Allergen-Specific Immunotherapy in Food Anaphylaxis
© World Allergy Organization; licensee BioMed Central Ltd. 2012
Received: 5 October 2007
Accepted: 18 December 2007
Published: 15 March 2008
Specific immunotherapy (SIT) protocols for nutritional allergens have only recently been established with a focus on oral allergy syndrome because of pollen cross-reacting antibodies. For these patients, a substantial number of studies have been published suggesting benefits from SIT. The situation in true anaphylaxis to food allergens such as peanut allergy is more complex, and therapeutic strategies are based on individual protocols rather than controlled studies. However, in defined cases, SIT represents a promising approach for a durable protection from life-threatening risks after accidental ingestion.
Keywordsallergen-specific immunotherapy food allergy long-term effect
Anaphylaxis to food is recognized as a common worldwide problem, and its incidence seems to increase. In the past years, investigations of allergic food proteins and immunologic responses have provided new knowledge on strategies to prevent food-induced anaphylaxis, one of them being the allergen-specific immunotherapy (ASIT) . In contrast to the prevalent "gold standard," the avoidance of the responsible food, or the application of pharmacological regimens, which target only the symptoms without affecting the allergic pathogenesis, it represents the only curative and specific approach for type I allergy [2, 3].
Mechanisms of ASIT
The mechanisms by which the desensitizing effect is achieved includes mainly the modulation of T cells and B cells, especially by the generation of allergen-specific T-regulatory cells leading to suppressed T-cell proliferation and an enhanced Th1/Th0 cytokine response against the allergen. Specific immunotherapy leads to an effective reduction of the threshold for mast cell and basophil activation and to a significant in-crease in allergen-specific immunoglobulin G4 (IgG4), IgG1, and IgA, and a decrease in IgE in the late stage of the disease . As a result, successful ASIT does not only rise the allergen concentration needed to induce immediate- or late-phase reaction in the target tissue, but also diminishes the response to nonspecific mucosal stimulation .
Problems of ASIT in food anaphylaxis
Although ASIT is a widely used immunomodulatory treatment of different allergic diseases, for example, seasonal allergic rhinitis, asthma, or insect venom hypersensitivity, there are several problems concerning ASIT in food anaphylaxis. In contrast to the diseases mentioned previously, the clinical relevance is not given without restrictions. The expression of food allergy varies with age, as for example, the sensitization against cow's milk's (CM) protein or egg occurs during the first 2 to 3 years of life, but is most likely to vanish within adolescence . Because of this, the indication for SIT is rather doubtful because avoidance of the responsible food is often manageable.
However, there are situations where avoidance is not that easily possible. Undeclared allergens in processed products represent a major health problem for sensitized persons. Peanut flour and gluten are known as potent food allergens. When evaluated with enzyme-linked immunosorbent assay, the hidden presence of gluten and peanut in Polish products was detected in 4 (11.8%) of 34 processed foods (corn crisps, wafers, cereal bar, and halva) and 5 (13.5%) of 37 foodstuffs (cornflakes, corn crisps, bouillon cube, vegetable soup for infants, curry powder) contained undeclared gluten [7, 8]. Until recently, most food-control authorities were not in the position to monitor hidden allergens and to take legal measures against their presence in foodstuffs . Under this aspect, immunotherapy would be a great benefit for people with severe anaphylaxis after ingestion of the acclaimed products.
In addition to the theoretical difficulties in the indication for ASIT therapy, there are major obstacles when it comes to the correct realization of this treatment. This is mainly the lack of standardized extracts from either native proteins or recombinant allergens. Moreover, there are several essential requirements that have to be guaranteed for the development of safe and efficient ASIT vaccines such as the reproducible clinical benefit, the lack of side effects, easy application, and a good onset-to-clinical success ratio [2, 4, 10].
Prevalent use of ASIT on food allergy
Standardized schemes of ASIT in pollen allergy and pollen-related oral allergy syndrome
The efficacy of ASIT in pollen allergy is already well established . Besides the conventional standards for ASIT with grass and tree pollen extracts like birch, alder, and hazel, a new focus has been reported toward the establishment of ASIT to olive pollen. In the Mediterranean countries and some areas of North America, allergy to Olea europaea pollen is a major health problem . The prevalence of pollinosis depends on the cultivation intensity and on the percentage of sensitization to olive pollen in individuals with allergic rhinitis varying from 15.2% in the Montpellier area  to greater than 80% found in the southern Spanish province Jaén [15, 16]. In addition, severe anaphylactic reactions to pollen products such as honey and jelly have been described recently [17–19]. Besides, as the IgE-binding pattern of olive pollen is complex and diverse, some olive allergens like Ole e 9 and Ole e10 also exhibit IgE cross-reactivity with proteins from latex and vegetable foods, such as tomato, kiwi, potato, and peach [20, 21]. Patients with allergies to these materials would benefit from ASIT against olive pollen, which is already the current standard of treatment to induce hyporesponsiveness by applying injections of increasing amounts of allergen extracts [22, 23]. Although the use of ASIT with standardized olive pollen extracts is considered to be an effective method to reduce symptoms of a type-I allergic reaction, there is still the risk of adverse reactions because of the high diversity of the allergenic components of olive pollen. Among them, 10 different allergens have been characterized by now, and it seems to be an important deficiency in the current standardization methods, that the amount and affinity of individual IgE antibodies directed against a particular allergen, either major or minor, are not adequately taken into account. A solution to increase the safety of allergen vaccines could be the reduction of minor allergen content, and for prevention of allergic reactions, a prophylactic intranasal treatment with recombinant allergen fragments might be a promising attempt . However, further studies will be required to assess new strategies and to fully determine the underlying mechanisms.
Pollen-related oral allergy syndrome
Specific immunotherapy is not only an established method used in pollen-induced allergies, but also in pollen-related allergic reactions to nonpollen products. Up to 70% of individuals with pollen allergy perceive symptoms like immediate itching in mouth and throat or mild-to-moderate angioedema after ingestion of fresh fruits of the Rosaceae family, nuts, or vegetables, also referred to as the oral allergy syndrome (OAS) [26, 27]. This phenomenon is caused by cross-reactive IgE antibodies that recognize homologous allergens in birch pollen and fruits,[28–30] the primary sensitizer being the major birch pollen allergen Bet v 1. Its fruit homologues are more liable and sensitive to processing in the stomach and therefore lack sensitization directly. Selective recognition of epitopes on fruit or vegetable homologues of Bet v 1 are found to be extremely rare, so that the spectrum of IgE specificities is broadest against the pollen allergen. Taking these aspects into account, several studies have investigated the effect of ASITwith tree pollen on OAS. It has been a long-standing debate whether immunotherapy for inhalant allergies indeed has a beneficial effect on associated food allergies, but despite some studies with limited effect/negative results,[32, 33] a positive impact has been demonstrated in most cases, with improvement of the OAS from 50% up to a complete loss of symptoms in subjects with monosensitized birch pollen allergy confronted by an open apple challenge . Reasons for the different outcomes might be the high dose dependence of the effect of ASIT and a strong difference in the concentration of the major allergen Bet v 1 in the commercial extracts or the existence of other less well-defined cross-reactive allergens, which are not present or sufficiently enough in the birch pollen extracts . According to these findings, further studies will be required to determine whether the most effective treatment of OAS can be achieved using ASIT with corecognized inhalant allergens or through cotreatment with purified pollen-related food allergens to guarantee a long-lasting effect .
Individual schemes of SIT
In contrast to the standardized schemes of SIT for pollen-induced and pollen-related allergies mentioned previously, in certain food allergies, individually adapted schemes have to be applied. Especially in protein allergy, like CM allergy in young children with atopic eczema, the variable response of each patient to the different allergen components may influence the potential clinical outcome. Therefore, the mode of application of ASIT is a very delicate matter and not seldom has to be interrupted and discontinued because of the occurrence of uncontrolled side effects that might indicate possible differences in the mechanism, which are known for classical immunotherapy with airway allergies. With respect to the fact that prolonged elimination diets are not without risks, such as deficiency and growth retardation, eating disorders, impaired psychosocial development,[38, 39] or even severe anaphylactic reactions, SIT has become a successfully used alternative, the major aim of which is not to alter the cause of food allergy, but to induce a tolerance toward the incriminated food and to increase the threshold dose to elicit allergic symptoms in case of continuous exposure. One current scheme for CM desensitization is to administer increasing amounts of CM starting from 1 drop of whole CM diluted 1:25 with water corresponding to approximately 0.06 mg of CM protein. Afterward, the doses are doubled first every 7 days until day 70, then subsequently every 16 days, until a daily intake of 200 mL is achieved (normally in about 6 months) . Besides, there are many different proposals how to receive successful results,[42, 43] their optimal adaptation for each individual patient probably being the best way to guarantee an effective clinical outcome. However, these schemes of daily application differ from the classical way of ASIT. To allow exposure to a gradually escalating dose of a specific allergen to decrease allergic and inflammatory responses, a buildup phase with once weekly applications is followed by a maintenance phase with monthly repetitions that has to be continued for several, normally 3 to 5, years . Daily application requires far more compliance of the patient and thus might bear a higher risk of adverse reactions if interrupted for some days. To most, applying these schemes is a very time-consuming procedure and demands discipline and experience. Despite previous tolerance, on reexposure to the allergen, moderate systemic reactions might easily occur if a certain maintenance dose is not guaranteed . Oral tolerance induction by ASIT in CM allergy is therefore not to be regarded without limitations and has to be discussed individually for each patient.
The current information on custom-made protocols for ASIT in severe food anaphylaxis is rather scarce. In cases in which avoidance is not possible, ASIT should, however, be considered. Most of the data come from approaches in severe peanut allergy, which is associated to life-threatening symptoms to a high degree. Although ASIT in peanut allergy has been considered extremely difficult, there are several reports encouraging this strategy [46–48]. We have undertaken an individualized ASIT approach to an adult patient with severe kiwi anaphylaxis who was effectively desensitized by a sublingual extract from fresh kiwi pulp. Although the whole procedure is extremely time consuming as one might have to start with a concentration of one tenth of the lowest positive concentration in skin prick test, recent findings could demonstrate the efficacy and long-lasting protective effect of the applied ASIT . This effect was also paralleled by a sub-stantial induction of kiwi-specific IgG4 .
In the future, the use of specific IgE antibodies such as omalizumab could be an interesting point of research to reduce the occurrence of adverse systemic reactions in immunotherapy. Some recently published studies outline the positive effects of the monoclonal anti-IgE antibody as a pretreatment in peanut allergy, rush immunotherapy for ragweed-induced seasonal allergic rhinitis, or in injection immunotherapy with a moderate dose of house dust mite extract in house dust-sensitive adults with atopic eczema .
In addition, new genetically engineered major allergens from food sources will enable better standardized and hopefully better tolerable protocols.
Taken together, immunotherapy in food anaphylaxis is a possible option but not always easily applicable because of the risk of side effects. Several standard schemes exist for pollen-induced and pollen-related food allergy, but still for some products, such as CM or peanut, individual procedures have to be applied to guarantee a successful tolerance induction. Even if only a few studies allow assumption of a generally long-lasting protective effect of ASIT by now, the results provided up to now are quite encouraging . To guarantee a safer and more convenient use of ASIT in the future, more studies will be necessary.
- Mansueto P, Montalto G, Pacor ML, Esposito-Pellitteri M, Ditta V, Lo Bianco C, et al: Food allergy in gastroenterologic diseases: review of literature. World J Gastroenterol. 2006, 12: 7744-7752.View ArticlePubMedPubMed CentralGoogle Scholar
- Bousquet J, Lockey R, Malling HJ: Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998, 102: 558-562. 10.1016/S0091-6749(98)70271-4.View ArticlePubMedGoogle Scholar
- Tsitoura DC, Tassios Y: Immunomodulation: the future cure for allergic diseases. Ann N Y Acad Sci. 2006, 1088: 100-115. 10.1196/annals.1366.026.View ArticlePubMedGoogle Scholar
- Akdis M, Akdis CA: Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol. 2007, 119: 780-791. 10.1016/j.jaci.2007.01.022.View ArticlePubMedGoogle Scholar
- Rak S, Lowhagen O, Venge P: The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen-allergic patients. J Allergy Clin Immunol. 1988, 82: 470-480. 10.1016/0091-6749(88)90021-8.View ArticlePubMedGoogle Scholar
- Halken S: Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy prevention. Pediatr Allergy Immunol. 2004, 15 (suppl 16): 4-5. [9-32]PubMedGoogle Scholar
- Borelli S, Anliker MD, Wuthrich B: Peanut anaphylaxis: the problem of hidden allergens. Dtsch Med Wochenschr. 1999, 124: 1197-1200. 10.1055/s-2007-1024513.View ArticlePubMedGoogle Scholar
- Hozyasz K, Gajewska J, Ambroszkiewicz J: Hidden food allergens: peanut and glutenVin Polish foodstuffs. Pol Merkur Lekarski. 2004, 17: 374-377.PubMedGoogle Scholar
- Schappi GF, Konrad V, Imhof D, Etter R, Wüthrich B: Hidden peanut allergens detected in various foods: findings and legal measures. Allergy. 2001, 56: 1216-1220. 10.1034/j.1398-9995.2001.00280.x.View ArticlePubMedGoogle Scholar
- Moingeon P: Sublingual immunotherapy: from biological extracts to recombinant allergens. Allergy. 2006, 61 (suppl 81): 15-19.View ArticlePubMedGoogle Scholar
- McEldowney SJ, Bush RK: Pollen immunotherapy: selection, prevention, and future directions. Curr Allergy Asthma Rep. 2006, 6: 420-426. 10.1007/s11882-996-0016-5.View ArticlePubMedGoogle Scholar
- Bolhaar ST, Tiemessen MM, Zuidmeer L, van Leeuwen A, Hoffmann-Sommergruber K, Bruijnzeel-Koomen CA, et al: Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind food challenges. Clin Exp Allergy. 2004, 34: 761-769. 10.1111/j.1365-2222.2004.1939.x.View ArticlePubMedGoogle Scholar
- Gonzalez EM, Villalba M, Rodriguez R: Allergenic cross-reactivity of olive pollen. Allergy. 2000, 55: 658-663. 10.1034/j.1398-9995.2000.00406.x.View ArticlePubMedGoogle Scholar
- Bousquet J, Cour P, Guerin B, Michel FB: Allergy in the Mediterranean area. I. Pollen counts and pollinosis of Montpellier. Clin Allergy. 1984, 14: 249-258. 10.1111/j.1365-2222.1984.tb02204.x.View ArticlePubMedGoogle Scholar
- Duffort O, Palomares O, Lombardero M, Villalba M, Barber D, et al: Variability of Ole e 9 allergen in olive pollen extracts: relevance of minor allergens in immunotherapy treatments. Int Arch Allergy Immunol. 2006, 140: 131-138. 10.1159/000092532.View ArticlePubMedGoogle Scholar
- Florido JF, Delgado PG, de San Pedro BS, Quiralte J, de Saavedra JM, Peralta V, et al: High levels of Olea europaea pollen and relation with clinical findings. Int Arch Allergy Immunol. 1999, 119: 133-137. 10.1159/000024188.View ArticlePubMedGoogle Scholar
- Fuiano N, Incorvaia C, Riario-Sforza GG, Casino G: Anaphylaxis to honey in pollinosis to mugwort: a case report. Allerg Immunol (Paris). 2006, 38: 364-365.Google Scholar
- Karakaya G, Fuat Kalyoncu A: Honey allergy in adult allergy practice. Allergol Immunopathol (Madr). 1999, 27: 271-272.Google Scholar
- Lombardi C, Senna GE, Gatti B, Feligioni M, Riva G, Bonadonna P, et al: Allergic reactions to honey and royal jelly and their relationship with sensitization to compositae. Allergol Immunopathol (Madr). 1998, 26: 288-290.Google Scholar
- Barral P, Batanero E, Palomares O, Quiralte J, Villalba M, Rodriguez R: A major allergen from pollen defines a novel family of plant proteins and shows intra- and interspecies [correction of interspecie] cross-reactivity. J Immunol. 2004, 172: 3644-3651.View ArticlePubMedGoogle Scholar
- Palomares O, Villalba M, Quiralte J, Rodriguez R: Allergenic contribution of the IgE-reactive domains of the 1,3-beta-glucanase Ole e 9: diagnostic value in olive pollen allergy. Ann Allergy Asthma Immunol. 2006, 97: 61-65. 10.1016/S1081-1206(10)61371-3.View ArticlePubMedGoogle Scholar
- Gonzalez P, Florido F, Saenz de San Pedro B, de la Torre F, Rico P, Martin S: Immunotherapy with an extract of Olea europaea quantified in mass units. Evaluation of the safety and efficacy after one year of treatment. J Investig Allergol Clin Immunol. 2002, 12: 263-271.PubMedGoogle Scholar
- Guerra F, Daza JC, Almeda E: Immunotherapy with a depigmented, polymerized vaccine of Olea europaea pollen allergens Significantly reduces specific bronchial and skin test reactivity in sensitized patients after one year of treatment. J Investig Allergol Clin Immunol. 2003, 13: 108-117.PubMedGoogle Scholar
- Rodriguez R, Villalba M, Monsalve RI, Batanero E: The spectrum of olive pollen allergens. Int Arch Allergy Immunol. 2001, 125: 185-195. 10.1159/000053815.View ArticlePubMedGoogle Scholar
- Palomares O, Batanero E, Canamero M, Villalba M, Rodriguez R: Prophylactic intranasal treatment with fragments of 1,3-beta-glucanase olive pollen allergen prevents airway inflammation in a murine model of type I allergy. Int Arch Allergy Immunol. 2006, 139: 175-180. 10.1159/000091162.View ArticlePubMedGoogle Scholar
- Ortolani C, Ispano M, Pastorello E, Bigi A, Ansaloni R: The oral allergy syndrome. Ann Allergy. 1988, 61: 47-52.PubMedGoogle Scholar
- Pastorello EA, Incorvaia C, Ortolani C: Mechanisms in adverse reactions to food. The mouth and pharynx. Allergy. 1995, 50: 40-45.View ArticlePubMedGoogle Scholar
- Ebner C, Hirschwehr R, Bauer L, Breiteneder H, Valenta R, Ebner H, et al: Identification of allergens in fruits and vegetables: IgE cross-reactivities with the important birch pollen allergens Bet v 1 and Bet v 2 (birch profilin). J Allergy Clin Immunol. 1995, 95: 962-969. 10.1016/S0091-6749(95)70096-X.View ArticlePubMedGoogle Scholar
- Inschlag C, Hoffmann-Sommergruber K, O'Riordain G, Ahorn H, Ebner C, Scheiner O, et al: Biochemical characterization of Pru a 2, a 23-kD thaumatin-like protein representing a potential major allergen in cherry (Prunus avium). Int Arch Allergy Immunol. 1998, 116: 22-28. 10.1159/000023920.View ArticlePubMedGoogle Scholar
- Vanek-Krebitz M, Hoffmann-Sommergruber K, Laimer da Camara Machado M, Susani M, Ebner C, et al: Cloning and sequencing of Mal d 1, the major allergen from apple (Malus domestica), and its immunological relationship to Bet v 1, the major birch pollen allergen. Biochem Biophys Res Commun. 1995, 214: 538-551. 10.1006/bbrc.1995.2320.View ArticlePubMedGoogle Scholar
- Moneo I, Gomez M, Sanchez-Monge R, Alday E, de las Heras M, et al: Lack of crossreaction with Bet v 1 in patients sensitized to Dau c 1, a carrot allergen. Ann Allergy Asthma Immunol. 1999, 83: 71-75. 10.1016/S1081-1206(10)63516-8.View ArticlePubMedGoogle Scholar
- Hansen KS, Khinchi MS, Skov PS, Bindslev-Jensen C, Poulsen LK, Malling HJ: Food allergy to apple and specific immunotherapy with birch pollen. Mol Nutr Food Res. 2004, 48: 441-448. 10.1002/mnfr.200400037.View ArticlePubMedGoogle Scholar
- Kinaciyan T, Jahn-Schmid B, Radakovics A, Zwolfer B, Schreiber C, et al: Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. J Allergy Clin Immunol. 2007, 119: 937-943. 10.1016/j.jaci.2006.11.010.View ArticlePubMedGoogle Scholar
- Asero R: Effects of birch pollen-specific immunotherapy on apple allergy in birch pollenYhypersensitive patients. Clin Exp Allergy. 1998, 28: 1368-1373. 10.1046/j.1365-2222.1998.00399.x.View ArticlePubMedGoogle Scholar
- Bucher X, Pichler WJ, Dahinden CA, Helbling A: Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut. Allergy. 2004, 59: 1272-1276. 10.1111/j.1398-9995.2004.00626.x.View ArticlePubMedGoogle Scholar
- Mari A, Ballmer-Weber BK, Vieths S: The oral allergy syndrome: improved diagnostic and treatment methods. Curr Opin Allergy Clin Immunol. 2005, 5: 267-273. 10.1097/01.all.0000168793.27948.b0.View ArticlePubMedGoogle Scholar
- Christie L, Hine RJ, Parker JG, Burks W: Food allergies in children affect nutrient intake and growth. J Am Diet Assoc. 2002, 102: 1648-1651. 10.1016/S0002-8223(02)90351-2.View ArticlePubMedGoogle Scholar
- Sampson HA: Food allergy. Part 2: diagnosis and management. J Allergy Clin Immunol. 1999, 103: 981-989. 10.1016/S0091-6749(99)70167-3.View ArticlePubMedGoogle Scholar
- Sicherer SH: The impact of maternal diets during breastfeeding on the prevention of food allergy. Curr Opin Allergy Clin Immunol. 2002, 2: 207-210. 10.1097/00130832-200206000-00009.View ArticlePubMedGoogle Scholar
- Flinterman AE, Knulst AC, Meijer Y, Bruijnzeel-Koomen CA, Pasmans SG: Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets. Allergy. 2006, 61: 370-374. 10.1111/j.1398-9995.2006.01018.x.View ArticlePubMedGoogle Scholar
- Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG: A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy. 2004, 59: 980-987. 10.1111/j.1398-9995.2004.00542.x.View ArticlePubMedGoogle Scholar
- Bauer A, Ekanayake Mudiyanselage S, Wigger-Alberti W, Elsner P: Oral rush desensitization to milk. Allergy. 1999, 54: 894-895. 10.1034/j.1398-9995.1999.00228.x.View ArticlePubMedGoogle Scholar
- Patriarca G, Schiavino D, Nucera E, Schinco G, Milani A, Gasbarrini GB: Food allergy in children: results of a standardized protocol for oral desensitization. Hepatogastroenterology. 1998, 45: 52-58.PubMedGoogle Scholar
- Rank MA, Li JT: Allergen immunotherapy. Mayo Clin Proc. 2007, 82: 1119-1123. 10.4065/82.9.1119.View ArticlePubMedGoogle Scholar
- Rolinck-Werninghaus C, Staden U, Mehl A, Hamelmann E, Beyer K, Niggemann B: Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?. Allergy. 2005, 60: 1320-1322. 10.1111/j.1398-9995.2005.00882.x.View ArticlePubMedGoogle Scholar
- Mansfield L: Successful oral desensitization for systemic peanut allergy. Ann Allergy Asthma Immunol. 2006, 97: 266-267. 10.1016/S1081-1206(10)60026-9.View ArticlePubMedGoogle Scholar
- Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY: Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol. 1992, 90: 256-262. 10.1016/0091-6749(92)90080-L.View ArticlePubMedGoogle Scholar
- Patriarca G, Nucera E, Pollastrini E, De Pasquale T, Lombardo C, et al: Oral rush desensitization in peanut allergy: a case report. Dig Dis Sci. 2006, 51: 471-473. 10.1007/s10620-006-3157-4.View ArticlePubMedGoogle Scholar
- Mempel M, Rakoski J, Ring J, Ollert M: Severe anaphylaxis to kiwi fruit: immunologic changes related to successful sublingual allergen immunotherapy. J Allergy Clin Immunol. 2003, 111: 1406-1409. 10.1067/mai.2003.1497.View ArticlePubMedGoogle Scholar
- Kerzl R, Simonowa A, Ring J, Ollert M, Mempel M: Life-threatening anaphylaxis to kiwi fruit: protective sublingual allergen immunotherapy effect persists even after discontinuation. J Allergy Clin Immunol. 2007, 119: 507-508. 10.1016/j.jaci.2006.09.041.View ArticlePubMedGoogle Scholar
- Leung DY, Sampson HA, Yunginger JW, Burks AW, Schneider LC, et al: Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med. 2003, 348: 986-993. 10.1056/NEJMoa022613.View ArticlePubMedGoogle Scholar
- Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, et al: Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006, 117: 134-140. 10.1016/j.jaci.2005.09.036.View ArticlePubMedGoogle Scholar
- Nelson HS: Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol. 2003, 111 (suppl): S793-S797.View ArticlePubMedGoogle Scholar
- Passalacqua G, Canonica GW: Long-lasting clinical efficacy of allergen specific immunotherapy. Allergy. 2002, 57: 275-276. 10.1034/j.1398-9995.2002.03264.x.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.