Cow’s milk allergy
Diagnostic approach
When first facing a child with a clinical picture suspicious of
CMA, the initial approach is based on a good clinical history
. The three first issues may orientate the physician
towards a higher or lower probability of allergy, but their
usefulness is very limited. The two last issues are much more
informative about the suspect mechanism of reaction.
It is important to try to identify if the patient has an IgE or
non-IgE reaction. The allergologic tests try to identify if there
is specific IgE against CM proteins5. This is accomplished
with the use of skin prick tests, and the quantification of
specific IgE in serum. Both tests have a good specificity but
a more modest sensitivity (Table 7.3). As some patients have
discordant responses in the tests, performing both gives the
best yield, but even so some patients will be misclassified as
non-IgE responders. The positivity of any of the tests proves
that there is a sensitization to CM; the relationship of
sensitization with clinical symptoms must be clarified
through the interpretation of the clinical history or
performing challenge tests. Sensitization to other allergens
must be assessed: it is not surprising to find out that the
patient is sensitized to other allergens, especially hen’s eggs.
The gold standard for the diagnosis of food allergy is the
double-blind placebo-controlled challenge test. This is often
required for investigational studies, but in the routine clinical
practice an open challenge is acceptable (Table 7.4). The
protocol must be adapted to every child, taking into account
the clinical history, previous reactions, and results of tests
(Table 7.5). More caution must be taken for those with posi -
tive IgE tests, while those with negative tests usually tolerate
greater amounts, and the protocol can be performed more
rapidly. Several days must elapse until a negative response can
be ascertained. The test is easily interpreted as positive when
immediately evident typical reactions appear, and easily
interpreted as negative when there is a long follow-up timewithout symptoms. However, between these extremes are
found a range of responses that are difficult to interpret. Thus,
repeated challenges are sometimes needed until a clear
interpretation can be reached. The positive response to the
challenge test permits a diagnosis of allergy, but it cannot
identify which mechanism is involved. The allergologic
evaluation is com plete when IgE tests and the challenge are
performed
Treatment
Treatment is based on a diet free of CM proteins. Breastfeeding
must be encouraged. The lactating mother has to
avoid CM proteins. If the mother has a varied diet, there is
no risk of nutritional deficits, except for calcium. If breastfeeding
is not possible, an alternative feeding regimen must
be chosen. The two approaches are based on the
modification of native CM proteins and on the use of
proteins of another, not related to CM, source6, 7.
To modify the CM proteins three steps are commonly
used. The action of heat and hydrolysis pretends to suppress
or lower the allergenicity of proteins through changes in
their structure. Ultrafiltration is directed at eliminating
enzymatic products used in the process of hydrolysis andalso eliminating peptides of large molecular weight.
When proteins are heated, their tertiary structure is
damaged. The chemical bonds are ‘broken’ and the protein
is unfolded. This separates the portions which form the
conformational epitopes, which lose their allergenic ability,
and are unable to bind the specific IgE. Enzymes are able to
break the bonds between the amino and the acid terminals
of amino acids and split the proteins into smaller fragments.
These resulting fragments, depending on their size, can hold
one to several dozen amino acids. The breakage of the
protein can result in fragments that keep whole undamaged
epitopes, able to bind to the specific IgE. A fragment can be
large enough to keep two or more epitopes, able to bindsimultaneously to molecules of IgE and trigger the allergic
reaction. This is called residual allergenicity, and is more
probable when the molecular weight of the fragments is
larger8. In elemental formulas, in which there are no
peptides but only amino acids, the ability to bind IgE is nil.
The first choice for IgE-mediated allergy to CM seems to
be soy formula, due to the absence of allergenicity, and also
the lower price. Some physicians are reluctant to use soy
formula in children under 6 months of age. When choosing
an extensively hydrolyzed formula, some requirements must
be met and others are advisable. All peptides must have a
molecular weight under 5,000 Da, and the formula must
have been tested and prove to have negative results in >90%
of children with CMA. The maximal admitted weight of the
peptides is 5 kD, but if the distribution of molecular weight
is provided the chances that residual allergenicity is present
can be estimated: the higher the percentage of very small
peptides, the lower the probability of residual allergenicity
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