Since there are few truly helpful laboratory tests for drug allergy, the history of the events surrounding the onset of a particular drug reaction is the single most important step used by doctors to determine the diagnosis. Most often the problem confronting your doctor is whether your symptoms are those related to a drug or to an infectious germ. If you develop allergy symptoms while taking several drugs for different conditions, pinpointing the precise cause becomes that much more complicated. But even when the cause has been narrowed to a specific drug, the reaction may not necessarily be the result of allergy to the active ingredient. Instead, it may be to one or more of the additives, which may not even be listed on the package label or package insert.

Laboratory Tests
Laboratory testing is less than helpful in the workup of most drug reactions. For one thing, the actual drug is seldom the direct cause of the problem. For another, we often do not know which of its breakdown byproducts or metabolites (with the notable exception of penicillin)is the problem or with which body proteins the drug may combine in order to trigger allergic symptoms. Although by no means diagnostic or specific, finding an elevated count of eosinophils (a special kind of white blood cell) in a routine blood test helps support a suspected diagnosis of drug allergy.

Direct skin testing to detect immediate hypersensitivity (IgE) drug allergies has so far proven consistently valuable for diagnosing only penicillin, insulin, and local anesthetic allergies. Likewise, the RAST has also to date proven of limited usefulness to physicians. In some cases of suspected drug-allergy-induced anemias or bleeding disorders, certain specialized blood tests have been helpful for establishing the diagnosis.

Patch testing, by contrast, has been proven invaluable in the workup of suspected cases of contact dermatitis or photoallergic dermatitis. In patch testing, tiny amounts of presumed allergens are placed against the skin under Band-Aid-like patches in an attempt to reproduce the allergic symptoms at the test site (see Appendix A). Photoallergy testing requires the additional step of exposing the test sites to ultraviolet A radiation in an effort to provoke the allergic response.

All things considered, the only conclusive way to prove that any drug is the cause of an allergic problem is to rechallenge the individual with the same drug after it has been discontinued and after all prior symptoms have cleared. Such a therapeutic (or drug) challenge, as doctors call it, is generally contemplated only when the particular medication in question is the only drug or is by far the best drug available to treat a condition.

In general, if the allergic symptoms are mild just itching, for example the risk of a therapeutic challenge is small. However, when airway constriction, falling blood pressure, or shock has occurred previously, the risk is great, and therefore the test should be done under the strictest medical supervision, if at all. Drug challenges are the only definitive means for confirming allergy to aspirin or radio-contrast media (materials that are commonly used in many types of diagnostic X-ray examinations). They are also an excellent means of determining allergies to local anesthetics.