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Allergy testing by allergists/immunologists and ENT specialists

Question:

Please compare and contrast allergy skin testing as done by Allergists vs ENT doctors, with pros and cons of each method, including discussion of relevant literature. Is one method scientifically better? Is there something we as Allergists could learn from how ENT doctors do it? I was also wondering if you knew if there is a historical reason why we differ on skin testing technique from ENT.

Answer:

It is difficult for me to respond to your question as there is no single method of skin testing used by allergists/immunologists and no single method used by ENT physicians. Therefore, it is misleading for me to respond as if there is uniformity among the two specialties. It is also not feasible within the framework of Ask The Expert to respond comprehensively to a question for which entire chapters of text books are devoted. For more detail, I refer you to Allergens and Allergen Immunotherapy 5th edition edited by Lockey and Ledford "In vivo testing for allergic diseases" and "Unproven and controversial forms of immunotherapy" and Middleton: Principles of Allergy and Immunology 8th edition edited by Adkinson et al Chapter 70 "In vivo methods for the study and diagnosis of allergy" and Chapter 101 "Unproven diagnostic tests".

Having provided this mea culpa I will respond with my observations. Allergists/immunologists have traditionally relied upon positive percutaneous testing to diagnose allergic sensitivity and negative intradermal testing for select allergens to exclude sensitivity. The sensitivity of intradermal testing exceeds percutaneous testing but the results have poor positive predictability and should not be used to confirm allergic sensitivity except for insect allergy, drug allergy and maybe in select cases of inhalant allergy. Intradermal testing does not predict a positive response to single challenge with airborne allergens nor benefit from immunotherapy. Therefore, many allergists/immunologists do not perform intradermal testing for inhalant allergens and no one uses intradermal testing for food, except perhaps for detecting galactose alpha-galactose or gelatin sensitivity. I think there may be value in certain situations for inhalant intradermal testing and I do perform select intradermal testing. This is generally interpreted in light of high pretest probability. Allergists/immunologists generally do not use allergy skin tests to predict the maintenance dose of immunotherapy but rely on clinical trial data showing a threshold dose is needed to achieve improvement irregardless of the degree of skin test reactivity. There may be a greater concern about systemic reactions with immunotherapy with greater skin test reactivity to potent allergen extracts, such as grass, and this may modify the schedule but does not usually change the target dose, generally 6-14 mcg/dose of target allergen.

The Practice Parameter on Allergy Diagnostic Testing: An Updated Practice Parameter (Annals Allergy Asthma and Immunol 2008;100: Supplement 3 )provides a great number of references and detailed discussion of these points. Three excerpts are provided below.

    "Although intracutaneous tests at strengths customarily performed
    (1:100 to 1:1,000 [wt/vol] from manufacturer’s concentrate)
    are more sensitive, there are conflicting results
    about their ability to predict clinical allergy. Several studies
    in the previously cited meta-analysis investigated how well
    intracutaneous tests predict symptoms after natural or laboratory
    allergen challenges.(110) Two high-quality studies conducted
    in cat- and grass-sensitive patients concluded that
    positive likelihood ratios were poor (0.89 and 1.05 for cat and
    grass, respectively) as were negative likelihood ratios (1.24
    and 0.98 for cat and grass, respectively).(111,167) By contrast, the
    accuracy of intracutaneous tests was excellent for Alternaria
    species, as evidenced by positive and negative likelihood
    ratios of 8.80 and 0.05, respectively.(114) These disparate results
    probably reflect the intrinsic variability of individual
    allergens among investigators and their abilities to predict
    clinical allergy.(113)"

    "One recent investigation demonstrated that SET, which is
    a modified quantitative testing method, is equivalent to prick/
    puncture testing for both positive and negative predictability
    of clinical allergy when both are compared with nasal challenge.
    90 The end point response in SET is the lowest concentration
    of allergen that produces a wheal: (1) that is the first
    wheal 2 mm larger than the negative control wheal and (2) is
    followed by a second wheal that is at least 2 mm larger than
    the preceding one.(90) It should be stressed, however, that SET
    is roughly equivalent to new skin prick tests only at dilutions
    ranging from 1:12,500 (wt/vol) to 1:312,000 (wt/vol). By
    comparison, most physicians who perform intracutaneous
    testing use dilutions ranging from 1:100 (wt/vol) to 1:1,000
    (wt/vol).90 Indeed, a study designed to test the predictive
    response of timothy prick/puncture and intracutaneous tests
    to nasal provocation revealed that the addition of a single
    intracutaneous test at a dilution of 1:500 (wt/vol) (No. 2 in the
    Rinkel nomenclature) adds no additional predictability when
    the prick test result is negative and therefore appears to be
    unwarranted.(91) Similar disappointing results were obtained
    when Alternaria intracutaneous tests at a dose of 1:500 (wt/
    vol) were compared with specific nasal challenge93 and contrasted
    sharply with a previous Alternaria study.(114)"

    "Summary Statement 31. For most allergens, a fixed dilution
    (1:1,000 [wt/vol]) of intracutaneous tests has poor efficiency
    in predicting organ challenge responses. (Evidence A)"

ENT allergists use a variety of skin testing methods as well but one unique to this specialty is referred to as the "Rinkle method". In this method serial 5 fold dilutions are used for intradermal testing until the concentration is reached that results in a 2 mm increase in the wheal compared to the next lower concentration. The test is interpreted within 10 minutes of application and without regard for the erythema. This concentration at which the 2 mm wheal occurs is accepted as the starting dose of allergen immunotherapy and the maintenance dose is calculated as 25-50 fold more concentrated. The result is generally the starting dose and maintenance dose of allergen extract is quiet low and does not approximate the target dose of 6-14 mcg/dose of the allergen. Although this method has similarities with the SET testing described above, the calculation of the maintenance dose from the Rinkle test and the lack of requirement of erythema make the value of this testing limited. The starting dose is safe but the calculated maintenance dose (25-50 fold greater than the end point) is too low and no more effective than placebo. (Van Metre TE, Adkinson NF, Amodio FJ, et al.: A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever. J Allergy Clin Immunol. 66:500-513 1980 PMID: 6159384

1. Van Metre TE, Adkinson NF Jr, Lichtenstein LM, et al.: A controlled study of the effectiveness of the Rinkel method: immunotherapy for ragweed pollen hay fever. J Allergy Clin Immunol. 65:288-297 1980 PMID: 6987291
2. Van Metre TE: Critique of controversial and unproven procedures for diagnosis and therapy of allergy disorders. Pediatr Clin North Am. 30:807 1983 PMID: 6353341)

In summary, there are a variety of testing methods for detecting specific IgE. There are issues related to the stability of testing reagents, standardization of testing reagents and testing methodology, and individual variability in testing. A critical factor is the history and physical examination that determines the pretest probability of allergy and without incorporating this component the value of most testing is diminished. There is no single method that is effective, but there is a rich literature to facilitate interpretation.

I hope this information is of help in your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI

    90. Gungor A, Houser SM, Aquino BF, et al. A comparison of skin
    endpoint titration and skin-prick testing in the diagnosis of allergic
    rhinitis. Ear Nose Throat J. 2004;83(1):54–60. (IIb)
    91. Krouse JH, Sadrazodi K, Kerswill K. Sensitivity and specificity of
    prick and intradermal testing in predicting response to nasal provocation
    with timothy grass antigen. Otolaryngol Head Neck Surg.
    2004;131(3):215–219. (IIb)
    110. Gendo K, Larson EB. Evidence-based diagnostic strategies for evaluating
    suspected allergic rhinitis. Ann Intern Med. 2004;140:
    278–289. (IV)
    111. Wood RA, Phipatanakul W, Hamilton RG, et al. A comparison of skin
    prick tests, intradermal skin tests, and RASTs in the diagnosis of cat
    allergy. J Allergy Clin Immunol. 1999;03:773–779. (III)
    113. Clarke PS. The diagnosis of perennial rhinitis due to house dust mite
    (Dermatophagoides pteronyssinus) demonstrated by nasal provocation
    tests. Ann Allergy. 1987;59:25–28. (III)
    114. Escudero AI, Sanchez-Guerrero IM, Mora AM, Soriano V, Lopez JD,
    Garcia FJ, et al. Cost-effectiveness of various methods of diagnosing
    hypersensitivity to Alternaria. Allergol Immunopathol (Madr). 1993;
    21:153–157 (III)
    167. Nelson HS, Oppenheimer JJ, Buchmeier A, et al. An assessment of
    the role of intradermal skin testing in the diagnosis of clinically
    relevant allergy to timothy grass. J Allergy Clin Immunol. 1996;97:
    1193–1201. (III)

Rinkel HJ: Inhalant allergy. 1. The whealing response of the skin to serial dilution testing. Ann Allergy. 7:625-630 1949 PMID: 18148596