Allergic rhinitis

Yada Sirisa, M.D.
16 September 2022
Division of Allergy, Immunology and Rheumatology Unit, Departement of Pediatrics
King Chulalongkorn Memorial Hospital
Allergic Rhinitis

Outline
• Definition and classification
• Epidemiology
• Pathophysiology and mechanisms
• Risk factors
• Evaluation and diagnosis
• Associated conditions
• Management

Outline
• Definition and classicfication
• Epidemiology
• Pathophysiology and mechanisms
• Risk factors
• Evaluation and diagnosis
• Associated conditions
• Management

Definition
• Allergic rhinitis is an IgE-mediated inflammatory nasal condition
resulting from allergen introduction in sensitized individual
• The classic cardinal symptoms
Pruritus of nose, palate, throat or ears
Nasal congestion
Rhinorrhea (usually clear and watery)
Sneezing
Bousquet J, et al. Allergy. (2008) 63:8–160.
Nelson’s Textbook of pediatric, 21th edition

Classification of AR (old)
Seasonal AR Perennial AR
Intermittent
(Cyclical exacerbation)
Persistent
(Year-round symptoms)
Outdoor allergens
Tree pollinate (spring)
Grasses (early summer)
Weeds (late summer)
Indoor allergens
House duct mites
Animal dander
Molds
Cockroaches
Bousquet J,et al. J Allergy Clin Immunol 2001;108(Suppl. 5):S147– S334.

ARIA classification of AR
(new)
Bousquet J, et al. Allergy. (2008) 63:8–160.
Middleton's’ Allergy: Principle and Practice, 9th edition

Classification of Rhinitis
Bousquet J,et al. J Allergy Clin Immunol 2001;108(Suppl. 5):S147– S334.
Hellings PW, et al. Allergy 72.11 (2017): 1657-1665.

Epidemiology
Akdis CA, et al, EAACI, Zürich (2015)
Middleton's’ Allergy: Principle and Practice, 9th
edition
The highest prevalence rates for rhinitis were observed in parts of Western Europe, North America
The lowest rates were found in parts of Eastern Europe and south and central Asia

Epidemiology
Chinratanapisit S, Suratannon N, et al. Asian Pac J Allergy Immunol. 2019 Dec;37(4):232-239.
• Thailand: The prevalence of current AR in all children 16.3%
(15% in aged 6–7 years and 17.5% in aged 13–14 years)
• AR is common disease among children residing in Bangkok
• Co-morbidity with asthma and eczema was 27.1% and 24.6%
• A family history of atopy, antibiotics given in the first year of life, current
paracetamol use, exercise, current cat exposure, and truck traffic on the street of
residence are important and significant risk factors for AR symptoms

The Atopic March
Development of FA,asthma, and AR in the young toddler age group is common after cutaneous manifestations
Czarnowicki T,et al. J Allergy Clin Immunol. 2017 Jun;139(6):1723-1734.

Pathophysilogy
• Sensitization: development of specific IgE
Allergen reach Antigen-Presenting Cells (APCs)
APCs promote Th2 polarization
Th2 promotes production of allergen-specific IgE
.

.
Bousquet, Jean, et al. Nature Reviews Disease Primers 6.1 (2020): 1-17.
Pathophysilogy

Sensitization: Th2 polarization
.
Ho IC, et al. Nat Rev Immunol. 2009 Feb;9(2):125-35

Sensitization
Specific IgE production
.
Geha R, et al. Nat Rev Immunol 3, 721–732 (2003).

Pathophysilogy
• Subsequent response: development of symptoms
Nasal symptoms: Early & Late phase response
Specific & non-specific hyperresponsiveness
Lower airways symptoms (United airway hypothesis)
.

Subsequent response
.
Geha R, et al. Nat Rev Immunol 3, 721–732 (2003).

.
The Calgary Guide to Understanding Disease allergic rhinitis

Pathophysilogy
Meltzer. Allergy, Asthma & Clinical Immunology. 17. 10.1186/s13223-021-00614-6
Middleton's’ Allergy: Principle and Practice, 9th
edition

United Airway Hypothesis
• Air-conditioning
• Inflammation
• Neural reflexes
Giavina B, et al. Journal of Asthma and Allergy 2016:9

Mouth Breathing and
Bronchoconstriction
• Patients with AR present partial or complete loss of function of the nose
due to mucosal congestion
• Mouth breathing bypass this filter and result in
> Inhalation of cold and dry air may directly induce
bronchoconstriction
> Opened to the entrance of allergens and pathogens, increasing
the risk of asthma exacerbation

Aspiration of nasal content
• Post nasal drip > aspirate > coughing
• Inflammatory secretions from the upper airway of patients with
rhinosinusitis or even with rhinitis are aspirated into the lower airway
with adverse consequences
• Stimulation of pharyngo-laryngeal receptors is more likely to be
responsible for a postnasal drip related cough

Nasobronchial reflex
The existence of a nasobronchial reflex that originates from the
sensory nerve endings in the nose
>> Travels to the CNS through the trigeminal nerve
>> Efferent pathway through the vagus nerve
>> Airway smooth-muscle contraction
• Upper and lower airways seem to constitute a unique system
• Share similarities in terms of histology, physiology, and pathology
• Triggered by a TH2 immune response of the airway, leading to an
extended inflammatory process that begins in nasal mucosa and
ends in bronchioles and alveoli

• Genetics
• Inhalant allergens
• Food allergens
• Pollution
• Tobacco smoke
• Socioeconomic factors
Incresed Risk
• Breast feeding
• Childhood exposure to pets
• Hygiene hypothesis
Protective Factors
Risk Factors
ISCAR: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb; 8(2): 108-352

• Genetics
• Food allergens
Incresed Risk
• Pollution
• Tobacco smoke
Risk Factors
GWAS: Single nucleotide polymorphisms associated with AR
Gene-enviroment interaction and epigentic effects

Leucine-rich repeat-containing protein 32
(LRRC32)
”Strongly associated with AR”
T-cell proliferation
Cytokine secretion
TGF-β activation

Genome-Wide
Association Study
(GWAS)
Most strong signal: HLA- DQB1
Function involve in
• Regulation of B and T cell
• Antigen recognition
Overlapped with asthma, eczema,
autoimmune diseases and non-AR
Known association
HLA-DQB1
J. Waage, et al.Nature Genetics 2018 Vol. 50 Issue 8 Pages 1072-1080

Gene-enviroment interaction and epigentic effects
DNA methylation in children is very strongly influenced by well-
known risk factors for allergic diseases
“maternal smoking during pregnancy and air pollution exposure”
D. Y. Wang, Therapeutics and Clinical Risk Management 2005 Vol. 1 Pages 115 - 123

• Genetics
• Food allergens
Incresed Risk
• Pollution
• Tobacco smoke
Risk Factors
Mites/Pollens/Animal dander/Fungal allergen

Huang CF, et al. World Allergy Organization Journal14.1 (2021): 100495.

Daily ambient
levels of pollen
were measured
during this period
Cumulative exposure to pollen
concentrations up to 6 months
was associated with aeroallergen
sensitization with the highest risk
occurring at 3 months
Erbas B, et al. Clinical & Experimental Allergy 43.3 (2013): 337-343.

Exposure to high levels of birch pollen in infancy
￪ the risk of sensitization allergen ￪ allergic asthma
“But not differ in AR and AD”
J Allergy Clin Immunol.2002 Jul;110 (1):78-84

Animal dander: conflicting results
Additional factors:
pet age, gender, and species
number of household pets
home characteristics
atopic predisposition of the pet owners

Early exposure to fungal allergens
￪ Risk of AR
Confounder
Home moisture level associated with the
presence of fungal allergens in the home
(and also increase level of mites)

Sher NC, et al. Epidemiology of allergic rhinitis and associated risk factors in Asia

• Genetics
• Food allergens
Incresed Risk
• Pollution
• Tobacco smoke
Risk Factors

Alduraywish SA, et al. Allergy. 2016 Jan;71(1):77-89
Food sensitization
￪ Risk of Allergic rhinitis

Asthma and AR significantly associated with
FA and allergic sensitization to food allergens
Pénard-Morand C, et al. Allergy. 60. 1165-71.

PM10, PM2.5, NO2, SO2, CO, and O3
Pollutions
• Direct surface damage to nasal mucosa
• Altered epigenetic mechanisms
(histone acetylation, expression of
microRNA and DNA methylation)
• Immune suppressive effect (nicotine)
Tobacco
• Injuring the nasal epithelium
• Altering the immune response
>>Increasing the allergenicity of antigens
• Airborne particles >> carry allergens >>
spread of allergens or the duration of
exposure

Limitations: socioeconomic status,
type of pollutant, geographic diversity,
pollution level measurement
Active and passive smoking are associated
with increased risk of allergic diseases in
children and adolescents

Smoking could be associated with increased risk of
developing airway remodeling and decreased lung
function in AR patients (not significant)
Active smokers do not
demonstrate impaired nasal
related quality of life or impact on
atopic inflammatory parameters,
compared to non-smokers
Acta Biomed 2019; Vol. 90, Supplement 7: 45-51
Gómez, René Maximiliano, et al. "World Allergy Organization Journal 14.2 (2021)
Tobacco Use and Allergic rhinitis

Higher income is associated with better living
conditions and hygiene behavior >> Reducing the
exposure to a variety of allergens >> ￪AR
Most studies show an association between high SES
and the diagnosis of AR additional factors (Sibling
number, breast feeding, diet, housing, overall hygiene) ISCAR: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb; 8(2): 108-352
Sher NC, et al. Epidemiology of allergic rhinitis and associated risk factors in Asia

• Breast feeding
• Hygiene hypothesis
• Number of siblings
• Farming
• Microbial diversity
Protective Factors

Nonsignificant protective effect overall
Protective effect close to statistical significance
in the general population
but not in children with a FH of atopic disease
Breast Feeding
Mimouni Bloch et al. Acta Paediatr. 2002: 91
Lodge CJ, et al. Acta Paediatr. 2015;104: 38-53.

￪ Number of siblings was associated with ↓ atopy
Significant relationship between children
with ↓ siblings (<3 siblings) and
￪prevalence of allergic rhinitis
Sastra S, et al. Paediatrica Indonesiana 56.1 (2016): 1-7.
Karmaus W, et al. A review Journal of Epidemiology & Community Health 56.3 (2002): 209-217.
Number of siblings

• Farm exposure in utero and in early childhood
protected against allergen sensitization
• The protective farm effect seems to be stronger
when exposed to farm animals and stables
• The protective effect is greatest with highest
exposure occurring early in life
Microbial diversity
Low diversity of gut microbiota in
early infancy has been related to
greater risk of asthma
The dysbiosis of the microbiome
driven by higher Bacteroides and
reduced Clostridia taxa in adulthood
was associated with greater
prevalence of seasonal and nut
allergies in adulthood

Clinical Manifestation
Classic symptoms of allergic rhinitis
• Nasal congestion or obstruction
Frequently alternateds between both sides
Persistent unilateral obstruction
>> Anatomical defect/Nasal polyps/Tumor
• Sneezing: often marked in by explosive paroxysms of ≥ 5-10 sneezes
• Rhinorrhea: often clear to white in color
Purulent secretions: chronic sinusitis
• Nasal pruritis
ISCAR: Allergic Rhinitis Int Forum Allergy Rhinol, 2018 Feb;8(2): 108-352
Middletons’s Allergy: Principle and Practice, 9th edition

• Ocular pruritis, ertyhema, and
tearing
• Oral cavity or pharyngeal pruritis
• Wheezing or cough (reactive
airway disease and/or asthma)
Associated symptoms
• Hyposmia or anosmia
• Snoring or sleep disordered breathing
• Aural congestion or pruritis
• Sore throat
• Halithosis
Additional symptoms

Presence of temporal patterns
• All rhinitis symptoms are most intense during the early morning
hours (circadian variation)
• Decrease in symptoms throughout the day: presece of indoor
allergen (HDM, animal dander, nold, cockroach)
• Clear cut worsening of symptoms in outside environments:
probability of allergy to an outdoor allergen (pollen, mold)

ARIA 2008: Symptoms of Allergic rhinitis

Physical examination
General observation:
• Facial pallor
• Elongated face
• Allergic gape or mouth breathing
• Gummy smile, dental malocclution
Eyes:
• Allergic shiner, Dennie-Morgan line
• Dermatitis outer eyelids
• Excessive lacrimation
• Erythema and swelling of bulbar conjunctiva
• Cobblestone papillae

Nose:
• Transverse nasal crease
• Allergic salute
• Nasal turbinate: hypertrophy, edema, pallor
• Clear nasal discharge
• Dried blood commonly is observe (trauma)
• Polyps (rarely)

Inferior turbinate classification system
Camacho et, al laryngoscope 125:296-392, 2015

Throat:
• Gothic arch/ high arch palate
• Dental malocclusion
• Halitosis
• Tonsillar hypertrophy
• Pharyngeal postnasal discharge
• Cobblestoning of oropharyngeal wall

Ears
• Middle ear effusion
• TM retraction
Chest
• Audible wheezing
• Diminished breath sound
Skin
• Eczema, urticaria, dermatographism

Diagnosis
The hallmark of allergic rhinitis is “specific IgE to relevant allergen”
• History and physical examination
• Laboratory Testing
Skin prick test
Blood Eosinophils and Total Serum IgE
Nasal Cytology
Radiographic Imaging
Measurements of Nasal Patency

Skin Prick Test (SPT)
Best method for detection of allergen-specific IgE
“ Confirm the diagnosis of AR”
• Inexpensive, sensitive and minimal risk
• High sensitivity and specificity
• Positive: wheal > 3 mm compared with negative control
• For avoid false-negative results should be withheld antihistamine

Medications that affect allergy skin testing

Blood Total Serum IgE
● Increase total serum IgE and
circulating blood eosinophils
● Useful if SPT cannot be done
● To distinguish AR from non-AR

Serum antigen specific IgE (sIgE)
• Radioallergosorbent test (RAST)
Radioactive anti-IgE for labeling IgE in serum
• The safety profile of serum sIgE testing is the best of all
available allergy test
• Not influenced by drugs or skin disease
• Level of sIgE may correlate with severity of AR symptoms

Nasal Cytology
Cytologic stains of mucus blown from the nose or epithelium scraped
from the inferior turbinate
● Assessed for multiple cell types, including eosinophils and neutrophils
● For differentiating AR from non-AR or sinusitis
● Presence of significant nasal eosinophilia (>10 cells/HPF) suggestive
for the diagnosis of AR

Radiographic Imaging
• Routine radiographic imaging is not recommended for the diagnosis of AR
The most accurate test for evaluating possible sinusitis is CT
• AR: mild mucoperiosteal thickening
• Considered in patients with not typical of chronic rhinitis
Chronic purulent rhinorrhea
Alterations in sense of smell
Headaches
Not responsive to therapy

Measurements of Nasal Patency
Assessment of nasal airway swelling
● Helpful in estimating the severity
● Objective evaluations
Assessing the anatomy of the airway: acoustic rhinometry
Measuring nasal airflow or resistance: nasal peak flow,
active rhinomanometry

Differential diagnosis in rhinitis
Bousquet J, et al. Allergy. 2008 Apr;63 Suppl 86:8-160.
Scadding GK, et al. Clin Exp Allergy. 2017 Jul;47(7):856-889.

Diagnosis in rhinitis
BSACI guideline Revised Edition 2017.C)in Exp Allergy. 2017 47:856-889.

Comorbid conditions and complications
Cingi C, et al. Clin Transl Allergy. 2017 Jun 1;7:17.

Immunotherapy
01
02
03
Management
Allergic avoidance
Pharmacotherapy

01 Allergic avoidance:
1st management step in AR

Environmental controls: HDM
• Threshold level of sensitization:
2 μg/g of group 1 mite allergen (allergic child)
≥ 20 μg/g of group 1 mite allergen (nonallergic child)
Use multiple intervention
• Effective barrier to exposure
• Kill/degrade mite & mite ova: heat, chemical method
• Regular cleaning: remove dust mite allergen, food source of mite
• Minimized reservoirs, make cleaning easier
• Minimized factor influencing mite growth (temperature, humidity)
Middleton’s Allergy Principle&Practice 9th edition. 2019
Pediatric allergy&Primary immune deficiency diseases. Indoor allergens. 35-60.

An Updated Practice Parameter. J Allergy Clin Immuno. 2008;122:s1-84.

Environmental controls: Cockroah
• Species are common in houses:
• Blattella germanica (German cockroach)
• Periplaneta american (American cockroach)
• Allergen derived from feces, saliva, debris from dead animals
• Major allergens in feces extract > body extract 6 times
• Highest levels of cockroach allergens: kitchen
• Dose-response relationship between cockroach allergen exposure
and sensitization
• Sensitized threshold: Bla g 1/Bla g 2 >2 unit/g (risk for develop
asthma : 35x)

• Poison bait
- Boric acid (damage foregut)
- Hydramethylnon, abamectin, fiproni
• Careful housekeeping to enclose all sources of food for the insects
• Cleaning to remove any accumulated allergen
sealing as many access points to the house as possible
Environmental controls: Cockroah

Environmental controls: Pets
• Allergen-producing animals (both domestic & occupational settings):
their dander, epithelia, fur, urine, or saliva being the main sources
• Major cat allergen: Fel d 1 (primary site: skin)
• Major dog allergen: Can f 1 (saliva > dander)
• Cat & dog allergens size 2-15 μm
- Small particle (<5 μm ): airborne in an undisturbed house & fall slowly
- Sticky particle of danders > carried on from house to other

Environmental controls: Pets

Environmental controls: Pollen & Outdoor moulds
Seedat R. Current Allergy&Clinical Immunology. 2019;32.
• Avoid outdoor activities during peak pollen and mould periods
• Keep doors/windows closed, use air conditioning
• Change clothing when returning home
• Mould-sensitive patients should avoid contact with decomposing leaves,
grasses and grains and avoid camping or walking in forests
• Using HEPA filter
• Frequent vacuuming
• Self protection equipment: mask

02 Pharmacotherapy
• Antihistamines: oral, topical
• Decongestants: oral, topical
• Corticosteroids: intranasal, systemic
• Leukotriene receptor antagonists
• Anticholinergics
• Cromolyn Sodium
• Normal saline irrigation
• Omalizumab
• Combination therapy
Okubo K, et al. Allergology International. 66. 10.1016/j.alit.2016.11.001.

S.N. Mandhane et al. / International Immunopharmacology 11 (2011) 1646–1662

The inactive state of histamine Hi receptor is in
equilibrium with the active state
The agonist, histamine, has affinity for the active state
Stabilizes the and shifts toward the active state
Anti-antihistamine (inverse agonist) has affinity for the inactive state
Stabilizes the receptor and shifts toward the inactive state
Anti-Histamine

• Lipophilic and crossed the BBB
• Induce sedation, drowsiness,
fatigue, impaired concentration
and memory, and anti-
muscarinic effects
• Not recommended for AR
1st generation antihistamine
• Similar effectiveness as 1st
generation antihistamine with lack
of brain penetration
• First-line therapy for mild to
moderate intermittent and mild
persistent rhinitis
2nd generation antihistamine
Oral antihistamine

2nd generation antihistamine dosage

Can be used while flying: Loratadine, Desloratadine and Fexofenadine
Kawauchi HY, et al, International Journal of Molecular Sciences. 20. 213. 10.3390/ijms20010213.

• Reduces nasal congestion, itching,
sneezing, and runny nose
• Rapid onset of action (15-30 mins)
• Can be administered on demand
• More effective for nasal congestion
than oral antihistamines
Benefits
• Alteration of taste sensation
• Systemic absorption: somnolence
• Tachyphylaxis
Azelastine hydrocloride
Olopatadine hydrocloride
Intranasal antihistamine
Not available in Thailand

Intranasal antihistamine
Seidman, et al. Otolaryngol Head Neck Surg. 2015; 152(1S):S1-S43

• α-adrenergic stimulation
→ vascular constriction and a reduction of nasal blood supply to the sinusoids
• Reduce nasal congestion but no significant effects on the symptoms of rhinitis
Decongestants

Decongestants
Decongestant Topical Oral
Commonly used Xylometazoline, Oxymetazoline Pseudoephedrine, Phenylephrine
Onset Rapid within 5-15 min Active within 30-60 min
Rebound effect Prolong use > 5-10 days may
lead to rhinitis medicamentosa
No
Systemic effect No Insomnia, nervousness, anxiety,
palpitation, headache, HT
Others Adverse effect: nasal burning,
stinging, dryness, epistaxis,
mucosal ulceration
Caution in Patient with HT, Heart
disease, seizure, BPH

Leukotriene receptor
antogonist (LTRA)
Jeffrey M, et al. N Engl J Med 1999; 340:197-206
Inhibitors of the
5-lipoxygenase pathway
(zileuton) and leukotriene
receptor antagonists
(montelukast and zafirlukast)

• Equal in effectiveness to
antihistamines for relief of all
ocular and nasal symptoms of AR
• Considered in patients with AR
and concomitant asthma.
• Equal to pseudoephedrine
Pro
• Less effective than INCS
• Less effective or equal to oral antihistamine
• Not recommended as monotherapy for AR
• Higher cost
Con
Leukotriene receptor
antogonist (LTRA)

Intranasal Anticholinergics
European Respiratory Journal 2018 52: 1701247
Intranasal Ipratropium bromide

Intranasal Anticholinergics
• Suppressive effects on sneezing and rhinorrhea,
• No influence on nasal airway resistance.
• No effect on itching, or nasal congestion
• Can be used in with drugs of other classes, such as
antihistamine or INCS
• Quick onset and short half-life
• Only local side effect → epistaxis, nasal dryness
• Contraindication → hypersensitivity to soy lecithin

Cromolyn Sodium
Stabilize the mast cell membrane and
inhibits release of the spasmogenic
mediators of Type I allergic reaction,
including Histamine and slow reacting
substance of anaphylaxis (SRS-A)
from sensitized mast cells
Intranasal cromolyn sodium 4% solution

Cromolyn Sodium
• Helpful for sneezing, itching, and rhinorrhea
• Less effective in relieving nasal congestion
• Very safe, especially in children and pregnant women
• Most effective when started before the onset of symptoms
• Better in SAR and PAR (both adult and children)
• Less effective than INCS (in nasal symptoms)
• Recommended dosage is 4-6 times daily → poor compliance

Combination therapy
• INCS and INAH combined → intranasal azelastine and fluticasone propionate
• Initial treatment of moderate/severe AR
• INCS and INAH is more effective at reducing symptoms of AR and has a faster
onset of action
• US FDA approved 6 years old
• Thai FDA approved 12 years old

Nasal saline irrigation
• A good adjunctive option with all other treatments of AR
• Mechanical effect
Remove mucus and inflammatory mediators
Dilute antigen
Promote mucociliary clearance
• Low adverse effect and low cost

Y. Wang, et al. Allergol Immunopathol (Madr). 2020;48(4):360-367

Saline irrigation vs.
non-irrigation
Saline irrigation showed
significant efficacy in both
children and adults groups
Saline irrigation vs.
medication
No statistical difference of
efficacy in children

Hypertonic saline vs.
isotonic saline
Efficacy of hypertonic saline
was superior to that of
isotonic saline in children
Saline with medication vs.
medication alone
No statistical difference of
efficacy in children

Bousquet J, et al. NATURE REVIEWS DISEASE PRIMERS.(2020) 6:95

Intranasal
Corticosteroids
• The most effective medication for AR
• Also first-line treatment, superior to antihistamines
• Effectively reduces inflammation of the nasal mucosa
Relieves nasal congestion, rhinorrhea and ocular symptoms
• Onset of action 6-8 hr after the first dose, reaches
maximal effect after 2 weeks
Mygind, et al. J ALLERGY CLIN IMMUNOL JULY 2001
• Side effects: local nasal irritation, sore throat and epistaxis

Intranasal Corticosteroids
Clinical and Experimental Immunology, 2009.158: 164–173

J allergy Clin Immunol 2008;122S1-84.

J allergy Clin Immunol 2008;122S1-84.
Local side effect
• Dryness, burning
sensation
• Epistaxis
• Septal perforations

INCS: Systemmic side effect
Systematic review of controlled trials did not demonstrate a clinically
relevant impact of INCS
• Ocular pressure
• Glaucoma
• Lens opacity
• Cataract formation
Valenzuela CV, et al. Laryngoscope. 2019 Jan;129(1):6-12.

INCS: Systemmic side effect
The data suggests that INCS might have deleterious effects on short-term
growth in children, but the heterogeneity in the stadiometry studies makes
the effects on long-term growth suppression unclear
Show no adverse effects in adult and children
• Morning cortisol concentrations
• 24-hour serum cortisol
• 24- hour urinary free cortisol

Mener DJ, et al. Int Forum Allergy Rhinol. 2015 Feb;5(2):95-103.
Study duration ranged from 2 to 4 weeks for
trials evaluating knemometry outcomes
Children may decrease short-term growth velocity

Mener DJ, et al. Int Forum Allergy Rhinol. 2015 Feb;5(2):95-103.
Study duration 12 months for trials
evaluating stadiometry outcomes
Effect on long-term growth not significant
Limitations of this study were the difficulty in predicting
longer-term or catch-up growth in children

INCS: Systemic bioavailability

Model-predicted changes in annual growth
velocity for a range of doses of INCS
Daley y, et al. Journal of Asthma and Allergy 2021:14; 1093-1104

Model-predicted changes in annual growth velocity
for combined inhaled and intranasal corticosteroid
Daley y, et al. Journal of Asthma and Allergy 2021:14; 1093-1104

Systemic Corticosteroids
• Limited because of their adverse effects and the limited morbidity of the disease
• Severe nasal obstruction → short course of oral prednisone, 30 mg daily for 3-5
days usually will significantly decrease nasal edema and allow for enhanced
penetration of INCS

Omalizumab
Priyanka V, et al. Expert Opin. Biol. Ther. (2013) 13(6)

• Omalizumab in treatment of AR can improve in quality of life and
decrease in the use of rescue medication
• Its use in AR has been limited due to its high cost and its injectable
dosage form requiring administration every 2 - 4 weeks
• FDA not approved as monotherapy for AR
Priyanka V, et al. Expert Opin. Biol. Ther. (2013) 13(6)

Yu C, et al. American Journal of Rhinology & Allergy 34.2 (2020): 196-208.
Omalizumab can reduce in DNSS and symptoms level in AR
Omalizumab

Mullol, JV, et al. Allergic Rhinitis. 10.1007/978-3-540-68940-9_18.
ARIA 2001

ARIA 2008
Bousquet J, et al. Allergy 63 (2008): 8-160.

Immunotherapy
03
Current Allergy and Asthma Reports (2021) 21: 2

Immunotherapy
03
Mohamed H, et al. J ALLERGY CLIN IMMUNOL MARCH 2022

•IgE mediated diseases
•Limited spectrum allergy
•Can not avoid allergen
•Not adequately controlled with
medications
•Able to comply with protocol
Indication
•Uncontrolled asthma
•Concurrent beta-blocker therapy
•Concurrent
•infection/inflammatory diseases
•Younger than 5-year old
•Pregnancy
Allergen Immunotherapy
Relative contraindication
Canonica GW, et al. World Allergy Organization Education Program, Updated October 2016.

Subcutaneous Immunotherapy (SCIT)
• High dose deep SC injection of allergen extract
• Up-dosing: weekly dose x 8-16 weeks
• Maintenance: monthly dose (optional extended to 6-8 weeks) x 3-5 years
• Adverse events management
Should measure peak-flow before and after 30 minutes of injection
Must be observed with physician availability for at least 30 minutes
Rhinitis, mild wheezing → antihistamine, bronchodilator
Asthma, urticaria, angioedema > antihistamine, IV hydrocortisone
Adrenaline 0.5 mg IM if symptom progress rapidly
Provide out-of-office-time contact & self-management advice
Delay reaction usually mild

Sublingual Immunotherapy (SLIT)
• A daily tablet, should be kept under the tongue for 2 minutes before swallow
• Usually well tolerated with minimal local side effect
• Tongue & lips swelling occur in up to 50% of patients, resolved within 1-2 weeks
• Systemic reactions are rare, dead has never been reported
Other routes
• Intranasal: local side effects, poorly tolerated
• Inhale: induce asthma
• Oral: less effective, limited study
• Epicutaneous: systemic side effects, limited study

SCIT SLIT
Effective for SAR High quality evidence High quality evidence
Effective for PAR Moderate quality evidence High quality evidence
Long-term remission Moderate quality evidence High quality evidence
Pediatrics Need more study Need more study
Local AE Pain & swelling Itching, lips & tongue
swelling
Systemic AE More frequent Rarely
Administration Specialist clinic Self-administration
Compliance Ensured Hard to monitor
SCIT and SLIT

Surgical treatment
Turbinate reduction surgery
• Indication: Patients with refractory mucosal edema only if pharmacotherapy and
immunotherapy have been tried and failed
Involve 2 different methods
1. Entire portions of the turbinate (turbinectomy)
2. Only the tissues between the mucosal covering and/or the bone of the turbinate
(submucous resection); or shrinking the volume of the turbinate (tissue ablation)
Seidman M, et al. Otolaryngology-Head and Neck surgery 2015, Vol. 152(1s)

J Allergy Clin Immunol. 2020;145(1): 70-80 e3.
•Grading of Recommendations Assessment, Development and Evaluation (GRADE)
•Real-world evidence (RWE)
•Visual analog scale

Untreated patient
1st Line drug
Anti-histamine
INCS
INCS + INAH No Anti-Histamine
Dymista

Treated patient
1st Line drug
Anti-histamine
INCS
INCS + INAH

ARIA 2016
SAR: INCS+OAH or INCS or INCS + INAH
Initial tx: INCS + INAH > INCS
PAR: INCS or INCS+INAH > INCS+OAH
US practice parameters 2017
Initial of SAR: INCS > INCS+OAH or LTRA
Mod-severe AR: INCS+INAH

The EAACI gudeline: suggests a stepwise therapeutic approach

Dymista

Step up treatment

Step down treatment

Allergic rhinitis

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