Differential Diagnosis for Bilateral Eyelid Swelling in a 31-Year-Old
The most critical first step is to immediately assess for orbital cellulitis red flags—proptosis, painful eye movements, vision loss, or fever—which require emergent hospitalization, IV antibiotics, and urgent ophthalmology consultation 1.
Immediate Red Flag Assessment
Examine specifically for:
- Proptosis or restricted/painful extraocular movements 1
- Vision changes or decreased visual acuity 1
- Fever or systemic toxicity 1
- Corneal involvement on fluorescein staining (mandatory in every case) 2
If any red flags are present, obtain contrast-enhanced CT of orbits and sinuses immediately and hospitalize for IV antibiotics 1.
Most Likely Infectious Etiologies
Viral Conjunctivitis
Adenoviral conjunctivitis is the most common infectious cause of bilateral eyelid swelling in this age group, typically presenting with watery discharge, bulbar conjunctival injection, chemosis, and follicular reaction of the inferior tarsal conjunctiva 3, 2. The condition is self-limited with improvement within 5-14 days 3, 2. Look for recent exposure to infected individuals or concurrent upper respiratory infection 3.
Bacterial Conjunctivitis
Gonococcal conjunctivitis presents with marked eyelid edema, marked bulbar conjunctival injection, and marked purulent discharge 3. In adults, this develops rapidly and is associated with urethritis or pelvic inflammatory disease 3. Non-gonococcal bacterial conjunctivitis shows purulent or mucopurulent discharge and may be associated with contact with infected individuals 3.
Herpes Simplex or Varicella Zoster
Examine carefully for eyelid vesicles or dermatomal rash, as these can progress to keratitis, corneal scarring, and perforation 3, 2. HSV typically presents unilaterally but can be bilateral in immunocompromised patients 3. VZV shows distinctive vesicular dermatomal rash or ulceration of eyelids 3.
Molluscum Contagiosum
Look for shiny, dome-shaped umbilicated lesions on the eyelid skin or margin with associated follicular conjunctivitis 3, 2. This is more common in immunocompromised patients (HIV) 3.
Non-Infectious Inflammatory Causes
Allergic/Contact Dermatitis
Cosmetics and ophthalmological topical preparations are the main causes of allergic contact eczema about the eye, presenting with conjunctival injection, blepharitis, periorbital dermatitis, and lid edema with itching 4. Consider recent exposure to new products 2.
Systemic Inflammatory Diseases
Sarcoidosis can present with isolated bilateral eyelid swelling years before other cutaneous findings develop 5. This diagnosis is particularly important in Black patients and requires biopsy showing non-necrotizing granulomatous inflammation 5.
Vasculitis (including granulomatosis with polyangiitis, Churg-Strauss syndrome) can cause bilateral conjunctivitis with conjunctival nodules, symblepharon, and systemic involvement of lungs, kidneys, and skin 3.
Stevens-Johnson syndrome/Toxic Epidermal Necrolysis presents with bilateral bulbar conjunctival injection, membranes, and conjunctival scarring, typically following systemic medications (sulfonamides, barbiturates, phenytoin) or infections 3.
Graft-versus-host disease should be considered in patients who have undergone allogeneic stem cell transplantation, presenting with bilateral conjunctival injection, chemosis, and pseudomembranous conjunctivitis 3.
Thyroid Eye Disease
Consider in patients with thyroid dysfunction, presenting with periorbital edema, proptosis, and restrictive myopathy 6.
Malignancy Considerations
Sebaceous carcinoma can masquerade as chronic unilateral blepharoconjunctivitis but may present bilaterally 1, 7. Biopsy is indicated for unifocal recurrent lesions, resistance to therapy, focal lash loss, and chronic presentation unresponsive to treatment 1, 7.
Ocular adnexal lymphoma presents as painless, pink "salmon patch" lesions with indolent fleshy swelling 7. Both ocular lymphoid hyperplasia and lymphoma cannot be differentiated clinically or radiologically and require biopsy 6.
Practical Diagnostic Algorithm
- Rule out orbital cellulitis with examination for proptosis, painful eye movements, vision loss, fever 1
- Perform fluorescein staining in every case to detect corneal involvement 2
- Examine for vesicles or dermatomal rash suggesting HSV/VZV 3, 2
- Assess discharge character: watery (viral), purulent (bacterial), none (inflammatory/allergic) 3
- Check for umbilicated lesions on lid margins (molluscum) 3
- Obtain exposure history: infected contacts, new cosmetics, medications, systemic illness 3, 4
- Consider biopsy if chronic (>4-6 weeks), unresponsive to treatment, or asymmetric presentation 7, 6
Initial Management Approach
For presumed viral conjunctivitis without red flags: cool compresses for symptomatic relief and mandatory follow-up in 3-4 days 2. Immediate ophthalmology referral is required for any visual changes, moderate to severe pain, corneal involvement, or suspected HSV/VZV 2.
For suspected preseptal cellulitis: high-dose amoxicillin-clavulanate with daily follow-up until definite improvement, and hospitalization for IV antibiotics if no improvement in 24-48 hours or progressive infection 1.