Page 654 - Clinical Immunology_ Principles and Practice ( PDFDrive )

628 ParT FIVE Allergic Diseases

Natural History Allergy persistence has also been associated with the rate of
The majority of food allergies are outgrown. Allergies to peanut, change of food-specific IgE levels or SPT wheal sizes. In clinical
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tree nuts, fish, and shellfish are more likely to persist. Clinical practice, food-specific IgE levels are typically checked yearly
characteristics and laboratory measures may help predict which except in patients whose specific IgE levels remain high and
food allergies will be outgrown and which are more likely to be unchanged over several years.
lifelong.
DIAGNOSIS
CLINICaL PEarLS
Important Diagnostic Considerations The diagnosis of food allergy begins with obtaining a detailed
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medical history. Food-induced allergic reactions result in
The patient’s history should support a diagnosis of immunoglobulin E reproducible characteristic symptoms, as described above. Vali-
(IgE) –mediated food allergy before performing either serum-specific dated testing modalities are only available for IgE-mediated food
IgE testing or the skin prick test. allergies and celiac disease. If the clinical history does not support
95% predictive probability cutoffs have been established for only a few either diagnosis, then food allergy serum or skin testing should
foods, including cow’s milk, hen’s egg, and peanut. not be done, since there is a risk of finding sensitization to
Even with negative specific IgE serum testing or skin testing, the patient
could be allergic if he or she has a convincing history. In this case a allergens which are not clinically relevant and multiple studies
physician-supervised oral food challenge may be required to confirm have shown the dangers of unnecessary dietary avoidance. When
the presence or absence of an IgE-mediated food allergy. the clinical history does support a diagnosis of food allergy, this
Testing for food allergies should be limited to the food(s) in question, can be confirmed by SPTs and detection of specific IgE in serum.
since positive IgE tests are not always clinically relevant. Unnecessary SPTs to food allergens can be performed in the office setting
avoidance of foods may lead to nutritional deficiencies. and are both safe and effective, with results being available within
minutes. A positive result of the SPT reflects the presence of
Cow’s milk is typically one of the first foods introduced to specific IgE bound to the surface of cutaneous mast cells, but
infants in the form of infant formula: it is present in diets across as with serum IgE testing, a positive test result does not always
cultural groups and is one of the most common allergens globally. indicate clinical reactivity. A positive test result is generally
Fortunately, cow’s milk allergy is typically outgrown without interpreted as 3 mm larger than the negative SPT control, and
intervention. Studies of natural resolution vary but about 50% the larger the SPT mean wheal diameter, the more likely it is
of children with milk allergy develop tolerance between 5 and indicative of a clinically relevant response. Negative SPT results
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10 years of age. High levels of milk-specific IgE generally indicate have been associated with a high negative predictive value and
a higher likelihood of persistent disease, but as many as 60% of may lead the physician either to offer an observed challenge or
children whose milk-specific IgE level peaks at over 50 kU/L will to counsel the patient on dietary reintroduction, depending on
achieve natural tolerance by age 18 years. Up to 75% of children the clinical history and circumstances.
with reactions to uncooked milk can tolerate baked milk products. Serum-specific IgE testing is useful in providing an objective
Consumption of heated milk products has been associated with measure of food-specific IgE antibody, especially if the patient
accelerated acquisition of tolerance. 14 cannot stop antihistamine therapy or has extensive skin disease
Hen’s egg allergy is another common food allergen across making it impossible to perform the SPT, and may be helpful
cultural groups. Most of the allergenic proteins in hen’s egg are in counseling patients on the natural history of their food allergy.
in the egg white. Allergy typically develops in the first year of Predictive values have been established for a limited number of
life, while in some children, especially those with atopic dermatitis, foods. Higher specific IgE levels are more likely to be associated
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it may develop before 4 months of age. Similar to cow’s milk with clinical reactivity, but the predictive value of specific IgE
allergy, egg allergy usually resolves during childhood without levels varies across patient populations and is affected by such
intervention. Roughly 50% of individuals with egg allergy in factors as the patient’s age, ethnicity, and time since last ingestion
infancy develop natural tolerance between 6 and 9 years of age. of allergen. Specific IgE levels may also help physicians decide
Baked egg is tolerated by approximately 70% of children with when an oral food challenge is or is not appropriate.
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egg allergy. Individuals who can tolerate baked egg are likely The component-resolved diagnostic (CRD) test uses allergenic
to develop tolerance to lightly cooked egg sooner compared with proteins derived from recombinant DNA technology or purifica-
individuals unable to tolerate baked egg. 16 tion from natural sources to identify the patient’s specific IgE
Although the majority of individuals allergic to peanut will reactivity to individual allergenic proteins rather than to the
remain reactive throughout life, approximately 20% of individuals whole allergen. Diagnostic accuracy can be enhanced in specific
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with peanut allergy may develop natural tolerance. Favorable circumstances (e.g., for peanut and hazelnut). However, CRD
prognostic factors include low levels of peanut-specific IgE is not routinely used for diagnosis and has not been shown to
antibodies in the first 2 years of life and decreasing levels of IgE provide significant additional clinical information for most
sensitization by 3 years. Those with peanut-specific IgE ≥3 kU/L allergens. CRD for peanut provides additional diagnostic informa-
and skin prick test (SPT) wheal diameter >6 mm before 2 years tion that is helpful to the clinician, but standardized decision-
of age are more likely to have persistent peanut allergy. 17 making cutoffs have not yet been established.
Allergy persistence, regardless of the food allergen, has been The basophil activation test (BAT) uses flow cytometry to
associated with the following factors: (i) earlier age at diagnosis; detect upregulation of cell-surface molecules, such as CD63 and
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(ii) concomitant presence of other allergic diseases (e.g., allergic CD203c, after stimulation with allergen. BAT has been reported
rhinitis, asthma, and eczema); (iii) severity of those allergic to be superior to the SPT, the CRD test, and the whole-allergen-
diseases; (iv) symptom severity after ingestion; and (v) lower specific IgE test for diagnosis of peanut allergy; however, testing
threshold dose required to elicit a reaction. The higher the food- has not been standardized. Further research is needed to standard-
specific IgE level, the more likely it is that the allergy will persist. ize the BAT and validate results with various food allergens.