CHAPTER 17
What Lies Ahead?
The authors have provided the reader with a practical and useful reference to assist in the practice of otolaryngic allergy. It is as up-to-the-minute as possible. Nevertheless, we realize that new procedures for both diagnosis and treatment of upper respiratory allergy will continue to appear. Furthermore, the practice of medicine will undoubtedly continue to undergo the radical changes that began during the past decade. In this chapter, we suggest to the reader some changes they may encounter in the future, and provide some philosophical advice that we hope will prove helpful.
DIAGNOSIS OF ALLERGY
Although mucosal challenge testing is a valid research tool in the realm of inhalant allergy, it does not appear destined for common use in the practitioner’s office. Rather, skin testing will probably remain the benchmark against which other tests are measured. This is driven in part by historical precedent, dating to the first efforts at skin testing by Blackley in 1873.1 Unfortunately, an equally powerful driving force is the body of specialty practitioners who maintain that because skin testing is the method by which they learned to test for allergy, all other methods that are new and/or different are suspect at best, and heretical at worst. Given the socioeconomic climate of the 21st century, there is no reason to suspect that this situation will change in the near future.
The skin test method most commonly used by general allergists is the prick test, which was described in the chapter on skin testing. This is a valid methodology that rapidly allows the identification of patients with significant degrees of sensitivity to aeroallergens. However, some patients may have negative prick test results yet show positive responses on dilutional intradermal testing or radioallergosorbent testing, and these patients quite frequently benefit from appropriate immunotherapy. Despite this, pressures by third-party payers have progressively forced practitioners to depend on screening tests, such as prick testing, for the diagnosis of inhalant allergy, rather than employ the more definitive methods mentioned.
Intradermal dilutional testing (IDT) has a long history of proven utility and safety, dating to its prototypical methodology, skin end-point titration (SET). Based in part on flawed studies of the technique, however, IDT continues to receive considerable criticism, which led to the change in terminology from SET to IDT. Despite a reasoned rebuttal and validation of the procedure,2 IDT is often classed as a “controversial technique” by those who use other methods. The practitioner who uses IDT has to be prepared to defend it against assaults by practitioners using other methods, and by insurance companies (who are strongly influenced by that group). Although the Food and Drug Administration uses titration in the standardization of extract, and opponents have sometimes grudgingly referred to it as the “Cadillac” of skin testing, it does not appear that IDT is likely in the near future to gain the respect it deserves, except from physicians using it and grateful patients.
In vitro testing, whether utilizing a radioisotope marker (radioallergosorbent testing, RAST) or an enzymatic or similar process (enzyme-linked immunosorbent assay, ELISA), offers numerous advantages in the identification and quantification of allergen-specific immunoglobulin E (IgE) in the serum of patients. In the four decades since the discovery that what had been previously termed reagin was IgE, and the development of methods to analyze for this substance, the in vitro diagnosis of inhalant allergy has enjoyed ever-increasing popularity. The advantages (and disadvantages) of RAST have been detailed elsewhere in this text. Despite the objections raised by traditionalists, as noted already, this methodology enjoys increasing popularity among those engaged in diagnosing and treating upper respiratory allergy.
Modifications involving both RAST and ELISA continue to be made. For example, the matrix to which the antigen is bound has undergone several changes. The development of more antigens for which in vitro testing can be performed, and automation, which makes the procedure more accurate and less labor-intensive, are continuing projects. Manufacturers are always striving to improve their product, and this holds true of those dealing with in vitro allergy tests. Nonetheless, it is well to review with care the controlled studies using these new technologies before switching from a system known to be accurate.
Although the death knell for in-office laboratories performing RAST and ELISA was effectively sounded by the passage in 1986 of the Clinical Laboratory Improvement Act (CLIA), RAST and related in vitro allergy tests remain widely available through several reference laboratories throughout the country As socioeconomic pressures further diminish the level of payment for medical services (including diagnostic procedures), some of these laboratories have been forced out of operation, while others are attempting to cut costs by increasing automation and developing more efficient operating procedures. More accurate RAST methodologies, improving both sensitivity and specificity, are constantly being sought. However, the practitioner who depends on a reference laboratory for such assays must be constantly on the alert for any change in technology or methodology that may affect test results. If vial tests on several patients yield unacceptable results, one area of immediate investigation should involve a call to the laboratory to inquire about any such changes.
Food Testing
As has been discussed in Chapter 13, the diagnosis and treatment of this problem has been hampered by the lack of a consensus as to what actually constitutes “food allergy.” Until and unless such a consensus is reached, the area of food hypersensitivity will remain a challenging one.3
The recognized “gold standard” test for food allergy (the double-blind, placebo-controlled food challenge test) is an impractical tool except in the reference laboratory. In the future, as in the past, efforts will continue to be made to find an accurate yet practical test for food allergy. Chapter 13 describes the more standard methods currently in use. The alternative ones mentioned here have not as yet been fully validated by research, but they may achieve this state in the future.
The dimethylsulfoxide food test (DIMSOFT) is not in general use, but in the hands of its developer it has been shown to be effective in detecting a wide variety of immunologically mediated food reactions.4 In this test, food extracts that have been frozen, dried, and reduced to a powder are suspended in dimethylsulfoxide (DMSO). The DMSO effectively carries both water-and fat-soluble antigens through the skin, obviating the need for injections. The DIMSOFT is applied as a patch test, and the skin reaction is read at intervals during a 4-day period. Reactions are graded clinically, on a scale of 0 to 4+, and the responses noted include erythema, edema, vesicles, and bullae. Biopsies of the positive sites have confirmed immunologic activity, whereas control sites showed no such finding. The test has produced no systemic reactions, even in patients prone to anaphylaxis. Further, the DIM-SOFT has been shown to diagnose effectively food allergies that involve all four of the Gell and Coombs reaction types. A drawback is that the use of DMSO generally causes an unpleasant, garlic-like scent on the patient’s breath and skin that lasts for up to 72 hours. Of greater concern is that the Food and Drug Administration has not approved the use of DMSO as a transcutaneous carrier for any substance, although research in this area is ongoing.5
The basophil histamine release test (BHRT) is predicated on the release of histamine during a hypersensitivity reaction, a phenomenon that is not confined to IgE-mediated reactions. If a food reaction occurs in the gut, histamine is released locally in the intestinal tract and by circulating basophils. Histamine binds with a high affinity to glass microfibers, and after appropriate steps, the amount of histamine present in blood may be read by spectro-fluorometric analysis of these microfibers.6 Fully automated methods for enzyme immunoassay of basophil histamine release have been developed, which may add to the utility of the test. Although the BHRT may diagnose a wider range of food hypersensitivity reactions than methods currently in use, it should be employed with caution until greater experience further validates its accuracy and utility.
The cytotoxic food test is based on the anecdotal observation, made decades ago, that during a food reaction a patient’s leukocyte count drops. As initially described by the Bryans, the test involves separating the buffy coat of a blood sample and exposing the living white blood cells to tiny amounts of food antigen on a microscope slide. In a normal response, the food undergoes phagocytosis by the cells, which continue to be active and apparently healthy. In food allergy, the white cells demonstrate slowed activity, swelling, and eventual disintegration.7 Through the years, it has been difficult to obtain consistently reproducible results between various laboratories and observers with the cytotoxic food test, and as a result third-party payers have disallowed payment for it. This has led to attempts to automate and standardize the test.
The antigen leukocyte cytotoxic antibody test (ALCAT) is based on the principle of the cytotoxic food test. In the ALCAT, after leukocytes have been exposed to the food antigen to be tested, they are passed through a small aperture in a modified Coulter counter. By measurements of electronic resistance, the number and size of the cells traversing the aperture can be determined. These results have compared favorably with those obtained by food challenge studies in patients with all types of food sensitivity.8 In addition to the determination of cell numbers and sizes, the supernatant fluid may be analyzed for food-specific immunoglobulins and mediators of inflammation. Efforts are ongoing to establish the validity of this test, which has not yet achieved wide acceptance. Furthermore, attempts by some commercial sources to use this test as an adjunct in formulating weight-reduction diets have not contributed to the scientific credibility assigned it by the medical community.
Another evolving test for food allergy is the ELISA/activated cell test lymphocyte response assay (ACT LRA). This modification of the ELISA, which has already been described, involves measurement of enzyme amplification and lymphocyte blastogenesis in an autologous environment (i.e., whole plasma rather than serum). Rather than the conventional “sandwich” technique of the ELISA, the ELISA/ACT LRA measures lymphocyte blastogenesis that occurs as a result of stimulation by a foreign substance. This reaction is specific for all types of delayed hypersensitivity (antibodies, immune complexes, and cell activation) but does not measure IgE-mediated reactions. Although in-house studies have been reported as showing good correlation between ELISA/ACT LRA results and subjective responses after elimination of the suspected foods,9 false-positive results may stem from the presence of food additives or contaminants. At present, controlled and scientific studies that validate this methodology and support its accuracy and usefulness are lacking.
At one time, it was hoped that assay of allergen-specific IgG4 for various foods might be a useful tool in diagnosing food allergy. However, controversy developed concerning the significance of positive responses. In 1997, a study by Nalebuff10 indicated that if the “cutoff point” for significance is set at or above a level of 10 μg/mL of food allergen-specific IgG4, positive responses indicate foods that are appropriate for further evaluation by challenge or other methods. However, the same information is often available through a well-kept diet diary.
One of the anticipated changes in the future practice of allergy is an increasing recognition of the importance of food allergy. Otolaryngic allergists have thought for years that food allergy is an important contributor to a myriad of symptoms involving the ears, nose, and throat. As research in this area continues, we are seeing support of previously anecdotal and observational data in this regard.11
TREATMENT OF ALLERGY
The best treatment of inhalant allergy remains avoidance. Future development of better means of air filtration will allow patients to create “safe havens” in their homes, in which they are not continually exposed to antigenic triggers. This will still require cooperation on the part of the patient, including an investment of both money and time. The development of affordable, disposable filters for heating and air conditioning systems that provide filtration equivalent to electronic units has been a significant step in the right direction. Unfortunately, it is doubtful that future technology will be able to influence the tendency of patients to comply with any prescription for avoidance only if it does not require changing their lifestyle or exerting any effort. Nevertheless, such tools as better and more comfortable impermeable barriers for bedding, treatments that kill dust mites and denature their protein, and methods to render the beloved cat less allergenic are eagerly awaited.
In the realm of pharmacotherapy, the day has long since passed when antihistamines were just “histamine blockers.” Newer preparations decrease the production or neutralize the effect of multiple mediators of inflammation involved in the allergic reaction. As further understanding of cytokines and their importance in allergy accrues, more targeted phar-macotherapeutic solutions to the problem have become available. This is already seen with the development of leukotriene inhibitors, which are extremely beneficial in the treatment of asthma and whose use has been extended to the treatment of rhinitis. More preparations (antihistamines, anticholinergics, corticosteroids) are available for topical delivery, and most pharmacotherapeutic agents for the treatment of allergy are now dosed once (or at most, twice) daily, with fewer drug interactions and potential adverse side effects.
An interesting potential new method of treating rhinitis involves the topical application of capsaicin. This is the substance responsible for the “hot” in “hot peppers.” The use of irritant substances within the nose to treat rhinitis is not new; the people of ancient India recommended pepper, mustard, oris root, and asafetida for that purpose.12 Although topically applied capsaicin in low doses produces rhinorrhea and nasal congestion, in high doses it appears to deplete neurotransmitters, resulting in a decrease in these symptoms. This has intrigued researchers, but to this point has not been put to practical use.
The steadily increasing availability of allergy relief medications without a prescription will mean that as patients come to the otolaryngic allergist, most will already have tried a variety of antihistamines, including one or more second-generation preparations. Many will also have tried nasal cromolyn, which became available over the counter in 1997. Rumors continue of efforts to make one or more topical nasal corticosteroids available without a prescription. Unfortunately, although more drugs are available to the allergic patient without a prescription, it still requires a medical evaluation to appropriately choose the correct medication to safely and effectively provide symptomatic relief. With all this, the physician dealing with patients suffering from allergic rhinitis must be aware of all the pharmacotherapeutic tools available to provide relief, and use them in a proper fashion. Even patients on immunotherapy require symptom relief from time to time, and failure to provide adequate control may result in the patient s becoming discouraged and discontinuing therapy.
NURSE’S NOTE
It is now popular for practice guidelines to be published that deal with various disease states and the measures available for treatment. The material that follows may be considered to reflect suggested practice guidelines for the allergy nurse or assistant.
The allergic reaction causes pruritus in the membranes of the respiratory tract and eyes, as well as increased secretions, mucosal edema, and malaise. Allergy patients may express their symptoms as sneezing spells, running nose, itching nose and eyes, headaches, “sinus” symptoms, and tiredness.
Appropriate identification of triggering allergens may be elicited by correlating the season and/or circumstance producing symptoms with the results of properly performed skin and/or blood tests for allergen-specific IgE.
Control of symptoms may be accomplished by instructing patients in the avoidance of inciting aJiergens, assisting in the proper use of medications ordered by the physician, and administering specific immunotherapy. The patient should receive an explanation of each step of therapy before its execution, in addition to an overall plan of therapy.
Immunotherapy, as prescribed by the physician, will include careful monitoring of the patient’s response to therapy in general, and specifically to each dose as it Is administered, with alteration of dose depending on circumstances and allergen exposure. After maintenance levels of immunotherapy have been achieved, patients who are acceptable candidates may receive their injections outside the office, However, they will first receive specific instructions in dealing with anaphylactic reactions and have appropriate medications available for that purpose.
On completion of a course of therapy, the patient not only should have achieved a marked improvement in symptoms, but aiso should have acquired the knowledge necessary to maintain symptom control in the future.
