Allergic rhinitis is an IgE-mediated inflammation of the nasal mucosa following exposure to an allergen. It affects 10-30% of people globally. Symptoms include sneezing, rhinorrhea, nasal obstruction, and itching. Diagnosis involves demonstrating IgE sensitivity, usually via skin prick testing or allergen-specific IgE blood tests. Treatment includes allergen avoidance, pharmacotherapy like antihistamines and intranasal corticosteroids, and immunotherapy for persistent cases. Immunotherapy aims to induce tolerance through repeated administration of allergen extracts.

1. Allergic rhinitis
Major Ahmad Rizvan

2. Definition
• Defined clinically by a combination of 2 or more nasal
symptoms
– Running
– Blocking
– Itching
– Sneezing
• IgE mediated following exposure to allergen

3. Classification

4. Prevalence

5. Prevalence
• About 40 per cent of the world’s population is atopic and
allergic rhinitis is the commonest of them. Allergic rhinitis
affects10-30 per cent in Asia
• Incidence rate of 26 per cent in India and its associated
disease asthma with 10-12 per cent incidence rate are on a rise
in India and other developing countries

6. Risk factors
• Family history of allergic rhinitis
• Genes involved include loci on 5q chromosome
– IL-4 and IL-13
• 11q,13 and 12q
• Requires further investigation in large
multicenter population studies

7. Risk factors
• Environment
– Developed countries
– Urban societies
– Lifestyle changes
– Increased exposure to allergen
– Pollution and irritants
– Dietary modifications
– Good hygiene

9. Ages affected
• Not seen until age 4 or 5
– (Takes approx 3 pollen season exposures)
• 10-15% in adolescents (adolescents and young adults)
• Peak age 30 (decades 2, 3 and 4)
• Incidence decreases in elderly

10. Allergens

11. Allergens

12. Pathophysiology
• Sensitization
• APCs like dendritic cells called
Langerhans cells
• Maturation of APCs
• Some form of signal like virus,
diesel exhaust,etc.
• Process and present the antigen to
naïve T cells
• T cell receptor recognition of a
peptide fragment associated with
MHC molecule plus co
stimulatory signals CD 28 and B7
and CD 40 ligand

13. Pathophysiology
• Sensitization
• Preferential development of a Th2
response
• Th2 cells secrete cytokine mainly
IL 4, IL 13 and IL 5
• Activate B lymphocyte and they
proliferate , migrate to the nasal
lining and produce antibody of
IgE type
• IgE is very rapidly and avidly
taken up by local cells possessing
FcER1 mainly mast cells
• Armed mast cells

14. Pathophysiology
• Subsequent reaction to allergen:
Early phase
• Sneezing, rhinorrhoea and itch
occur within min
• Mast cells degranulate once there
cell bound IgE has been cross
linked by allergen
• Preformed or manufactured from
cell membrane arachidonic acid
• Histamine: action on sensory
nerves causes itch and sneezing
• Action on endothelial cells and
blood vessels results in
vasodilatation, plasma exudation
and edema

15. Pathophysiology
• Subsequent reaction to allergen:
Early phase
• Increases glandular secretion
• Upregulation of adhesion
molecules on vascular endothelial
cells
• Increased production of IL 6 and
IL 8 by endothelial cells
• Activation of epithelial cells with
ICAM 1 expression and cytokine
production
• PGD2 induces sustained nasal
obstruction

16. Pathophysiology
• Subsequent reaction to allergen:
Early phase
• Leukotrienes
• Sulphido peptide or cysteinyl
leukotrienes
• Induce vascular permeability and
edema in the nose and eosinophil
recruitment
• LTB4 neutrophil recruitment
• LTC4 and B4 found in nasal
lavage fluid
• Kinins are generated from plasma
proteins via the action of
kininogen

17. Pathophysiology
• Subsequent reaction to allergen:
Early phase
• Kinins cause rhinorrhoea,
sneezing, obstruction and pain
• Release of TH2 cytokines IL-5,
IL-13 and proimflammatory
cytokines IL-6, IL-8, IL-10 and
TNF alpha
• GMCSF, MCP1, RANTES,
(MIP)1-alpha, CC chemokines

18. Pathophysiology
• Late phase response
• Inflammatory in nature and
involves ingress of cells
• Eosinophils
• Less than 1% of circulating cells
• Migrate into tissues upon signals
by cytokines, chemokines and
adhesion molecules
• GMCSF and IL-5 enhance
recruitment, maturation and
expression of adhesion molecules
• RANTES and eotaxin:
recruitment and activation

19. Pathophysiology
• Late phase response
• Synthesize and release IL-3, IL-5,
GMCSF and proinflammatory
cytokines
• Chemokines
• IL-8 MIP1-alpha
• TGF beta-1
• Cysteinyl leukotrienes, PG E1,
TX B2, PAF
• ROI
• Histaminase
• Increase local vascular
permeability and mucus secretion
and inflammatory cell influx

20. Pathophysiology
• Late phase response
• Endothelial cells: recruitment of
leukocytes
• Increased ICAM-1 and VCAM-1
• Source of cytokines and
chemokines
• Express H1 receptors
• IL-1,IL-4, IL-13, eotaxin and
RANTES enhance local adhesion
molecule expression
• Increased basophils in nasal
mucosa of allergic rhinitis patients

21. Pathophysiology
• Late phase response
• Basophils:
• Major source of histamine in the
late phase response
• Cytokines such as IL-4 and IL-13
• Increased number of CD4+
andfCD25+
• Increase in macrophages

22. Pathophysiology
• Late phase response
• Epithelial cells:
• Barrier and mucociliary clearance
function
• Increased expression of adhesion
molecules, increased expression
and production of inflammatory
mediators such as IL-6, IL-8,
GMCSF and TNF-alpha ,
increased release of RANTES,
eotaxin,growth factors and
metallopreitinases
• More sensitive to air pollutants
• MHC class II

23. Pathophysiology
• Late phase response
• Fibroblast:
• Capable of producing cytokines
and chemokines such as GMCSF,
IL-8, RANTES and eotaxin
• Neutrophils:
• Minor upregulation in allergic
rhinitis

24. Pathophysiology
• Sytemic activation
• Up regulation of production and
release of eosinophil and
basophil precursors from the bone
marrow
• Attracted to reaction site and other
parts of respiratory tract by
selectin and adhesion molecules

25. Summary

26. Clinical presentation
• Immediate – Sneezing / Rhinorrhoea / Itching
• Perennial – Nasal Obstruction / Hyperreactivity / Poor Smell

27. Symptoms
• Nasal congestion
• Rhinorrhea
• Pruritus
• Sneezing
• Eye tearing & pruritus
• Ear & palate pruritus
• Post nasal drip
• Anosmia
• Sore throat
• Chronic cough
• Mouth breathing

28. Differential diagnosis
• Acute
– Viral
– Bacterial
• Chronic
– Idiopathic rhinitis(NANIPER)
– Non allergic occupational rhinitis
– Hormonal rhinitis
– NARES

29. Differential diagnosis
– Rhinitis due to physical and chemical factors
– Food induced rhinitis
– Emotion induced rhinitis
– Nasal neoplasm
– Trauma
– FB
– CSF rhinorrhoea

30. Diagnosis of Allergic Rhinitis
• Signs of atopy and recurrent or persistent rhinitis

31. Health Effects of Allergic Rhinitis
• Fatigue
• Depression
• Irritability
• Anxiety
• Sleep disturbance
• Poor concentration
• Reduced productivity
• Impaired learning, decision making and psychomotor speed
• Co-morbidities: conjunctivitis, asthma, sinusitis, otitis
media, sleep disorders, LRI and dental occlusion

32. Diagnosis of Allergic Rhinitis
• Demonstration of IgE allergy

33. Allergy diagnosis
• Skin prick test
• Rationale: allergen introduced into the skin causes
degranulation of IgE sensitized mast cells with mediator release
and formation of a wheal and flare
• Method: a drop of standardized allergen over volar aspect of
forearm and then pricked
• Include positive and negative control
• Mean wheal diameter at 15 min
• More than 2mm in under fives and 3mm in older subjects
• Negative control give positive reaction and positive control give
negative reaction- Invalid

34. Allergy diagnosis
• Skin prick test
• Exclusion
• Patient on antihistamines
• Severe eczema
• Previous life threatening anaphylaxis
• Dermagraphism
• Sensitivity and specificity
• Positive SPT occurs in 25-30% adults, only 10-15% develop
symptoms

35. Allergy diagnosis
• Blood test for allergy
• Rationale
• Stabilized allergen is incubated with the patient’s serum any
specific IgE binds to allergen and is identified by a second
incubation with labeled anti IgE
• Total IgE
• Rarely helpful in uncomplicated rhinitis since 50% normal
levels

36. Allergy diagnosis
• Blood test for allergy
• Specific IgE
• RAST: allergen bound to solid phase
• CAP RAST: allergen is coupled to a cellulose carrier and anti
IgE is enzyme labeled with a fluorescent substrate acting as
the developing agent
• ELISA : allergen is in fluid phase and IgE is enzyme labeled

37. Comparison
SPT RAST
Time for results Immediate result Days to weeks
Cost Cheap Expensive
Safety Safe- inhalant only Very safe
Sensitivity Sensitive Slightly less sensitive
Affected by therapy Yes no
Other requirements Training for performance
and interpretation
Trained operator and
interpreter required

38. Allergy diagnosis
• Nasal allergen challenge
• Rationale: allergen is introduced into the nose and any
reaction is measured and compared to placebo
• Gold standard of allergy diagnosis
• Subjective(symptom scores, visual analogue scales)
• Objective(sneeze count, nasal inspiratory peak flow,
rhinomanometry, acoustic rhinometry, spirometry or
pulmonary peak flow)
• Measure mediators, cytokines or cells

39. Treatment
• Allergen avoidance and environmental control
• Pharmacotherapy
• Education
• Immunotherapy

40. Allergen avoidance and environmental
control
• Primary prevention
• Secondary prevention
• House dust mite avoidance
• Encase mattress and pillows in plastic covers
• Hot wash bedding(550C)
• Remove objects that accumulate dust
• Store clothing in drawers use leather, plastic or vinyl furniture
• Remove carpets
• Use washable curtains or venetian blinds
• Replace or wash air filters on air conditioners every month

41. Allergen avoidance
• Cockroaches
• Eradicate cockroaches with appropriate gel-type, non-volatile,
insecticides
• Eliminate dampness, cracks in floors, ceilings, cover food; wash
surfaces, fabrics to remove allergen
• Pollen
• Remain indoors with windows closed at peak pollen times
• Wear sunglasses
• Use air-conditioning, where possible
• Install car pollen filter

42. Pharmacotherapy
• Antihistamines (first and second generation)
• Decongestants
• Corticosteroids
• Cromolyn Sodium
• Ipratropium
• Leukotriene Antagonist

43. Pharmacotherapy
Itch/sneezing Discharge Blockage Impaired smell
Sodium
cromoglycate
+ + +/- -
Oral
antihistamines
+++ ++ +/- -
Ipratropium
bromide
- +++ - -
Topical
decongestant
- - +++ -
Topical
corticosteroids
+++ +++ ++ +
Oral
corticosteroids
+++ +++ +++ ++
Antileukotrienes - ++ + +/-

44. Antihistamines
• 1st generation
• Diphenhydramine, Chlorpheniramine, Promethazine
• Currently the primary drug for treatment of nasal allergy.
• Compete with Histamine for the H1 receptor.
• Most effective when taken prophylactically
• Anticholinergic, antiserotatonergic, and anti alpha adrenergic.
• Lipid soluble and cross the Blood Brain Barrier

45. Antihistamines
• 2nd generation
• Loratidine, Fexofenadine, Cetrizine, and azelastine
• Cross BBB less and have reduced CNS effects
• Longer half lives
• Side Effects
– Terfenadine, astemizole, diphenhydramine, hydroxyzine
interfere with potassium reuptake channels, causing QTc
prolongation and cardiac arrhythmias
– Ebastine, mizolastine and loratidine only at high doses
– They should not be combined with drugs metabloized by
P450 like erythromycin and ketoconazole

46. Decongestants (oral/topical)
• Pseudoephedrine, phenylpropanolamine,
oxy/xylometazoline
• Mechanism: alpha-adrenergic agonist.
• Effect: vasoconstriction restricts blood flow to nasal mucosa
decreasing nasal obstruction (no influence on pruritus,
sneezing or nasal secretion).
• Side effects:
– Oral: Nervousness, irritability, tachycardia, palpitations,
insomnia.
– Topical(nasal): prolonged use (>5-7 days) leads to rhinitis
medicamentosa

47. Decongestants
Rhinitis Medicamentosa (RM)
• Prolonged use of topical decongestant may induce
rebound congestion upon withdrawal
• Leads to inflammatory hypertrophy of nasal mucosa
• Caused by down regulation of alpha-adrenoreceptors -->
less sensitive to endogenously released NE and
exogenously applied vasoconstrictors.
• T/t: wean over 7-10 days while reducing inflammation by
intranasal steroids.

48. Intranasal Corticosteroids
• Primarily block the late phase reaction.
• Only a small fraction is absorbed locally
• Mechanism:
– reduce inflammation
– suppress neutrophil chemotaxis
– mildly vasoconstrictive
– reduce intracellular edema
• Side effectsEpistaxis 5-8%Nasal burning
• Reduced the relative risk of asthma exacerbation
/hospitalisation by 50%

49. Intranasal Corticosteroids
• Budesonide, Mometasone, fluticasone,beclomethasone
– Increased potency
– Reduced systemic availability and activity
– Quicker onset of action
• More effective than oral antihistamines at relieving all nasal
symptoms as well as improving the total nasal symptom score
• May be appropriate for replacing antihistamines as first line
therapy for management of nasal allergy.

50. Cromolyn Sodium (intranasal)
• 4% intranasal cromolyn
• Mechanism: mast cell stabilizing agent --> reduces release of
histamine and other mediators.
• Effects: reduces nasal pruritus, sneezing, rhinorrhoea and
congestion.
• Note:
– prophylactic use: start before pollinosis symptoms or
unavoidable/predictable exposures.
– disadvantage: frequent dosing (q4hrs).
• Side effects: locally, <10% of pts (sneezing, nasal stinging,
burning, irritation,laryngeal oedema).
Bronchospasm , Joint Swelling

51. Ipratropium (intranasal)
• Mechanism: inhibits muscarinic cholinergic receptors.
• Effect: reduces watery rhinorrhea (no effect on nasal itching,
sneezing or nasal congestion).
• Note:
– limited to control of watery secretions.
– effective at reducing both “cold-air” and
“gustatory”rhinitis.
• Side effects: worsening of glaucoma, prostatism and dry
mouth and eyes

52. Leukotriene antagonists
• Monteleukast
• Act similar to antihistamines by competitive inhibition of the
leukotriene receptor.
• Very successful in Asthma
• The data available to date do not clearly support a unique role
of leukotriene inhibitors in the treatment of allergic rhinitis.

53. Saline (intranasal)
• Effects: relief from crusting and can be soothing.

54. Immunotherapy
• It involves repeated
administration of an allergen
extract in order to induce a
state of immunological
tolerance, with a reduction
in clinical symptoms and
requirement for medication
during subsequent natural
allergen exposure

55. Immunotherapy
• It should be considered
• Pharmacotherapy insufficiently controls symptoms or
produces undesirable side effects
• Limited spectrum of allergies
• Objective confirmation of IgE sensitivity

56. Immunotherapy
• Efficacy
• In selected patients immunotherapy may be highly
effective[Grade A]
• Upto 50% reduction in symptoms and 80% reduction in rescue
medication
• Treatment for 3-4 yrs results in sustained improvement for at
least 3 yrs following discontinuation[Grade A]
• In a study of children with seasonal rhinitis, immunotherapy
for 3 yrs resulted in a 2-3 fold reduction in the risk of
developing bronchial asthma[Grade B]

57. Immunotherapy
• Side effects
• Local reactions: often trivial
• Systemic reactions in up to 10% patients particularly during up
dosing phase and include rhinitis or asthma
• Occasionally urticaria, more severe asthma and rarely
anaphylaxis
• Large majority of systemic reactions occur within 30 min of
injections

58. Immunotherapy
Inclusion criteria Contraindications
IgE mediated
disease(+SPT/RAST)
Co existent asthma
Inability to avoid allergen Patient taking beta blockers
Inadequacy of drug treatment Other medical/immunologic
disease
Limited spectrum of allergies Children less than 5 years
Patients who understand risk
and limitations of treatment
Pregnancy(maintenance therapy
may be continued)

59. Immunotherapy
• Practical immunotherapy
• Up dosing phase involves weekly injections for 8-16 weeks
followed by maintenance injections at 4-8 weekly intervals for
3-5 yrs
• Performed by trained staff
• Standardized whole allergen extract with documented clinical
efficacy should be employed
• Patients should be observed for at least 60 min following
injection
• Facilities for resuscitation

60. Immunotherapy
• Mechanism
• It results in blunting of seasonal increases in allergen specific
IgE, an increase in ‘blocking IgG’ antibodies and inhibition of
recruitment and activation of inflammatory cells to mucosal
surfaces including mast cells and basophils
• Immune deviation from Th2 type to Th1 type response
• Production of IL-10 and TGF beta

61. Immunotherapy
• Novel immunotherapy strategies
• Side effects of subcutaneous immunotherapy
• Sublingual route
• Use of adjuvant such as bacterial DNA sequences(CpG) which
when conjugated to allergen induce preferential Th1 responses
• Use of allergen peptides retain only immunologic property

62. Surgery
• Marked septal deviation[Grade D]
• Bony turbinate enlargement[GradeD]
• Mucosal hypertrophy[Grade C]
• Endoscopic sinus surgery [Grade B]

63. Treatment

64. Special circumstances
• Pediatric rhinitis
• Diagnosis is difficult
• Only intranasal formulation licensed for younger children is
sodium cromoglycate
• Saline drops or sprays may also be useful in children under 2
yrs
• Fluticasone propionate >4 yrs
• Flunisolide > 5 yrs
• Triamcinolone, beclomethsone and mometasone > 6yrs
• Budesonide not licensed for children

65. Special circumstances
• Pregnancy
• Existing rhinitis may be exacerbated
• Can occur de novo in pregnancy due to high oestrogen
• No medication completely safe
• Least absorbed topical nasal steroid
• Often resistant to treatment
• Topical decongestants can lead to fetal abdominal
malformations

66. Special circumstances
• Asthma
• 1/3 of allergic rhinitis patients have asthma
• Leukotriene receptor antagonist
• Levocetrizine and desloratidine have some effects on nasal
obstruction and improves seasonal asthma
• Anti IgE and immunotherapy

67. Recent advances
• New management options
• Ramatroban: TXA2 receptor anatgonist improves nasal
obstruction
• Omalizumab: humanized monoclonal anti IgE antibody
• Botulinum toxin
• Phototherapy systems

68. THANK YOU