Docstoc

Allergic Rhinitis and Chronic Urticaria Management of Histamine

Document Sample
Allergic Rhinitis and Chronic Urticaria Management of Histamine Powered By Docstoc
					Planning Committee
Michael S. Blaiss, MD
Clinical Professor of Pediatrics and Medicine
                                                                        CONTINUING MEDICAL EDUCATION
Division of Clinical Immunology/Allergy
University of Tennessee Health Science Center



                                                                      Allergic Rhinitis and
Memphis, Tennessee

Anthony Montanaro, MD
Professor of Medicine
Chair, Division of Allergy and Clinical Immunology


                                                                      Chronic Urticaria:
Oregon Health and Science University
Portland, Oregon

Devera Pine



                                                                      Management of
Network for Continuing Medical Education
Secaucus, New Jersey




                                                                      Histamine-induced
     Statement of Disclosure and Independence

Planning Committee Disclosures:
Dr. Blaiss is on the speaker’s bureau for AstraZeneca and Dey,



                                                                      Disorders
and is on the advisory boards and speaker’s bureau for Alcon,
Genentech, GlaxoSmithKline, Merck & Co., Novartis, sanofi-
aventis, Schering Plough, and Sepracor.
Dr. Montanaro is on the speaker’s bureau for AstraZeneca,
Genentech, GlaxoSmithKline, Merck & Co., and Schering Plough.
Ms. Pine has no relevant financial relationships to disclose.
Review Committee Disclosure: In accordance with PCN pol-              Michael S. Blaiss, MD
icy, all content is reviewed by external independent peer reviewers
for balance, objectivity, and commercial bias. The peer reviewers,
                                                                      Anthony Montanaro, MD
staff, and other individuals who control content have no relevant
financial relationships to disclose.
Curtis P. Schreiber, MD has received research grant support
from Allergan, AmeriLabs, ANS, BioAlliance, Boston Scientific,        Allergic rhinitis is frequently underdiagnosed and undertreated,
Capnia, Endo Pharmaceuticals, GlaxoSmithKline, Hoffman
La Roche, Map Pharmaceuticals, Merck & Company, Minster               and chronic urticaria is often managed inappropriately.
Pharmaceuticals, NeurAxon, Novartis, NuPath, Pfizer, Takeda,
and Wyeth.
Grant Statement: This activity is supported through an educa-
tional grant from sanofi-aventis US and UCB, Inc.                     Learning Objectives
Target Audience: This activity is targeted to any primary care        After completing this activity, the learner will be better able to
provider who treats patients with allergic rhinitis or chronic
urticaria.                                                            • Identify strategies to overcome barriers for adequate control of allergic rhinitis symptoms
Unlabeled Use Declaration: During this activity, author(s)            • Create treatment strategies based on the most current evidence for the management
may discuss an unlabeled use or an investigational use not              of chronic idiopathic urticaria for better patient outcomes
approved for a commercial product. Each author is required to
disclose this information to the participants when referring to
an unlabeled or investigational use.                                  Overview
Accreditation: Primary Care Network, Inc. is accredited by            Allergic rhinitis and chronic idiopathic urticaria are histamine-induced conditions that have a
the Accreditation Council for Continuing Medical Education to         substantial impact on patient health and quality of life. Allergic rhinitis, which affects more
provide continuing medical education for physicians.
Physicians: Primary Care Network designates this educational
                                                                      than 14% of adults in the United States, can impact both work and school productivity and
activity for a maximum of .75 AMA PRA Category 1 Credit™.             is associated with comorbidities including asthma, sinusitis, and sleep disorders. Chronic
Physicians should only claim credit commensurate with the             idiopathic urticaria affects 0.5% to 1.0% of the American population and is highly debilitat-
extent of their participation in the activity.
                                                                      ing, negatively impacting sleep, mobility, and energy, as well as home, work, and social life.
Nonphysicians: All other healthcare professionals will be
issued a certificate of participation.                                Although antihistamines are common first-line treatments for both conditions, significant
Release Date: September 28, 2009                                      barriers remain to successful outcomes. Allergic rhinitis is frequently underdiagnosed and
Expiration Date: September 28, 2010                                   undertreated, and chronic idiopathic urticaria is often managed inappropriately.
Medium: eNewsletter
Method of Participation: To receive credit for this activity, you
must read the CME article. Upon finishing the article, complete
                                                                      Allergic Rhinitis
the session post-test, evaluation, and all required personal
information. To receive your CME certificate you will need to
pass the post-test with 70% accuracy or better. If you receive
                                                                      The Etiology and Impact of AR
less than 70%, review the article and take the test again.            Allergic rhinitis (AR) is caused by an immunoglobulin E (IgE)-mediated reaction of the nasal
Post-test and Evaluation: Upon completing the CME article,            mucosa to 1 or more allergens.1 The US classification of AR consists of 2 categories: sea-
revisit the online PDF and click on the Post-test button at the       sonal allergic rhinitis, or SAR, and perennial allergic rhinitis, or PAR. In SAR, symptoms are
end of the article. Upon successful completion of the post-test,
you will be asked to fill out a program evaluation form and           periodic and correlate with seasonal variations in airborne allergens. Common allergens that
prompted to print your CME certificate. Or complete the post-         cause SAR include grass, tree, and weed pollens, and, in some areas of the United States,
test and evaluation at the end of this article and fax to
417-841-3609. Upon successful completion of the post-test,            fungal (mold) spores.
you will receive your CME certificate within 4 to 6 weeks.

                                                                      In contrast, PAR shows little or no seasonal variation. Typically, the allergens associated with
          Hardware/Software Requirements
                                                                      PAR are found indoors and include house dust mites, animal danders, cockroaches, and
             Privacy/Confidentiality Policy                           mold spores. SAR and PAR often coexist in the same individual.1

                          Copyright                                   Characteristic symptoms of AR include clear rhinorrhea, nasal congestion, repetitive sneez-
                                                                      ing, and itching of eyes, nose, ears, and throat. Conjunctiva, middle ear, and paranasal
                    Contact Information                               sinuses may be involved.1 In addition, AR is frequently associated with cough, headache, and
                                                                      pressure over the cheeks and forehead. Malaise, irritability, and fatigue may also be present. >>



                                                                                                                                                     CME
                         Disclaimer

                                                                                                                                  Primary Issues Vol 11, No 5            24
                                                                                             Rhinitis and
                                                                                 >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                                    induced
 When not all of the typical rhinitis symptoms
 are expressed, the diagnosis is more difficult
 to make. Distinct temporal patterns of symp-
 tom production may aid diagnosis. SAR symp-
 toms typically appear during a defined season.              similar symptoms. Key differential diagnoses           nasal allergy sufferers documented that 80%
 In contrast, indoor allergens responsible for               of AR include rhinitis medicamentosa due to            of them complained of tiredness, at the same
 PAR are present in the environment through-                 OTC topical decongestant nasal sprays, infec-          time two-thirds felt “miserable” or “irritable”
 out the year.                                               tious rhinitis, anatomic obstruction, hormonal         during allergy season.8 When coupled with
                                                             rhinitis, nonallergic eosinophilic rhinitis, and       general feelings of sadness or depression,4
 Case Study                                                  idiopathic nonallergic rhinitis.1 It is important to   this can significantly impair daily activity.
 Helen is a 42-year-old stay-at-home mom with                remember that not all rhinitis is caused
 a history of seasonal allergies. Every spring               by allergies.                                          Treatment of AR
 since she was 14, Helen has begun sneezing                                                                         Diagnosis of AR requires a detailed and accu-
 and has had nasal itching and rhinor-                                   A study conducted in a group of            rate history.1 Because symptoms of allergic
 rhea. In the past, she managed her                                      804 patients who presented with            and nonallergic rhinitis are often similar, the
 nasal symptoms with an over-the-                                        AR symptoms (Figure 1) reported            patient should be asked about specific
 counter (OTC) antihistamine. How-                                       rhinorrhea in 85.9% of patients,           symptoms and symptom patterns, including
 ever, this spring the OTC treatment                                     nasal congestion in 86.6%, and             onset, progression, severity, and relationship
 has not been effective, her symp-                                       sneezing in 89.7%. Patients with           to seasons. Personal and family histories of
 toms are getting worse, and she                                         moderate to severe AR showed               allergic disease are also important. Physical
 complains of a “constant stuffed                                        significantly higher symptom               examination should focus on the nose, eyes,
 nose. In addition, for the first time,
       ”                                                                 scores for rhinorrhea, nasal con-          and ears, and should also include examination
 her husband has been complaining                                        gestion, nasal itch, conjunctivitis,       of the lungs and skin.1 The patient should be
 that she snores at night. Helen admits that                 headache, and somnolence than the patients             observed for mouth breathing, repeated nose
 she is tired in the morning and feels as if                 with mild AR showed.2 These results illus-             wiggling, wiping, and pushing (the “allergic
 she is dragging herself through the day. She                trate that AR is more than a runny nose. It is         salute”), a nasal crease, “allergic shiners”
 has a red nose and rubs her eyes and nose                   multidimensional in nature and may have a              (a darkening of the infraorbital skin resulting
 frequently during the examination. There are                profound effect on a patient’s quality of life.        from venous dilation and indicative of chronic
 dark circles under her eyes, and she is obvi-                                                                      nasal congestion, particularly in children), and
 ously breathing through her mouth. On exam-                 AR has been shown to impair cognitive                  related eye symptoms.
 ination, all other signs are normal.                        behavior, memory, and learning functions.3 In
                                                             general, patients report reduced motivation,           Determination of specific IgE, preferably by
 Please read more to learn how you might                     lower energy levels, increased tiredness, and          skin testing, may be needed to provide evi-
 diagnose and treat this patient’s condition.                mental fatigue.4-6 Symptoms of nasal conges-           dence of an allergic basis for the patient’s
                                                             tion often disrupt sleep and lead to daytime           symptoms, to confirm or exclude suspected
 The diagnosis of AR can be a challenge                      somnolence,7 which can affect productivity             causes of symptoms, or to assess the sensi-
 because a variety of other conditions produce               at work and/or school.4,8 A recent survey of           tivity to a specific allergen for avoidance
                                                                                                                                        measures and/or allergen
                                                                                                                                        immunotherapy. Nasal
 Figure 1. Typical Clinical Symptoms of AR                                                                                              smears for eosinophils are
                                                                                                                                        not necessary for routine
               70           Never/rarely          Occasionally                   Frequently        Always                               use in diagnosing AR.
                                                                                                                                        Although CT is not indicated
               60                                                                                                                       for the evaluation of patients
                                                                                                                                        with uncomplicated rhinitis,
                                                                                                                                        it may be useful with sus-
               50                                                                                                                       pected complications or
                                                                                                                                        comorbidities such as nasal
Patients (%)




               40                                                                                                                       polyposis and/or concomi-
                                                                                                                                        tant sinusitis. Standard
                                                                                                                                        radiographs are generally
               30                                                                                                                       not indicated because of
                                                                                                                                        the availability of preferred
               20                                                                                                                       procedures.1

                                                                                                                                      Case Study
               10
                                                                                                                                      Speaking with Helen to
                                                                                                                                      obtain a detailed picture of
               0                                                                                                                      her symptoms, you learn that
                    Rhinorrhea      Nasal            Nasal           Sneezing              Eye       Headache       Somnolence        her symptoms are continu-
                                  congestion          Itch                              Symptoms                                      ous throughout the year, but
                                                                     Symptom                                                          worse in the spring. When >>




                                                                                                                                                   CME
 Reprinted with permission from Van Hoecke H, et al. Allergy. 2006;61:705-711.

                                                                                                                               Primary Issues Vol 11, No 5          25
                                                                                        Rhinitis and
                                                                            >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                               induced
you examine Helen, you can see the allergic
shiners under both eyes and the allergic crease
across the bridge of her nose. There is also
prominent and severe nasal blockage and
congestion, with boggy pale turbinates and                  controls are not always practical or effective,       Table 1. Overview of Conventional
evidence of postnasal drainage.                             and supplemental medical management may               Pharmacotherapeutic Options
                                                            be required.1
Since Helen appears to have SAR, you could                                                                        • Oral antihistamines, sedating*
go straight to treatment. However, it would                 Case Study                                            • Oral antihistamines, nonsedating/low
also be appropriate to recommend tests to                   In Helen’s case, allergen avoidance and envi-           sedating†
determine sensitivity to specific allergens.                ronmental control measures aim to reduce
Allergic skin prick tests are cost effective, but                                                                 • Intranasal antihistamines
                                                            exposure to both seasonal and perennial
need to be performed by a trained specialist.               allergens. To minimize her seasonal symp-             • Decongestants
In vitro specific-IgE tests (eg, radioallergo-              toms, you advise Helen to keep the windows            • Intranasal corticosteroids
sorbent test [RAST]) are an alternative to skin             and doors shut and to use air conditioning
testing.1                                                   when possible because indoor pollen levels            • Oral corticosteroids
                                                            are increased by window or attic fans. You tell       • Intranasal cromolyn
Laboratory evaluation shows that Helen has a                Helen to limit outdoor activities during times        • Intranasal anticholinergics
positive RAST to tree and grass pollens and                 of high pollen counts, such as the early morn-
dust mites. She shows seasonal pollen sensi-                ing or during dry, windy periods, and that the        • Leukotriene modifiers
tivity as well as sensitivity to an indoor aller-           best time for outdoor activities is after it rains,   *Also referred to as first-generation antihistamines.
gen. You diagnose PAR and SAR.                              when pollen counts are low. Furthermore, you          †Also referred to as second-generation antihistamines.
                                                            recommend that she washes her bedding
Please read more to learn how the treatment                 weekly in hot water to help control dust mites        Lanier B. Allergy Asthma Proc. 2007;28:16-19.
plan is designed to maximize patient adher-                 and that she uses allergen-impermeable cov-
ence, which is strongly related to treatment                ers on her pillow, mattress, and box spring. You      allergic rhinitis.1 They are effective, are equal
success.                                                    explain to her that, ideally, she should remove       to or superior to second-generation oral anti-
                                                            carpet from the bedroom floor.                        histamines for the treatment of SAR, and are
There are 4 general principles of allergy man-                                                                    associated with a clinically significant effect
agement, shown in Figure 2.1                                Pharmacotherapy                                       on nasal congestion. Furthermore, nasal anti-
1. Avoid environmental factors that cause                   The goal of pharmacotherapy, the second prin-         histamines may have some anti-inflammatory
   symptoms                                                 ciple of allergy management, is to alleviate and      effect. For example, in addition to histamine
2. Use appropriate treatments. The goal of                  prevent the patient’s symptoms. Medications           antagonism, in clinical trials, azelastine has
   pharmacotherapy is to alleviate and prevent              used to treat AR,9 shown in Table 1, are briefly      been shown to have inhibitory effects on
   symptoms. Palliative treatment—nasal                     reviewed in this section.                             leukotrienes, bradykinin, and substance P11   .
   lavage and mist inhalation—may also be
   helpful                                                  Antihistamines                                        Although intranasal corticosteroids (ICS)
3. Evaluate for immunotherapy                               Antihistamines are a mainstay of pharmaco-            remain the most effective medication class for
4. Educate and follow up. Use appropriate                   therapy for mild and intermittent AR.1 Although       controlling symptoms of AR,1 intranasal anti-
   patient education materials                              the efficacy of first-generation agents has           histamines have a quicker onset of action than
                                                            been established, they have long been                 ICS have, and they show sustained improve-
Environmental Controls                                      replaced by second-generation compounds               ment over time.12 Clinical studies suggest that
Environmental controls should be addressed                  as the preferred treatment for AR. National           using both an intranasal antihistamine and an
at the onset of intervention and should be                  and international guidelines note that a more         ICS increase treatment efficacy more than
tailored to the individual patient’s exposures              favorable risk-benefit ratio and enhanced             40% compared with either agent alone. Dual
and sensitivities.1 Unfortunately, environmental            pharmacokinetics make second-generation               treatment may benefit some patients.
                                                                                  drugs preferable to
                                                                                  first-generation drugs.1,10     The side-effect profile of the intranasal anti-
Figure 2. Treatment of Allergic Rhinitis                                          Second-generation anti-         histamines includes bitter taste and sedation.2
                                                                                  histamines can be used          Newer agents, such as olopatadine hydrochlo-
                                 Allergen                                         on an intermittent basis,       ride and azelastine HCL have been formulated
                                Avoidance                                         but for control of SAR and      to decrease bitter taste.13,14
                                                                                  PAR, continuous use is
                                                                                  most effective.                 Decongestants
                                                                                                                  Decongestants are highly effective in relieving
                                                                                  Intranasal Antihistamines       obstructive nasal symptoms but are not effec-
 Pharmacotherapy                                     Immunotherapy
                                                                                  According to the 2008           tive in treating other major symptoms of AR,
                                                                                  Joint Task Force on             such as rhinorrhea, nasal itching, and sneez-
                                                                                  Practice Parameters for         ing.15 Oral decongestants, such as pseudo-
                                                                                  Allergy and Immunology,         ephedrine and phenylephrine, are most
                                                                                  intranasal antihistamines       effective when used in combination with
                                 Patient                                          may be considered for           antihistamines. Oral decongestants have a
                                Education                                         use as first-line treatment     number of important adverse effects, >>



                                                                                                                                                     CME
                                                                                  for allergic and non-
Bousquet J, et al. J Allergy Clin Immunol. 2001;108(5 suppl):S147-S334.
                                                                                                                              Primary Issues Vol 11, No 5                  26
                                                                               Rhinitis and
                                                                   >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                      induced
including nervousness, irritability, insomnia,
and palpitations. They can increase blood
pressure in patients with hypertension, and in
some older men oral decongestants can lead
to urinary retention. Because of their use in       and rhinorrhea. It does not improve ocular          Because studies show that approximately one-
possible illicit drugs, there are restrictions on   symptoms. Cromolyn sodium is not as effec-          third of patients are expected to be nonadher-
the sale of pseudoephedrine.16                      tive in treating the symptoms of AR as ICS          ent to treatment, part of the challenge for
                                                    are. Adverse effects are generally minor and        healthcare professionals is to help improve
Topical decongestants, such as oxymetazo-           include sneezing and burning.1                      patient adherence. It should be the respon-
line and phenylephrine, can be used for 3 to                                                            sibility of the healthcare provider to address
5 days. Their use in chronic conditions, such       Leukotriene receptor antagonists are antag-         each patient’s treatment plan with the patient
as AR, is relatively limited because of the         onists of cysteinyl leukotrienes-chemical           and determine if it is a reasonable strategy
potential for rebound congestion (rhinitis          mediators of airway inflammation. The biologi-      for that individual. There are several key fac-
medicamentosa).15                                   cal effects of cysteinyl leukotrienes include       tors that lead to nonadherence, including the
                                                    increased mucus secretion and vascular              frequency and ease of the use of the medica-
Intranasal Corticosteroids                          permeability. Antileukotrienes act as receptor      tion prescribed, adverse effects, poor com-
Intranasal corticosteroids are the most effec-      antagonists to prevent leukotriene-mediated         munication regarding precise management,
tive medication class in controlling the symp-      inflammation.20 Studies show they are equal to      psychosocial factors (such as depression and
toms of AR, including the 4 major symptoms:         or less efficacious than oral antihistamines are    poor interpersonal skills and coping strategies),
sneezing, itching, rhinorrhea, and nasal con-       in AR. Common adverse effects include head-         and rejection of the diagnosis.24 Table 2 lists
gestion. ICS have minimal local adverse             ache, infection, GI disturbances, and cough.21,22   measures that can be taken to help ensure
effects. When used on an as-needed basis,                                                               better adherence.
ICS may provide relief of SAR and PAR. How-         Intranasal anticholinergics provide relief from
ever, when used in this manner, ICS may not         excessive rhinorrhea not controlled by other        Table 2: Increasing Adherence
be as effective as when used on a continu-          medications. Intranasal anticholinergics do         to Treatment 24
ous basis.1                                         not relieve nasal congestion, nasal itching, or
                                                    sneezing. Common local adverse effects are          • Keep it simple: Once-a-day treatments have
Patient preference should be taken into con-        dose related, and include nasal dryness and           the highest adherence rates
sideration when prescribing ICS because             bloody nasal discharge.1                            • Deliver it effectively: Teach patients the
patient preference affects adherence.17,18 In                                                             proper technique for using medicines, espe-
addition, patients should be taught proper          Immunotherapy                                         cially intranasal sprays
administration of ICS to help avert local adverse   Subcutaneous immunotherapy, also known
                                                                                                        • Avoid its problems: Inform patients clearly of
effects such as epistaxis.                          as hyposensitization, is the third principle of
                                                                                                          treatment benefits, possible adverse effects,
                                                    allergy management. It requires sequential
                                                                                                          and length of treatment
Systemic Glucocorticoids                            subcutaneous introduction of increasing dos-
Systemic glucocorticoids are rarely a first-line    ages of specific allergens to which the patient     • Call it medicine: The term “drug” may have a
therapy and are generally reserved for the          is sensitive.                                         negative connotation to some patients
                         most severe cases                                                              • Provide it readily: Providing patients with
                         of AR that are not         Factors that justify the consideration of immu-       samples of medication can help determine
                         responsive to other        notherapy include1,23:                                efficacy and possible adverse effects before
                         treatments, especially     • Severity and duration of symptoms                   patients have to pay for the medication
                         cases involving nasal      • Responsiveness to other forms of therapy          • Review its usage: On each visit, ask patients
                         polyposis.1 They are       • Unacceptable adverse effects of medications         when and how they are using their medi-
                         generally prescribed       • Patient’s desire to avoid long-term pharmaco-       cines. Ask them to show you their technique,
                         for short bursts (3-7        therapy                                             especially for ICS use
                         days) followed by dose     • Reduction of the risk of future asthma
                         tapering. Clinicians       • Presence of comorbid conditions such as           • Link it with lifestyle: Linking medication
should avoid use of long-acting intramuscular         sinusitis or asthma                                 usage with another routine activity, such
preparations because of adverse effects such                                                              as brushing the teeth or eating meals, can
as bone and skin thinning, cataracts, and           Common adverse effects of immunotherapy               improve adherence
glaucoma.1 Furthermore, with systemic gluco-        include local swelling at the injection site and,   • Put it in writing: Offer written instructions
corticoids, the risk of systemic adverse effects    rarely, anaphylactic shock. All immunotherapy         with the dose and time of administration of
increases with longer duration of treatment         injections should therefore be administered           the medication
(adverse effects include hypothalamic-pituitary-    in a physician’s office where anaphylaxis can       • Support it psychosocially: Build a partner-
adrenal [HPA] axis suppression and Cushing’s        be rapidly treated. Sublingual immunotherapy,         ship with the patient; discuss his/her con-
syndrome).19                                        although approved in other countries, is not          cerns about treatment
                                                    approved by the US Food and Drug
                                                                                                        • Minimize its cost: Cost of medicine and
Additional Pharmacotherapies                        Administration (FDA).
                                                                                                          immunotherapy can greatly affect adherence
Additional pharmacotherapies include mast
cell stabilizers, leukotriene receptor antago-      Patient Education                                                                               >>
nists, and intranasal anticholinergics. Cro-        Successful treatment of AR requires good
molyn sodium, a topical mast cell stabilizer,       long-term patient adherence, which is based
blocks the early- and late-phase nasal allergic     on patient education, the fourth principle of



                                                                                                                                      CME
response, minimizing nasal pruritus, sneezing,      allergy management.18

                                                                                                                   Primary Issues Vol 11, No 5         27
                                                                                 Rhinitis and
                                                                     >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                        induced
The Allergies in America™ survey asked nasal
allergy sufferers if they were dissatisfied with
their allergy medicine and why.8 The survey
reported that of those patients who were dis-
satisfied with their current allergy medication,     Figure 3. Urticaria                                  Nonimmunologic mechanisms include28,29
most (66%) were dissatisfied because it was                                                               • Direct mast cell releasing agents
not effective. Bothersome side effects (21%)                                                              • Agents that alter arachadonic acid
were a very distant second to effectiveness                                                                 metabolism
as the reason for dissatisfaction with allergy                                                            • Physical stimuli
medication. Effectiveness wearing off (12%)                                                               • Some foods
and not providing 24-hour relief (10%) also
caused patients to ask their clinician to change                                                          Chronic idiopathic urticaria (CIU) affects 0.5%
their allergy medication. In contrast, almost no                                                          to 1% of the population, with autoimmune
patients gave the following reasons for their                                                             urticaria/angioedema accounting for 30%
dissatisfaction with a medication: insurance                                                              to 50% of these cases.28 Although CIU can
coverage (1%), cost or copayment (1%), dif-                                                               be self-limiting, with approximately 50% of
ficulty in administering the medication (1%),                                                             cases showing a spontaneous remission
or some other reason (4%). There are cases                                                                after 1 year,27 20% of patients still have the
                                                     Greaves MW. N Engl J Med. 1995;332(26):1767-1772.
when referral to a specialist may be appropri-       Copyright ©1995 Massachusetts Medical Society. All   disease after 20 years have elapsed.26
ate.1 Reasons for referral of patients with AR       rights reserved.
include cases where the etiology is not clear,                                                            The etiology of chronic urticaria and angio-
symptoms are not being adequately managed,           and become confluent, larger lesions may             edema can only be confirmed in 5% to 20%
the patient has multiple complications or comor-     occur. A single lesion usually lasts less than       of patients.25 Urticaria is accompanied by
bidities, and management of immunotherapy            24 hours.25,26 Angioedema involves swelling of       angioedema in 40% of patients; 50% of
is indicated.1                                       deep subcutaneous regions in the skin and/or         patients have hives alone. The remaining
                                                     mucous membranes, such as lips, face, hand,          10% have angioedema alone.28 In urticaria,
According to the 2008 Practice Parameters            and tongue, etc. Lesions may persist for 2 to 3      lesions typically develop spontaneously, peak
for the diagnosis and management of AR,              days.25,26 Figure 3 shows a man with urticaria.      between 8 and 12 hours, and then resolve by
management of AR should be individualized                                                                 24 hours. Unlike the lesions of urticarial vascu-
and taken into consideration1:                       Urticaria is generally classified as either acute    litis, these lesions are not purpuric.
• Symptom spectrum, duration, severity               or chronic, and both types may occur with or
• Physical examination findings                      without angioedema.25 Urticaria that lasts less      Case Study
• Comorbidities                                      than 6 weeks is considered acute; chronic            Macy is a 30-year-old single
• Patient age                                        urticaria persists or recurs over 6 weeks,25 and     woman working as an executive
• Patient preferences                                can persist over months or years.27                  secretary at a large corporation.
                                                                                                          She has come to your office
In addition, a treatment plan should use step-       The etiology of acute urticaria is often appar-      complaining of severe itching,
up and step-down approaches:                         ent to the patient and clinician, with food          with hives on her stomach and
• Step-up when therapy is inadequate                 allergy, drug reaction, and insect sting among       axilla. She has not had this con-
• Step-down after symptom relief is achieved         the most common causes.25,27 Urticaria/              dition previously and is con-
  or maximized                                       angioedema can also be triggered by physical         cerned because the hives have
                                                     stimuli, systemic disease, or chronic infec-         persisted for the past 3 months. She reports
Case Study                                           tion.25,27 However, chronic urticaria and/or         that the hives appear to come and go during
Based on the diagnosis of PAR and SAR, you           angioedema is most often idiopathic, with no         the week, but usually last an entire day, getting
discuss allergen avoidance and recommend             identifiable cause. It is estimated that 15%         worse at night. Furthermore, during the previ-
that Helen begin using an intranasal cortico-        to 24% of the US population will experience          ous week, her lips swelled up. This frightened
steroid daily. You also recommend a second-          acute urticaria and/or angioedema at some            her, and brought her to you for treatment.
generation oral antihistamine as needed.             time in their lives.25
                                                                                                          Please read more to learn how you might diag-
Helen agrees to return in 4 weeks so that you        Pathogenic mechanisms causing histamine              nose and treat this patient’s condition.
can review the treatment plan with her. At that      release lead to urticaria/angioedema. These
time, if needed, you both will consider further      mechanisms can be either immunologic                 As with other potentially allergic conditions, a
options, including referral to an allergy special-   based or nonimmunologic based.                       first step in obtaining clues about the etiology
ist for consultation or comanagement.                                                                     of urticaria/angioedema is to ask when and
                                                     Immunologic mechanisms include28                     where the lesions have occurred and have not
Chronic Idiopathic Urticaria                         • IgE cross linking to IgE receptors on mast         occurred.28 Asking what the patient suspects
                                                       cells                                              is routine, but may give valid clues. Thereafter,
The Etiology and Impact of Chronic                   • Complement activation                              appropriate questions to assess the possible
Idiopathic Urticaria                                 • Other plasma effector systems (cytotoxic-          etiologic factors (listed in Table 3) are pursued
Urticaria, or hives, is superficial skin lesions       antibody mediated, antigen-antibody medi-          with the understanding from the outset that
characterized by roughly circular, pruritic, ery-      ated, delayed hypersensitivity)                    success is much more likely to be achieved
thematous lesions. These lesions (or wheals)         • Autoimmune disease                                 in acute or intermittent cases than achieved
range from a few millimeters to several cen-         • Idiopathic                                         in chronic urticaria/angioedema (if the >>



                                                                                                                                         CME
timeters in diameter, but if they run together

                                                                                                                     Primary Issues Vol 11, No 5         28
                                                                                     Rhinitis and
                                                                         >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                            induced
physical urticarias are excluded). Drugs are
common causes of urticaria/angioedema,
mediated either through IgE antibodies or act-
ing as pharmacologic histamine liberators. It is
important to elicit histories of all medications,       and changed her laundry detergent, but that         Case Study
prescription, nonprescription, and alternative          nothing helped. She tried taking OTC antihista-     The results of Macy’s physical examination
(herbal), taken by all routes of administration.        mines, but they made her too sleepy to work         show no neck, chest, abdomen, joint, muscu-
                                                        during the day. You begin a physical examina-       lar, or neurologic abnormalities, and no thyroid
Table 3. Possible Etiologies in                         tion and recommend several laboratory tests.        enlargement. The hives on her stomach and
Urticaria/Angioedema                                                                                        axilla are red wheals about 1 to 3 inches in
                                                        When a patient presents with urticaria, taking      diameter. They are slightly raised, have an
• Drugs                         • Connective tissue     a detailed history of urticaria and angioedema      irregular outline, and according to Macy, are
• Foods                           disease               is absolutely essential. It should fully document   intensely itchy. Her medical history reveals no
• Infection                     • Neoplasms             the attacks, including frequency, circumstances     chronic illnesses or prior diagnosed allergies.
                                                        of onset, timing, pattern of recurrence, and        She has no pets at home. The laboratory tests
• Psychosocial issues           • Genetic types         duration. The history should also document          show normal CBC, ESR, urinalysis, and liver
• Inhalants                     • Physical urticarias   medications, pre-existing allergies, family med-    function. Thyroid function is also normal. You
• Bites and stings              • Miscellaneous         ical history, and exposure to physical stimuli.     tell Macy that the diagnosis is CIU and explain
                                                        The clinical history often identifies triggers      what that means. You also tell her that the
• Contact urticaria
                                                        and can help direct further investigation.27,28     condition is self-limiting and that there is effec-
Powell RJ, et al. Clin Exp Allergy. 2007;37:631-650.    A comprehensive physical examination can            tive treatment. You reassure her that although
                                                        reveal important diagnostic clues that might        she was frightened when her lips swelled, CIU
Chronic urticaria appears to be an autoimmune           help diagnose comorbidities, and basic labora-      rarely progresses to a life-threatening situa-
disorder in a substantial fraction of patients.         tory tests based on the patient’s history may       tion, and that together you will work on a plan
Approximately 35% to 40% of patients with               be of value in further identifying triggers.        to help control her symptoms and allow her to
chronic urticaria have a circulating IgG antibody                                                           get back to a normal life.
directed against the a subunit of the IgE               Table 4 presents specific topics that should
receptor.30 Thyroid autoimmunity, such as               be covered when taking a detailed history in        Please read more to learn how the treatment
Hashimoto’s disease, has a clear association            patients with chronic urticaria.28 These topics     plan was designed to maximize the patient’s
with chronic autoimmune urticaria and angio-            correspond to the etiologies most commonly          response to therapy.
edema. Occasionally, chronic urticaria and              noted in chronic urticaria.
angioedema are manifestations of an underly-                                                                Nonpharmacologic Treatment
ing connective-tissue disorder, malignancy,             Table 4. Diagnosis: Medical History                 The management of urticaria/angioedema
or a systemic vasculitis. However, cutaneous                                                                depends in part on the etiology. When causal
vasculitis occurs in less than 1% of patients.          History is critical                                 factors are identified, the patient should be
                                                        Consider...                                         given clear instructions to avoid, or at least
Chronic urticaria, although not a life-                                                                     minimize, exposure. Causal factors include
                                                        • Drug reactions
threatening condition, should not be trivial-                                                               physical stimuli, such as cold, which can pro-
ized. The itching and unsightly wheals asso-            • Reactions to foods                                voke symptoms, and nonspecific agents that
ciated with urticaria cause great misery; in            • Inhalation of, ingestion of, or contact with      are known to exacerbate urticaria/angioedema,
addition, chronic urticaria may also be associ-           antigens                                          such as NSAIDS. Modulating factors, such as
ated with sleep disturbances, social isolation,         • Insect bites                                      stress, should also be minimized.25,34 Frequent
altered emotions, and difficulties with activi-                                                             tepid showers and application of 1% menthol
                                                        • Collagen vascular diseases
ties of daily living, including home manage-                                                                or calamine in aqueous cream/lotion can be
ment, personal care, recreation and social              • Exacerbation by NSAIDs or food additives          prescribed as cooling agents.34 Patients also
interaction, mobility, emotional factors, sleep,        • Environmental and physical factors,               need to be aware of factors that can exacer-
rest, and work.31-33                                      including                                         bate their disease (eg, hot showers, exercise,
                                                            cold - heat - pressure - sun/UV - water         alcohol), physical pressure or vibration (eg,
Patients with chronic urticaria reported lower          • Malignancy                                        waistbands), and medications (eg, NSAIDs,
satisfaction levels compared with a reference                                                               ACE inhibitors).
sample in quantity and quality of sleep, physi-         • Systemic mastocytosis
cal well-being, and resistance to stress and            • Thyroid disease                                   Pharmacologic Treatment
mood. Compared with patients with respira-                                                                  For almost all patients with urticaria and/or
tory allergy, patients with chronic urticaria           Routine laboratory tests, including chest X-ray,    angioedema, pharmacologic treatment will be
reported lower satisfaction levels in many              complete blood count (CBC), erythrocyte sedi-       necessary.25 Oral H1 antihistamines are the
aspects of daily life related to sleep, eating          mentation rate (ESR), serology, chemistry           mainstay of management. Other options include
behavior, psychological functioning, and work.32        panel, thyroid function studies, and thyroid        H1 and H2 antihistamine combinations, leuko -
                                                        autoantibodies and liver function tests, can be     triene antagonists (LTRA), and corticosteroids.
Treatment of Chronic Idiopathic Urticaria               helpful in diagnosing chronic urticaria, but
Case Study                                              should be selective, depending on patient his-      H1 Antihistamines
Speaking with Macy, you question her to learn           tory and results of the physical examination.25     Symptomatic treatment with H1 antihistamines
if she can identify anything that makes her                                                                 remains the mainstay of management.25 First-
symptoms better or worse. Macy reports that                                                                 generation H1 antihistamines are associated >>



                                                                                                                                           CME
she has eliminated certain foods from her diet

                                                                                                                       Primary Issues Vol 11, No 5           29
                                                                                         Rhinitis and
                                                                             >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                                induced
with sedation resulting from effects on the
central nervous system (CNS) function.
Although sedation may be desirable for reduc-
ing the discomfort of pruritis associated
with urticaria, particularly at bedtime, it may          in a small group of patients with moderate to       urticaria. Each agent has been shown to be
also cause undesirable adverse effects that              severe chronic urticaria who were showing           superior to placebo in the chronic treatment
can include cognitive and/or motor impairment,           poor control at recommended doses. Despite          of urticaria although neither one has been
resulting in decreased work productivity and             a regimen that was 3 times the recommended          approved by the FDA for this use.30 Both agents
vehicular accidents. In many cases, patients             dose, only 1 patient responded satisfactorily       are well tolerated. The most common adverse
do not perceive that they are impaired.25                to the increased dose. In the other 21 patients,    effects include headache, influenza/infection,
These agents are also associated with anti-              urticaria scores did not change and the patients    gastrointestinal disturbance, and cough.39,40
cholinergic effects related to their poor H1             needed to be treated with steroids. Disease
selectivity.1 Furthermore, these agents must             control was eventually gained in all patients.      Oral Corticosteroids
be taken every 4 to 6 hours, which is inconve-           This study suggests that the proportion of          Oral corticosteroids
nient for most patients.                                 patients with severe chronic urticaria that may     may be considered for
                                                         gain better control of their disease with high,     patients with chronic
In contrast to the first-generation H1 antihista-        off-label doses of antihistamine may be small.36    urticaria who have an
mines, the second-generation agents have a                                                                   inadequate response
large molecular size and are relatively lipopho-         Combined H1 and H2 Antihistamine                    to treatment even
bic, all of which contribute to poor penetration         Treatment                                           with a combination
of the CNS, thus decreasing or eliminating               H2 receptors make up 10% to 15% of the total        of H1 antihistamines,
sedation.35 The second-generation agents also            number of histamine receptors in the skin, the      H1 and H2 combina-
show a preferential binding to peripheral H1             remaining 85% to 90% are H1 receptors. The          tion therapy, and leu-
receptors and exhibit minimal anticholinergic            addition of an H2 antihistamine, such as cimet-     kotriene antagonists.28
effects. Unlike first-generation agents, the             idine or ranitidine, to an H1 antihistamine may     Controlled studies have not been conducted
second-generation H1 antihistamines are mostly           provide additional treatment benefit once           and these drugs are not approved by the FDA
dosed once daily.1                                       monotherapy with an H1 antihistamine has            for this use, but there is general acceptance
                                                         been maximized.30 The most common adverse           of the efficacy of oral corticosteroids. They
For treatment of chronic urticaria, second-              effects noted with H2 antihistamines are head-      remain agents of last resort and are recom-
generation antihistamines require administra-            ache, constipation, diarrhea, nausea, vomiting,     mended to be used at the lowest possible
tion only once or twice daily.28 Pharmacologic           and abdominal discomfort/pain.37                    dose and the shortest duration of time, due to
treatment should begin with the recommended                                                                  the potential adverse reactions.
dose of a nonsedating H1 antihistamine (Table            Doxepin, a tricyclic antidepressant, blocks both
5). Treatment should be modified according               types of histamine receptors and is a more          These drugs are effective, but should be
to treatment response and development of                 potent inhibitor of H1 receptors than is diphen-    administered by a specialist.28 Prolonged daily
adverse drug reactions.                                  hydramine or hydroxyzine, first-generation H1       use of oral corticosteroids should be avoided.
                                                         antihistamines. However, sedation is a prob-        Common adverse effects include weight gain,
According to the British Society for Allergy             lem and may limit the usefulness of doxepin.30      striae, premature cataracts, easy bruising,
and Clinical Immunology (BSACI) guidelines,              Other adverse effects include dry mouth,            osteoporosis, aseptic necrosis, elevated
it is common practice to increase the dose               blurred vision, and urinary retention.38 H2 anti-   blood pressure, and hyperglycemia.30
of antihistamine above the recommended                   histamines and doxepin are not approved by
dose when potential benefits are considered              the FDA for use in chronic urticaria.               Other Pharmaceutical Options
to outweigh the risks in patients who do not                                                                 The anti-IgE therapeutic agent, omalizumab,
achieve adequate symptom relief at standard              Leukotriene Receptor Antagonists                    is a humanized monoclonal antibody that
doses.28 However, this recommendation is not             The addition of leukotriene antagonists, such       binds to free IgE. Omalizumab is indicated for
evidence based. A recent study assessed the              as zafirlukast and montelukast, to H1 antihista-    the treatment of moderate-to-severe allergic
efficacy of increased doses of antihistamines            mines may benefit some patients with chronic        asthma.41,42 Although the cause of chronic urti-
                                                                                                             caria remains unclear, 40% to 50% of patients
                                                                                                             are thought to have an autoimmune-associated
Table 5. Second-generation Antihistamines Recommended Starting Doses in
                                                                                                             pathogenesis.41 In a published report of 3
Chronic Urticaria*
                                                                                                             patients with intractable urticaria treated with
                                                                                                             omalizumab, there was a complete clearing of
      Product                         Children                              Adults
                                                                                                             urticaria in all cases. Further study is needed
                                                                                                             to confirm the possible beneficial effect of
      Cetirizine               2.5 to 10 mg once daily†                 10 mg daily
                                                                                                             omalizumab and to better understand the
                                                                                                             mechanism of action, onset and duration of
   Levocetirizine                2.5 mg once daily ‡                        5 mg daily                       action, and proper dosing.
     Loratadine                  5 mg once daily**                      10 mg daily                          Other agents reported in the literature include
                                                                                                             colchicine, hydroxychloroquine, and cyclo-
   Desloratadine               1 to 5 mg once daily †                       5 mg daily                       sporine.43-45 These treatment options are not
                                                                                                             approved by the FDA despite reports of
   Fexofenadine                  30 mg twice daily ‡                60 mg twice daily
                                                                                                             successful treatment of chronic urticaria. >>



                                                                                                                                           CME
* Respective package inserts      † Dose increases from 6 months-11 years
** 2-5 years                      ‡ 6-11 years
                                                                                                                       Primary Issues Vol 11, No 5         30
                                                                                                                                                     Rhinitis and
                                                                                                                                         >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                                                                                            induced
Treatment Plan
A general management plan for chronic urti-
caria and angioedema is shown in Figure 4.
If identification of avoidable triggers can be
made, patients should be given clear instruc-                  Figure 4. Step-up Treatment Plan for Chronic Urticaria
tions on avoidance strategies. When further
treatment is required, both step-up and step-                  Treatment should be stepped down once control is achieved
down approaches should be used, based on
the patient’s response to therapy.28
                                                                                                                                       6) Add or substitute other second-line agents




                                                                                                 Education and Avoidance of Triggers
Case Study                                                                                                                                (ie, cyclosporine or a low-dose corticosteroid*)
You prescribe a second-generation H1 anti-




                                                                    Identification of Triggers
                                                                                                                                       5) Consider adding or substituting with second-
histamine for Macy and advise her to avoid
                                                                                                                                          line agent (ie, antileukotriene)
potential triggers such as alcohol, aspirin,
NSAIDs, and ACE inhibitors. You discuss poten-
tial adverse effects of treatment, especially                                                                                          4) Consider sedating antihistamine at night
sedation, and explain that CIU can wax and
wane. You stress that a medication adjustment                                                                                          3) Add second nonsedating H1 antihistamine (regular or
may be required, and schedule a follow-up                                                                                                 as required)
appointment to discuss treatment effective-
ness and, if needed, addition of an H2 blocker                                                                                         2) Higher dose of H1 antihistamine
and leukotriene receptor antagonist. If her
condition is refractory, you may consider refer-
ral to a specialist.                                                                                                                   1) Standard dose of nonsedating H1 antihistamine

Clinical Pearls
• Assess the impact of allergic rhinitis or                    Recommendations of the British Society for Allergy and Clinical Immunology
  chronic idiopathic urticaria on patient quality              *Low-dose daily corticosteroid (5-10 mg/day) or low-dose alternative day corticosteroid
  of life                                                      (15-20 mg alt day) could be considered.
• Devise treatment strategies that can mini-                   Reproduced with permission from Powell RJ, et al. Clin Exp Allergy. 2007;37:631-650.
  mize adverse effects and improve patient
  outcomes and satisfaction
• Educate patients about the importance of                     5
                                                                            Bousquet J, Neukirch F, Bousquet PJ, et al. Severity                                          14
                                                                                                                                                                               Berger WE. Pharmacokinetic characteristics and
  adhering to treatment strategies and about                                and impairment of allergic rhinitis in patients con-                                               safety and tolerability of a reformulated azelastine
  the safe and effective use of medications                                 sulting in primary care. J Allergy Clin Immunol. 2006;                                             hydrochloride nasal spray in patients with chronic
                                                                            117(1):158-162.                                                                                    rhinitis. Expert Opin Drug Metab Toxicol. 2009;5(1):
                                                               6
                                                                            Léger D, Annesi-Maesano I, Carat F, et al. Allergic                                                91-102.
                                                                            rhinitis and its consequences on quality of sleep: an                                         15
                                                                                                                                                                               Nash D. Allergic rhinitis. Pediatr Ann. 1998;27:799-808.
                                                                            unexplored area. Arch Intern Med. 2006;166(16):                                               16
                                                                                                                                                                               Department of Justice. Drug Enforcement
                                                                            1744-1748.                                                                                         Administration, Justice. Retail sales of scheduled
                                                               7
                                                                            Lamb CE, Ratner PH, Johnson CE, et al. Economic                                                    listed chemical products; self-certification of regu-
                                                                            impact of workplace productivity losses due to allergic                                            lated sellers of scheduled listed chemical products.
                                                                            rhinitis compared with select medical conditions in                                                Fed Regist. 2006;71(186):56008-56027.
                                                                            the United States from an employer perspective. Curr                                          17
                                                                                                                                                                               Brunton SA, Fromer LM. Treatment options for
                                                                            Med Res Opin. 2006;22(6):1203-1210.                                                                the management of perennial allergic rhinitis, with
                                                               8
                                                                            Allergies in America: a landmark survey of nasal allergy                                           a focus on intranasal corticosteroids. South Med J.
                                                                            sufferers [executive summary]. http://www.mmcpub.com/                                              2007;100(7):701-708.
References                                                                  scsaia/AdultSummary.pdf. Accessed February 25, 2009.                                          18
                                                                                                                                                                               Loh CY, Chao SS, Chan YH, Wang DY. A clinical
                                                               9
                                                                            Lanier B. Allergic rhinitis: selective comparisons of                                              survey on compliance in the treatment of rhinitis using
1
    Wallace DV, Dykewicz MS, Bernstein DI, et al. The                       the pharmaceutical options for management. Allergy                                                 nasal steroids. Allergy. 2004;59(11):1168-1172.
    diagnosis and management of rhinitis: an updated                        Asthma Proc. 2007;28(1):16-19.                                                                19
                                                                                                                                                                               Drugs@FDA. US Food and Drug Administration Web
    practice parameter. J Allergy Clin Immunol. 2008;          10
                                                                            Blaiss MS. Diphenhydramine vs desloratadine com-                                                   site. http://www.accessdata.fda.gov/scripts/cder/
    122(2 suppl):S1-S84.                                                    parisons must consider risk-benefit ratio. Ann Allergy                                             drugsatfda/index.cfm. Updated daily. Accessed
2
    Van Hoecke H, Vastesaeger N, Dewulf L, Sys L,                           Asthma Immunol. 2006;97(1):121-122.                                                                February 27, 2009.
    van Cauwenberge P. Classification and management           11
                                                                            Corren J, Storms W, Bernstein J, Berger W, Nayak A,                                           20
                                                                                                                                                                               Aprile A, Lucarelli S, Vagnucci B, Frediani T. The use
    of allergic rhinitis patients in general practice during                Sacks H. Effectiveness of azelastine nasal spray                                                   of antileukotrienes in paediatrics. Eur Rev Med
    pollen season. Allergy. 2006;61(6):705-711.                             compared with oral cetirizine in patients with sea-                                                Pharmacol Sci. 2001;5(2):53-57.
3
    Wilken JA, Berkowitz R, Kane R. Decrements in                           sonal allergic rhinitis. Clin Ther. 2005;27(5):543-553.                                       21
                                                                                                                                                                               Fish JE, Kemp JP, Lockey RF, Glass M, Hanby LA,
    vigilance and cognitive functioning associated with        12
                                                                            Kaliner M. A novel and effective approach to treating                                              Bonuccelli CM. Zafirlukast for symptomatic mild-to-
    ragweed-induced allergic rhinitis. Ann Allergy Asthma                   rhinitis with nasal antihistamines. Ann Allergy                                                    moderate asthma: a 13-week multicenter study. The
    Immunol. 2002;89(4):372-380.                                            Asthma Immunol. 2007;99(5):383-391.                                                                Zafirlukast Trialists Group. Clin Ther. 1997;19(4):
4
    Marshall PS, O’Hara C, Steinberg P. Effects of             13
                                                                            Laustsen G, Carrillo F, Johnson J, Smith C. Drug                                                   675-690.                           (continued on page 34)
    seasonal allergic rhinitis on fatigue levels and mood.                  approvals: ’08 in review. Olopatadine hydrochloride



                                                                                                                                                                                                                 CME
    Psychosom Med. 2002;64(4):684-691.                                      (Patanase) nasal spray. Nurse Pract. 2009;34(2):29.

                                                                                                                                                                                         Primary Issues Vol 11, No 5                 31
 PI 127c
 PRIMARY ISSUES CME POST-TEST AND EVALUATION



Allergic Rhinitis and
Chronic Urticaria:
Management of Histamine-
induced Disorders
  POST-TEST
                       1. Andrew, a 39-year-old accountant,         4. Carla, a 48-year-old librarian,
                          presents at your office complaining          presents at your office with red,
                          of itchy eyes and nasal congestion           itchy wheals on her stomach. She
                          that gets particularly bad in the            notes that she has been troubled
                          spring. He is overweight and is cur-         by the hives for the past 4 weeks,
                          rently taking a beta blocker for hyper-      but then adds that the hives also
                          tension. Which over-the-counter              appeared last year over the course
                          allergy medication would you advise          of about 2 months, then disap-
                          him to avoid?                                peared. At the time she was not
                           A. Oral decongestants                       able to determine a cause of the
                           B. Oral antihistamines                      hives, despite eliminating foods
                           C. Intranasal corticosteroids               and not being on any medications.
                           D. Leukotriene receptor antagonists         Based on this information, you
                                                                       diagnose her urticaria as
                                                                         A. Acute
              2. Andrew indicates that he has tried allergy              B. Chronic
                medications before, but was never satisfied              C. Intermittent
                with the results. According to patient surveys,          D. Unknown
                which reason is he most likely to cite as the
                cause of his dissatisfaction?
                  A. The medicine is hard to administer             5. Your physical examination of Carla reveals no
                  B. The treatment is not effective                    thyroid enlargement, as well as no neck,
                  C. The treatment has bothersome adverse              chest, abdomen, joint, muscular, or neuro-
                     effects                                           logic abnormalities. Which of the following
                  D. Unsure                                            tests would you initially order to aid your diag-
                                                                       nosis of Carla?
                                                                        A. CBC, ESR, serology, chemistry panel
              3. Despite initial treatment with an intranasal           B. Thyroid function studies and liver function
                 corticosteroid, Andrew’s allergic rhinitis                test
                 worsens as the allergy season progresses.              C. RAST or allergy prick tests for foods and
                 Which of the following treatments would you               inhalants
                 not progress to next?                                  D. A and B
                  A. Add an intranasal antihistamine to the             E. A and C
                      treatment plan                                    F. B and C
                  B. Prescribe a second-generation antihista-
                     mine to be used on an as-needed basis
                  C. Administer a long-acting intramuscular
                      injection of a glucocorticoid
                  D. Refer Andrew to an allergy specialist




                                                                                                                           CME
                                                                                                        Primary Issues Vol 11, No 5   32
         PI 127c
         PRIMARY ISSUES CME POST-TEST AND EVALUATION                                                                                                                              Fax to 417-841-3609

Allergic Rhinitis and Chronic Urticaria: Management of Histamine-induced Disorders
EVALUATION




                                                                                                                                                                                                                     Strongly Disagree
First Name ___________________________________________________                                               Education Activity Overall




                                                                                                                                                                       Strongly Agree
Last Name ___________________________________________________




                                                                                                                                                                                                          Disagree
                                                                                                                                                                                                Neutral
Degree ______________________________________________________




                                                                                                                                                                                        Agree
Email________________________________________________________
Address ______________________________________________________                                               This activity provided new information to me.                 5             4        3         2              1
City__________________________________________ State __________
                                                                                                             The educational approach used in this program was
Zip Code _______________ Phone ____________________________________                                                                                                        5             4        3         2              1
                                                                                                             conducive to my learning experience.
Fax ________________________________________
                                                                                                             I learned information that is directly applicable to my
                                                                                                                                                                           5             4        3         2              1
Please answer the questions on the previous page by selecting the answer (insert letter                      clinical practice.
below) you feel is correct for each question. You will need to pass the post-test with
70% accuracy to earn CME credit. If you receive less than 70% accuracy, you will be                          I learned information that will help improve my
                                                                                                                                                                           5             4        3         2              1
contacted. Thank you.                                                                                        patients’ outcomes.
1. ___________________ 2. ___________________ 3. ___________________
                                                                                                             After completing this educational activity, I plan to implement the following in my practice:
4. ___________________ 5. ___________________

Thank you for reading this article. Please rate the activity using the indicated scale.
Base your rating on both the quality of the activity and value of the information
presented.

Commercial Bias
Definition: A personal judgment in favor of a commercial interest; any entity producing,
marketing, or distributing health goods or services consumed by, or used on, patients.
                                                                                                             Are there any barriers that would keep you from implementing the practice paradigms
I feel that the activity materials are free of commercial bias.          q Yes             q No              discussed in this educational activity?

If you answered No, please tell us why:




                                                                                                             Is there specific additional information and/or materials that you think would enhance
                                                                                                             this educational activity?




Learning Objectives
                                                                     Very Good
                                                         Excellent



                                                                                 Average



                                                                                                   Failing




To what extent did this article meet its stated
                                                                                            Poor




objectives?                                                                                                  Please give us your comments regarding the overall activity.


Identify strategies to overcome barriers for adequate
                                                           A           B           C         D       F
control of allergic rhinitis symptoms



Create treatment strategies based on the most
current evidence for the management of chronic             A           B           C         D       F
idiopathic urticaria for better patient outcomes                                                             I certify that I have participated in _____ hour (hour-for-hour basis for a maximum of
                                                                                                             .75 hour) of this educational activity and request a CME certificate indicating that number
                                                                                                             of credit hours. I will claim only the total number of hours for which I participated.


                                                                                                                                                           Primary Issues Vol 11, No 5
                                                                                                                                                                                                CME                                      33
                                                                                              Rhinitis and
                                                                                  >> Allergic Disorders Chronic Urticaria: Management of Histamine-
                                                                                     induced
(continued from page 31)
22
     Knorr B, Franchi LM, Bisgaard H, et al. Montelukast,
     a leukotriene receptor antagonist, for the treatment
     of persistent asthma in children aged 2 to 5 years.
     Pediatrics. 2001;108(3):e48.                              30
                                                                  Kaplan AP. Chronic urticaria and angioedema. N Engl         37
                                                                                                                                 Zantac [package insert]. Research Triangle Park, NC:
23
     Bousquet J, Lockey R, Malling HJ, et al. Allergen            J Med. 2002;346(3):175-179.                                    GlaxoSmithKline; 2009.
     immunotherapy: therapeutic vaccines for allergic          31
                                                                  O’Donnell BF, Lawlor F, Simpson J, Morgan M,                38
                                                                                                                                 Sinequan [package insert]. New York, NY: Pfizer Inc;
     diseases. Ann Allergy Asthma Immunol. 1998;81                Greaves MW. The impact of chronic urticaria on the             2007.
     (5 pt 1):401-405.                                            quality of life. Br J Dermatol. 1997;136(2):197-201.        39
                                                                                                                                 Accolate [package insert]. Wilmington, DE: AstraZeneca
24
     Meltzer EO. An overview of current pharmacotherapy        32
                                                                  Nelson HS, Reynolds R, Mason J. Fexofenadine HCl               Pharmaceuticals LP; 2004.
     in perennial rhinitis. J Allergy Clin Immunol. 1995;         is safe and effective for treatment of chronic idiopathic   40
                                                                                                                                 Singulair [package insert]. Whitehouse Station, NJ:
     95(5 pt 2):1097-1110.                                        urticaria. Ann Allergy Asthma Immunol. 2000;84(5):             Merck & Co., Inc.; 2008.
25
     Joint Task Force on Practice Parameters. The diagno-         517-522.                                                    41
                                                                                                                                 Spector SL, Tan RA. Effect of omalizumab on patients
     sis and management of urticaria: a practice parameter     33
                                                                  Baiardini I, Giardini A, Pasquali M, et al. Quality of         with chronic urticaria. Ann Allergy Asthma Immunol.
     part I: acute urticaria/angioedema part II: chronic          life and patients’ satisfaction in chronic urticaria and       2007;99(2):190-193.
     urticaria/angioedema. Ann Allergy Asthma Immunol.            respiratory allergy. Allergy. 2003;58(7):621-623.           42
                                                                                                                                 Xolair [package insert]. East Hanover, NJ: Novartis
     2000;85(6 pt 2):521-544.                                  34
                                                                  Yadav S, Upadhyay A, Bajaj AK. Chronic urticaria: an           Pharmaceuticals Corporation; 2008.
26
     Greaves M. Chronic urticaria. J Allergy Clin Immunol.        overview. Indian J Dermatol. 2006;51(3):171-177.            43
                                                                                                                                 Plaquenil [package insert]. Bridgewater, NJ: sanofi-
     2000;105(4):664-672.                                      35
                                                                  Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis            aventis; 2006.
27
     Muller BA. Urticaria and angioedema: a practical             and management of rhinitis: complete guidelines of          44
                                                                                                                                 Probenecid and Colchicine [package insert]. Corona,
     approach. Am Fam Physician. 2004;69(5):1123-1128.            the Joint Task Force on Practice Parameters in                 CA: Watson Laboratories, Inc.; 2006.
28
     Powell RJ, Du Toit GL, Siddique N, et al. BSACI              Allergy, Asthma and Immunology. American Academy            45
                                                                                                                                 Sandimmune [package insert]. East Hanover, NJ:
     guidelines for the management of chronic urticaria           of Allergy, Asthma, and Immunology. Ann Allergy                Novartis Pharmaceuticals Corporation; 2007.
     and angio-oedema. Clin Exp Allergy. 2007;37(5):              Asthma Immunol. 1998;81(5 pt 2):478-518.
     631-650.                                                  36
                                                                  Asero R. Chronic unremitting urticaria: is the use of
29
     Grattan CE. Aspirin sensitivity and urticaria. Clin Exp      antihistamines above the licensed dose effective? A
     Dermatol. 2003;28(2):123-127.                                preliminary study of cetirizine at licensed and above-
                                                                  licensed doses. Clin Exp Dermatol. 2007;32(1):34-38.



Don’t Give the Swine Flu a Hand
Are you going to lend a hand to your patients                  Remind your staff and your patients about the                    the paper towel to flush the toilet and open
by giving them ways to beat the flu? The first                 4 main principles of hand awareness:                             the doors)
week in December is National Handwashing                       1. Wash your hands when they are dirty and                     • Always use soap and water if your hands are
Awareness Week and a great opportunity for                        before eating                                                 visibly dirty
you to talk to your patients and staff about                   2. Do not cough into your hands*
hand hygiene. With all the complaints and con-                 3. Do not sneeze into your hands*                              As the CDC says, “Remember, Clean Hands
cerns of medical care costs, the best thing you,               4. Above all, do not put your fingers into your                Save Lives!”2 Let’s do our best to not give
your staff, and your patients can do to prevent                   eyes, nose, or mouth                                        the swine flu (or other illnesses) a hand this
illness and infection, and the least expensive,                                                                               winter.
is to wash those hands.
                                                                                * Do it in Our Sleeves
                                                                                                                              Resources
The Centers for Disease Control (CDC) agrees                   A great and funny source to share around the
that washing your hands is the most impor-                     office and with your patients                                                        Hand Hygiene
tant thing you can do to keep from getting
sick. The HealthReach Community Health                         Post a reminder in your office about the correct                                 Infection Prevention
Centers, however, showed some unnerving                        way to wash your hands when using soap and
statistics1:                                                   water. You might be surprised how many of                                       Clean Hands Coalition
• Only ⅔ of adults in the United States wash                   your patients are not really aware of the proper
  hands after using the bathroom                               techniques.2                                                        Guidelines for Hand Hygiene In Healthcare Settings
• 1 in 4 adults doesn’t wash hands after chang-                • Wet your hands with clean running water and
  ing diapers                                                    apply soap. Use warm water (not hot or
• Less than ½ of Americans wash hands after                      cold) if it is available                                     References
  cleaning up after pets                                       • Rub hands together to make a lather and
• 1 in 3 washes hands after sneezing/coughing                    scrub all surfaces (remember your wrists and                 1
                                                                                                                                HealthReach Community Health Centers. Health tip:
• Less than 1 in 5 washes hands after touching                   between your fingers)                                          National Hand Washing Awareness Week: December
  money                                                        • Continue rubbing hands for 15 to 20 seconds:                   4-10. http://www.healthreachchc.org/news/health
• 1 in 3 E. coli occurrence is caused from not                   think of singing “Happy Birthday” twice                        Tip.php?IDT=39. Accessed July 29, 2009.
  washing hands before handling food                           • Rinse hands well under running water                         2
                                                                                                                                Centers for Disease Control and Prevention. CDC fea-
                                                               • Dry your hands using a paper towel or air                      tures: wash your hands. http://www.cdc.gov/Features/
Now think about that the next time you shake                     dryer; if possible, use the paper towel to                     HandWashing/. Last updated April 27, 2009. Accessed
a patients hand!                                                 turn off the faucet (in public restrooms use                   July 29, 2009.

                                                                                                                                           Primary Issues Vol 11, No 5                  34