In-Vivo Diagnostic tests of IgE Dependent Reactions
(Scratch, Prick or Puncture) and Intracutaneous In-Vivo Diagnostic Skin Tests
testing to drugs is generally unreliable, except for the penicillin’s and
macromolecular agents, such as foreign antisera, hormone (e.g., insulin),
enzymes (e.g., L-Asparaginase, streptokinase, Chymopapain), and egg-containing
allowing that SET is a valid method for obtaining semi-quantitative information
about a person’s sensitivity and for determining a safe beginning dose for
immunotherapy, the American College of Physicians (ACP) advises that the primary
use of SET is to identify hymenoptera venom (yellow jacket, honey bee, hornet,
wasp, fire ant) sensitivity and to determine the safe starting dose for venom
provocation or challenge testing, a suspected allergen in a clinically relevant
exposure is administered in an attempt to reproduce symptoms. Challenge tests
have been broadly applied under research conditions for many years, but there
are some clinical situations in which they can be useful for confirmation of
clinical disease. Considerable experience with these methods is required for
proper interpretation and analysis.
testing is an accepted method of differentiating allergic contact dermatitis and
irritant contact dermatitis. Twenty to thirty antigens are used in the usual
routine screening panel of patch tests. The patches are removed after 48 hours
and an initial reading is taken 1 hour later. The final reading is taken a
further 48 hours later.
chemicals or medications (e.g., lomefloxacin, Ofloxacin, ciprofloxacin, and
Norfloxacin) produce an allergic reaction only when exposed to light (usually
ultraviolet type A, UVA). Patients who are over-sensitive to light and those
with a rash that appears on parts of the body normally exposed to light but that
does not appear in areas shielded from the light should have a photo-patch test.
With photo patch testing, two identical sets of allergens are placed onto the
patient`s back on day-1. One of the sets is exposed to UVA light, and the sites
are then examined as described above for patch testing. A positive photo patch
test is recorded when an allergic reaction appears only on the light-exposed
testing is skin irradiation with a specific range of ultraviolet light. Photo
tests are performed for the evaluation of photosensitivity disorders.
challenge testing is an accepted method of diagnosing exercise induced
bronchospasm in asthmatic and non-asthmatic patients.
(oral) challenge testing is an accepted method of diagnosing allergies to food,
drug or other substances (i.e., Metabisulfite). Drug challenge testing should
not be confused with cutaneous or sublingual provocation and neutralization
therapy, which is a non-covered modality.
Conjunctival Provocative or Challenge Tests
conjunctival provocative or challenge tests employed for the diagnosis of either
food or inhalant allergies, involve the direct administration of the allergen to
the mucosa. The patient is then observed for signs and symptoms and the presence
of symptoms is interpreted as a positive indication of allergies. These tests
are time consuming; only one antigen may be administered per session, a
non-standardized quantity of allergen is administered, and they have the
potential of inducing severe symptoms. There is currently no standard technique
for nasal or conjunctival challenge tests that can be applied to clinical
or P-K Testing
Prausnitz-Kustner testing has been used in patients with Dermatographia or
generalized skin eruptions. A control site on the forearm of a non-allergic
recipient is selected. This site is injected intradermally with allergy serum
from a patient on whom direct skin tests cannot be done. Allergenic extract is
later injected intradermally into the initial injection site of the recipient
and observed for the development of a wheal and flare. Because of the risk of
transmitting hepatitis or AIDS, this test is contraindicated.
Provocation-Neutralization (Rinkel Test)
Provocation-neutralization is a method of testing for the presence of food,
inhalant or environmental chemical allergies by exposing the individual to test
doses of these substances intradermally, subcutaneously, or sublingually with
the purpose of either producing or preventing subjective symptoms.
Both the ACP and
the American Academy of Allergy and Immunology (AAAI) consider
provocation-neutralization therapy an unproven modality. In a Training Program
Directors` Committee Report on Controversial Practices published by the AAAI,
provocation-neutralization testing and neutralization therapy are listed as
unproven. The AMA`s Council on Scientific Affairs, based on the reports in the
peer-reviewed scientific literature, stated that there are no well-controlled
studies establishing a clear mechanism or cause for multiple chemical
sensitivity syndromes. More importantly, there are no well-controlled studies
that have demonstrated either diagnostic or therapeutic value for
Provocation-neutralization must not be confused with the recognized forms of
target-organ challenge testing (bronchial, ingestion, patch testing), which are
(Allergen Specific IgE Testing)
allergens, in-vitro allergen - specific immunoassays detect IgE antibody in the
serum of most but not all patients who respond clinically to those allergens.
The precise sensitivity of these immunoassays compared with skin tests has been
reported to range from < 50% to > 90% with the average being about 70 to 75%.
In a joint statement, the American Academy of Allergy, Asthma and Immunology,
the American College of Allergy, Asthma, and Immunology, and the Joint Council
of allergy, Asthma and Immunology (the Joint Council) concluded that allergen
skin testing is the most sensitive method for detecting specific IgE antibody.
Therefore, skin tests are presently the preferred tests for the diagnosis of
IgE-mediated sensitivity. Because of the inherent pitfalls in the sensitivity
and reliability of IgE specific immunoassays, clinical applications are not
completely defined and are still evolving.
According to the
Joint Council, although skin tests are presently the preferred method of testing
in making the diagnosis of allergy, in vitro tests may also be useful in
specific clinical situations. Specific IgE immunoassays may be preferable to
skin testing under special clinical circumstances: 1) testing of patients with
severe Dermatographism, ichthyosis, or generalized eczema; 2) testing in
patients who have been receiving long-acting antihistamines, tricyclic
antidepressants, beta blockers, systemic corticosteroids or other medications
that interfere with skin testing and may put the patient at undo risk if they
are discontinued; 3) testing of uncooperative patients with mental or physical
impairments; 4) the evaluation of cross-reactivity between insect venoms; 5)
postmortem examination for IgE antibodies to identify allergens responsible for
lethal anaphylaxis; 6) as adjunctive laboratory tests for disease activity of
allergic bronchopulmonary aspergillosis and certain parasitic diseases; 7) when
clinical history suggests an unusually greater risk of anaphylaxis from skin
testing than usual; and 8) direct skin testing is inconclusive.
tests, rather than in-vitro tests, should be used for the definitive diagnosis
of anaphylactic sensitivities to stinging insects and drugs.
Total Serum IgE
elevated serum IgE level is one of the diagnostic criteria of allergic
bronchopulmonary aspergillosis (ABPA). IgE levels can be used to follow the
course of the disease. Serum IgE levels will fall when the disease is
successfully treated with corticosteroids; rising IgE levels indicate disease
Total serum level
of IgE is correlated with allergic disease in only a general way. Elevated
levels are associated with the presence of allergy, while normal levels are not.
However there are many individuals with clinical symptoms and allergen-specific
IgE who have serum IgE levels within the normal range. Because of this, routine
measurement of serum IgE is not a useful screening test for allergy.
no evidence that IgG antibodies are responsible for delayed allergic symptoms or
intolerance to foods.
food allergy testing utilizes an indirect method of measuring mediator releases
and the effects of other pathogenic mechanisms of allergy and delayed
hypersensitivity. It employs semi-automated Coulter Electronics and fully
automated computer analysis. This automated testing has not been validated
and has not been established as a useful allergy test in clinical practice.
testing is based on the theory that the addition of a specific allergen to
either whole blood or a serum leukocyte suspension from a suspected allergic
patient will result in reduction of the white blood cell count or death of the
leukocytes, thereby indicating the presence of an immune response. Controlled
studies have failed to substantiate the value of cytotoxic testing for the
diagnosis of allergies, whether they are airborne, foods, or chemicals.
tests lymphocytes in a laboratory culture for their reaction to up to 300
purified foods, preservatives, chemicals and minerals. This test is not FDA
approved and is not established as a useful test in clinical practice.
Complex Assays (FICA)
based on the standard solid phase radioimmunoassay methodology. These assays
have not yet been subjected to rigorous study of potential false-negative and
false-positive results. Clinical studies to date indicate that circulating
immune complexes can be found in a normal population of people having no food
allergy. The value of the measurement of FICA toward the diagnosis of food
allergy remains unproven and does not have a place in current clinical practice.
skin window test is an immunologic test in which the skin is abraded with a
scalpel. Laboratory cover slips are placed over the abraded areas for 24 hours.
The coverslips are then stained and analyzed. An immune deficiency may be
present if there is an abnormality of monocytes displayed either by their
absence or their inability to migrate to intracellular sites of antigen within
12 hours. This test is not useful in documenting allergies since other
immunodeficiency’s can be found in patients with allergic conditions.
Histamine Release Test
leukocyte histamine release test is a measurement of the amount of histamine
released in-vitro. Varying concentrations of an allergen extract are added to
the patient`s peripheral blood leukocytes. Histamine is normally released as a
consequence of the interaction of allergen with cell-bound IgE antibodies. If an
individual is atopic to a specific antigen, the leukocytes will not release the
histamine in-vitro. Only a limited number of allergens can be tested from a
single aliquot of blood and quality control studies have shown considerable
variability in the measurement of histamine results.
release test (MRT) (Signet Diagnostic Corporation) has primarily been used to
detect intolerance to foods and additives in patients with irritable bowel
The MRT-directed patient-specific diet is one component of the Lifestyle Eating
and Performance (LEAP) Disease Management Program (Don Self & Associates, Inc.,
Whitehouse, TX). The LEAP program is based on the theory that symptoms irritable
bowel syndrome and other certain conditions are caused by the physiological
effects of non-IgE mediated immune reactions in response to sensitivities to
specific foods and food additives.
According to the manufacturer, the LEAP program has been successful in reducing
or eliminating symptoms in 84 percent of patients with irritable bowel syndrome,
functional diarrhea, and related conditions. However, there is no evidence in
the peer-reviewed published medical literature to substantiate these claims.
release test has also been promoted for use in patients with chronic fatigue
syndrome, metabolic conditions (e.g., diabetes, obesity), gastrointestinal
disorders (e.g., gastro esophageal reflux disease, chronic ulcerative colitis,
and Crohn`s disease), neurologic disorders (e.g., migraine headaches, cluster
headaches), rheumatologic disorders (inflammatory arthritis, arthralgia’s,
fibromyalgia), Otolaryngologic disorders (e.g., perennial rhinitis, chronic
sinusitis, chronic otitis media with effusion), dermatologic conditions (e.g.,
eczema, urticarial, dermatitis), and in patients with behavioral conditions
(e.g., attention deficit disorder, hyperactivity, frequent mood swings,
inability to concentrate). There are, however, no studies of the mediator
release test reported in the peer-reviewed published medical literature that
demonstrate improvements in clinical outcomes by incorporating the mediator
release test and associated dietary modifications into the clinical management
of patients with these conditions. Thus, the mediator release test is
considered experimental and investigational.