What are the differential diagnoses for unilateral eyelid swelling?

Differential Diagnosis for Unilateral Eyelid Swelling

Viral conjunctivitis, particularly adenoviral, is the most common cause of unilateral eyelid swelling without trauma or vision impairment, presenting with eyelid edema, erythema, watery discharge, and bulbar conjunctival injection that often progresses to sequential bilateral involvement within days. 1

Immediate Red Flag Assessment

Before considering benign etiologies, you must rule out vision-threatening conditions:

• Check visual acuity immediately – any decrease requires same-day ophthalmology referral 1, 2
• Perform fluorescein staining in every case – this is mandatory even when vision appears normal to detect corneal involvement 1, 2
• Assess for proptosis or painful/restricted extraocular movements – these indicate orbital cellulitis requiring emergent hospitalization and IV antibiotics 1, 2
• Examine for eyelid vesicles or dermatomal rash – suggests HSV or VZV which can progress to corneal perforation 1, 2
• Check for fever or systemic toxicity – indicates possible orbital cellulitis 1

Most Common Infectious Causes

Viral Conjunctivitis (Most Frequent)

Adenoviral conjunctivitis presents with:

• Unilateral eyelid swelling and erythema that often becomes sequentially bilateral 3, 1
• Watery discharge with bulbar conjunctival injection 3, 1
• Follicular reaction of inferior tarsal conjunctiva 3
• Chemosis and preauricular lymphadenopathy 3
• Recent exposure to infected individuals or concurrent upper respiratory infection 3, 1
• Self-limited course with improvement within 5-14 days 3, 1

Herpes Simplex Virus (HSV)

HSV conjunctivitis typically presents with:

• Usually unilateral presentation 3, 2
• Bulbar conjunctival injection with watery discharge 3
• Mild follicular reaction and palpable preauricular lymphadenopathy 3, 2
• Can progress to epithelial keratitis, stromal keratitis, corneal scarring, and perforation if untreated 3, 2
• Triggered by stress, febrile illness, UV exposure, surgery, or trauma 3

Varicella Zoster Virus (VZV)

VZV infection presents with:

• Usually unilateral with vesicular dermatomal rash or ulceration of eyelids 3, 2
• Conjunctival injection, watery discharge, and follicular reaction 3
• Can cause conjunctival scarring, cicatricial ectropion, late corneal anesthesia, and dry eye 3, 2
• Distinctive pleomorphic or nonexcavated pseudodendritic epithelial keratitis 3

Molluscum Contagiosum

Molluscum typically presents with:

• Typically unilateral with mild to severe follicular reaction 3, 2
• Punctate epithelial keratitis and possible corneal pannus if long-standing 3
• Distinctive single or multiple shiny, dome-shaped umbilicated lesions on eyelid skin or margin 3, 2
• More common in immunocompromised patients (HIV) 3

Bacterial Causes

Nongonococcal Bacterial Conjunctivitis

• Unilateral or bilateral presentation with bulbar conjunctival injection 3
• Purulent or mucopurulent discharge 3, 2
• Generally self-limited in adults but may cause corneal infection 3

Gonococcal Conjunctivitis

Gonococcal infection presents with:

• Marked eyelid edema with marked bulbar conjunctival injection 3
• Marked purulent discharge and preauricular lymphadenopathy 3
• Critical finding: corneal infiltrate or ulcer (often begins superiorly) that may lead to perforation 3
• Associated with urethritis or pelvic inflammatory disease; consider sexual abuse in children 3

Preseptal Cellulitis

Preseptal cellulitis presents with:

• Eyelid erythema, edema, and tenderness 2, 4
• No proptosis, painful eye movements, or vision changes (distinguishes from orbital cellulitis) 2
• Requires high-dose amoxicillin-clavulanate with daily follow-up 1, 2

Parinaud Oculoglandular Syndrome

• Unilateral granulomatous follicular conjunctivitis 3
• Associated ipsilateral regional lymphadenopathy (preauricular and submandibular) 3
• Fever, eyelid swelling, conjunctival granulomas, and serous discharge 3
• Most commonly from cat scratch disease (Bartonella henselae) or tularemia 3

Malignancy Considerations

Sebaceous Carcinoma

Sebaceous carcinoma can masquerade as chronic unilateral blepharoconjunctivitis:

• Hard nodular, nonmobile mass of tarsal plate with yellowish discoloration 3
• May appear as subconjunctival, multilobulated yellow mass or resemble chalazion 3
• Biopsy indicated for: unifocal recurrent lesions, resistance to therapy, focal lash loss, chronic presentation unresponsive to treatment 2

Ocular Surface Squamous Neoplasia

• Conjunctival hyperemia with papillomatous or sessile nodules 3
• Associated with HPV and significant UV exposure 3
• May be mistreated as unresponsive blepharoconjunctivitis 3

Melanoma

• Painless, flat or nodular, brown or white-pink lesion on bulbar or palpebral conjunctiva 3
• Enlargement, blood vessels, or thickening often trigger presentation 3

Less Common Causes

• Chronic lymphedema: associated with acne rosacea, radiotherapy, or trauma; presents with persistent swelling >3 months 5
• Chlamydial conjunctivitis: follicular conjunctivitis with chemosis, papillary hypertrophy, and limbal follicles 3
• Pediculosis palpebrarum: follicular conjunctivitis with adult lice at eyelash base and nits adherent to lash shafts 2

Practical Diagnostic Algorithm

1. Rule out orbital cellulitis: check for proptosis, painful eye movements, vision loss, fever 1, 2
2. Perform fluorescein staining: mandatory in every case to detect corneal involvement 1, 2
3. Examine for vesicles or dermatomal rash: suggests HSV/VZV requiring urgent treatment 1, 2
4. Assess discharge character: watery (viral), purulent (bacterial), none (inflammatory/allergic) 1, 2
5. Check for umbilicated lesions on lid margins: indicates molluscum 1, 2
6. Obtain exposure history: infected contacts, new cosmetics, medications, systemic illness 1, 2
7. Consider biopsy if: chronic (>4-6 weeks), unresponsive to treatment, or asymmetric presentation 1

Initial Management Approach

For presumed viral conjunctivitis without red flags:

• Cool compresses for symptomatic relief 1, 2
• Mandatory follow-up in 3-4 days to assess for improvement 1, 2

Immediate ophthalmology referral required for:

• Any visual changes 1, 2
• Moderate to severe pain 1, 2
• Corneal involvement on fluorescein examination 1, 2
• Suspected HSV/VZV with vesicles 1, 2
• Any red flag features 1, 2

For suspected preseptal cellulitis:

• High-dose amoxicillin-clavulanate with daily follow-up until definite improvement 1, 2
• Hospitalization for IV antibiotics if no improvement in 24-48 hours or progressive infection 1, 2

Critical Pitfalls to Avoid

• Do not assume absence of drainage excludes infection – early viral conjunctivitis may have minimal watery discharge 2
• Do not skip fluorescein staining – corneal involvement may not be clinically apparent without staining 1
• Do not dismiss low-grade findings – unclear results such as low-grade eosinophilia should not be ignored 6
• Do not delay biopsy for chronic unresponsive cases – sebaceous carcinoma can masquerade as chronic blepharoconjunctivitis 2