The natural history of IgE-mediated cow's milk allergy

Article Outline

• Abstract
• Methods
  • Statistical analysis
• Results
  • Study population
  • CMA resolution
  • Predictors of prognosis
• Discussion
• Acknowledgment
• References
• Copyright

Background

Cow's milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2% to 3% of the general population. Most studies have shown the prognosis of developing tolerance to cow's milk to be good, with most outgrowing their allergy by age 3 years.

Objective

To define the natural course of CMA and identify the factors that best predict outcome in a large referral population of children with CMA.

Methods

Clinical history, test results, and final outcome were collected on 807 patients with IgE-mediated CMA. Patients were considered tolerant after they passed a challenge or experienced no reactions in the past 12 months and had a cow's milk IgE (cm-IgE) level <3 kU/L.

Results

Rates of resolution were 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Patients with persistent allergy had higher cm-IgE levels at all ages to age 16 years. The highest cm-IgE for each patient, defined as peak cm-IgE, was found to be highly predictive of outcome (P < .001). Coexisting asthma (P < .001) and allergic rhinitis (P < .001) were also significant predictors of outcome.

Conclusion

The prognosis for CMA in this population is worse than previously reported. However, some patients developed tolerance during adolescence, indicating that follow-up and re-evaluation of CMA patients is important in their care. cm-IgE level is highly predictive of outcome.

Clinical implications

The increasing potential for persistence of CMA, along with cm-IgE level's effect on prognosis, should be considered when counseling families regarding expected clinical course.

Key words: Cow's milk, food allergy, IgE, prognosis, tolerance

Abbreviations used: CMA, Cow's milk allergy, cm-IgE, Cow's milk IgE

Cow's milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2% to 3% of the general population.¹, ², ³, ⁴ Most studies have shown the prognosis of developing tolerance to cow's milk to be good, with the majority outgrowing their allergy by age 3 years.¹, ⁴ Other studies have found less optimistic results, however, and the prognosis for developing tolerance in older children with persistent CMA remains less clear.⁵, ⁶, ⁷, ⁸ Saarinen et al⁶ found 15% of children with previously diagnosed IgE-mediated CMA to have persistent sensitivity at age 8.6 years. There is limited information available regarding the clinical or laboratory factors that may predict the development of tolerance to cow's milk, although children with non–IgE-mediated disease have consistently been shown to develop tolerance earlier and more frequently than those with IgE-mediated allergy.

In our clinic population, we have followed a large group of children with CMA. The purposes of this study were to define the clinical characteristics of this population, define the rate of allergy resolution over time, and identify the clinical and laboratory features that may predict the outcome of CMA over time.

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Methods 

This is a retrospective review of the clinical records of 4117 patients seen by the principal investigator (R.A.W.) at 2 pediatric allergy clinics, 1 private and 1 university-based, between 1993 and present. There were 1368 with food allergy, of whom 1073 were diagnosed with milk allergy. Two hundred thirteen patients with milk allergy were not included in the analysis because they were only seen once and the visit was before 2004, making the likelihood of at least 1 follow-up unlikely, and an additional 53 patients with only non–IgE-mediated disease were excluded. There were 807 patients with IgE-mediated CMA on whom data were collected. Data collected included sex, other food allergies, other atopic conditions, dietary history, family history of atopy, age at onset of symptoms, symptoms associated with exposure, age and symptoms with accidental exposures to milk, results of previous skin tests, cow's milk–specific IgE levels (cm-IgE), food challenge results, the reported outcomes of home milk introductions, and the outcome of other food allergies. Patients with milk allergy who are followed in our clinic typically have food-specific IgE levels checked annually using the Phadia CAP System FEIA (Phadia, Uppsala, Sweden). The diagnosis of CMA was made on the basis of a history of symptoms clearly associated with exposure to milk, a positive oral food challenge, and/or a clear improvement in eczema or other symptoms with milk avoidance. IgE-mediated disease was defined as having a skin prick test with a wheal diameter ≥3 mm and/or a cm-IgE ≥0.35 kU/L.

The diagnosis of asthma, eczema, or allergic rhinitis was made by the investigator. These data were collected on all patients from their initial visit and then updated from their last visit available. Allergy to other foods was defined as having had a clear symptomatic reaction to the food and/or having had a positive SPT or food-specific IgE level.

The primary outcome of interest was acquisition of oral tolerance. Oral milk challenges were routinely performed when, in the judgment of the principal investigator, the patient had at least a 50% chance of passing the challenge.⁹ Patients who were not likely to have acquired tolerance, on the basis of either a history of recent reactions or elevated cm-IgE levels, typically did not undergo oral challenges, but continued to be followed.

For this study, several definitions of oral tolerance were used to estimate a range of incidence rates for oral tolerance. The definitions of oral tolerance were based on criteria that ranged from most stringent to least stringent (Table I). During analysis of the data, each definition was applied to the entire population. Under the most stringent set of criteria (criteria 1), only patients who passed a formal milk challenge or successfully introduced milk or concentrated milk products at home were considered tolerant. All other patients were considered to have persistent milk allergy. To take into account the fact that some patients who had not undergone a milk challenge at home or in the clinic could have acquired tolerance, a second definition (criteria 2) of tolerance was also used. Under this second definition, patients who had a cm-IgE level <3 kU/L at their last clinic visit and had no history of clinical reactivity in the previous 12 months were considered to be tolerant, along with those who had passed home or office challenges. Therefore, patients with persistent CMA had either experienced symptoms after accidental exposure or a milk challenge in the past 12 months or had a cm-IgE level ≥3 kU/L. This second set of criteria for oral tolerance is based on a previous study in the same clinic population that found that 84% of children with cm-IgE ≥ 3kU/L exhibited clinical reactivity on milk challenge.⁹ For the third, and least stringent, set of criteria (criteria 3) for oral tolerance, patients who had a cm-IgE level <15 kU/L at their last clinic visit and had no history of clinical reactivity in the previous 12 months were considered to be tolerant, along with those who had passed home or office challenges. The cutoff point was set at 15 kU/L for this third definition of oral tolerance because this threshold has been found to have a 95% positive predictive value for symptomatic allergy in a previous study.¹⁰

Table I. Criteria for clinical tolerance

Statistical analysis 

All analyses were performed with StataSE 8.0 (College Station, Tex). cm-IgE levels were recorded as <0.35 kU/L, >100 kU/L, or, if between these values, the specific value was recorded. For purposes of statistical analysis, each result of <0.35 kU/L was assigned a value of ½ the lower limit, or 0.18 kU/L, and each value of >100 kU/L was assigned a value of 101 kU/L. The highest cm-IgE recorded for each patient was considered the peak level. Peak cm-IgE levels were stratified into 6 categories: <2 kU/L, 2 to 4.9, 5 to 9.9, 10 to 19.9, 20 to 49.9, and ≥50. The log-rank test was used to compare clinical characteristics in resolved versus persistent CMA. Kaplan-Meier curves were generated to depict the development of cow's milk tolerance over time. Data for all subjects were censored for Kaplan-Meier analysis. Cox proportional hazards regression was used to model relationships between cm-IgE levels and oral tolerance. To meet assumptions of parallel hazards, 3 strata of cm-IgE levels were used instead of the 6 strata (<5, 5-19.9, and 20+ kU/L). In addition, other predictors of the development of tolerance (such as other atopic disease) in bivariate analyses were included in the final multivariate model if they also met assumptions of parallel hazards. Nonparametric smoothing was used to depict trends in cm-IgE levels over time using the lowess command with a bandwidth of 0.8. Multiple cm-IgE levels from any given patient are depicted in either Fig 2, A, or B, depending on their final CMA status. These repeated measures are depicted graphically and the trend line plotted, but results of longitudinal analysis techniques accounting for repeated measures are not presented. A 2-tailed P value <.05 was considered statistically significant.

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• Fig 1. 

  CMA resolution over time. Kaplan-Meier survival curves for development of tolerance to cow's milk over time using 3 definitions for tolerance. The black line is the survival curve for criteria 1, the red line is the survival curve for criteria 2, and the blue line is the survival curve for criteria 3.

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• Fig 2. 

  Trend in cm-IgE levels over time by final CMA status. Scatter plots of all cm-IgE levels recorded, by age, to age 18 years (n = 2498). A, All values in the group with persistent CMA (n = 1651). B, All values in the group with resolved CMA (n = 847). Nonparametric smoothed curves show the trend in cm-IgE levels over time. These curves approximate the mean value at any given age.

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Results 

Study population 

Eight hundred seven patients with IgE-mediated CMA were included (Table II). There was a 2:1 male:female ratio, with age at the initial visit ranging from 1 month to 209 months (median, 13 months). The median duration of follow-up was 54 months, and the median number of visits was 5. Other atopic conditions were common (49% had asthma, 40% had allergic rhinitis, and 71% had eczema by the time of their most recent follow-up visit). Most patients (91%) had at least 1 other food allergy; egg and peanut were most common, followed by tree nuts, soy, wheat, shellfish, sesame, beef, and fish.

Table II. Patient characteristics

Characteristic	Number
Total number of patients	807
Age at initial visit, median (range)	13 mo (1-209)
Duration of follow-up, median (range)	54 mo (4-285)
Follow-up visits, median (range)	5 (1-25)
Sex, n (%)
Male	527 (65)
Female	280 (35)
Other atopic conditions, n (%)
Asthma	393 (49)
Allergic rhinitis	326 (40)
Eczema	572 (71)
Any food allergy besides cow's milk, n (%)	732 (91)
Egg	634 (79)
Peanut	592 (73)
Tree nut	412 (51)
Soy	331 (41)
Wheat	290 (36)
Other	457 (57)
Initial symptoms of CMA, n (%)
Skin	687 (85)
Gastrointestinal	369 (46)
Lower respiratory	115 (14)
Upper respiratory	47 (6)
Poor Growth	48 (6)
1 System affected	402 (50)
2 Systems affected	285 (35)
3+ Systems affected	94 (12)
cm-IgE levels (kU/L), median (IQR)
Initial (n = 804)	7.2 (1.8-31.9)
Peak (n = 804)	13.1 (2.8-59)
Resolved CMA, n (%)
Definition 1∗	120 (15)
Definition 2†	307 (38)
Definition 3‡	439 (54)

The most common presenting symptoms of milk allergy were skin-related reactions (85%), including urticaria, angioedema, eczema, or other unspecified rash. Gastrointestinal symptoms, including vomiting, diarrhea, bloody stools, and/or gastroesophageal reflux, occurred in 46%, lower respiratory symptoms (wheezing, cough, stridor, or difficulty breathing) occurred in 14%, upper respiratory symptoms (rhinitis or nasal congestion) occurred in 6%, and poor growth (weight <5th percentile for age) occurred in 6%. The median cm-IgE level at the initial visit was 7.2 kU/L (interquartile range [IQR], 1.8-31.9), and the median peak cm-IgE was 13.1 kU/L (IQR, 2.8-59).

Breast-feeding history was recorded for 80% of patients, and formula history was recorded for 81%. Of children whose formula history was recorded, about half (51%) received a cow's milk formula in infancy, 53% a soy formula, 40% an extensively hydrolyzed formula, and 15% an amino acid formula. Among those whose breast-feeding history was known, 86% were breast-fed, and the median breast-feeding duration was 8 months, with a range from 1 to 46 months.

CMA resolution 

The patients underwent a total of 289 milk challenges, 68 of which occurred at home and 221 of which occurred in the clinic. There was an overall pass rate of 57%. Sixty-seven percent of clinic challenges were passed, and 24% of home challenges were passed. Three sets of criteria were created to define the acquisition of milk tolerance. Each set of criteria was applied separately to the entire population (n = 807). When tolerance was defined using the most stringent criteria, as passing a milk challenge, we found that only 5% outgrew their allergy by age 4 years, 21% by age 8 years, 37% by age 12 years, and 55% by age 16 years. When tolerance was defined as passing a challenge or a cm-IgE <3 kU/L and no reaction in the past 12 months, the rates of resolution were 19% at age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. When we also considered children with a cm-IgE <15 kU/L and no reaction in the past 12 months to be tolerant, we found 26% tolerant by age 4 years, 56% by age 8 years, 77% by age 12 years, and 88% by 16 years (Table III; Fig 1).

Table III. Incidence of CMA resolution

Predictors of prognosis 

There were 2498 cm-IgE levels recorded. Patients with persistent allergy had higher cm-IgE levels in the first 2 years of life than those who developed tolerance (median 19.0 kU/L vs 1.8 kU/L; P < .001), and this difference was maintained up through age 18 years (Table IV). Trends in IgE levels also differed, with the group with persistent allergy exhibiting increasing levels over the first 3 to 4 years of life, followed by a plateau, and then a gradual decrease up to age 18 years, whereas the resolved group showed a decrease over the first 1 to 2 years of life, after which cm-IgE levels remained stable (Fig 2).

Table IV. cm-IgE levels in patients with persistent vs resolved CMA

We further examined the relationship between the acquisition of oral tolerance and cm-IgE levels by calculating incidence rates of oral tolerance over time for each of 6 peak cm-IgE categories (<2, 2-4.9, 5-9.9, 10-19.9, 20-49.9, and ≥50 kU/L; Fig 3). In general, the higher the peak cm-IgE was, the lower the likelihood of developing tolerance. Children with peak cm-IgE levels less than 5 kU/L had the best prognosis, children with peak cm-IgE levels from 5 to 19.9 kU/L had a somewhat worse prognosis, and children with peak cm-IgE levels of 20 kU/L or greater had the worst prognosis. For example, by 4 years, 57% with a peak cm-IgE <2 kU/L, 37% with a peak level of 2 to 4.9 kU/L, 20% with a peak level of 5 to 9.9 kU/L, 8% with a peak level of 10 to 19.9 kU/L, 3% with a peak level of 20 to 49.9 kU/L, and <1% with a peak level of 50 kU/L or greater had become tolerant. By 10 years, 87% with a peak cm-IgE <2 kU/L and 5% with a peak cm-IgE of 50 kU/L or greater had become tolerant.

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• Fig 3. 

  Relationship of peak cm-IgE level to resolution of IgE-mediated CMA over the period of the first 18 years of life. Patients were stratified by peak cm-IgE level, and survival curves for each stratum of peak cm-IgE level were plotted. The number of patients in each stratum was as follows: <2 kU/L (n = 162); 2-4.9 (n = 106); 5-9.9 (n = 85); 10-19.9 (n = 115); 20-49.9 (n = 107); 50+ (n = 229).

Other predictors of developing oral tolerance included asthma, allergic rhinitis, and a history of being fed formula (Table V). Eczema, other food allergies, sex, and breast-feeding were not predictive of acquisition of oral tolerance. After adjusting for asthma and rhinitis in a proportional hazards model, peak cm-IgE remained a strong predictor of acquiring tolerance. To meet assumptions of proportional risk required for this statistical model, peak cm-IgE was stratified into 3 categories (<5 kU/L, 5-19.9 kU/L, and >20 kU/L), and each step up in peak cm-IgE category was associated with a 68% reduction in the likelihood of acquiring oral tolerance (hazard ratio [95% CI], 0.32 [.27-.38]).

Table V. Predictors of oral tolerance to cow's milk

	Incidence of oral tolerance
	4 y	8 y	12 y	P value∗
Asthma
Yes	6%	15%	50%	<.0001
No	33%	65%	84%
Allergic rhinitis
Yes	6%	19%	55%	<.0001
No	30%	55%	72%
Eczema
Yes	20%	43%	67%	.57
No	16%	41%	61%
Other food allergy
Yes	18%	42%	64%	.07
No	29%	50%	67%
Breast-fed, ever (n = 646)
Yes	21%	45%	70%	.46
No	26%	48%	71%
Formula-fed, ever (n = 655)
Yes	18%	40%	63%	.005
No	35%	53%	89%
Sex
Male	16%	42%	63%	.14
Female	15%	44%	66%

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Discussion 

In this referral population of children with milk allergy, the prognosis for developing tolerance is worse than previously estimated. Using 3 sets of increasingly broad criteria to define tolerance, incidence rates of tolerance at 4 years ranged from <1% to 26% in our study, substantially lower than previously reported. Our findings stand in marked contrast to the study that is most often quoted, which found that 75% of children with IgE-mediated milk allergy were tolerant by the age of 3 years.⁴ One positive finding is that patients did continue to achieve tolerance well into adolescence. This contradicts previous data suggesting that CMA is unlikely to be lost if it has persisted into their school-age years⁵, ⁶ and clearly indicates that there is no age at which outgrowing CMA is impossible. In addition, we found that the peak cm-IgE level was an important predictor of acquisition of oral tolerance and could be used to provide important information for patients and their families regarding their long-term prognosis of CMA.

Defining tolerance as passing a challenge or having a cm-IgE <3 kU/L and no reactions over the previous year, we found rates of tolerance of 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by age 16 years. This definition of tolerance is arguably the most accurate of the 3 definitions used in this study, and the incidence rates using this definition are most likely closest to this population's true incidence of tolerance. Although using the most liberal tolerance definition that relies on a cm-IgE cutoff of 15 kU/L will minimize the number of children falsely classified as persistently allergic, it almost certainly overestimates the number developing tolerance, because a majority of the children with cm-IgE levels between 3 and 15 kU/L are still allergic.⁹, ¹⁰ On the other hand, the most stringent criteria for tolerance, passing a milk challenge, will underestimate the number of children developing tolerance because many children who have not passed a milk challenge may actually be tolerant. No matter which definition of tolerance is used, it is clear that the prognosis for outgrowing milk allergy in this population is quite poor.

It is also important to recognize, however, that even our criteria 2 definition of tolerance may actually underestimate or overestimate the true rate of outgrowing milk allergy. For example, there may be a lower rate of resolution in those lost to follow-up than in those still followed, because it is possible that many children with persistently high cm-IgE levels would stop coming for regular evaluations. A second factor that could lead to an overestimation of the rate of resolution is that many children with a cm-IgE <3 are certainly still allergic.⁹ In fact, in the study by Perry et al,⁹ 58% of children with cm-IgE between 0.35 and 3 kU/L reacted at a formal food challenge.

There are also several issues with this study that could lead to an underestimation of the true rate of resolution of CMA. Children lost to follow-up might have actually had a higher rate of resolution than those still followed at any given age. These children may have tolerated milk in unsupervised, home-administered challenges, eliminating the need for follow-up with us. Another factor could be that children we assumed to still have milk allergy had actually outgrown their allergy but had never been challenged. Most importantly, in comparing our data to the general population of CMA, it is likely that these patients who had been referred to a tertiary care center represent the patients with most severe allergy who logically might have the poorest prognosis.

There were several clinical and laboratory features we found to be significant in predicting the resolution of CMA. cm-IgE level was by far the most significant, and probably the most clinically useful. By using each patient's highest cm-IgE, we found that a higher peak was significantly associated with a reduced chance of developing tolerance. We realize that peak cm-IgE can be an impractical measure because it cannot be applied with the same confidence to younger children. However, higher cm-IgE levels were associated with poorer prognosis at all ages and, even in younger children, the peak cm-IgE categories can be applied as a best case scenario in counseling families about prognosis. These data are in agreement with several previous studies that support this association between increasing cm-IgE level and worse prognosis.⁴, ⁵, ¹⁰, ¹¹

The presence of both asthma and allergic rhinitis were also associated with a lower likelihood of developing tolerance. These factors remained significant even in the multivariate analysis when controlling for peak cm-IgE level. In previous studies, markers of atopy or IgE-mediated disease—for example, the presence of urticaria or IgE-sensitization to certain foods such as egg—have been associated with worse prognosis.⁶ However, it is important to note that asthma and rhinitis may appear to be associated with a poorer prognosis because children who are followed longer are more likely to carry these diagnoses as well as more likely to have retained milk allergy. In this population, the presence of other food allergies was also associated with a worse prognosis, although this association was not statistically significant. In addition, a worse prognosis was observed among patients who had ever received formula. However, this association may be biased because these data were missing for 20% of the population, and these findings should be confirmed in future studies.

In previous studies, rates of development of tolerance for IgE-mediated or immediate-onset–type allergy have varied: 76% by age 3 years,⁴ 74% by age 5 years,⁶ and 22% by age 18 months to 13 years.⁵ The wide differences in these rates are likely related most to the population studied, with the study by Host and Halken⁴ including an unselected group of children with milk allergy, and the study by Hill et al⁵ focusing on a referral population more similar to ours. Most previous studies did not report details on cm-IgE levels, but from the information available, it appears that our population has higher levels on average, with peak cm-IgE levels exceeding 2 kU/L in 80% of the population, and exceeding 50 kU/L in 30%. Other markers of the high degree of atopy in our population include 91% having at least 1 other food allergy, 49% with asthma, 40% with allergic rhinitis, and 71% with eczema, although these rates of asthma, eczema, and allergic rhinitis are consistent with those found in previous studies.⁶, ¹⁰, ¹²

Although the poor prognosis demonstrated in this study may be a result of this highly atopic referral population, it may also be that the character of CMA has changed over time, and that CMA may now truly be a more persistent disease. In fact, many of the previous studies in this area are now nearly 2 decades old. In our clinic population, we continue to see an increasing number of children whose milk allergy persists into school age and even into adolescence. We speculate that the factors driving the rising prevalence of food allergy and other atopic conditions may also be contributing to the changing character of CMA, and potentially other food allergies.

In conclusion, we have found in the largest cohort of children with milk allergy ever reported that the prognosis for the resolution of IgE-mediated CMA appears significantly worse than what has been previously reported. Sensitivity persists into school age and beyond in the majority of our patients. cm-IgE is highly predictive of outcome and should be used in counseling patients on prognosis. Prospective studies are needed to confirm this potential increasing persistence of CMA.

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We thank Elizabeth Johnson, MS, for her review of the statistical analyses.

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References 

1. Bock SA. Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life. Pediatrics. 1987;79:683–688
   • View In Article
   • MEDLINE
2. Saarinen KM, Juntunen-Backman K, Jarvenpaa AL, Kuitunen P, Lope L, Renlund M, et al. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: a prospective study of 6209 infants. J Allergy Clin Immunol. 1999;104:457–461
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (43 KB)
   • CrossRef
3. 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
   • View In Article
   • MEDLINE
   • CrossRef
4. 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;45:587–596
   • View In Article
   • MEDLINE
   • CrossRef
5. Hill DJ, Firer MA, Ball G, Hosking CS. Natural history of cows' milk allergy in children: immunological outcome over 2 years. Clin Exp Allergy. 1993;23:124–131
   • View In Article
   • MEDLINE
   • CrossRef
6. 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
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (187 KB)
   • CrossRef
7. Bishop JM, Hill DJ, Hosking CS. Natural history of cow milk allergy: clinical outcome. J Pediatr. 1990;116:862–867
   • View In Article
   • Abstract
   • Full-Text PDF (506 KB)
   • CrossRef
8. Hill DJ, Davidson GP, Cameron DJ, Barnes GL. The spectrum of cow's milk allergy in childhood. Clinical, gastroenterological and immunological studies. Acta Paediatr Scand. 1979;68:847–852
   • View In Article
   • MEDLINE
9. Perry TT, Matsui EC, Kay Conover-Walker M, Wood RA. The relationship of allergen-specific IgE levels and oral food challenge outcome. J Allergy Clin Immunol. 2004;114:144–149
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (107 KB)
   • CrossRef
10. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol. 2001;107:891–896
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (98 KB)
    • CrossRef
11. Shek LP, Soderstrom L, Ahlstedt S, Beyer K, Sampson HA. Determination of food specific IgE levels over time can predict the development of tolerance in cow's milk and hen's egg allergy. J Allergy Clin Immunol. 2004;114:387–391
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (351 KB)
    • CrossRef
12. Vanto T, Helppila S, Juntunen-Backman K, Kalimo K, Klemola T, Korpela R, et al. Prediction of the development of tolerance to milk in children with cow's milk hypersensitivity. J Pediatr. 2004;144:218–222
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (200 KB)
    • CrossRef