Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis?
2006; Elsevier BV; Volume: 118; Issue: 6 Linguagem: Inglês
10.1016/j.jaci.2006.07.054
ISSN1097-6825
AutoresCaroline Bußmann, Annette Böckenhoff, Henning Henke, Thomas Werfel, N NOVAK,
Tópico(s)Food Allergy and Anaphylaxis Research
ResumoHouse dust mite (HDM) allergens are perennial indoor allergens, which may play a role as allergic trigger factors in atopic dermatitis (AD). Facilitated by their high enzymatic activity, HDM allergens are capable of penetrating the impaired epidermal skin barrier in patients with AD, gaining access to immune cells. In this way, HDM allergens induce both allergic reactions of the immediate type and allergic reactions of the delayed type, which contribute to impairment of AD. Because allergen reduction achieved by encasing strategies does not always lead to significant improvement of clinical symptoms, specific immunotherapy (SIT) might represent an attractive therapeutic option for long-time treatment of this subgroup of patients with AD. However, systematic studies on the effectiveness of SIT in patients with AD are rare. Furthermore, data on the immunologic changes induced by SIT in patients with AD are not well studied. In this review, we provide an overview of the pathogenic impact of HDM allergens as an example for aeroallergens on the course of AD. In addition, we discuss prophylactic and therapeutic options for the treatment of HDM allergy in patients with AD, including a summary of the current data available on SIT as a potential therapeutic option for patients with AD. House dust mite (HDM) allergens are perennial indoor allergens, which may play a role as allergic trigger factors in atopic dermatitis (AD). Facilitated by their high enzymatic activity, HDM allergens are capable of penetrating the impaired epidermal skin barrier in patients with AD, gaining access to immune cells. In this way, HDM allergens induce both allergic reactions of the immediate type and allergic reactions of the delayed type, which contribute to impairment of AD. Because allergen reduction achieved by encasing strategies does not always lead to significant improvement of clinical symptoms, specific immunotherapy (SIT) might represent an attractive therapeutic option for long-time treatment of this subgroup of patients with AD. However, systematic studies on the effectiveness of SIT in patients with AD are rare. Furthermore, data on the immunologic changes induced by SIT in patients with AD are not well studied. In this review, we provide an overview of the pathogenic impact of HDM allergens as an example for aeroallergens on the course of AD. In addition, we discuss prophylactic and therapeutic options for the treatment of HDM allergy in patients with AD, including a summary of the current data available on SIT as a potential therapeutic option for patients with AD. Atopic diseases, including atopic dermatitis (AD),1Johansson S.G. Hourihane J.O. Bousquet J. Bruijnzeel-Koomen C. Dreborg S. Haahtela T. et al.A revised nomenclature for allergy: an EAACI position statement from the EAACI nomenclature task force.Allergy. 2001; 56: 813-824Crossref PubMed Scopus (1569) Google Scholar, 2Akdis CA. Akdis M. Bieber T. Bindslev-Jensen C. Boguniewicz M. Eigenmann P. et al.European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus report.J Allergy Clin Immunol. 2006; 118: 152-169Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar allergic rhinoconjunctivitis, and allergic asthma, have been rising in prevalence in Western societies. It is well known that a subgroup of atopic patients goes through an atopic march during their lifetime, which usually starts with AD in early childhood (between the 1st and 7th years of life), followed by the development of allergic bronchial asthma (between the 3rd and 9th years of life) and the manifestation of allergic rhinoconjunctivitis later (between the 7th and 13th years).3Leung D.Y. Boguniewicz M. Howell M.D. Nomura I. Hamid Q.A. New insights into atopic dermatitis.J Clin Invest. 2004; 113: 651-657Crossref PubMed Scopus (1179) Google Scholar Many attempts have been made to explain the modern trend toward allergic diseases. One of the most accepted explanatory approaches for this development is the so-called hygiene hypothesis. According to this concept, the high incidence of atopic diseases is correlated with decreasing exposure of our immune system to protective microbial stimuli, which are considered important promoters of the maturation of the immune system, in particular during early infancy. Further, microbial stimuli are suspected to be important facilitators of the switch from TH2 immune responses, which predominate in utero and early periods of life, to a preferentially TH1 predominated micromilieu, which is regarded to exert protective influences on the manifestation of atopic disorders.4Wills-Karp M. Santeliz J. Karp C.L. The germless theory of allergic disease: revisiting the hygiene hypothesis.Nat Rev Immunol. 2001; 1: 69-75Crossref PubMed Scopus (653) Google Scholar In parallel, our immune system is under attack by a steadily increasing number of allergens from the environment, which are suspected to promote the manifestation of atopic diseases in genetically susceptible individuals.5Boguniewicz M. Schmid-Grendelmeier P. Leung D.Y. Atopic dermatitis.J Allergy Clin Immunol. 2006; 118: 40-43Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 6Morar N. Willis-Owen S.A. Moffatt M.F. Cookson W.O. The genetics of atopic dermatitis.J Allergy Clin Immunol. 2006; 118: 24-34Abstract Full Text Full Text PDF PubMed Scopus (210) Google ScholarOur lifestyle and the lifestyle of house dust mitesChanges in our lifestyle go along with an increasing effect of unperceived residents in our lives, which have moved into our dwellings. House dust mites (HDMs) are normal inhabitants of human skin and are not allergenic during their lifetimes. Their desiccated body and feces, which are deposited in fomites, are highly allergenic. Therefore, HDMs in addition to cockroaches represent prominent allergenic indwellers of the living environment in Western societies. HDMs are 8-legged invertebrates that belong to the subclass of Acari. The most common HDMs are the Pyroglyphidae Dermatophagoides farinae (Der f), Dermatophagoides pteronyssinus (Der p), and Euroglyphus maynei. HDMs inhabit human dwellings all over the world, and maintain both gas exchange and water intake through their cuticles, which makes them dependent on humidity. HDMs are 170 to 500 μm tall, they prefer dark places with a humidity of 65% to 80% combined with a temperature of 20°C to 30°C, and they feed on human and animal skin scales. Looking at the typical lifestyle of HDMs, we find some attributes that HDMs share with our privileged lifestyle, especially with regard to our sleeping habits. Common preferences of HDMs and human beings explain why pillows, blankets, carpets, soft toys, and mattresses (a person evaporates 500 mL water a night) are preferred habitats of HDMs.7Warner A. Bostrom S. Moller C. Kjellman N.I. Mite fauna in the home and sensitivity to house-dust and storage mites.Allergy. 1999; 54: 681-690Crossref PubMed Scopus (50) Google Scholar, 8Arlian L.G. House-dust-mite allergens: a review.Exp Appl Acarol. 1991; 10: 167-186Crossref PubMed Scopus (67) Google Scholar, 9Arlian L.G. Platts-Mills T.A. The biology of dust mites and the remediation of mite allergens in allergic disease.J Allergy Clin Immunol. 2001; 107: S406-S413Abstract Full Text Full Text PDF PubMed Scopus (246) Google ScholarAn important characteristic feature of HDMs is their high enzymatic activity and irritative character. With the help of the enzymatic activity, HDM allergens are capable of disrupting the epithelial tight junctions and facilitate the transport of the allergenic components through the epithelium.10Brown A. Farmer K. MacDonald L. Kalsheker N. Pritchard D. Haslett C. et al.House dust mite Der p 1 downregulates defenses of the lung by inactivating elastase inhibitors.Am J Respir Cell Mol Biol. 2003; 29: 381-389Crossref PubMed Scopus (81) Google Scholar Therefore, HDM allergens may act as irritants on contact with the impaired epidermal skin barrier in patients with AD.11Cork M.J. Robinson D.A. Vasilopoulos Y. Ferguson A. Moustafa M. MacGowan A. et al.New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions.J Allergy Clin Immunol. 2006; 118: 3-21Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar Some of the enzymes HDM allergens contain are serine and cystine proteinases, which activate proteinase-activated receptors (PARs), a family of G-protein–coupled transmembrane–domain receptors. PARs (especially PAR-1 and PAR-2) have been described to be expressed in the respiratory, gastrointestinal, and nervous systems and in the skin. The activation of PAR by HDM allergens induces the release of inflammatory mediators such as IL-6 and IL-8, leading to inflammation, increased vascular permeability, leukocyte infiltration, and airway hyperreactivity, which together characterize an additional unspecific inflammatory immune response induced by HDM allergens.12Kawabata A. Kawao N. Physiology and pathophysiology of proteinase-activated receptors (PARs): PARs in the respiratory system: cellular signaling and physiological/pathological roles.J Pharmacol Sci. 2005; 97: 20-24Crossref PubMed Scopus (61) Google Scholar, 13Cork M.J. Robinson D. Vasilopoulos Y. Ferguson A. Moustafa M. Mac G.A. et al.Predisposition to sensitive skin and atopic eczema.Commun Pract. 2005; 78: 440-442PubMed Google ScholarPreventive measures against HDM allergyAccording to the Association of Allergology and Clinical Immunology, a relevant mite concentration in house dust for the development of sensitizations starts from 2 μg HDM per gram dust.14Platts-Mills T.A. Thomas W.R. Aalberse R.C. Vervloet D. Champman M.D. Dust mite allergens and asthma: report of a second international workshop.J Allergy Clin Immunol. 1992; 89: 1046-1060Abstract Full Text PDF PubMed Scopus (576) Google Scholar Measured values of more than 10 μg HDM per gram dust seem to be the main risk factor for acute exacerbations of asthma in patients with HDM allergy.14Platts-Mills T.A. Thomas W.R. Aalberse R.C. Vervloet D. Champman M.D. Dust mite allergens and asthma: report of a second international workshop.J Allergy Clin Immunol. 1992; 89: 1046-1060Abstract Full Text PDF PubMed Scopus (576) Google Scholar Values of less than 2 μg per gram dust have been considered of lower importance.14Platts-Mills T.A. Thomas W.R. Aalberse R.C. Vervloet D. Champman M.D. Dust mite allergens and asthma: report of a second international workshop.J Allergy Clin Immunol. 1992; 89: 1046-1060Abstract Full Text PDF PubMed Scopus (576) Google ScholarAs a preventive measure, mite-proof beddings called encasings reduce the level of exposure to mite allergens. A reduction of the quantity of HDM allergens by encasing of mattresses and pillows with mite-proof but vapor-permeable covers has been proven in several studies.15Tan B.B. Weald D. Strickland I. Friedmann P.S. Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis.Lancet. 1996; 347: 15-18Abstract Full Text PDF PubMed Scopus (404) Google Scholar, 16Terreehorst I. Hak E. Oosting A.J. Tempels-Pavlica Z. de Monchy J.G. Bruijnzeel-Koomen C.A. et al.Evaluation of impermeable covers for bedding in patients with allergic rhinitis.N Engl J Med. 2003; 349: 237-246Crossref PubMed Scopus (194) Google Scholar Encasing might significantly reduce symptoms in some but not in all HDM-sensitive patients.15Tan B.B. Weald D. Strickland I. Friedmann P.S. Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis.Lancet. 1996; 347: 15-18Abstract Full Text PDF PubMed Scopus (404) Google Scholar, 17Rijssenbeek-Nouwens L.H. Oosting A.J. de Monchy J.G. Bregman I. Postma D.S. De Bruin-Weller M.S. The effect of anti-allergic mattress encasings on house dust mite-induced early- and late-airway reactions in asthmatic patients: a double-blind, placebo-controlled study.Clin Exp Allergy. 2002; 32: 117-125Crossref PubMed Scopus (25) Google Scholar Moreover, reduction or elimination of the HDM allergens alone does not seem to be a sufficient and clinically effective strategy.16Terreehorst I. Hak E. Oosting A.J. Tempels-Pavlica Z. de Monchy J.G. Bruijnzeel-Koomen C.A. et al.Evaluation of impermeable covers for bedding in patients with allergic rhinitis.N Engl J Med. 2003; 349: 237-246Crossref PubMed Scopus (194) Google Scholar, 18Woodcock A. Forster L. Matthews E. Martin J. Letley L. Vickers M. et al.Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.N Engl J Med. 2003; 349: 225-236Crossref PubMed Scopus (283) Google Scholar In addition, it is known that the level of house dust patients are exposed to outside their homes, such as at schools, work, or day care centers, is also quite high when around fomites. It is obvious that consequent reduction of the HDM allergen exposure even in these environments is important but difficult to achieve.19Engelhart S. Bieber T. Exner M. House dust mite allergen levels in German day-care centers.Int J Hyg Environ Health. 2002; 205: 453-457Crossref PubMed Scopus (25) Google ScholarAdvances in subcutaneous immunotherapy against HDM allergyIn addition to preventive measures in patients with relevant clinical sensitizations, specific immunotherapy (SIT) with HDM extracts is a therapeutic option for long-time treatment of patients with allergic rhinoconjunctivitis or mild asthma in older children and adults.20Des 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: 450-453Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar At present, SIT is the only curative therapy available for the treatment of allergic diseases, aimed at the induction of allergen-specific tolerance in sensitized individuals. During SIT, defined amounts of allergen extracts the individual is sensitized to are injected into the subcutis or, in recent times, also administered sublingually in increasing doses.21Cox 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 Scholar, 22Malling HJ. Sublingual immunotherapy: efficacy-methodology and outcome of clinical trials.Allergy. 2006; 61: 24-28Crossref PubMed Scopus (28) Google Scholar After this therapy, an immune switch into a modified TH2 immune response going along with the production of protective IgG4 instead of IgE by B cells is induced. In this context, regulatory T cells releasing anti-inflammatory tolerogenic cytokines such as IL-10 and TGF-β have been shown to play an important role.23Verhagen J. Taylor A. Blaser K. Akdis M. Akdis C.A. T regulatory cells in allergen-specific immunotherapy.Int Rev Immunol. 2005; 24: 533-548Crossref PubMed Scopus (20) Google Scholar, 24Till S.J. Francis J.N. Nouri-Aria K. Durham S.R. Mechanisms of immunotherapy.J Allergy Clin Immunol. 2004; 113: 1025-1034Abstract Full Text Full Text PDF PubMed Scopus (329) Google ScholarThe first trial of a SIT against HDM allergens in patients with asthma was conducted and published by Bruun25Bruun E. Control examination of the specificity of specific desensitization in asthma.Acta Allergol. 1949; 2: 122-128Crossref PubMed Scopus (35) Google Scholar in 1949. Since then, many clinical studies on the safety and efficacy of SIT with HDM extracts have been performed.26Smith A.P. Hyposensitization with Dermatophagoides pteronyssinus antigen: trial in asthma induced by house dust.BMJ. 1971; 4: 204-206Crossref PubMed Scopus (81) Google Scholar, 27Corrado O.J. Pastorello E. Ollier S. Cresswell L. Zanussi C. Ortolani C. et al.A double-blind study of hyposensitization with an alginate conjugated extract of D. pteronyssinus (Conjuvac) in patients with perennial rhinitis, 1: clinical aspects.Allergy. 1989; 44: 108-115Crossref PubMed Scopus (56) Google Scholar, 28Grembiale R.D. Camporota L. Naty S. Tranfa C.M. Djukanovic R. Marsico S.A. Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness.Am J Respir Crit Care Med. 2000; 162: 2048-2052Crossref PubMed Scopus (133) Google Scholar A positive effect of SIT on symptom scores of patients with HDM allergen-induced allergic rhinitis and allergic asthma has been shown. In allergic rhinoconjunctivitis, the reduction of the symptom and medication score was 30%.29Kleine-Tebbe J. Bergmann K.-C. Friedrichs F. Fuchs T. Jung K. Klimek L. et al.Die spezifische Immuntherpie (Hyposensibilisierung) bei IgE-vermittelten allergischen Erkrankungen.Allergo J. 2006; 15: 56-74Google Scholar Furthermore, preventive effects on the onset of new sensitizations in monosensitized children with asthma and alleviation of asthma in adult patients with SIT against HDM allergy during infancy have been observed.20Des 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: 450-453Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar, 30Bousquet J. Demoly P. Michel F.B. Specific immunotherapy in rhinitis and asthma.Ann Allergy Asthma Immunol. 2001; 87: 38-42Abstract Full Text PDF PubMed Scopus (73) Google Scholar, 31Maestrelli P. Zanolla L. Pozzan M. Fabbri L.M. Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite.J Allergy Clin Immunol. 2004; 113: 643-649Abstract Full Text Full Text PDF PubMed Scopus (85) Google ScholarPros and cons of allergen SIT as a putative therapeutic option in patients with ADIn more than 85% of adult patients, AD is associated with IgE mediated sensitization mirrored by increased total IgE serum levels and allergen specific IgE against different aeroallergens or food allergens and positive skin prick tests combined with respective clinical symptoms after allergen exposure.32Schmid-Grendelmeier P. Simon D. Simon HU. Akdis CA. Wüthrich B. Epidemiology, clinical features, and immunology of the "intrinsic" (non IgE-mediated) type of atopic dermatitis (constitutional dermatitis).Allergy. 2001; 56: 841-849Crossref PubMed Scopus (247) Google Scholar In this context, both inhalation of aeroallergens via the respiratory tract and the application and exposure of these aeroallergens to the skin of these patients can lead to severe exacerbations of AD and cause severe flare-ups of skin lesions in some patients with moderate to severe AD.33Tupker R.A. de Monchy J.G. Coenraads P.J. Homan A. van der Meer J.B. Induction of atopic dermatitis by inhalation of house dust mite.J Allergy Clin Immunol. 1996; 97: 1064-1070Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar Further, the degree of sensitization to aeroallergens has been shown to be correlated with the severity of the disease in some studies.Facilitated by their high enzymatic activity, HDM allergens are capable of penetrating the impaired epidermal skin barrier in patients with AD to get access to immune cells, such as mast cells or dendritic cells. In this way, HDM allergens induce both allergic reactions of the immediate type and allergic reactions of the delayed type, which contribute to flare-ups of eczema and impairment of the course of AD.Concerning HDM allergy, the high rate of relevant sensitizations against HDM allergens together with the modified skin barrier of patients with AD,11Cork M.J. Robinson D.A. Vasilopoulos Y. Ferguson A. Moustafa M. MacGowan A. et al.New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions.J Allergy Clin Immunol. 2006; 118: 3-21Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar the ubiquitous and combined exposition of patients with AD to HDM allergens via the respiratory tract as well as the skin, and the difficulty of implementing allergen avoidance strategies explain the outstanding role of HDM sensitizations in patients with AD. This is of particular importance in view of the recent finding that mutations in the filaggrin gene might be associated with AD and the impaired skin barrier in these patients and predispose a subgroup of patients with AD to the development of several sensitizations via this deficient skin barrier shield.34Weidinger S. Illig T. Baurecht H. Irvine A.D. Rodriguez E. Diaz-Lacava A. et al.Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations.J Allergy Clin Immunol. 2006; 118: 214-219Abstract Full Text Full Text PDF PubMed Scopus (494) Google Scholar, 35Palmer C.N. Irvine A.D. Terron-Kwiatkowski A. Zhao Y. Liao H. Lee S.P. et al.Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.Nat Genet. 2006; 38: 441-446Crossref PubMed Scopus (2235) Google ScholarState of the art: systematic overview of studies on allergen SIT in ADSpecific immunotherapy against HDM sensitizations is not generally indicated for AD without concomitant allergic rhinoconjunctivitis or mild allergic asthma at present. One reason for this is the risk of exacerbations of eczema or potential relapses of AD in patients with latent AD or a history of AD under SIT.36Di Prisco de Fuenmayor M.C. Champion R.H. Specific hyposensitization in atopic dermatitis.Br J Dermatol. 1979; 101: 697-700Crossref PubMed Scopus (35) Google ScholarTo get an overview about the state of the art of SIT in AD, we conducted a systematic search in several databases such as MEDLINE, EMBASE, and CENTRAL. The following key words were used for the search: "atopic eczema" or "atopic dermatitis" and "specific immunotherapy" or "hyposensitization" combined with a second search for "side effects" or "adverse events" and "atopic eczema" or "atopic dermatitis" and "specific immunotherapy" or "hyposensitization." As a result, we identified a total of 23 studies about subcutaneous or sublingual allergen SIT in AD with different allergens. Ten of these studies conducted between 1974 and 2006 were observational studies36Di Prisco de Fuenmayor M.C. Champion R.H. Specific hyposensitization in atopic dermatitis.Br J Dermatol. 1979; 101: 697-700Crossref PubMed Scopus (35) Google Scholar, 37Grewe M. Hyposensibilisierung beim atopischen Ekzem.Allergo J. 2000; 9: 351-353Google Scholar, 38Heijer A. Hyposensitzation with aeroallergens in atopic eczema.Allergo J. 1993; 2: 3-7Google Scholar, 39Mosca M. Albani-Rocchetti G. Vigini M.A. Ubezio S. Nume G. Di Silverio A. La vaccinoterapia sulinguale nella dermatite atopica.Ital Dermatol Venerol. 1993; 128: 79-83Google Scholar, 40Mastrandrea F. Serio G. Minelli M. Specific sublingual immunotherapy in atopic dermatitis: results of a 6-year-year follow-up of 35 consecutive patients.Allergol Immunopathol (Madr). 2000; 28: 54-62PubMed Google Scholar, 41Pacor M.L. Biasi D. Maleknia T. [The efficacy of long-term specific immunotherapy for Dermatophagoides pteronyssinus in patients with atopic dermatitis].Recenti Prog Med. 1994; 85: 273-277PubMed Google Scholar, 42Trofimowicz A. Rzepecka E. Hofman J. Clinical effects of specific immunotherapy in children with atopic dermatitis.Rocz Akad Med Bialymst. 1995; 40: 414-422PubMed Google Scholar, 43Zachariae H. Cramers M. Herlin T. Jensen J. Kragballe K. Ternowitz T. et al.Non-specific immunotherapy and specific hyposensitization in severe atopic dermatitis.Acta Derm Venereol Suppl (Stockh). 1985; 114: 48-54PubMed Google Scholar, 44Zwacka G. Glaser S. Rieger B. Therapeutische Erfahrungen mit Pangramin-SLIT im Vergleich zu einer subcutanen Immuntherapie und zur symptomatischen medikamentösen Behandlung bei Kindern mit Asthma bronchiale, Rhinokonjunktivitis und atopischer Dermatitis.Allergologie. 1996; 19: 580-592Google Scholar (see this article's Table E1 in the Online Repository at www.jacionline.org), 11 controlled studies (Table I),45Galli E. Chini L. Nardi S. Benincori N. Panei P. Fraioli G. et al.Use of a specific oral hyposensitization therapy to Dermatophagoides pteronyssinus in children with atopic dermatitis.Allergol Immunopathol (Madr). 1994; 22: 18-22PubMed Google Scholar, 46Glover M.T. Atherton D.J. A double-blind controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with atopic eczema.Clin Exp Allergy. 1992; 22: 440-446Crossref PubMed Scopus (138) Google Scholar, 47Kaufmann H.S. Roth H.L. Hyposensitization with alum precipitated extracts in atopic dermatitis: a placebo controlled study.Ann Allergy. 1974; 32: 321-330PubMed Google Scholar, 48Leroy B.P. Boden G. Lachapelle J.M. Jacquemin M.G. Saint-Remy J.M. A novel therapy for atopic dermatitis with allergen-antibody complexes: a double-blind, placebo-controlled study.J Am Acad Dermatol. 1993; 28: 232-239Abstract Full Text PDF PubMed Scopus (72) Google Scholar, 49Noh G.W. Lee K.Y. Blood eosinophils and serum IgE as predictors for prognosis of interferon-gamma therapy in atopic dermatitis.Allergy. 1998; 53: 1202-1207Crossref PubMed Scopus (55) Google Scholar, 50Petrova S.I. Berzhets V.M. Albanova V.I. Bystriskaia T.F. Petrova N.S. Immunotherapy in the complex treatment of patients with atopic dermatitis with sensitization to house dust mites.Zh Mikrobiol Epidemiol Immunobiol. 2006; 1: 33-36PubMed Google Scholar, 51Ring J. Successful hyposensitization treatment in atopic eczema: results of a trial in monozygotic twins.Br J Dermatol. 1982; 107: 597-602Crossref PubMed Scopus (62) Google Scholar, 52Silny W. Czarnecka-Operacz M. Silny P. [Efficacy of specific immunotherapy in the treatment of children and youngsters suffering from atopic dermatitis, part I: evaluation of clinical score].Wiad Lek. 2005; 58: 47-55PubMed Google Scholar, 53Silny W. Czarnecka-Operacz M. Spezifische Immuntherapie bei der Behandlung von Patienten mit atopischer Dermatitis.Allergologie. 2006; 29: 171-183Crossref Google Scholar, 54Warner J.O. Price J.F. Soothill J.F. Hey E.N. Controlled trial of hyposensitisation to Dermatophagoides pteronyssinus in children with asthma.Lancet. 1978; 2: 912-915Abstract PubMed Scopus (282) Google Scholar, 55Werfel T. Breuer K. Rueff F. Przybilla B. Worm M. Grewe M. et al.Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study.Allergy. 2006; 61: 202-205Crossref PubMed Scopus (241) Google Scholar and 2 case reports56Michils A. Farber C.M. Van Vooren J.P. Yernault J.C. Duchateau J. Sustained benefit of interferon-alpha therapy and oral hyposensitization in severe atopic dermatitis.Br J Dermatol. 1994; 130: 134-135Crossref PubMed Scopus (15) Google Scholar, 57Chait I. Allkins V. Remission of life-long atopic dermatitis after hyposensitisation to house dust mite.Practitioner. 1985; 229 (612): 609PubMed Google Scholar (see this article's Table E1 in the Online Repository at www.jacionline.org). The studies included both children and adults with AD.Table IControlled studies of SIT in ADTotal patients (n)Age (y)Type of immunotherapyAllergensTotal duration of therapy (mo)OutcomeReference262-47SCITAnimal dander, HDM, molds, pollen24Active group•Improvement in 13 patients (81.3%)Placebo group•Improvement in 4 patients (40%)47Kaufmann H.S. Roth H.L. Hyposensitization with alum precipitated extracts in atopic dermatitis: a placebo controlled study.Ann Allergy. 1974; 32: 321-330PubMed Google Scholar205-14SCITHDM12Active group•Improvement in 7 patients (77.8%)•No change or worsening in 2 patients (22.2%)Placebo group•Improvement in 3 patients (27.3%)•No change or worsening in 8 patients (72.7%)54Warner J.O. Price J.F. Soothill J.F. Hey E.N. Controlled trial of hyposensitisation to Dermatophagoides pteronyssinus in children with asthma.Lancet. 1978; 2: 912-915Abstract PubMed Scopus (282) Google Scholar210SCITGrass pollen24Active group•Improvement from score 30→10Placebo group•Improvement from score 26→2151Ring J. Successful hyposensitization treatment in atopic eczema: results of a trial in monozygotic twins.Br J Dermatol. 1982; 107: 597-602Crossref PubMed Scopus (62) Google Scholar245-16SCITHDM13.5Active group•Better: 8 patients (61.5%)•Same: 4 patients (30.8%)•Worse: 1 patient (7.7%)Placebo group•Better: 9 patients (81.8%)•Same: 2 patients (18.2%)•Worse: no patient (0%)→Placebo effect higher46Glover M.T. Atherton D.J. A double-blind controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with atopic eczema.Clin Exp Allergy. 1992; 22: 440-446Crossref PubMed Scopus (138) Google Scholar245-50Allergen-antibody complexesHDM16•Significant improvement in 82% of patients of the active group48Leroy B.P. Boden G. Lachapelle J.M. Jacquemin M.G. Saint-Remy J.M. A novel therapy for atopic dermatitis with allergen-antibody complexes: a double-blind, placebo-controlled study.J Am Acad Dermatol. 1993; 28: 232-239Abstract Full Text PDF PubMed Scopus (72) Google Scholar9915-62SLITHDMNM•Improvement in the SLIT group50Petrova S.I. Berzhets V.M. Albanova V.I. Bystriskaia T.F. Petrova N.S. Immunotherapy in the complex treatment of patients with atopic dermatitis with sensitization to house dust mites.Zh Mikrobiol Epidemiol Immunobiol. 2006; 1: 33-36PubMed Google Scholar205-40SCITHDM, grass pollen12Active group•Better in 8 patients (80%)•Remission in 1 patient•Exacerbation in 2 patients (20%)Placebo group•Remission in 1 patient (10%)•Worsening in 9 patients (90%)Difference between active group and placebo group (P < .01)53Silny W. Czarnecka-Operacz M. Spezifische Immuntherapie bei der Be
Referência(s)