Dousing the Flames of Allergic Eye Disease

The College of
Optometrists
Optometry Tomorrow 2011
Dousing the Flames of
Allergic Eye Disease
Dr Robert Harvey
Consultant Ophthalmologist at
Royal Alexandra Hospital, Paisley, Scotland.
Plan
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A bit of theory – immunology
Diagnosing allergy – usually easy
Rationale of treatment
Risks and benefits of treatments
New Paradigm
POM
Prescription Only Medicine
P
Pharmacy only
GSL
General Sale List
R
Prescription only
OTC
Over The Counter
Certificate of European conformity
China Export
Immune Reactions
• Type I
Hypersensitivity Reactions
– Atopic diseases
• Type II Hypersensitivity Reactions
– Antibody cytotoxic effect
• Type III Hypersensitivity Reactions
– Immune complex diseases
• Type IV Hypersensitivity Reactions
– Delayed cell mediated hypersensitivity
Type I
Hypersensitivity Reactions
Atopic diseases
• IgE / mast cell mediated histamine
release.
• Disease entities include:
allergic conjunctivitis,
atopic dermatitis,
latex allergy and
extrinsic asthma.
Type II Hypersensitivity Reaction
Antibody cytotoxic effect
• Cell injury
• Disease entities include: Incompatible blood transfusions
anti-A and Anti-B antibodies directly bind complement
leading to rapid haemolysis.
• In Graves' disease an antibody to the thyroid stimulating
hormone (TSH) receptor occurs that simulates the effect
of TSH on its receptor thereby causing hyperthyroidism.
• In myasthenia gravis antibodies to the acetylcholine
receptor occurs and in pregnancy 20% of mothers have
an infant affected by neonatal MG for 3 weeks. This is a
transient myasthenia due to the transplacental transfer of
antibodies.
Type III Hypersensitivity Reactions
Immune complex diseases
• 1) Vasculitis; 2) Arthus reaction (localised rapid
skin reaction); 3) Serum sickness due to serum,
drugs, or viral hepatitis
• Disease entities include SLE; RA; polyarteritis;
acute glomerulonephritis.
• Diagnosis may depend on finding circulating
antigen, (e.g. altered IgG (rheumatoid factor), or
• Measuring complement levels ( total or early
components (C1, C4, or C2). Depressed levels
indicate a classic complement activation and
therefore a type III reaction.
Type IV Hypersensitivity Reactions
Delayed cell mediated hypersensitivity
• Memory cells (primarily T cells and
macrophages) cause a later (secondary) cellular
response.
• Response appears 48 to 72 hours after antigen
exposure.
• Disease entities include contact dermatitis,,
granulomas due to intracellular organisms like
Tuberculosis,
• Late graft rejection e.g. penetrating corneal graft
rejection.
Types of Allergic Conjunctivitis
• SEASONAL ALLERGIC
• VERNAL KERATOCONJUNCTIVITIS
• ATOPIC KERATOCONJUNCTIVITIS
• GIANT PAPILLARY CONJUNCTIVITIS
• CONTACT ALLERGY
Type I
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Hypersensitivity Reactions
Atopic diseases
The main players are quite simple…
Immunoglobulin IgE
Mast cells
Eosinophils
Histamine
• The intended effect is protection of the host from
external threats. The protection itself needs regulation
(homeostasis).
Immunoglobulin E
IgE
• IgE production by B
cell lymphocytes
(plama cells)
• Y shaped molecule
with two arms
(antigen detection)
and a functional end
to trigger an effect
FC receptor
(attaches to the
mast cell).
IgE
• Hyper
variable
region
• Hinge
region
Mast cell
• Fc region
Lymphocytes
Mainly either T cells or B cells
T cells have a role in
detection and control.
Cell mediated immunity
B cells responsible for
antibody production
Cytokines
Plasma
cell
Antigen presenting cell
Dendritic cell
Langerhans cell
Found in the cornea
and mucous
membranes
MALT
Mucous membrane
assoc lymphatic tissue
APC - antigen processing
• Birkbeck granules
within
Langerhan’s cell
Eosinophils
• Granules stain with the acidic dye
eosin which is pink.
• Granules, contain histamine and
proteins eosinophil peroxidase,
RNase, DNases, lipase, plasminogen,
and Major Basic Protein.
• Chemicals released by degranulation
following activation of the eosinophil,
(toxic to both parasite and host
tissues).
• Useful in dealing with parasites like
hookworm infestation – not much use
with hayfever!
Mast cell
Granules
contain
histamine
and
heparin.
Degranulating Mast Cell
Histamine
causes
vasodilatation
and increased
vascular
permeability
Allergy
SENSITISATION
Intervene by
blocking the
pathway at
various steps
REACTION
Pollen Grains
Grass pollen
Scots pine
Golden rod
Pollen
chart
Early season
Extended season
Wimbledon
Glorious 12th August
Grass pollen - Hayfever
Not just pollen
House Dust Mite
Iatrogenic
• Chronic
(neomycin)
• Acute
allergy
Management
HISTORY
• New soap, shampoo, hair dye, lash tinting.
handling chemicals, occupation / gardening
Any contact with feathers, animal danders.
Contact lens wear, cleaning solutions, eye drops,
• Duration, days, weeks…
• Intensity
• Other known allergies
• Use of antihistamines
• Reconsider diagnosis e.g. possible infection with
adenovirus…
Presentation of Allergic Conjunctivitis
COMMON CHARACTERISTICS:
BILATERAL itching,
Pale milky conjunctiva,
Ropy mucoid discharge,
Papillary hypertrophy of conjunctiva,
also nasal symptoms.
SEASONAL ALLERGIC CONJUNCTIVITIS
SAC
• Commonest, hypersensitivity to airborne allergens (pollens) Hayfever
• Perennial if secondary to house dust mite or animal dander
• Nasal symptoms are common, as is atopy
• Itchy, red, watery eyes with milky conjunctiva and puffy lids.
• Conjunctival chemosis.
SAC
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PATHOLOGY
Biphasic response
Mast cells degranulate causing histamine release
Esosinophils recruited causing a second wave of histamine release.
• INVESTIGATION
• Conjunctival scraping = >1 eosinophil on Giemsa stain
• TREATMENT
• Avoid allergens / pollens
• In Britain the pollen count rises in summer to very high levels
particularly on hot windy days. The pollen source varies according
to season…
• During the spring (March to May) generally tree pollen
• From May to July mainly grass pollen
• In the autumn months weeds such as nettles and docks, late
flowering plants and mould spores.
Rx Seasonal Allergic Conjunctivitis
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Normal saline irrigation.
Topical mast cell stabilisers (safe).
Topical / systemic antihistamines.
Topical NSAID (synergistic effect with
antihistamines). Short term use only.
• Desensitisation treatment
(ironically increases serum antibody level).
Topical mast cell stabilisers
• Disodium cromoglycate, Opticrom ™ 4 x
day. Off-patent - readily availalable.
• Olapatadine Opatanol ™ 2 x day
• Nedocromil Rapitil ™ 2 x
• Lodoxamide Alomide ™ 4 x
Topical Antihistamines
• LODOXAMIDE Alomide ™ 0.1% solution
allergic conjunctivitis or vernal keratoconjunctivitis.
(preservative: BZK). 4 x age over 4 yrs
• AZELASTINE Optilast ™ allergic conjunctivitis 2 x
• LEVOCABASTINE Livostin ™ allergic conjunctivitis
• ANTAZOLINE Otrivine-antistin ™ allergic conjunctivitis. Also contains
xylometazoline (a vasoconstrictor - temporarily whitens the eye, but
later rebound redness). 2-3 x
• EMEDASTINE Emadine ™. (preservative: BZK). Potent H1 antagonist
Side effects include local irritation, pruritis, erythema, chemosis,
blurred vision. 2 x, age over 3 yrs
• OLAPATADINE Opatanol ™ 2 x day
• 2 x age over 3 years
(has a dual effect)
SYSTEMIC ANTIHISTAMINES
• SYSTEMIC ANTIHISTAMINES:
• Older generation May cause drowsiness. Can be useful especially
if itching is a problem at night. Potentiation of sedation in
combination with alcohol or other sedating drugs. Risk of dry mouth,
angle closure glaucoma due to anticholinergic side effects.
• CHLORPHENIRAMINE Piriton ™ tabs or syrup. Adults 4 mg tablets
(max 6 per day)
• CLEMASTINE Tavegil ™ Adults 1 mg tablets,
1 twice daily (max 6 per day).
Children over 1 yr 250mcg twice daily.
• PROMETHAZINE Phenergan ™
Also available as iv injection
25 - 50 mg (given slowly)
for use in anaphylaxis after adrenaline.
Newer generation Anti-Hist
• Do not cause drowsiness. Especially useful if there is a
need to stay awake, drive etc.
• CETIRIZINE (non-propr) 10 mg tab once daily
• LORATADINE Clarityn ™ 10 mg tab. Not so good for
relieving itchy skin as the sedating antihistamines.
• DESLORATADINE Neoclarityn ™ or Aerius ™ 5 mg tab.
Long acting up to 24 hours. Max 2 per day.
Non-Steroidal Anti-Inflammatories
NSAI
• Topical NSAID (synergistic effect with antihistamines).
For short term use only.
• E.g. Ketorolac trometamol (Acular) ™
Used 3 x day.
• Or Diclofenac (Voltarol) ™
• CAUTION
• NSAIs have a local anaesthetic action so beware abuse
which can result in neurotrophic keratitis
(ULCER FORMATION).
Topical steroids
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Effective but….
Risk of causing steroid induced glaucoma
Risk of cataract
Reactivation of Herpes simplex causing
large geographical ulcer.
Systemic steroids
• Effective but there are also SYSTEMIC SIDE EFFECTS…
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1. Decreased wound healing, gastric ulcers,
2. Endocrine effects :- hyperglycaemia,
3. Hypertension, fluid retention, hypokalaemia,
4. Osteoporosis, bone fractures, vertebral collapse
5. Adrenal suppression leading to possible shock,
6. Weight gain
7. Infections- candida and herpetic
8. Psychiatric- florid in 10% on high doses, elation / depressn.
9. Avascular necrosis head of femur
10. Raised intracranial pressure (ICP)
11. Warn patients of the risk of generalised Varicella
12. Reactivation of Tuberculosis.
13. Steroid myopathy
Rationale
SENSITISATION
REACTION
Rationale
Rationale
Rationale
SENSITISATION
REACTION
Inflammation may produce a positive feedback loop so the
reaction becomes progressively more intense due to recruitment
of more inflammatory cells and the release of more mediators.
CORTICOSTEROIDS
STEROIDS
can
interrupt
the
inflammatory
process
LEUKOTRIENE ANTAGONISTS
• Montelukast
Singulair ™
• Montelukast blocks leukotriene receptors.
• DOSAGE
• Montelukast 10 mg once daily in the evening regularly
(can be used over age 15 years).
• INDICATIONS
• Asthma in addition to standard treatment when steroids
and bronchodilators are not fully effective.
• Hay-fever to relieve nasal congestion and sneezing and
epiphora.
VERNAL KERATOCONJUNCTIVITIS
Vernal Catarrh VKC
• Rare, 7-14 years (eventually self-limiting)
Lasts up to 10 years
• M>F
• Bilateral, seasonal and recurrent
• Commoner in warm climates
• 50% atopic
VERNAL KC
• CLINICAL
• Palpebral commoner in whites;
limbal type commoner in blacks
• SYMPTOMS
• include itching, gritty, photophobia, excessive
mucus
• CONJUNCTIVA
• Eosinophils ++
in conjunctival
scrape.
Vernal KC
• Giant papillae
Cobblestones
upper tarsus
(Polygonal, > 1 mm),
• +/-Pseudomembrane
Vernal KC - Corneal changes
• Limbal papillae
• “limbitis”
• Trantas´ dots
(Horner-Trantas' dots)
are small white
elevated spots due to
esosinophil clumping/
concretions
Vernal KC - severe
• Superior punctate
epithelial erosions,
micropannus,
• Shield ulcer,
Mucous plaque,
pseudogerontoxin
(superior arcus).
Rx - Vernal KC
• Topical mast cell stabilisers
(regular application).
• Topical / systemic antihistamines
• Topical steroids for a few weeks then
slowly reduce frequency and strength).
ATOPIC KERATOCONJUNCTIVITIS
• M>F,
• 30-50yrs (not self limiting)
• Associated with atopic dermatitis
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FEATURES
Bilateral, red, itchy eyes with copious discharge
Blepharitis and lid dermatitis
Thickened conjunctiva inferior tarsus
Limbal papillae
Trantas' dots +/-,
AKS
• Punctate epithelial
erosions +/- pannus,
• HSV and Staphylococcus
infections are common
• Increased frequency
of cataracts
(anterior subcapsular ops)
or steroid induced
post subcapsular lens ops,
• +/- Ectropion
• Incr incidence of keratoconus is linked to atopy.
Rx Atopic KC
• TREATMENT
• Lid hygiene and hot
compresses …
• As for vernal KC + steroid
cream to lids (watch IOPs),
• Topical antibiotic
• Treat rosacea with oral
tetracycline or doxycycline
• Cataract surgery when,
if required.
Giant Papillary Conjunctivitis.
• Giant Papillae are over 1mm in diameter.
• (VKC have extreme giant papillae with flat tops
“cobblestones”).
• Associated with foreign body
e.g. contact lenses
or protruding suture material
Contact Allergy
• Chemosis, hyperaemia,
Conjunctival papillae,
lid skin dermatitis.
• Delayed hypersensitivity
reaction.
• TREATMENT
• Stop the allergen!
• ? Steroids as required
to hasten resolution.
Photo from Practical Ophthalmology
Red Eye due to eye Rx
• Drops for various eye conditions may
cause conjunctival hyperaemia:
• Prostas: Lumigan > Travatan > Xalatan
• CAI: Trusopt or Azopt
• Preservatives e.g. lubricants for dry eyes
Lanolin even in lacrilube.
• Allergies to antibiotics: chloram, neomycin
Stevens Johnson Syndrome
Acute inflammatory vesiculobullous reaction of skin and mucous membranes
EM MAJOR
Skin lesions + 2 or more
mucous membranes
Systemic toxicity
Lasts 6 weeks
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EM MINOR
Skin involvement +/- 1 mucous
membrane
Lasts 4 weeks
M = F, <30 years
CAUSE
Infections- HSV, Mycoplasma pneumoniae, virus, bacteria,
fungi
Drugs- sulphonamides, penicillin, salicylate, phenytoin,
barbiturates. Vaccines, Collagen vascular diseases
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PATHOGENESIS
Circulating immune complexes deposit at dermal-epidermal
junction causing vasculitis
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CLINICAL
1. prodrome - malaise, fever, headache, URTI
2. rash - target lesions, vesicles, bullae, extremities >
trunk
3. mucous membranes conjunctiva (60%), mouth (100%), genitalia
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Ocular Effects of SJS
• Conjunctivitis or pseudomembranous conjunctivitis,
• Scarring, symblephara
(tethering of the conjunctiva
to form bands).
ankyloblephara (fusing of
sections of the upper and
lower lid margins).
• Dry eye syndrome,
entropion, trichiasis,
corneal exposure,
lagophthalmos.
Photos from Practical Ophthalmology
LIGNEOUS CONJUNCTIVITIS
• Rare bilateral idiopathic chronic conjunctivitis occurring
in children.
• Acute onset, fibrinous exudate,
• White membrane affecting upper tarsus.
• May affect vagina and mouth.
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TREATMENT
Topical steroids,
Ciclosporin,
Mucolytics,
Hyaluronidase,
alpha chymotrypsin,
Heparin.
Sonja Klebe Br J Ophthalmol1999;83:878
Thank You
More information on Interactive CD-ROM
Email: [email protected]
Practical Ophthalmology
1993
to
2011