What is the differential diagnosis for an adult patient with inflammation of the upper eyelid and no significant medical history?

Differential Diagnosis for Upper Eyelid Inflammation

The differential diagnosis for upper eyelid inflammation in an adult with no significant medical history includes preseptal cellulitis, hordeolum/chalazion, ethmoid sinusitis with periorbital extension, floppy eyelid syndrome, giant papillary conjunctivitis, dacryoadenitis, and critically—sebaceous carcinoma masquerading as chronic inflammation. 1

Immediate Red Flag Assessment

Before considering benign causes, exclude orbital cellulitis immediately by assessing for:

• Proptosis
• Painful or restricted eye movements
• Decreased vision
• Fever or systemic toxicity 1

If any red flags are present, hospitalize immediately, obtain contrast-enhanced CT of orbits and sinuses, start IV antibiotics, and consult ophthalmology, otolaryngology, and infectious disease urgently. 1

Most Common Infectious/Inflammatory Causes

Preseptal Cellulitis

• Most common cause of upper eyelid swelling with warmth, tenderness, and erythema 1, 2
• No proptosis, normal eye movements, and preserved vision distinguish it from orbital cellulitis 1
• Treat with high-dose amoxicillin-clavulanate and daily follow-up until definite improvement 1
• Hospitalize for IV antibiotics if no improvement in 24-48 hours or progressive infection 1

Hordeolum and Chalazion

• Hordeolum presents as acute, painful, localized eyelid margin swelling 2
• Chalazion presents as chronic, painless nodule within the tarsal plate 2
• Manage initially with warm compresses, lid hygiene, and observation for 4-6 weeks 3
• Biopsy if lesion persists, recurs in same location, or shows atypical features 3

Ethmoid Sinusitis with Periorbital Extension

• Consider when upper eyelid swelling is accompanied by medial canthal swelling, purulent nasal discharge, and facial tenderness 1
• Key examination finding is purulent exudates in the middle meatus 1
• In children, acute ethmoiditis presents with fever and painful edema of the internal upper eyelid, requiring urgent parenteral antibiotics 4

Dacryoadenitis

• Presents with swelling of lateral upper eyelid with palpable, tender lacrimal gland 5
• Can be viral (adenovirus, EBV, mumps) or idiopathic 5
• May be associated with epidemic keratoconjunctivitis 5

Non-Infectious Mechanical Causes

Floppy Eyelid Syndrome

• Upper eyelid edema with easily everted upper lid and horizontal lid laxity 4, 1
• Associated with obesity, sleep apnea, and thyroid disease 4, 1
• Diffuse papillary reaction of superior tarsal conjunctiva with punctate epithelial keratopathy 4

Giant Papillary Conjunctivitis

• Papillary hypertrophy of superior tarsal conjunctiva with mucoid discharge in contact lens wearers 4, 1
• Risk factors include soft contact lenses, infrequent replacement, prolonged wearing time, and poor hygiene 4
• Treatment includes discontinuing contact lens wear, switching to daily disposables, and using preservative-free solutions 1

Giant Fornix Syndrome

• Enlarged superior fornix with coagulum of mucopurulent material and ptosis 4
• Typically affects elderly women (eighth to tenth decade) 4
• Chronic mucopurulent conjunctivitis that waxes and wanes 4

Critical Malignancy Warning Signs

Sebaceous Carcinoma

This is the most dangerous diagnostic pitfall—sebaceous carcinoma can masquerade as chronic unilateral blepharoconjunctivitis. 1, 3

Biopsy indications include:

• Chronic unilateral presentation unresponsive to standard therapy 1, 3, 6
• Recurrent "chalazion" in same location 3
• Unifocal recurrent lesions 1
• Focal lash loss 1
• Hard, non-mobile tarsal mass with yellowish discoloration 3
• Resistance to therapy for more than 4-6 weeks 1, 3

Less Common Causes to Consider

Medication-Induced Keratoconjunctivitis

• Conjunctival injection and punctal edema from glaucoma medications, topical NSAIDs, antibiotics, or preservatives 4
• Most common with multiple eye medications and frequent dosing 4

Pediculosis Palpebrarum

• Follicular conjunctivitis with adult lice at eyelash base and nits adherent to lash shafts 4
• Blood-tinged debris on eyelashes and eyelids 4

Retained Foreign Body

• Organic foreign bodies (especially wood) can remain asymptomatic for months before causing inflammation 7
• In cases of trauma history with persistent inflammation, examine under anesthesia if patient is uncooperative 7

Granulomatous Inflammation

• Can occur after cosmetic procedures such as autologous fat injection in forehead 8
• Presents as firm periorbital mass with chronic granulomatous inflammation on histology 8

Common Pitfalls to Avoid

• Do not prescribe topical antibiotics empirically without evidence of infection—this adds preservative exposure and potential toxicity 6
• Do not use topical corticosteroids without slit-lamp examination to rule out corneal pathology—steroids can worsen herpetic or fungal infections and cause glaucoma 6
• Do not dismiss chronic unilateral cases as simple irritation—sebaceous carcinoma can present as chronic unresponsive unilateral inflammation 1, 6
• Do not delay biopsy in atypical or non-resolving cases—marked asymmetry or unifocal recurrence demands biopsy 3