Früherkennung allergischer Erkrankungen

L. Klimek

doi:10.1055/s-2007-995537

Laryngo-Rhino-Otologie, Table of Contents

Laryngorhinootologie 2008; 87: S32-S53
DOI: 10.1055/s-2007-995537

Früherkennung

Früherkennung allergischer Erkrankungen

L. Klimek¹

¹Zentrum für Rhinologie und Allergologie, Wiesbaden

Abstract

Zusammenfassung

Asthmatische Beschwerden existieren seit der Antike, der „Heuschnupfen” wurde Ende des 18. Jahrhunderts erstmals beschrieben. Heute, knapp 100 Jahre nach der Einführung des Begriffs der Allergie, sind allergische Erkrankungen zur Volkskrankheit geworden, die in der westlichen Welt ein Drittel der Bevölkerung betreffen. Diese Erkrankungen gehören heute zu den häufigsten chronischen Erkrankungen, machen einen beträchtlichen Teil der gesamten Gesundheitskosten aus und sind von großer gesundheitspolitischer Relevanz.Bedingt durch genetische sowie Umweltfaktoren ist die Bandbreite an IgE-vermittelten allergischen Erkrankungen recht groß; zu ihnen gehören z. B. die atopische Dermatitis, das Asthma bronchiale oder die Rhinitis allergika. In dieser Übersichtsarbeit soll - aufgrund des Schwerpunkts im HNO-Bereich - die allergische Rhinitis im Mittelpunkt der Überlegungen zur Früherkennung allergischer Erkrankungen stehen.

Schlüsselwörter

Rhinitis allergika - atopische/allergische Erkrankungen - In-vitro-Diagnostik - Spezifische Immuntherapie

Full Text

References

Literatur

1 Bousquet J, Van CP, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001; 108 S147-S334
2 Pariente P D, LePen C, Los F, Bousquet J. Quality-of-life outcomes and the use of antihistamines in a French national population-based sample of patients with perennial rhinitis. Pharmacoeconomics. 1997; 12 585-595
3 Ring J, Wenning J. Weißbuch: Allergie in Deutschland 2000. Deutsche Gesellschaft für Allergie und klinische Immunologie. München; Urban und Vogel 2000
4 Statistisches Bundesamt .Gesundheitsbericht für Deutschland. Spezialbericht Allergien. Stuttgart; Metzler-Poeschel 2000
5 Klimek L, Reichenbach M, Mewes T, Mann W. Untersuchungen zur Reproduzierbarkeit und jahreszeitlichen Abhängigkeit von spezifischen intranasalen Provokationstests bei Birkenpollenallergikern. Laryngorhinootologie. 1997; 76 475-479
6 Connell J T. Quantitative intranasal pollen challenges. 3. The priming effect in allergic rhinitis. J Allergy. 1969; 43 33-44
7 Ciprandi G, Buscaglia S, Pesce G, Pronzato C, Ricca V, Parmiani S, Bagnasco M, Canonica G W. Minimal persistent inflammation is present at mucosal level in patients with asymptomatic rhinitis and mite allergy. J Allergy Clin Immunol. 1995; 96 971-979
8 Kripke M L, Munn C G, Jeevan A, Tang J M, Bucana C. Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization. J Immunol. 1990; 145 2833-2838
9 Picker L J. Control of lymphocyte homing. Curr Opin Immunol. 1994; 6 394-406
10 Johnson J G, Jenkins M K. Co-stimulatory functions of antigen-presenting cells. J Invest Dermatol. 1992; 99 62S-65S
11 Mosmann T R, Cherwinski H, Bond M W, Giedlin M A, Coffman R L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. 1986. J Immunol. 2005; 175 5-14
12 Maggi E, Parronchi P, Manetti R, Simonelli C, Piccinni M P, Rugiu F S, Carti M, Ricci M, Romagnani S. Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. J Immunol. 1992; 148 2142-2147
13 Modlin R L. Th1-Th2 paradigm: insights from leprosy. J Invest Dermatol. 1994; 102 828-832
14 Jones H E, Inouye J C, McGerity J L, Lewis C W. Atopic disease and serum immunoglobulin-E. Br J Dermatol. 1975; 92 17-25
15 Enk A H, Katz S I. Identification and induction of keratinocyte-derived IL-10. J Immunol. 1992; 149 92-95
16 Vercelli D. Regulation of IgE synthesis. Allergy Proc. 1993; 14 413-416
17 van Reijsen F C, Bruijnzeel-Koomen C A, Kalthoff F S, Maggi E, Romagnani S, Westland J K, Mudde G C. Skin-derived aeroallergen-specific T-cell clones of Th2 phenotype in patients with atopic dermatitis. J Allergy Clin Immunol. 1992; 90 184-193
18 Kay A B, Ying S, Varney V, Gaga M, Durham S R, Moqbel R, Wardlaw A J, Hamid Q. Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects. J Exp Med. 1991; 173 775-778
19 Schartz L, Huff T. Biology of mast cells and Basophils. In: Middleton EJ, Reed CE, Ellis EF (eds) Allergy, Principles and Practice. St. Louis; Mosby-Year-Book 1993
20 Church M K, el-Lati S, Caulfield J P. Neuropeptide-induced secretion from human skin mast cells. Int Arch Allergy Appl Immunol. 1991; 94 310-318
21 Wardlaw A J, Moqbel R, Cromwell O, Kay A B. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J Clin Invest. 1986; 78 1701-1706
22 Wang J M, Rambaldi A, Biondi A, Chen Z G, Sanderson C J, Mantovani A. Recombinant human interleukin 5 is a selective eosinophil chemoattractant. Eur J Immunol. 1989; 19 701-705
23 Schleimer R P, Sterbinsky S A, Kaiser J, Bickel C A, Klunk D A, Tomioka K, Newman W, Luscinskas F W, Gimbrone Jr M A, McIntyre B W. IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J Immunol. 1992; 148 1086-1092
24 Skoner D P. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol. 2001; 108 S2-S8
25 Craig T J, Teets S, Lehman E B, Chinchilli V M, Zwillich C. Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids. J Allergy Clin Immunol. 1998; 101 633-637
26 Vuurman E F, vanVeggel L M, Uiterwijk M M, Leutner D, O’Hanlon J F. Seasonal allergic rhinitis and antihistamine effects on children’s learning. Ann Allergy. 1993; 71 121-126
27 Lack G. Pediatric allergic rhinitis and comorbid disorders. J Allergy Clin Immunol. 2001; 108 S9-S15
28 Wright A L, Holberg C J, Martinez F D, Halonen M, Morgan W, Taussig L M. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994; 94 895-901
29 Leynaert B, Bousquet J, Neukirch C, Liard R, Neukirch F. Perennial rhinitis: An independent risk factor for asthma in nonatopic subjects: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol. 1999; 104 301-304
30 Ruoppi P, Seppa J, Nuutinen J. Acute frontal sinusitis: etiological factors and treatment outcome. Acta Otolaryngol. 1993; 113 201-205
31 Keith P K, Conway M, Evans S, Wong D A, Jordana G, Pengelly D, Dolovich J. Nasal polyps: effects of seasonal allergen exposure. J Allergy Clin Immunol. 1994; 93 567-574
32 Bachert C, Hormann K, Mosges R, Rasp G, Riechelmann H, Muller R, Luckhaupt H, Stuck B A, Rudack C. An update on the diagnosis and treatment of sinusitis and nasal polyposis. Allergy. 2003; 58 176-191
33 Corey J P, Adham R E, Abbass A H, Seligman I. The role of IgE-mediated hypersensitivity in otitis media with effusion. Am J Otolaryngol. 1994; 15 138-144
34 McColley S A, Carroll J L, Curtis S, Loughlin G M, Sampson H A. High prevalence of allergic sensitization in children with habitual snoring and obstructive sleep apnea. Chest. 1997; 111 170-173
35 Mutius E, Martinez F D, Fritzsch C, Nicolai T, Roell G, Thiemann H H. Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med. 1994; 149 358-364
36 Mutius E. Epidemiologie des Asthma bronchiale im Kindesalter. Pneumologie. 1997; 51 949-961
37 Martinez F D, Wright A L, Taussig L M, Holberg C J, Halonen M, Morgan W J. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995; 332 133-138
38 Martinez F D. Role of viral infections in the inception of asthma and allergies during childhood: could they be protective?. Thorax. 1994; 49 1189-1191
39 Silverman M. Childhood asthma and other weezing disorders. Chapman & Hall Medical 1995
40 Mutius E. Air pollution and asthma. Immunotherapy in Asthma. Marcel Dekker Ltd 1995
41 . Health effects of atmospheric acids and their precursors. Report of the ATS workshop on the Health Effects of Atmospheric Acids and their Precursors. Am Rev Respir Dis. 1991; 144 464-467
42 Committee Of The Environmental And Occupational Health Assembly Of The American Thoracic Society (ATS) . Health effects of outdoor air pollution, Part 1. Am J Respir Crit Care Med. 1996; 153 3-50
43 Delacourt C, Labbe D, Vassault A, Brunet-Langot D, de Blic J, Scheinmann P. Sensitization to inhalant allergens in wheezing infants is predictive of the development of infantile asthma. Allergy. 1994; 49 843-847
44 Hosoi J, Murphy G F, Egan C L, Lerner E A, Grabbe S, Asahina A, Granstein R D. Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Nature. 1993; 363 159-163
45 Wiesner-Menzel L, Schulz B, Vakilzadeh F, Czarnetzki B M. Electron microscopical evidence for a direct contact between nerve fibres and mast cells. Acta Derm Venereol. 1981; 61 465-469
46 Stingl G, Katz S I, Clement L, Green I, Shevach E M. Immunologic functions of Ia-bearing epidermal Langerhans cells. J Immunol. 1978; 121 2005-2013
47 Inaba K, Schuler G, Witmer M D, Valinksy J, Atassi B, Steinman R M. Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes. J Exp Med. 1986; 164 605-613
48 Robertson I, Greaves M W. Responses of human skin blood vessels to synthetic histamine analogues. Br J Clin Pharmacol. 1978; 5 319-322
49 Smith J S, Mansfield L E, de Shazo R, Nelson H S. An evaluation of the pharmacologic inhibition of the immediate and late cutaneous effect to allergen. J Allergy Clin Immunol. 1980; 65 188
50 Rietschel R L, Fowler Jr J F. Fisher’s Contact Dermatitis. Baltimore; Williams and Wilkin 1995
51 Lockey R F, Benedict L M, Turkeltaub P C, Bukantz S C. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol. 1987; 79 660-677
52 American Academy of Allergy and Immunology . The waiting period after allergen skin testing and immunotherapy. J Allergy Clin Immunol. 1990; 85 526-527
53 Pepys J. Skin testing. Br J Hosp Med. 1975; 14 412
54 Brown H M, Su S, Thantrey N. Prick testing for allergens standardized by using a precision needle. Clin Allergy. 1981; 11 95-98
55 Osterballe O, Weeke B. A new lancet for skin prick testing. Allergy. 1979; 34 209-212
56 Dreborg S. Food allergy in pollen-sensitive patients. Ann Allergy. 1988; 61 41-46
57 Dreborg S, Backman A, Basomba A. Skin tests used in type I allergy testing. Position paper of the European Academy of Allergy and Clinical Immunology. Allergy. 1989; 44 1
58 Mantoux C. Intradermoréaction de la tuberculose. Cr Acad Sci. 1908; 147 355
59 Chipps B E, Talamo R C, Mellits E D, Valentine M D. Immediate (IgE-mediated) skin testing in the diagnosis of allergic disease. Ann Allergy. 1978; 41 211-215
60 Voorhorst R. Perfection of skin testing technique. A review. Allergy. 1980; 35 247-250
61 Aas K, Belin L. Suggestions for biologic qualitative testing and standardization of allergen extracts. Acta Allergol. 1974; 29 238
62 Skassa-Brociek W, Manderscheid J C, Michel F B, Bousquet J. Skin test reactivity to histamine from infancy to old age. J Allergy Clin Immunol. 1987; 80 711-716
63 Bernstein I L. Proceeding of the task force of guidelines for standardizing old and new technologies used for the diagnosis and treatment of allergic diseases. J Allergy Clin Immunol. 1988; 82 487
64 Bousquet J. In vivo methods for study of allergy: skin tests. In: Middleton EJ, Reed CE, Ellis EF (eds) Allergy, Principles and Practice. St. Louis; Mosby-Year-Book 1988
65 Lindblad J H, Farr R S. The incidence of positive intradermal reactions and the demonstration of skin sensitizing antibody to extracts of ragweed and dust in humans without history of rhinitis or asthma. J Allergy. 1961; 32 392-401
66 Hagy G W, Settipane G A. Risk factors for developing asthma and allergic rhinitis. A 7-year follow-up study of college students. J Allergy Clin Immunol. 1976; 58 330-336
67 Holgate A T, Church M K. Allergy. London, New York; Gower Medical Publishing 1993
68 Leynadier F, Sansarricq M, Didier J M, Dry J. Prick tests in the diagnosis of anaphylaxis to general anaesthetics. Br J Anaesth. 1987; 59 683-689
69 . Workshop on experimental methodology for clinical studies of adverse reactions to foods and food additives. J Allergy Clin Immunol. 1990; 86 421-442
70 Sutton B J, Gould H J. The human IgE network. Nature. 1993; 366 421-428
71 Kulig M, Tacke U, Forster J, Edenharter G, Bergmann R, Lau S, Wahn V, Zepp F, Wahn U. Serum IgE levels during the first 6 years of life. J Pediatr. 1999; 134 453-458
72 Holford-Strevens V, Warren P, Wong C, Manfreda J. Serum total immunoglobulin E levels in Canadian adults. J Allergy Clin Immunol. 1984; 73 516-522
73 Sitzmann F. Normalwerte. München; Hans Marseille Verlag 1986
74 Mensing H. Zur Differenzialdiagnose der Dermatitis atopica. Allergologie. 1994; 17 477-480
75 Rothenberg M E. Eosinophilia. N Engl J Med. 1998; 338 1592-1600
76 Burney P, Malmberg E, Chinn S, Jarvis D, Luczynska C, Lai E. The distribution of total and specific serum IgE in the European Community Respiratory Health Survey. J Allergy Clin Immunol. 1997; 99 314-322
77 Bergmann R L, Edenharter G, Bergmann K E, Guggenmoos-Holzmann I, Forster J, Bauer C P, Wahn V, Zepp F, Wahn U. Predictability of early atopy by cord blood-IgE and parental history. Clin Exp Allergy. 1997; 27 752-760
78 Wahn V. Differenzialdiagnose kindlicher Immundefekte. Prädiat Prax. 1998; 55 79-100
79 Boccagni P, Favari F, Zanoni G, Pezzini A, Tridente G. Comparison of four in vitro assays for specific IgE detection. Int J Clin Lab Res. 1994; 24 102-105
80 Bjorksten B. Immunological outcome measures. Eur Respir J Suppl. 1996; 21 22s-27s
81 Boluda L, Fernandez-Caldas E, Berrens L. The role of IgG in type-I allergy: an unsolved problem. J Investig Allergol Clin Immunol. 1997; 7 205-210
82 Galli S J. Mast cells and basophils. Curr Opin Hematol. 2000; 7 32-39
83 Hammar E, Berglund A, Hedin A, Norrman A, Rustas K, Ytterstrom U, Akerblom E. An immunoassay for histamine based on monoclonal antibodies. J Immunol Methods. 1990; 128 51-58
84 Brockow K, Vieluf D, Puschel K, Grosch J, Ring J. Increased postmortem serum mast cell tryptase in a fatal anaphylactoid reaction to nonionic radiocontrast medium. J Allergy Clin Immunol. 1999; 104 237-238
85 Biedermann T, Rueff F, Sander C A, Przybilla B. Mastocytosis associated with severe wasp sting anaphylaxis detected by elevated serum mast cell tryptase levels. Br J Dermatol. 1999; 141 1110-1112
86 Schwartz L B, Yunginger J W, Miller J, Bokhari R, Dull D. Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest. 1989; 83 1551-1555
87 Beyer K, Niggemann B, Schulze S, Wahn U. Serum tryptase and urinary 1-methylhistamine as parameters for monitoring oral food challenges in children. Int Arch Allergy Immunol. 1994; 104 348-351
88 Venge P, Bystrom J, Carlson M, Hakansson L, Karawacjzyk M, Peterson C, Seveus L, Trulson A. Eosinophil cationic protein (ECP): molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease. Clin Exp Allergy. 1999; 29 1172-1186
89 Winther L, Moseholm L, Reimert C M, Stahl S P, Kaergaard P L. Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis. Allergy. 1999; 54 436-445
90 Czech W, Krutmann J, Schopf E, Kapp A. Serum eosinophil cationic protein (ECP) is a sensitive measure for disease activity in atopic dermatitis. Br J Dermatol. 1992; 126 351-355
91 MacGlashan Jr D W. Releasability of human basophils: cellular sensitivity and maximal histamine release are independent variables. J Allergy Clin Immunol. 1993; 91 605-615
92 Kleine-Tebbe J. Basophil histamine release by freshly prepared food extracts. Allergy Proc. 1993; 14 255-258
93 de Weck A L. Zellulärer Allergen-Stimulierungs-Test (CAST). Allergologie. 1997; 20 487-502
94 MacGlashan Jr D W, Peters S P, Warner J, Lichtenstein L M. Characteristics of human basophil sulfidopeptide leukotriene release: releasability defined as the ability of the basophil to respond to dimeric cross-links. J Immunol. 1986; 136 2231-2239
95 Kepley C L, Youssef L, Andrews R P, Wilson B S, Oliver J M. Multiple defects in Fc epsilon RI signaling in Syk-deficient nonreleaser basophils and IL-3-induced recovery of Syk expression and secretion. J Immunol. 2000; 165 5913-5920
96 Wedi B. In vitro diagnostic of pseudoallergic reactions - new aspects. ACI Int. 1996; 8 113-115
97 Cahen Y D, Maly F E, Wuthrich B. Cellular antigen stimulation test (CAST) - applicability in the diagnosis of insect toxin allergies. Schweiz Med Wochenschr. 1997; 127 5-11
98 Lebel B, Messaad D, Kvedariene V, Rongier M, Bousquet J, Demoly P. Cysteinyl-leukotriene release test (CAST) in the diagnosis of immediate drug reactions. Allergy. 2001; 56 688-692
99 Knol E F, Mul F P, Jansen H, Calafat J, Roos D. Monitoring human basophil activation via CD63 monoclonal antibody 435. J Allergy Clin Immunol. 1991; 88 328-338
100 Saporta M, Kamei S, Persi L, Bousquet J, Arnoux B. Basophil activation during pollen season in patients monosensitized to grass pollens. Allergy. 2001; 56 442-445
101 Sainte-Laudy J, Sabbah A, Drouet M, Lauret M G, Loiry M. Diagnosis of venom allergy by flow cytometry. Correlation with clinical history, skin tests, specific IgE, histamine and leukotriene C4 release. Clin Exp Allergy. 2000; 30 1166-1171
102 Moneret-Vautrin D A, Sainte-Laudy J, Kanny G, Fremont S. Human basophil activation measured by CD63 expression and LTC4 release in IgE-mediated food allergy. Ann Allergy Asthma Immunol. 1999; 82 33-40
103 Berg P A, Daniel P T, Brattig N. Immunologie und Nachweis medikamentöser Allergien. In: Fuchs E, Schulz KH (eds) Manuale Allergologicum IV. Deisenhofen; Dustri Verlag Dr. Karl Feistle 1996: 1-13
104 Hertl M, Merk H F. Lymphocyte activation in cutaneous drug reactions. J Invest Dermatol. 1995; 105 95S-98S
105 Koponen M, Pichler W J, de Weck A L. T cell reactivity to penicillin: phenotypic analysis of in vitro activated cell subsets. J Allergy Clin Immunol. 1986; 78 645-652
106 Pichler W J. Der Lymphozytentransformationstest in der Diagnostik von unerwünschten Arzneimittelreaktionen. In: Merk HF (ed) Allergische und pseudoallergische Arzneimittelreaktionen. 1993: 119-130
107 Stejskal V D, Olin R G, Forsbeck M. The lymphocyte transformation test for diagnosis of drug-induced occupational allergy. J Allergy Clin Immunol. 1986; 77 411-426
108 Mauri-Hellweg D, Bettens F, Mauri D, Brander C, Hunziker T, Pichler W J. Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine. J Immunol. 1995; 155 462-472
109 May A, Weber A, Gall H, Kaufmann R, Zollner T M. Means of increasing sensitivity of an in vitro diagnostic test for aspirin intolerance. Clin Exp Allergy. 1999; 29 1402-1411
110 Nyfeler B, Pichler W J. The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity. Clin Exp Allergy. 1997; 27 175-181
111 Kondo N, Agata H, Fukutomi O, Motoyoshi F, Orii T. Lymphocyte responses to food antigens in patients with atopic dermatitis who are sensitive to foods. J Allergy Clin Immunol. 1990; 86 253-260
112 Werfel T, Ahlers G, Schmidt P, Boeker M, Kapp A. Detection of a kappa-casein-specific lymphocyte response in milk-responsive atopic dermatitis. Clin Exp Allergy. 1996; 26 1380-1386
113 Werfel T, Ahlers G, Schmidt P, Boeker M, Kapp A, Neumann C. Milk-responsive atopic dermatitis is associated with a casein-specific lymphocyte response in adolescent and adult patients. J Allergy Clin Immunol. 1997; 99 124-133
114 Wistokat-Wulfing A, Schmidt P, Darsow U, Ring J, Kapp A, Werfel T. Atopy patch test reactions are associated with T lymphocyte-mediated allergen-specific immune responses in atopic dermatitis. Clin Exp Allergy. 1999; 29 513-521
115 Karplus T E, Ulevitch R J, Wilson C B. A new method for reduction of endotoxin contamination from protein solutions. J Immunol Methods. 1987; 105 211-220
116 Rasanen L, Sainio H, Lehto M, Reunala T. Lymphocyte proliferation test as a diagnostic aid in chromium contact sensitivity. Contact Dermatitis. 1991; 25 25-29
117 Rasanen L, Tuomi M L. Diagnostic value of the lymphocyte proliferation test in nickel contact allergy and provocation in occupational coin dermatitis. Contact Dermatitis. 1992; 27 250-254
118 Werfel T, Hentschel M, Kapp A, Renz H. Dichotomy of blood- and skin-derived IL-4-producing allergen-specific T cells and restricted V beta repertoire in nickel-mediated contact dermatitis. J Immunol. 1997; 158 2500-2505
119 Schreiber J, Zissel G, Greinert U, Galle J, Schulz K H, Schlaak M, Muller-Quernheim J. Diagnosis of chronic berylliosis. Pneumologie. 1999; 53 193-198
120 Cederbrant K, Hultman P, Marcusson J A, Tibbling L. In vitro lymphocyte proliferation as compared to patch test using gold, palladium and nickel. Int Arch Allergy Immunol. 1997; 112 212-217
121 Merk H F. In-vitro-Diagnostik bei Arzneimittel-Allergien. Allergologie. 1988; 11 57-59
122 Roujeau J C, Albengres E, Moritz S, Piacentino A, Cuny M, Revuz J, Touraine R. Lymphocyte transformation test in drug-induced toxic epidermal necrolysis. Int Arch Allergy Appl Immunol. 1985; 78 22-24
123 Merk H F. Arzneimittelallergie: Einfluss des Fremdstoff-Metabolismus. Allergologie. 1989; 12 171-173
124 Bodycote J, Wolff S. Metabolic breakdown of [3H]thymidine and the inability to measure human lymphocyte proliferation by incorporation of radioactivity. Proc Natl Acad Sci U S A. 1986; 83 4749-4753
125 Wells A D, Gudmundsdottir H, Turka L A. Following the fate of individual T cells throughout activation and clonal expansion. Signals from T cell receptor and CD28 differentially regulate the induction and duration of a proliferative response. J Clin Invest. 1997; 100 3173-3183
126 Boeker M, Werfel T. In vitro Untersuchungen von Antigen- und Allergen-spezifisch aktivierten mononukleären Zellen. Allergologie. 1994; 17 374-379
127 Werfel T, Boeker M, Kapp A. Rapid expression of the CD69 antigen on T cells and natural killer cells upon antigenic stimulation of peripheral blood mononuclear cell suspensions. Allergy. 1997; 52 465-469
128 Abernathy-Carver K J, Sampson H A, Picker L J, Leung D Y. Milk-induced eczema is associated with the expansion of T cells expressing cutaneous lymphocyte antigen. J Clin Invest. 1995; 95 913-918
129 Reekers R, Busche M, Wittmann M, Kapp A, Werfel T. Birch pollen-related foods trigger atopic dermatitis in patients with specific cutaneous T-cell responses to birch pollen antigens. J Allergy Clin Immunol. 1999; 104 466-472
130 Eigenmann P A, Tropia L, Hauser C. The mucosal adhesion receptor alpha4beta7 integrin is selectively increased in lymphocytes stimulated with beta-lactoglobulin in children allergic to cow’s milk. J Allergy Clin Immunol. 1999; 103 931-936
131 Klimek L, Malling H J. Die spezifische Immuntherapie (Hyposensibilisierung) bei allergischer Rhinokonjunktivitis. Metaanalyse zu Wirksamkeit und Nebenwirkungen. HNO. 1999; 47 602-610
132 Klimek L. Die allergenspezifische Immuntherapie (Hyposensibilisierung) Teil 1: Grundlagen und subkutane Applikation. HNO. 2000; 48 116-122
133 Fuchs T, Klimek L. Die allergenspezifische Immuntherapie (Hyposensibilisierung) Teil 2. HNO. 2000; 48 158-164
134 Greiner W, Graf von der Schulenberg J M, Gillissen A. Kosten und Nutzen der Hyposensibilisierung bei allergischem Asthma und Rhinitis. Gesundh ökon Qual manag. 2002; 7 179-186
135 Schadlich P K, Brecht J G. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics. 2000; 17 37-52
136 Moller C, Dreborg S, Ferdousi H A, Halken S, Host A, Jacobsen L, Koivikko A, Koller D Y, Niggemann B, Norberg L A, Urbanek R, Valovirta E, Wahn U. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. 2002; 109 251-256
137 Jacobsen L, Niggemann B, Dreborg S, Ferdousi H A, Halken S, Host A, Koivikko A, Norberg L A, Valovirta E, Wahn U, Moller C. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy. 2007; 62 943-948
138 Des R A, Paradis L, Menardo J L, Bouges S, Daures J P, Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol. 1997; 99 450-453
139 Purello-D’Ambrosio F, Gangemi S, Merendino R A, Isola S, Puccinelli P, Parmiani S, Ricciardi L. Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study. Clin Exp Allergy. 2001; 31 1295-1302
140 Coombs R R, Gell P GH. The classification of allergic reactions underlying disease. Clinical Aspects of Immunology. 1963; 317
141 Klimek L. Labordiagnostik allergischer Erkrankungen. CME Praktische Fortbildung Hals-Nasen-Ohrenheilkunde . 2007; 1

Prof. Dr. med. Ludger Klimek

Zentrum für Rhinologie und Allergologie

An den Quellen 10
65183 Wiesbaden

Email: Ludger.Klimek@HNO-Wiesbaden.de