------------------------------------------------------------------------------ TITLE: ALLERGIC RHINITIS SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds DATE: November 2, 1994 RESIDENT PHYSICIAN: Carl "Rusty" Stevens, MD FACULTY/DISCUSSANT: Ronald Deskin, MD DISCUSSANT: J. R. B. Hutchinson, M.D., Atlanta, GA DATABASE ADMINISTRATOR: Melinda McCracken, M.S. ------------------------------------------------------------------------------ "This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion." Introduction Allergic rhinitis effects more than 40 million Americans and it is estimated that approximately one-half of all new patients evaluated by otolaryngologist have a cheif complaint that is at least partially related to allergies. Other disorders that are associated with allergic rhinitis include sinusitis, otitis media, sleep disorders, nasal polyps and asthma. PATHOPHYSIOLOGY Allergic rhinitis is precipitated by an IgE mediated Gell and Couumbs Type I reaction. After an initial exposure to an allergen, the immune system is primed and produces allergen specific IgE antibodies. These antibodies bind to mast cells and basophils in the mucosa of the upper respiratory tract. Later exposure to the antigen produces IgE-antigen complexes and subsequent release of histamine and other chemical mediators from the basophils or mast cells. These chemical mediators act on the nasal mucosa(producing itching and sneezing), on nasal mucosal glands(producing rhinorrhea), and on stromal vessels(producing vasodilatation and congestion). These symptoms characterize the acute phase reaction and usually begin 2-5 minutes after exposure and peak 15-20 minutes later. Additionally, other inflammatory cells are drawn into the area by these chemical mediators. These cells contribute to the overall inflammatory reaction and produce a second, "late" phase reaction that occurs 4-6 hours after antigen exposure. This phase is characterized by an increased responsiveness to histamine and also to various non antigenic stimuli. DIAGNOSIS The patient's history is of utmost importance in the initial recognition and evaluation of allergies. As mentioned above, common symptoms include clear runny nose, nasal congestion, and itchy eyes, ears, nasal and pharyngeal mucosa. They may give a history of recurrent sinusitis, otitis media, or nasal polyps. There may also be a history of lower respiratory tract disorders such as asthma. Attempts should be made to determine the usual onset of symptoms and and likely inciting allergens. If the symptoms are seasonal , this should be documented. The physical exam of a person with allergies can be impressive but more often is not. The nasal mucosa is pale and boggy in appearence and a clear rhinorrhea is usually present. This picture can be altered significantly if other disease processes such as sinusitis are superimposed. Although all polyps are not related to atopy, if they are found on exam, an allergy evaluation should be considered. Extra-nasal manifestations include dard circles (allergic shiners) under the eyes from venous congestion, and conjunctival inflammation. The classic manuvers associated with allergic rhinitis include the allergic salute (and associated transverse nasal crease) and repeated nose and mouth wrinkling. These are more commonly found in children with allergic rhinitis. Additionally, chronic mouth breathing is often related more to nasal congestion than adenoidal hypertrophy. Microscopic evaluation of nasal mucous can help in the evalulation of allergic rhinitis. Specimens are obtained with a cotton tipped swab from the superior surface of the inferior turbinate. A smear is made and stained with Hansel's stain. Eosinophils, goblet cells, and mast cells are all characteristic of an allergic process. Neutrophils and epithelial debris are more consistent with an infectious etiology. The cellularity of the mucous is altered by nasal steriods and these should be discontinued prior to specimen collection. Allergy testing can be performed to more accurately determine whether atopy is present and if so, to determine the specific allergens involved. This may occur early in the workup to assist with environmental control or later to guide immunotherapy. There are essentially two types of allergy testing - skin testing and in vitro testing. Scratch, prick, and intradermal injections of allergen are considered semiquantitative forms of skin testing. They differ only in their mode of allergen introduction and the resultant reproducability with intradermal injections being the most reliable. The wheal produced in these test is either graded or compared to a known positive (histamine) and a known negative (diluent). Skin endpoint titration (SET) testing is a more quantitative form of skin testing that is a bioassay of the patient's sensitivity to a given allergen. Progressively stronger concentrations of an allergen are introduced intradermally until either a negative test is established or a response is noted. If the next higher dose produces progressive whealing, the dose at which the initial response occurred is labled the endpoint dilution. This not only indicates atopy for this antigen but also represents a safe immunotherapy starting dose. This represents one of the main advantages of SET testing over the semiquantitative forms of skin testing. Additionally, because SET is a titration test, it is safer for testing of coseasonal allergens. It should be noted that certain medications such as antihistamines and tricyclic antidepressants can inhibit the whealing response and must be discontinued prior to any form of skin testing. In vitro test for allergen specific IgE were first developed in the late 1960's. Early radioallergosorbent test (RAST) suffered from poor sensitivity when compared to the results from skin test. A modified RAST was introduced in 1979 that had a lower cut off for positive test. The results from this modified RAST compare closely with those obtained from SET testing. The technique used in all forms of in vitro allergy tests involves mixing a sample of the patient's serum with a matrix that contains a specific allergen. If any IgE specific for this allergen is present, it will bind to the matrix bound allergen. A washing solution is applied followed by labled anti-IgE antibody. A final washing step is performed and the amount of remaining lable is directly related to the amount of antigen specific IgE in the patient's serum. The main advantages of in vitro testing are patient comfort (one venipuncture verses multiple intradermal injections) and safety (no risk of anaphylaxis). It also can be used to test many patients who are either uncooperative with or unable to tolerate skin testing such as those who cannot be withdrawn from their medications. Immunotherapy can be based on RAST results but an initial intradermal test (vial test) should be performed. Semiquantitative ELISA test are available as screening test but require more extensive testing prior to initiation of immunotherapy. Selection of antigens is an important part of allergy testing no matter what type of testing is performed. There are approximately 1358 species of grass, 1775 species of weed, and 650 species of trees in the United States. Fortunately there is a significant amount of cross reactivity among the grasses and weeds. This allows testing of these classes with 2-3 representative species. There is less cross reactivity among trees and therefore, test should be based on local prevalence. The above three classes plus important molds, the house dust mite antigen, and any relavent animal danders will give an adaquate screening panal. If testing for the screening panel is negative, the likelihood of a significant inhaled allergy is less than five percent. TREATMENT Treatment of otolaryngic allergy can be involved and time consuming but has the potential to significantly improve the patient's symptoms. In most cases it should follow a logical stepwise progression that includes identification and avoidence of the inciting allergen, appropriate pharmacotherapy, and finally immunotherapy for refractory cases. Environmental control is often difficult or impossible to achieve. However, an initial attempt should be made in most cases. The patient's socioeconomic status and attitude toward the allergen (i.e. cat) must be considered to avoid unreasonable recommendations. One of the most common allergens is that of the house dust mite. The mite thrives at temperatures and humidities that are also comfortable to humans. The antigen itself is contained in the mite dung and is relatively heavy when compared to other allergens. For this reason it is only airborne when disturbed. It is deposited in carpet, bedding, soft toys, upholstered furniture and cloths. Control in most effective by eliminating reserviors in primary living space (especially the bedroom). This can be accomplished by removing carpet, upholstered furniture, and dust collecting objects from these areas. Use of plastic pillows and mattress covers can also decrease antigen exposure. Keeping the indoor humidity between 25-45 % will inhibit mite growth. Placing bedding, furniture and cloths in a freezer for one to two days is effective but rarely practical. Electric blankets set on high for approximately eight hours each day have been shown to decrease the mite count by fifty percent. Chemical control with Benzyl benzoate (Acarosan) for carpets and furniture or Tannic acid for cloths can be expensive and time consuming but is effective for extended periods. High-efficiency particulate air (HEPA) filters are useful for removing dust mite antigen as well as many other allergens. Animal dander is another important indoor allergen that can be effectively treatedby environmental control. Cat dander allergen (Fel d I ) has been studied extensively and is formed from cat subaceous glands. It is relatively light and can remain in an area for months after the cat has gone. As with all other allergens, the best results are obtained by removing the source ( i.e. the cat). This is not an option in many cases. Fortunately, with strict control of other factors, the patient can keep the animal and still reduce allergen exposure by ninety percent. First, the cat must be kept out of primary living and sleep areas. Second, bathing the animal at least weekly is essencial. As with other allergens, removal of carpet and upholstered furniture is beneficial, as is the use of HEPA filters. Other animal danders have not been studied as extensively but it is likely that the above measures would apply. Cockroach antigen is becoming increasingly recognized as an important allergen. An entire industry is devoted to eliminating this source with somewhat variable results. Currently, this represents the most effective strategy but future work to produce chemicals that denature the antigen may one day provide a more effective approach. Mold allergen (contained in spores) represents an important allergen both indoors and outdoors. Warm, moist areas provide the best growth for molds. Indoors they are found in house plants, damp carpet, shower curtains and refrigerator drip pans. Flower beds, leaf piles and compost bins are their preferred location outdoors. Once again, elimination of the source indoors (i.e. house plants, carpets) and avoidence outdoors are the keys to effective control. As with the house dust mite, keeping the indoor humidity between 25 and 45 % is also helpful. Pollen is a well known allergen that causes significant allergic morbidity. It is difficult to avoid outdoors but can be reasonably well controlled indoors. This is accomplished by keeping windows closed and using appropriately filtered air conditioning and heating systems. Removing indoor plants is important and as mentioned above will also help reduce mold allergen. Showering immediately after outdoor activity will also decrease exposure. Additionally, the patient should be instructed to wear a mask when performing outdoor activities such as lawn mowing or gardening. PHARMACOTHERAPY Pharmacotherapy has been discussed in detail in a recent grand rounds and will be only briefly mentioned here. Antihistamines block H1 receptors and are the mainstay of pharmacotherapy. They are most effective against the "wet" symptoms of allergic rhinitis (rhinorrhea, itching and sneezing). The first generation antihistamines are effective but are also sedating and generally have more drug interactions than second generation agents. Additionally, there is an increased degree of tachyphylaxis with the first generation agents. Second generation antihistamines are lipophobic and therefore do not cross the blood brain barrier. They have fewer anticholenergic effects and can be used in patients with glaucoma or prostatic hypertrophy. Although second generation agents have fewer drug interactions, terfenadine and astemizole have been associated with fatal arrhythmias in overdose or when combined with certain macrolide antibiotics or antifungal agents. Decongestants are effective in reducing the mucosal edema associated with allergic rhinitis. This is accomplished by alpha adrenergic vasoconstriction of the stromal vessels. Topically, these agents are extremely effective but can lead to a rebound hyperemia after five to seven days of use. Decongestants are also effective systemically but appropriate precautions reguarding drug interactions ( tricycic antidepressants and MAO inhibitors) and cardiovascular toxicity must be observed. Cromolyn stabilizes effector cell membranes and therefore inhibits degranulation. It is effective during both acute and late phases of allergic rhinitis but must be administered prior to antigen exposure. For this reason it should have a scheduled dosing with extra doses given prior to a known exposure. Cromolyn has little systemic absorption and essencially no adverse effects. Corticosteriods are powerful anti-inflammatory agents that are also very effective at reducing the acute and late phase symptoms. The more pronounced adverse reactions related to systemic administration include adrenal suppression, gastric hyperacidity, and central nervous system stimulation. Topical use has few associated problems but can lead to nasal drying, epistaxis, and occasionally nasal septal perforation. IMMUNOTHERAPY Immunotherapy offers the only "cure" for allergies. It is generally reserved for those who have triggering allergens that are not readily avoidable or controllable with pharmacotherapy. The patient's symptoms should be present during more than one season and he/she must be cooperative and motivated to complete the course of therapy. The mechanism of action of immunotherapy is related to an initial rise followed by a slow decline in antigen specific IgE, and an increase in antigen specific IgG blocking antibody. Also, basophils become less reactive, and lymphocyte antigen specific responsiveness and surface markers are altered. Immunotherapy technique involves injecting progressively larger doses of allergen intramuscularly. The initial starting dose is based on the results of one of the previously described testing techniques. If semiquantitative skin tests were used, all positive antigens are started at a standard, low dose. As mentioned above, one advantage of SET testing is that the starting dose for each antigen is its endpoint dilution. Each dilution is independent of the others and the mixture is therefore taylored to the patient's relative sensitivities. If RAST testing was utilized, an initial intradermal "vial" test should be performed prior to intramuscular injection. Once initiated, the injections are administered weekly and the dosage is advanced to the highest tolerate dose which improves symptoms, while not causing excessive local reaction or worsening of symptoms. This dose is then maintained for an extended period, usually at least three years. Adjustments may be required periodically because of changes related to seasonal exposures. If symptoms do not improve with injections, consideration should be given to possible antigens not included in the mixture or to other chemical or non-atopic triggers. Underdosing and overdosing can lead to treatment failure as can an imbalance in the dosage of antigens in the mixture. An improper diagnosis of allergy must be considered if adjustment of the above problems does not produce improvement. Complications related to immunotherapy are rare, especially when dosages are monitored closely and adjusted appropriately. However, the possibility of an anaphylactic reaction is present and any physician providing immunotherapy must be trained and prepared to handle this life threatening complication. ----------------------------------------------------------------------- DISCUSSANT'S REMARKS FOR OTOLARYNGOLOGY GRAND ROUNDS: ALLERGIC RHINITIS RONALD DESKIN, M.D., ASSOCIATE PROFESSOR, OTOLOARYNGOLOGY & PEDIATRICS The evaluation and management of allergic rhinitis is a natural part of the field of Otorhinolaryngology - Head and Neck Surgery. Otolaryngologist involved with the care of these patients should understand the basic immunology and pharmacology involved. He or she should attend courses sponsored by the Academy of Otolaryngic Allergy and become involved with the network set up by this group. A competent interested registered nurse is necessary to do these evaluations in your office. The nurse should be well trained and conversant with allergy terminology, be able to trouble shoot problems and be involved in with the skin testing and preparation of allergy extract. Depending on the community or hospital location of the Otolaryngologist, he or she will need to decide whether they want to be involved in working up only their own patients or whether they want to actively seek referrals for allergy evaluation, skin testing, and immunotherapy. Some practical thoughts to think about are what will be your relationship with the general allergist in your community or hospital. Will the direct competition for testing and treating allergy patients discourage referrals of surgical problems from the allergist? How much will allergy involvement cut into your surgical time? In other words, we have to give up a day of surgery to attend to allergy matters in your office. The testing of allergy patients and the build-up of shots should be done with a physician in the office who is able to help if emergencies arise during the testing or building-up of shots. Allergy extract preparation and reordering of these supplies by the patient of course can go on without direct involvement from the physician. Other practical points that were not mentioned in the discussion of allergic rhinitis today include a very characteristic symptom of allergic conditions being a complaint of "itching of the roof of the mouth". Also, RAST testing may be a good way to test young children who are unable to cooperate with skin testing to get an idea about the nature of the child's allergies for planning of avoidance therapy, environmental control, etc. DISCUSSANT'S REMARKS FOR OTOLARYNGOLOGY GRAND ROUNDS: ALLERGIC RHINITIS J. R. B. Hutchinson, Atlanta, Georgia 1. When allergy testing has been performed by in vitro methods e.g. Rast, it is imperative that a test wheal be applied prior to beginning immunoRx since the patient has never been exposed to the antigen during testing, as in the case of skin testing. The discussant stated that this " should " be done. 2. Cat control is extremely difficult. Cats go and do as they please and in my experience it is the exception rather than the rule that one can control this. Since the patient would prefer to remove the allergist from their environment rather than lose the cat, I have just advised them of the limited benefit and increased risks involved and moved on from there. Only in the case of an asthmatic have I found it necessary to insist on removal of the pet. This was done to protect the physician as well as impress upon the parent the importance of this matter. 3. Astemizole blocks the reactivity of the skin and precludes skin testing and thus removes an important monitor for patients on immunoRx. This effect has been reported to last up to seven weeks and I have seen it last for four in some of my patients. It would also preclude performance of a test wheal prior to starting immunoRx and thus I do not use this medication if immunotherapy is a possibility. 4. While it is unfortunate that there is a division amongst allergy physicians treating allergy patients it may be best to refer to the " General " Allergist by their long formal name as agreed to many years ago. This is an allergist certified by the conjoint board of Internal Medicine and Pediatric Allergy. 5. The role of immunoRx appears to be of diminished importance with the advent of non sedating antihistamines and steroid nasal sprays. These give significant relief and in the patient that has a seasonal problem only, are usually safe. Life style changes in our society make compliance more difficult than in past times. Socioeconomic issues have changed the outlook on therapy as well. The percentage of patients requiring immunoRx has thus decreased over the past decade. While immunoRx is effective in the majority of patients; the length of therapy, expense, time consumed and other factors need be considered when offering this therapy. -------------------------------------------------------------------------- BIBLIOGRAPHY Bailey, Byron J., ed. Head and Neck Surgery - Otolaryngology. Philadelphia, PA.: J.B. Lippincott, 1993 Calhoun, K.: Diagnosis and management of sinusitis in the allergic patient. Otolaryngology Head and Neck Surg. 1992;107: 850-854 Corey, J.: Environmental control of allergens. Oto - HNS. 1994; 111 340-347 Gordon, B.: Prevention and Management of Office Allergy Emergencies. Oto Cl of North Am; 25:Feb.1992; 119-134 King, H.: Skin Endpoint Titration: Still the Standard? Oto Cl of North Am.;25:Feb.1992; 13-26 Krause, H.: Therapeutic advances in the management of allergic rhinitis and uticaria. Otolaryngology - Head and Neck Surgery. 1994; 111:364-372. Krause, Helen F. Otolaryngic Allergy and Immunology. Philadelphia,PA: W.B. Saunders, 1989 Mabry, R.: Skin Endpoint Titration: History, Theory and Practice. 1992 Marks, M.: Physical Signs of Allergy in Children. 1967 Meyerhoff,W. and D. Rice: Otolaryngology - Head and Neck Surgery. Philadelphia PA: W.B. Saunders, 1992 Nacherio, R. and F. Baroody: Observations on the response of the nasal mucosa to allergens. Otolaryngology - Head and Neck Surgery. 1994; 111: 355-363. Renfro,B.: Pediatric Otolaryngic Allergy. Oto Cl. of N. Am. Feb. 1992 181-196 Squillance S.: Environmental Control. Oto-HNS. 1992;107:831-834 Watson, W., A Becker, F Simons.: Treatment of allergic rhinitis with intranasal steroids in patients with mild asthma:effect on lower airway responsiveness. J Allergy Clinical Immunology. 1993;91:97-101 --------------------------------END----------------------------------------