Post on 22-Aug-2018
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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 symptoms
PressurePressure
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-D’Ambrosio 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• Sampter’s 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• Wegener’s granulomatosis
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Systemic Autoimmunity/Vasculitis• Sarcoidosis
Treat underlying conditionTopical corticosteroids
• Sjogren’s 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 β2-transferrin
• Is the new vasomotor rhinitis
• Corresponds to “neural” or “reflex”rhinitis
• “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 Children’s 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, Dennie’s 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 of the clinical history
Skin Testing
Population Data
J Allergy Clin Immunol 2005;116:377-83.
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• A number describing the amount of allergen specific IgE
• Should be interpreted in context of total IgE, symptoms
• No defined level for each antigen to predict clinical symptoms
RAST Testing
• Can be used to qualify a patient for anti-IgE therapy
• Not all antigens have defined cutoff values
• Longer turn around time, cost ($35-45+ per antigen)
RAST Testing
Test Performance-Cat Allergy
J Allergy Clin Immunol 1999;103:773-9.
86.4 (+7.1)87.2(+6.9)
87.1 (+6.0)93.6 (+4.3) 90.1 (+5.3)
91.1 (+5.9)
ARIA ClassificationIntermittent
Less that 4 days/week OR less than 4 weeks/year
PersistentMore than 4 days/week AND
more than 4 weeks/year
Mild
No Sleep Disturbance
No Impairment of school, work or desired activities
No “Troublesome” symptoms
Moderate-Severe
Sleep Disturbance
Impairment of school, work or desired activities
“Troublesome” symptoms
Bousquet J. Et al. JACI 2001; 108(suppl) S147-334.
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Treat the early and late phase symptoms
Bousquet J. Et al. JACI 2001; 108(suppl) S147-334.
Stepwise treatment--Allergic
Stepwise treatment--Allergic
Step 1: Antihistamine or Nasal Corticosteroid
Stepwise treatment--Allergic
Step 1: Antihistamine or Nasal Corticosteroid
Step 2: Nasal Corticosteroid AND Antihistamine or Leukotriene modifier
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Stepwise treatment--Allergic
Step 1: Antihistamine or Nasal Corticosteroid
Step 2: Nasal Corticosteroid AND Antihistamine or Leukotriene modifier
Step 3: Nasal Steroid/Antihistamine/Leukotriene modifier
Stepwise treatment--Allergic
Step 1: Antihistamine or Nasal Corticosteroid
Step 2: Nasal Corticosteroid AND Antihistamine or Leukotriene modifier
Step 3: Nasal Steroid/Antihistamine/Leukotriene modifier
AllergenImmunotherapy
Referral for testing at any stage
Stepwise treatment--Allergic
Step 1: Antihistamine or Nasal Corticosteroid
Step 2: Nasal Corticosteroid AND Antihistamine or Leukotriene modifier
Step 3: Nasal Steroid/Antihistamine/Leukotriene modifier
Saline Irrigation/Lavage
AllergenImmunotherapy
Referral for testing at any stage
• Primarily — Itch, Sneeze, Rhinorrhea
• Antihistamine (oral or intranasal)
• Weekend symptoms
Treat the Symptoms
J Allergy Clin Immunol 2006;118:985-96.
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• Primarily Congestion
• First line should be nasal corticosteroid
• Leukotriene modifier
• Decongestant
Treat the Symptoms
J Allergy Clin Immunol 2006;118:985-96.
• Failure of medical treatment
• Desire to decrease long term medication use
• Intolerance to medication of side effects
• Allergic rhinitis and asthma (or possible prevention of asthma)
• Venom anaphylaxis
Indications for Immunotherapy
Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy
Durham SR et al N Engl J Med 1999; 341: 468-475
Initial Placebo Trial Current Trial
Polle
n C
ount
(gra
ins/
m3 )
Sym
ptom
Scor
e
May June July Aug.
May June July Aug.
May June July Aug.
May June July Aug.1989 1993 1994 1995
Study groupImmunotherapyPlacebo
ImmunotherapyMaintenanceDiscontinuationNone (control)
SLIT• Sublingual Immunotherapy--a future
alternative to subcutaneous IT
• Multiple dosing forms exist (extract, tablet)
• Increased safety profile
• Can be done at home
• Dose varies by antigen, not established yet for US extracts
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SLIT• Currently undergoing clinic trials in the
US
• Similar immunologic changes to Subcutaneous immunotherapy
• Increased Treg cells
• Blunted seasonal rise in IgE, increased antigen specific IgG4
ISS Conjugated Proteins
• ISS is unmethylated CpG DNA, a strong immune stimulus
• Stimulate TLR-9
• Published use in ragweed allergy
Creticos, PS et al. NEJM 2006;355:1445-1455
ISS Conjugated Proteins
• Amb a 1-ISS has shown benefit in ragweed allergic patients
• Administered as six escalating doses before 2001 pollen season
• Followed for 2001 and 2002Creticos, PS et al. NEJM 2006;355:1445-1455
Ragweed Results
Creticos, PS et al. NEJM 2006;355:1445-1455
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• Treat the patient’s symptoms and pick the treatment to fit the symptoms
• Discover and remove triggers
• Diagnosis—History/Exam will exclude likely causes
• Re-evaluate if symptoms don’t respond
• Patients often have multiple causes
Allergic Rhinitis--Summary
• Often a combination of medication is necessary—stepwise approach to treatment aids decision making
• Immunotherapy has multiple indications
• Multiple new administration methods and preparations in future
Treatment Summary