Title: Sublingual immunotherapy: The optimism and the issues
Abstract: The acceptability of sublingual immunotherapy (SLIT) in guidelines or statements has recently increased. SLIT is currently used in Europe, Asia, and Australia for the treatment of allergic respiratory diseases. Four meta-analyses have shown that SLIT is an effective tool for the treatment of patients with asthma and/or rhinitis, and only conflicting results were reported for children with allergic rhinitis. Moreover, it offers logistic advantages and is safe. However, some unmet needs are to be faced, such as the difficulty of manufacturers to achieve the homogeneity of standardized vaccines, the magnitude of their clinical efficacy, and the pivotal question of an early intervention with SLIT in young children with IgE-mediated disorders. Altogether, SLIT has already given convincing results in respiratory diseases both in adults and children. In the future, this route of administration of allergic vaccines may improve even the treatment of patients with IgE-mediated food allergy. These patients indeed deserve better than allergen avoidance. The immunomodulatory treatment of allergic diseases probably has found a new tool; however, a more balanced understanding of this form of allergen immunotherapy is needed. This aim could be achieved through: (1) the improvement of products standardization quality; (2) an attempt to modify in children the natural course of allergic diseases; and (3) new research on mechanisms of action. The acceptability of sublingual immunotherapy (SLIT) in guidelines or statements has recently increased. SLIT is currently used in Europe, Asia, and Australia for the treatment of allergic respiratory diseases. Four meta-analyses have shown that SLIT is an effective tool for the treatment of patients with asthma and/or rhinitis, and only conflicting results were reported for children with allergic rhinitis. Moreover, it offers logistic advantages and is safe. However, some unmet needs are to be faced, such as the difficulty of manufacturers to achieve the homogeneity of standardized vaccines, the magnitude of their clinical efficacy, and the pivotal question of an early intervention with SLIT in young children with IgE-mediated disorders. Altogether, SLIT has already given convincing results in respiratory diseases both in adults and children. In the future, this route of administration of allergic vaccines may improve even the treatment of patients with IgE-mediated food allergy. These patients indeed deserve better than allergen avoidance. The immunomodulatory treatment of allergic diseases probably has found a new tool; however, a more balanced understanding of this form of allergen immunotherapy is needed. This aim could be achieved through: (1) the improvement of products standardization quality; (2) an attempt to modify in children the natural course of allergic diseases; and (3) new research on mechanisms of action. Allergen immunotherapy is a subject widely debated by allergists. For many decades, the discussion on allergen immunotherapy had focused on subcutaneous route of administration of the vaccines (subcutaneous immunotherapy [SCIT]); currently, “pro” and “con” sessions are focused on the sublingual route (sublingual immunotherapy [SLIT]).SLIT has been used thus far in Europe, Asia, and Australia for the treatment of allergic respiratory diseases1Potter P.C. Update on sublingual immunotherapy.Ann Allergy Asthma Immunol. 2006; 96: S22-S25Abstract Full Text PDF PubMed Scopus (28) Google Scholar and is now considered an efficacious and safe alternative to SCIT, whereas the use of local nasal immunotherapy (LNIT) is progressively declining.2Canonica G.W. Passalacqua G. Noninjection routes for immunotherapy.J Allergy Clin Immunol. 2003; 111: 437-448Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar, 3Kowalski M.L. Systemic and specific treatment for a global disease: allergen immunotherapy revisited.Allergy. 2006; 61: 791-795Crossref PubMed Scopus (10) Google Scholar Moreover, recent published data have highlighted the effectiveness of SLIT in patients with sensitization to foods4Enrique E. Pineda F. Malek T. Bartra J. Basagana M. Tella R. et al.Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract.J Allergy Clin Immunol. 2005; 116: 1073-1079Abstract Full Text Full Text PDF PubMed Scopus (369) Google Scholar and also in children with a mild form of atopic dermatitis (AD).5Pajno G.B. Vita D. Caminiti L. Arrigo T. Lombardo F. Barberio G. House dust mite sublingual Immunotherapy (SLIT) for atopic dermatitis (AD): a randomized controlled trial.J Allergy Clin Immunol. 2006; 117 ([abstract]): S233Abstract Full Text Full Text PDF PubMed Google ScholarThe historical studies with SCIT were performed in children aged 3 to 14 years,6Johnstone J.E. Dutton A. The value of hyposensitization therapy for bronchial asthma in children—a 14-year study.Pediatrics. 1968; 5: 793-802Google Scholar, 7Aas K. Hyposensitization in house dust allergy asthma. A double-blind controlled study with evaluation of the effect on bronchial sensitivity to house dust.Acta Paediatr Scand. 1971; 60: 264-268Crossref PubMed Scopus (133) Google Scholar and neither serious side effects nor life-threatening events were reported. Nonetheless, a subsequent well-conducted trial reported severe asthma, generalized urticaria, angioedema, and anaphylaxis in treated children less than 5 years of age.8Hejjaoui A. Dhivert H. Michel F.B. Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. IV. Systemic reactions according to the immunotherapy schedule.J Allergy Clin Immunol. 1990; 85: 473-479Abstract Full Text PDF PubMed Scopus (99) Google ScholarSince then, the preschool age is regarded as a prudent limit for immunotherapy in view of the possible risk of severe side effects. Indeed, this age is considered a relative contraindication for SCIT,9Bousquet J. Lockey R. Malling H.J. World Health Organization Position Paper. Allergen immunotherapy: therapeutical vaccines for allergic diseases.Allergy. 1998; 44: 1-43Google Scholar because severe side effects are more difficult to treat in very young children, and injection immunotherapy carries the risk of important untoward reactions.10Ostergaard P.A. Kaad P.H. Kristensen T. A prospective study on the safety of immunotherapy in children with severe asthma.Allergy. 1986; 41: 588-593Crossref PubMed Scopus (44) Google Scholar Recent data, however, have demonstrated that SLIT is safe in young children and offers new possibilities for the treatment of pediatric patients.11Rienzo V.D. Minelli M. Musarra A. Sambugaro R. Pecora S. Canonica W.G. et al.Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years.Clin Exp Allergy. 2005; 35: 560-564Crossref PubMed Scopus (141) Google Scholar, 12Fiocchi A. Pajno G. La Grutta S. Pezzuto F. Incorvaia C. Sensi L. et al.Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years.Ann Allergy Asthma Immunol. 2005; 95: 254-258Abstract Full Text PDF PubMed Scopus (115) Google ScholarAlthough the precise mechanisms underlying the induction of immune tolerance by SLIT remain unclear, the contact of the allergen with antigen-presenting cells (APCs) in oral mucosa is likely to be critical. Therefore, one explanation for the specific mechanisms of action of SLIT may be the profound difference between both oral APCs and oral Langerhans cells (LCs) and their skin counterparts.13Allam J.P. Novak N. Fuchs C. Asen S. Berge S. Appel T. et al.Characterization of dendritic cells from human oral mucosa: a new Langerhans' cell type with high constitutive FcɛRI expression.J Allergy Clin Immunol. 2003; 112: 141-148Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar, 14Hasseus B. Jontell M. Bergenholtz G. Dahlgren U.I. Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.Clin Exp Immunol. 2004; 136: 483-489Crossref PubMed Scopus (23) Google ScholarThe sublingual route has attracted the greatest interest in recent years, as shown by the number of double-blind, placebo-controlled trials and the fact that SLIT has spread widely in Europe15Alvarez-Cuesta E. Bousquet J. Canonica G.W. Durham S.R. Malling H.J. Valovirta E. et al.Standards for practical allergen-specific immunotherapy.Allergy. 2006; 61: 1-20Crossref PubMed Scopus (375) Google Scholar; however, some issues with SLIT still need to be addressed, such as the actual difficulties in determining the optimal doses of the vaccines, the magnitude of their clinical efficacy, the pivotal challenge of early intervention in young allergic children, and the choice of future developments. Another unresolved question concerns the multiallergen mixes by SLIT. So far in the United States, vaccines are often used as multiple allergens; however, in Europe, they are used as single allergens or antigen(s) with multiple component activities.Allergen standardization(s)The quality of the allergen vaccines is critical for both diagnosis and treatment. Where possible, standardized vaccines of known potency and shelf life should be used. The most common vaccines used in clinical allergy practice are now available as standardized products, but this standardization is currently nonhomogeneous.The vaccines administered by the sublingual route are based on the aqueous biological extracts from the natural allergen sources as both drops (in glycerosaline solution) or fast-dissolving tablets. Sublingual vaccines prepared from raw allergic materials, such as grass or tree pollens,16Lowenstein H. Larsen J.N. Recombinant allergens/allergen standardization.Curr Allergy Asthma Rep. 2001; 1: 474-479Crossref PubMed Scopus (15) Google Scholar, 17Moingeon P. Batard T. Fadel R. Frati F. Sieber J. Van Overtvelt L. Immune mechanisms of allergen-specific sublingual immunotherapy.Allergy. 2006; 61: 151-165Crossref PubMed Scopus (266) Google Scholar are previously exposed to both macroscopic and microscopic examination in order to determine electrophoretic profiling and evaluate of bacteriological load and biological activity.Allergens are commonly extracted at 4°C with an ammonium bicarbonate solution, and their protein extract is ultrafiltrated to remove small (<1 kd) molecules. The resulting extract contains all the water-soluble allergens and proteins from the raw material; these include active ingredients (major or minor allergens) as well as nonbioactive components, such as other proteins, glycoproteins, and carbohydrates.18Moingeon P. Sublingual immunotherapy: from biological extracts to recombinant allergens.Allergy. 2006; 61: 15-19Crossref PubMed Scopus (39) Google ScholarIn some instances, allergens are previously modified in order to produce allergoids; chemical modification involves formaldehyde or glutaraldehyde treatment to cross link the proteins. To produce monomeric allergoids appropriate for SLIT, carbamilation of the aminogroups in lysine residues is often used, which maintains native allergen molecular size and confers resistance to gastroenteric enzymes.19Mistrello G. Brenna O. Roncarolo D. Zanoni D. Gentili M. Falagiani P. Monomeric chemically modified allergens: immunologic and physicochemical characterization.Allergy. 1996; 51: 8-15PubMed Google ScholarEach manufacturer has its in-house reference preparation (IHPR) to determine the immunologic activity of an allergen preparation. The IHPR is subsequently used as a reference to adjust allergenic activity of each commercial batch in vitro (Table I).Table IMain standardization references used among the several sublingual vaccines with different allergen units currently produced by manufacturers• IU: International unit• AU: Allergy unit• BAU: Biological allergy unit• BU: Biologic unit• IR: Index of reactivity• TU: Therapeutic unitsMaintenance doses from 0.5 μg up to 210 μg per week can be achieved with SLIT according to the different allergens used. Open table in a new tab The production of whole standardized vaccines is now a realistic goal that should be reached. However, current barriers to achieve whole and common standardization include the use of global IgE binding by radiollergosorbent test (RAST) or enzyme-linked immunosorbent assay (ELISA) using pooled sera from allergic individuals as a measure of total potency.20van Ree R. Dorpema J.W. Vieths S. Allergy vaccines: a need for standardisation in mass units of major allergen.Pharmeuropa Bio. 2005; 2005: 27-30PubMed Google ScholarIgE-binding assays (RASTs) are often unable to detect the differences in individual major quantities or ratios between major allergens for products with multiple components activities, such as grass pollens and at lesser extent house dust mites.21Grier T.J. Hazelhurst D.M. Duncan E.A. West T.K. Esch R.E. Major allergen measurements: sources of variability, validation, quality assurance, and utility for laboratories, manufacturers, and clinics.Allergy Asthma Proc. 2002; 23: 125-131PubMed Google ScholarTo overcome these drawbacks, the European Commission has been funding a large, multidisciplinary project to improve allergen standardization in Europe. The project aims to develop candidate reference materials consisting of purified natural or recombinant major allergens.22van Ree R. The CREATE project: EU support for the improvement of allergen standardization in Europe.Allergy. 2004; 59: 571-574Crossref PubMed Scopus (71) Google Scholar Because each supplier uses its own standardization procedure, it is not possible to compare the amounts of allergens present in the extracts of the different manufacturers. Therefore, it is suitable that actual situation will change in the near future; however, the drawback regarding this issue is the fact that the production of the allergen extract is often part of the allergy companies' intellectual property.The Allergic Rhinitis and its Impact on Asthma document (ARIA) identified that SLIT doses higher than those in SCIT are required to obtain clinical efficacy.23Bousquet J. Van Cauwenberge P. Khaltaev N. Aria Workshop Group World Health Organization. Allergic rhinitis and its impact on asthma.J Allergy Clin Immunol. 2001; 108: S147-S334Abstract Full Text Full Text PDF PubMed Scopus (2156) Google Scholar In clinical trials, antigen doses from 5 up to 375 SLIT/SCIT ratio were used.2Canonica G.W. Passalacqua G. Noninjection routes for immunotherapy.J Allergy Clin Immunol. 2003; 111: 437-448Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar Other studies, on the contrary, have shown that cumulative doses close to those used for SCIT can be successfully used.24Di Rienzo V. Marcucci F. Puccinelli P. Parmiani S. Frati F. Sensi L. et al.Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study.Clin Exp Allergy. 2003; 33: 206-210Crossref PubMed Scopus (346) Google Scholar, 25Novembre E. Galli E. Landi F. Caffarelli C. Pifferi M. De Marco E. et al.Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2004; 114: 851-857Abstract Full Text Full Text PDF PubMed Scopus (440) Google ScholarIn SCIT, the antigen in combination with adjuvants such as calcium phosphate or alum is directly injected into the subcutis underlying the epithelium, where professional APCs as LCs reside.In SLIT, antigen first has to be exposed to the oral mucosa before it can be taken by LCs or other APCs; of note, the oral mucosa shows limited absorption of allergens. One explanation for the claimed dose dependence might be that an insufficient amount of the antigen is available for the presentation by APCs using the sublingual route at low allergen doses.Therefore, high-dose regimens likely facilitate capture of sufficient amounts of allergens by sentinel dendritic cells within the oral mucosa, which represents a critical step to induce an adequate and long-lasting T-cell response.26Martin-Fontecha A. Sebastiani S. Höpken U.E. Uguccioni M. Lipp M. Lanzavecchia A. et al.Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming.J Exp Med. 2003; 198: 615-621Crossref PubMed Scopus (731) Google Scholar, 27Taams L.S. van Eden W. Wauben M.H. Dose-dependent induction of distinct anergic phenotypes: multiple levels of T cell anergy.J Immunol. 1999; 162: 1974-1981PubMed Google ScholarThus, an implement of the standardization(s) of allergen products for the therapy is required by manufacturers in order to avoid large differences among different suppliers.The efficacy and the safetyIn 1993, the European Academy of Allergy and Clinical Immunology position paper on specific immunotherapy proposed that SLIT might be used as a therapy to be investigated in order to prove its efficacy and safety.28Malling H. Weeke B. Position paper of the European Academy of Allergy and Clinical Immunology.Allergy. 1993; 48: 9-35Crossref PubMed Scopus (408) Google Scholar In 1998, the World Health Organization position paper9Bousquet J. Lockey R. Malling H.J. World Health Organization Position Paper. Allergen immunotherapy: therapeutical vaccines for allergic diseases.Allergy. 1998; 44: 1-43Google Scholar found 4 double-blind, placebo-controlled trials on SLIT and proposed that SLIT may be used in adults with allergic rhinitis, whereas there was insufficient evidence to use it in children.In 2001, the ARIA document examined 10 double-blind, placebo-controlled studies and indicated that SLIT has been evaluated in studies carried out on allergic rhinitis induced by certain pollens and mites.23Bousquet J. Van Cauwenberge P. Khaltaev N. Aria Workshop Group World Health Organization. Allergic rhinitis and its impact on asthma.J Allergy Clin Immunol. 2001; 108: S147-S334Abstract Full Text Full Text PDF PubMed Scopus (2156) Google ScholarThe American Academy of Allergy, Asthma & Immunology (AAAAI)- American College of Allergy, Asthma and Immunology (ACAAI) clinical guidelines published in 200329Li J.T. Lockey R.F. Bernstein I.L. Portnoy J.M. Nicklas R.A. Allergen immunotherapy: a practice parameter. American Academy of Allergy, Asthma and Immunology. American College of Allergy, Asthma and Immunology.Ann Allergy Asthma Immunol. 2003; 90: 1-40Abstract Full Text PDF Scopus (172) Google Scholar concluded that SLIT requires further evaluation before it can be recommended in routine clinical practice. The American Societies of Allergy underlined that currently no vaccines for sublingual use were available in United States. However, both the AAAAI and ACAAI formed a joint task force with the purpose of providing a comprehensive and updated report on SLIT for the North American allergy community.30Cox L.S. Linnemann D.L. Nolte H. Weldon D. Finegold I. Nelson H.S. Sublingual immunotherapy: a comprehensive review.J Allergy Clin Immunol. 2006; 117: 1021-1035Abstract Full Text Full Text PDF PubMed Scopus (358) Google ScholarMeanwhile, 4 meta-analyses on the efficacy and safety of SLIT in the treatment of rhinitis in adults and children31Wilson D.R. Torres Lima M. Durham S.R. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis.Allergy. 2005; 60: 4-12Crossref PubMed Scopus (609) Google Scholar and both asthma and rhinitis32Olaguibel J.M. Álvarez Puebla M.J. Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis.J Investig Allergol Clin Immunol. 2005; 15: 9-16PubMed Google Scholar, 33Calamita Z. Saconato H. Pela A.B. Atallah A.N. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method.Allergy. 2006; 61: 1162-1172Crossref PubMed Scopus (282) Google Scholar, 34Penagos M. Compalati E. Tarantini F. Baena-Cagnani R. Huerta J. Passalacqua G. et al.Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials.Ann Allergy Asthma Immunol. 2006; 97: 141-148Abstract Full Text PDF PubMed Scopus (283) Google Scholar were produced. The conclusions of these studies recommended the use of SLIT in patients with allergic respiratory diseases, except for children with allergic rhinitis in whom the results are more controversial. The balance sheet for SLIT is improving, and the efficacy of this treatment is recognized in patients with both asthma and rhinitis.However the degree of efficacy of SLIT has not been frequently compared with that of SCIT; only a double-blind, double-dummy controlled trial provided evidence that no significant difference exists between SCIT and SLIT in term of symptom improvement and rescue medication use.35Khinchi M.S. Poulsen L.K. Carat F. Andre C. Hansen A.B. Malling H.J. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study.Allergy. 2004; 59: 45-53Crossref PubMed Scopus (325) Google Scholar In this field, other comparative trials would be suitable, particularly in patients who are allergic to “strong pollens” such as Parietaria judaica or grass pollens.There is a robust evidence to support the excellent safety profile of SLIT; in more than 20 years of clinical trials, no life-threatening events or fatality have ever been reported36Gidaro G.B. Marcucci F. Sensi L. Incorvaia C. Frati F. Ciprandi G. The safety of sublingual-swallow immunotherapy: an analysis of published studies.Clin Exp Allergy. 2005; 35: 565-571Crossref PubMed Scopus (156) Google Scholar; its safety profile has been confirmed in clinical trials with children less than 5 years old in whom the most frequently reported side effects were related to local itching and oral discomfort.12Fiocchi A. Pajno G. La Grutta S. Pezzuto F. Incorvaia C. Sensi L. et al.Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years.Ann Allergy Asthma Immunol. 2005; 95: 254-258Abstract Full Text PDF PubMed Scopus (115) Google Scholar Abdominal pain and/or diarrhea occurred in some cases, which could be reduced by temporary dose decrease.The worsening of allergic symptoms such as rhinoconjuctivitis, wheezing, and urticaria is uncommon, but the appearance of mild to moderate systemic adverse events should be taken into consideration as a possible side effect.37Pajno G.B. Peroni D.G. Vita D. Pietrobelli A. Parmiani S. Boner A.L. Safety of sublingual immunotherapy in children with asthma.Paediatr Drugs. 2003; 5: 777-781Crossref PubMed Scopus (60) Google Scholar Recently, for the first time, 2 cases of anaphylaxis were reported in adult patients during administration of rush SLIT to latex38Antico A. Pagani M. Crema A. Anaphylaxis by latex sublingual immunotherapy.Allergy. 2006; 61: 1236-1237Crossref PubMed Scopus (111) Google Scholar or during SLIT with mixed extracts of inhalant allergens.39Dunsky E.H. Goldstein M.F. Dvorin D.J. Belecanech G.A. Anaphylaxis to sublingual immunotherapy.Allergy. 2006; 61: 1235Crossref PubMed Scopus (132) Google ScholarTreatment of children: the pivotal challengeThe concept of specific desensitization lies at the heart of our speciality because allergen immunotherapy is the only antigen-specific immunomodulatory treatment routinely available. At the core of this concept, there is the likely hypothesis of a critical window in early life during which immunologic and respiratory response phenotypes are commonly programmed. If this hypothesis is correct, damping the cycles of early viral- and/or allergy-mediated damage in at-risk subjects or in children at the beginning of disease progression would facilitate transit through this life phase without development of persistent diseases.With respect to the allergy pathway, the intervention on allergy TH2 memory development may be a successful strategy for asthma prophylaxis or early therapy.Immunotherapy confers long-term benefit up to 12 years after its discontinuation,40Durham S.R. Walker S.M. Varga E.M. Jacobson M.R. O'Brien F. Noble W. et al.Long-term clinical efficacy of grass-pollen immunotherapy.N Engl J Med. 1999; 341: 468-475Crossref PubMed Scopus (1246) Google Scholar, 41Eng P.A. Borer-Reinhold M. Heijnen I.A. Gnehm H.P. Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood.Allergy. 2006; 61: 198-201Crossref PubMed Scopus (235) Google Scholar and in children, immunotherapy has been shown to prevent the onset of new sensitizations42Pajno G.B. Barberio G. De Luca F. Morabito L. Parmiani S. Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study.Clin Exp Allergy. 2001; 31: 1392-1397Crossref PubMed Scopus (539) Google Scholar and to reduce the evolution from rhinitis to asthma.43Niggemann B. Jacobsen L. Dreborg S. Ferdousi H.A. Halken S. Host A. et al.Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children.Allergy. 2006; 61: 855-859Crossref PubMed Scopus (292) Google Scholar Also, SLIT shows long-lasting effects24Di Rienzo V. Marcucci F. Puccinelli P. Parmiani S. Frati F. Sensi L. et al.Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study.Clin Exp Allergy. 2003; 33: 206-210Crossref PubMed Scopus (346) Google Scholar and interferes with the progression of rhinitis towards asthma.25Novembre E. Galli E. Landi F. Caffarelli C. Pifferi M. De Marco E. et al.Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2004; 114: 851-857Abstract Full Text Full Text PDF PubMed Scopus (440) Google ScholarAll these are pivotal approaches because immunotherapy might be even more effective in younger children in whom allergen-specific TH2 memory is less well established and hence more susceptible to downregulation.44Holt P.G. Upham J.W. Sly P.D. Contemporaneous maturation of immunologic and respiratory functions during early childhood: implications for development of asthma prevention strategies.J Allergy Clin Immunol. 2005; 116: 16-24Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar Therefore, by translating our basic science into clinical practice, the secondary prevention of asthma and allergy with allergen immunotherapy may offer more possibilities of success for the treatment of IgE-mediated disorders in the future (Fig 1).The single notion of atopic march—that is, that a child progresses from atopic dermatitis to asthma and hay fever with increasing age—is currently considered elusive.45Williams H. Flohr C. How epidemiology has challenged: 3 prevailing concepts about atopic dermatitis.J Allergy Clin Immunol. 2006; 118: 209-213Abstract Full Text Full Text PDF PubMed Scopus (253) Google ScholarThe Multi-Centre Allergy Study, a German birth cohort study that followed 1314 children from birth to 7 years of age,46Illi S. von Mutius E. Lau S. Nickel R. Gruber C. Niggemann B. et al.The natural course of atopic dermatitis from birth to age 7 years and the association with asthma.J Allergy Clin Immunol. 2004; 113: 925-931Abstract Full Text Full Text PDF PubMed Scopus (596) Google Scholar showed that early wheeze and specific sensitization patterns are able to predict wheezing and asthma at school age irrespective of early eczema or rhinitis. Therefore, the best method for early treatment of IgE-mediated disorders is treating more allergen sensitizations and symptoms than diseases themselves.Precocious allergen immunotherapy should be adopted particularly in young children allergic to perennial allergens: allergy to house dust mites and/or animal dander should be the main target of this strategy.47Illi S. von Mutius E. Lau S. Niggemann B. Gruber C. Wahn U. et al.Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study.Lancet. 2006; 368: 763-770Abstract Full Text Full Text PDF PubMed Scopus (591) Google Scholar Food-allergic disorders affect 6% to 8% of children in their first 3 years of life48Bock S.A. Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life.Pediatrics. 1987; 79: 683-688PubMed Google Scholar and then decrease in prevalence over the first decade. However, it is estimated that about 4% of the population is affected by food allergies.49Sicherer S.H. Munoz-Furlong A. Sampson H.A. Prevalence of seafood allergy in the United States determined by a random telephone survey.J Allergy Clin Immunol. 2004; 114: 159-165Abstract Full Text Full Text PDF PubMed Scopus (447) Google ScholarThe issue of the natural course of food allergy is currently more controversial than considered in past years. It is generally thought that milk allergy is short lived; however, in a recent study of 118 children with cow's milk allergy followed to 8.5 years,50Saarinen K.M. Pelkonen A.S. Makela M.J. Savilahti E. Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status.J Allergy Clin Immunol. 2005; 116: 869-875Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar the authors found that for those with IgE-mediated cow's milk allergy, only 75% were tolerant by the age of 5 years and 15% were still allergic by the age of 8.5 years. This study indicated that after the age of 5 years, the rate of allergy loss is quite slow.Although resolution is also reported, persistence of childhood food allergies is common with certain foods, especially peanuts, tree nuts, and seafood.51American College of Allergy, Asthma & Immunology Food all
Publication Year: 2007
Publication Date: 2007-04-01
Language: en
Type: review
Indexed In: ['crossref', 'pubmed']
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