Nursen CİGERCİ GÜNAYDIN, Esen DEMİR, Remziye TANAÇ, Figen GÜLEN

Oral Immunotherapy for Cow’s Milk Allergy: Five Years’ Experience from a Single Center in Turkey

Background: Oral immunotherapy for cow’s milk allergy is an effective treatment option because of its ability to increase the threshold for clinical reactions.Aims: To present our experience of oral immunotherapy for cow’s milk allergy in the pediatric allergy outpatient clinic, and to evaluate the long-term efficacy of oral immunotherapy and risk factors for adverse reactions during oral immunotherapy.Study Design: Single-center retrospective cohort study.Methods:Forty-twopatientswithImmunoglobulin-E-mediatedcow’s milk allergy who complied with the oral immunotherapy protocol were evaluated in this study. The treatment consisted of a rapid escalation phase with an oral food challenge step that included milk doses. During the build-up phase, increasing quantities of cow’s milk were administered until the patient was able to consume 200 mL of cow’s milk daily.Results: The mean age of starting the oral immunotherapy was 40.2±3.2 (range, 36-156) months, and 54.8% (n=23) of the patients were males. The mean duration of the build-up phase was 18.1±5.6 (range, 9-41) weeks, and the mean maintenance phase was 29.1±11.6 (range, 12-63) months. During the oral immunotherapy, 36 adverse reactions (78% mild and 22% moderate) occurred in 16 (38%) patients. There were no differences in the age of starting the oral immunotherapy (p=0.19), cow’s milk-specific Immunoglobulin-E levels (p=0.17), and cumulative provocative doses of oral food challenges (p=0.78) between the two groups of patients with and without adverse reactions. The wheal diameters to cow’s milk were higher in the group with adverse reactions (p=0.03). There was no difference in the oral immunotherapy onset age between patients with and without a history of anaphylaxis (p=0.38). The patients with a history of anaphylaxis had more adverse reactions (p=0.04) and a higher number of reactions during the oral immunotherapy (p=0.01), and a higher mean duration of the up-dosing phase (p=0.04) compared with patients without anaphylaxis.Conclusion: Oral immunotherapy is a treatment option in patients withcow’smilkallergybecauseofitshighefficacy.Adversereactions occur in about 40% of cases and are mostly mild. It should be administered with caution to patients with a history of anaphylaxis and a higher wheal diameter to cow’s milk in the skin prick test.

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1. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and management of food allergy in the United States: Summary of the NIAID-Sponsored Expert Panel. J Allergy Clin Immunol 2010;126:1-58.
2. Flokstra-de Blok BM, DunnGalvin A, Vlieg-Boerstra BJ, Oude Elberink JN, Duiverman EJ, Hourihane JO, et al. Development and validation of the selfadministered Food Allergy Quality of Life Questionnaire for adolescents. J Allergy Clin Immunol 2008;122:139-44.
3. Host A. Frequency of cow's milk allergy in childhood. Ann Allergy Asthma Immunol 2002;89:33-7.
4. Nwaru BI, Hickstein L, Panesar SS, Roberts G, Muraro A, Sheikh A. EAACI Food Allergy and Anaphylaxis Guidelines Group. Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy 2014;69:992-1007.
5. Host A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life: clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy 1990;45:587-96.
6. Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow’s milk allergy. J Allergy Clin Immunol 2007;120:1172-7.
7. Garcia-Ara MC, Boyano-Martinez MT, Diaz-Pena JM, Martin-Munoz MF, Martin- Esteban M. Cow’s milk-specific immunoglobulin E levels as predictors of clinical reactivity in the follow-up of the cow’s milk allergy infants. Clin Exp Allergy 2004;34:866-70.
8. Fiocchi A, Brozek J, Schünemann H, Bahne SL, Von Berg A, Beyer K, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. Pediatr Allergy Immunol 2010;21:1-125.
9. Wang J, Sampson HA. Food allergy. J Clin Invest 2011;121:827-35.
10. Nowak-Wegrzyn A, Sampson HA. Future therapies for food allergies. J Allergy Clin Immunol 2011;127:558-73.
11. Cohen BL, Noone S, Munoz-Furlong A, Sicherer SH. Development of a questionnaire to measure quality of life in families with a child with food allergy. J Allergy Clin Immunol 2004;114:1159-63.
12. Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol 2008;122:1154-60.
13. Zapatero L, Alonso E, Fuentes V, Martínez MI. Oral desensitization in children with cow's milk allergy. J Investig Allergol Clin Immunol 2008;18:389-96.
14. Feuille E, Nowak-Węgrzyn A. Oral Immunotherapy for food allergies. Ann Nutr Metab 2016;68:19-31.
15. Kauppila TK, Paassilta M, Kukkonen AK, Kuitunen M, Pelkonen AS, Makela MJ. Outcome of oral immunotherapy for persistent cow's milk allergy from 11 years of experience in Finland. Pediatr Allergy Immunol 2019;30:356-62.
16. Alves-Correia M, Gaspar A, Borrego LM, Azeyedo J, Martins C, Morais-Almeida M. Successful oral desensitization in children with cow's milk anaphylaxis: Clinical and laboratory evaluation up to nine-years follow-up. Allergol Immunopathol (Madr) 2019;47:133-40.
17. Clark AT, Ewan PW. Food allergy in childhood. Arch Dis Child 2003;88:79-81.
18. Vázquez-Ortiz M, Alvaro-Lozano M, Alsina L, Garcia-Paba MB, Piquer-Gilbert M, Giner-Munoz MT, et al. Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test. Clin Exp Allergy 2013;43:92-102.
19. 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;59:980-7.
20. Martorell A, De la Hoz B, Ibanez MD, Bone J, Terratos MS, Michauila A, et al. Oral desensitization as a useful treatment in 2-year-old children with cow’s milk allergy. Clin Exp Allergy 2011;41:1297-304.
21. Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 2007;62:1261-9.
22. Patriarca G, Nucera E, Roncallo C, Pollastrini E, Bartolozzi F, De Paquale T. Oral desensitizing treatment in food allergy: clinical and immunological results. Aliment Pharmacol Ther 2003;17:459-65.
23. Pajno GB, Caminiti L, Ruggeri P, De Luca R, Vita D, La Rosa M, et al. Oral immunotherapy for cow’s milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study. Ann Allergy Asthma Immunol 2010;105:376-81.
24. Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, et al. Specific oral tolerance induction in children with very severe cow’s milk-induced reactions. J Allergy Clin Immunol 2008;121:343-7.
25. Kaneko H, Teramoto T, Kondo M, Morita H, Ohnishi H, Orji K, et al. Efficacy of the slow dose-up method for specific oral tolerance induction in children with cow’s milk allergy: comparison with reported protocols. J Investig Allergol Clin Immunol 2010;20:538-9.
26. Brozek JL, Terracciano L, Hsu J, Kreis J, Compalati E, Santesso N, et al. Oral immunotherapy for IgE-mediated cow’s milk allergy: a systematic review and metaanalysis. Clin Exp Allergy 2011;42:363-74.
27. Savilahti EM, Kuitunen M,Valori M, Rantanen V, Bardina L, Gimenez G, et al. Use of IgE and IgG4 epitope binding to predict the outcome of oral immunotherapy in cow's milk allergy. Pediatr Allergy Immunol 2014;25:227-35.
28. Jagdis A, Berlin N, Barron C, Giruparajah M, Leader N, Maclachlan S, et al. Effect of ketotifen premedication on adverse reactions during peanut oral immunotherapy. Allergy Asthma Clin Immunol 2014;10:36.
29. Sanchez-Garcia S, Rodriquez del Rio P, Escudero C, Garcia-Fernandez C, Ramirez A, Ibanez MD. Efficacy of oral immunotherapy protocol for specific oral tolerance induction in children with cow’s milk allergy. Isr Med Assoc J 2012;14:43-7.
30. Alvaro M, Giner MT, Vazquez M, Lozano J, Dominguez O, Piquer M, et al. Specific oral desensitization in children with IgE-mediated cow's milk allergy. Evolution in one year. Eur J Pediatr 2012;171:1389-95.
31. Sato S, Yanagida N, Ogura K, Asaumi T, Okada Y, Koike Y, et al. Immunotherapy in food allergy: towards new strategies. Asian Pac J Allergy Immunol 2014;32:195-202.
32. Buchanan AD, Green TD, Jones SM, Scurlock AM, Christie L, Althage KA, et al. Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol 2007;119:199-205.
33. Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 2012;129:448-55.