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Conjunctivitis, Allergic
Author: Parag A Majmudar, MD, Fellowship Co-Director, Department of Ophthalmology,
Cornea and Refractive Surgery Service, Assistant Professor, Rush-Presbyterian-St Luke's
Medical CenterContributor Information and Disclosures
Updated: Aug 4, 2010
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Overview Differential Diagnoses & Workup Treatment & Medication Follow-up References Keywords
Introduction
Background
Immunologic reactions of conjunctiva and cornea
The ocular surface may exhibit a wide variety of immunologic responses that may result in
conjunctival and corneal inflammation. In the Gell and Coombs classification system for
various immunologic hypersensitivity reactions, 5 classes of reactions are recognized.
Type I (immediate) hypersensitivity reactions occur when a sensitized individual comes in
contact with a specific antigen. Immunoglobulin E (IgE) has a strong affinity for mast cells,
and the cross-linking of 2 adjacent IgE molecules by the antigen triggers mast cell
degranulation. This, in turn, causes the release of various preformed and newly formed
mediators of the inflammatory cascade, including histamine, tryptase, chymase, heparin,
chondroitin sulfate, prostaglandins, thromboxanes, and leukotrienes. These various
inflammatory mediators, together with various chemotactic factors, result in increased
vascular permeability and migration of eosinophils and neutrophils. The principal ocular type
I hypersensitivity reaction is allergic conjunctivitis, which is discussed in further detail in this
article.
Type II hypersensitivity reactions are autoimmune reactions and may be complement
mediated. These reactions may be the underlying cause of various ocular conditions, such as
cicatricial pemphigoid and Mooren ulcer.
Type III hypersensitivity reactions result in antigen-antibody immune complexes, whichdeposit in tissues and cause inflammation. Classic type III reaction systemically is the Arthus
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reaction, and ocular type III hypersensitivity reactions include Stevens-Johnson syndrome
and marginal infiltrates of the cornea. Corneal immune (Wesley) rings are also an example of
type III reactions.
Type IV hypersensitivity reactions, also known as cell-mediated immunity, are mediated by T
lymphocytes. While type I reaction is immediate hypersensitivity, this reaction is also knownas delayed-type hypersensitivity, since its onset is generally after 48 hours. Type IV
hypersensitivity reactions imply immunocompetence on the part of the individual since an
intact immune system is required to mount the cell-mediated response. Ocular examples of
type IV hypersensitivity include phlyctenular keratoconjunctivitis, corneal allograft rejection,
contact dermatitis, and drug allergies.
This section focuses primarily on the major type I hypersensitivity reactions involving the
conjunctiva, more commonly referred to as allergic conjunctivitis.
Types of allergic conjunctivitis
Allergic conjunctivitis may be divided into 5 major subcategories. Seasonal allergic
conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are commonly grouped
together. Vernal keratoconjunctivitis (VKC),atopic keratoconjunctivitis(AKC), andgiant
papillary conjunctivitis(GPC) constitute the remaining subtypes of allergic conjunctivitis.
Pathophysiology
Seasonal and perennial allergic conjunctivitis
Since conjunctiva is a mucosal surface similar to the nasal mucosa, the same allergens thattrigger allergic rhinitis may be involved in the pathogenesis of allergic conjunctivitis.
Common airborne antigens, including pollen, grass, and weeds, may provoke the symptoms
of acute allergic conjunctivitis, such as ocular itching, redness, burning, and tearing. The
main distinction between SAC and PAC, as implied by the name, is the timing of symptoms.
Individuals with SAC typically have symptoms of acute allergic conjunctivitis for a defined
period of time, that is, in spring, when the predominant airborne allergen is tree pollen; in
summer, when the predominant allergen is grass pollen; or in fall, when the predominant
allergen is weed pollen. Typically, persons with SAC are symptom-free during the winter
months in cooler climates because of the decreased airborne transmission of these allergens.
In contrast, individuals with PAC may have symptoms that last the whole year; thus, PAC
may not be caused exclusively by seasonal allergens, although they may play a role. Other
common household allergens, such as dust mite, cockroaches, and pet dander, may be
responsible for the symptoms of PAC.
Vernal keratoconjunctivitis
VKC is a chronic bilateral inflammation of the conjunctiva, commonly associated with a
personal and/or family history of atopy. More than 90% of patients with VKC exhibit one or
more atopic conditions, such as asthma, eczema, or seasonal allergic rhinitis.
Atopic keratoconjunctivitis
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AKC is a bilateral inflammation of conjunctiva and eyelids, which has a strong association
with atopic dermatitis. It is also a type I hypersensitivity disorder with many similarities to
VKC, yet AKC is distinct in a number of ways.
In 1953, Hogan first described the association between atopic dermatitis and conjunctival
inflammation.1
He reported 5 cases of conjunctival inflammation in male patients with atopicdermatitis.
1Atopic dermatitis is a common hereditary disorder that usually has its onset in
childhood; symptoms may regress with advancing age. Approximately 3% of the population
is afflicted with atopic dermatitis, and, of these, approximately 25% have ocular involvement.
Giant papillary conjunctivitis
GPC is an immune-mediated inflammatory disorder of superior tarsal conjunctiva. As the
name implies, the primary finding is the presence of "giant" papillae, which are typically
greater than 0.3 mm in diameter. It is believed that GPC represents an immunologic reaction
to a variety of foreign bodies, which may cause prolonged mechanical irritation to the
superior tarsal conjunctiva. Although contact lenses (hard and soft) are the most commonirritant, ocular prostheses, extruded scleral buckles, and exposed sutures following previous
surgical intervention may precipitate GPC.
Frequency
United States
Allergic conjunctivitis occurs very frequently and is seen most commonly in areas with high
seasonal allergens.
Mortality/Morbidity
Allergic conjunctivitis rarely causes any visual loss.
Race
VKC occurs predominantly in areas with tropical and temperate climates, such as the
Mediterranean, the Middle East, and Africa.
The limbal form of VKC commonly occurs in dark-skinned individuals from Africa and
India.
Sex
VKC has a significant male preponderance.
Age
VKC typically affects young males with onset generally in the first decade and with duration
up to one decade. Its symptoms usually peak prior to the onset of puberty and then subside.
Clinical
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History
Seasonal and perennial allergic conjunctivitis
Diagnosis of allergic conjunctivitis generally is made by taking a thorough history and by
careful clinical observation.
Important features of history include a personal or family history of atopic disease, such as
allergic rhinitis, bronchial asthma, and/or atopic dermatitis. Perhaps the most important
feature in the clinical history is the symptom of itching. Without itching, the diagnosis of
allergic conjunctivitis is suspect.
Vernal keratoconjunctivitis
As with other allergic or type I hypersensitivity disorders, itching is the most important and
most common symptom.
Other commonly reported symptoms are photophobia, foreign body sensation, tearing, and
blepharospasm.
Ocular signs of VKC commonly are seen in the cornea and conjunctiva. In contrast to AKC,
the eyelid skin usually is not involved.
Atopic keratoconjunctivitis
In contrast to the symptoms of VKC, the symptoms in AKC are perennial. However, there
may be seasonal variation with worsening symptoms during winter months.
The single most common symptom is bilateral itching of the eyelids, but watery discharge,
redness, photophobia, and pain may be associated.
Giant papillary conjunctivitis
Primary symptoms in GPC are ocular itching with a mucoid or ropy discharge, very similar to
that seen in VKC.
Another symptom may be a persistent foreign body sensation when using contact lenses,
resulting in an inability to wear contact lenses for the desired length of time.
Physical
Seasonal and perennial allergic conjunctivitis
Classic signs of allergic conjunctivitis include injection of conjunctival vessels as well as
varying degrees of chemosis (conjunctival edema) and eyelid edema.
The conjunctiva often has a milky appearance due to obscuration of superficial blood vessels
by edema within the substantia propria of the conjunctiva. Edema is generally believed to be
the direct result of increased vascular permeability caused by release of histamine fromconjunctival mast cells.
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Vernal keratoconjunctivitis
VKC may be subdivided into 2 varieties, as follows: palpebral and limbal. The classic
conjunctival sign in palpebral VKC is the presence of giant papillae. They most commonly
occur on the superior tarsal conjunctiva; usually, the inferior tarsal conjunctiva is unaffected.
Giant papillae assume a flattop appearance, which often is described as "cobblestonepapillae." In severe cases, large papillae may cause mechanical ptosis.
A ropy mucous discharge may be present, which commonly is associated with tarsal papillae.
Large numbers of eosinophils are present in the discharge.
The limbal form of VKC commonly occurs in dark-skinned individuals, such as those from
Africa or India. As the name implies, papillae tend to occur at the limbus and have a thick
gelatinous appearance. They commonly are associated with multiple white spots (Horner-
Trantas dots), which are collections of degenerated epithelial cells and eosinophils. Horner-
Trantas dots are transient, with each appearance rarely lasting more than 1 week.
While corneal vascularization is rare, the cornea may be affected in a variety of ways.
Punctate epithelial keratopathy (PEK) may be due to the toxic effect of inflammatory
mediators released from the conjunctiva and may be a precursor of the characteristic shield
ulcer, which is pathognomonic of VKC. As the areas of PEK coalesce, they may result in
frank epithelial erosion resulting in shield ulcer, which is typically shallow with white
irregular epithelial borders. Although the pathogenesis of shield ulcer is not well understood,
a major factor in promoting development may be chronic mechanical irritation from the giant
tarsal papillae. Some evidence suggests that the major basic protein released from eosinophils
may promote ulceration.
Another type of corneal involvement is vernal pseudogerontoxon, which is a degenerative
lesion in the peripheral cornea resembling corneal arcus. Keratoconus may be seen in chronic
cases, which may be associated with chronic eye rubbing.
Atopic keratoconjunctivitis
AKC may affect eyelid skin and lid margin, conjunctiva, cornea, and lens. Skin of the eyelids
may exhibit eczematoid dermatitis with dry, scaly, and inflamed skin. Lid margins may show
meibomian gland dysfunction and keratinization. Staphylococcal colonization of eyelid
margins is very common and may result in blepharitis. Conjunctiva may show chemosis and
typically a papillary reaction, which is more prominent in the inferior tarsal conjunctiva, incontrast to that seen in vernal keratoconjunctivitis.
Hyperplasia of limbal regions may result in a gelatinous thickening, similar to the limbal
variant of VKC, and Horner-Trantas dots also may be present, although rarely. Fibrosis or
scarring of the conjunctiva may result in a shortened fornix or symblepharon formation with
chronic inflammation. Corneal involvement ranges from punctate epithelial keratopathy early
in the course of the disease, to neovascularization, stromal scarring, and possibly ulceration.
There is a strong association between herpes simplex viral keratitis and AKC.
Another corneal finding, which may be associated with AKC, is keratoconus, which may
stem from chronic eye rubbing. Characteristic lenticular changes in AKC include anterior orposterior subcapsular cataract formation. Lens opacities are usually bilateral and present in
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the second decade of life but progress very slowly. There may be an association with the
long-term use of topical corticosteroids. Note that there is an increased incidence of retinal
detachment following surgical removal of cataracts in patients with atopic dermatitis; the
exact mechanism is unknown.
Table. Major Differentiating Factors Between VKC and AKC
Opentable in new window
[CLOSE WINDOW]
Table
Characteristics VKC AKC
Age at onset Generally presents at a younger age -
Sex Males are affected preferentially. No sex predilection
Seasonal variation Typically occurs during spring months Generally perennial
Discharge Thick mucoid discharge Watery and clear discharge
Conjunctival scarring - Higher incidence of
conjunctival scarring
Horner-Trantas dots Horner-Trantas dots and shield ulcers
are commonly seen.
Presence of Horner-Trantas
dots is rare.
Corneal neovascularization Not present Tends to develop deep
corneal neovascularization
Presence of eosinophils in
conjunctival scraping
Conjunctival scraping reveals
eosinophils to a greater degree in VKC
than in AKC.
Presence of eosinophils is less
likely.
Characteristics VKC AKC
Age at onset Generally presents at a younger age -
Sex Males are affected preferentially. No sex predilection
Seasonal variation Typically occurs during spring months Generally perennial
Discharge Thick mucoid discharge Watery and clear discharge
Conjunctival scarring - Higher incidence of
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conjunctival scarring
Horner-Trantas dots Horner-Trantas dots and shield ulcers
are commonly seen.
Presence of Horner-Trantas
dots is rare.
Corneal neovascularization Not present Tends to develop deep
corneal neovascularization
Presence of eosinophils in
conjunctival scraping
Conjunctival scraping reveals
eosinophils to a greater degree in VKC
than in AKC.
Presence of eosinophils is less
likely.
Giant papillary conjunctivitis
Examination of superior tarsal conjunctiva reveals the presence of large cobblestone papillae,which are generally 0.3 mm or greater in diameter and, in severe cases, may cause
mechanical ptosis of the upper lid.
In his original description of GPC in 1977, Allansmith described 3 zones of superior tarsal
conjunctiva.2
Zone 1 is located closest to the fornix and is the most inferior portion of the
tarsal conjunctiva seen when the upper eyelid is everted. Zone 3 is located closest to the
eyelid margin. Zone 2 is located between zone 1 and zone 3.
Papillae typically associated with soft contact lensrelated GPC initially appear in zone 1 and
progress toward zone 3, while those associated with rigid gas permeable contact lenses
exhibit a reverse pattern, with zone 3 affected first. GPC associated with a localized irritant,such as an exposed suture or a filtering bleb, is typically localized to the area overlying these
inciting lesions.
Another clinical sign of GPC may be chronic bulbar conjunctival injection and inflammation
due to prolonged and persistent use of contact lenses.