Ophthalmology – Phlyctenular Keratoconjunctivitis

Basics

Description

Phlyctenular keratoconjunctivitis (PKC) is an inflammatory disorder of the conjunctiva and/or cornea caused by a delayed type IV hypersensitivity reaction to microbial antigens.

It typically presents as a small:

• White
• Yellow-white
• Pink-white

elevated inflammatory nodule near the limbus.

It is seen most commonly in:

• Children
• Adolescents
• Young adults

The disorder may involve:

• Conjunctiva alone
• Cornea
• Both conjunctiva and cornea

Corneal involvement is usually more symptomatic and carries the greatest risk of visual sequelae.

Pathophysiology

PKC is not usually an active infection of the cornea.

Instead:

Microbial antigen exposure → delayed hypersensitivity reaction → localized lymphocytic inflammation at the limbus/cornea

The inflammatory lesion is called a:

Phlyctenule

Etiology

The most common antigenic stimulus in many modern clinical settings is:

Staphylococcal blepharitis

Other recognized triggers include:

• Mycobacterium tuberculosis
• Chlamydial infection
• Rosacea-associated lid disease
• Less commonly other bacterial, fungal, or parasitic antigens

The relative importance of tuberculosis depends strongly on:

• Geographic region
• Local prevalence
• Individual exposure risk

Associated Conditions

The strongest common association is:

Chronic blepharitis / meibomian gland dysfunction

Other associations include:

• Ocular rosacea
• Recurrent styes or chalazia
• Tuberculosis in endemic or high-risk settings
• Chronic lid colonization with Staphylococcus

Epidemiology

PKC occurs most often in younger patients.

It may be:

• Unilateral
• Bilateral
• Recurrent

Historically a female predominance has been reported, but this is not essential for diagnosis.

Risk Factors

Important risk factors include:

• Chronic blepharitis
• Meibomian gland dysfunction
• Poor lid hygiene
• Ocular rosacea
• Tuberculosis exposure
• Recurrent bacterial lid disease

History

Symptoms depend on whether the lesion is primarily conjunctival or corneal.

Conjunctival Phlyctenule

May cause:

• Mild redness
• Foreign-body sensation
• Tearing
• Irritation

Symptoms may be relatively mild.

Corneal Phlyctenule

Usually causes more prominent:

• Photophobia
• Pain
• Tearing
• Blepharospasm
• Foreign-body sensation
• Redness
• Reduced vision if central involvement occurs

Physical Examination

Conjunctival Phlyctenule

Typical appearance:

• Small
• Round
• Elevated
• Yellow-white or pink-white

nodule close to the:

Limbus

It may be surrounded by:

• Conjunctival injection
• Local vascular congestion

Corneal Phlyctenule

A corneal lesion often begins near the:

Limbus

and may migrate centrally.

Findings may include:

• Elevated peripheral corneal infiltrate
• Overlying epithelial defect
• Focal stromal inflammation
• Associated superficial vascularization

Leash of Vessels

A classic finding is:

A superficial vascular leash extending from the limbus toward the phlyctenule

This may become particularly evident in recurrent or migrating corneal disease.

Migrating Phlyctenule

A corneal phlyctenule may:

• Begin at the limbus
• Progress centrally
• Leave superficial neovascularization behind

Repeated episodes can produce:

• Corneal scar
• Lipid deposition
• Irregular astigmatism

Corneal Ulceration

The overlying epithelium may break down, producing:

• Small epithelial defect
• Shallow peripheral ulcer

Severe disease can rarely progress to:

• Stromal thinning
• Significant scarring

Blepharitis Findings

Look carefully for:

• Lid-margin erythema
• Collarettes
• Crusting
• Meibomian gland plugging
• Telangiectasia
• Recurrent chalazia

because treatment of the lid disease is critical for preventing recurrence.

Visual Acuity

Vision is usually preserved when lesions remain peripheral.

Reduced vision may result from:

• Central corneal involvement
• Scarring
• Irregular astigmatism
• Significant photophobia

Diagnosis

Diagnosis is primarily:

Clinical

based on:

• Characteristic limbal/corneal nodule
• Associated blepharitis
• Typical symptoms

Routine laboratory testing is unnecessary in straightforward staphylococcal-associated disease.

Tuberculosis Evaluation

Investigate for TB when there are:

• Epidemiologic risk factors
• Known exposure
• Travel or residence in endemic areas
• Recurrent or severe PKC without obvious lid disease
• Systemic symptoms

Testing may include:

• IGRA
• Tuberculin skin test
• Chest imaging when indicated

IGRA is often preferred in BCG-vaccinated patients.

Important Modern Point

TB testing should be:

Risk-based rather than routine in every patient

unless local prevalence or clinical circumstances justify universal screening.

Corneal Cultures

Culture or scraping is appropriate if the lesion appears more consistent with:

Infectious keratitis

especially when there is:

• Large epithelial defect
• Dense stromal infiltrate
• Purulent discharge
• Hypopyon
• Rapid progression

Histopathology

Phlyctenules contain predominantly:

• Lymphocytes
• Histiocytes
• Plasma cells

reflecting a delayed hypersensitivity inflammatory response.

Differential Diagnosis

Important differentials include:

• Staphylococcal marginal keratitis
• Microbial keratitis
• Herpes simplex keratitis
• Nodular episcleritis
• Ocular rosacea
• Inflamed pinguecula
• Peripheral ulcerative keratitis
• Contact-lens-related infiltrates

PKC vs Staphylococcal Marginal Keratitis

Both may be associated with blepharitis.

PKC

• Focal limbal nodule
• May migrate centrally
• May develop vascular leash
• Common in younger patients

Marginal Keratitis

• Peripheral stromal infiltrates
• Often multiple
• Typically separated from limbus by a clear zone
• Strong association with staphylococcal lid disease

PKC vs Microbial Keratitis

Features favoring microbial keratitis include:

• Larger epithelial defect
• Dense focal stromal infiltrate
• Purulent discharge
• Significant anterior chamber reaction
• Hypopyon
• Rapid progression

If infection is possible:

Do not treat with corticosteroid alone.

PKC vs HSV Keratitis

HSV may show:

• Dendritic epithelial ulcer
• Reduced corneal sensation
• Recurrent unilateral disease

Corneal HSV should be excluded before using topical steroid if the diagnosis is uncertain.

Treatment Principles

Treatment has two major goals:

1. Suppress the hypersensitivity inflammation
2. Treat the underlying antigenic source, especially blepharitis

Lid Hygiene

Management of blepharitis is essential.

Measures include:

• Warm compresses
• Lid hygiene
• Gentle lid-margin cleaning
• Artificial tears as needed

This reduces:

• Bacterial antigen load
• Recurrence risk

Topical Antibiotic

If significant bacterial lid disease is present, options may include:

• Erythromycin ophthalmic ointment
• Bacitracin ophthalmic ointment

applied to the lid margins.

These treat the associated blepharitis rather than the immune lesion itself.

Topical Corticosteroids

For symptomatic conjunctival or corneal PKC:

Topical corticosteroid is the main anti-inflammatory treatment

provided infectious keratitis has been excluded.

Options may include:

• Prednisolone acetate
• Loteprednol
• Fluorometholone

depending on severity.

Steroid Response

Phlyctenular inflammation often improves rapidly with corticosteroid therapy.

Treatment is usually:

• Short term
• Tapered according to clinical response

Avoid abrupt withdrawal in recurrent or severe disease.

Steroid Monitoring

With repeated or prolonged topical steroid use, monitor for:

• Ocular hypertension
• Glaucoma
• Cataract
• Secondary infection

Antibiotic–Steroid Combination

A combination preparation may be reasonable when there is:

• Significant concurrent blepharitis
• Epithelial breakdown
• Concern for secondary bacterial colonization

However, combination therapy is not mandatory in every case.

Oral Tetracycline-Class Therapy

For recurrent PKC associated with:

• Ocular rosacea
• Severe meibomian gland dysfunction
• Chronic blepharitis

an oral tetracycline-class drug may be useful because of:

• Anti-inflammatory effects
• Reduction in bacterial lipase activity

Doxycycline

In adults and appropriate older adolescents, doxycycline is generally preferred over older high-dose tetracycline regimens.

It can help control:

• Ocular rosacea
• MGD
• Recurrent phlyctenulosis

Pediatric Considerations

Avoid tetracycline-class drugs in young children when age-related safety concerns apply.

Alternatives for associated lid disease may include:

• Oral azithromycin
• Erythromycin

when systemic therapy is necessary.

Exact therapy should be individualized by age and clinical context.

Pregnancy Considerations

Tetracyclines are generally avoided during:

• Pregnancy

Alternative antibiotics should be selected when needed.

Tuberculosis-Associated PKC

If TB is identified:

Treat the tuberculosis itself

with appropriate multidrug therapy coordinated with:

• Infectious disease
• Pulmonology
• Public-health services

Topical steroids may still be used for ocular inflammation when appropriate, but they do not replace systemic TB therapy.

Ocular Rosacea

In patients with rosacea-associated disease, management may include:

• Lid hygiene
• Warm compresses
• Artificial tears
• Topical anti-inflammatory therapy
• Oral doxycycline or macrolide in selected patients

Recurrent Disease

Frequent recurrences should prompt reassessment for:

• Poorly controlled blepharitis
• Ocular rosacea
• Tuberculosis exposure
• Incorrect diagnosis
• Steroid dependence

Follow-Up

Follow-up depends on severity.

Mild conjunctival disease may be reviewed within:

• 1–2 weeks

Corneal disease may require earlier review, particularly if there is:

• Epithelial defect
• Stromal thinning
• Central progression

Monitoring

Monitor for:

• Resolution of infiltrate
• Epithelial healing
• Corneal vascularization
• Stromal thinning
• Scar formation
• IOP during steroid treatment

Prognosis

Overall prognosis is:

Good

Most lesions resolve with appropriate treatment.

Visual prognosis is excellent when:

• Disease remains peripheral
• Recurrences are controlled
• Corneal scarring is avoided

Poorer Visual Outcome

Vision may be reduced by:

• Central corneal scar
• Irregular astigmatism
• Corneal neovascularization
• Recurrent central lesions

Complications

Possible complications include:

• Corneal scarring
• Corneal neovascularization
• Irregular astigmatism
• Reduced visual acuity
• Recurrent keratitis
• Rare stromal thinning

Steroid-related complications include:

• Ocular hypertension
• Glaucoma
• Cataract
• Secondary infection

Ophthalmology Pearls

• Phlyctenular keratoconjunctivitis is a type IV delayed hypersensitivity reaction to microbial antigens.
• In many modern settings, the most common trigger is staphylococcal blepharitis, not active corneal infection.
• A phlyctenule is a small yellow-white inflammatory nodule near the limbus.
• Corneal involvement causes much more pain and photophobia than isolated conjunctival disease.
• A corneal phlyctenule may migrate centrally with a characteristic leash of superficial vessels.
• Always look for and treat blepharitis or meibomian gland dysfunction, because lid disease drives recurrence.
• Topical corticosteroids are the main treatment for significant inflammation once infectious keratitis has been excluded.
• Antibiotic ointment is directed mainly at associated lid-margin bacterial disease.
• Recurrent disease should prompt consideration of ocular rosacea and tuberculosis risk.
• TB evaluation should be risk-based, using IGRA/skin testing and chest imaging when indicated.
• Doxycycline can be useful in older patients with recurrent blepharitis/rosacea-associated disease; use age-appropriate alternatives in children.
• Severe or recurrent corneal disease can leave permanent scar, neovascularization, irregular astigmatism, and reduced vision.