Allergic conjunctivitis: Clinical manifestations and diagnosis

INTRODUCTION — The most prevalent forms of allergic conjunctivitis are acute allergic conjunctivitis, which develops upon episodic exposure to an allergen, as well as seasonal and perennial allergic conjunctivitis. These are relatively benign ocular diseases that cause significant suffering and use of health care resources, although they typically do not threaten vision.

The clinical manifestations, epidemiology, pathogenesis, diagnosis, and differential diagnosis of seasonal and perennial allergic conjunctivitis are reviewed here. The management of these disorders is reviewed separately. (See "Allergic conjunctivitis: Management".)

An overview of conjunctivitis and discussions of other specific types of atopic conjunctivitis are presented elsewhere. (See "Conjunctivitis" and "Vernal keratoconjunctivitis" and "Atopic keratoconjunctivitis" and "Giant papillary conjunctivitis".)

EPIDEMIOLOGY — Ocular allergy is estimated to affect at least 20 percent of the population on an annual basis, and the incidence is increasing [1-4]. It is predominantly a disease of young adults, with an average age of onset of 20 years. Symptoms tend to decrease with age, but older adults can continue to have severe symptoms.

It is possible to develop allergic conjunctivitis for the first time as an older adult, although this is not typical. The patient should be questioned about environmental changes (eg, a newly acquired pet or a new living arrangement) and symptoms earlier in life. In older adults, dry eye disease, blepharitis, and toxic conjunctivitis can mimic allergic conjunctivitis. (See 'Differential diagnosis' below.)

Allergic conjunctivitis is associated with other allergic diseases, particularly allergic rhinitis [5]. Asthma and atopic dermatitis are other common comorbidities.

PATHOPHYSIOLOGY — Allergic conjunctivitis results from allergens contacting the surface of the eye in a person who is allergic to that specific allergen. It is a classic type I immunoglobulin E (IgE)-mediated hypersensitivity, which is similar to the pathophysiology of other atopic diseases.

Analysis of conjunctival scrapings reveals two phases of the allergic response, similar to the early and late phases of cutaneous, nasal, and pulmonary responses to allergen.

●The immediate response to allergens is mediated predominantly by mast cells, which are present in high concentrations in the conjunctival epithelium and increase further in patients with allergic conjunctivitis [6]. Mast cells become activated when allergens cross-link allergen-specific IgE on the cell surface, and chemical mediators are released by exocytosis. Histamine is the main mediator of the early response. It causes vasodilatation, vasopermeability, and itching. Both H1 receptors and H2 receptors play a role in ocular allergy. Elevated levels of histamine in tears have been measured in patients with seasonal allergic conjunctivitis (SAC) [7].

●The late phase of the allergic reaction begins with the influx of other inflammatory cells, which are attracted by the cytokines and chemokines released by mast cells in the immediate phase. Eosinophils, basophils, and neutrophils appear 6 to 10 hours after allergen challenge, followed by lymphocytes and monocytes [8-12]. Eosinophils produce and release leukotriene C₄, eosinophilic peroxidase, eosinophilic cationic protein, and histamine into the tear fluid [8]. The activity of these cells creates continued inflammation. More detailed discussions of the cellular and molecular mechanisms of atopy are found elsewhere. (See "The biology of IgE" and "Pathogenesis of allergic rhinitis (rhinosinusitis)".)

Eosinophils can be demonstrated in conjunctival scrapings in up to 80 percent of patients with acute allergic conjunctivitis [13].

Elevated levels of IgE in tear film are characteristic of allergic conjunctivitis [14]. Serum total IgE may also be elevated in such patients [15]. Histamine and tryptase levels can be measured in tears following conjunctival allergen challenge.

TYPES OF ALLERGIC CONJUNCTIVITIS — Allergic conjunctivitis can be subdivided into three specific conditions:

●Acute allergic conjunctivitis

●Seasonal allergic conjunctivitis (SAC)

●Perennial allergic conjunctivitis (PAC)

Acute allergic conjunctivitis — Acute allergic conjunctivitis is a sudden-onset hypersensitivity reaction that is caused by environmental exposure, usually to a known allergen, such as cat dander [16]. Symptoms can develop rapidly (ie, as quickly as 30 minutes). Once exposure to the allergen has ended, symptoms generally resolve within 24 hours. Thus, the acute form of allergic conjunctivitis is characterized by intense episodes of itching, hyperemia, tearing, chemosis, and eyelid edema [17].

Seasonal allergic conjunctivitis — Seasonal allergic conjunctivitis (SAC) goes by several other names, including allergic conjunctivitis, hay fever type conjunctivitis, or allergic rhinoconjunctivitis (when nasal symptoms are also present). It is frequently associated with rhinitis and is attributable to outdoor airborne pollens [5]. SAC typically has a less dramatic onset compared with acute allergic conjunctivitis, developing over days to weeks, and a predictable course that corresponds to one or more specific pollen seasons.

Seasonal allergens include tree pollens in the spring, grass pollens in the summer, and weed pollens in the late summer and fall, although there is some variation based upon geographic location (figure 1). (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)

Perennial allergic conjunctivitis — Perennial allergic conjunctivitis (PAC) is a mild, chronic, waxing and waning allergic conjunctivitis related to environmental exposure to year-round, usually indoor allergens, such as dust mites, animal danders, and molds.

CLINICAL MANIFESTATIONS

Symptoms — Ocular itching is a prominent symptom, such that the absence of itching should prompt consideration of other disorders. Patients may report burning. Redness is also nearly universal. Eyelid edema is common. Symptoms are usually bilateral. However, one eye can be affected more than the other. Patients may report some mild crusting upon awakening, but the discharge is characteristically watery and nonpurulent. Mild photophobia may be present.

Eye pain is not characteristic of allergic conjunctivitis. Ocular pain should raise concern for more serious disorders, such as angle-closure glaucoma, scleritis, or episcleritis. (See 'Differential diagnosis' below.)

Clinical history — Patients with allergic conjunctivitis often have a history of atopy, seasonal allergy, or specific allergy (eg, to cats or dust mites). Accordingly, they should be asked about similar symptoms in the past and the presumed triggers for the symptoms. (See 'Types of allergic conjunctivitis' above.)

Physical examination — Physical findings include redness (hyperemia), tearing or clear watery discharge, burning, and conjunctival edema (chemosis) (picture 1). In extreme instances, the edematous conjunctiva can extend forward, beyond the lid margins. Eyelid edema is also common.

Allergic eye disease primarily affects the conjunctiva. The redness or injection in allergic conjunctivitis should be diffuse, involving the bulbar (globe) conjunctiva, as well as the palpebral or tarsal conjunctiva (the mucus membrane on the inner surface of the lids).

●Another diagnosis such as foreign body, pterygium, scleritis, or episcleritis should be considered if the conjunctival injection is localized rather than diffuse. (See "Pterygium" and "Episcleritis".)

●Redness that is most intense around the iris (a ciliary flush pattern) should prompt consideration of serious conditions (iritis, acute angle closure), and patients with this finding should be referred to an ophthalmologist. (See "The red eye: Evaluation and management".)

Conjunctival papillae may be detected if the underside of the eyelid is examined by eversion. Video instructions for everting the upper eyelid are found separately. (See "Corneal abrasions and corneal foreign bodies: Clinical manifestations and diagnosis", section on 'Eyelid eversion'.)

Papillae are structures that may form in response to inflammation and range in size from tiny red dots to polygonal elevations 1 mm or more in diameter. Each papilla has a vascular core of fine, dilated telangiectatic blood vessels. They are usually found on the upper tarsal conjunctiva.

Conjunctival follicles are less commonly seen in allergic conjunctivitis, although they may be present in chronic disease. Follicles are more common in longstanding, T cell-mediated conditions. They are lymphoid germinal centers that appear as smooth, rounded nodules beneath the conjunctival epithelium. The upper surface is avascular, and the base is surrounded by fine vessels. Follicles are most common in the lower fornix, at the margin between bulbar and palpebral conjunctiva.

Cobblestoning and giant papillae should not be present (picture 2). These findings suggest more severe forms of ocular allergy (ie, vernal keratoconjunctivitis, atopic keratoconjunctivitis, or giant papillary keratoconjunctivitis). (See 'Differential diagnosis' below.)

Infraorbital edema and darkening may be present due to subcutaneous venodilation, findings that are sometimes referred to as "allergic shiners." Patients with longstanding symptoms may show accentuated transverse lines or folds below the lower lids (Dennie-Morgan lines).

In patients with concomitant symptoms of allergic rhinitis, examination of the nasal mucosa can show several characteristic findings:

●A pale bluish hue or pallor of the nasal mucosa

●Edema of the nasal turbinates

●Clear rhinorrhea may be visible in the nasal cavity

If the nasal passages are obstructed, clear rhinorrhea may be visible dripping down the posterior pharynx.

Finally, examination of the tympanic membranes in patients with significant nasal mucosal swelling and eustachian tube dysfunction may show accumulation of clear serous fluid. (See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis", section on 'Physical findings'.)

DIAGNOSIS — The diagnosis of allergic conjunctivitis is made clinically based upon a suggestive clinical history and consistent signs and symptoms. (See 'Clinical manifestations' above.)

Laboratory tests are generally not needed in order to initiate therapy. However, evaluation for allergy to specific substances should be pursued if the patient does not respond as expected to therapy. (See 'Referral' below.)

Referral — Referral to an ophthalmologist should be considered in situations where the diagnosis is unclear.

Referral to an allergy specialist should be considered if it is unclear to what allergen the patient is likely reactive, since identification of the culprit allergen(s) will facilitate avoidance. This is discussed elsewhere. (See "Allergic conjunctivitis: Management", section on 'Referral'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of these findings includes infectious conjunctivitis, blepharitis, dry eye, and more severe forms of allergic eye disease. There are no universally specific signs or symptoms that differentiate these conditions in all cases, and more than one condition can coexist in the same patient. However, there are several features that can help distinguish allergic conjunctivitis from other disorders:

●More severe forms of allergic ocular disease – More severe disorders that have an allergic etiology include vernal conjunctivitis, giant papillary keratoconjunctivitis, and atopic keratoconjunctivitis.

•Vernal keratoconjunctivitis is a more severe disorder that usually affects boys living in warm, dry, subtropical climates. It presents with intense ocular itching, stringy mucoid discharge, and cobblestoning. Like allergic conjunctivitis, it can vary with the seasons. (See "Vernal keratoconjunctivitis".)

•Giant papillary conjunctivitis is a form of hypersensitivity reaction to contact lenses, ocular sutures, or ocular implants. It presents with itching and a sensation of grittiness or foreign body. Giant papillae are seen in this disorder but not in allergic conjunctivitis. (See "Giant papillary conjunctivitis".)

•Atopic keratoconjunctivitis is a chronic and severe disorder that can affect the eyelid, conjunctiva, and cornea. Patients are typically adults between 30 and 50 years of age with atopic dermatitis. The most common symptom is severe itching, sometimes with seasonal variability. Eyelids can become thickened and lichenified. (See "Atopic keratoconjunctivitis".)

●Viral infection – Allergic conjunctivitis is often accompanied by significant ocular itching, whereas this is not very common in infection. Infection is usually unilateral, although it can be bilateral, whereas allergic conjunctivitis is usually bilateral. Bacterial infections produce some degree of purulent discharge and are unlikely to be mistaken for allergic conjunctivitis, but viral infections can present more subtly. (See "Conjunctivitis", section on 'Viral conjunctivitis'.)

●Dry eye – Allergic conjunctivitis principally affects the conjunctiva, whereas the principal target tissue in dry eye is the cornea. Corneal involvement is characterized by vital dye uptake. This test can readily be performed by an ophthalmologist. (See "Dry eye disease".)

●Blepharitis – Blepharitis principally affects the eyelids or lid margins, whereas allergic conjunctivitis affects the conjunctiva. Eyelid involvement is characterized by vascularization of lids, changes in meibomian glands, and presence of lid dander. (See "Blepharitis".)

●Toxic conjunctivitis – Toxic conjunctivitis is an irritant reaction to ocular medications, and affected patients have typically been using ocular medications for extended periods of time. The most commonly implicated agents are preservatives in eye medications, contact lens solutions, and artificial tears. Conjunctival injection, chemosis, mucus discharge, papillary or follicular reaction of the palpebral conjunctiva, and itching are common. The eyelids can become swollen, thickened, and excoriated, findings which are uncommon in allergic conjunctivitis. (See "Toxic conjunctivitis".)

●Ocular rosacea – Ocular rosacea commonly presents with burning, itching, foreign body sensation, dryness, tearing, or photophobia. Physical findings include conjunctival hyperemia, blepharitis, and lid margin telangiectasias. Often, the severity of these symptoms is greater than would be expected, based upon the objective clinical findings.

●Keratitis – Allergic conjunctivitis is often bilateral, affecting the cornea. Keratitis, which can be sterile (eg, due to contact lens wear) or infectious, typically presents unilaterally with corneal involvement and may be associated with vision loss. The presence of corneal infiltrates distinguishes this condition from allergic conjunctivitis, although corneal involvement may be subtle. (See "Complications of contact lenses" and "Herpes simplex keratitis".)

●Angle-closure glaucoma – Allergic conjunctivitis is often bilateral and not associated with vision loss or pain. Angle-closure glaucoma is most always associated with severe unilateral pain and vision loss, due to corneal edema. However, angle-closure glaucoma can be mistaken for allergic conjunctivitis, since both disorders may cause redness. (See "Angle-closure glaucoma".)

●Episcleritis/scleritis – Allergic conjunctivitis is generally not associated with pain, while both scleritis and episcleritis are associated with significant pain, although the pain of episcleritis may be delayed. (See "Episcleritis" and "Clinical manifestations and diagnosis of scleritis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Allergic eye disease".)

SUMMARY

●Seasonal and perennial allergic conjunctivitis are estimated to affect at least 20 percent of the population on an annual basis, and the incidence is increasing. (See 'Epidemiology' above.)

●Allergic conjunctivitis results from allergens contacting the surface of the eye in a person who is allergic to that specific allergen and is a type I immunoglobulin E (IgE)-mediated hypersensitivity reaction. (See 'Pathophysiology' above.)

●The signs and symptoms of allergic conjunctivitis include ocular itching, redness (hyperemia), tearing, watery discharge, burning, and conjunctival edema (chemosis) (picture 1). Eyelid edema is also common. Symptoms are usually bilateral, although one eye can be affected more than the other. Many patients have concomitant symptoms and physical findings of allergic rhinitis. (See 'Clinical manifestations' above.)

●Allergic conjunctivitis can be subdivided into acute allergic conjunctivitis, seasonal allergic conjunctivitis (SAC), and perennial allergic conjunctivitis (PAC). (See 'Types of allergic conjunctivitis' above.)

•Acute allergic conjunctivitis is a sudden-onset (minutes to hours) hypersensitivity reaction caused by an isolated environmental exposure and resolves promptly with removal of the allergen.

•SAC typically has a more gradual onset (days to weeks) and a course that corresponds to one or more specific pollen seasons (figure 1).

•PAC is a mild, chronic conjunctivitis related to environmental exposure to year-round, usually indoor, allergens.

●The diagnosis of allergic conjunctivitis is made clinically based upon a suggestive clinical history and consistent signs and symptoms. The presence of itching is particularly helpful in distinguishing allergic conjunctivitis from other conditions. (See 'Diagnosis' above.)

●The differential diagnosis of allergic conjunctivitis includes dry eye, more severe forms of ocular allergy (vernal and giant papillary conjunctivitis, atopic keratoconjunctivitis), blepharitis, toxic conjunctivitis, and several other ocular disorders. (See 'Differential diagnosis' above.)