Background: This study aimed to investigate the efficacy and safety of low-dose-induction oral immunotherapy (OIT) with 3 ml of milk, which is a lower target volume than is conventionally used. Methods: Children aged ≥5 years with milk allergies [confirmed by oral food challenge (OFC) against 3 ml of milk] were enrolled. The OIT group was admitted to the hospital for 5 days for build-up. Subsequently, at home, the volume was gradually increased by up to a maximum of 3 ml every 5 days. While the OIT group ingested a small amount of milk every day, the control group completely eliminated their milk intake. Both groups underwent OFCs approximately 1 year later in order to assess their responsiveness to 3 ml and 25 ml of cow's milk. Results: The OIT and control groups had no background differences; the proportion of patients unresponsive to 3 ml of milk after 1 year was 58.3% (7/12) and 13.8% (4/25), respectively (p = 0.018), while the proportion unresponsive to 25 ml of milk was 33.3% (4/12) and 0.0% (0/25), respectively (p = 0.007). Furthermore, a significant decrease in the casein-specific immunoglobulin E levels was seen after 12 months when compared to baseline in the OIT group (p = 0.033). Adverse allergic reactions were rare and most symptoms were mild. Conclusion: This study of a high-risk population reacting to very low amounts of milk showed that low-dose-induction OIT appeared effective for acquiring unresponsiveness to 3 ml and 25 ml of milk, with severe symptoms being rare, indicating that for improvement of food allergies, continuous intake of small amounts may be as effective as intake of larger amounts.

Boyce JA, Assa'ad A, Burks AW, et al: Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010;126(6 suppl):S1-S58.
Muraro A, Werfel T, Hoffmann-Sommergruber K, et al: EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy. Allergy 2014;69:1008-1025.
Lifschitz C, Szajewska H: Cow's milk allergy: evidence-based diagnosis and management for the practitioner. Eur J Pediatr 2015;174:141-150.
Elizur A, Rajuan N, Goldberg MR, Leshno M, Cohen A, Katz Y: Natural course and risk factors for persistence of IgE-mediated cow's milk allergy. J Pediatr 2012;161:482-487.e1.
Wood RA, Sicherer SH, Vickery BP, Jones SM, Liu AH, Fleischer DM, Henning AK, Mayer L, Burks AW, Grishin A, Stablein D, Sampson HA: The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol 2013;131:805-812.
Sackesen C, Assa'ad A, Baena-Cagnani C, Ebisawa M, Fiocchi A, Heine RG, Von Berg A, Kalayci O: Cow's milk allergy as a global challenge. Curr Opin Allergy Clin Immunol 2011;11:243-248.
Yeung JP, Kloda LA, McDevitt J, Ben-Shoshan M, Alizadehfar R: Oral immunotherapy for milk allergy. Cochrane Database Syst Rev 2012;11:CD009542.
Brożek JL, Terracciano L, Hsu J, Kreis J, Compalati E, Santesso N, Fiocchi A, Schünemann HJ: Oral immunotherapy for IgE-mediated cow's milk allergy: a systematic review and meta-analysis. Clin Exp Allergy 2012;42:363-374.
Sato S, Yanagida N, Ogura K, Imai T, Utsunomiya T, Iikura K, Goto M, Asaumi T, Okada Y, Koike Y, Syukuya A, Ebisawa M: Clinical studies in oral allergen-specific immunotherapy: differences among allergens. Int Arch Allergy Immunol 2014;164:1-9.
Keet CA, Seopaul S, Knorr S, Narisety S, Skripak J, Wood RA: Long-term follow-up of oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol 2013;132:737-739.e6.
Savilahti EM, Savilahti E: Development of natural tolerance and induced desensitization in cow's milk allergy. Pediatr Allergy Immunol 2013;24:114-121.
Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A: Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol 2008;121:343-347.
Yanagida N, Minoura T, Kitaoka S: Butter tolerance in children allergic to cow's milk. Allergy Asthma Immunol Res 2015;7:186-189.
Wang J, Sampson HA: Oral and sublingual immunotherapy for food allergy. Asian Pac J Allergy Immunol 2013;31:198-209.
Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, Steele P, Driggers S, Burks AW, Wood RA: The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 2012;129:448-455.
Ahrens B, Lopes de Oliveira LC, Grabenhenrich L, Schulz G, Niggemann B, Wahn U, Beyer K: Individual cow's milk allergens as prognostic markers for tolerance development? Clin Exp Allergy 2012;42:1630-1637.
Sicherer SH, Wood RA, Vickery BP, Jones SM, Liu AH, Fleischer DM, Dawson P, Mayer L, Burks AW, Grishin A, Stablein D, Sampson HA: The natural history of egg allergy in an observational cohort. J Allergy Clin Immunol 2014;133:492-499.
Costa LC, Rezende ER, Segundo GR: Growth parameters impairment in patients with food allergies. J Allergy (Cairo) 2014;2014:980735.
Mehta H, Ramesh M, Feuille E, Groetch M, Wang J: Growth comparison in children with and without food allergies in 2 different demographic populations. J Pediatr 2014;165:842-848.
Flammarion S, Santos C, Guimber D, Jouannic L, Thumerelle C, Gottrand F, Deschildre A: Diet and nutritional status of children with food allergies. Pediatr Allergy Immunol 2011;22:161-165.
Skripak JM, Matsui EC, Mudd K, Wood RA: The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol 2007;120:1172-1177.
Lomas JM, Bingemann TA: Clinical predictors for favorable outcomes in an oral immunotherapy program for IgE-mediated cow's milk allergy. Pediatrics 2014;134(suppl 3):S156.
Levy MB, Elizur A, Goldberg MR, Nachshon L, Katz Y: Clinical predictors for favorable outcomes in an oral immunotherapy program for IgE-mediated cow's milk allergy. Ann Allergy Asthma Immunol 2014;112:58-63.e1.
Barbi E, Longo G, Berti I, Neri E, Saccari A, Rubert L, Matarazzo L, Montico M, Ventura A: Adverse effects during specific oral tolerance induction: in-hospital ‘rush' phase. Eur Ann Allergy Clin Immunol 2012;44:18-25.
Casale TB, Stokes JR: Immunotherapy: what lies beyond. J Allergy Clin Immunol 2014;133:612-619.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.