NEW DEVELOPMENTS AND CONCEPTS IN THE AREA OF ALLERGY AND ENVIRONMENTAL MEDICINE
by Robert W. Boxer, MD, Fellow of the American Academy of Environmental Medicine, the American Academy of Allergy, Asthma, and Immunology, and the American College of Allergy, Asthma, and Immunology.
There are many developments and some new concepts and products and medications in allergy and environmental medicine. This Doctorís Corner will attempt to discuss a few important ones, particularly the ones that I am most familiar with, and give you my perspective as well as that of the field in general. Iíll try to distinguish between the two at times. Since this is a rapidly changing picture, it is important that this be of general interest only and that you work with your health professional for your own specific needs.
In the more conventional allergy area, there has been a greater emphasis on how significant the impact of allergic rhinitis is on the quality of life, general health, and even the economics of the country. There has been emphasis on the interference with work, sleep, and social life.
There are a number of so-called second and third generation antihistamines which essentially have evolved to be relatively free of side effects, particularly drug interactions causing cardiac arrhythmias, and with a lessened incidence of somnolence or sedation. Seldane and Hismanal are no longer available primarily because of the tendency to cause interference with the Cytochrome P450 detoxification mechanism in the liver, particularly when given in conjunction with Erythromycin or other macrolides or azole antifungals, leading it, in some forms, to serious and even fatal cardiac arrythmias. Out of that have come Allegra in several forms, including a newer 180 mg. once-a-day tablet, Zyrtec, which evolved from Atari, and Claritin. Some of these are combined with decongestants, in some forms. We do find that the more tools we have, the more likely we are to find something that works well for a particular patient.
Astelin, which is the Azelastine nasal spray, is also an antihistamine and does have potential for sedation but has been effective in some patients. Nasalcrom is now over-the-counter and continues to be one of the safest, and often effective, topical nasal preparations. There are wide varieties of steroids, both in;the regular form and in an aqueous form for patients who tend to have dryness. Many of the manufacturers of these products claim superiority in terms of lessened systemic corticosteroid effect, but it is my feeling that steroids still carry a potential risk, and, in fact, when a patient is facing long term use, even though it is a topical steroid, even in a male, we will often obtain baseline bone densitometry studies and follow-up periodically. Although this is controversial and debated, I think there is a slightly higher incidence of glaucoma and cataract in patients using these preparations, perhaps with an onset at an earlier age. There is a decrease in velocity of growth in children who, when they discontinue the medication tend to catch up. There is the remote possibility of ulceration of the septum leading to perforation if the steroid is continued, along with minor complications such as yeast overgrowth, etc. Overall, the topical corticosteroids are very useful, particularly for short term or limited use, and especially in the hands of those who are experienced with them.
Atrovent, which is an atropine derivative, is used as a nasal spray in some instances, perhaps particularly when patients need drying, or when they are overly reactive to weather or pressure changes.
There are a number of newer eye preparations. Cromolyn has become available again in the form of Crolom. Patanol, which is both antihistaminic and a Mast cell stabilizer, and Nedocromil or Alacril, which is fairly similar to Crolom and is also a Mast cell stabilizer, are also available as eyedrops. Our experience has been that these are frequently useful, as are moisturizing eyedrops, which seem to form a barrier between the allergen and the conjunctiva.
In the area of asthma, there is much discussion and emphasis and controversy regarding so-called remodeling of the airway. Itís felt that if beta agonists (bronchodilators), such a Albuterol, are the only medications used, especially if used on a daily basis, there is a greater tendency for chronic inflammation and ultimate scarring leading to permanent changes and decreased pulmonary function. I believe that this is yet to be conclusively demonstrated, but nevertheless, the point is well taken in the sense that if a patient has to use beta agonists frequently, they should be on an anti-inflammatory, as well. One anti-inflammatory is Intal, which has a unique safety profile and is frequently effective. Whether or not this or topical corticosteroids, such as Vancerik, Azmacort, Aerobid, Flovent, etc., will truly prevent or change the course of chronic asthma has yet to be conclusively established, at least in my opinion. From a clinical point of view, we certainly do not want to see patients overuse the beta agonists or the Albuterol metered dose inhalers because they tend to become ineffective and sometimes can cause worsening of symptoms.
It would appear that it is important to follow pulmonary function tests in patients with asthma to be sure that the changes that occur with aging are not accelerated because of insufficient control of the asthma.
In addition to the newer corticosteroids, and again claims of superiority are routinely made, there are also available three leukotriene inhibitors or antagonists. The original Zyflo has limited use because of potential toxicity to the liver requiring more careful monitoring. Accolate and Singulair are more widely used leukotriene inhibitors or antagonists. There have been side effects in a few patients, some serious, most attributed to too rapid reduction in corticosteroids, but in some patients, apparently unrelated to this. It seems like in all of medicine, one always has to weigh the risk versus the benefit. The problem with newer medications is that the risk is not always clear for a number of years and, therefore, those of us who are conservative will use newer medications when we feel that the risk is justified but, in general, will tend to stay with more older established medications for those reasons.
A longer acting beta agonist, such as Serevent, has been useful for some patients who have trouble sleeping through the night. Some of us have been concerned about its misuse, and also what we call down regulation of beta receptors where patients can become unresponsive to Albuterol and run into serious problems. It is felt that the likelihood is lessened if the patient is on an anti-inflammatory also, and I suspect that Serevent will ultimately have a useful niche in our armamentarium, particularly when used by those experienced in its potential drawbacks as well as its benefits.
The Theophylline preparations have somewhat fallen out of favor with the advent of some of the newer products, but it seems like over many years, there have been cycles and there still are patients who do very well on Theophylline. Although it may have a variety of side effects and levels have to be monitored, at least we are fairly aware of the problems associated with Theophylline because it has been round for forty-five or more years.
Weíve used much more Guaifensin in the last few years, particularly as an expectorant and especially since the use of a saturated solution of potassium iodide has decreased greatly because of potential side effects. The Guaifensin is a fairly effective expectorant and helps some cases of asthma where mucous is too thick and also is helpful in some cases of chronic nasal or sinus disease where, again, thinning of mucous is important.
Atrovent as an inhaled medication is also sometimes useful in acute and chronic asthma and, again, this is an Atropine derivative.
In the area of hives, or urticaria, we have always known that there are multiple systemic causes, varying from allergy, to infection, to hormones, to stress, to collagen vascular disorders, to neoplasms, etc. Fortunately, most cases of urticaria are benign in nature, but awareness of the potential continues to be important.
In the area of eczema, or atopic dermatitis, there is growing awareness of the contributing role of food allergies, and even the role of inhalant sensitivity. This has been fairly apparent to a number of us for the last thirty-five years and it is good to see the field of dermatology and allergy, in general, beginning to become more aware of this since it does change part of the management of the disorder. There are some newer topical treatments, which have been effective in some patients.
My interest in ADHD and ADD and autism and its relationship to allergy continues to be satisfying in terms of helping some of the children who duffer from these problems.
There is little doubt that allergy can affect the central nervous system causing a variety of problems and, therefore, when a patient has any nervous system problem and allergy, it is important to treat the allergy. We continue to find that sensitivity to artificial coloring and flavoring, preservatives, natural and artificial sweeteners, and specific food allergens, as well as inhalant allergies, can play a definite role in some patients with the above disorders.
Secretin is a hormone produced in the duodenum, which seems to help some patients with autism. It is still early in understanding the potential side effects as well as the benefits.
We have used Serenaid, which is a newer peptidase, an enzyme that helps to break down the opioid-like peptides that are produced from some foods, including gluten and casein, from some grains and dairy products. The breakdown products of these foods can have receptor sites in the central nervous system and can aggravate autism and other disorders along that spectrum. This awareness has opened up a whole new avenue for helping the victims of these problems.
Speaking of autism, there is some thought that vitamin A, particularly in the form of Cod Liver oil, may be beneficial and there is even some suggestion that gluten sensitivity may blunt or destroy the tips of the villi in the intestine, which might be important in absorbing vitamin A. We look forward to some exciting new developments in this area. Itís conceivable that those children who seem to have developed autism after vaccination may have either some immune deficiency or even deficiency in vitamin A secondary to gluten or other allergy or intolerance. Obviously this work is in the early stages, but it is exciting.
Speaking about vaccines, those of us who are interested in the relationship to some of these neurologic syndromes, feel that vaccines should continue to be administered cautiously and only when children are in good health. I, and others, think that there are too many combinations and that many children should be given separate injections so as to minimize the impact on the immune system. I, and others, also think that injections should not be started as early as they are currently being recommended. This is obviously a hot topic and is very controversial and you will find authorities with valid arguments on both sides.
There is renewed interest in the so-called sinopulmonary reflex, i.e., asthma that may be precipitated by sinus disease. There is also increased awareness that there may be a common and shared pathophysiology of rhinitis and asthma.
Much more interest and knowledge has developed regarding drug interactions. Specific isoenzymes in the Cytochrome P450 system have been identified for many medications, making it possible to predict, in some instances, drug interactions even if they are not listed in the PDR (Physicians Desk Reference) Companion or other sources of drug interactions.
In the future, even greater awareness of how medications are detoxified will lead to even better prediction of problems, and it would seem that ultimately this will require the use of computers to promptly solve these problems.
Our office has been working with Comprehensive Digestive Stool Analyses for the last five or six years and we find that this is often one way of evaluating the health of the gut. It would seem that the gastrointestinal tract is a so-called second brain and is important in the overall health of the patient, including the function of the central nervous system. The so-called leaky gut syndrome can lead to absorption of larger partially digested molecules of proteins causing increased allergy. Gastrointestinal inflammation can also lead to malabsorption or decreased absorption of nutrients, particularly vitamins and minerals.
The role of yeast imbalance in health and disease continues to be controversial. Weíve worked with this for twenty-five years now and have evaluated some 3,000 patients. There is a blood test, which is useful, but periodically the various labs seem to have had problems and those of us who are doing this test need to be aware of this fact and whenever there is a sudden change in the expected results, when our patient population hasnít changed, we have need to act accordingly. In the end, clinical suspicion and experience and intuition and judgment probably take precedence, but it is nice to have some science to back you up. Also, blood tests are a nice way to follow the progress of the patient and in our office we use them as somewhat of a guide as to when to begin to taper treatment and become a little less rigid on the diet.
In the area of environmental control, there is an increasing awareness that mold can cause not only allergic problems but cause toxic reactions, as well. Much emphasis has been placed on Stachybotris and it would seem to me that more industrial hygienists and other people skilled in environmental surveys should be available to make assessments of environments in the future. In the past, allergists have done this but specific identification of molds and other items and specific qualification is probably a specialized area that could be handled by other specialists. Also, these specialists become expert at remediation, and this involves knowledge of building construction, architecture, and remodeling.
It is now pretty well accepted that exposure to dust mites and their fecal products is something that needs to be prevented.
There was a miticide, a material designed to kill mites, which came out a few months ago and it was to be applied monthly. Although it was actively advertised and claimed to have been allergy tested and physician approved, it turned out that it had an offending fragrance and caused many allergic and other problems for individuals who used it and it was withdrawn from the market. I would urge readers to be cautious in purchasing any item like this and to check with their physician.
There has been much emphasis on fungal sinusitis and there needs to be a distinction made between invasive, or pathogenic fungal sinusitis, which requires strong anti-fungals to control, versus allergic fungal sinusitis, which acts somewhat as allergic bronchopulmonary aspergillosis and usually is treated by steroids. This is an evolving area and we are anxious to see new developments.
There has again been documentation of something that was actually documented years ago, specifically, that diesel exhaust fumes are an inducer of IgE production in asthma. Actually, it was shown thirty years ago that air pollution enhanced IgE production and clinical allergies including asthma.
We continue to be interested in the evolving dental situation in the sense that silver mercury amalgams are not as widely used as before. We find more and more dentists who, while they may not accept everything that is said about silver mercury amalgams, are more likely to put in composites, or other materials that are non-metallic, to avoid the possible exposure to mercury. Obviously, there are other potential exposures to mercury such as certain fish, etc.
There is current interest in cavitation necrosis, which suggests that after extraction of a tooth, if all of the infection is not removed from the root, there can be an indolent source of problems that can affect health.
The areas of multiple chemical sensitivities and chronic fatigue syndrome remain controversial, although chronic fatigue syndrome seems to have been well accepted by a number of governmental agencies, and it is my understanding that multiple chemical sensitivity has also, but still insurers and other third parties are reluctant. It is always a problem, in a sense, to know what is real and what is imagined and what is malingering and I think this is what some third parties struggle with. We do need more objective parameters and I see this emerging in the future.
Anti-leukotrienes, or leukotriene antagonists, are probably helpful in chronic sinus disease, particularly the aspirin sensitive or polypoid type of chronic or recurrent sinusitis. While this use hasnít been approved by the FDA, I would look for it to be approved as a use for the leukotriene antagonists in the not too distant future.
Leukocyte Histamine Release testing, which has been available for the last fifteen years and is probably the only way to test for many drug sensitivities in most patients, is being talked about at some of the national meetings and its use has been extended to include other allergens, including molds and duct and pollens and even foods. Weíve used it for a number of years for medications and it has remained an under-utilized, controversial tool. We look for future clarification of this as an extra tool.
A number of extracts are being standardized and this is supposed to be an advantage to allergists and our patients. Theoretically, extracts from a number of different companies, if standardized according to regulations, could be roughly interchangeable and would be more likely consistent from lot to lot. Our experience with standardized stinging insect venoms and with house dust mites and with cat dander has been good, but our experience with the newer standardized grass extract has been less encouraging. We do think that manufactures, and the field in general, will work toward continuously improving these modalities.
The awareness that allergy can affect all areas of the body, including the joints, the heart, the colon, and the musculoskeletal system, as well as the brain, is slowly emerging in the literature. I think that this is something that was obvious to a number of clinicians half a century ago, but in medicine, it takes about that length of time for many concepts to gain acceptance.
With asthma treatment, the use of spacers is becoming more common. It is difficult for some people to time inspiration with the activation of the metered dose inhaler and the spacer solves this problem.
Peak flow meters, simple inexpensive devices that they are, are an excellent way of monitoring asthma and while we used to use them mainly in severe and moderately severe asthma, we now are beginning to see their utility for even mild asthmatic patients. This is simply a device where patients take as deep a breath as they can and blow out as hard and as fast as they can and they record a value. Many times these values will significantly diminish, hours or even days before a patient begins to sense difficulty. This allows the patient and the physician to make reasonable and appropriate adjustments in medication ahead of time and allergy certainly is a cascade-type of immunologic phenomenon and the earlier you catch it, the easier it is to treat.
Molecular mimicry means that if a patient has certain organisms in their intestinal tract, and if they make antibodies to them, these antibodies may also attack another body structures and it is felt that, in some cases, rheumatic arthritis may have this as part of its pathophysiology. This is akin to patients with group A strep developing antibodies, which attack the heart valves or the kidneys weeks later. The concept of molecular mimicry may end up applying to more than we realize.
Researchers are working on an antigen to skin test patients for latex sensitivity, possibly ultimately leading to the ability to desensitize some patients. Certainly, the awareness of the magnitude of the problem, particularly in the health professions, has grown dramatically in the past five to ten years.
There is awareness now that grapefruit juice can enhance certain medications, including antihistamines, hormones, and some anti-hypertensives, and perhaps other medications, and Iím sure more knowledge will evolve, not only in regard to grapefruit juice, but perhaps in terms of other effects of other substances, as well.
Awareness that vocal cord dysfunction and hiatus hernia with gastroesophageal reflux, can mimic asthma has increased.
Space allows for presentation here of only a smattering of the exciting new developments and concepts in allergy and environmental medicine, as medicine in general rapidly advances.
Article from NOHA NEWS, Vol. XXV, No. 3, Summer 2000, pages 3-8.