More than half of children with cow’s milk allergy acquire tolerance by age 12 years
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Key takeaways:
- 31% of children were tolerant by age 9 years.
- Tolerant children had lower cow’s milk specific IgE levels than those who were not tolerant.
- 86% of children with no risk factors achieved tolerance.
More than half of the children with an IgE-mediated cow’s milk allergy at age 6 years acquired tolerance to cow’s milk by age 12 years without oral immunotherapy, according to a study published in Pediatric Allergy and Immunology.
Risk factors for persistent cow’s milk allergy at age 12 years included elevated cow’s milk specific IgE levels, previous anaphylaxis due to cow’s milk and complete dietary elimination of cow’s milk, Kei Kubota, Clinical Research Center for Allergology and Rheumatology, NHO Sagamihara National Hospital, and colleagues wrote.
The single-center, retrospective review evaluated data from 80 children (55 boys) born between January 2002 and December 2005 who had visited NHO Sagamihara National Hospital with an IgE-mediated cow’s milk allergy before age 6 years.
The cohort included 30 (38%) with previous anaphylaxis due to cow’s milk and 40 (50%) who had completely eliminated cow’s milk from their diet. None of these children received any oral immunotherapy for cow’s milk.
At age 6 years, the median cow’s milk specific IgE level was 12 kUA/L (95% CI, 3.4-39.1), and the median casein specific IgE level was 18.4 kUA/L (95% CI, 3.6-42.1). The median total IgE was 1,120 IU/mL (95% CI, 655-1,875).
By age 9 years, 25 (31%) had acquired tolerance, defined as passing an oral food challenge of 200 mL of unheated cow’s milk or consuming 200 mL of cow’s milk without any allergic symptoms at home. By age 12 years, that total increased to 46 (58%) children.
The 34 (42%) remaining children were classified with persistent cow’s milk allergy, defined as fulfilling neither of these criteria. This group included 20 (25%) with partial elimination and 14 (18%) with complete elimination of cow’s milk from their diet at age 12 years.
There were statistically significant differences between the children who did and did not acquire tolerance based on history of anaphylaxis due to cow’s milk before age 6 years, elimination of cow’s milk at age 6 years and specific cow’s milk and casein IgE levels, the researchers said.
Cow’s milk specific IgE levels were highest among children aged 6 and 7 years before seeing annual decreases, except for children aged 8 and 9 years in the group that acquired tolerance. These levels were significantly higher in the persistent group compared with the tolerant group between ages 6 and 12 years as well, the researchers said.
Adjusted hazard ratios for persistent cow’s milk allergy included 2.07 (95% CI, 1.06-4.02) for previous anaphylaxis from cow’s milk, 3.12 (95% CI, 1.46-6.67) for complete elimination of cow’s milk at age 6 years and 2.29 per tenfold increase (95% CI, 1.41-3.73) for higher cow’s milk specific IgE levels at age 6 years.
Specifically, 12 of 37 (32%) children with cow’s milk specific IgE levels of 12.7 kUA/L or higher acquired tolerance, compared with 34 of 43 (79%) of children with cow’s milk specific IgE levels of less than 12 kUA/L.
Similarly, 12 of 40 (30%) children with complete cow’s milk elimination acquired tolerance, compared with 34 of 40 (85%) children who did not have complete cow’s milk elimination.
Twelve of 30 (40%) children who had previous anaphylaxis for cow’s milk and 34 of 50 (68%) of those who did not acquired tolerance as well.
Nineteen of the 22 (86%) children who did not have any of these three risk factors acquired tolerance, but none of the 14 children who had all three risk factors acquired tolerance.
A sub-analysis of 43 children who had received OIT for cow’s milk by age 12 years found that approximately 50% acquired tolerance, defined as short-term unresponsiveness to 200 mL of unheated cow’s milk.
Also, approximately 37% of the children in this group classified with persistent cow’s milk allergy who specifically had OIT between ages 6 and 12 years acquired tolerance by age 12 years.
Based on these findings, the researchers said that physicians should proactively assess children with cow’s milk allergy who do not have any of the three identified risk factors with OFCs. Physicians also should consider OIT for children with all three of these risk factors, the researchers continued.
Perspective
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We have limited data on how many children become tolerant to cow’s milk and on predictors for tolerance development. This paper gives some indication data from a Japanese cohort. In my practice, we do not often seen development of tolerance post-school age, although it does happen.
Still, regular follow-up and reassessment of food allergic status is crucial in all children. We need better data in the United States and worldwide on tolerance development to milk post-school age and on country-specific predictive factors.
Perspective
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The results of this observational study support previous reports on the natural history of cow’s milk allergy. They were within the expected range and were not surprising. In fact, in our clinical practice, the acquisition rate of tolerance to cow’s milk allergy in school age is lower than that of pre-school age.
It is important to tell school age patients with cow’s milk allergy that they may acquire tolerance to cow’s milk in approximately 40% to 60% of cases by age 12 years. By doing so, patients may prefer to avoid complete elimination of cow’s milk protein.
On the other hand, school age patients with cow’s milk allergy who already have all the factors of greater cow’s milk specific IgE levels, previous anaphylaxis to cow’s milk, and complete cow’s milk elimination should promptly consult with a specialized facility to undergo oral immunotherapy.
Complete elimination of cow’s milk protein is one of the important risk factors that inhibits the acquisition of tolerance to cow’s milk allergy, but recent reports have shown that temporary allergen ingestion has a negative impact on the development of food allergies.
It is still unclear whether cow’s milk protein can be taken only occasionally or whether it must be taken daily to promote tolerance. Future research is needed to determine the optimal frequency of cow’s milk protein intake to prevent persistent cow’s milk allergy.
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