The diagnosis of IgE mediated latex allergy is not always a straight forward process. It begins with a clinical history and physical examination to determine whether a patient's symptoms are associated with exposure to latex allergens. The history is often subjective (and thus susceptible to bias) and complex as various other substances and
pathologies can induce similar symptoms. Therefore only a few individuals with clearly identified latex exposure related symptoms can be diagnosed with a high degree of accuracy through clinical history. Fortunately, there are several procedures available to confirm suspicions raised through clinical history. These procedures fall into two general categories - those which focus on symptoms and those which focus on proof of sensitization.
Symptoms
Procedures which focus upon symptoms include challenge tests, avoidance trials, and medication trials. These tests are cumbersome and time consuming1. In addition, challenge tests can be dangerous, are
not sensitive, and often are not comparable to real life situations2. They are highly dependent upon dosage, time of exposure and source of challenge material, which is generally uncharacterized. A positive
challenge test with a defined source of latex allergens is more relevant than a negative challenge test but the possibility of false-positive results due to nonspecific effects of irritants, chemicals, and psycho physiologic aspects of the patient must always be considered. False negative challenge tests due to quality and quantity of challenge material and route of exposure must also be investigated.
Proof of Sensitization
Procedures for determining sensitization (production of specific IgE antibodies) in patients include skin tests and in vitro tests designed to detect the presence of specific IgE directed against allergens derived from latex. The skin test is referred to as a procedure while the in vitro methods are actual tests with defined limits of detection, positive and negative controls, and linear ranges providing a degree of quantification. Although these procedures and tests are somewhat indirect, the production of specific IgE antibodies is highly correlated with symptoms in latex sensitized individuals and they have the advantage that their analytical performance characteristics can be predetermined within limits which indicates the accuracy of the results3.
Tests for sensitization depend upon sufficient amounts of allergens being present in the extract used relevant to the patient being tested4. This is difficult to establish with skin testing because different individuals can react to different allergens. Since no standardized preparation of latex is available in the U.S., it is unknown whether different skin test preparations of unknown stability (usually "home-brew") contain sufficient allergen content to cause positive results in sensitized individuals. In addition, there are no standardized methods of applying or interpreting the results. The skin test also requires that the individual being tested not be under the influence of a number of skin test suppressive drugs which can negatively influence results. The largest problem with skin tests is that there is no way to demonstrate their specificity. For example, it is possible that the extracts contain non-specific irritants and materials other than allergens which are responsible for the positive results. Despite these problems and the variable danger of inducing a systemic reaction, skin testing continues to be considered a valid test for latex sensitization and is heavily utilized for these purposes.
The in vitro tests for specific IgE to latex allergens are amenable to the
determination of their analytical specificity using inhibition tests, and analytical sensitivity using statistics. This minimizes, but not eliminates, false positive and false negative results. Further, the allergens present on a solid phase to which the specific IgE antibodies bind can be defined in quantity, quality and stability. Although the results of an
in vitro test do not always correlate with the severity of the symptoms
and different test methods have been developed which are sometimes not comparable, the FDA has approved two different methods of performing these tests for diagnostic purposes. (Pharcia Immunology, DDL, Alastat).
In the diagnosis of any allergy it must be pointed out that tests for sensitization are not tests for sensitivity. However, their correlation with clinical symptoms is usually quite high. Some of these offer the added advantage of being quantitative which can also be used to monitor the success or failure of various treatments. Furthermore, when these tests are positive in lieu of negative clinical history, this usually forebodes future problems for the patient in which prophylactic measures can be taken. One problem with assessment of how well these tests work is our method of determining their clinical sensitivity and specificity, a combination of which is used to judge their efficacy. In the past this has entailed comparing the history of one test result and using this to judge the others performance. Since patient history is subjective and or safety purposes physicians usually err on the positive side, these assessments are likely to be wrong. In fact, if the history has a significant false-positive component, even a negative result would be judged falsely to have poor specificity.
In the diagnosis of latex allergy due to specific IgE antibodies, there are clear cut cases where all tests agree5. This happens in a majority of the patients be they positive or negative. However, since this is not always the case and because we have distorted the importance and accuracy of the clinical history and some of the test results used to
support this, I submit that our ideas of prevalence and diagnosis of latex allergy have not all been derived from objective data. This leaves the diagnosed, but unconfirmed, latex sensitive patient in a very difficult position. Since a "gold standard" is not present in this field, our assessment must come from agreements of different approaches and resolution of their differences. Research continues to resolve these problems.
REFERENCES
- Melillo G, Bonini S, Cocco G, Davies RJ, et al. Provocation tests with allergens. Allergy 35; 52: 5-35.
- Lowhagen B, Linholm NB: Standardized allergen provocation test. Allergy 1980; 15: 349-56.
- Williams PB, Dolen WK, Koepke JW, Selner JC: Comparison of skin testing and three in vitro assays for specific IgE in the clinical evaluation of immediate hypersensitivity. Ann. Allergy 1992; 68: 35-45.
- Lowenstein H: Report on behalf of the International Union of Immunological Societies (IUIS). Allergen Subcommittee. Arb Paul Ehrlich Inst. 1983: 78: 41-48.
- Kelly KR, Kurup V, Zacharisen M, Resnick A, Fink JN: Skin and serologic
