ALLERGY UPDATE
| RHINITIS: NOTHING BUT THE TRUTH —Martin I. Sachs, DO, PhD, Professor of Pediatrics, Mayo Medical
School, Mayo Clinic, Rochester, Minnesota
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| Chronic rhinitis: allergic rhinitis and nonallergic rhinitis with eosinophilia occur at similar rates; rhinitis without involvement
of eosinophils uncommon; allergic rhinitis—IgE antibody bound to mast cell reacts with specific allergen;
activated mast cell degranulates and releases mediators that cause symptoms and attract eosinophils (have
primary role in disease); new treatments (eg, intranasal corticosteroids) directed at eosinophils; nonallergic rhinitis
with eosinophilia—mucosal disease, primarily activated by eosinophils; no allergic component (ie, mast cells not involved);
no benefit from antihistamines; large number of eosinophils present in mucosa and submucosa
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| Signs and symptoms: allergic rhinitis—release of histamine results in nasal symptoms (itch, sneezing, rhinorrhea,
and congestion) and ocular symptoms (itch, redness, tearing, and swelling); photophobia does not occur with allergic
conjunctivitis (indicates corneal disease and requires referral to ophthalmologist); nonallergic rhinitis with
eosinophilia—no eye symptoms (important for distinguishing from allergic rhinitis); hay fever—seasonal allergies
with predominance of nasal symptoms; ocular symptoms common; itching (eg, palate, ear canals) caused by release
of large amounts of histamine; absence of cough (if present, consider other diagnosis, eg, asthma); note—allergic
rhinitis rare in children <4 yr of age (ie, rhinitis in young children unlikely to respond to antihistamines)
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| Physical examination: findings essentially normal; “shiners” (dark circles under eyes) and transverse crease across
nose (caused by repeated rubbing) may occur with any chronic rhinitis; no physical findings specific to allergic
rhinitis; obstructions—rule out nasal obstructions (eg, polyps); spray nasal decongestant to shrink lining of nose
(improvement indicates mucosal involvement); look for evidence of obstruction (sneezing and coryza predominate
in patients with obstructive disease)
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 | Case: child, 7 yr of age, has seasonal symptoms in August and September and no concomitant atopic disease (rhinitis
seen with atopic diseases typically nonallergic); symptoms include coryza, nasal congestion, and eye symptoms;
diagnosis—seasonal allergic rhinoconjunctivitis
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| Treatment of allergic rhinitis: avoidance when possible; antihistamines now take secondary role to intranasal corticosteroids
(more effective than antihistamines; affect eosinophils); immunotherapy reserved as last resort
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| Antihistamines: sedation—fexofenadine (Allegra), loratadine (eg, Claritin), and desloratadine (Clarinex) do not
perfuse blood-brain barrier (ie, nonsedating); cetirizine (Zyrtec) sedating in 7% to 10% of patients; efficacy—
Zyrtec most potent H1 -blocker, followed by Allegra; Claritin and Clarinex considerably less effective;
convenience—once-daily dosing; safety—some sedation with Zyrtec; cost—Claritin available over-the-counter
(OTC); use—avoid using antihistamines on daily basis; consider treatment with intranasal corticosteroid during
allergy season; give antihistamine prn to address eye symptoms
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| Corticosteroids: available steroids (triamcinolone, mometasone, fluticasone, and budesonide) have similar efficacies
for treating rhinitis; use—1 spray in each nostril, generally once daily; efficacy—no additional treatment
necessary in 80% of patients with allergic rhinitis, but potential problems with compliance; effective monotherapy
in patients with nonallergic rhinitis; cost—less expensive than antihistamines; adverse effects—nosebleed occurs
in 1% of patients, but avoiding septum by directing spray straight into nasal canal decreases risk; 1 report of
septal perforation; local irritation (burning) occurs in 1% to 2% of patients; no reports of nasal candidiasis in
healthy patients; no suppression of hypothalamus-pituitary-adrenal (HPA) axis at doses ≥2 times recommended
dose; note—additive to inhaled corticosteroids; important to calculate total amount given for nose and chest; inhibition
of growth—does not occur at doses 4 times recommended dose; reported only with beclomethasone (no
longer used)
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| Alternative treatments: intranasal antihistamines (eg, azelastine [Astelin]) only for patients with allergic rhinitis;
leukotriene inhibitors (eg, montelukast [Singulair]) as effective as antihistamines, but no added benefit when
used in combination with antihistamines; nasal decongestants only for short-term use (extended use results in rebound
vasodilation)
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| Testing for allergic rhinitis: allergy testing recommended when treatment strategy includes avoidance (eg, pets or dust
mites) or immunotherapy; skin puncture test as effective as allergen-specific IgE antibody test (RAST), cheaper, and
easier to perform (but single RAST recommended to confirm suspected allergy to dust mites); note—only allergens
that evoke symptoms upon exposure clinically significant, regardless of positive RAST
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| Immunotherapy: not all allergens used in immunotherapy well-standardized; tree pollen, grass pollen, dust mite, and
weed allergens most standardized; no standardization among indoor mold allergens (eliminates role in immunotherapy);
risks—anaphylactic shock may result in death in sufficiently sensitive individuals; primary care physicians
who perform immunotherapy in office must be fully prepared to resuscitate patient, if necessary; all patients should
wait 30 min in office after injections (95% of serious reactions occur within 30 min); benefits—5-yr course (once
weekly for 6 mo, then once monthly for 4.5 yr) may eliminate allergic response to specific allergen (but if no improvement
after 2 yr, discontinue immunotherapy); disease progression—immunotherapy unlikely to prevent
asthma (often occurs before rhinitis in “atopic march”), but good option for patients with allergic symptoms in nose
and chest; patient selection—specific allergen identified; symptoms uncontrolled with intranasal steroids and antihistamines
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| Allergic conjunctivitis: treatment options—eye drops with antihistamine and decongestant or antihistamine alone;
mast cell stabilizer (eg, olopatadine ophthalmic [Patanol]); oral antihistamines; oral corticosteroids for short-term
treatment; immunotherapy less effective for treating conjunctivitis than rhinitis; topical steroids not used in eyes
because of risk for cataracts, infections, and glaucoma; speaker recommends intensive short-term therapy with antihistamines
(eg, 1 nonsedating antihistamine in morning and 1 Zyrtec at night) when allergies most severe
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| Nonallergic rhinitis with eosinophilia: common perennial disease; no histamine released; many patients also have
asthma (part of atopic march); eosinophilic inflammatory sinusitis or gastroenteritis may also occur
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| Case: child, 11 yr of age, with perennial nasal congestion and no eye symptoms; no fixed obstructions (important to
assess, especially when patient has primary complaint of congestion, snoring, or dependent mouth-breathing);
atopic family history, including asthma; nasal eosinophilia present; diagnosis—nonallergic rhinitis with eosinophilia;
treatment—intranasal corticosteroids
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| Differential diagnosis: obstructive nasal disease—boy, 11 mo of age, dependent mouth-breather since birth; choanal
atresia ruled out; problems include snoring and difficulty breathing while eating; no coryza, sneezing, or eye symptoms;
medical history and physical examination otherwise normal; otolaryngology consult found bilateral polyps;
diagnosis of cystic fibrosis made; bilateral periorbital swelling—boy, 2 yr of age, with periorbital swelling, primarily
in morning; no ocular pruritus, tearing, or erythema; no nasal symptoms; age and symptoms inconsistent with allergic
conjunctivitis; diagnosis of nephrotic syndrome
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| More treatment options: ipratropium (Atrovent)—for treatment of patients with vasomotor rhinitis (consider diagnosis
in patients who do not respond to intranasal steroids); anti-IgE—monoclonal antibody against IgE; injections given
every 1 to 3 mo; no adverse effects, but high cost; beneficial for patients with food allergies, not well studied in patients
with allergic rhinitis; questions remain about efficacy and duration of protection; oral immunotherapy—large
dose of allergen; no reports of anaphylaxis; adverse effects include gastrointestinal upset; expensive
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| IMMUNOTHERAPY IN CHILDREN —Joann Blessing-Moore, MD, Associate Clinical Professor of Pediatrics,
Stanford University, School of Medicine, Stanford, California
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| Development of allergies and asthma: genetic predisposition alone insufficient; environmental factors (eg, ozone
levels and pollution) and infections also influence development of asthma, allergic rhinitis, and atopic dermatitis; T
cells—TH 2 cells stimulate production of IgE; normally, TH 1 cells increase in number just after birth; imbalance in
TH 1 and TH 2 cells (genetically influenced) increases risk of developing allergies
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| Atopy: systemic disease that includes atopic dermatitis, allergic rhinitis, conjunctivitis, sinusitis, and asthma;
diagnosis—history critical; skin tests and in vitro tests help establish diagnosis, but IgE in absence of symptoms not
diagnostic (eg, 25% of adults have IgE to bee venom, but only 4% have allergic reaction to bee stings)
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| Testing: skin tests—prick and intradermal; intradermal tests good for diagnosing allergies to inhalants, drugs, and
venoms, but not to foods; intradermal tests more sensitive than prick tests; serologic tests—good clinical tool but
less sensitive than skin tests (75%-90% sensitive; sensitivity and specificity vary with specific IgE and testing
method); food—Pharmacia CAP System for RAST predicts 95% of allergies when sufficient levels of IgE present
(dependent on food type); inhalants—sensitivity of RAST 80% to 85% (less sensitive than skin test); sufficient for
survey when specific allergen suspected; total amount of IgE not predictive of clinical relevance; venom—RAST
augments sensitivity of skin test; latex—no standardized test currently approved by Food and Drug Administration
(FDA); low sensitivity
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| Immunotherapy: can change pattern of cytokines to restore balance between TH 1 and TH 2 cells, slow progression of
allergic march, and reduce development of asthma; decreases sensitivity to insect stings in 94% to 97% of patients;
not recommended for patients with food allergies, urticaria, or angioedema; asthma—decreases incidence by ≥3-
fold, as shown in Preventive Asthma Treatment (PAT) study (3-yr study of 205 children, 6 to 14 yr of age)
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| Guidelines for immunotherapy: national guidelines available on American College of Allergy and Immunology
Web site; risk—life-threatening reactions from allergy shots rare (≤1 in 2.5 million injections); note—patient may
still need to take medications to control symptoms; environmental controls (ie, reducing exposure to allergens) still
important; other considerations—patient preferences and compliance to injection schedule for 3 to 5 yr; previous response
to immunotherapy; access to medical office with trained staff; risk for anaphylaxis (high-risk patients
treated by allergist); pregnancy—continue shots but do not advance dose; airway—important to ensure clear, open
airway before giving shots; antigen preparation—dilutions standardized to color of cap; label must include name of
patient, antigen, dilution, and expiration date; antigens sensitive to temperature (keep cold)
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| Injection schedule: traditional—one shot every 7 to 10 days, advancing dose over time; cluster—7 shots each visit,
waiting 30 min between shots and advancing dose each time (observe patient closely); note—reduce dose for patients
who missed injections or have new antigen added to regimen; questions—important to ask about new medications
(eg, β-blockers interfere with epinephrine used in treatment of patients in anaphylaxis) and recent illnesses
(consider measuring peak flow in all patients); accountability—patient or guardian checks label to confirm information
and commits to waiting 30 min before leaving office
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| Omalizumab (Xolair): humanized monoclonal antibody to IgE binds free IgE; mast cells without IgE cannot react to
antigens; circulating IgE decreased by 96%; indications—currently approved for patients ≥12 yr of age; initially approved
for patients with asthma, but also effective in patients with allergic rhinitis and drug and food allergies; beneficial
in combination with immunotherapy (different mechanisms of action); benefits—life-saving in some
patients; may improve asthma
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| Sublingual vaccines: single-antigen therapy used in Europe; reduces symptoms and medication requirements in
adults (also used in children)
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| Anaphylaxis: epinephrine—first-line treatment; fatalities associated with anaphylaxis typically result from delayed
administration of epinephrine; intramuscular epinephrine (EpiPen) recommended for patients with severe allergies
to foods or insect stings (important to teach patient how to administer); antihistamines—helpful, but do not replace
epinephrine; steroids—helpful against delayed (but not acute) response; other agents—O2 , bronchodilators, and
antileukotrienes have roles in treatment of anaphylaxis
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Educational Objectives
| The goal of this activity is to provide information about the diagnosis and treatment of allergies in children. After
hearing and assimilating this program, the clinician will be better able to:
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| 1. Discuss mechanisms of disease for allergic rhinitis and nonallergic rhinitis with eosinophilia.
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| 2. Diagnose patients with allergic and nonallergic rhinitis and discuss medical and nonmedical options for treatment.
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| 3. Discuss differences in sensitivity and specificity among methods for allergy testing.
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| 4. List indications and contraindications for immunotherapy.
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| 5. Identify patients likely to benefit from anti-IgE (omalizumab) therapy.
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Discussed on This Program
Azelastine HCl [Astelin]
Beclomethasone dipropionate [Beconase, Beconase AQ, QVAR, Vancenase, Vancenase AQ 84 mcg, Vancenase
Pockethaler, Vanceril, Vanceril Double Strength]
Budesonide [Entocort EC, Pulmicort Respules, Pulmicort Turbuhaler, Rhinocort, Rhinocort Aqua]
Cetirizine HCl [Zyrtec]
Desloratadine [Clarinex]
Epinephrine [Adrenalin Chloride, Adrenalin Chloride Solution, Epifrin, EpiPen, EpiPen Jr., Glaucon, microNefrin,
Nephron, Primatene Mist, S2]
Fexofenadine [Allegra]
Fluticasone propionate [Cutivate, Flovent, Flovent HFA, Flovent Diskus, Flovent Rotadisk, Flonase]
Ipratroprium bromide [Atrovent]
Loratadine [several formulations and trade names]
Mometasone furoate monohydrate [Nasonex]
Montelukast sodium [Singulair]
Olopatadine HCl [Patanol]
Omalizumab [Xolair]
Triamcinolone acetonide [several formulations and trade names]
Suggested Reading
Brussee, JE, et al: Allergen exposure in infancy and the development of sensitization, wheeze, and asthma at four
years. J Allergy Clin Immunol 115:946, 2005; Costa Carvalho BT, et al: Immunological evaluation of allergic respiratory
children with recurrent sinusitis. Pediatr Allergy Immunol 16:534, 2005; Dodig S, et al: Anti-IgE therapy with
omalizumab in asthma and allergic rhinitis. Acta Pharm 55:123, 2005; Eigenmann PA: Diagnosis of allergy syndromes:
Do symptoms always mean allergy? Allergy 60 Suppl 79:6, 2005; Finegold I: Immunotherapy in the age of
anti-IgE. Clin Rev Allergy Immunol 27:75, 2004; Kurukulaaratchy RJ, et al: Defining childhood atopic phenotypes to investigate
the association of atopic sensitization with allergic disease. Allergy 60:1280, 2005; Lieberman P, et al:
Open-label evaluation of azelastine nasal spray in patients with seasonal allergic rhinits and nonallergic vasomotor
rhinitis. Curr Med Res Opin 21:611, 2005; Marcucci F, et al: Three-year follow-up of clinical and inflammation parameters
in children monosensitized to mites undergoing sublingual immunotherapy. Pediatr Allergy Immunol 16:519,
2005; Meltzer EO: Evaluation of the optimal oral antihistamine for patients with allergic rhinitis. Mayo Clin Proc
80:1170, 2005; Ong YE, et al: Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat
skin allergen challenge. J Allergy Clin Immunol 116:558, 2005; Polosa R, et al: Effect of immunotherapy on
asthma progression, BHR and sputum eosinophils in allergic rhinitis. Allergy 59:1224, 2004; Riedl MA, et al: initial
high-dose nasal allergen exposure prevents allergic sensitization to a neoantigen. J Immunol 174:7440, 2005; Szeinbach
SL, et al: Influence of patient care provider on patient health outcomes in allergic rhinitis. Ann Allergy Asthma Immunol
95:167, 2005; Wheeler PW, Wheeler SF: Vasomotor rhinitis. Am Fam Physician 72:1057, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the faculty reported nothing to disclose.
Dr. Sachs was recorded in Scottsdale at 28th Pediatric Update, sponsored by Phoenix Children’s Hospital, and held
February 28 to March 3, 2005; Dr. Blessing-Moore was recorded in San Francisco at Advances and Controversies in
Clinical Pediatrics, sponsored by Department of Pediatrics, University of California, San Francisco, School of Medicine,
and held June 2-4, 2005. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
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