ALLERGY FOR THE OTOLOGIST

ALLERGY MANAGEMENT FOR THE OTOLARYNGOLOGIST 0030-6665/98$8.00 + .OO

ALLERGY FOR THE OTOLOGIST External Canal to Inner Ear

M. Jennifer Derebery, MD, and Karen I. Berliner, PhD

Approximately 20% of Americans suffer from hypersensitivity diseases. The head and neck are the most commonly affected target organs of the allergic reaction, and the effect of allergic reactions in producing nasal symptoms was first reported by Dr. French K.

The ear also has been suspected of being a target organ for an allergic reaction. The first case reports suggesting an allergic basis for labyrinthine symptoms were in 1893, although Duke published the first clinical report of a suspected allergic etiology for Meniere’s disease in 1923.17, 77 Likewise, anecdotal information concerning an allergic basis for otitis media with effusion has been reported for generations.

This chapter reviews the immune and allergic activity of the ear as we currently understand it, and suggests mechanisms by which a classic allergic or autoimmune response may result in the production of otologic symptoms. Various treatment modalities, including specific allergic testing and treatment techniques, are described.

IMMUNOLOGY

In 1925, Coca and Cooke introduced the term “atopy,” derived from the Greek word that means ”strange thing,” to explain abnormal hypersensitivities not associated with infection or anaphylaxis.8 The distinct immunologic factor of atopy is the presence of IgE antibody as

From the House Ear Clinic (MJD); and the House Ear Institute (KIB, MJD), Los Angeles, California

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

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158 DEKEBERY & BERLINER

demonstrated by skin testing. Under normal circumstances, the mediators released during an allergic reaction help to form a defensive inflammatory reaction. With a massive release of mediators under abnormal conditions, such as the atopic state, the predominating broncho- constrictive and vasodilatory effects can produce troublesome symptoms.

After an individual’s first contact with an antigen prompts the immunologic system to react, later contact with that antigen causes a secondary boosting of the immune response. The response is sometimes excessive, causing gross tissue damage if the antigen exposure is excessive, or if the humoral or cellular immune reaction is heightened. These exaggerated reactions, based on normal body mechanisms to combat infective agents, are called hypersensitivity reactions.

Gel1 and Coombs described four types of hypersensitivity; a fifth type was added later.9 Type I reactions are mediated by IgE, which was formerly known as reagin. Cross-linking of IgE antibodies bound to a mast cell by an antigen will trigger degranulation of the mast cell with mediator release. Slow-reacting substances of anaphylaxis (SRS-A), also termed leukotrienes, and platelet activating factor (PAF) exert profound pharmacologic changes, producing symptoms of allergy. Short-term skin-sensitizing IgG4 antibodies also may participate in immediate reactions.

Type 11, or cytotoxic, reactions involve antibodies directed against the cell itself. Examples include Goodpasture’s syndrome and Hashi- moto’s thyroiditis.

Type I11 reactions involve the formation of immune complexes from an antigen-antibody interaction, and usually fix complement by the classic or alternative pathway. These complexes may disseminate throughout the body and be trapped in different organs. Examples of diseases caused by Type 111 reactions include systemic lupus erythemato- sus (SLE) and bronchopulmonary aspergillosis.

Type IV reactions involve receptors bound to the surface of lympho- cytes. Because of the longer time course involved in these reactions, they were, in the past, referred to as delayed-type hypersensitivity reactions. Examples include the tuberculin reaction, allograft rejection, and contact dermatitis.

Type V reactions involve antibodies that react with tissue receptor sites. An example would be Graves’ disease, in which the antibody actually stimulates thyroid hormone production.

OTOLOGIC MANIFESTATIONS

Allergy may affect the external ear, middle ear, and/or labyrinth (Table 1). We will discuss the role that allergy plays in diseases of each of these parts of the ear.

ALLERGY FOR THE OTOLOGIST 159

Table 1. OTOLOGIC MANIFESTATIONS OF ALLERGY

External ear Chronic external otitis (COE)

Sensitization to otic drops Contact sensitivity (hearing aid ear molds, nickel)

Dermatophytid reaction to fungal infection Red auricle (vasodilatation to foods)

Eustachian tube dysfunction Patulous eustachian tube Otitis media with effusion (OME) Chronic otitis mediddraining ear

Meniere’s disease Vestibular hydrops Cochlear hydrops Dizziness Tinnitus

Middle ear

Inner ear

External Ear

Chronic external otitis (COE), characterized by an erythematous, scaling, pruritic dermatitis, may develop from an eczema of the auricle or external auditory canal (EAC). The auricle or EAC may become sensitized to the topical application of otic drops preparations, especially those containing neomycin. The involved skin typically will be injected and edematous, but have little pain. Usually, removal of the offending drops will alleviate the problem, although it may be necessary to apply topical steroid ophthalmic drops for a short period as well.

Patients will develop occasionally a contact sensitivity to the plastic or silastic used in hearing aid molds. The resulting COE, which will erupt only in the areas of skin in contact with the hearing aid mold, may prevent useful amplification. The problem usually can be alleviated by boiling the offending mold for 30 seconds to lessen the antigenicity, or by the substitution of a less reactive plastic for the hearing aid mold. In severe cases, the mold may be plated with a thin film of gold.

Contact sensitivity to metals used in earrings, especially nickel and chromium, also occurs not infrequently. Treatment is to use earring posts of surgical stainless steel, or in more extreme cases, 14 karat gold or titanium.

The auricle may at times appear bright red because of vasodilatation from food reactions. Although this is a self-limiting condition, it may cause concern among parents or may be confused with perichondritis by a primary care provider.

A dermatophytid (ID) reaction is a secondary allergic skin eruption occurring in specifically sensitized individuals as a result of the hemato- logic spread of fungi or their allergenic products from a primary focus of fungal infection. The site of the ID reaction may be the auricle or EAC. Classically, the conditions deemed necessary for an ID reaction include:

160 DEREBERY & BERLINER

1. A demonstrable primary focus containing the pathogenic fungi,

2. Absence of fungi in the skin lesion at the ID reaction. 3. Spontaneous resolution of the dermatitis when the primary fun-

gal infection has been eradicated. 4. A positive immediate skin test response, demonstrating a Type

I, IgE-mediated reaction to an intradermal test of the fungal antigen.38

remote from the ID lesion.

Common sites for the primary focus of fungal infection include the nails (onychomycosis), skin, and vagina (monilial vaginitis). The most common fungus involved is Trickopkyton, although Cundidu (Oidomy- cetes) and Epiderrnopkyton also have been de~cribed.~

The treatment for an ID reaction is the identification and treatment of the primary focus of fungal infection, desensitization with allergenic extract of the infecting fungus to lessen the allergic component, and control of any complicating secondary bacterial infections.

We recently reviewed experience with the ID reaction at the House Ear Clinic.I2 Fourteen patients were seen who were felt to have a possible ID reaction and were skin tested for Trickopkyton, Oidomycetes, and Epiderrnopkyton (TOE) and dust mite, and desensitized to these antigens. Patients were questioned and examined for a primary source of fungal infections, such as chronic tinea pedis infections (athlete’s foot) or recurrent vaginitis, but location of the primary fungal infection was identified in only 4 of the 14 patients.

Desensitization began with weekly injections of TOE extract. All patients were empirically asked to eliminate yeast from their diet. Pa- tients underwent immunotherapy for a minimum of 6 months. Ten of the patients complied with the diet eliminating yeast. In approximately half of the patients (57.1%), the COE resolved completely following immunotherapy. It was improved in another 21.4%. No patients had any complications from therapy.

Middle Ear

Ear fullness is one of the most common presenting symptoms in an otologic practice. A relationship among upper respiratory tract infections, allergy, and poor eustachian tube (ET) function long has been recognized. Allergy may play a role not only in ET dysfunction, but in some cases of a patulous ET. The ear fullness secondary to ET dysfunction can result in diverse complaints, ranging from a minor annoyance to a loss of employability.

ET dysfunction has resulted after provocative intranasal challenges of pollen, house dust mite, and histamine.1,39,40,45 The role of food allergy in the production of ET dysfunction has not been commonly evaluated. We recently completed a study of 151 patients presenting with eustachian tube dysfunction who had evidence of allergy and underwent


allergy testing and treatment.l' Of the patients, 92.3% were positive to one or more foods, and all had reactivity to inhalants. Nearly all had used one or more other treatments without success prior to allergy therapy. After treatment with immunotherapy and diet, fullness was rated as improved in 71% of patients, with allergy symptoms and well- being improved in 83% and 80% of patients, respectively. Adherence to the recommended elimination diet was significantly related to outcome in those with food allergies. Even refractory cases of patulous eustachian tube and eustachian tube obstruction may do well on specific allergy therapy.

Otitis media with effusion (OME) is the most common cause of hearing loss in children today. The published incidence of allergy in OME has been reported to range from 0 to more than 95'?'0.~ This variability reflects the controversy regarding the role of allergy in production of OME, the different sensitivity of skin test techniques used for testing, and the fact that food allergens often are not included in the testing panel in many reported case series.

Reports documenting the production of ET obstruction by both intranasal challenge or natural exposure to histamine, pollen, and dust mite support the prominent role that allergy may play in the production of OME?3, 39, 4* The middle ear also has been shown to be capable of the local production of IgE antibody, although this incidence was reported as only 8% in studies on atopic patients with recurrent OME.5 Histamine and other biologic mediators of inflammation have been identified in the middle ear fluid of patients with otitis media with effusion? The incidence of OME in allergic children also has been found to be twice that of nonallergic children.16

Common arguments given against a significant role of allergy in the production of OME include the fact that allergy is typically thought of as a seasonal, mild-weather, pollen-initiated disease; the highest incidence of OME is in the winter. Also, an IgE-mediated reaction is brief, and the immediate phase reaction is not likely by itself to be sustained long enough to produce ET obstruction. Finally, in no case has an intranasal challenge actually produced a middle ear effusion.

Although it is true that the highest incidence of OME does not coincide with the major spring and fall pollinating seasons, it does coincide with the time of year that dust and mold counts tend to be highest; ET obstruction has recently been shown to develop after intranasal challenge with dust mite extract.39

Although an IgE-mediated reaction is brief, a late phase reaction occurs some 2 to 6 hours after the immediate reaction, and may persist for several hours. Mediators released from this reaction may persist long enough to produce a chronic eustachian tube obstruction and the eventual production of OME.

Finally, although the lack of a middle ear effusion in any provocative challenge test is indeed compelling, we should keep in mind that, in the animal model, even complete ET obstruction produced by sectioning the tensor veli palatini will not actually result in the production of a middle


ear effusion for some 1 to 4 weeks.15 As the tubal obstruction produced by intranasal provocative challenge testing only persists for several hours to a few days, it is likely that this is not a long enough period of time to actually result in the production of a middle ear effusion.

The role of food antigens in the production of OME is rarely ad- dressed. An elevation in serum IgG to foods in the serum of otitis-prone children when compared to controls has been demonstrated, despite a lack of IgE-mediated sensitivity to the same foods: This is consistent with the belief of most otolaryngic allergists that most adverse food reactions are not IgE-mediated, and this area needs to be studied further.

Although the nasal mucosa, ET, and nasopharyngeal mucosa are all involved in the pathogenesis of OME, Bemstein concludes that the mucosa of the nasopharyngeal portion of the eustachian tube is the most probable target organ of the allergic reaction.‘j He theorizes that an immune reaction produces edema of the posterior nasopharynx, occlud- ing the proximal portion of the ET, thus debilitating the active muscle- assisted tubal opening. Based on review of the literature, a reasonable approximation of the incidence of OME related to allergy would be 35% to 45% of cases.

Secondary infections of a middle ear effusion eventually may result in the production of chronic otitis media. Untreated allergies also may be a cause of persistent drainage from a perforation or from a pressure equalizing (PE) tube placed for treatment of OME. Specific treatment for the allergies (desensitization/diet) can produce a dry ear and/or prevent tubal extubation.

Inner Ear

Meniere’s Disease

The first published report of Meniere’s disease secondary to allergy was in 1923.17 Both inhalant and food allergies have been linked with symptoms of Meniere’s disease and cochlear hydrops.34 Changes in electronystagmography and electrocochleography recordings have been noted on patients injected with food extracts during provocative food testing.36, 43

Many of the clinical characteristics of Meniere’s disease suggest an underlying autoimmune etiology. Its notorious propensity to wax and wane, becoming active again after long periods of remission, suggests an inflammatory component. It is bilateral in a significant number of cases. A delayed Meniere’s-like picture may develop in a normal ear following trauma to the contralateral ear. It is often responsive, at least initially, to steroid treatment. An increased level of circulating immune complexes has been found to be present in 96% of patients with Meniere’s disease.I3

The seat of immunoactivity in the inner ear appears to reside in the endolymphatic sac and in the endolymphatic duct. Immunoglobulins G,


M, A, and secretory component are all found in the sac, although numerous plasma cells, mast cells, and macrophages have been found in the perisaccular connective tissue.2

The endolymphatic sac is capable of both processing antigen and producing a local antibody response.23 Antigen and inflammatory responses both are noted to be decreased following surgical destruction of endolymphatic sac or obliteration of endolymphatic

The endolymphatic sac has a highly vascular subepithelial space containing numerous fenestrated blood vessels."" Most immunologically competent cells may be found in the interosseous or rugose portion of the endolymphatic sac because of its unique blood supply. Arteriole branches of the posterior meningeal artery (off of the occipital branch of the external carotid) supply the sac and duct.'O Although for the most part the labyrinth is similar to the rest of the central nervous system in being protected by blood-labyrinthine barrier, the posterior meningeal artery is fenestrated and offers a peripheral portal of circulation. In other parts of the body, fenestrated vessels supplying organs involved in resorption (e.g., kidney, choroid) are especially susceptible to damage by immune complex deposition.

Despite the aforementioned evidence of immune activity, only 30% of patients with Meniere's disease show evidence of a true autoantibody response to specific anticochlear antibody by western blot assay.24 Tests of abnormal cell-mediated immunity, such as the lymphocyte transfer test and the lymphocyte migration inhibition assay, have either been inconsistent, or have been found to be normal even in patients with known causes of autoimmune dysfunction of the inner ear, such as Cogan's

The suggestion is strong that Meniere's disease can be caused or influenced by autoimmune factors, yet the most accurate tests currently available to diagnose an autoimmune abnormality are normal. However, there may be other immune-mediated causes for the development of symptoms. With an incidence of 20%, allergy is the most common "autoimmune" disease clinically. An elevated level of circulating immune complexes (CICs) has been reported in patients with allergic rhinitis and asthma, as well as those with Meniere's disease.I3, 47 The tendency for allergic reactions to be intermittent as Meniere's symptoms are led to the original misdiagnosis of allergy as an "effluvium" emanat- ing from freshly mown hay. Additionally, allergy is also steroid responsive.

Although allergic Meniere's disease may affect only one ear, we have found a much higher incidence of bilaterality in these cases than is typically reported.I4 Ninety-three patients with Meniere's disease, diagnosed according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) standards, were tested and found positive for allergies; 40% of patients had bilateral involvement. Nearly one third (32.6%) of the patients felt that a reaction to a food provoked their Meniere's disease symptoms. Many patients also felt that their symptoms were related to weather (23.7%) or seasonal changes (47.3%). The


large majority of patients had significant symptoms of a systemic disor- der suggesting allergies; 87% had a history of nasal congestion.

Following immunotherapy, 56 of the 90 patients with follow-up (62%) reported a decrease in both frequency and severity of vertigo attacks. Fifty percent of patients also reported an improvement in tinnitus, and 59% improved in other (extralabyrinthine) symptoms, the most common of which was nasal congestion. Complete or substantial control of vertigo, using the AAO-HNS definition, occurred in 86% of those patients for whom sufficient information was available to calculate the number of spells per month.

Cochlear and Vestibular Hydrops

can play a role in the production of cochlear and vestibular h y d r ~ p s . ~ ~ By the same presumed mechanism described above, allergies also

Dizziness

Allergic patients may complain also of vague dizziness rather than true vertigo, or a sensation of floating.35 Typically, these are young adults with a normal neurotologic examination and audiogram. Their symptoms are usually perennial, but their complaint of dizziness is accompanied almost always by other symptoms suggestive of allergy, especially nasal congestion or chronic rhinitis.

Other metabolic conditions, such as thyroid dysfunction or hypoglycemia, may give similar complaints and may need to be ruled out by appropriate laboratory tests. These patients often have been treated with various medications with no relief in their symptoms. That, along with the almost universal association of other allergic symptoms, should suggest a possible underlying atopic cause for symptoms that will mark- edly improve after the institution of specific allergic treatment.

Tinnitus

Allergic patients also may complain of tinnitus. Two studies evaluating tinnitus in patients with other allergic symptoms severe enough to warrant skin testing found that nearly 40% of all such patients reported the presence of significant tinnitus.1° In one study, a tinnitus questionnaire was completed by a sample of allergy patients with tinnitus. Results indicated that tinnitus was rated as usually being of moderate or loud intensity, but did not interfere greatly in daily life. In the second study, patients with Meniere’s disease described their tinnitus before and after treatment for allergy. Ratings regarding the frequency of occur- rence of tinnitus, the severity, and the interference with daily activities after treatment for allergy were significantly better than ratings describ- ing tinnitus before treatment. Tinnitus appeared less severe in the treated patients than in a group of patients who did not receive treatment.

An indirect cause of tinnitus in the allergic patient may be an


exaggeration of symptoms produced by the side effects of the decongestant drugs that often are used as an adjunct in treatment. Many of these medications have vasoconstricting properties similar to caffeine, which has long been recognized by its ability to exacerbate tinnitus.

EVALUATION

History

A comprehensive allergic and medical history is essential, and a history of coexisting diseases that may influence the allergic problem should be sought. A questionnaire can facilitate greatly history-taking.

History also should include medications. Drugs such as beta block- ers may not only exacerbate allergic symptoms such as asthma, but also may affect decisions regarding therapeutic modalities, such as immunotherapy.

Past surgical procedures may suggest an underlying allergic predis- position. For example, patients with a history of multiple operations in the upper respiratory tract, such as repeated intubations of the tympanic membrane, tonsillectomy, and adenoidectomy, or repeated sinus procedures, would be suspected of a possible underlying allergic diathesis.

Allergy is inherited. A family history often will reveal other cohorts with suspected allergic diseases. Often, the involved individual was never termed "allergic," but the particular symptoms, such as asthma, catarrh, or chronic sinusitis, will suggest an underlying allergic problem.

Physical Examination

Allergy frequently involves several organ systems, resulting in multiple complaints. Therefore, it is essential to rule out other significant diseases that it may mimic. Because many symptoms of allergy occur in the head and neck, careful evaluation of this area is especially important.

Ears

The auricles, particularly in children, should be examined for unusual erythema. The postauricular area may appear fissured in patients with a mold allergy or a dermatophytid reaction. Examination of the EACs may show excessive desquamation secondary to a chronic ecze- matoid external otitis. The tympanic membrane should be examined for signs of tympanosclerosis, which may be evidence of repeated childhood infections that the adult patient has "forgotten." Retraction, especially in the attic area, or atelectasis, may indicate chronic eustachian tube dysfunction. A serous effusion should be evaluated by direct examination and by pneumo-otoscopy. Of course, any unilateral effusion will

166 DEKEBERY & BERLINER

warrant a thorough nasopharyngeal examination or possibly an MR imaging scan to rule out a neoplasm.

Nose

The nose is the organ most frequently involved in allergic complaints. The allergic patient whose primary complaint is in an unrelated target area, such as the labyrinth or skin, may deny specific nasal complaints, even when examination reveals that his or her ”normal” nose is not normal!

Clear, watery nasal discharge is common in allergic rhinitis. The mucous membranes should be examined for color and edema. The classic blue of allergic rhinitis is secondary to venous engorgement of the mucosal blood vessels. The mucosa of the turbinates and septum should be evaluated for excessive edema or polypoid changes.

Patients who clear their throat excessively may develop vocal pol- yps secondary to posterior nasal discharge. A globus sensation may result from the pooling of excess secretions in the vallecular piriform sinus, or edema may be caused by a secondary inflammatory reaction.

Neck

A field examination of the neck should be performed to look for regional lymphadenopathy, which may be evidence of chronic infection. If a unilateral chronic serous otitis media or evidence of nasopharyngeal disease has been noted, the jugulo-digastric area and posterior cervical chain should be examined to rule out metastatic nasopharyngeal carci- noma.

Laboratory Tests

Laboratory tests may aid in the diagnosis of allergies. A complete blood count may show evidence of recent viral or bacterial infection. Children with recurrent sinusitis and otitis media should have a total serum IgG and IgA drawn to rule out an immunodeficiency. Measure- ments of IgG subtypes may reveal a specific subtype deficiency even with a normal total IgG.

Though the diagnosis of allergy is not made by measurement of total IgE, an elevated IgE would support the possibility. A carefully selected regional mini-screen modified radioallergosorbent test (RAST) is much more useful in the diagnosis. An extremely elevated Igp may indicate another problem, such as chronic parasitic infection, IgE my- eloma, or Job’s syndrome.

Patients evaluated for dizziness, true vertigo, or Meniere’s disease should have a complete neurotologic evaluation, including audiometry and electronystagmography to rule out a retrocochlear cause, although results of these tests will be normal in the majority of cases. These


patients also may need a metabolic evaluation to rule out conditions such as a thyroid abnormality or hypoglycemia.

Allergy Testing

Testing techniques endorsed by the American Academy of Otolaryn- gic Allergy (AAOA) and AAO-HNS determine not only what a patient is sensitive to, but also quantify how sensitive the patient is to each individual allergen, thereby establishing a safe starting dosage of immunotherapy. Recommended techniques for the diagnosis of IgE-mediated inhalant allergy include skin end point titration (SET) and the RAST test. Both techniques give qualitative and quantitative information on specific allergens, and each correlates well with the other in terms of specificity and sensitivity. The beginning practitioner should have a working knowledge of skin testing to compare to in vitro techniques. Both of these topics are covered in this volume and e l ~ e w h e r e . ~ ~ , ~ ~

Advantages of SET include a high degree of sensitivity, allowing safe co-seasonal testing initiation of immunotherapy when the patient is most symptomatic. The results are available immediately, allowing little delay between testing and the initiation of immunotherapy. Individual or unusual allergens suggested by the patient’s history can be tested easily without the need for obtaining an expensive in vitro test panel. Finally, it serves as a bioassay to verify patient sensitivity to a given allergen.

Disadvantages of SET include suppression of test results by antihistamines, tranquilizers, and antidepressants. Accordingly, antihistamines should be stopped at least 24 to 48 hours before testing. The use of positive controls, such as histamine, and negative controls, such as saline and glycerin, at the onset of testing helps establish the reliability of the skin test response. Physiologic factors, such as dermatographism, eczema, infancy, or senility, also may influence test responses.

Advantages of RAST include patient and physician convenience and no inherent risk to the patient of severe reactions to testing. The test is useful in young or apprehensive patients or those with dermatologic conditions precluding skin testing. It also may be used for diagnosis when it is impossible to stop medications, such as antihistamines, that may affect the skin test response.

Disadvantages include a slightly lower level of sensitivity than SET, as well as results not as immediately available as they are in skin testing. RAST testing is more expensive than skin testing, although the cost may be offset by the use of a diagnostic ”mini-screen” before a full RAST

Food Allergies

Food allergies are increasingly being recognized as an important cause of chronic clinical symptoms. As with inhalant allergy, the propen-


sity to develop a food allergy is inherited. Additionally, the allergic individual usually must be exposed repetitiously to the food to develop sensitivity; biochemically, certain foods appear more likely to stimulate an immune response than others. Cow’s milk, for example, would cer- tainly be the most prevalent food allergen worldwide.

Indications of a possible food allergy include craving or addiction to a particular food(s); perennial symptoms; a history of infantile allergy to foods producing symptoms such as frequent croup, eczema, and colic; excess fluid retention; improved symptoms after religious or surgical fast; and failure to improve perennial symptoms after adequate control of inhalant allergies. Although inhalant allergy is an immediate, Type 1- mediated immune reaction, all four Gel1 and Coombs reactions have been shown to be stimulated by food antigens?* Two excellent articles on testing techniques for evaluating food allergies are found elsewhere in this volume.21, 26

ALLERGY TREATMENT

The best treatment for the allergic patient is avoidance of the offending allergen. Booklets on nonspecific environmental control mea- sures for common allergens, such as dust mite and mold, can prove useful for many patients.

For patients sensitive to multiple allergens, the majority, avoidance is rarely sufficient to control symptoms. Pharmacotherapy, immunotherapy, or both may be necessary for relief. The benefits of pharmacotherapy alone may be enhanced by in vivo or in vitro tests to determine the specific inhalant allergens involved and to assess the potential need of adding immunotherapy to the treatment regimen.

Pharmacotherapy

Antihistamines

The proper use of antihistamines is the cornerstone of pharmacotherapy of inhalant allergy, particularly when the symptoms are nasal and are produced by pollens or are seasonal. Antihistamines alleviate symptoms of nasal allergy such as sneezing, rhinorrhea, and itching. The drying action against these “wet“ symptoms is primarily due to the antimuscarinic effect of the drug.

However, studies have shown that the post-challenge use of antihistamines and decongestants is not efficacious in preventing ET obsQruc- tion after provocative intranasal challenge tests, nor in promoting the resolution of middle ear effusions in children with OME.7 Fireman has reported that pretreatment with antihistamines prior to provocative antigen challenge ablated the development of ET obstruction in 40% of patients studied.l8 The difference in these results probably is related to


a beneficial effect of pretreatment with antihistamines versus their use only after symptoms have already become manifest. Also, it is possible that the prevention of ET obstruction associated with provocative intranasal challenge is more easily accomplished than that due to prolonged natural pollen exposure.

Virtually all patients with Meniere’s disease receive antihistamines at some point during their treatment. Indeed, for the primary care physician, meclizine, an antihistamine of the piperazine class, is often the initial drug prescribed for patients seen with suspected labyrinthine problems such as Meniere’s disease. Although antihistamines may offer some stabilizing effect on the labyrinth, presumably from anticholinergic effects, they do nothing to change the underlying hydropic distention of the endolymphatic system felt to largely contribute to the production of Meniere’s symptoms. The senior author has found the routine use of antihistamines in patients with suspected allergic Meniere’s disease to be limited to lessening the severity of vertigo attacks, or improving extralabyrinthine symptoms of allergy.

Decongestants

Decongestants reduce swelling by causing the alpha adrenergic receptors in the mucosa of the respiratory tract to vasoconstrict. The addition of common decongestants such as ephedrine, pseudoephedrine, or phenylpropanolamine HC1 to an antihistamine preparation may improve the clinical efficacy and allow a lower dose of antihistamine to be used, and balance the sedative effects of antihistamines against the stimulatory ones of decongestants.

Decongestants may be given orally or applied topically in nasal sprays or drops. Although the efficacy of topical application is greater, the rapid development of rebound rhinitis and the potential for eventual development of rhinitis medicamentosa limit the use of topical decongestants to short-term or self-limited illness, such as colds or sinusitis. The use of decongestants may be helpful for short-term improvement in ET dysfunction prior to flying or altitude change.

Cromolyn Sodium

Cromolyn sodium, inhaled as an oral powder, was used for years to manage asthma before it was finally available in solutions for nasal and ocular applications. Derived from a middle eastern plant, cromolyn sodium is applied topically to a mucous membrane containing sensitized mast cells, and prevents degranulation and mediator release by reducing the calcium transport across mast cell membranes.19

Cromolyn sodium alleviates both seasonal and perennial allergic rhinitis and may prevent the acute and late-phase allergic reaction. The drug is most effective when used before the allergen challenge, and it appears to work best in patients with high preseasonal IgE.30 Fireman


found that pretreatment with cromolyn prior to an intranasal antigen challenge ablated ET obstruction in 64% of patients studied.I8

Corticosteroids The anti-inflammatory action of corticosteroids is not in the actual

prevention of antigen-antibody interaction, with its subsequent mediator release. Rather, these agents decrease the resultant effects through several mechanisms, including stabilization of lysosomal membranes, blockage of the effect of migratory inhibitory factor, and a decrease in ~ermeability.~~

Corticosteroids may provide effective relief of allergic symptoms, but do so at the cost of potentially hazardous side effects. Systemic corticosteroids may be a useful adjunct in the management of the patient with allergic Meniere’s disease. Amounts needed are typically large, with an initial dose of 60 mg per day being given at least 2 weeks before being tapered. The first author has not found the use of the short-term commercially prepared dose-package to be of much use in the treatment of labyrinthine symptoms of allergy.

Corticosteroid sprays, with their more concentrated therapeutic effect directed to the nasal mucosa, may avoid the problems associated with systemic steroids in the treatment of ET dysfunction. Although not useful in the treatment of allergic Meniere’s disease, it has been reported that the use of topical flunisolide accelerated the return of normal eustachian tube function in allergic children.18 However, systemic effects from absorption through the nasal mucosa may occur after using high doses, requiring physician supervision for prolonged prescribing periods.

For those patients who do not obtain adequate relief with the medications mentioned, especially those with perennial or labyrinthine symptoms, immunotherapy, with its ability to alter the abnormal immune response, may offer substantial improvement.

lmmunotherapy Most patients will develop a significant improvement in their symp-

toms within 3 months of starting immunotherapy by SET. SET does not establish the final volume or strength to be used for desensitization; that is determined either by clinical response to immunotherapy or by unacceptable local or systemic reactions to progressive dose escalation.

The results of the RAST test may be used directly to calculate treatment sets and dose escalations for immunotherapy using techniques derived from Before RAST-based treatment, positive and negative controls of histamine, saline, and glycerin should be applied to the skin, as in SET. It is also essential to perform a skin test with a proposed treatment set calculated by the RAST scores, both to assess the biologic potency of the mixture and to ascertain that no excessive local reaction occurs.


Both SET and RAST offer safe, effective quantitative approaches for the diagnosis and treatment of inhalant allergies. Both techniques may be applied safely by the otolaryngologist in an office setting. They play an inherently valuable role in the continuum of medical and surgical treatment available in our specialty to provide the most effective treatment for the patient with significant otologic symptoms due to allergy.

Diet

Once diagnosed, food hypersensitivities are best treated by eliminating the offending food(s) from the diet in all forms until clinical improvement appears, eventually followed by the development of limited immune tolerance. That point, which usually takes at least 3 months of dietary avoidance for an adult to achieve, is determined by a deliberate challenge feeding test. If no symptoms are produced, the patient may reintroduce the food back into the diet. A rotation diet, or eating the food no more than one day out of every four, usually maintains tolerance. A very small percentage of patients will not develop tolerance; rather, they will have a "fixed" reaction to the food that persists despite dietary avoidance.

Alternatively, if there are multiple food allergens or the patient is unable to avoid eating the food, treatment by injection or sublingual drops of the "neutralizing dose" established during provocative food testing will provide clinical improvement for many.27, 29

SUMMARY

Allergy may affect the outer, the middle, or the inner ear. Although the otologic manifestations of allergy are not by themselves diagnostic, the history, including family history and associated symptoms in other target organs, will often help lead to the correct diagnosis and institution of therapy.

Patients with significant and chronic symptoms, including those with labyrinthine symptoms of allergy, will respond well to specific immunotherapy and/or dietary elimination.

ACKNOWLEDGMENTS

The authors would like to thank Ms. Stacy Dorcas for manuscript preparation and typing, and Ms. Liz Gnerre for library services.

References

1. Ackerman MN, Friedman RA, Doyle WJ, et al: Antigen-induced eustachian tube obstruction: An intranasal provocative challenge test. j Allergy Clin Immunol 73:604, 1984


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1971

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