It is now known that IgE is produced
by plasma cells, predominantly in lymphoid tissue adjacent to
the respiratory and gastrointestinal tracts. Adult levels of IgE
are reached by the age of 10 - 15 years, and are present in a
non-linear distribution in the population, with seasonal variation
of two to four fold throughout the year.
Elevated Total IgE is observed in only 30% of patients with allergic rhinitis, 60% of patients with asthma and in 80 - 90% of patients with significant atopic eczema. It can also be elevated in 10 - 20% of patients with non-allergic rhinitis or non-allergic asthma, or other conditions such as allergic bronchopulmonary aspergillosis, some forms of immunodeficiency, neoplasia such as lymphoma, and parasitic disease.
The measurement of Total IgE is the sum total of multiple individual allergen specific IgE levels. Total IgE therefore has a poor positive or negative predictive value for the presence or absence of atopic disease. A more useful test is the measurement of allergen specific IgE by either skin testing or RAST testing.
RAST stands for Radioallergosorbent
test. Allergen specific IgE is measured from blood samples. In
general, skin testing is more sensitive and specific, and has
the advantage of lower cost and almost immediate results. The
main indication for RAST testing is when skin testing is either
impossible or unreliable. Examples include dermographism (where
the patient will weal and flare with any skin trauma regardless
of allergy), severe dermatitis (skin testing needs to be performed
on relatively intact skin), lack of cooperation (eg: young children)
or where access to skin testing facilities is difficult or impossible.
False positives and negatives do occur, the former particularly
in patients with atopic eczema.
Medicare currently rebates patients for only 4 tests at a time. Rational and cost-effective use of RAST testing for aero allergen sensitivity therefore uses allergen mixes such as grass or weed mixes, dust mite and mold mixes. In the absence of a clear history of food-allergic problems, RASTs for food mixes often provides confusing or misleading information.
The technical aspects of RAST testing are quite interesting. Allergen
is first bound to the surface of "discs", most commonly
made from nitrocellulose. A disc is then incubated with the human
test serum. If allergen-specific IgE is present, it will bind
to the allergen and thus the disc. Excess serum is then washed
away, and the disc incubated with an a radiolabelled ANTI-IgE
antibody, then washed as before. The radioactivity of the disc
is measured and compared to standards. If the disc is radioactive,
then the radiolabelled antibody must be bound, which means that
the original serum must have contained IgE against the allergen
bound to the disc. The higher the radioactivity, the greater the
amount of IgE in the original sample. Unfortunately, RAST testing
suffers from problems of poor sensitivity and specificity for
predicting the presence or absence of allergic disease. In general,
skin testing is more sensitive.
The presence of allergen-specific IgE
may be evaluated by skin testing, which results in the introduction
of small amounts of protein into the dermis by pricking the skin
through a drop of allergen extract. If the patient is allergic,
this allergen will cross link to IgE molecules on the surface
of cutaneous mast cells, resulting in histamine release, and the
observation of a weal and flare after a period of 15 - 30 minutes.
This is why antihistamines can inhibit the results of skin testing.
It should be remembered, however, that not all patients with symptoms
of asthma, respiratory disease or eczema are atopic. Approximately
20% of patients seen with asthma, eczema or symptoms suggestive
of allergic rhinitis have no evidence of atopic disease whatsoever.
The implications of such findings are that allergen avoidance
measures, and desensitization are not warranted.
Indications
Skin testing is indicated for the evaluation of patients with
suspected atopic disease such as allergic rhinitis, asthma, atopic
eczema, or allergic or anaphylactic reactions to either foods,
venoms or drugs. Correct interpretation of results will allow
for appropriate advice to be given regarding allergen avoidance
if possible, as well as the identification of clinically relevant
allergens for desensitization if that is indicated.
Procedure
Skin testing is most commonly performed on the forearm, although
the back is sometimes used, although is more sensitive than the
arm. The arm is first cleansed with alcohol (several times if
patients have used moisturizers recently; otherwise allergen extracts
run). The arm is then marked with non-indelible ink, and drops
of a negative control, positive control (histamine) or allergen
extract are placed close to the marks. The skin is then pricked
with a small lancet without drawing blood. The lancet is wiped
with an alcohol swab between each allergen, thereby removing essentially
all residual allergen from the previous test. At the end of the
procedure, the arm is dabbed lightly with a tissue to remove excess
fluid. The test is read between 15 and 30 minutes later and the
size of the weal and flare is compared to that of the positive
and negative controls. A negative control checks for evidence
of dermographism, whereas the positive control serves as a check
for patients who have inadvertently ingested antihistamines (such
as in some cough medicines) or other drugs with antihistamine
activity (see below).
Alternative methods such as scratch testing have generally abandon because of poor reproducibility, and increased discomfort to the patient. Intradermal skin testing is practiced in some countries, but in general whilst more sensitive, is more likely to lead to false positives which are not clinically relevant. Intradermal testing is most commonly used for evaluation of patients with potential antibiotic sensitivity or insect venom allergy.
False negative skin tests
A number of factors may influence the interpretation and performance
of skin testing. It is a reliable test of presence of allergen
specific IgE in patients of all ages, although infants tend to
give smaller weals and have a higher incidence of false negatives.
Positive reactions therefore need to be compared to the size of
the positive control. An increased incidence of anergy (falsely
negative skin test) is seen in elderly patients, in patients with
malignancy or on haemodialysis, and occasionally in patients with
peripheral neuropathy such as diabetes.
Since false negatives may be also seen in patients who have suffered from a recent episode of anaphylaxis (presumably due to exhaustion of mast cell mediators), it is usually recommended that patients requiring evaluation for anaphylaxis should have their investigations deferred for 4 - 6 weeks after the event. A number of medications can also influence the results, antihistamines in particularly. Phenothiazines as well as tricyclic anti-depressants have antihistamine activity, and therefore need to be avoided for 1 - 2 weeks prior to skin testing. Most conventional antihistamines should be ceased 5 - 7 days before evaluation. The exception is Hismanal (Astemizole), which can give false negative reactions from 4 - 6 weeks after cessation. Ranitidine has been reported to inhibit skin testing, although in general this is rarely observed. Long term oral steroids at a dose greater than 25 mgs can inhibit skin testing, as can potent topical steroids.
False positive skin tests
False positives are observed from time to time as well, particularly
when skin testing with food derived extracts, or when testing
patients with atopic eczema. Skin testing therefore always needs
to be evaluated in the context of a clinical history. Random skin
testing with food derived extracts or with aero allergens will
give misleading results unless interpreted appropriately. The
evaluation of patients with non-specific and non-allergic symptoms
by skin testing with a battery of common food derived allergens
almost inevitably leads to misleading results and inappropriate
therapy.
Eosinophils are specialized white cells
that are designed to kill worms and parasites. They also can cause
inflammation in the tissues in allergy. High levels are most commonly
observed in blood samples from people with Hay fever, asthma and
atopic eczema.
