Nowadays, it is reported that 0.6–2.5% of preschoolers, 0.3% of
older children and teens and less than 0.5% of adults suffer from
CMA [13]. The prevalence of CMA is increasing which may be explained
by a decrease in breast feeding and an increased feeding
with cow’s milk-based formulas [15].
Several factors which may increase the risk for developing CMA
are described such as genetic predisposition for allergy (i.e., atopy),
early ingestion of small amounts of CM and also factors related to
the intestinal microbiome [16].
Interestingly, the majority of CM allergic infants outgrow their
CMA. One study reports that 45–50% grow out at 1 year, 60–75%
at 2 years, and 85–90% at 3 years of age [17]. Although another
study did not confirm exactly these numbers and the time course
for the development of tolerance, it is reported that CMA resolved
in 19% of the children by 4 years of age, in 42% by 8 years of age, in
64% by 12 years of age and in 79% by 16 years of age [18]. The
mechanisms underlying the development of clinical tolerance are
not fully understood. Several factors may be involved in the development
of tolerance. They may include a decline of IgE antibodies
due to avoidance, the development of blocking IgG antibodies due
to regular intake of CM and/or the presence of IgE antibodies
against mainly conformational epitopes and not against sequential
epitopes [19–21]. One study has shown that reactions to less than
10 ml of milk during an oral food challenge and large wheal size
reactions in SPT predict a higher risk for persistence [22]. Several
other studies have confirmed that low levels of milk-specific IgE
and small wheals during SPTs are good indicators for resolution
[23–25]. A recent observational study considered the severity of
atopic dermatitis (AD) for the natural course of milk allergy and
came up with a web-based calculator for the prognosis of milk allergy
for infants younger than 15 months that is based on milkspecific
IgE levels, SPT wheal sizes and severity of AD [26].