Transcript Overview of Allergy Testing

Duke Internal Medicine Residency Curriculum
Overview of Allergy Testing
Author:????
Editor: Amy Shaheen, MD, Assistant Professor
of Clinical Medicine
Duke University Medical Center
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Allergic Rhinitis — Basic Principles: Epidemiology
• Epidemiology.
– Allergic rhinitis (AR) is one of the most prevalent
diseases, affecting approximately 10-30% of all
adults. The morbidity associated with AR is
manifested through lost work and productivity, as
well as an increasingly well-documented link
between AR and the development of asthma. The
“one airway” hypothesis has shown that
inflammation in rhinitis is associated with
inflammation of the lower airways, as seen in
asthma.
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Allergic Rhinitis — Basic Principles: History & Physical Exam
• History & Physical Exam
– Physical findings
• “Allergic shiners”, which are dark circles around the eyes
from persistent rubbing
• “Allergic salute” is a horizontal crease in the skin over the
juncture of nasal septal cartilage and bone, resulting from
constant wiping of the nose in childhood.
• The nasopharynx is classically pale and edematous in AR.
• Nasal exam is important to exclude polyps, obstructing
lesions, or purulent mucous, any of which might suggest
other causes of symptoms
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Allergic Rhinitis — Basic Principles: Differential Diagnosis
• Differential diagnosis.
– Other causes of similar symptoms include infectious
rhinitis, nasal polyps, vasomotor rhinitis, gustatory
rhinitis, hormonally influenced rhinitis (i.e.,
hypothyroidism or pregnancy), tumor, NARES (nonallergic rhinitis with eosinophilia syndrome), and
drug-induced rhinitis (i.e., rhinitis medicamentosa
secondary to overuse of topical decongestants, or
side effects from medications including Aspirin, ACE
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Allergic Rhinitis — Basic Principles: Classification of AR symptoms
Classification of AR
symptoms. Formerly, AR
was described as
seasonal or perennial,
based on whether
symptoms occur
intermittently or
throughout the year. More
recently, it has been
proposed to change the
classification to
intermittent or persistent.
The WHO guidelines for
classifying AR are as
follows:
Table 1. WHO Guidelines for
Classifying Allergic Rhinitis
Frequency
Intermittent
<4 days/week or <4
weeks
Persistent
>4 days/week and > 4
weeks
Severity
Mild
No impairment of sleep or
daily activities
Moderate-severe
Impairment of sleep or
daily activities (I.e. work
or school), or
“troublesome symptoms”
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Allergic Rhinitis — Basic Principles
After using the history and physical exam to
make a presumptive diagnosis of AR, the next
step in its management is usually a therapeutic
trial Given the extremely high prevalence of
AR, and the minimal adverse effects from
medications to treat it, treating AR
presumptively is a generally followed practice
supported by guidelines.
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Allergic Rhinitis — Treatment of AR
Treatment of
AR. Available
a.
medications to treat
AR act to thwart the
pathologic response
to allergen.
Table 2. Treatment of Allergic Rhinitis According to
Symptom Severity. For all degrees of severity, avoidance
of identified allergic triggers may help relieve symptoms.
Classification
Treatment
Mild Intermittent
Antihistamines, Topical or oral
decongestants, nasal saline
spray
Mild Persistent
Nasal corticosteroids, daily
antihistamine, nasal cromolyn
Moderate-severe
Persistent
Nasal corticosteroids,
antihistamine, consider
immunotherapy
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Allergic Rhinitis — Allergen Avoidance & Antihistamines
• Allergen avoidance.
– Although clearly helpful in easily identified allergic triggers such as
pets, some evidence suggests that commonly recommended
practices such as dust covers for mattresses are not helpful in
reducing AR symptoms (Terreehorst et al, N Engl J Med. 2003 Jul
17;349(3):237-46). Barring further evidence, the recommendations
have been to wash bedsheets weekly in hot water, avoid or remove
carpets in homes, and minimize exposure to pets if a patient suffers
from indoor allergies.
• Antiihistamines
– act by blocking the H1 receptor to decrease histamine-mediated
symptoms such as sneezing, itchy eyes, and rhinorrhea (i.e., early
response symptoms). They are not effective for treating nasal
congestion. Nonsedating antihistamines include fexofenadine,
loratadine, and cetirizine. Even these agents can have a sedating
effect, with fexofenadine having the least propensity to induce
drowsiness.
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Allergic Rhinitis — Topicals and Nasal cromolyn
• Topical corticosteroids such as flunisolide reduce
inflammation in the nasopharynx, and relieve
symptoms of congestion. They are not effective for
itchy eyes. Patients intolerant to aerosolized topical
corticosteroids may be able to use aqueous solutions
instead.
• Topical opthalmic preparations such as Patanol are
effective for red or persistently itchy eyes.
• Nasal cromolyn acts to stabilize mast cells in the nasal
mucosa, inhibiting the release of histamine and
improving symptoms. The frequent dosing necessary
for effect (3 or more times per day) makes compliance
more difficult.
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Allergic Rhinitis — Allergen Immunotherapy
• Allergen immunotherapy consists of a series of
allergen “shots” in increasing doses to alter the
immune response to specific allergens. The theoretical
basis is that the Th2 immune response (i.e., IgEmediated response with prominent eosinophilia, IL-4,
IL-5, and IL-13) is shifted to a Th1 response
(characterized by TNF-alpha, IFN-gamma, IL-1).
Before undergoing allergen immunotherapy, a patient
must be identified as having IgE responses to specific
allergens.
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Allergy Testing: Indications for allergy testing
• Allergy Testing
• As seen in the previous slide, there are multiple
therapeutic options to treat AR empirically prior to
the identification of specific allergens. Allergy testing
in the setting of AR identifies IgE antibodies to a
particular antigen that may be triggering a
pathologic response, leading to symptoms.
• Indications for allergy testing:
• Failure of initial medical therapy
• Need to confirm the diagnosis of allergic rhinitis
• Plan to pursue allergen immunotherapy
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Skin Testing
• Priniciples: Skin testing involves introduction of an allergen into
the skin to provoke an IgE-mediated response that correlates with
allergic triggers of AR.
• Techniques: Two types of skin testing (Figure 1) are:
– Puncture testing. In this technique, a small needle is dipped in a
standardized allergen solution, then applied to the skin with a prick
that breaks the epidermis but does not draw blood or pierce the
dermis.
– Intradermal testing Intradermal testing is essentially similar to PPD
testing for TB in technique, where a small amount of allergen is
injected into the dermis.
• Puncture testing is slightly less sensitive than intradermal
testing, but intradermal testing is associated with a
0.02% to 0.04% risk of moderate to severe adverse
reaction, such as urticaria.
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Allergy Testing: Controls & Allergen Selection
• Controls & Allergen Selection
– Skin tests use positive and negative controls to ensure
accuracy of the results. The positive control is
histamine, which induces a “wheal and flare” reaction.
The negative control is the diluent solution for the
allergens. The allergens tested usually include a panel
of several (up to dozens) of standardized compounds
that are derived from outdoor allergens such as
grasses, trees, and pollens, and indoor allergens such
as dust mite, animal dander, and molds. The specific
allergens used vary by geographic location (i.e., the
grasses and trees in North Carolina differ from those in
Oregon, and necessitate testing for different
allergens).
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Allergy Testing: Causes of inaccurate results & precautions
• Causes of inaccurate results and precautions. Factors
affecting reaction to positive control (and subsequent allergy
testing results) include:
– Dermographism. Patients who have a wheal-and-flare reaction to
simple scratching of the skin will have false positive results.
– Age. Greater age correlates with reduced skin test reactivity
– Use of rx such as antihistamines, topical corticosteroids, clonidine,
tricyclic antidepressants, or phenothiazines. These medications will
blunt the skin response, and either should be discontinued 10 days
prior to skin testing, or patients on these medications should undergo
alternate means of allergy testing.
– Patients on beta blockers and ACE inhibitors. These patients should
not undergo allergy testing unless it is possible to discontinue the
medication temporarily for the test, as these medications will interfere
with the rare need to treat adverse systemic reactions, such as
urticaria/angioedema.
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Allergy Testing: Common methods of allergy skin testing
Figure 1:Common Methods for allergy skin testing
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Allergy Testing: Interpretation & Accuracy
• Interpretation of results
– The degree of wheal (induration) and flare (erythema) response is
assessed at the time of maximal IgE-mediated response (about 15-20
minutes) to determine whether there is a specific IgE response to a
given allergen. The wheal is measured and given a semi-quantitative
value. A positive result must be interpreted with the patient’s
symptoms to determine whether an allergen is a true trigger of
symptoms. Positive results for specific allergens confirm the
diagnosis of allergic rhinitis and, if necessary, guide the formulation of
specific allergen immunotherapy.
• Accuracy of Skin Test Results.
– The sensitivity of puncture skin tests range from 90-95% in most
studies, and specificity is from 80-90% in most studies1. Skin test
results must be interpreted in the context of the patient’s symptoms.
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In Vitro Allergy Testing (RAST)
•
•
Principles and Techniques. - in vitro allergy testing is based on detecting
specific IgE in the blood that recognizes allergens likely to cause
symptoms of AR. The most commonly used test is RAST
(radioallergosorbent testing). In this test, allergen is bound to a cellulose
disk, and serum added to the disk. Specific IgE in the serum binds to the
allergen, and subsequently detected using radioisotope-tagged antihuman IgE antibodies. The amount of specific IgE can be detected this
way. **Note that measurement of serum total IgE is not a useful test in
the diagnosis of allergic rhinitis, as it is neither sensitive nor specific**
Interpretation of Results. RAST testing is not as sensitive as skin testing
in detecting specific IgE responses. Part of the explanation for this is that
it detects only IgE in the serum, whereas most IgE important for allergic
responses is located in the peripheral tissue. However, one of the
benefits of RAST is that patients on medications that contraindicate skin
testing (i.e., beta blockers or TCA antidepressants) may still undergo
allergy testing.
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In Vitro Allergy Testing (RAST) - continued
• Other in vitro Techniques. There are more
advanced tests such as multiallergen
screening tests and tests for markers of
basophil activation that are beyond the scope
of this topic.
• Accuracy of Results. The sensitivity of in vitro
allergy testing ranges from 60-80% in most
studies, and specificity ranges from 70-90% in
most studies1.
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Allergy Testing: Recommendations
• Recommendations
– The benefits of skin testing include lower
cost, more specificity, and a functional
measure of the IgE immune response. The
benefits of in vitro allergy testing include lack
of contraindication if a patient is on certain
medications, albeit at more expense.
Currently, the AAAAI, ACAAI, and ECAAI
recommend either skin testing or in vitro
testing as an initial approach to diagnosing
allergic rhinitis. This is supported by a recent
meta-analysis and review of allergy
diagnostic testing1
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Other indications for Allergy Testing
•
•
•
•
Penicillin Allergy Testing. Penicillin skin testing is reasonably well
standardized and, if negative, can exclude the possibility of anaphylaxis
to penicillin or other beta-lactams enough to allow treatment. This could
be clinically relevant given cited statistics that perhaps only 15% of
patients who report an allergy to penicillin are actually skin test positive.
Venom Immunotherapy. For patients who have had anaphylactic
reactions to hymenoptera stings, venom immunotherapy will decrease the
risk of recurrent anaphylaxis if stung again. Skin testing can help identify
which patients should undergo immunotherapy for hymenoptera venom.
Food Allergy Testing. More common in the pediatric population than
adults, skin testing to food allergens is less standardized and carries less
diagnostic accuracy than testing for inhalant allergens such as grasses,
trees, pollens, and molds.
Allergic Contact Dermatitis. Patch testing, in which common inducers
of allergic contact dermatitis are applied and the skin subsequently
checked for a reaction, is another method of allergy testing.
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References
• Gendo K, Larson EB. Evidence-based diagnostic strategies for
evaluating suspected allergic rhinitis. .Ann Intern Med. 2004 Feb
17;140(4):278-89.
• Terreehorst et al, Evaluation of impermeable covers for bedding in
patients with allergic rhinitis. N Engl J Med 2003 Jul
17;349(3):237-46
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