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Treatment of Allergic Rhinitis/Acute Rhinosinusitis in Primary and Urgent Care

Wendy L. Wright, MS, APRN, BC, FAANP, FAANAdult / Family Nurse Practitioner

Owner - Wright & Associates Family HealthcareAmherst, New Hampshire

Owner – Wright & Associates Family HealthcareConcord, New Hampshire

Owner – Partners in Healthcare Education, LLC

Disclosures

• Speaker Bureau: Sanofi-Pasteur, Merck, Takeda

• Consultant: Pfizer, Sanofi-Pasteur, Merck, Arbor

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Objectives

• Upon completion of this lecture, the participant will be able to:– Discuss the pathophysiology of allergic rhinitis and acute

rhinosinusitis– Identify the non-pharmacologic and pharmacologic agents

available for the treatment of allergic rhinitis and acute rhinosinusitis

– Compare and contrast newer pharmacologic agents with older agents with regard to benefits, risks, side effects, and drug interactions.

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Impact of Allergic Rhinitis in the United States

• 17 million individuals in US have diagnosed allergic rhinitis– This accounts for 14% of the US population– Recent prevalence studies show that it may be present in

31.5% of all adults

• 10-20% of this number is children– Most common chronic medical condition of childhood

• 79.5 million Americans have undiagnosed allergic rhinitis

• Average age of onset: 10 years of age

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Impact of Allergic Rhinitis in the United States

• 2 million school days lost yearly• Annual drug expenditure for allergic rhinitis is

3.4 billion dollars; + 2 billion for lost work time• Associated with an number of other conditions

including: – Otitis media, sinusitis, asthma, facial growth

abnormalities, behavioral issues, and GERD– Sleep apnea; adenoid hypertrophy, conjunctivitis

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Pathophysiology of Allergic Rhinitis

• Results from repeated exposure to allergens in the individual already equipped with the genetic predisposition

• Upon exposure to an allergen, there is a release of IgE antibodies

• IgE antibody binds with the antigen • It then attaches itself to the mast cells on the nasal

and bronchial mucosa• Release of numerous chemical mediators; including

leukotrienes and histamine

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Histamine

• Histamine is stored mainly in the mast cell• Circulated in the blood via the basophil• Causes an increase in blood flow to the affected area.

– This increase in blood flow causes the introduction of more fluids to the area

– Responsible for the increased nasal discharge, edematous mucous membranes, sneezing, itchy nose and eyes, and hives

– Also associated with airway inflammation and bronchoconstriction

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Asthma and Allergic Rhinitis: Closely Related Diseases

• Similar risk factors, pathophysiology, patterns of inflammation and triggers

• Approximately 74%-80% of children and adults with asthma have associated rhinitis

• Approximately 5-15% of individuals with allergic rhinitis will develop asthma

• It is said that if you don’t treat the nose in the patient with asthma, you will never get their asthma under control

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One Airway, One Disease

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Allergic Rhinitis: A Risk Factor for Asthma

• Brown University Study– 690 students– 162 diagnosed with allergic rhinitis– 528 without allergic rhinitis– 23 years later

• Of the 162 with allergic rhinitis, 10.5% had developed asthma compared with 3.6% of those without allergic rhinitis

Settipane, RJ et al. allergy Proc. 1994; 15:21-25.

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Symptoms of Allergic Rhinitis

• Nasal congestion• Sneezing• Profuse watery

discharge from nose and/or eyes

• Itching of nose, eyes, and palate

• Frequent clearing of the throat

• Nose picking• Grimacing or twitching

• Cough• Mouth breathing• Fatigue• Irritability• Decreased appetite• Decreased hearing• Hoarse voice• Decreased smell• Sniffling• Epistaxis

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Physical Examination Findings in the Individual With Allergic Rhinitis

• Pale, boggy mucosa and turbinates

• Allergic shiners• Allergic salute• Conjunctival injection• Cobblestoning• Allergic facies• Dennie’s lines

• Watery discharge in nose and eyes

• Ulcerations on nasal mucosa

• Pharyngeal edema• Lymphoid tissue• Nasal polyps• High arched palate

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Triggers

• Inhalant allergens are the most common triggers for both asthma and allergic rhinitis– House dust– Pollens– Mold spores– Animal and insect emanations

• Cockroach feces

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Triggers

• Chemicals– Occupational setting (Carpenters, Hair Stylists)

• Perfumes• Foods

– Sulfites (wine), shrimp, dried fruit, processed potatoes, beer

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Triggers

• Latex• House Plants

– Large amount of mold

• Tobacco smoke• Pollution

– Work exposures

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Diagnosis of Allergic Rhinitis

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Diagnosis of Allergic Rhinitis

• History and physical examination• Skin tests

– Exposure to a number of allergen via prick test or intradermal

– Positive response: hive or wheal within 15-20 minutes

– Up to 17% false negatives– More sensitive and specific– Yields information quickly

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Diagnosis of Allergic Rhinitis

• Skin tests– Less expensive– Contraindications:

• Beta blockers– Reason: if an anaphylaxis occurs, diminished

response from epinephrine• Pregnancy• Generalized skin disorders• Currently taking antihistamines

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Diagnosis of Allergic Rhinitis

• CAP testing

–Much more advanced than previous RAST testing

–Numerous panels available–Blood test– In vitro quantitative assay measures allergen

specific IgE in human serum

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Why Treat Allergic Rhinitis:Treating Allergic Rhinitis Will Improve

Asthma

• Treatment of children with nasal steroids, nonsteroidal antiinflammatory drugs (such as cromolyn), or non-sedating antihistamines has been shown to improve lung function short and long term

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Treating Allergic Rhinitis Will Improve Memory and Mood

• Study in Minnesota examined individuals with allergic rhinitis– Memory and mood were assessed during allergy

season and during non-allergy season– Untreated group showed significant reduction in

memory and mood when compared with the treatment group

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Treatment Options

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Remember…

• May need to treat the eyes in individuals with allergic rhinitis

• AND must treat the eyes and nose in children and adults with asthma...

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Environmental Modification

• Environmental modification is recommended as first line therapy for the individual with allergic rhinitis

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Environmental Control: A Useful but Often Ignored Step

• Dust Mite Avoidance – Bed linens must be laundered 1-2 times/week– Maintain humidity at <50% – Wash in hot water (Temp > 130 degrees Fahrenheit)– Remove carpets– Encase pillows and mattresses– Frequent vacuuming

• Remember: 30 minutes after vacuuming: increased dust mite emanations in the air

• Individuals with significant asthma should avoid vacuuming or avoid the room for 30 minutes after vacuuming

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Environmental Control: A Useful but Often Ignored Step

• Pollen Avoidance– Air-conditioning– Minimize outdoor exposures during times of highest pollen

counts– Keep bedroom windows closed– Air filters

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Environmental Control

• Animal Avoidance– Keep animals out of the bedroom– If the family has a cat, weekly washing of the cat

significantly reduces the allergen load– May have to remove animals from home– Dry clean upholstery and carpets– Cover with an air filter any ducts leading into the

bedroom

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Environmental Control

• Mold Avoidance– Children/adolescents with allergic rhinitis and/or

asthma should not be sleeping in a damp basement– Keep humidity at <50%– Clean moldy surfaces– Avoid houseplants– Avoid chores that involve damp grass, leaves

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Reliever Medications

• Antihistamines– First Generation– Second Generation

• Decongestants

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First Generation Antihistamines

• Number of Products Available– Brompheniramine (Bromfed, Dimetapp)– Chlorpheniramine (Chlor-trimeton, Allerest)– Clemastine (Tavist)– Diphenhydramine (Benadryl)– Hydroxyzine (Atarax)– Promethazine (Phenergan )– Triprolidine hydrochloride (Actifed)

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Side Effects of First Generation Antihistamines

• First generation antihistamines have been utilized since the 1950’s

• Pass readily through the blood-brain barrier• Rapidly absorbed and reach peak plasma

concentrations in 2-3 hours• Side effects; Somnolence, drowsiness, impaired

functioning, anticholinergic effects

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Driving Performance Study (US)Study Design

• Single-center, randomized, double-blind, crossover study

• 40 Fall SAR patients (during season)

• 4 Treatments: – Placebo

– Fexofenadine HCl 60 mg

– Diphenhydramine 50 mg

– Alcohol (to 0.1% blood alcohol concentration)

• Simulated drivingWeiler et al. Ann Allergy Asthma Immunol1999;82:112.

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Second Generation Antihistamines

• These have emerged as first line rescue medications– Loratadine (Claritin)

• 2 years and up: 5 - 10mg daily

– Desloratadine (Clarinex)• 6 months of age and up• 1 mg – 5 mg daily depending upon age

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Second Generation Antihistamines• Fexofenadine (Allegra)

– 60mg bid; 180 mg once daily: 12 years and up– 30 mg bid: age 2 years of age – 11 years of age– 15 mg bid: 6 months – 1 year (urticaria)

• Cetirizine (Zyrtec)– 2-5 years: 2.5-5 mg daily– 6 or greater: 5-10 mg daily6

• Levocetirizine (Xyzal)– 1.25 mg once daily: 2 – 5 years of age– 2.5 mg once daily: 6 – 11 years of age– 2.5 mg – 5 mg once daily: 12 years of age and older

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Decongestants may offer some benefit

• According to a survey of allergy patients who take medications more than 180 days per year– 9 out of 10 seasonal allergy patients experience

nasal congestion– Nasal congestion is the single most frustrating

symptom for seasonal allergy patients– Over 90% of seasonal allergy patients with nasal

congestion want faster relief

Source: IAS 2004

Controller Medications

• Mast Cell Stabilizers• Nasal Corticosteroids

– Preferred controller therapy• Nasal Antihistamines

– (seasonal, perennial, and allergic rhinitis)• Nasal Anticholinergics• Leukotriene Antagonists

– Recommends against using monotherapy• Accupuncture

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Inhaled Nasal Corticosteroids

• Numerous Products– Beclomethasone dipropionate (Qnasal, Beconase A!) * 4

years of age and older– Budesonide (Rhinocort Aqua) **6 and older– Flunisolide (Nasarel) **6 and older– Fluticasone (Flonase, Veramyst) **4 and older– Mometasone (Nasonex) **Age 2 and older– Triamcinolone acetonide (Nasacort AQ) **2 and older– Ciclesonide (Omnaris, Zetonna) **6 years of age and older

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According to the Guidelines

• Corticosteroids are first line for the person with moderate to severe allergic rhinitis

• Very potent and effective– Most corticosteroids are equally efficacious

• Many are now available OTC

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Inhaled Corticosteroids

• Most potent antiinflammatory on the market• Side effects

– Nasal irritation, epistaxis

• Precautions– High dosages: Increased systemic absorption

leading to HPA axis suppression

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Controversy Regarding Inhaled Corticosteroids

• Concern that inhaled corticosteroids are associated with hypothalamic-pituitary-adrenal suppression

• Concerns also expressed that the long-term use of these medications may be associated with an increase in cataract formation and an increase in intraocular pressure

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Schenkel, E. et. al

• 98 patients randomized to either placebo or mometasone furoate aqueous nasal spray

• Ages: 3 - 9 years• After 1 year, there was no suppression of height in the

children using the nasal corticosteroid when compared with the child using placebo

Pediatrics Vol 105 No. 2 February 2000, p. 22

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Mast Cell Stabilizers• Cromolyn Sodium (Nasalcrom)

– Best for children or adults with mild to moderate symptoms

– Indication: 2 years and up– 1 spray each nostril tid-qid; maximum; 6 times/day– Side effects: stinging

• Olopatadine nasal (Patanase)– 6 years of age and older– 1 spray – 2 sprays each nostril once daily

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Leukotriene Receptor Antagonists

• Cysteinyl leukotriene production in the body has been associated with airway edema, smooth muscle constriction and the inflammatory process

• These medications block the leukotriene receptors which in turn is able to prevent inflammation and bronchoconstriction

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Montelukast (Singulair)

• (Montelukast) Singulair– 4 mg tablet for children 12 months – 5 years of age– 5mg qhs for ages 6-14– 10mg qhs for ages 15 and older– Caution: mood destabilization

Other Nasal Spray Options

• Azelastine (Astelin, Astepro)• Azelastine/fluticasone (Dymista)• Ipratropium bromide (Atrovent)

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Sublingual Allergen Extract

• Oralair (other products: ragwitek, grastek)– Treatment of allergic rhinitis with or without allergic

conjunctivitis– For those allergic to certain grass pollens age 10 –

65 years– First dose administered in healthcare providers

office with observation for minimum of 30 minutes• If tolerated, patient may then use at home• Once daily, initiated 4 months before allergy season

– Box warning: anaphylaxis

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Immunotherapy

• Reserved for the most severe cases; those unresponsive to treatment, unwilling or unable to tolerate pharmacologic treatments

• Successful therapy causes an initial rise in IgE levels and then a subsequent decline in levels and symptomatology

• Treatment for 6 months or longer is required before benefits will be seen

• Entire course of treatment: 3-5 years

Acute Rhinosinusitis

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Pathogens and Resistance

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Causative Pathogens in ABRS

Streptococcus pneumoniae

Haemophilus influenzae

Moraxella catarrhalis

Major pathogens in sinusitis

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Streptococcus pneumoniae

• Gram positive diplococci • Most common cause of Community Acquired

Pneumonia– Also the most common bacterial cause of OM

and sinusitis

• 70% of children and 30% of adults have nasopharyngeal colonization

• Disease results from a microaspiration

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Mechanism for the Development of Antimicrobial Resistance

• Streptococcus pneumoniae–Many mechanisms for resistance–Most common mechanism: Resistance

from an alteration in the penicillin binding proteins which reduce/eliminate binding of penicillin to the proteins

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Mechanism for the Development of Antimicrobial Resistance

• Streptococcus pneumoniae–Erythromycin resistance: ribosome

modification and alteration in antibiotic transport• Of increasing concern is the ermAM gene. This

gene confers cross-resistance to other 14, 15, and 16 membered rings (clarith, azith)

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Where are we now?

• S. pneumoniae– 25% - 50% is not fully responsive to penicillin– 33% is resistant to macrolides

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Of Increasing Concern…

• The first clinical isolate of S. pneumoniaeto exhibit a high level of resistance to fluoroquinolones was found in 2001 in Taiwan

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Streptococcus pneumoniae

• Most likely to be present with recurrent disease and least likely of all pathogens to resolve without treatment

• <30% chance of spontaneous resolution; Some sources say <10%

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H. influenzae

• Gram negative coccobacillus– Bronchotrachial tree becomes colonized and

microaspiration occurs

• Most commonly seen among smokers, children of smokers and daycare children– 33% - 35% of H. influenzae is beta lactamase producing– TRUST results (Tracking Resistance in the United States)

• 31.3% produced B lactamase in 99-2000• TMP-SMX resistance increased to 14% from 11.9%• Ampicillin resistance decreased from 33.9% to 30.7%

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M. catarrhalis

• Gram negative bacillus• Implicated in recurrent OM and Sinusitis• Will often spontaneously resolve if left

untreated• 90% - 98% beta lactamase producing

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Acute Bacterial Rhinosinusitis

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Tammy

• 27 year old woman with an 12 day history of nasal discharge

• Seemed to be improving until past 2 days; developed worsening of post-nasal drip and pain over both cheeks. Temp past 1-2 days: 99.8 – 100.5

• Last antimicrobial use: 1 year ago• PMH: Noncontributory; No tobacco, No allergies• LMP: 2 weeks ago; denies pregnancy• PE: Nasal mucosa erythematous. Maxillary sinuses

2+ tender

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Remember…

• Secondary bacterial infection of the paranasal sinuses following a viral URI is relatively uncommon, estimated to be 0.5%–2% of adult cases and approximately 5% in children

• A national survey of antibiotic prescriptions for URI in the outpatient setting showed that antibiotics were prescribed for 81% of adults with acute rhinosinusitis despite the fact that approximately 70% of patients improve spontaneously in placebo-controlled randomized clinical trials

http://guidelines.gov/content.aspx?id=36681 accessed 12-29-2012

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Pathophysiology of ABRS

• Normally, bacteria is removed from the sinuses by the mucous and the action of the cilia

• Ostia of a sinus becomes blocked • Bacteria is normally present in the sinus• Once the sinus opening is blocked, the

bacteria is trapped and begins to grow in number

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Pathophysiology of ABRS

• Mucosa of the sinuses become inflamed and swollen; The body responds by sending neutrophils to the area

• Result: Increased production of thick, green discharge; Pain in affected sinus(es)

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Predisposing Factors of ABRS

Upper respiratory infections

Colds

Allergy

Smoking

Immunodeficiency syndromes

Anatomical abnormalities

Dental infections

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Diagnosis of Bacterial Acute Sinusitis

• Who should be treated with antimicrobial:– Persistent symptoms or signs compatible with acute

rhinosinusitis, lasting for ≥10 days without any evidence of clinical improvement

– Onset with severe symptoms or signs of high fever (≥39°C [102°F]) and purulent nasal discharge or facial pain lasting for at least 3–4 consecutive days at the beginning of illness

– Onset with worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection (URI) that lasted 5–6 days and were initially improving ("double sickening")

Wright, 2017 71http://guidelines.gov/content.aspx?id=36681 accessed 12-29-2012

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Diagnostic Testing

• Sinus X-rays– Allows visualization of the maxillary and frontal

sinuses– Lack of specificity is a limiting factor– US Agency on Healthcare Policy – not cost effective

• CT Scan– Best visualization of the paranasal sinuses– Not recommended unless patient suspected to

have suppurative complications2

http://www.medscape.com/viewarticle/557184_2 accessed 01-28-20102http://guidelines.gov/content.aspx?id=36681 accessed 12-29-2012

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Cultures: What and When to Recommend

• Cultures should be obtained by direct sinus aspiration rather than by nasopharyngeal swab in patients with suspected sinus infection who have failed to respond to empiric antimicrobial therapy

• Endoscopically guided cultures of the middle meatus may be considered as an alternative in adults, but their reliability in children has not been established

• Nasopharyngeal cultures are unreliable and are not recommended for the microbiologic diagnosis of ABRS

Wright, 2017 73http://guidelines.gov/content.aspx?id=36681 accessed 12-29-2012

IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis

in Children and AdultsClinical Infectious Diseases Advance

Access published March 20, 2012

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http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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Goals of Treatment

• Restore integrity and function of ostiomeatal complex–Reduce inflammation–Restore drainage–Eradicate bacterial infection

http://www.medscape.com/viewprogram/5621 accessed 01-22-07

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Treatment of Acute Bacterial Rhinosinusitis

• Nonpharmacologic Therapies– Cold steam vaporizer– Increased water intake– Intranasal saline irrigations with either

physiologic or hypertonic saline are recommended as an adjunctive treatment in adults with ABRS1

1http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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Management Strategies in ABRS

• Antihistamines or decongestants– No longer recommended

• Topical corticosteroids– Intranasal corticosteroids are recommended as an adjunct

to antibiotics in the empiric treatment of ABRS, primarily in patients with a history of allergic rhinitis1

• Corticosteroids

1http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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IDSA

• Who should be treated with antimicrobials– 10 or more days of illness not improving– Double sickening– 3-4 days of severe illness

1http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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• First line therapy– Amoxicillin-clavulanate rather than amoxicillin alone

is recommended as empiric antimicrobial therapy for ABRS in adults and children

– Standard dosage:• 500 mg/125 mg 1 pill po three times daily or….• 875mg/125mg 1 pill two times daily

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Initial Antimicrobial Regimenfor Adults with ABRS

http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

• Individuals with B-lactam allergy– Doxycycline

• 100 mg 1 pill two times daily or 200 mg once daily or…

– Levofloxacin• 500 mg 1 pill once daily or….

– Moxifloxacin• 400 mg 1 pill once daily

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Initial Antimicrobial Regimenfor Adults with ABRS

http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

Initial Antimicrobial Regimenfor Adults with ABRS (Risk for resistance)

• Second line therapy– Amoxicillin-clavulanate

• 2000mg/125 mg 1 pill two times daily or….

– Doxycycline• 100 mg 1 pill two times daily or 200 mg once daily

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http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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Antimicrobial Regimen for ABRS in Adults at Risk for Resistance or Failed Initial

Therapy

– Amoxicillin-clavulanate• 2000 mg/125mg 1 pill two times daily or…

– Levofloxacin• 500 mg 1 pill once daily or….

– Moxifloxacin• 400 mg 1 pill once daily

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http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlaccessed 12-29-2012

FDA recommending

• Restrictions on fluoroquinolones for uncomplicated UTIs, bronchitis and ABRS– Ciprofloxacin, moxifloxacin, gemifloxacin,

levofloxacin and ofloxacin

http://www.consultant360.com/topic/fda-alerts accessed 05-12-2016 Wright, 2017 83

What Constitutes at Risk for Resistance?

• Age < 2 years or > 65 years• Daycare• Antimicrobial within past 1 month• Hospitalization within past 5 days• Comorbidities• Immunocompromised

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http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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Important Changes

• Macrolides (clarithromycin and azithromycin) are not recommended due to high rates of resistance among S. pneumoniae (30%)

• TMP/SMX is not recommended due to high rates of resistance among both S. pneumoniae and H. influenzae (30%–40%)

• Second and third-generation cephalosporins are no longer recommended due to variable rates of resistance among S. pneumoniae.

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http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlaccessed 12-29-2012

Length of treatment

• The recommended duration of therapy for uncomplicated ABRS in adults is 5–7 days

• In children with ABRS, the longer treatment duration of 10–14 days is still recommended

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http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

When to Change Treatments

• An alternative treatment should be considered if symptoms worsen after 48–72 hours of initial empiric antimicrobial therapy, or when the individual fails to improve despite 3–5 days of antimicrobial therapy

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http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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When to Refer

• Recalcitrant infection• 3-4 infections in 1 year• Evaluation for immunotherapy• Severe infection• Immunocompromised host• Fungal sinusitis

Wright, 2017 88http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+htmlAccessed 12-29-2012

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End of Presentation!

Thank you for your time and attention.

Wendy L. Wright, MS, APRN, BC, FAANP

WendyARNP@aol.com