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CHaPtEr 95 Assessment of Human Allergic Diseases 1287
TABLE 95.1 Grading System for Puncture Oral Food Challenge Tests
and Intradermal Skin testing Using
Histamine as a reference a Oral food challenges remain the definitive test for food hyper-
sensitivity, since in vitro and other in vivo diagnostic methods
32
Erythema Size suffer from suboptimal diagnostic specificity. They are performed
Grade or Class Wheal Size (mm) (mm) to establish an accurate diagnosis of food allergy or when skin
Skin testing Grading System tests are not possible because of atopic dermatitis or allergic GI
0 No discernible wheal disease or to assess the development of tolerance to a food. Passing
1+ ≤3 histamine wheal a direct food challenge ideally permits reintroduction of the
2+ >3 histamine and <13 food into the patient’s diet. Food-induced GI reactions (e.g.,
histamine wheal nausea, colic, vomiting, and diarrhea) can occur minutes to hours
3+ = size of histamine wheal after the consumption of food allergens by a sensitized indi-
± 1 mm 33
4+ >13 histamine wheal and vidual. Commonly eaten foods that contain potent allergens
<23 histamine wheal include cow milk (caseins, β-lactoglobulin, α-lactalbumin,
5+ >23 histamine wheal lactoferrin, and bovine serum albumin), chicken egg white
(ovalbumin, ovomucoid, ovotransferrin), cereal grains (wheat,
alternative Skin test Grading System for Intradermal rye, barley, oats), legumes (peanut, soybean, white bean), and
Skin testing Only Involving Interpretation of Wheal fish and seafood (shrimp, crab, lobster, oyster).
and Erythema responses † Diagnosis of a food allergy begins with a medical history,
0 <5 <5 which includes an assessment of diet diaries and elimination
+/− 5–10 5–10
1+ 5–10 11–20 diets, as necessary. Skin tests and serological tests for IgE antibody
2+ 5–10 21–30 to extracted food allergens and open food challenges with fresh
3+ 10–15 31–40 and cooked foods can be used to confirm sensitization to suspected
4+ >15 with pseudopods 41–50 foods. No evidence is available to indicate that food-specific IgG
34
or IgG4 antibody levels have any diagnostic value. The double-
a Prick/puncture histamine (3–10 mg/mL); ID histamine (100 µg/mL).
(Modified from Norman PS. Skin testing. In: Middleton E, Ellis EF, Reed CE, editors. blind placebo-controlled food challenge (DBPCFC) is considered
32
Allergy: principles and practice. 2nd ed. St. Louis: CV Mosby; 1982, with permission the definitive diagnostic test for food allergy. The open food
from Elsevier.) challenge has its utility in clinical practice as a first-line challenge
procedure as it is easier than DBPCFCs. Moreover, they are
especially useful when the probability of a negative challenge is
high, since a negative open challenge result can obviate the need
60 for a DBPCFC and it reduces anxiety and thus reduces the risk
n = 304 duplicate skin tests
55 Norman Grading Scheme of bias in infants and young adults. An extensive discussion of
50 open challenges, DBPCFCs, and variables that influence their
32,33
outcome is presented elsewhere.
In 2001, prospectively collected sera from 100 children and
45 4+ adolescents who had been previously evaluated by a skin test
Intradermal erythema (mm) 35 3+ (Thermo Fisher Scientific/Phadia, Uppsala, Sweden) for food-
40
and DBPCFC were analyzed in the ImmunoCAP autoanalyzer
35
specific IgE antibody. A diagnostic level of IgE antibody specific
30
for egg (7 kU/L), milk (17 kU/L), peanut (14 kU/L), and fish
(20 kU/L) was identified, above which clinical reactivity could
25
2+
be predicted with more than 95% certainty. The study concluded
20
with the ImmunoCAP system, a subset of children who were
15 1+ that by measuring the concentration of food-specific IgE antibody
highly likely (>95% probability) to experience a clinical reaction
10
+/– to egg, milk, peanut, or fish could be identified. Importantly, this
5 study and others subsequently have shown that judicious use
0 +/– 1+ 2+ 3+ 4+ of quantitative serological measurements for food-specific IgE
0 antibody as measured by ImmunoCAP may be able to eliminate
0 2 4 6 8 10 12 14 16 18 20 the need for time-consuming DBPCFCs in a significant number
Intradermal wheal (mm) of children who are suspected of having food allergy. The relation-
FIG 95.3 Correlation plot of the mean wheal (x-axis) and erythema ship between IgE antichicken egg, cow’s milk, and peanut as
(y-axis) in millimeters for the mean of 304 duplicate intradermal measured in the ImmunoCAP and Immulite (Siemens Healthcare
skin tests to dust mite (Dermatophagoides pteronyssinus) Diagnostics, Tarrytown, NY, USA) has been investigated in an
obtained in a population of individuals with sensitivity to dust- effort to extend published ImmunoCAP predictive values to
mites. The relationship is highly correlated (r = 0.82; p < 0.001) reported Immulite measurements of IgE antibody to these foods. 36
in grades 0 to 3+, indicating that either can be used to judge
the degree of intradermal skin sensitivity. In highly allergic individu- IN VITRO TESTING
als (>35 mm erythema), however, the slope declines dramatically,
indicating that wheal size may be more discriminating than Clinical immunology laboratories worldwide offer serological
erythema. tests that are useful in the diagnosis and management of human

