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Nonallergic RhinitisEvaluation and Treatment

Charity C. Fox, M.D.Clinical Assistant Professor

Allergy and ImmunologyDepartment of Internal Medicine

The Ohio State University Medical Center

A Diagnosis of Exclusion Candidates have

Negative allergy skin tests or RAST testsNo infectious process

No definitive diagnostic test Diagnosis based primarily on clinical

features and associated conditions

Nonallergic Rhinitis

Overlap in Common Causes of Rhinitis

AllergicRhinitis

NonAllergicRhinitis

Infection(Sinusitis)

Three major types of chronic rhinitis

Nonallergic Rhinitis Little prevalence data for nonallergic

rhinitis syndromes

52% of patients seen in an allergy clinic were found to have nonallergic rhinitis

Female>male in a few studies looking at epidemiology

Mullarkey et al J Allergy Clin Immunol 65: 122, 1980.Sibbald et all. Thorax 6:895, 1991.

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Overlap in Non-Infectious Causes of Rhinitis

Lieberman et al All Asthma Proc 24:95,2003

AllergicRhinitis

NonAllergicRhinitis

Pure Allergic43%

Mixed34%

Pure Nonallergic

23%

CombinedNonallergic

57%

RhinitisNonallergicAllergic

Sneezing Sneezing

Itch Itch

Posterior Rhinorrhea

Eye symptoms Eye symptomsPressurePressure

Headache Headache

Posterior RhinorrheaCongestion Congestion

Mechanistic Classificationof Rhinitis

Inflammatory(Leukocytes)

Non Inflammatory (No Leukocytes)

Eosinophil Neutrophil Mixed EpithelialDysplasia

Neural Hormonal Structural

Allergy

NARES

CESS

Polyps

NSAIDSensitivity

Allergic FungalSinusitis

BacterialSinusitis

CiliaryDysfunction

ImmuneDeficiency

Dentogenic

Foreign Body

Viral

Vasculitis

Glandular Sinusitis

Atrophic

Sjogrens

Oxidants

Mucosaldisruption

Nociceptive

Parasympathetic

Sympathetic

Olfactory

Thyroid

Pregnancy

Anatomic/Trauma

Tumors

Occupational Meltzer et al. J AllergyClin Immunol114:S155, 2004.

Mechanistic Classification: Nonallergic Noninfectious Rhinitis

InflammatoryEosinophils NARES/BENARES Polyps NSAID sensitivity

Neutrophils or Mixed Vasculitis/Autoimmune

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Mechanistic Classification: Nonallergic Noninfectious Rhinitis Non-Inflammatory

Drug InducedEpithelial dysfunctionOccupational/IrritantHormonalStructuralIdiopathic/Neural/Vasomotor

Perennial symptoms similar to allergic rhinitis

Sneezing, rhinorrhea, nasal itch, congestion, anosmia

Eosinophilia on nasal smears Negative allergy skin tests or RAST

tests Associated with asthma, aspirin

intolerance and nasal polyps

Nonallergic Rhinitis with Eosinophilia Syndrome

(NARES)

Good response to intranasal corticosteroids. Budesonide, beclomethasone and fluticasonehave indications for nonallergic rhinitis.

Oral antihistamines some efficacy in only a few studies.

Subtypes of the condition with blood eosinophilia(BENARES)

Patients sometimes describe antigen triggers

Nonallergic Rhinitis with Eosinophilia Syndrome

(NARES)

Purello-DAmbrosio et al. Clin Exp Allergy 29:1143, 1999.

Positive nasal allergen challenges in patients with

persistent nonallergic rhinitisEvidence for localized allergic response

Rondon et al. J Allergy Clin Immunol 119:899,2007.

54% of persistent nonallergicrhinitispatients (PNAR) showed positive nasal allergen provocation tests (NAPT) to D. pteronyssinus (DP) dust mite

22% had nasal specific IgE to DP mite in the face of negative skin tests and serum specific IgE to DP

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Nasal Polyps

Photo courtesy of David M. Powell M.D.

David M Powell MD

Benign polypoidmasses arising from inflamed nasal mucosa.

Contain eosinophils,Lymphocytes, plasma cells and mucin with few nerves.

Nasal PolypsAssociated with Aspirin intolerance Sampters syndrome

aspirin intolerance,asthma, nasal polyps, sinusitis.

Cystic Fibrosis Churg-Strauss syndrome Chronic sinusitis Ciliary dyskinesia Young syndrome Allergic fungal sinusitis

David M Powell MD

Pathophysiology unknown Recurrent infections contribute Increased histamine, leukotrienes and

serotonin Not IgE-mediated Respond to corticosteroids Possible role for leukotriene inhibitors

Nasal Polyps

Systemic Autoimmunity/Vasculitis

Churg-Strauss syndrome Systemic lupus granulomatosis Wegeners granulomatosis

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Systemic Autoimmunity/Vasculitis Sarcoidosis

Treat underlying conditionTopical corticosteroids

Sjogrens syndromeTreatment of xerostomia with nasal saline sprays, moisturizing nasal gels, sialogogues

Non-Steroidal Anti-Inflammatory Drugs(NSAID Rhinitis, ASA Triad)

AntihypertensivesACE Inhibitors

Hydralazine

Beta-blockers

Drug Induced Nonallergic Rhinitis

Rhinitis MedicamentosaTopical decongestants

Oral Contraceptives/Hormone Replacement Therapy

Psychotropic agents

Drug Induced Nonallergic Rhinitis

Epithelial DysfunctionAtrophic Rhinitis1) Epistaxis, nasal crusting, stuffiness,

halitosis1) Excessive surgical removal of nasal

mucosa1) Treatment with nasal saline rinses and

moisturizing agents2) Klebsiella infection in elderly

1) Treatment with antibiotics

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Epithelial Dysfunction2) Profuse rhinorrhea in elderly

1) Possible parasympathetic overactivity

1) Treatment with intranasal ipratropium bromide

Many causative agents in the workplace or home

Can be inflammatory or non-inflammatory

Immunologic responses

Comparable to agents of occupational lung disease

Occupational/Irritant

Corrosive effects with epithelial injury

Irritant Rhinitis

Smoke, paint, air pollution, dust

Physical Stimuli

Cold dry air, bright lights

Occupational/Irritant

Hormone Induced Nonallergic Rhinitis

Rhinitis of Pregnancy

Hormone replacement therapy and oral contraceptive associated rhinitis

Hypothyroidism

Acromegaly

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Structural Rhinitis Septal deviation or other obstructing

abnormality can aggravate rhinitis

Tumors

Cerebral Spinal fluid leak

Associated with trauma or surgery

CSF contains glucose and 2-transferrin

Is the new vasomotor rhinitis

Corresponds to neural or reflexrhinitis

After having excluded all known causes of chronic rhinitis

Nasal hyperreactivity key feature

Idiopathic Rhinitis

Exclusion criteriaPositive allergy testSmokingNasal polypsAnatomical abnormalityInfectionPregnancy, lactation, hormone replacementMedications affecting nasal functionBeneficial effect of nasal corticosteroid (NARES)

Idiopathic Rhinitis

Rijswijk et al. Allergy 60:1471, 2005.

Selection criterionNasal hyperreactivity

To nonspecific stimuli

Smoke, spices, strong odors, and other irritants

Idiopathic Rhinitis

Rijswijk et al. Allergy 60:1471, 2005.

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Importance of neurologic vascular control Hyperactive parasympathetic system

Hypoactive sympathetic system

Overactivity of C-fibers of the nonadrenergic noncholinergic system

Enhanced release of substance p and other neuropeptides

Idiopathic Rhinitis

Efficacy of topical antihistamine in idiopathic

rhinitisAzelastineeffective for thetreatment ofIdiopathic(vasomotor)rhinitis in twoDBPC trials.

From Gehanno et al. ORL J Otorhinolaryngol Relat Spec 63:76, 2001.

Summary: Treatment of Nonallergic Rhinitis

Inflammatory Non Inflammatory

PruritisSneezingCongestionRhinorrheaCongestion

Eliminate triggers and treat identifiable causes

azelastine

Consider ipratropium or cromoglycate

nasal corticosteroid

Nasal corticosteroid

AddAntihistamine

Oral or Azelastine

(Leukotrieneinhibitors Proposed)

Rhinorrhea

Ipratropium

(EspGustatory Or Atrophic

Rhinitis)

Azelastine

With or without nasal saline rinses

Allergic Rhinitis:Initial Diagnosis and

TreatmentDavid W. Hauswirth, M.D.

Clinical Assistant ProfessorAllergy and Immunology,

Internal Medicine and PediatricsThe Ohio State University Medical Center

Nationwide Childrens Hospital

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Sneezing Runny Nose Nasal Congestion Facial Pressure Headache Facial Pain Ear Pressure/fullness Eyes water or itch

Chief Complaint

Decreased Smell Decreased Taste Bad Breath Cough Sore Throat Throat Clearing Throat Drainage Sinus Infections

Chief Complaint

Adolescents and AdultsAllergic RhinitisNon-Allergic Rhinitis/Vasomotor RhinitisInfection (viral URI or sinusitis)Obstructing polyps, septaldeviation

Age Matters

ChildrenInfection Allergic Rhinitis (generally >2 y/o)Non-Allergic Rhinitis/Vasomotor Rhinitis

Irritant (esp. tobacco smoke)Obstruction (Adenoid hypertrophy, foreign body)

Age Matters

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Exam Pearls Edema and venous sinusoid congestion

leads to swollen pale or blue turbinates

Clear middle ear fluid is common with significant congestion

The eyes are important (redness, swelling, shiners, Dennies lines)

Other sign of atopy--asthma, eczema

Testing should be to relevant local antigens

Pollen seasons and indoor allergen patterns help interpret history

Spring-Trees; Summer-Grass; Fall-Weeds

Skin Testing

History dictates what antigens are to be tested

Interpreted only in the context