol 1902; 54:170–172/Trav Labor Physiol 1902;5:506. 26 Hanzlik PJ, Karsner HT: Anaphylactoid phenomena from the intravenous administration of various colloids, arsenicals and other agents. J Pharmacol Exp Ther 1920; 14:379. 27 Kallos P, Schlumberger HD: Allergie und allergische Krankheiten. Cologne, 1978, p 28 ff. 28 Ring J: Anaphylaktoische Reaktionen nach Infusion kolloidaler Volumenersatzmittel. Berlin, Springer, 1978. 29 Danielopolu D: Paraphylaxie et choc paraphylactique. Paris, 1943. 30 Danielopolu D: Rôle réspectif de l’acétylcholine et de l’histamine dans le choc paraphylactique (anaphylactique). Schweiz Med Wochenschr 1948;78:567. 31 Danielopolu D: Nouvelles preuves de la nature acétylcholinique du choc paraphylactique (anaphylactique). Recherches sur l’organe isolé. Acta Med Scand 1947; 126: 589.
32 Momsen K: Allgemeine Bemerkungen zum Thema Allergie, speziell der pathologischen Physiologie; in Holler G, et al (eds): Das akute allergische Phänomen. Wien, 1958, p 7. 33 Besredka A, Steinhardt E: Du mécanisme de l’antianaphylaxie. Ann Inst Pasteur 1907; 21:384. 34 Champy C, Gley E: Sur la toxicité des extraits de corps jaune. Immunisation rapide consécutive à l’injection de petites doses de ces extraits (tachyphylaxie). CR Soc Biol 1911;63:159. 35 Jousset A: The myth of anaphylaxis. Med Press 1919;108:250. 36 Schadewaldt H: Premières mentions historiques des affections allergiques. Acta Allerg 1959;13:223. 37 Moro E, Keller W: Über die Parallergie. Klin Wochenschr 1935;14. 38 Heubner W: Über Pathobiose. Nachr Ges Wiss Göttingen (Math Phys Klasse) 1929; 96. 39 Abderhalden R: Grundriss der Allergie. Basel, Schwabe, 1950. 40 Rössle R: Geschichte der Allergieforschung; in Hansen K (ed): Allergie, ed 3. Stuttgart, Thieme, 1957. 41 Kämmerer H: Allergische Diathese und allergische Erkrankungen. Munich, Bergmann, 1926. 42 Brocq L: L’eczéma considéré comme une réaction cutaneé. Ann Dermatol Syph 1903;4:172. 43 Simons E (ed): Ancestors of Allergy. New York, Global Medical Communications, 1994. 44 Prausitz K, Küstner H: Studien über die Überempfindlichkeit. Zbl Bakt (Orig) 1921; 86:160. 45 Ring J, Ruzicka T, Przybilla B (eds): Handbook of Atopic Eczema, ed 2. Berlin, Springer, 2006. 46 Wüthrich B: Neurodermitis atopica sive constitutionalis. Ein pathogenetisches Modell aus der Sicht des Allergologen. Aktuel Dermatol 1983;9:1–7. 47 Otto R: Zur Frage der Serumüberempfindlichkeit. Münch Med Wochenschr 1907;54: 1665. 48 Rackemann FM: Professor Willem Storm van Leeuwen and the asthma problem. Acta Allerg 1958;12:407.
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Ring
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Prof. Dr. med. Dr. phil. Johannes Ring Department of Dermatology and Allergy Biederstein Biedersteinerstrasse 29 DE–80802 München (Germany) E-Mail johannes.ring @ lrz.tu-muenchen.de
Terminology of Allergic Phenomena Johannes Ring Department of Dermatology and Allergy Biederstein, Christine Kuehne Center for Allergy Research and Education (CK-CARE), Technical University of Munich, Munich, Germany
Over the last 2,000 years a variety of terms have been used for the description of phenomena possibly related to allergy. Many have been forgotten, while some of them have remained. In Greco-Roman literature the term ‘idiosyncrasy’ was used to describe an individual characterization of a health condition, possibly comparable to ‘constitution’. The same term was also used to describe individual reaction patterns, and the term ‘antipathy’ was used in a similar sense. ‘Hypersensitivity’ originated from the German word ‘Überempfindlichkeit’ and was first used in a medical sense by Emil von Behring when he described untoward reactions to his antitoxin containing serum therapy. ‘Anaphylaxis’ was coined by Richet and Portier to describe the new phenomenon of a life-threatening general pathogenic reaction after repeated injection of antigen. In 1906, Clemens von Pirquet introduced the term ‘allergy’ in order to bring more clarity to the confusing debate regarding protective and harmful immunity. In order to characterize the familial occurrence of hypersensitivity reactions such as asthma, hay fever and others, the American allergists A.F. Coca and R.A. Cooke in-
troduced the term ‘atopy’. Contrary to anaphylaxis, which was experimentally induced, this type of ‘hypersensitiveness’ occurred spontaneously. The nature of the pathogenic factor was called the ‘atopic reagin’ and was found to be transferable with serum by Prausnitz and Küstner. After the detection of immunoglobulin (Ig) E as the carrier of this type of hypersensitivity, the term ‘atopy’ gained a new sense, since IgE is a characteristic – yet not exclusive – parameter of the so-called atopic diseases. Clinically similar diseases such as asthma, rhinoconjunctivitis or eczema can be found in the absence of IgE, and are then called ‘intrinsic’ variants of the same disease. © 2014 S. Karger AG, Basel
It is impossible to write a history of allergy without discussing terminology. This is because many and contrasting terms were and are used for the description of a variety of clinical conditions. Over the centuries or millennia it was not the development of new diseases – as shown in the opening two chapters of this volume – and neither was it the occurrence of new elicitors (pollen or indoor allergens), but rather Downloaded by: UCONN Storrs 198.143.38.1 - 7/6/2015 7:39:33 PM
Abstract
Idiosyncrasy The earliest term we can find in the context of descriptions of possible allergic phenomena in medical history might be the term ‘idiosyncrasy’, which was used in Hippocratic medicine and was better described probably, for the first time, by Ptolemaios (885–960 AD) [5, vol. 1, p. 8; 6, 7]. This term described the uniqueness or individuality of a single human being and was based on the Hippocratic concept of the four humors, which have to be in the correct mixture within the individual. Earlier sources possibly described the term ‘symmixis’, which was used by the philosopher Anaxagoras [8]. Today, the term ‘idiosyncrasy’ could probably be best translated as ‘constitution’. The word is derived from the Greek ‘synkerannimi’, meaning ‘mix’, and ‘idios’, meaning ‘own’ or ‘itself’. Occasionally the expression also describes the specific reaction patterns of an individual. In some sources, besides or instead of idiosyncrasy, the terms ‘idiosystasy’, ‘idiaesthesy’ or ‘idiosynkrisy’ are found [5, vol. 1, p. 12]: Quite often (susceptible) people are suffering with regard to their body from idiosynkrasy, e.g. certain foods or drinks as for example after heavy intake of wine. [9]
Terminology of Allergic Phenomena
Galen uses the term in a pharmacological sense when he describes unexpected drug effects which cannot be explained by the effect of the substance, but rather by the property of a certain patient [5, vol. 1, p. 13]:
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And someone who did not know this drug, prepared it in a weaker form and in a finer powder, and thus it did not have any effect with regard to the stool but a rather stronger effect with regard to the urine. He reported this observation because he was surprised and he wanted to find the true cause. He himself thought that a certain idiosyncrasy of the respective patient was the cause of the phenomenon and he called it like that. [10]
In a variety of texts of antiquity, idiosyncrasy is used to explain various phenotypes or differences between races and skin colors, as well as different tolerability of foods or luxury foods [8]. The same author used this term in the description of a special tolerance regarding poisons, in cases where certain persons were tolerating otherwise fatal or lethal poisons without any adverse reactions, or when it described different degrees of susceptibility to pain in different individuals or population groups. Later, the term was used for psychological phenomena or philosophical conditions. For example, Immanuel Kant [11] (1724–1804) spoke about this in the sense of ‘hobby’ or ‘crank’: Idiosyncrasy … wanted to be popular term which does not find acceptance with wise people … but rather behaves like a cricket in the head and is chirping without to be heard by anybody else.
In a letter from November 24, 1812, to a lady serving the Empress of Austria, Johann Wolfgang von Goethe (1749–1832) used the word ‘idiosyncrasy’ to describe his distaste of writing letters [5, vol. 1, p. 21; 12, vol. 9, p. 677]. The same Goethe also used the term in a medical sense when he described a strange disease with complaints in the throat and the esophagus which could not be explained by the physicians and which he suspected to be caused by his activity in etching and erasing copperplates [5, vol. 1, p. 28]. I felt quite well in this time after my work, although during these days I was attacked by an evil which I had never known before. The throat was quite sore and especially the part which is called uvula was inflamed.
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a new understanding of a pathophysiologic mechanism on the basis of an altered and thereby pathogenic immune response which was new. That was the intention of Clemens von Pirquet when he created the term ‘allergy’ in his short essay in the Münchner Medizinische Wochenschrift of 24 July 1906 [1]. This term itself is neither the beginning nor the end of the history of allergy terminology, it has itself changed in meaning over the decades, including in the 20th century. In the following we want to briefly discuss some of the most important terms used in the description of allergic phenomena in the past. From time to time regional and international organizations have tried to standardize terminology and give clear-cut definitions [2–4]. Not all these endeavors were successful. With increasing knowledge new concepts arose and new interpretations and names developed.
I could only swallow with great pain and the doctors did not know what to do. They tortured me with gargling and brushing yet without relieving me from this pain. Finally I realized intuitively that when I was etching not carefully and especially when I did it more often and with passion, I acquired this evil and it came back repeatedly. Now the doctors agreed and saw the plausibility and finally when I stopped the etching and erasing – especially because my experiments were not at all good – … I found the easier consolation the sooner I was liberated from this unpleasant evil. [12, vol. 10, p. 382]
In the sense of ‘constitution’, the term idiosyncrasy was also sometimes replaced by the following other terms: ‘idiopathy’ (Galenos), ‘diathesis’ (in Latin ‘dispositio’), ‘schisis’ (posture of body and appearance; in Latin ‘habitus’), and ‘physis’ (in Latin ‘natura’). The term ‘diathesis’ will be discussed together with ‘atopy’, below.
Other authors used the term ‘idiosyncrasy’ in order to describe compulsory neurotic conditions, like an acute desire to urinate when listening to lute music or singultus after coitus [5, vol. 1, p. 27; 13]. By such widely differing meanings the term became more and more diluted, leading Wolf Eissner [14] (1877–1848) to feel it should be preserved for allergic reactions:
It is surprising that the term ‘hypersensitivity’, which today is the main term for the various immunologically or non-immunologically mediated reactions against environmental substances, was only discovered in the 19th century for medical use. It was Emil von Behring (1854–1917) who used it in the year 1893 in order to describe untoward reactions to his serum therapy [5, vol. 1, p. 45; 18, 19]:
A large number of idiosyncrasies can now be explained as hypersensitivity against the application of foreign protein, especially occurring after previous injections of the respective protein when a hypersensitivity against this substance has developed.
Let us understand the result of the milk and serum tests: so maybe at a first glance it looks paradoxical that an animal which in its blood and also in the secretions contains considerable amounts of tetanus antitoxin should develop less resistance against the tetanus poison than it had at a time, when it had not developed antitoxin in its organism. [20]
Antipathy Over the centuries another term – today mostly used in a psychological context – was ‘antipathy’, which also described incompatibility symptoms against certain substances or against colors. Occasionally classic allergic conditions were also described as sequels of antipathy, such as by Johann Samuel Eggers from Halle in the year 1730, who classified cases of rose fever under ‘antipathy’ [5, vol. 1, p. 41; 17].
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Von Behring and his co-worker Wladimiroff used the term ‘paradoxical reaction’ for a phenomenon when organisms, which should actually be protected by immunization, reacted pathogenically. The phenomenon itself was not new; Robert Koch had already noted – and von Behring [21] also mentioned this – that stronger skin reactions could be observed after repeated injections of tuberculin. Clemens von Pirquet and Béla Schick also used the term in the sense of the later introduced term ‘allergy’ when they wrote an article entitled ‘Überempfindlichkeit und beschleunigte Reaktionen’ (‘Hypersensitivity and accelerated reactions’) [22]. There they described increased second-set reactions by an increased reaction of the organism to a second injection of antigen in the form of hypersensitivity. Coca and Cooke used the German term as ‘hypersensitiveness’ in English, and later as ‘hypersensitivity’ when they described a special form of this hypersensitiveness as ‘atopy’ [23]. Today, hypersensitivity is used in order to describe a ‘reaction exceeding the normal’.
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In modern allergology the term was used to distinguish certain genetically defined non-allergic hypersensitivity reactions, for instance together with enzyme defects like the favism or lathyrism, when intoxication symptoms occur after the application of chickpeas. Today, idiosyncrasy is used in Anglo-Saxon literature in order to describe non-immunologic hypersensitivity reactions, the symptoms of which differ in quality from the pharmacological effect of the substance, e.g. aspirin idiosyncrasy [15, 16].
Hypersensitivity
Anaphylaxis The birth of the term ‘anaphylaxis’ has been described and commented on often in allergy history, and rightly so: it shows the importance of giving names to a newly discovered phenomenon. This will be discussed in detail in the chapter by Ring et al. [this vol., pp. 54–61]. Here we only reflect the terms used in context with the discovery of Richet and Portier [24, 25] in the 20th century and beyond. Richet used the term to describe potentially lifethreatening generalized reactions after repeated injection of protein. As an adjective, ‘anaphylactic’ was very well accepted. Von Behring, who had seen such reactions and called them ‘paradoxical’ or ‘hypersensitivity’, now called reactions without preceding antigen injections which showed a clinically similar symptomatology ‘anaphylactoid’: These processes which are symptomatic for anaphylactic (anatoxic) poisoning, in their origin yet markedly differ and occur not in an organism which is hypersensitive or sensitized, I want to call ‘anapyhlactoid’. [21]
Later, several authors tried to differentiate nonimmunologic reactions with the symptoms of anaphylaxis by calling them ‘anaphylactoid’ [26]; other terms used include ‘allergoid’, ‘allergy-like’ or ‘pseudo-allergic’ [27]. The new definition of the World Allergy Organization (WAO) is based on the clinical symptomatology and defines anaphylaxis as ‘acute generalized potentially life-threatening reaction with varying symptomatology’ [4]. It is independent from the pathomechanism; there is an immunologic (allergic) anaphylaxis and a non-immunologic anaphylaxis. With this all other terms, such as anaphylactoid, are superfluous [28]. Several authors tried to improve the etymologically incorrect term ‘anaphylaxis’ by calling it ‘paraphylaxis’ [29–31] or ‘aristophylaxy’ (Karl Momsen) when there is natural sensitization [32]. However, these ideas were not acknowledged by the public.
Terminology of Allergic Phenomena
After a large dose of antigen a phase of tolerance was sometimes observed and was called ‘sceptophylaxis’ (‘sceptos’ means ‘acute thunderstorm’). Alexandre Besredka used the term ‘antianaphylaxis’ for a state of tolerance after desensitization [33]. In modern pharmacology, the term ‘tachyphylaxis’ is still used to describe a phenomenon where the effect of a substance is weakened after its repeated application [34]. Elicitors of these reactions were called ‘anaphylactogen’ or ‘anaphylactin’. In the decades after the term was born, ‘anaphylaxis’ conquered the world; many authors used it equally with allergy or to describe all kinds of hypersensitivity. The term became so popular that some authors felt they should warn of the ‘myth of anaphylaxis’ or the danger of an ‘anaphylactomania’ [35]. Today, ‘anaphylaxis’ is a clearly defined term which describes a subgroup of hypersensitivity reactions which may be allergic but also non-immunologic in nature.
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Allergy When in 1906 Clemens von Pirquet wrote his famous essay of one and a half pages, he used an artificial new creation which he justifies as follows: We need a new general not-prejudicing word for the change in condition which exists in an organism after knowing some organic living or dead poison … For this general condition of altered reactivity I propose the term ‘allergy’. ‘Allos’ means the deviation of an original condition, of a behavior of normality, like allorhythmy, allotropy, … The new names do not alter the existing special nomenclature. The well-defined terms like antitoxins, cytolysins, hemolysins, precipitins, agglutinins, coagulins are not affected. Hypersensitivity is a new field in which only recently the formation of terms takes place under painful adaptation to old names. From this feeling and in order to bring clarity in this formation of terms I propose the new terms and hope that by making the external forms more simple, the investigation of the interesting processes in this field will be facilitated for the co-workers. [1]
This proposal was based on the clinical situation which he had observed in his studies on serum sickness together with Béla Schick. The term did not contain bacteriological or immunological mecha-
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This does not necessarily have immunological implications [4, 16]; the term can also be used for psychological phenomena or increased pain sensitivity.
Allergy is an acquired qualitatively altered capacity of living tissue to react induced by a specific allergen. [2]
Besides this term others were developed, such as ‘parallergy’ or ‘metallergy’, which aimed to describe that during the development of hypersensitivity against one antigen, increased reactions to another non-related antigen can be observed [36, 37]. The inherent dilemma of one common definition for clinical symptoms and basic pathomechanisms at the same time continues. Often the fact that these are different categories which are not necessarily connected is not considered. Four aspects remain until today: (1) altered reactivity (mostly increased); (2) specificity; (3) involvement of the immune system, and (4) a pathogenic effect. Therefore, in agreement with most authors, ‘allergy’ can today be defined as follows: Allergy is a specific alteration of the immune response leading to a pathogenic hypersensitivity. [16]
The nomenclature task force of the WAO made the following definition: Allergy is an immunologically mediated specific hypersensitivity. [4]
Terms like ‘neuroallergy’, ‘psychoallergy’ or ‘panallergy’ should be mentioned, although they did not become established [5]. Other authors tried to describe the phenomenon as ‘pathobiosis’ [38] and ‘allobiosis’, or, in the example of the surgeon August Bier, ‘metakinesis’ [5, vol. 1, p. 91; 39, p. 11]. In the description of allergy-related diseases various names were created, like the term ‘allergoses’,
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further divided into ‘rhinallergoses’, ‘ophthallergoses’, ‘bronchiallergoses’, ‘enterallergoses’, ‘dermallergoses’, etc. Erich Hoffmann subsumed allergic occupational diseases in the term ‘ergasidermatoses’ (in Greek ‘ergasia’, meaning ‘occupation’) [40]. The tendency of an individual to develop allergic reactions was called allergic diathesis by Kämmerer [41]. This leads us directly to the term ‘atopy’.
Atopy While the immense progress of early allergology was mainly due to experimental investigations (e.g. anaphylaxis) or immunological studies following active of passive vaccinations, the mere clinical observation was not so important. It was well known that diseases like hay fever and asthma, and also the skin disease called ‘neurodermite’ by Brocq and Jacquet [42], often occurred in one and the same patient, but even more often in various family members. This familial disposition – in contrast to the artificially induced situation of anaphylaxis – was adopted by the American allergists Arthur Fernandez Coca (1875–1955) and Robert Anderson Cooke (1880– 1960), and was newly defined. They were modest with regard to their linguistic etymologic competence and consulted the Graeco-philologist Edward Perry (1856–1938) from the Columbia University of New York. Perry proposed the term ‘atopy’, which he created from the Greek word ‘atopos’ (meaning ‘unusual, strange, not in the right place’). Coca and Cooke [23] proposed this term in an article in 1923 in a series on ‘Phenomena of hypersensitiveness’, and intended to describe patients who suffered either from seasonal allergic rhinitis, bronchial asthma or other allergic phenomena: The individuals as a group possess a peculiar capacity to become sensitive to certain proteins to which the environment and habits of life frequently expose them. [43, p. 122]
Since there were no precipitating antibodies in hay fever patients, which were well-known from serum sickness, other relevant agents were suspected which were named ‘atopic reagins’ and were transferrable by serum, as shown by Prausnitz and Küstner [44] in 1921.
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nisms [22]. From the philological viewpoint, the word is not strictly correct since the melting of ‘ο’ (omicron) and ‘ε’ (epsilon) in Greek would lead to ‘ου’. In his meaning, von Pirquet’s altered reactivity also included deviations from the norm to the lesser, i.e. weakened reactions. This has been lost over time. After many discussions in international nomenclature committees, the following was decided at the 3rd International Congress for Allergology in 1958 in Paris:
Atopy is the tendency to produce immunoglobulin E antibodies against environmental substances leading to clinical symptoms. [4]
The other definition from the Handbook of Atopic Eczema is: Atopy is the familial tendency to develop certain diseases (asthma, rhinoconjunctivitis, eczema) on the basis of a hypersensitivity of skin and mucus membranes against environmental substances associated with increased IgE production and/or altered non-specific reactivity. [45]
This latter definition originates from the clinical symptom observed by the physician, before he or she is able to measure IgE in the serum. Today one might connect this altered reactivity probably to epithelial barrier dysfunction. Both definitions differ essentially insofar as in the first (WAO), increased IgE levels must be present per definition in order to call a disease ‘atopic’. However, it is a general clinical experience that exactly the
References
Terminology of Allergic Phenomena
same clinical diseases, namely rhinoconjunctivitis, bronchial asthma and eczema, can occur with and without elevated IgE levels. This may be due to a lack of methodology for measuring IgE antibodies against specific allergens not yet known. However, it is more likely that the disease itself can exist as hypersensitivity of the skin and mucus membranes without a necessary involvement of IgE antibodies. Therefore, the concept for asthma with an ‘intrinsic’ versus ‘extrinsic’ form is also valid for rhinoconjunctivitis where the nonIgE-associated form is often called ‘vasomotor’. Wüthrich [46] transferred this concept to atopic eczema and postulated an extrinsic and intrinsic variant of atopic eczema. The problem of the term ‘intrinsic’ is its negative nature – it can only be diagnosed by exclusion of detectable immune reactions. This weakens the defining potency. As soon as there was a positive marker of the intrinsic variant, this dilemma would be solved. For allergy practice it is important to measure IgE antibodies. Only when they are detectable should specific therapeutic regimens, such as avoidance recommendation or allergen-specific immunotherapy, be commenced.
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Conclusion The knowledge and the discussion of terminology is no child’s play, nor is it for sophisticated selfpurpose [47, 48]. Underlying each term there is a more or less well thought out concept regarding the understanding of a disease or a pathomechanism, and their practical consequences for diagnosis and therapy. Therefore, it is important to clearly define what one is talking about!
1 von Pirquet C: Allergie. Münch Med Wochenschr 1906;53:1457. 2 International Association of Allergology and Clinical Immunology (IAACI): Definitions of ‘allergy’ and ‘allergen’. Ann Allergy 1958;16:680. 3 Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela
T, Kowalski ML, Mygind N, Ring J, van Cauwenberge P, van Hage-Hamsten M, Wuthrich B; EAACI (the European Academy of Allergology and Clinical Immunology) Nomenclature Task Force: A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001:56:813-824.
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For certain forms of food hypersensitivity where Coca could not see positive skin tests, as well as certain forms of drug hypersensitivity, he proposed the term ‘idioblapsis’ (‘idios’ meaning ‘own, itself’ and ‘blaptein’ meaning ‘damage’), equally following the advice of the Graeco-philologist Kurt von Fritz [5, vol. 1, p. 101]. This term did not succeed, whereas ‘atopy’ was well accepted and gained increasing importance, especially after the detection of the nature of reaginic antibodies such as immunoglobulin (Ig) E [see the chapter by Johansson, this vol., pp.150– 154). Yet also here, as was the case with the term ‘allergy’, the discussion between immunological-experimental investigators and clinicians continued, meaning there are at least two similar but not identical definitions for ‘atopy’, one originating from the tendency to form IgE, the other from the clinical situation (WAO definition):
4 Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, Motala C, Ortega Martell JA, Platts-Mills TA, Rng J, Thien F, Van Cauwenberge P, Williams HC: Revised nomenclauture for allergy for global use: report of the Nomenclauture Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004;113:832–836. 5 Schadewaldt H: Geschichte der Allergie. Munich, Dustri, 1979/1980, vol 1. 6 Nielsen CB: History and present status of tissue anaphylaxis. Stanf Med Bull 1961;19: 120. 7 Ptolemaios: Tetrabiblos; in Doll F, Boer AE (eds): Opera quae exstant omnia. Leipzig, 1957, vol 3.1. 8 Sextus Empiricus: Pyrrhoniarum hypotyposeon; in Bury RG (ed): Opera Graece et Latine (first ed Leipzig 1718: Opera). London, Loeb Classical Library 1, 1933, vol 1. 9 Dioskorides: Pedanii Dioscorides Anazerbei libri; in Kühn CG (ed): Medicorum Graecorum Opera. Leipzig, 1829, vol 25-1, p 184/ Leipzig, 1830, vol 26-2, p 4. 10 Galenos: Opera (Kühn CG ed). Leipzig, 1821–1833. Corpus Medicorum Graecorum. (Mewaldt J et al/Koch UK et al eds). Leipzig, 1914/1923, vol 5.4.2/5.9.1. Oeuvres anatomiques, physiologiques et médicales (von Daremberg C ed). Paris, 1854, vol 1, p 549. 11 Kant I: Anthropologie in pragmatischer Hinsicht; in Schbert F (ed): Sämtliche Werke. Leipzig, vol 7.2. 12 von Goethe JW: Gesammelte Werke Artemis Ausgabe. Zürich, 1949, vol 9, p 677/vol 10, p 382. 13 Baumgarten-Crusius M: Periodologie oder die Lehre von den periodischen Veränderungen im Leben des gesunden und kranken Menschen (Gruber JGG ed). Halle, 1831, vol 344, p 296 ff. 14 Woff-Eisner A: Das Heufieber, sein Wesen und seine Behandlung. Munich, 1906. 15 Middleton H, Ellis F, Reed C (eds): Allergy: Principles and Practice. St Louis, Mosby, 2008. 16 Ring J: Allergy in Practice. Berlin, Springer, 2005. 17 Eggers HS (Präses: M. Alberti): De sensibilitate personali. Med Inaug Diss, HalleMagdeburg, 1730, p 23.
18 von Behring E: Über Idiosynkrasie, Anaphylaxie, Toxin-Überempfindlichkeit, Disposition und Diathese. Schmidts Jb Ges Med 1914;319:113. 19 von Behring E: Experimentelle Analyse und Theorie der anaphylaktischen und apotoxischen Vergiftung. Dtsch Med Wochenschr 1914;40:1749. 20 Wladimiroff A: Über die antitoxinerzeugende und immunisierende Wirkung des Tetanusgiftes bei Thieren. Hyg Infekt Kr 1893;15:405. 21 von Behring E: Über Idiosynkrasie, Anaphylaxie, Toxin-Überempfindlichkeit, Disposition and Diathese. Schmidts Jb Ges Med 1914; 319: 113/Gesammelte Abhandlungen, NF No 23. Bonn, 1915, p 175 ff. 22 von Pirquet C, Schick B: Überempfindlichkeit und beschleunigte Reaktion. Münch Med Wochenschr 1906;53:66. 23 Coca AF, Cooke RA: On the classification of the phenomena of hypersensitiveness. J Immunol 1923;8:163. 24 Richet C: De l’anaphylaxie ou sensibilité croissante des organismes à des doses successives de poison. Arch Fisiol 1903/1904;1: 129. 25 Portier P, Richet C: De l’action anaphylactique de certains vénins. CR Soc Biol 1902; 54:170–172/Trav Labor Physiol 1902;5:506. 26 Hanzlik PJ, Karsner HT: Anaphylactoid phenomena from the intravenous administration of various colloids, arsenicals and other agents. J Pharmacol Exp Ther 1920; 14:379. 27 Kallos P, Schlumberger HD: Allergie und allergische Krankheiten. Cologne, 1978, p 28 ff. 28 Ring J: Anaphylaktoische Reaktionen nach Infusion kolloidaler Volumenersatzmittel. Berlin, Springer, 1978. 29 Danielopolu D: Paraphylaxie et choc paraphylactique. Paris, 1943. 30 Danielopolu D: Rôle réspectif de l’acétylcholine et de l’histamine dans le choc paraphylactique (anaphylactique). Schweiz Med Wochenschr 1948;78:567. 31 Danielopolu D: Nouvelles preuves de la nature acétylcholinique du choc paraphylactique (anaphylactique). Recherches sur l’organe isolé. Acta Med Scand 1947; 126: 589.
32 Momsen K: Allgemeine Bemerkungen zum Thema Allergie, speziell der pathologischen Physiologie; in Holler G, et al (eds): Das akute allergische Phänomen. Wien, 1958, p 7. 33 Besredka A, Steinhardt E: Du mécanisme de l’antianaphylaxie. Ann Inst Pasteur 1907; 21:384. 34 Champy C, Gley E: Sur la toxicité des extraits de corps jaune. Immunisation rapide consécutive à l’injection de petites doses de ces extraits (tachyphylaxie). CR Soc Biol 1911;63:159. 35 Jousset A: The myth of anaphylaxis. Med Press 1919;108:250. 36 Schadewaldt H: Premières mentions historiques des affections allergiques. Acta Allerg 1959;13:223. 37 Moro E, Keller W: Über die Parallergie. Klin Wochenschr 1935;14. 38 Heubner W: Über Pathobiose. Nachr Ges Wiss Göttingen (Math Phys Klasse) 1929; 96. 39 Abderhalden R: Grundriss der Allergie. Basel, Schwabe, 1950. 40 Rössle R: Geschichte der Allergieforschung; in Hansen K (ed): Allergie, ed 3. Stuttgart, Thieme, 1957. 41 Kämmerer H: Allergische Diathese und allergische Erkrankungen. Munich, Bergmann, 1926. 42 Brocq L: L’eczéma considéré comme une réaction cutaneé. Ann Dermatol Syph 1903;4:172. 43 Simons E (ed): Ancestors of Allergy. New York, Global Medical Communications, 1994. 44 Prausitz K, Küstner H: Studien über die Überempfindlichkeit. Zbl Bakt (Orig) 1921; 86:160. 45 Ring J, Ruzicka T, Przybilla B (eds): Handbook of Atopic Eczema, ed 2. Berlin, Springer, 2006. 46 Wüthrich B: Neurodermitis atopica sive constitutionalis. Ein pathogenetisches Modell aus der Sicht des Allergologen. Aktuel Dermatol 1983;9:1–7. 47 Otto R: Zur Frage der Serumüberempfindlichkeit. Münch Med Wochenschr 1907;54: 1665. 48 Rackemann FM: Professor Willem Storm van Leeuwen and the asthma problem. Acta Allerg 1958;12:407.
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Ring
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Prof. Dr. med. Dr. phil. Johannes Ring Department of Dermatology and Allergy Biederstein Biedersteinerstrasse 29 DE–80802 München (Germany) E-Mail johannes.ring @ lrz.tu-muenchen.de
