Background: Cow’s milk (CM) allergy is the second most common food allergy developed during infancy in Japan. To identify predictors of persistent CM allergy, we investigated the tolerance acquisition rate based on an oral food challenge in children under 6 years of age, diagnosed with immediate-type CM allergy. Methods: This retrospective cohort study included 131 children born in 2005 with a history of immediate allergic reaction to CM, of whom 39 were excluded because of ongoing oral immunotherapy (n = 18) or a lack of follow-up data (n = 21). The 92 remaining participants were followed for 6 years. Tolerance was defined as no adverse reaction to 200 mL of CM and regular intake of milk at home. Subjects were divided into 3 groups based on age at tolerance acquisition: group I (<3 years; n = 31), group II (3–6 years; n = 42), and group III (persistent allergic group; n = 19). Results: Tolerance acquisition rates by 3, 5, and 6 years of age were 32.6% (30/92), 64.1% (59/92), and 84.8% (70/92), respectively. Age at first hospital visit was significantly higher in groups II and III than in group I (p < 0.001). The incidence of anaphylaxis to other foods was also higher in group III than in group I (p = 0.04), as was CM-induced anaphylaxis (p = 0.03). Furthermore, milk and casein-specific immunoglobulin E (IgE) levels were significantly higher in group III than in group II after birth and remained high thereafter (p < 0.05). Conclusions: The history of anaphylaxis and high milk-specific IgE levels were associated with persistent CM allergy.

Schoemaker AA, Sprikkelman AB, Grimshaw KE, Roberts G, Grabenhenrich L, Rosenfeld L, Siegert S, Dubakiene R, Rudzeviciene O, Reche M, Fiandor A, Papadopoulos NG, Malamitsi-Puchner A, Fiocchi A, Dahdah L, Sigurdardottir ST, Clausen M, Stańczyk-Przyłuska A, Zeman K, Mills EN, McBride D, Keil T, Beyer K: Incidence and natural history of challenge-proven cow’s milk allergy in European children – EuroPrevall birth cohort. Allergy 2015; 70: 963–972.
Warren CM, Jhaveri S, Warrier MR, Smith B, Gupta RS: The epidemiology of milk allergy in US children. Ann Allergy Asthma Immunol 2013; 110: 370–374.
Schrander JJ, van den Bogart JP, Forget PP, Schrander-Stumpel CT, Kuijten RH, Kester AD: Cow’s milk protein intolerance in infants under 1 year of age: a prospective epidemiological study. Eur J Pediatr 1993; 152: 640–644.
Jassica S, Scott S, Robert W: The natural history of food allergy. J Allergy Clin Immunol 2016; 4: 196–203.
Ebisawa M, Ito K, Fujisawa T; Committee for Japanese Pediatric Guideline for Food Allergy; Japanese Society of Pediatric Allergy and Clinical Immunology; Japanese Society of Allergology: Japanese guidelines for food allergy 2017. Allergol Int 2017; 66: 248–264.
Wood RA, Sicherer SH, Vickery BP, Jones SM, Liu AH, Fleischer MD, 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.
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.
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.
Saarinen KM, Pelkonen AS, Makela MJ, Savilahti E: Clinical course and prognosis of cow’s milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol 2005; 116: 869–875.
Ikematsu K, Tachimoto H, Sugisaki C, Syukuya A, Ebisawa M: Feature of food allergy developed during infancy. 2. Acquisition of tolerance against hen’s egg, cow’s milk, wheat, and soybean up to 3 years old (in Japanese). Arerugi 2006; 55: 533–541.
Imai T, Komata T, Ogata M, Tomikawa M, Tachimoto H, Shukuya A, Ebisawa M: Prolonged type of food allergy (in Japanese). Arerugi 2007; 56: 1285–1292.
Ebisawa M, Nishima S, Ohnisi H, Kondo N: Pediatric allergy and immunology in Japan. Pediatr Allergy Immunol 2013; 24: 704–714.
Okada Y, Yanagida N, Sato S, Ebisawa M: Better management of cow’s milk allergy using a very low dose food challenge test: a retrospective study. Allergol Int 2015; 64: 272–276.
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