Professional Documents
Culture Documents
A Revised Nomenclature For Allergy: Position Paper
A Revised Nomenclature For Allergy: Position Paper
Position paper
This report has been prepared by an EAACI task force representing the five S. G. O. Johansson1,
EAACI Sections and the EAACI Executive Committee composed of specialists J. O’B Hourihane2, J. Bousquet3,
that reflect the broad opinion on allergy expressed by various clinical and basic C. Bruijnzeel-Koomen4, S. Dreborg5,
specialties dealing with allergy. The aim of this report is to propose a revised T. Haahtela6, M. L. Kowalski7,
nomenclature for allergic and related reactions that can be used independently of N. Mygind8, J. Ring9,
target organ or patient age group. The nomenclature is based on the present P. van Cauwenberge10,
knowledge of the mechanisms which initiate and mediate allergic reactions. M. van Hage-Hamsten1,
However, the intention has not been to revise the nomenclature of nonallergic B. Wüthrich11
hypersensitivity. 1
Department of Medicine, Unit of Clinical Immunology
and Allergy, Karolinska Hospital, Stockholm, Sweden;
2
Allergy and Inflammation Sciences Division,
University of Southampton, Southampton, UK; 3Service
des Maladies Respiratoires, Hôpital Arnaud de
Villeneuve, Montpellier, France; 4Department of
Dermatology, State University Hospital, Utrecht, The
Netherlands; 5Voksentoppen, Oslo, Norway; 6Division
of Allergy, Skin and Allergy Hospital, Helsinki
University Central Hospital, Helsinki, Finland;
7
Department of Clinical Immunology and Allergy,
Faculty of Medicine, Łódz, Poland; 8Department of
Respiratory Diseases, University Hospital of Aarhus,
Aarhus, Denmark; 9Klinik und Poliklinik Dermatologie/
Allergologie, Technische Unviersität München,
Munich, Germany; 10Department of Oto-Rhino-
Laryngology, University Hospital, Ghent, Belgium;
11
Department of Dermatology, Allergy Unit, University
Hospital, Zurich, Switzerland
Prof. S. G. O. Johansson
Department of Medicine
Unit of Clinical Immunology and Allergy
Karolinska Hospital, L2:03
SE-171 76 Stockholm
Sweden
813
Johansson et al.
physicians should adopt very clear designations of the allergic reactions introduced by Gell & Coombs in
allergic disorders and adhere to this nomenclature in 1968 (25) (the familiar types I–IV hypersensitivities) has
their professional and public communications. been useful. However, too much emphasis has been
In the early 1920s, Coca & Cooke (20) introduced the given to the supposedly distinct and mutually exclusive
term ‘‘atopy’’ to designate some phenomena of hyper- roles of antibodies and immunocompetent cells. This
sensitiveness in man. They considered ‘‘atopy’’ to be all dichotomy is not consistent with our present knowledge
of the following: of the dynamic immune response, as orchestrated by
dendritic cells and T helper cells, and mediated by
1) hereditary
effector cells of several types, antibodies, chemokines,
2) limited to a small group of patients
and cytokines. The last two groups have been mostly
3) different from ‘‘anaphylaxis’’ in referring to a lack
identified since Gell & Coombs produced their classi-
of protection, and from ‘‘allergy’’ meaning an
fication of allergic reactions. Therefore, a revised
altered reactivity
nomenclature is much needed.
4) ‘‘qualitatively an abnormal response’’ occurring
In 1968, the WHO International Reference Center for
only in particular individuals (atopics)
Immunoglobulins decided that enough critical data were
5) clinically characterized by hay fever and bronchial
available to announce the presence of a fifth immuno-
asthma
globulin isotype, IgE (12). The classical ‘‘reaginic
6) associated with immediate-type (wheal-and-flare)
activity’’ could be linked to IgE (41, 82). Whether
skin reactions.
other types of tissue-sensitizing activity present in
At this time, they were evidently unaware of the work animals, such as short-term sensitizing antibody (67),
that Prausnitz & Küstner (73) published in 1921 about occur also in man is still not settled.
the passive transfer of immediate hypersensitivity in In the mid-1970s, classical, IgE-mediated allergic
man by serum. In their original definition of ‘‘atopy’’, reactions to inhalant allergens were termed by Pepys
Coca & Cooke included only allergic rhinitis and ‘‘atopic allergy’’ (69). The term ‘‘atopic’’ is today used
bronchial asthma. Wise & Sulzberger proposed the synonymously with ‘‘IgE-mediated’’ by most doctors
term ‘‘atopic dermatitis’’ to denote ‘‘confusing types of and scientists involved in allergy. However, others,
localised and generalised lichenification, generalised especially pediatricians and dermatologists, also con-
neurodermatitis or manifestation of atopy’’ (93). sider ‘‘atopy’’ a constitutional trait. They find ‘‘atopy’’
Coca and Grove investigated atopy further (21), to be a clinically useful term since IgE-mediated allergy
throwing light on certain important aspects but reaching is common in children and young adults, and often runs
some curious conclusions (70). They reported the in families.
presence of heat-labile ‘‘bodies’’, which they called Typical allergic symptoms include asthma, rhino-
‘‘reagins’’ by virtue of their similarity in this respect to conjunctivitis, gastrointestinal symptoms, and charac-
the heat-labile reagins (complement) of the Wassermann teristic skin lesions, generally referred to as ‘‘atopic
reaction. They concluded that it is ‘‘advisable for the diseases’’ (for the new nomenclature of some of these
present to avoid the term ‘antibodies’ ’’, because there diseases, see below). Typically, an atopic patient
was ‘‘no evidence that these bodies appeared as the develops a spectrum of ‘‘atopic diseases’’ with age,
result of immunological stimulation’’. sometimes referred to as ‘‘the atopic march’’. During the
In the following decades, many population studies, first years, gastrointestinal and eczematous skin symp-
particularly those by Schwartz (81) and by Schnyder toms, often caused by food allergens, predominate.
(80), and follow-up studies of children first seen with Asthma and rhinitis to inhalant allergens develop later.
infantile eczema (60, 83) demonstrated the classic atopic Atopy is inherited. For example, the risk of a child
diseases and the close association of asthma, hay fever, developing an IgE-mediated allergy is 40–60% if both
perennial rhinitis, atopic dermatitis, and food allergies parents are atopic. This risk used to be 5–10% if neither
in such infants. It was later shown that serum IgE levels parent was atopic (49), but the percentage is increasing.
(42) are increased, on average, in ‘‘atopic dermatitis’’ In ‘‘highly atopic’’ children, IgE sensitization and atopic
(46, 64), and that this serum IgE increase is related to the diseases develop early in life. Associations between
increase of IgE specific against several environmental several gene loci and asthma, high IgE levels, and other
allergens (35, 96, 107). However, it was also observed conditions have been reported (10, 52). However, so far,
that in moderate or mild forms, and even in a few cases no specific genetic markers for atopy have been
of severe ‘‘atopic dermatitis’’ without coexistent asthma identified. The most likely explanation is that atopy is
or rhinitis, the IgE values may lie in the normal range a polygenic disorder.
(79, 106). Some individuals that cannot be described as atopic
The field of allergy has developed rapidly during the escape sensitization to common allergens in childhood
last 50 years. Knowledge about immunologic mechan- and adolescence, but develop IgE-mediated allergy later
isms and pharmacologic effects has improved our in life when exposed to high doses of allergen, often
understanding (61). The classical nomenclature for together with some adjuvant, such as tobacco smoke
814
Allergy nomenclature
(66). This situation is illustrated by many cases of immune protection against bacterial and viral infec-
occupational allergy (74), as to laboratory animals such tions, and Th2 cells protect the body from helminth
as mice (90), enzymes such as a-amylase (11, 101), infestations and perhaps also maintain pregnancy (37).
Bacillus subtilis protease (95), and houseplants such as It should be remembered that cells and mediators of the
Ficus benjamina (7, 78). There are some indications that, immune system are also found in biopsies of inflamma-
in addition to the IgE trait, atopy includes some kind of tory sites, as immunologic reactions are of course
target organ sensitivity, as shown, for example, by the involved in mediating and initiating inflammatory as
adverse effect of exercise in some patients, the finding of well as allergic responses. Inflammatory reactions,
nonallergen-specific bronchial hyperreactivity in especially the Th2-driven ones, are also involved in the
patients with allergic asthma, and the disturbed barrier immune defense, as against helminths, and eosinophilia
function of atopic skin. can be stimulated by bacterial and viral infections.
Without a genetic marker, the atopic individual Various types of inflammatory reactions, especially
cannot be identified before developing allergen-specific eosinophilic inflammation, are of fundamental impor-
IgE sensitization. However, it is not widely appreciated tance in allergic reactions. Thus, the presence in the
by nonspecialists in allergic disease that the presence of tissue or circulation of increased numbers of eosino-
IgE antibodies does not necessarily mean clinically phils, IL-5, or even polyclonal IgE without significant
active disease, although such antibodies represent a risk antibody activity does not necessarily indicate an
in the appropriate circumstances; for example, allergen allergic reaction. On the other hand, the presence of
exposure and a concomitant promoter such as infection IgE antibodies to classical allergens is always the sign of
or exercise. In addition, the presence of IgE antibodies a potentially significant allergic reaction.
may have a predictive value. Several groups have found The same cytokines and interleukins of the Th2 system
that even without symptoms, the presence of IgE are involved in both the beneficial and harmful effects.
antibodies to hen’s egg white in infants predicts the In addition, various substances can act as adjuvants and
development of atopic symptoms before 7–10 years of polyclonal IgE stimulants. One example is the enter-
age (31, 62). otoxins of Staphylococcus aureus, sometimes referred to
In a typical case of atopy, the dose of inhalant allergen as ‘‘superantigens’’, that seem to be capable of
necessary to induce sensitization and symptoms is stimulating eosinophilic inflammation and a polyclonal
extremely low. Estimates based on pollen counts IgE response in ‘‘atopic dermatitis’’ (53) and also in
indicate an annual dose of a few micrograms (57), and typically nonallergic nasal polyps (8). Other examples
sensitization to cat allergen Fel d 1 can occur (88) at are cigarette smoke (26), cytomegalovirus (CMV)
levels around 25 ng/g of dust. Levels of animal allergens infection (63), and graft versus host disease (GVHD)
in the air of public buildings such as schools have been (76). Similarly, the microscopic and immunologic
found to be in the ng/m3 range, i.e., about the same level appearance of the bronchial mucosa is similar in the
of exposure as to pollens. biopsies of both classical allergic asthma (previously
IgE-mediated mechanisms are often involved in also referred to as extrinsic or exogenous asthma) and
allergies to insect venom (58, 59), usually in the same nonallergic asthma (previously referred to as intrinsic or
frequency as in individuals that cannot be described as endogenous asthma) (16, 38). The same is true also of
atopic, and to certain drugs (87). An IgE involvement, allergic and nonallergic rhinitis (6) and different kinds of
with markedly raised serum levels of IgE and the eczema/dermatitis (5, 51, 79, 89).
presence of specific IgE antibodies, has been detected in In the following paragraphs, we propose that
helminth infestations (36, 43, 77), and it is thought that ‘‘hypersensitivity’’ be used as an umbrella term (see
the beneficial function of IgE is related to our defense below), and that the term ‘‘allergy’’ be reserved for
against helminth parasites. However, more studies are clinical reactions in which an immunologic mechanism is
needed to explain the entire possible range of beneficial proven or strongly implicated. The term ‘‘atopy’’,
functions of IgE. discussed above, has also been revised. We propose
The IgE antibody response may represent a remark- that the term ‘‘atopy’’ be used to describe a familial or
ably large proportion of the IgE pool; in some cases of personal tendency to develop allergen-specific IgE on
allergic rhinitis, as much as 50–60% of IgE in a serum exposure to environmental allergens, and to suffer
sample can be recovered as antibody to the pollen typical allergic symptoms.
allergen (44). However, in other cases, e.g., IgE-
mediated ‘‘atopic’’ dermatitis, the polyclonal produc-
tion is considerable, and the IgE antibody can represent
as little as 2% or less of the total IgE production (99, 1 Hypersensitivity
106). There has been a tendency during the last couple of
According to the currently favored hypothesis of how decades to use the word ‘‘allergy’’ to describe not only
the immune system is controlled, there is a balance allergy as defined below but all kinds of unexpected
between Th1 and Th2 helper cells. Th1 cells promote reactions in the skin and mucosal surfaces. These include
815
Johansson et al.
Figure 1.
all kinds of controversial adverse reactions to food and tivity’’ and ‘‘multiple chemical sensitivity’’ (27), as well
food additives (17, 65), side-effects to drugs, psycholo- as reactions attributed to amalgam in tooth fillings (55)
gical reactions blamed on environmental factors and electromagnetic waves, should not be called
(‘‘allergy to electricity’’) (54), behavioral disorders, hypersensitivity.
and others. We propose to use the term nonallergic hypersensitiv-
We propose that the term hypersensitivity be used as ity when immunologic mechanisms cannot be proven, as
the ‘‘umbrella’’ term to cover such reactions (Fig. 1), in hypersensitivity to aspirin (84). The term ‘‘pseudo-
and that its definition should be as follows: allergy’’, introduced many years ago (22) and still
occasionally used in some European countries, should
Hypersensitivity causes objectively reproducible symptoms or be abandoned.
signs, initiated by exposure to a defined stimulus at a dose The term ‘‘nonallergic hypersensitivity’’ embraces
tolerated by normal subjects. many different disorders. However, it is not within the
remit of this group to classify these entities.
This definition does not accommodate classical
responses to infection, autoimmunity, or toxic reac-
tions. It is important that the hypersensitivity reaction 2 Atopy
be reproducible in the sense that there is reasonable
evidence from history, examination, or investigation of We propose that the definition of atopy should be as
follows:
a link between the symptoms and the environmental
factors to which the patients attribute their symptoms.
Atopy is a personal or familial tendency to produce IgE
In this context, ‘‘reproducible’’ does not mean, for antibodies in response to low doses of allergens, usually
example, that a food provocation test of a patient in the proteins, and to develop typical symptoms such as asthma,
doctor’s office must be positive at any time. The old rhinoconjunctivitis, or eczema/dermatitis.
term ‘‘idiosyncrasy’’ is no longer needed. Furthermore,
hypersensitivity must be distinguished from hyper- We propose that the terms atopy and atopic be
reactivity, which is an exaggerated normal response to a reserved to describe this clinical trait and predisposition,
stimulus. and not be used to describe diseases. The first
As a consequence of this stringent definition of manifestations of atopy in a child are often ‘‘allergic’’
hypersensitivity, many entities within the field of symptoms, such as diarrhea, wheezing, and skin rashes,
‘‘environmental medicine’’, such as ‘‘total drug sensi- and only later can the responsible IgE antibody be
816
Allergy nomenclature
817
Johansson et al.
Figure 4.
818
Allergy nomenclature
819
Johansson et al.
820
Allergy nomenclature
(9, 100). Therefore, these food allergies can present with (58), i.e., several micrograms of major allergens per
symptoms in other organ systems that do not justify a sting, an amount similar to the annual dose of inhaled
diagnosis of anaphylaxis (see below). pollen allergen. This is probably the reason for almost
the same prevalence of atopy among patients with IgE
8.1 Food allergy sensitization to venom as in the normal population (14).
We propose that any venom hypersensitivity reaction
We propose that an adverse reaction to food should be
called food hypersensitivity (Fig. 8). When immunologic (Fig. 10) mediated by immunologic mechanisms be
called allergy, as in bee venom allergy. To highlight the
mechanisms have been demonstrated, the appropriate
term is food allergy, and, if the role of IgE is highlighted, role of IgE antibody, we may use a term such as
IgE-mediated bee venom allergy. A term such as
the term is IgE-mediated food allergy. All other
reactions, previously sometimes referred to as ‘‘food nonallergic bee venom hypersensitivity should be used
to denote other reactions.
intolerance’’, should be referred to as nonallergic food
hypersensitivity (17, 65). Severe, generalized allergic
reactions to food can be classified as anaphylaxis (see
below). 9 Anaphylaxis
The term ‘‘anaphylaxis’’ is applied in various regions
8.2 Drug allergy and by various physicians to different clinical entities
The side-effects of drugs of the type discussed here and immunologic mechanisms. Some doctors confine
should be referred to as drug hypersensitivity (Fig. 9). application of the term ‘‘anaphylaxis’’ to reactions in
When immunologic mechanisms have been shown, which critical hypotension is evident – ‘‘anaphylactic
either antibody or cell mediated, the reactions should be shock’’ – with an IgE-mediated mechanism. Others
referred to as drug allergy. By adding the adjective extend its application beyond anaphylactic shock to
immediate/late or delayed, we can both describe the include severe, life-threatening attacks of broncho-
onset of symptoms and indicate the probable mediating spasm. Still other clinicians use it to describe any
mechanisms, IgE and lymphocytes (71), respectively. If generalized or systemic allergic reactions, even if
we wish to highlight the role of IgE antibody in a hypotension and severe bronchospasm are absent. We
reaction, it may be called IgE-mediated drug allergy. All propose the following broad definition:
other reactions should be referred to as nonallergic drug
hypersensitivity. Such reactions may have identifiable Anaphylaxis is a severe, life-threatening, generalized or
associations, such as G6PD deficiency, or unknown systemic hypersensitivity reaction.
mechanisms. A positive intradermal skin test or a weak
(<3 mm) skin prick test is not an objective or sufficient The reaction usually develops gradually, most often
measure of an immunologic reaction – for example, starting with itching of the gums/throat, the palms, or
compare direct mediator release by certain neuropep- the soles, and local urticaria; developing to a multiple
tides and basic secretagogues such as compound 48/80 organ reaction often dominated by severe asthma; and
(18) – and should not be accepted as the only evidence culminating in hypotension and shock. Hypotension
for a possible immunologic mechanism. and severe bronchospasm do not have to be present for
a reaction to be classified as anaphylaxis.
The term allergic anaphylaxis (Fig. 11) should be
8.3 Insect sting allergy used when an immunologic mechanism can be shown to
As with drugs, individuals stung, for example, by a be important, as in an IgG immune complex, comple-
Hymenoptera insect are exposed to large quantities ment-related, or immune cell-mediated mechanism, or
821
Johansson et al.
References
1. AALBERSE RC, vAN REE R. 13. BESNIER ME. Première note et 24. FÖTISCH K, ALTMANN F, HAUSTEIN D,
Crossreactive carbohydrate observations préliminaires pour servir VIETHS S. Involvement of carbohydrate
determinants. Clin Rev Allergy d’introduction à l’étude des prurigos epitopes in the IgE response of celery-
Immunol 1997;15:375–387. diathésiques (dermatites multiformes allergic patients. Int Arch Allergy
2. AALBERSE RC, AKKERDAAS JH, vAN REE prurigineuses chroniques exacerbantes Immunol 1999;120:30–42.
R. Cross-reactivity of IgE antibodies et paroxystiques, du type prurigo de 25. GELL PGH, COOMBS RRA. Clinical
to allergens. Allergy 2001;56:478–490. Hebra). Ann Dermatol Syph (Paris) aspects of immunology. 2nd ed.
3. AAS K. The biochemical and 1982;3:634–648. Oxford: Blackwell, 1968:575–596.
immunological basis of bronchial 14. BIRNBAUM J, VERVLOET D, CHARPIN D. 26. GERRARD JW, HEINER DC, KO CG,
asthma. Charles C Thomas, 1972. Atopy and systemic reactions to MINK J, MEYERS A, DOSMAN JA.
4. ABELSON MB, editor. Allergic diseases Hymenoptera stings. Allergy Proc Immunoglobulin levels in smokers and
of the eye. WB Saunders, 2000. 1994;15:49–52. non-smokers. Ann Allergy
5. ADKIS CA, ADKIS M, SIMON D, et al. 15. BROCQ L. Quelques aperçus sur les 1980;44:261–262.
T cells and T cell-derived cytokines as dermatoses prurigineuses et sur les 27. GOTS RE, HAMOSH TD, FLAMM WG,
pathogenic factors in the nonallergic anciens lichens. Ann Dermatol Syph CARR CJ. Multiple chemical
form of atopic dermatitis. J Invest (Paris) 1982;3:1100–1117. sensitivities: a symposium on the state
Dermatol 1999;113:628–634. 16. BRUIJNZEEL P, HAMELINK M, PRINS J, of the science. Regul Toxicol
6. AMIN K, RINNE J, HAAHTELA T, et al. REMMERT G, MEYLING FG. Pharmacol 1993;18:61–78.
Inflammatory cell and epithelial Immunological aspects of extrinsic and 28. HAAHTELA T, HEISKALA M, SUONIEMI I.
characteristics of perennial allergic and intrinsic asthma. Agents Actions Suppl Allergic disorders and immediate skin
nonallergic rhinitis with a symptom 1989;28:233–238. test reactivity in Finnish adolescents.
history of 1 to 3 years’ duration. J 17. BRUIJNZEEL-KOOMEN C, ORTOLANI C, Allergy 1980;35:433–441.
Allergy Clin Immunol et al. Adverse reactions to food. 29. HALSTENSEN TS, BRANDTZAEG P.
2001;107:249–257. Position paper. Allergy Activated T lymphocytes in the celiac
7. AXELSSON IGK, JOHANSSON SGO, 1995;50:623–635. lesion: non-proliferative activation
ZETTERSTRÖM O. Occupational allergy 18. CHURCH MK, EL-LATI S, CAULFIELD JP. (CD25) of CD4+ alpha/beta cells in
to weeping fig in plant keepers. Allergy Neuropeptide-induced secretion from the lamina propria and proliferation
1987;42:161–167. human skin mast cells. Int Arch (Ki-67) of alpha/beta and gamma/delta
8. BACHERT C, GEVAERT P, HOLTAPPELS G, Allergy Appl Immunol cells in the epithelium. Eur J Immunol
JOHANSSON SGO, vAN CAUWENBERGE P. 1991;94:310–318. 1993;23:505–510.
Total and specific IgE in nasal polyps 19. COCA AF. Familial non-reaginic food 30. HANIFIN JM, RAJKA G. Diagnostic
is related to local eosinophilic allergy. Springfield: Thomas, 1953. features of atopic dermatitis. Acta
inflammation. J Allergy Clin Immunol 20. COCA AF, COOKE RA. On the Derm Venereol Suppl (Stockh)
2001;107:607–614. classification of the phenomena of 1980;92:44–47.
9. BALLMER-WEBER B, VIETHS S, LÜTTKOPF hypersensitiveness. J Immunol 31. HATTEVIG G, KJELLMAN B, JOHANSSON
D, HEUSCHMANN P, WÜTHRICH B. Celery 1923;8:163–182. SGO, BJÖRKSTÉN B. Clinical symptoms
allergy confirmed by double-blind, 21. COCA AF, GROVE EF. Studies in and IgE responses to common food
placebo-controlled food challenge: a hypersensitiveness. XIII. A study of proteins in atopic and healthy children.
clinical study in 32 subjects with a the atopic reagins. J Immunol Clin Allergy 1984;14:551–559.
history of adverse reactions to celery 1925;10:445–464. 32. HEDIN H, RICHTER W, RING J. Dextran-
root. J Allergy Clin Immunol 22. DUKOR P, KALLÓS P, SCHLUMBERGER induced anaphylactoid reactions in
2000;106:373–378. HD, WEST GB, editors. In: PAR man. Role of dextran reactive
10. BARNES KC. Atopy and asthma genes – pseudo-allergic reactions. Involvement antibodies. Int Arch Allergy Appl
where do we stand? Allergy of drugs and chemicals. Vol. I. Genetic Immunol 1976;52:145–159.
2000;55:803–817. aspects and anaphylactoid reactions. 33. HERZ U, BUNIKOWSKI R, RENZ H. Role
11. BAUR X, POSCH A. Characterized Basel: Karger, 1980. of T cells in atopic dermatitis. Int Arch
allergens causing baker’s asthma. 23. ERIKSSON NE. Food sensitivity Allergy Immunol 1998;115:179–190.
Allergy 1998;53:562–566. reported by patients with asthma and 34. HJORT N, ROED-PETERSEN J.
12. BENNICH HH, ISHIZAKA K, JOHANSSON hay fever. A relationship between food Occupational protein contact
SGO, ROWE DS, STANWORTH DR, sensitivity and birch pollen-allergy and dermatitis in food handlers. Contact
TERRY WD. Immunoglobulin E, a new between food sensitivity and Dermatitis 1976;2:28–42.
class of human immunoglobulin. Bull acetylsalicylic acid intolerance. Allergy 35. HOFFMAN DR, YAMAMOTO FY, GELLER
World Health Organ 1968;38:151–152. 1978;33:189–196. B, HADDID Z. Specific IgE antibodies in
atopic eczema. J Allergy Clin Immunol
1974;55:256–267.
822
Allergy nomenclature
36. HOGARTH-SCOTT RS, JOHANSSON SGO, 50. KONDO N, AGATA H, FKUTOMI O, 64. OGAWA M, BERGER PA, MCINTYRE OR,
BENNICH H. Antibodies to Toxocara in MOTOYOSHI F, ORII T. Lymphocyte CLENDENNING WE, HANOVER NH,
the sera of visceral larva migrans responses to food antigens in patients ISHIZAKA K. IgE in atopic dermatitis.
patients: the significance of raised with atopic dermatitis who are Arch Dermatol 1971;103:575–580.
levels of IgE. Clin Exp Immunol sensitive to foods. J Allergy Clin 65. ORTOLANI C, BRUIJNZEEL-KOOMEN C,
1969;5:619–625. Immunol 1990;86:253–260. BENGTSSON U, et al. Controversial
37. HOLT PG, JONES CA. The immunology 51. KÄGI MK, WÜTHRICH B, MONTANO E, aspects of adverse reactions to food.
of fetuses and infants. The BARANDUN J, BLASER K, WALKER C. Position paper. Allergy 1999;55:27–45.
development of the immune system Differential cytokine profiles in 66. OSTERMAN K, ZETTERSTRÖM O,
during pregnancy and early life. peripheral blood lymphocyte JOHANSSON SGO. Coffee worker’s
Allergy 2000;55:688–697. supernatants and skin biopsies from allergy. Allergy 1982;37:313–322.
38. HUMBERT M, MENZ G, YING S, et al. patients with different forms of atopic 67. PARISH WE. Short-term anaphylactic
The immunopathology of extrinsic dermatitis, psoriasis and normal IgG antibodies in human sera. Lancet
(atopic) and intrinsic (non-atopic) individuals. Int Arch Allergy Immunol 1970;2:791.
asthma: more similarities than 1994;104:332–340. 68. PATTERSON R, GREENBERGER PA,
differences. Immunol Today 52. LAITINEN T, DALY MJ, RIOUX JD, et al. HALWIG JM, LIOTTA JL, ROBERTS M.
1999;20:528–533. A susceptibility locus for asthma- ABPA natural history and
39. HUSBY S. Dietary antigens: uptake and related traits on chromosome 7 classification of early disease by
humoral immunity in man. APMIS revealed by genome-wide scan in a serologic and roentgenographic
Suppl 1988;1:1–40. founder population. Nat Genet studies. Arch Intern Med
40. ILIEV D, WÜTHRICH B. Conjunctivitis to 2001;28:87–91. 1986;146:916–921.
thimerosal mistaken as hay fever. 53. LEUNG DY, HARBECK R, BINA P, et al. 69. PEPYS J. Atopy. In: GILL PGH, COOMBS
Allergy 1998;53:333–334. Presence of IgE antibodies to RRA, LACHMANN PJ, editors. Clinical
41. ISHIZAKA K, ISHIZAKA T, HORNBROOK staphylococcal exotoxins on the skin aspects of immunology. 3rd ed.
MM. Physicochemical properties of of patients with atopic dermatitis. J Oxford: Blackwell Scientific,
reaginic antibody. V. Correlation of Clin Invest 1993;92:1374–1380. 1975:877–902.
reaginic activity with cE-globulin 54. LIDÉN S. Sensitivity to electricity – a 70. PEPYS J. ‘‘Atopy’’: a study in definition
antibody. J Immunol 1966;97:840. newcomer among environmental [Editorial]. Allergy 1994;49:397–399.
42. JOHANSSON SGO. Serum IgND levels in epidemics. Allergy 1996;51:519–544. 71. PICHLER WJ, SCHNYDER B, ZANNI MP,
healthy children and adults. Int Arch 55. LÜBBE J, WÜTHRICH B. HARI Y, vON GREYERZ S. Role of T cells
Allergy 1968;34:1–8. Amalgamallergie und in drug allergies. Allergy
43. JOHANSSON SGO, MELLBIN T, VAHLQUIST Amalgamkontroverse. Schweiz Med 1998;53:225–232.
B. Immunoglobulin levels in Ethiopian Wochenschr 1996;126:661–665. 72. POLEY GE, SLATER JE. Latex allergy. J
preschool children with special 56. LÜTTKOPF D, BALLMER-WEBER BK, Allergy Clin Immunol
reference to high concentrations of WÜTHRICH B, VIETHS S. Celery allergens 2000;105:1054–1062.
immunoglobulin E (IgND). Lancet in patients with positive double-blind 73. PRAUSNITZ C, KÜSTNER H. Studien über
1968;25:1118–1121. placebo-controlled food challenge. J die Überempfindlichkeit. Zentralbl
44. JOHANSSON SGO. Unpublished Allergy Clin Immunol Bakt Parasits Infect I Abt Orig
observation, 2001. 2000;106:390–399. 1921;86:160–169.
45. JUHLIN-DANNFELDT C. On the 57. MARSH DG. Allergens. In: SELA M, 74. QUIRCE S, SASTRE J. Occupational
significance of exposure and editor. The antigens. New York: asthma. Allergy 1998;53:633–641.
provocation tests in allergic Academic Press, 1975:271–359. 75. RAJKA G. Atopic dermatitis. WB
diagnostics. Acta Med Scand 1946;130 58. MÜLLER UR. Insect sting allergy. Saunders, 1975.
Suppl 206:320–327. Clinical pictures, diagnosis and 76. RINGDÉN O, PERSSON U, JOHANSSON
46. JUHLIN L, JOHANSSON SGO, BENNICH H, treatment. Gustav Stuttgart: Fischer, SGO, et al. Markedly elevated serum
HÖGMAN C, THYRESSON N. 1990. IgE levels following allogeneic and
Immunoglobulin E in dermatoses: 59. MÜLLER UR. New developments in the syngeneic bone marrow
levels in atopic dermatitis and diagnosis and treatment of transplantation. Blood
urticaria. Arch Dermatol Hymenoptera venom allergy. Int Arch 1983;61:1190–1195.
1969;100:12–16. Allergy Immunol 2001;124:447–453. 77. ROSENBERG EB, WHALEN GE, BENNICH
47. KAROL MH, IOSET HH, ALARIE YC. 60. MUSGROVE K, MORGAN JK. Infantile H, JOHANSSON SGO. Increased
Tolyl-specific IgE antibodies in eczema: a long-term follow-up study. circulating IgE in a new parasitic
workers with hypersensitivity to Br J Dermatol 1967;95:365–372. disease – human intestinal capillariasis.
toluene diisocyanate. Am Ind Hyg 61. MYGIND N, DAHL R, PEDERSEN S, N Engl J Med 1970;283:1148–1149.
Assoc J 1978;39:454–458. THESTRUP-PEDERSEN K. Essential 78. SCHMID P, STÖGER P, WÜTHRICH B.
48. KIVILOOG J, IRNELL L, EKLUND G. The allergy. 2nd ed. Blackwell Science, Severe isolated allergy to Ficus
prevalence of bronchial asthma and 1996. benjamina after bedroom exposure.
chronic bronchitis in smokers and non- 62. NICKEL R, KULIG M, FORSTER J, et al. Allergy 1993;48:466–467.
smokers in a representative local Sensitisation to hen’s egg at the age of 79. SCHMID (-GRENDELMEIER) P, SIMON D,
Swedish population. Scand J Respir twelve months is predictive for allergic SIMON H-U, ADKIS CA, WÜTHRICH B.
Dis 1974;55:262–269. sensitisation to common indoor and Epidemiology, clinical features and
49. KJELLMAN N-IM. Atopic disease in outdoor allergens at the age of three immunology of the ‘‘intrinsic’’ (non-
seven-year-old children. Incidence in years. J Allergy Clin Immunol IgE-mediated) type of atopic
relation to family history. Acta 1997;99:613–617. dermatitis (constitutional dermatitis).
Paediatr Scand 1977;66:465–471. 63. NORDBRING F, JOHANSSON SGO. IgM in Allergy 2001;56:841–849.
cytomegalovirus mononucleosis.
Scand J Infect Dis 1971;3:87–90.
823
Johansson et al.
80. SCHNYDER UW. Neurodermitis – 90. WEISSENBACH T, WÜTHRICH B, WEIHE 99. WÜTHRICH B. Serum IgE in atopic
Asthma – Rhinitis. Eine genetisch- WH. Labortier-Allergie. Eine dermatitis. Relationship to severity of
allergologische Studie. Int Arch epidemiologische, allergologische cutaneous involvement and course of
Allergy 1960;178 (Suppl):1–106. Studie bei Labortier-exponierten diseases as well as coexistence of atopic
81. SCHWARTZ M. Heredity in bronchial Personen. Schweiz Med Wochenschr respiratory diseases. Clin Allergy
asthma: a clinical and genetic study of 1988;118:930–938. 1978;8:241–248.
191 asthma probands and 50 probands 91. WERFEL T, AHLERS G, SCHMIDT P, 100. WÜTHRICH B, STÄGER J, JOHANSSON
with baker’s asthma. Acta Allergol BOCKER M, KAPP A. Detection of a SGO. Celery allergy associated with
1952;5 Suppl 2. kappa-casein-specific lymphocyte birch and mugwort pollinosis. Allergy
82. STANWORTH DR, HUMPHREY JH, response in milk-responsive atopic 1990;45:566–571.
BENNICH H, JOHANSSON SGO. Specific dermatitis. Clin Exp Allergy 101. WÜTHRICH B, BAUR X. Backmittel,
inhibition of the Prausnitz-Küstner 1996;26:1380–1386. insbesondere Alpha-Amylase, als
reaction by an atypical human 92. WILLIAMS HC, editor. What is atopic berufliche Inhalationsallergene in der
myeloma protein. Lancet dermatitis and how should it be Backwarenindustrie. Schweiz Med
1967;ii:330–332. defined in epidemiological studies? Wochenschr 1990;120:446–450.
83. STIFLER WC. A 21-year follow-up of Cambridge University Press, 2000. 102. WÜTHRICH B. Minimal forms of atopic
infantile eczema. J Pediatr 93. WISE F, SULZBERGER MB. Footnote on eczema. In: RUZICKA T, RING J,
1965;66:166–169. problem of eczema, neurodermatitis PRZYBILLA B, editors. Handbook of
84. SZCZEKLIK A. Mechanisms of aspirin- and lichenification. In: WISE F, atopic eczema. Berlin: Springer,
induced asthma. Allergy SULZBERGER MB, editors. The 1933 1991:46–53.
1997;52:619–619. Year Book of Dermatology and 103. WÜTHRICH B. Protein contact
85. TURJANMAA K, ALENIUS H, MÄKINEN- Syphilology. Chicago: Year Book dermatitis. Br J Dermatol
KILJUNEN S, REUNALA T, PALOSUO T. Publishers, 1993:38–39. 1996;135:332–333.
Natural rubber latex allergy. Allergy 94. WOLLENBER A, BIEBER T. Atopic 104. WÜTHRICH B, STRAUMANN F. Pollen
1996;51:593–602. dermatitis: from the genes to skin cross-reactivity. Can we establish a
86. VALENTA R, MAURER D, STEINER R, lesions. Allergy 2000;55:205–213. link between the in vitro results and the
et al. Immunoglobulin E response to 95. WÜTHRICH B, SCHWARZ-SPECK M. clinical situation? Allergy
human proteins in atopic patients. J Asthma bronchiale nach beruflicher 1997;52:1187–1193.
Invest Dermatol 1996;107:203–208. Exposition mit proteolytischen 105. WÜTHRICH B. Clinical aspects,
87. VERVLOET D, DURHAM S. ABC of Enzymen (Bacillus subtilis-Proteasen). epidemiology, and prognosis of atopic
allergies. Adverse reactions to drugs. Schweiz Med Wochenschr dermatitis. Ann Allergy Asthma
BMJ 1998;316:1511–1514. 1970;100:1908–1914. Immunol 1999;83:464–470.
88. WAHN U, LAU S, BERGMANN R, et al. 96. WÜTHRICH B. Allergen-spezifische IgE 106. ÖHMAN S, JOHANSSON SGO, JUHLIN L.
Indoor allergen exposure is a risk im Radio-Allergo-Sorbens-Test bei Immunoglobulins in atopic dermatitis.
factor for sensitisation during the first Neurodermitis. Hautarzt Proceedings of the VIII European
three years of life. J Allergy Clin 1974;25:603–605. Congress of Allergology 1971.
Immunol 1997;99:763–769. 97. WÜTHRICH B, GILLIET F, HITZIG WH. Excerpta Medica International
89. WALKER C, KÄGI MK, INGOLD P, Pollinosis als Überempfindlichkeit Congress Series, no. 251, pp.119–126.
BRAUN P, BLASER K, WÜTHRICH B. vom Spättyp. Schweiz Med 107. ÖHMAN S, JOHANSSON SGO. Allergen-
Atopic dermatitis: correlation of Wochenschr 1974;104:534–539. specific IgE in atopic dermatitis. Acta
peripheral blood T cell activation, 98. WÜTHRICH B. Zur Immunpathologie Derm Venereol (Stock)
eosinophilia and serum factors with der Neurodermitis constitutionalis. 1974;55:283–290.
clinical severity. Clin Exp Allergy Eine klinisch-immunologische Studie
1993;23:45–154. mit besonderer Berücksichtigung der
Immunglobuline E und der
spezifischen Reagine im zeitlichen
Verlauf. Bern: Hans Huber,
1975:92–124.
824