What are the differential diagnoses for a patient presenting with unilateral erythema (redness) and tenderness around the eye?

Differential Diagnoses for Unilateral Erythema and Tenderness Around Eye

Viral conjunctivitis, particularly adenoviral, is the most common cause of unilateral eye erythema and tenderness without trauma, presenting with eyelid swelling, watery discharge, and bulbar conjunctival injection that typically self-resolves within 5-14 days. 1

Immediate Red Flag Assessment

Before considering benign diagnoses, urgent evaluation is mandatory for any patient with visual changes, moderate-to-severe pain (beyond irritation), corneal involvement on fluorescein staining, proptosis, painful extraocular movements, or fever, as these indicate vision-threatening conditions requiring same-day ophthalmology referral. 1 Unilateral redness with any red flag feature should prompt emergency ophthalmology consultation within 24 hours. 2

Fluorescein staining must be performed in every case, even when vision appears normal, to detect corneal involvement that may not be clinically apparent. 1

Most Likely Infectious Etiologies

Viral Conjunctivitis

• Adenoviral conjunctivitis presents with unilateral eyelid swelling and erythema, watery discharge, bulbar conjunctival injection, chemosis, and follicular reaction of the inferior tarsal conjunctiva. 2, 1
• Associated with recent exposure to infected individuals or concurrent upper respiratory infection. 2
• Self-limited course with improvement within 5-14 days without treatment, though may progress to sequential bilateral involvement. 2, 1
• Potential complications include subepithelial corneal infiltrates in epidemic keratoconjunctivitis. 2

Herpes Simplex Virus (HSV)

• Usually unilateral with bulbar conjunctival injection, watery discharge, mild follicular reaction, and palpable preauricular lymphadenopathy. 2
• Critical diagnostic clue: examine for vesicles, erosions, or crusting on eyelids, which signal herpetic infection requiring immediate antiviral therapy. 2, 3
• Can progress to epithelial keratitis, stromal keratitis, corneal scarring, perforation, and uveitis if untreated. 2
• Triggered by stress, febrile illness, ultraviolet exposure, surgery, or trauma. 2

Varicella Zoster Virus (VZV)

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

Molluscum Contagiosum

• Typically unilateral with mild to severe follicular reaction and punctate epithelial keratitis. 2
• Pathognomonic finding: single or multiple shiny, dome-shaped umbilicated lesions on eyelid skin or margin. 2, 1
• More common in immunocompromised patients (HIV) with multiple large lesions. 2

Bacterial Conjunctivitis

• Nongonococcal: unilateral or bilateral with bulbar conjunctival injection and purulent or mucopurulent discharge; generally self-limited in adults. 2
• Gonococcal: marked eyelid edema, marked bulbar injection, marked purulent discharge, and preauricular lymphadenopathy with rapid progression. 2
• Gonococcal infection can cause corneal infiltrate or ulcer (often beginning superiorly) leading to perforation; requires urgent treatment. 2

Non-Infectious Inflammatory Causes

Episcleritis

• Acute onset redness with lacrimation and photophobia, more common in women aged 40-50 years. 4
• Key differentiating feature: minimal to no pain or tenderness; significant eye pain should raise concern for scleritis requiring ophthalmology referral. 4
• Most cases idiopathic; resolves within 1-3 months with conservative management. 4

Contact Dermatitis/Atopic Dermatitis

• Eyelid erythema and edema with scaling, often bilateral but can be asymmetric. 3
• History of new cosmetics, medications, or known atopic disease. 3
• Responds to topical corticosteroids and removal of offending agent. 3

Blepharitis

• Chronic eyelid margin inflammation with erythema, scaling, and crusting. 3, 5
• Often bilateral but may present asymmetrically. 3
• Managed with eyelid hygiene and warm compresses. 3

Serious Conditions Requiring Urgent Evaluation

Preseptal vs. Orbital Cellulitis

• Preseptal cellulitis: eyelid erythema, edema, and tenderness without proptosis, painful eye movements, or vision changes. 3
• Orbital cellulitis: severe infection with proptosis, ophthalmoplegia, vision loss, and fever requiring emergent hospitalization and IV antibiotics. 6, 3
• Critical distinction: examine for proptosis, restricted/painful extraocular movements, and visual acuity changes. 6

Pediculosis Palpebrarum

• Unilateral or bilateral follicular conjunctivitis with adult lice at eyelash base and nits adherent to lash shafts. 2
• Blood-tinged debris on eyelashes and eyelids. 2
• Typically sexually transmitted; in children may indicate sexual abuse. 2

Malignancy Considerations

• Sebaceous carcinoma can masquerade as chronic unilateral blepharoconjunctivitis. 6
• Biopsy indicated for: unifocal recurrent lesions, resistance to therapy, focal lash loss, chronic presentation (>4-6 weeks) unresponsive to treatment. 6

Practical Diagnostic Algorithm

1. Rule out vision-threatening emergencies: Check visual acuity, extraocular movements, proptosis, pupil reactivity, and perform fluorescein staining. 1, 6

2. Assess discharge character: Watery suggests viral; purulent suggests bacterial; absent suggests inflammatory or allergic etiology. 6, 5

3. Examine eyelids carefully: Look for vesicles (HSV/VZV), umbilicated lesions (molluscum), lice/nits (pediculosis), or nodules. 2, 1

4. Obtain targeted history: Recent exposures, upper respiratory symptoms, contact lens wear, new cosmetics/medications, systemic illness, sexual history. 2

5. Determine laterality and duration: True unilateral presentation lasting >4-6 weeks warrants biopsy consideration for malignancy. 6

Initial Management Approach

For presumed viral conjunctivitis without red flags: Cool compresses for symptomatic relief with mandatory follow-up in 3-4 days to assess improvement. 1

Immediate ophthalmology referral required for: Visual changes, moderate-to-severe pain, corneal involvement on fluorescein examination, suspected HSV/VZV with vesicles, or any red flag features. 1

For suspected preseptal cellulitis: High-dose amoxicillin-clavulanate with daily follow-up; hospitalize for IV antibiotics if no improvement in 24-48 hours or progressive infection. 6

Common pitfall: Assuming all unilateral red eye is benign conjunctivitis without performing fluorescein staining or checking for herpetic vesicles, which can lead to missed vision-threatening keratitis. 1