Diseases Commonly Mistaken for Preseptal (Preorbital) Cellulitis
Direct Answer
Adenoviral conjunctivitis is the most frequently mistaken condition for preseptal cellulitis, as it can present with eyelid swelling, erythema, and chemosis that closely resembles orbital cellulitis on examination. 1
Primary Mimics to Consider
Viral Conjunctivitis (Most Common Mimic)
- Adenoviral conjunctivitis presents with eyelid swelling, erythema, and chemosis that can resemble orbital cellulitis, making it the most common infectious mimic 1
- Herpes simplex virus (HSV) conjunctivitis can cause bulbar conjunctival injection with watery discharge and may be bilateral in atopic or immunocompromised patients, mimicking preseptal infection 1
- Varicella zoster virus (VZV) presents with vesicular dermatomal rash or ulceration of eyelids, which can be confused with cellulitis when severe pain and eyelid involvement are prominent 1
- Epstein-Barr virus can cause hemorrhagic conjunctivitis with periorbital edema 2
Neoplastic Conditions (Critical Not to Miss)
- Sebaceous carcinoma presents with intense bulbar conjunctival injection and is commonly misdiagnosed as chronic blepharoconjunctivitis—this is a critical diagnostic pitfall 3
- Conjunctival lymphoma appears as painless, pink "salmon patch" lesions with indolent fleshy swelling, often presenting with chronic follicles that can mimic chronic infection 1, 3
- Particularly relevant in patients with autoimmune conditions (Sjögren's syndrome, Hashimoto's, IgG4-related disease) 1
- Ocular surface squamous neoplasia causes conjunctival hyperemia and may be mistaken for unresponsive blepharoconjunctivitis 1, 3
- Melanoma presents as painless brown or fleshy-pink lesions on the conjunctiva 2
Autoimmune/Inflammatory Conditions
- Ocular cicatricial pemphigoid (OCP) presents with bilateral conjunctival injection and papillary conjunctivitis, often asymmetric, with keratitis and eyelid thickening 4
- The American Academy of Ophthalmology specifically recommends considering preseptal or orbital cellulitis in the differential diagnosis of OCP when massive eye swelling occurs 4
- Wells syndrome (eosinophilic cellulitis) presents as diffuse preseptal edema, erythema, and woody induration that is nonresponsive to antibiotics—a rare but important mimic in atypical presentations 5
Bacterial Infections
- Gonococcal conjunctivitis causes marked eyelid edema, marked bulbar conjunctival injection, and marked purulent discharge with preauricular lymphadenopathy 1, 4
- Nongonococcal bacterial conjunctivitis with purulent or mucopurulent discharge can present with significant eyelid involvement 1
Other Important Mimics
- Stevens-Johnson syndrome/TEN causes acute bilateral conjunctival inflammation with membranes and should be considered with massive eye swelling 4
- Contact lens-related complications including giant papillary conjunctivitis can cause lid swelling and ptosis 1, 3
- Medication-induced/preservative-induced keratoconjunctivitis from glaucoma medications or other topical agents causes conjunctival injection and punctal edema 1
Clinical Approach for Older Adults with Autoimmune Disease
Key Distinguishing Features to Assess
- Pain and tenderness: True preseptal cellulitis is typically painful; viral conjunctivitis and lymphoma are usually painless 1, 6
- Discharge character: Purulent suggests bacterial; watery suggests viral; mucoid suggests allergic/chronic 1
- Response to antibiotics: Lack of improvement after 48-72 hours should prompt reconsideration of diagnosis 5, 7
- Bilateral vs unilateral: Bilateral presentation favors viral, autoimmune, or medication-related causes 1, 4
- Chronicity: Recurrent or chronic presentations suggest neoplasm, autoimmune disease, or non-infectious etiology 7
High-Risk Features in Autoimmune Patients
- Patients with autoimmune conditions (Sjögren's, Hashimoto's, IgG4-related disease) have increased risk of conjunctival lymphoma 1
- Previous eye conditions increase risk of medication-induced conjunctivitis from chronic topical therapy 1
- Immunosuppression increases risk of bilateral HSV and atypical presentations 1
Critical Pitfalls to Avoid
- Do not assume infection without confirming: Blood and skin cultures are usually negative in preseptal cellulitis 8, 9
- Biopsy any persistent or atypical lesions: Recurrent subconjunctival hemorrhage with nodules or masses requires biopsy to exclude malignancy 2
- Consider imaging early: CT scan is essential to differentiate preseptal from orbital cellulitis and identify underlying sinusitis 9
- Reassess if not improving: Continuous clinical reassessment is necessary for recurrent cases to identify underlying non-infectious causes 7