Pathophysiology, diagnosis and management of Allergic Rhinitis

1. Allergic Rhinitis
Dr Sukanta Sen
MD, DNB, MNAMS
Kolkata, India

2. What is Allergic Rhinitis?
Rhinitis is broadly defined as
inflammation of the nasal mucosa.
Allergic rhinitis is a common
disorder that is strongly linked to
asthma and conjunctivitis.
It is usually a longstanding
condition that often goes
undetected in the primary-care
setting.

3. The scale of the problem
Rhinitis is a common disorder that affects up to
40% of the population.
Allergic rhinitis is the most common type of
chronic rhinitis, affecting 10 to 20% of the
population, and evidence suggests that the
prevalence of the disorder is increasing.
Ref:The Canadian Rhinitis Working Group: Rhinitis: A practical and
comprehensive approach to assessment and therapy. J Otolaryngol
2007, 36(Suppl 1):S5-S27.

4. Family history:
Children with parents who have allergies or
asthma are more likely to be affected.
If a child has one parent with allergies, chances
are 30% that a child will have allergic rhinitis.
This increases to 50-70% if both parents have
allergies or atopic asthma.
Related medical history:
Patients with a history of infantile eczema (atopic
dermatitis) have a 70% chance of having allergic
rhinitis, asthma, or both.
Patients with a history of asthma also have higher
incidence of allergic rhinitis.

5. Pathophysiology
A. Immediate allergic reaction A-1.
Sensitization phase
B-1. Challenge phase
B. Late phase allergic reaction
: inflammation, cellular infiltration, tissue
destruction

7. The T cells infiltrating the nasal mucosa are predominantly
T helper (Th)2 in nature and release cytokines (e.g.,
interleukin [IL]-3, IL-4, IL-5, and IL-13) that promote
immunoglobulin E (IgE) production by plasma cells.
IgE production, in turn, triggers the release of mediators,
such as histamine and leukotrienes, that are responsible
for arteriolar dilation, increased vascular permeability,
itching, rhinorrhea (runny nose), mucous secretion, and
smooth muscle contraction.
Ref: Dykewicz MS, Hamilos DL: Rhinitis and sinusitis. J Allergy Clin Immunol 2010,
125:S103-115.

8. Classification
Rhinitis is classified into one of the following categories
according to etiology: IgE-mediated (allergic),
autonomic, infectious and idiopathic (unknown).
Traditionally, allergic rhinitis has been categorized as
seasonal (occurs during a specific season) or perennial
(occurs throughout the year).
It is now classified according to symptom duration
(intermittent or persistent) and severity (mild,
moderate or severe)

9. Figure : Classification of allergic rhinitis according to symptom duration
and severity. Adapted from Small et al., 2007, Bousquet et al., 2008.

10. Table : Etiological classification of rhinitis
Description
IgEmediated
(allergic)
• IgE-mediated inflammation of the nasal
mucosa, resulting in eosinophilic and Th2cell infiltration of the nasal lining
• Further classified as intermittent or
persistent
Autonomic
• Drug-induced (rhinitis medicamentosa)
• Hypothyroidism
• Hormonal
• Non-allergic rhinitis with eosinophilia
syndrome (NARES)
Infectious
Precipitated by viral (most common),
bacterial, or fungal infection
Idiopathic
• Etiology cannot be determined

12. DDx of non-allergic & allergic rhinitis
Non-allergic
Allergic
Temporal pattern of
symptoms
perennial
seasonal or perennial
with seasonal
exacerbations
Type of symptoms
congestion,
rhinorrhea, posterior
drainage, sinus pressure
sneezing,
pruritus, congestion,
rhinorrhea, posterior
drainage, sinus pressure
Age of onset
70% are older than 20
70% are younger than 20
Precipitating factors
nonspecific irritants
specific
antigens± nonspecific
irritants
Other atopic disease
not present
frequently present
Family history of
rhinitis
not frequent
frequent

13. Clinical Presentation
AR is characterized by the presence of four
classic symptoms:
sneezing, itching, rhinorrhea, and nasal
congestion.
 In addition to these nasal symptoms of AR,
patients often present with nonnasal symptoms
such as conjunctival irritation, palatal itching,
and epiphora as well.
 Patients may also describe symptoms such as
frontal and periorbital headaches, loss of taste
or smell, and pressure and fullness in the ears.

14. Components of a complete history and physical
examination for suspected rhinitis
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Personal
Nasal itch
Rhinorrhea
Sneezing
Eye involvement
Seasonality
Triggers
Family
Allergy
Asthma
Environmental
Pollens
Animals
Flooring/upholstery
Mould
Humidity
Tobacco exposure

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Medication/drug use
Beta-blockers
ASA
NSAIDs
ACE inhibitors
Hormone therapy
Recreational cocaine use
Quality of life
Rhinitis-specific questionnaire
Comorbidities
Asthma
Mouth breathing
Snoring
Sinus involvement
Otitis media
Nasal polyps
Conjunctivitis
Response to previous medications
Second-generation oral antihistamines
Intranasal corticosteroids

16. Physical examination
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Outward signs
Mouth breathing
Rubbing the nose/transverse nasal crease
Frequent sniffling and/or throat clearing
Allergic shiners (dark circles under eyes)
Nose
Mucosal swelling, bleeding
Pale, thin secretions
Polyps or other structural abnormalities
Ears
Generally normal
Pneumatic otoscopy to assess for Eustachian tube dysfunction
Valsalva’s maneuver to assess for fluid behind the ear drum
Sinuses
• Palpation of sinuses for signs of tenderness
• Maxillary tooth sensitivity
Posterior oropharynx
Postnasal drip
Lymphoid hyperplasia (“cobblestoning”)
Tonsillar hypertrophy
Chest and skin
Atopic disease
Wheezing

17. Allergic Rhinitis management

18. Most cases of allergic rhinitis respond to pharmacotherapy.
Patients with intermittent symptoms are often treated
adequately with oral antihistamines, decongestants, or both
as needed.
Regular use of an intranasal steroid spray may be more
appropriate for patients with chronic symptoms. Daily use
of an antihistamine, decongestant, or both can be
considered either instead of or in addition to nasal steroids.
The newer, second-generation (ie, nonsedating)
antihistamines are usually preferable to avoid sedation
and other adverse effects associated with the older, firstgeneration antihistamines. Ocular antihistamine drops (for
eye symptoms), intranasal antihistamine sprays, intranasal
cromolyn, intranasal anticholinergic sprays, and short
courses of oral corticosteroids (reserved for severe, acute
episodes only) may also provide relief.

19. Goals of allergic rhinitis management
Freedom from
Symptoms
Acute attacks and emergency hospital visits
Frequent absenteeism from work/school
Limitation of physical activity
Adverse effects of drugs

20. How is allergic rhinitis managed?
step 1 : Avoidance &
Environmental control
step 2 : Antihistamine,
Decongestant, Mast cell stabilizer
step 3 : Corticosteroids
step 4 : Immunotherapy

21. TABLE-PHARMACOLOGIC OPTIONS FOR
RHINITIS: EFFECTS ON SYMPTOMS
Agent
Sneezing
Itching
Congestion
Rhinorrhea
Eye
Symptoms
Oral
antihistamines
++
++
+/-
++
++
Nasal
antihistamines
+
+
+
+
-
Intranasal
corticosteroid
++
++
+++
++
+
Leukotriene
modifiers
+
+
+
+
+
Oral
decongestants
-
-
++
-
-
Nasal
decongestants
-
-
+++
-
-
Nasal mast-cell
stabilizers
+
+
+
+
-

22. The following medications are used in patients with allergic rhinitis:
Second-generation antihistamines (eg, cetirizine,
levocetirizine, loratadine, desloratadine, fexofenadine)
Intranasal antihistamines (eg, azelastine, intranasal
olopatadine)
Intranasal corticosteroids (eg, intranasal beclomethasone,
intranasal budesonide, intranasal ciclesonide, intranasal
flunisolide, intranasal fluticasone, intranasal mometasone,
intranasal triamcinolone)
Intranasal antihistamine/corticosteroid (eg,
azelastine/fluticasone intranasal)
Intranasal decongestants (eg, ipratropium intranasal)
Intranasal mast cell stabilizers (eg, intranasal cromolyn
sodium)
Leukotriene receptor antagonists (eg, montelukast)

24. Second-generation antihistamines
Often referred to as the nonsedating
antihistamines.
They compete with histamine for histamine
receptor type 1 (H1) receptor sites in the blood
vessels, GI tract, and respiratory tract, which, in
turn, inhibits physiologic effects that histamine
normally induces at the H1 receptor sites.
Some do not appear to produce clinically significant
sedation at usual doses, while others have a low
rate of sedation.

25. Intranasal antihistamines
Alternative to oral antihistamines to treat allergic rhinitis.
Azelastine
Use prn or on a regular basis. Use alone or in combination with
other medications. Unlike oral antihistamines, has some effect
on nasal congestion. Helpful for vasomotor rhinitis. Some
patients experience a bitter taste. Systemic absorption may
occur, resulting in sedation (reported in approximately 11% of
patients).
Olopatadine intranasal
For relief of symptoms of seasonal allergic rhinitis. Before initial
use, prime product by releasing 5 sprays or until fine mist
appears. When product has not been used for more than 7
days, re-prime by releasing 2 sprays. Avoid spraying into eyes.

27. Intranasal cromolyns
Produce mast cell stabilization and antiallergic effects that
inhibit degranulation of mast cells. Have no direct antiinflammatory or antihistaminic effects. Effective for
prophylaxis. May be used just before exposure to a known
allergen (eg, animal, occupational). Begin treatment 1-2
wk before pollen season and continue daily to prevent
seasonal allergic rhinitis. Effect is modest compared with
that of intranasal corticosteroids. Excellent safety profile
and are thought to be safe for use in children and
pregnancy.
Cromolyn sodium
Used daily for seasonal or perennial allergic rhinitis.
Significant effect may not be observed for 4-7 d. For
patients with isolated and predictable periods of exposure
(eg, animal allergy, occupational allergy), administer just
before exposure. Generally less effective than nasal
corticosteroids.

28. Intranasal corticosteroids:
• Intranasal corticosteroids are highly effective in preventing
and relieving nasal symptoms associated with both earlyand late-phase allergic responses.
• In general, they relieve nasal congestion and itching,
rhinorrhea, and sneezing, and in some studies they almost
completely prevented late-phase symptoms.
• Although some relief may occur within a few days, a full
response to the drugs may take up to several weeks.
Ref: 1. Mygind N. Glucocorticosteroids and rhinitis. Allergy 1993;48:476-90.
2. Onrust SV, Lamb HM. Mometasone furoate: a review of its intranasal use in allergic rhinitis. Drugs
1998;56:725-45.

29. Leukotriene modifiers
Use in children now widely approved for allergic
rhinitis in children over 12 months.
Few side effects-reported liver effects
Drug interactions with theophylline, warfarin,
terfenadine
Oral formulations once daily
Work to decrease leukotrienes and decrease
inflammation
Studies on montelukast alone or in combination with
loratadine/ cetrizine/ levocetrizine is well tolerated
and provides clinical and quality-of-life benefits
for patients with seasonal allergic rhinitis

31. Rationality of using combined Montelukast and
Levocetirizine as Treatment for Allergic Rhinitis
Antihistamines are effective in reducing pruritis, sneezing
and watery rhinorrhea, and are a mainstay therapy for
allergic rhinitis.
Although first generation antihistamines are generally
more effective in controlling rhinorrhea compared with
second generation antihistamines, their use is markedly
limited due to greater anticholinergic effects.
Second generation antihistamines have shown favourable
effect on sleep in patients with allergic rhinitis and are in
general recommended for mild to moderate disease as
first-line therapy, but not effective in nasal congestion.
Ref: Camelo-Nunes IC (2006) New antihistamines: a critical review. J Pediatr
(Rio J) 82: S173-S180.

32. Montelukast serves a role in helping reduce symptoms of
allergic rhinitis that are not controlled with antihistamines
alone by competitively and reversibly inhibits cysteinyl
leukotrienes (CysLTs), specifically leukotrienes D4 (LTD4),
theoretically decreasing congestion and stuffiness
associated with allergic rhinitis.
Montelukast, as monotherapy has been effective in improving
daytime and nighttime symptoms in patients with allergic
rhinitis and in comparison to antihistamines appear to have
significantly better improvement in night time symptoms.
Ref:1. Philip G, Malmstrom K, Hampel FC, Weinstein SF, LaForce CF, et al. (2002) Montelukast for treating
seasonal allergic rhinitis: a randomized, double blind, placebo-controlled trial performed in the spring.
Clin Exp Allergy 32: 1020-1028.
2) Nayak AS, Philip G, Lu S, Malice MP, Reiss TF, et al. (2002) Efficacy and tolerability of montelukast
alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double
blind, placebo controlled trial performed in the fall. Ann Allergy Asthma Immunol 88: 592-600.
3) van Adelsberg J, Philip G, LaForce CF, Weinstein SF, Menten J, et al. (2003) Randomized controlled trial
evaluating clinical benefit of montelukast for treating spring seasonal allergic rhinitis. Ann Allergy
Asthma Immunol 90: 214-222.

33. Hence, a combination therapy of montelukast with
antihistamines could provide enhancing and
complementary effects, thereby reducing both the
daytime and night time symptoms effectively.
Combination of levocetirizine with montelukast has
shown a significant improvement in patients with
allergic rhinitis.
There was a significant improvement in both daytime
and nighttime symptoms in patients on combination
therapy as compared to placebo and giving both the
drugs as monotherapy.
Ref:
1) Ciebiada M, Ciebiada MG, Kmieck T, Dumuske LM, Gorski P (2008) Quality of life in
patients with persistent allergic rhinitis treated with montelukast alone or in combination
with levocetirizine or desloratidine. J Invest Allergol Clin Immunol 18: 343-349.
2) Ciebiada M, Ciebiada MG, Dubuske LM, Gorski P (2006) Montelukast with desloratidine or
levocetirizine for the treatment of persistent allergic rhinitis. Ann Allergy Asthma Immunol
5: 664-671.

34. Intranasal anticholinergic agents
Used for reducing rhinorrhea in patients with allergic or
vasomotor rhinitis. No significant effect on other symptoms.
Can be used alone or in conjunction with other
medications. Ipratropium bromide (Atrovent Nasal Spray) is
available in a concentration of 0.03% (officially indicated
for treatment of allergic and nonallergic rhinitis) and 0.06%
(officially indicated for the treatment of rhinorrhea
associated with common cold). The 0.03% strength is
discussed.
Ipratropium ( Nasal Spray 0.03%)
Chemically related to atropine. Has anti-secretory
properties, and when applied locally, inhibits secretions
from serous and seromucous glands lining the nasal
mucosa. Poor absorption by nasal mucosa; therefore, not
associated with adverse systemic effects.

37. Thank you