ALLERGY AND THE OTOLARYNGOLOGIST
| ADDING ALLERGY MANAGEMENT TO YOUR PRACTICE —David Greene, MD, Adjunct Faculty, Cleveland
Clinic Head and Neck Institute, and Chair, Department of Otolaryngology, Medical Surgical Specialists, Cleveland
Clinic Florida, Naples, FL
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| Relevance to otolaryngology: discussing (and treating) allergies part of good medical care; ≥40% of otolaryngology
patients suffer from allergic disease; medical trends shifting toward identifying and treating underlying causes
of disease (not just alleviating symptoms); many otolaryngologic diseases linked to allergy (eg, sinusitis, rhinitis,
laryngitis)
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| Immunotherapy: decreases symptoms and need for medication; alters course of allergic disease; prevents development
of additional allergen sensitivities; prevents progression to asthma (allergic march); practical aspects—
American Board of Otolaryngology recognizes allergy as core part of specialty (ie, not subspecialty); American
Academy of Otolaryngic Allergy (AAOA) provides additional training and certification; allergy immunology required
by all otolaryngology residency programs; 34% of otolaryngologists provide immunology; economics—
patients already in practice constitute captive market; high demand for allergy management; patients prefer on-site
diagnosis and treatment; reimbursement for some otolaryngologic services and procedures decreasing, but reimbursement
for evaluation and management services increasing; expanding practice to include allergy management
often increases revenue by $100,000 to $180,000 in first year
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| Start-up: minimal cost; initial requirements—one full-time equivalent “allergy nurse”; dedicated room; refrigerator;
tray of allergen extracts; income—practice that brings in 10 patients/mo (assume 60% of patients undergo allergy
testing and 70% of those begin immunotherapy), can expect $183,000 in annual revenue; average practice
brings in ≈$250,000 annually; overhead typically costs <50% of revenue; minimal investment in time and effort
required
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 | Practical steps: start with existing office staff and facilities (no initial change in overhead); attend AAOA basic and advanced
courses; review treatment for anaphylaxis (rare, but life-threatening complication); add allergen testing first;
testing—Multitest II fast and simple; insurance reimburses $150 for 30-allergen test; larger-scale testing not necessary
(in Europe, standard to test for 1-3 allergens; crossover reactions common); simplify startup—allergen providers
offer complimentary consultation and staff training (interested in building relationships and training allergists);
use of prepared extract vials (sublingual and subdermal) minimizes in-office work and reduces barrier to entry into
field of allergy (no need to perform dilutions); upcoming regulations—in-office dilutions will require clean room
with hood and trained staff; using prepared vials circumvents need for expensive overhead; meticulous procedures
require nurse dedicated only to mixing and diluting allergens; scaling up—determined by patient demand and professional
interest
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| Testing options: in vitro tests—eg, radioallergosorbent test (RAST); easiest technique; blood samples sent to outside
laboratory for analysis; companies provide equipment and training; no additional resources needed; skin-prick
testing—eg, Multitest II; basic version tests 24 allergens (on forearm) in 30 sec; fast, simple, and painless technique;
minimal overhead and time required; 60-prong tester (applied to stomach) less accurate because uneven surface
results in uneven penetration; skin end-point titration (SET)—old version, costly and time-consuming;
insurance companies limited reimbursement; modified SET technique begins with skin-prick test, then selects allergens
to test intradermally; titrations (based on size of wheal and flare) further refine results
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| Immunotherapy options: subcutaneous immunotherapy (SCIT)—industry standard in United States; injections
given multiple times each week, then taper to once monthly; treatment continues for 3 to 5 yr; sublingual immunotherapy
(SLIT)—commonly used in Europe; good support in literature; patients place drops under tongue, 3
times/day (at home); therapy continues 3 to 5 yr; negligible risk for anaphylaxis; may be somewhat less effective
than SCIT
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| Resources required for SCIT: one full-time-equivalent nurse or medical assistant; dedicated room; vial storage; vial
mixing facility (optional); staff training; space for patients to wait after injections (to monitor reaction); crash
cart (to respond to anaphylaxis); certification for basic and advanced cardiac life support
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| Other practice issues: SCIT—covered by insurance; generates ≈$1000/patient per year; requires time commitment
by patient (may dissuade some); easy to add to practice (especially if using prepared vials); SLIT—not covered
by insurance; revenue based on market value; convenient for patients; less common in United States; easy and
safe
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| Summary: allergy management—natural extension of otolaryngology practice; critical to treatment of most common
diagnoses in otolaryngology; beneficial service to patients; simple to implement and cost-effective
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| AN OVERVIEW OF THERAPEUTIC OPTIONS —Keith A. Sale, MD, Assistant Professor, Department of Otolaryngology-Head
and Neck Surgery, University of Kansas Medical Center, Kansas City
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| Impact: affects ≈20% of US population; accounts for \>2 million lost days of school and \>3.5 million lost days of work;
decreases worker productivity by ≈25%; estimated financial impact—\>$5.3 billion annually (direct and indirect costs)
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| Seasonal allergies: type and prevalence vary geographically and temporally; Asthma and Allergy Foundation of
America publishes pollen counts and ranks cities by allergen prevalence; seasonal changes in pollen—in Midwest,
trees predominate in spring, grasses in summer, and weeds in fall; other allergens—dust mites and pets more problematic
in winter; molds prevalent year-round
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| Allergic cascade: initial exposure—antigen absorbed by macrophage; T2 helper cell response initiated; B-cells
stimulated to produce IgE antibodies; subsequent exposures—antigen crosslinks to IgE antibodies on mast cells;
degranulation occurs, resulting in symptoms (early phase); endothelial activation recruits white blood cells (primarily
eosinophils and basophils), resulting in late phase of allergic reaction
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| Phases: early—dominated by production of histamines; results in increased vascular permeability, vasodilation,
and smooth muscle contraction; characterized by classic symptoms (eg, itching, sneezing); leukotrienes and interleukins
recruit cells that participate in late phase; late—dominated by eosinophils; mediated by leukotrienes,
interleukins, and prostaglandins; also responsible for delayed allergic reactions
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| Target organs: ears; nose; throat; larynx; gastrointestinal system; lungs and bronchial tree; skin; others
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| Avoidance: dust mites—washing sheets in hot water (130°F to 140°F) or freezing sheets kills mites (most dryers not
hot enough to kill mites); animal dander—remove pets or minimize exposure (eg, limit access to furniture);
pollen—remain indoors; wear face mask outdoors when necessary
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| Nasal irrigation: salt-water flush increases mucociliary clearance, removes antigens and inflammatory mediators
from nose, and decreases edema; well tolerated; minimal adverse effects; good adjunct for managing rhinosinusitis or
allergy
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| Systemic antihistamines: first-generation—lipophilic molecules cross blood-brain barrier, resulting in sedation;
associated with anticholinergic effects (eg, urinary retention; dry mouth); second-generation—lipophobic molecules
cause less sedation and have less anticholinergic activity
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| Desloratadine: metabolite of loratadine has more rapid onset; safe to use during pregnancy (category B); liquid formulation
available for children
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| Cetirizine (Zyrtec): metabolite of hydroxyzine, has some anti-inflammatory properties (useful for patients with nasal
polyps), and affects T-cells, reducing formation of IgE antibodies; some sedation seen in 10% to 15% of patients;
liquid formulation available
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| Fexofenadine (Allegra): generic formulation available; metabolite of terfenadine (removed from market because of
adverse cardiac events), has some anti-inflammatory activity (less than cetirizine); liquid formulation available
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| Azelastine: only antihistamine available in nasal spray formulation; oral formulation available only in Europe;
effects—reduces early- and late-phase symptoms; affects histamines, leukotrienes, and cytokines (mechanism
unclear); does not cause sedation; may have bitter metallic taste; other indications—vasomotor rhinitis (good option
if cause of rhinitis unclear); approved for use in children
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| Comparative efficacy: inhibition of wheal and flare response—cetirizine most effective, followed by fexofenadine;
cetirizine associated with most consistent and durable antihistamine response; control of seasonal rhinitis—small
studies show superiority of cetirizine over others
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| Adverse effects: cetirizine associated with sedation; task-performance studies—randomized double-blind trials using
driving simulator found performance of patients taking fexofenadine similar to performance of those taking
placebo; cognitive tests—patients taking cetirizine or loratadine perform similarly to those taking placebo
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| Nasal symptoms: azelastine superior to oral antihistamines in reducing nasal congestion and (sometimes) rhinorrhea
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| Leukotriene inhibitors: eg, montelukast (Singulair); efficacy—equal to or less than that of most antihistamines in
controlling seasonal allergic rhinitis; less effective than nasal steroid sprays; combination therapy—montelukast
acts synergistically with antihistamines; combination more effective than either agent alone
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| Mast cell stabilizers: eg, cromolyn (eg, NasalCrom); taken before exposure to antigen; prevent allergic reaction; no
benefit if taken after exposure
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| Nasal steroid sprays: lipophilic; affect transcription and translation; result in decreased recruitment and migration
of eosinophils into tissues and increased apoptosis; impair basophils and mast cells, resulting in decreased production
of histamine; down-regulate cells involved in allergic cascade
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| Efficacy: similar for all formulations; potency—inhibition of interleukin (IL)-4; fluticasone and mometasone most
potent, followed by budesonide; beclomethasone and triamcinolone least potent; systemic bioavailability—lowest
with mometasone, followed by fluticasone furoate (Veramyst) then fluticasone propionate (Flonase); symptom
control—study compared fluticasone and triamcinolone; similar overall responses (total nasal symptom score
plus total eye symptom score); nasal steroids decrease symptoms immediately; benefit increases with continued
use; application—aiming spray at lateral nasal wall more effective than spraying in middle of nose
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| Effect on growth: studies report conflicting data; use in children—weigh potential risk for growth inhibition; monitor
growth; titrate to minimum effective dose
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| Combination therapy: study showed addition of fluticasone to antihistamine or leukotriene antagonist decreased
nasal congestion; fluticasone alone performed better than montelukast, antihistamine, and combination of montelukast
plus antihistamine; adding antihistamine to fluticasone therapy improved symptom control (but not statistically
significant); other studies had similar results and found reduced daytime somnolence with nasal steroid
spray
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| Clinical pearls: nasal steroid spray considered first-line therapy for allergic rhinitis; speaker begins with 6-wk trial,
along with hypertonic saline irrigation (follows with sinus imaging or antibody testing for unresponsive patients);
for patients unable to tolerate nasal steroid spray, combination therapy with antihistamine and montelukast often
effective; children—begin with antihistamine to avoid risk for growth inhibition
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| Allergy testing and immunotherapy: desensitization for life-threatening allergies (eg, bee stings) only absolute
indication; note—consider nonallergic etiology if results from allergy testing and symptom chronology do not
match; when to perform allergy testing—speaker performs allergy testing only in patients who have failed medical
therapy; practice differs among allergists
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| Contraindications to immunotherapy: poorly controlled asthma (risk for severe attack); β-blocker therapy (potentiates
anaphylactic response; increases risk; minimizes effectiveness of medications used to reverse anaphylaxis);
pregnancy (avoid testing or increasing dose of immunotherapy; acceptable to maintain pregnant women on current
dose)
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| Mechanism of action: not fully elucidated; theories—increases antigen-specific suppression of T cells; creates IgG
antibody that blocks production of IgE when exposed to antigens
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| Duration of therapy: generally 3 to 5 yr; begin with weekly injections until symptoms controlled, then decrease frequency
(usually after 1-1.5 yr); discontinue therapy once patient and physician expectations met (ideally, patient
has no symptoms and requires no allergy medications, but other outcomes acceptable); follow up at 6 mo and 1
yr (20%-30% of patients relapse at some point)
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| Closing comment: compliance key; assess compliance with previous regimens before labeling them as failed treatments
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Suggested Reading
Cox L: Sublingual immunotherapy in pediatric allergic rhinitis and asthma: efficacy, safety, and practical considerations.
Curr Allergy Asthma Rep 7:410, 2007; Ferguson BJ: Environmental control of allergies. Otolaryngol Clin
North Am 41:411, 2008; Garavello W et al: Nasal rinsing with hypertonic solution: an adjunctive treatment for pediatric
seasonal allergic rhinoconjunctivitis. Int Arch Allergy Immunol 137:310, 2005; Gluck J et al: Allergen immunotherapy
in intermittent allergic rhinitis reduces the intracellular expression of IL-r by CD8+ T cells. Vaccine 26:77,
2007; Haydon RC: Allergic rhinitis-current approaches to skin and in vitro testing. Otolaryngol Clin North Am
41:331, 2008; Herman H: Once-daily administration of intranasal corticosteroids for allergic rhinitis: a comparative
review of efficacy, safety, patient preference, and cost. Am J Rhinol 21:70, 2007; Ho CY, Tan CT: Comparison of
antileukotrienes and antihistamines in the treatment of allergic rhinitis. Am J Rhinol 21:439, 2007; Krouse JH: Allergic
rhinitis-current pharmacotherapy. Otolaryngol Clin North Am 41:347, 2008; Leatherman B: Injection and sublingual
immunotherapy in the management of allergies affecting the unified airway. Otolaryngol Clin North Am 41:359,
2008; Martin BG et al: Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for the
treatment of seasonal allergic rhinitis symptoms. Ann Allergy Asthma Immunol 96:851, 2006; Montoro J et al: Allergic
rhinitis: continuous or on demand antihistamine therapy? J Investig Allergol Clin Immunol 17(Suppl 2):21, 2007;
Ratner PH et al: Combination therapy with azelastine hydrochloride nasal spray and fluticasone propionate nasal
spray in the treatment of patients with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 100:74, 2008; Schad
CA, Skoner DP: Antihistamines in the pediatric population: Achieving optimal outcomes when treating seasonal
allergic rhinitis and chronic urticaria. Allergy Asthma Proc 29:7, 2008; Settipane RA, Charnock DR: Epidemiology
of rhinitis: allergic and nonallergic. Clin Allergy Immunol 19:23, 2007; Ventura MT et al: Local and systemic
reactions occurring during immunotherapy: an epidemiological evaluation and a prospective safety-monitoring study.
Immunopharmacol Immunotoxicol 30:153, 2008.
Educational Objectives
| The goal of this program is to improve the management of allergies and allergic rhinitis. After hearing and assimilating
this program, the clinician will be better able to:
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| 1. Discuss the clinical and socioeconomic relevance of allergy.
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| 2. Outline the steps involved in initiating allergy management services in an existing otolaryngology practice.
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| 3. Compare currently available techniques for allergy testing and immunotherapy.
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| 4. List the medical options for controlling allergic rhinitis and compare their efficacies and adverse effects.
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| 5. Design and implement evidence-based management plans for patients with allergic rhinitis.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, the following has been
disclosed: Dr. Greene receives research support from Arthrocare and Ellman. Dr. Sale and the planning committee reported
nothing to disclose.
Acknowledgments
Dr. Greene was recorded at 6th Annual Cleveland Clinic Otolaryngology Symposium, sponsored by Physicians Regional
Medical Center, and held March 15-17, 2007, in Naples, FL; Dr. Sale was recorded at Kansas City Society of Ophthalmology
and Otolaryngology Annual Clinical Conference, held January 11-12, 2008, in Overland Park, KS. The
Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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