2. • Allergy is a clinical manifestation of an exaggerated immune
response following repeated exposures to allergens in a
genetically predisposed ‘‘atopic’’ patient.
3. • Rhinitis is defined clinically by a combination of two or more
nasal symptoms:
1)running
2)blocking
3)itching
4)sneezing
• Allergic rhinitis is characterized by inflammatory
changes in the nasal mucosa caused by
exposure to inhaled allergens.
• Allergic rhinitis occurs when these symptoms are a result of IgE
mediated inflammation following exposure to allergen.
4. • Rhinitis is defined clinically as having two or
more symptoms
• anterior or posterior rhinorrhoea,
• sneezing,
• Nasal blockage and/or
• itching of the nose during two or more
consecutive days for more than one hour on
most days.
5. • Seasonal allergic rhinitis is defined by symptoms that occur
during exposure to seasonal allergens, such as ragweed,
grasses, outdoor molds, and tree pollens.
• Perennial allergic rhinitis defined as nasal symptoms for > 2
hours per day for >9 months of the year, occurs when
allergies develop to house dust mites, indoor molds, animal
dander, and cockroaches.
• Episodic rhinitis refers to nasal symptoms on exposure to
allergens not normally present in the environment
7. • Prevalence : It is a common disease, affecting
between 0.8 and 39.7% of the world
population(depending on location)
• with prevalence in Western Europe of 23%.
• approximately 75% of patients will be
diagnosed as having a persistent rhinitis and
25% intermittent.
8. • Steep increase in allergic rhinitis over the last 40
years though this may now be slowing.
• The reasons for this increase are uncertain.
• Children who live on farms and have contact with
livestock are less likely to develop allergic rhinitis
than their urban peers suggesting a possible
protective effect of microbial exposure.
• Larger family size, more frequent infections and
unhygienic contact may all be protective – the
hygiene hypothesis.
9. RISK FACTORS
• Genetics:
• Chromosome 5q where genes exist for interleukin (IL)-4 and IL-13, with
markers associated with the presence of a high level of serum IgE.
• Chromosome 14 has been linked to eczema and specific HLA
haplotypes are linked to the development of IgE.
• Chromosome 11q high total IgE concentration or specific IgE.
• Chromosome 13q in Japanese
• Chromosome 12q
• Family history
• Age: patients are usually young
•
• Sex: males are affected more(M:F is 3:2)
10. • Environment
- Many possible factors have been suggested:
• Lifestyle changes
• Increased exposure to allergen, pollution and irritants
• Dietary modifications responsible for diminution of protective
nutrients
• Decrease in infections, leading to a reduction in Th1-type
immune response (the hygiene hypothesis) and stress
13. PATHOPHYSIOLOGY
Immediate or type 1 hypersensitivity is a rapidly developing
immunological reaction occurring within minutes of allergen binding
with antibody( bound to mast cells) in individuals previously
sensitized to that antigen.
The allergic reaction can be considered in 4 phases:-
1)Sensitization
2)Subsequent reaction to allergen-early phase
3)Late phase reaction
4)Systemic activation
14. • Many type 1 hypersensitivity reaction has two well defined
phases:
• 1) Immediate or initial response:
• 5 to 30 mins after allergen exposure and tend to subside by
1hr.
• Vasodilatation , vascular leakage, glandular secretion
• 2)Late phase reaction:
• Sets in 2 to 24 hrs ,without additional exposure to allergen .
May last for several days.
• Infiltration of tissue with eosinophils , neutrophils ,
basophils,CD4+cells with epithelial destruction seen
15.
16. sensitisation
• During the first contact of the host with the antigen,
sensitisation takes place.
• Antigen presenting cells(langerhans cells) form a network in mucosal
surface of upper airways
• They capture antigens, process it and present to naïve T cells in local
lymph nodes
• These naïve T cells mature to Th2 subclass of CD4+ type
• These Th2 type T cells secrete IL-4,IL-5 and IL-13
• IL-4 and IL-13 leads to IgE production by stimulating B lymphocytes
17. • IL-5 leads to eosinophil chemotaxis
• IgE antibodies so formed bind to the Fc
receptors present in plenty on the surface of
mast cells and basophils, which are the main
effector cells of type I reaction.
• The patient is thus sensitized.
• Around 30% of the population is sensitized by grass pollen,
but not all of them develop allergic rhinitis
18. EARLY PHASE REACTION
• Early phase reaction occurs from degranulation of mast cells
during the second contact with the same antigen :
• Primary mediators/preformed mediators:
• a)Biogenic amines-
• Histamine causes rhinorrhoea, sneezing, itching. Effects on
nasal obstruction are less marked and causes vasodilatation,
exudation, oedema.
• b) Enzymes-
• Chymase, tryptase, acid hydrolase
causes tissue damage
19. • The effects of TH2 cytokines are all conducive to the
promotion of
• allergic inflammation:
• IL-5 promotes the differentiation, vascular adhesion, and
in vitro survival of eosinophils and enhances histamine
release from basophils;
• IL-4 is a mast cell growth factor that promotes the
switching of B cells to the production of IgE and
• IL-13, independent from the other two cytokines, and is
necessary and sufficient to induce key features of
inflammation such as eosinophil recruitment, mucus
hyperproduction, and airway hyperresponsiveness.
20.
21. • Secondary mediators
a) Lipid mediators-generated from mast cell membrane phospholipid by phospholipase A2
which produces arachidonic acid.
• From this,leukotrienes are produced by lipoxygenase pathway and prostaglandins by
cycloxygenase pathway.
• leukotrienes C4 and D4 are most potent vasoactive and spasmogenic agent
• Prostaglandin D2 causes sustained nasal obstruction,ten times more potent than
histamine
b) Cytokines- IL-4,IL-5,IL-13,IL-6,IL-8, and TNF-alpha, GM-CSF.
• Multiple cytokines and other factors are important in
upregulating adhesion molecules on circulating
leukocytes and vascular endothelium and are crucial in
chemotaxis and leukocyte survival within the tissues.
22.
23.
24.
25.
26.
27. • FIGURE 38-6. Pathophysiology of allergic rhinitis.
• The first stage of development of allergic rhinitis involves antigen processing
and the production of specific immunoglobulin E (IgE) antibodies, which attach
to mast cells, basophils, and other inflammatory cells. On subsequent exposure
to the same allergen, IgE
• receptors on the surface of mast cells are cross-linked, which leads to the
degranulation of these cells and to the release of preformed and newly
synthesized mediators responsible for symptoms of the disease.
• Recruitment of inflammatory cells to the nasal mucosa also occurs, as does a
resultant state of chronic
• inflammation with a heightened state of reactivity to specific and nonspecific
stimuli—a hallmark of allergic nasal disease.
• In addition to the early and late inflammatory responses, exposure to allergen
leads to a secondary immune response with increased production of specific
IgE and a perpetuation of the state of susceptibility to allergen.
28. LATE REACTION
• Its inflammatory in nature.
• Involves eosinophil, basophil, mast cells, T lymphocytes ,
neutrophils, macrophages
• These cells migrate to local reaction site
• Main symptoms are nasal obstruction and hyperreactivity.
• Mature eosinophils can be seen in nasal mucosa and nasal
secretions.
29. SYSTEMIC ACTIVATION
• There is evidence of upregulation of production and release of
eosinophils and basophil precursors from the bone marrow , in
response to allergen contact in nose or lung
• The resultant circulating precursors are attracted towards the
reaction site by selectin and adhesion molecules
30. • These inflammatory mediators cause the classic
symptoms of allergic rhinitis:
• nerve irritation causing sneezing and itching,
• loss of mucosal integrity causing rhinorrhoea and
• vascular engorgement causing block.
• Histamine drives the majority of acute nasal
symptoms such as sneezing and itching with
• leukotrienes and prostaglandins being involved in
longer term symptoms such as block.
31. CLINICAL PRESENTATION
• Immediate-type allergic symptoms:-
➢ Sneezing
➢ Rhinorrhoea
➢ Itch
• Perennial allergic inflammation:-
➢ Nasal obstruction
➢ Hyperreactivity to allergens
➢ Poor sense of smell
32. Classical signs associated with allergic
rhinitis:
• Allergic shiners-purple gray
discolouration beneath lower eyelid,
related to nasal congestion causing
vascular congestion of small veins
under eyes.
• Allergic salute- habitual wiping or
rubbing nose in upwards manner by
palm or fingers.
• Dennie-Morgan (or Dennie’s) lines-
infraorbital fold or line in skin below
lower eyelid. 25% cases with atopic
dermatitis. Proposed mechanism-
continuous spasm of superior TARSAL
muscle and skin edema due to hypoxia
from poor circulation.
• Nasal crease-persistent transverse line
across junction of lower and middle
34. DIAGNOSIS
• Most allergic rhinitis patients can be diagnosed by a combination of
1) History
2) Examination
3) Skin tests : Scratch Testing
Skin prick test/subcuticular test
Intradermal skin test
Skin endpoint titration (SET)
4) Nasal challenge/provocation test
5) Nasal cytology
6) Total serum IgE
7) Specific serum IgE
8) Radio allergo absorbent tests (RAST) for specific IgE.
35. • Scratch Testing:
• This method of skin testing involves using a needle dipped in specific
antigen to place a small scratch on the skin.
• Area is reexamined for erythema and induration
• Limitations:
• Highly subjective and lacks sensitivity
• Limited no of antigens can be tested
• Inability to predict the exact amount of exposure that the patient
will get to the antigen applied
36.
37. SKIN PRICK TESTS
• Allergen introduced into the skin causes degranulation of IgE sensitized
mast cells with mediator release and wheal and flare reaction
• A drop of standardized allergen is placed on volar aspect of forearm and
pricked into skin using a new lancet.
• A positive control(histamine) and a negative control(saline)is used.
• Mean wheal diameter is read at 15 minutes
38. • >2 mm in under fives and >3 mm in olders are considered positive
• Indications: RHINOSINUSITIS, ATOPIC DERMATITIS,
RHINOCONJUNTIVITIS, ASTHMA, FOOD REACTIONS ,
• EXCLUDED IN:-Eczema,
• Dermographism
• History of anaphylaxis,
• Patients on antihistaminics
» Diffuse dermatological conditions
• Antihistaminics are avoided for minimum 48 hours before testing.
• Relative contraindications: persistent severe asthma, babies and
infants, pt on beta-blockers, pregnancy
39. Sensitivity and specificity:-
• A positive skin prick test is not indicative of allergy unless supported
by relevant history.
• Positive skin prick test occurs in 25 to 30% patients
• Only 10 to 15% develop symptoms
• The risk of clinical allergy increases with size of skin reaction
• False negative test can occur when allergy is localised
40. • Advantages :
• It allows relatively safe testing of a large no of antigens
• Low cost in short period of time
• Disadvantages:
• Its relative degree of inaccuracy
• Difficulty in Starting dose for allergic immunotherapy
• Fails to detect borderline cases of allergy
41. • Intradermal Testing:
• Single dose intradermal testing involves injection of a test dose of antigen
(0.1 ml) directly into the dermis using needle
• After 10 min the size of the wheal is measured and compared to a negative
control
• Screening test : 1:1000 dilution solution is used
• Confirmatory test: the dose depends on the degree of reaction observed
during screening
• This method is commonly used as a confirmatory test after prick testing
• Not often used as a screening test because of the difficulty in determining an
appropriate test dose
42. • Skin End Point Titration:
• Method of choice for allergy testing
• Small amounts of diluted allergen extracts are
injected into the skin.
• After waiting ten minutes, the skin is examined
for a reaction.
• This procedure is repeated using two to three
dilutions of the EXTRACTS with sequential
increasing concentration each time.
• Once skin reacts positively to a particular
allergen(s), the test is complete.
43. • Advantages:
• Determines the presence or absence of a specific allergy with a high
degree of accuracy and reliability
• Determines the lowest concentration with which the antigen produces
reaction
• Gold standard for allergy testing
• Disadvantages:
• Time consuming takes 60-70 mins to test approximately 12 to 18 antigens
in a single session
• Poor screening method as only limited no of antigens can be tested
44. • In Vitro Testing
• Use of blood samples to measure circulating IgE antibodies
• Stabilized allergen is incubated with the patient’s serum. Any
specific IgE binds to allergen and is identified by a second incubation
with labelled anti-IgE.
• A)Total serum IgE:
• Rarely helpful , as 50% of AR patients have there total serum IgE in
normal limits.
• B)Specific IgE:
• By RAST or ELISA
45. RADIOALLERGO SORBENT TEST(RAST)
• Allergen bound to a solid phase is incubated with patients serum
• IgE molecules bind to allergen
• Radiolabelled anti IgE is added
• Radioactivity is measured
• CAP-RAST:
• Newer modification of RAST
• Antigen is coupled to a cellulose carrier
• Anti- IgE is enzyme labelled with a fluoroscent substrate acting as a
developing agent.
46. • Advantages:
• Determines the lowest concentration with which the antigen
produces reaction comparable with SET
• Disadvantages:
• Delayed results
• Expensive
47. NASAL ALLERGEN CHALLENGE
• Nasal allergen is introduced into nose and any reaction noted
compared to placebo.
• It is used where a positive suggestive history is accompanied by
negative skin prick tests.
• Gradually increasing doses are used with careful monitoring of both
upper and lower respiratory tract symptoms.
48. • Lysine aspirin can be used in this fashion as a test for aspirin
sensitivity.
• Whereas with allergen the nasal reaction is immediate, occurring
within 1 to 2 minutes and being maximal at around 15 to 20 minutes
• With aspirin the reaction does not begin until about 45 minutes after
nasal application and may persist for many hours.
• Nasal challenge testing is time-consuming, difficult and requires
extensive laboratory facilities.
• Resuscitation equipment and trained staff are also necessary.
49. TREATMENT
1)Allergen avoidance and environmental control:
2)Pharmacotherapy:
a) Antihistamines
b) Topical glucocorticosteroids
c) Sodium chromoglycate
d) Decongestants
e) Ipratopium bromide
f) Systemic corticosteroids
g) Antileukotrines
3)Nasal douching
4)Immunotherapy
5)Surgery
56. • Terfenadine and astemizole are the earliest second generation H1
antihistamines that are now banned.
• Cyclizine,buclizine, dimethindine, mebhydroline are conventional
antihistamines that have become unavailable.
58. SIDE EFFECTS OF ANTIHISTAMINICS
1ST GENERATION:
Lack of selectivity for the H1 receptor and anticholinergic activity
Sedation
Dizziness
Blurred vision
Euphoria
Dry mouth
2ND GENERATION: More selective less side effects
Drowsiness
Fatigue
Headache
Dry mouth
64. TOPICAL GLUCOCORTICOIDS
• Inhibits phospholipase responsible for synthesis of arachidonic acid from
cell wall phospholipids.
• Block recruitment of inflammatory cells into the mucosa
• Suppress cytokine production and restore normal structure of mucosa
• Stabilize lysosomal membranes , maintain capillary integrity and block
migration of immune complexes across basement membranes
• Final effect is to markedly diminish the inflammation in the nasal and
sinus mucosa
65.
66. • Chronic Allergic rhinitis
• Reduces eye symptoms, nasal symptoms, Improves sense of smell
• Onset of action is slow(6-12 hrs)
• maximum effect occurs only after several days
• Lowest bioavailability seen with fluticasone and mometasone
Low toxicity ,excellent safety profile ,high rate of symptomatic relief
Low systemic absorption
SIDE EFFECTS:
1)Mucosal irritation
2)Crusting
3)Epistaxis
4)Septal perforation
Nozzle should be directed away from septum
70. ANTILEUKOTRIENES
• Monteleukast
• Zafirleukast
• Competitively antagonize cyst L1 receptors(LT-C4/D4) mediated
bronchoconstriction , increased vascular permeability, and
eosinophil recruitment
Very safe drugs with few SIDE EFFECTS:
1)Headache
2)Rashes
3)Eosinophilia and Neuropathy(rare)
Plasma t1/2 is 3-6 hrs
ZILEUTON:5-LOX inhibitor. Blocks LT-C4/D4/B4 synthesis
Has hepatotoxic potential.
71.
72.
73. SODIUM CHROMOGLYCATE
• Mast cell stabilizer
• Given before allergen exposure
• This spray is weakly effective against all rhinitis symptoms.
• Needs to be used four times daily. This limits compliance.
• It is used in children( < 4years)
• Cromoglicate eye drops can be effective
against ocular itching.
74.
75.
76.
77. DECONGESTANTS
• Alpha adrenergic agonist
• Acute nasal congestion
• Used topically , these drops reduces nasal obstructions , but increases
rhinorrhoea
• When used for a longer time , can result in rhinitis medicamentosa
• Very short term use is recommended.
• Systemic decongestants are relatively ineffective and have side effects
like hyperreactivity and insomnia
78.
79.
80.
81. IPRATROPIUM BROMIDE
• Topical anticholinergic
• Blocks muscarinic receptors ( M2 and M3 ) on which acetyl choline
released from cholinergic nerve endings act.
• Used in allergic rhinits with prominent rhinorrhea
• If regularly used,may be curative
• Side effects:
Worsening of glaucoma
Dry mouth and eyes
82.
83. • IPRAVENT 20 μg and 40
μg/puff metered dose
inhaler, 2 puffs
• 3–4 times daily; 250
μg/ml respirator soln.,
0.4–2 ml nebulized
• in conjunction with a β2
agonist 2–4 times daily.
84. SYSTEMIC CORTICOSTEROIDS
• Used in late phase allergic reactions
• This can be used to unblock the nose at the start of treatment
• Useful for very severe symptoms during the hayfever season.
• Occasional intermittent use is recommended.
• They should be combined with topical corticosteroids spray.
• Injections of depot steroids into turbinates and polyps has been
associated with blindness and is not recommended.
85. IMMUNOTHERAPY
• Allergen immunotherapy involves repeated administration of an
allergen extract in order to induce a state of immunological
tolerance,with a reduction of symptoms during subsequent
exposure.
86. EFFICACY:
• 50% reduction in sign and symptoms and 80% reduction in rescue
medication use.
• Treatment for 3 to 4 years resulted in sustained improvement for 3
years after discontinuation.
• 2 to 3 fold reduction of the risk of developing bronchial asthma.
87. SIDE EFFECTS:
• Local reactions-edema, erythema, tenderness, and pruritis at the
site of injection.
• Systemic reaction can occur in up to 10% of patients during
updosing phase. It can occur in the form of mild asthma or rhinitis,
dyspnea, fever, fatigue, angioedema, urticaria, and anaphylactic
shock
88. DOSAGE:
• The updosing phase involves weekly injections for 8-16 weeks
• In a cluster immunotherapy model, two to three injections are
administered per day, on nonconsecutive days, which shortens the
time frame for reaching the maintenance dose to 4 to 8 weeks.
• Maintenance injections at four to eight weekly intervals for three to
five years.
89. • Standardized whole allergen extracts with documented clinical
efficacy should be employed.
• Facilities for vaccine storage at +4°C are needed.
• Patients should be observed for at least 60 minutes following
injections in view of the rare systemic complications
90. • ALLERGEN SELECTION
• The most commonly used allergen extracts are derived from dust
mites, cat and dog dander, cockroach, molds, and pollens of trees,
grasses, and weeds.
• Extracts are prepared in aqueous, alum-precipitated, or lyophilized
solutions.
• Standardized extracts are supplied in concentrations expressed in
allergen units (AU) or bioequivalent allergy units (BAU).
91. • MECHANISM OF IMMUNOTHERAPY:
Immunotherapy results in blunting of seasonal allergen induced rise in IgE.
• It causes increase in IgG antibody
• It results in inhibition of recruitment and migration of inflammatory cells to
mucosal surface, including mast cells and basophils.
• Immunotherapy causes an “immune deviation” from Th2 type to more
protective Th1 type T cell response.
• Produces inhibitory cytokines IL-10 and TNF beta, which inhibits Th2
response.
92. • SubLingual Immunotherapy ( SLIT)
• Interest in SLIT steadily increased after sublingual administration of dust
mite allergen was reported in 1986.
• Immunologic Response
• Several studies have shown that one of the most consistent changes in
inflammatory mediators is the reduction of serum eosinophil cationic
protein (ECP).
• This decrease has been seen in both children and adults after 6 to 24
months of treatment with SLIT
93. • The most widely studied antibody responses to SLIT include changes in IgE
and IgG4.
• Studies show decreases in antigen-specific IgE after treatment with SLIT
• Antigen-specific serum IgG4 has shown a dose–response increase to SLIT
after the first year of use
• The immunologic changes seen after SLIT administration are similar to
those seen after administration of SCIT.
• Both induce changes in skin testing, increases in allergen-specific IgG4, and
decreases in antigen-specific IgE.
94. • Efficacy
• No clear cut answer seems to exist regarding the efficacy of SLIT versus
SCIT
• Adverse Reactions:
• Local reactions include oral irritation and itching, with an estimated
prevalence of 0.68 per 1000 doses.
• Systemic reactions to SLIT include asthma, urticaria, gastrointestinal
symptoms
95. • Safety
• The rate of systemic reactions was 0.6% for SCIT versus 0.056% SLIT
• Prevalence of death was 1 per 2.5 million for SCIT versus no reported
deaths for SLIT.
• These findings indicate an improved safety profile of SLIT over SCIT.
• Additional contraindications specific to SLIT
• Persistent lesions of buccal mucosal ulcers, persistent periodontal diseases
96. SURGERY
• Reduction of the inferior turbinate is the primary means of augmenting the
nasal airway in allergic rhinitis patients.
• Surgical reduction of inferior turbinate tissue, including
• outfracture, submucous resection, laser vaporization, radiofrequency
ablation, and coblation , cryosurgery
• Septoplasty alone has little role in the treatment of nasal obstruction for
allergic rhinitis.
• Endoscopic sinus surgery is an important treatment method for allergic
rhinitis when it contributes to chronic sinusitis, nasal polyposis, or allergic
fungal disease.
• No single operation has evolved as the gold standard for treatment of
nasal obstruction in allergic rhinitis
101. PREGNANCY AND ALLERGIC RHINITIS
• Existing rhinitis can be exacerbated by pregnancy ,due to high
circulating oestrogen level.
• The symptoms usually disappear after delivery.
• Immunotherapy and intranasal sodium cromoglycate (cromolyn) and
beclo-methasone would be considered as first-line therapy.
• Lack of association with congenital abnormalities and their superior
efficacy to other agents
• First-generation antihistamines are favoured over their second
generation counterparts based on their longevity, leading to more
conclusive evidence of safety.
102. • Occasional use of topical decongestants to aid sleep can be advised,
though evidences of foetal abdominal malformations are there.
• Oral, intranasal and ophthalmic decongestants (e.g.
pseudoephedrine, phenylephrine and oxymetazoline, respectively)
should be considered as second-line therapy
• Rhinitis of pregnancy is often resistant to treatment.
Editor's Notes
Recommendations in 2016 apply to mod-severe patients.
