Download Allergic Rhinitis

Allergic rhinitis
Before we start….
• It is important to know that although similar
types of drugs are used to treat the
symptoms of allergic rhinitis and the
common cold, each condition is caused by
distinctly different mechanism, thus
different approaches to therapy are used.
SINUSES
Anatomy
and Physiology
• “hollow cavities in the skull bones which
communicate with the nose”
• Functions: 1. Drain posteriorly to the pharynx;
thus lighten the cranium; 2. Serve as resonating
chambers for speech
• There are four pairs of sinuses: frontal, maxillary,
ethmoidal and sphenoidal
Sinuses
Allergic Rhinitis
• The most common atopic disease
• Hallmark of ~: temporal relationship between
exposure to allergens & development of nasal
symptoms
• It takes at least 2 years of exposure to aeroallergens
(airborne environmental allergens) to develop AR
(thus, very rare in children <1 year)
• Prevalence of AR: lowest in children < 5 yrs
highest 2nd---- 4th decades
• Genetic predisposition (60%)
Allergic Rhinitis
• AR is classified as seasonal or perennial
• Seasonal: repetitive & predictable
symptoms (severe)
• Perennial: symptoms persist throughout
year without any obvious seasonal pattern
• WHO: replaced terms with intermittent or
persistent
Comparison between different types of rhinitis
Allergic
rhinitis
Infectious
rhinitis
Vasomotor rhinitis
Rhinitis
Medicamentosa
Etiology
Allergen
Viral or
bacterial
Unknown
Tachyphylaxis to
topical decongestants
Symptoms
Rhinorrhea,
congestion,
sneezing,
pruritis, cough
with postnasal
drip ocular
itching etc
Fever (more
common in
children),
mucupurulent
rhinorrhea,
scratchy throat,
congestion,
cough
Rhinorrhea,
congestion
Congestion
Pattern
Perennial or
seasonal
Any time
Any time
Temporal relationship
with use of topical
decongestant
Associated
Factors
Concurrent
None
atopic disease,
family history
Affects women
primarily, strong
odours, alcohol, stress,
change in humidity
and temperature
Overuse of topical
decongestants,
concurrent use of
antihypertensive
therapy
Perennial Allergic Rhinitis
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• Caused by continuous exposure to many different
types of allergens
• Dust Mite the most common cause of perennial
allergic rhinitis
• Commonly: household dust mites, molds,
cockroaches, house pets
• Less commonly: cottonseed & flaxseed (found in
fertilizers, hair setting preparations and foods); some
vegetable gums (found in hair setting prep & foods)
Caused by:
Dust mites
Perennial Allergic Rhinitis
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• Dust mite: thrive in carpets, beddings & reproduce best in
warm (18-21ºC) humid (>50%) environment found in most
homes
• Mites feed on human skin scales and their own faeces.
• Mite itself is not allergen, the main allergen is the
glycoprotein that coats their faeces.
• Dust mite remain airborne for about 30 minutes after being
disturbed
• Molds: grow best in warm, moist environment
• Cat-derived allergens: light small proteins secreted through
the sebaceous glands in the skin. May remain airborne for up
to 6 hrs. Can be detected at home even 6 months after removal
of the cat.
Seasonal Allergic Rhinitis
• Caused by wind-borne plant pollens (e.g.
tree, grass. etc)
• “hay fever” & “rose fever” are terms
related to seasons associated grass
pollinosis and NOT associated with
FEVER!
Pathophysiology
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Complex pathogenesis involving numerous cells &
mediators
Histamine one of the most important but not the sole
Histamine: itching, pain, paroxysmal sneezing,
vasodilation, and plasma exudation
Sensory neural stimulation: nasal itch, sneeze,
rhinorrhea
Kinins, PG & Leukotrienes: nasal blockage, plasma
protein exudation & glandular secretion
Pathophysiology
Phases:
1. Sensitization: initial allergen exposure stimulates IG-E
production by beta lymphocytes
2. Early phase response: subsequent allergen exposure results
in rapid release of preformed mast cells mediators +
production of additional mediators itching, sneezing and
discomfort within minutes
3. Cellular-recruitment: inflammatory granulocytes & mast
cells infiltrates the mu7cosa
4. Late phase response: a chronic inflammatory response,
begins several hours after allergen exposure mucus
hypersecretion secondary to infiltration of nasal mucosa
with eosinophils, basophils, neutrophils and macrophages
Mast cells degranulating and releasing vasoactive
amines.
Complications
1.
2.
3.
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Sinusitis
Recurrent otitis media & hearing loss
Patients who develop:
fever,
purulent nasal discharge,
refer to Dr. for evaluation
frequent HA,
and treatment
earache
Symptoms of Allergic Rhinitis
• Ocular: itching, lacrimation, mild soreness, puffiness
& conjuctival erythema
• Nasal: congestion, watery rhinorrhea, itching,
sneezing, postnasal drip and nasal pruritus
• Head & Neck: loss of taste and smell, mild sore throat
due to postnasal drip, earache, sinus HA, itching of the
palate and throat
• Systemic: malaise & fatigue:
Physical Assessment
• “allergic shiners”  venous/lymphatic congestion
• Chronic mouth breathing highly arched palate
• A horizontal crease across the lower third of the
nose (in patients repeatedly rub their noses
upward)
• Nasal mucosa: pale & swollen
• Nasal secretions: clear & watery
• Eyes: watery with scleral & conjuctival erythema
and periorbital edema
Allergic shiners
Arched palate because of mouth
breathing
Periorbital edema
Diagnostic Testing
1. Skin tests can differentiate allergic from nonallergic reactions
• Although –ve result non allergic reaction
+ve reaction can’t be positively associated
with a specific allergen unless a relationship can
be established between the exposure to an
allergen and a characteristic symptom
Diagnostic Testing
Currently used Skin Tests:
• Skin-prick test: the initial test for house dust mite,
mold & pollens). Involves placing a drop of the
Ag on the skin & puncturing the skin superficially
with a needle, the localised reaction is evaluated
subjectively
• Intradermal Skin Test: injecting the Ag
intradermally, the wheal & flare reaction is then
evaluated subjectively using a scale of 0-4
Diagnostic Testing
• Skin Endpoint Titration (SET) Test: The only
quantitative skin test; involves making a series
of injections with increasingly higher
concentration of the allergen and then
evaluating the reaction
Diagnostic Testing
2. Obtaining intensive patient history is very
important
• Food allergies are more common in children <
1 year old
• In case of aeroallergen: 2-4 years of exposure
are needed to develop sensitivity
Diagnostic Testing
3. Serologic Tests total IgE level
- Serum IgE radioallergosorbent (RAST) test
4. Nasal Cytology: microscopic evaluation of the
nasal secretions. Helps differentiate between AR
( raised eosinophils) and infectious rhinitis
(raised neutrophils)
5. Plain X-ray, MRI & CT-scan sinuses
6. Chest radiography & pulmonary function tests
to rule out asthma
7. Nasal endoscopy identify any structural
abnormalities
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Disease Management
1. First step: avoidance of the offending allergens
2. Pharmacotherapy is used if the avoidance
measures are not feasible or do not adequately
relieve the symptoms
• Treatment of allergic rhinitis should be
targeted at the patient’s specific symptoms
• Drugs: antihistamines, decongestants, mast
cell-stabilizers, mucolytics & corticosteroids
Disease Management
3. Immunotherapy is indicated for patients: (a)
whose symptoms can’t be adequately
controlled with medication or (b) symptoms
occur most days of the year
Preventative Measures
• patients allergic to outdoor allergens should keep
house and car windows closed and use airconditioners
• Avoid grass if allergic etc
• Reduce indoor mold by: - venting moist bathroom
and kitchens, - using dehumidifiers
How to reduce house dust mite exposure?
House dust mite by
1.
2.
3.
4.
5.
Reduce indoor humidity to < 50%
Pillows, mattresses should be encased with a plastic cover
that is cleaned weekly by a damp cloth
Items that collect dust should be removed from bedrooms
(e.g. open bookshelves)
All beddings, including mattresses should be cleaned
weekly with hot water
Vacuum cleaners should be equipped with special filters
(HEPA) to avoid aerosolising the house dust mite faeces
when vacuuming
Animal allergen exposure: remove totally or at
least from bedrooms. Wash cat fortnightly!
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Symptomatic OTC drug treatment
of allergic rhinitis
Symptoms
Treatment
Ocular itching,
lacrimation, puffiness
Chemosis, conjuctival
redness
Rhinorrhea, nasal
itching, postnasal drip
Nasal congestion
Ophthalmic antihistamines,
systemic antihistamines
Ophthalmic decongestants
Systemic antihistamines
Systemic decongestants (topical is
an option but overuse potential is high)
Headache, earache, sinus
pain
Systemic analgesics (decongestants
may relief sinus pain due to sinus
congestion)
Antihistamines
• First line for prophylaxis and treatment of
allergic rhinitis
• Usefulness is limited as they compete only with
one mediator (histamine)
• Antihistamines:
- very effective in relieving symptoms of sneezing &
itching
- somewhat effective for reducing rhinorrhea
- have no effect on nasal congestion
Antihistamines
Dry mouth, urinary
retention, tachycardia,
blurred vision
anticholinergic
Side Effects:
• 1st generation:
Sedation, impaired mental
performance
Increase appetite and cause wt
gain (Cyproheptadine)
• 2nd generation AH: astemizole, cetrizine,
loratidine & terfenadine are: nonsedating (not
lipophilic), do not have any anticholinergic,
antiemetic or local anaesthetic activity
Topical Intranasal decongestants
Short acting (4-6 hr duration)
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Ephedrine
Epinephrine
Naphazoline
Phenylephrine
Tetrahydrozoline
Intermediate acting (8-10 hr duration)
• Xylometazoline
Long acting
• Oxymetazoline
Ophthalmic Decongestants
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Epinephrine
Naphazoline
Oxymetazoline
Phenylephrine
Tetrahydrozoline
Systemic Decongestants
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Ephedrine
Pseudoephedrine
Phenylephrine
Phenylpropanolamine (withdrawn from
market because of its relation with
haemorrhagic stroke)
Inhalers:
• Desoxyephedrine
• Propylhexedrine
Decongestants
Side Effects of topical decongestants:
• Topical decongestants are minimally absorbed,
thus, systemic S.E: infrequent & minimal
1. May cause local irritation because of the
propellant or vehicle
2. Rebound congestion “rhinitis medicamentosa”
when topical decongestant is used > 3-5 days
- more common with short acting than long acting
decongestants
Treatment of rebound congestion
1. Slow withdrawal of topical decongestant (one
nostril at a time)
2. Replacement of topical decongestant with
topical normal saline (soothe & moisten)
3. (if needed) topical corticosteroids & systemic
decongestants
The mucous membrane would return to
normal 1-2 weeks following discontinuation of
the topical decongestant
Decongestants
Product Selection Guidelines:
• Depends on the expected duration of treatment
and presence of concomitant disease
• Patients of seasonal allergic rhinitis, requires
decongestants throughout the period of exposure
to allergens
• Nasal sprays: the simplest drug delivery methods
& preferred for older children and adults
Decongestants
Dosage
form
Advantages
Disadvantages
Sprays
Simple to use, fast onset
of action, relatively
inexpensive, large
surface coverage
Imprecise dosage, high risk of
aspiration of nasal mucus into
bottle, tendency for tip to become
clogged
Drops
Preferred for small
children
Awkward to use, high risk for
contamination of medication from
dropper, limited coverage of nasal
mucosa, easy passage into larynx
Inhalers
Small and unobtrusive,
easy to handle and
carry
Unobstructed airway & sufficient
airflow needed to distributed drug
to nasal mucosa, limited durability
of 2-3 moths even when tightly
capped
Decongestants
• Anatomical abnormalities (nasal polyps, severe
septal deviation) interfere with drug
administration by blocking access to nares
• Systemic decongestants relatively safe for use
over the long term
• Systemic decongestants are short acting (4-6
hours). Thus, for long term administration,
most patients prefer sustained release products
(Efidac)/24 (pseudoephedrine HCL 240 mg) is
the first SR dosage form.
Decongestants
• Some side effects (nervousness, tremor,anxiety,
dizziness) are similar to those associated with
hyperglycemia or hypoglycemia patient may
inappropriate,y seek medical advice while
symptoms are drug-related or delay seeking
treatment when symptoms are related to glycemic
dysregulation
• Should be used in pregnancy only if potential
benefit >>> risk for foetus (Category C)
• Breast-feeding women: use with caution (decrease
lactation)
Athletes (decongestants are stimulants):
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Phenylephrine
Ephedrine
Pseudoephedrine
Propylhexedrine
should be avoided
• Physical performance may be impaired by: 1st
generation antihistamines (sedation and &
anticholinergic effects) immunotherapy (owing to
discomfort at site of injection)
Topical anti-inflammatory drugs
• Corticosteroids: the most potent & most
effective drugs available for management of
allergic rhinitis
Inhibit release of preformed mediators
from mast cells & basophils
• Corticosteroids
migration of eosinophils
and neutrophils into nasal
mucosa
synthesis of
inflammatory mediators
Edema &
inflammation
Therefore, cortecosteroids are effective against all stages of
allergic response
Topical anti-inflammatory agents
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Intranasal administration corticosteoids is the
route of choice as it minimizes the risk of
systemic side effects
• The side effects of intranasal ~:
1. Local irritation
2. Epistaxis
• However, short term use of systemic
cortecosteroids may be required for severe
symptoms
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Cromolyn sodium (Na
cromoglycate)
• Applied intranasally
• Most effective: if started before seasonal
symptoms.
• 3-7 days for initial efficacy. 2-4 weeks of
continued therapy for maximum benefit
• Inhibits release of mediators from mast cells
• Protects mast cells from immune-mediated and
non-immune mediated (cold, air,
hypersensitivity, exercise) triggers
Cromolyn sodium (Na
cromoglycate)
• Has to be applied 1 spray per nostril: 4-6 times
daily to be effective (t1/2= 1-2 hours)
• Not as effective as corticosteroids for patients
with more severe symptoms, used as adjunctive
therapy
• Not associated with systemic side effects (< 7%
absorption)
• The most common S.E: sneezing then nasal
stinging and burning
Cromolyn sodium (Na
cromoglycate)
• No drug interactions
• Relative C/I: children < 5 year old, Hx of
hypersensitity.
• Wide margin of safety: safe during pregnancy,
elderly and in children > 6 year old
Mucolytics
• Drugs that thin the mucus, making it easier to
expel secretions
• Mucus= mucin, epithelial cells, leukocytes &
various inorganic salts suspended in water
• Hydration (by fluid intake or steam inhalation)
will aid in the formation of a less viscid, more
liquid mucus that is easy to expel
• E.g. Ambroxol, Bromhexin
Expectorants
• Facilitates mucociliary transport
• E.g. Guaifensin, ammonia and ipecacuanha
mixture, BP
• but their efficacy in allergic rhinitis has not
been proved
Immunotherapy
• “ desensitization” “hyposensitization”
• Most effective for pollen-related allergens
• Indication:
- in patients whose symptoms are not controlled
by drugs
- who have severe conditions or perennial
symptoms
- who are allergic to allergens that are difficult
to avoid
Immunotherapy
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Exact mechanism is not known yet BUT…
Thought to work by:
production of Ig-E antibodies
Production of Ig-G blocking antibodies
Generating antigen-specific suppressor Tlymphocytes
- mononuclear cell-derived histamine releasing
factor
Immunotherapy
Administration Technique:
• Consists of a series of injections with extracts of
allergens identified as the cause of the
symptoms
• Treatment is initiated with very dilute
solutions.
• Injections then repeated weekly using
gradually increasing concentrations
• The top “maintenance” dose is generally
reached within 4-8 months
Immunotherapy
• Injections of this dose are repeated every 3-4
weeks for 3-5 years
• Patients may improve as early as 3 months
after initiation of immunotherpay
• About 80% of patients have significant relief
while receiving immunotherapy
• Approximately 60% will remain symptom-free
after the discontinuation of the immunotherapy
Immunotherapy
• Relative C/I: autoimmune disease, unstable
CAD, unstable angina and concurrent therapy
with B-blockers
• Although it must not be initiated during
pregnancy, maintenance therapy can be
continued
Patient Counselling
• Self-reading: Handbook of Nonprescription
Drugs
• Enjoy!