eMedicine Specialties > Ophthalmology > Conjunctiva

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 Center
Contributor Information and Disclosures

Updated: Oct 16, 2009

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, which deposit in tissues and cause inflammation. Classic type III reaction systemically is the Arthus 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 known as 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), and giant 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 that trigger 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

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 atopic dermatitis.¹ Atopic 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 common irritant, 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

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 from conjunctival mast cells.
• 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 "cobblestone papillae." 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, in contrast 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 or posterior subcapsular cataract formation. Lens opacities are usually bilateral and present in 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.
• Major Differentiating Factors Between VKC and AKC

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• 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 lens–related 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.

Causes

See Pathophysiology.

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