What are the differential diagnoses for a red, tender lump on the upper eyelid?

Differential Diagnoses for Red Lump on Upper Eyelid

The most common causes of a red, tender lump on the upper eyelid are hordeolum (stye), chalazion, and preseptal cellulitis, with the critical first step being to rule out orbital cellulitis by assessing for proptosis, painful eye movements, vision loss, or fever. 1

Immediate Red Flag Assessment

Before considering benign causes, you must immediately evaluate for orbital cellulitis, which requires urgent hospitalization:

• Check for proptosis, painful or impaired eye movements, decreased vision, fever, or systemic toxicity 1
• If any red flags are present, hospitalize immediately for contrast-enhanced CT of orbits and sinuses, start IV antibiotics, and consult ophthalmology, otolaryngology, and infectious disease urgently 1
• Consider ethmoid sinusitis with periorbital extension, especially if there is medial canthal swelling, purulent nasal discharge, and facial tenderness 1

Most Likely Benign Causes

Hordeolum (Internal Stye)

• Presents as a well-defined, painful, red mass at the lid margin or within the eyelid substance 2
• Caused by bacterial infection of the meibomian glands (internal) or glands of Zeis/Moll (external) 3
• Often drains spontaneously, but can progress to chalazion if unresolved 4
• Treatment includes warm compresses and topical antibiotics, though evidence for specific interventions is limited 4

Chalazion

• Appears as a firm, non-tender or minimally tender mass within the midportion of the eyelid 2
• Results from chronic granulomatous inflammation of meibomian glands 3
• Distinguished from hordeolum by subacute onset and less acute inflammation 2
• Warning: Unifocal recurrent chalazia that do not respond to therapy require biopsy to exclude sebaceous carcinoma 5

Preseptal Cellulitis

• Presents with diffuse eyelid swelling, erythema, and warmth without vision changes or ophthalmoplegia 2
• Extraocular movements and vision remain normal, distinguishing it from orbital cellulitis 2
• 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

Malignancy Warning Signs (Critical Not to Miss)

Sebaceous Carcinoma

• Can masquerade as chronic unilateral blepharoconjunctivitis with recurrent "chalazia" 1, 6
• Biopsy indications include: 5, 1
  • Marked asymmetry or unilateral presentation
  • Resistance to standard therapy
  • Unifocal recurrent lesions in the same location
  • Focal lash loss (ciliary madarosis)
  • Loss of normal eyelid margin anatomy
• May appear as hard nodular mass with yellowish discoloration or subconjunctival multilobulated yellow mass 5, 6
• Before biopsy, consult pathologist regarding need for frozen sections and mapping for pagetoid spread; fresh tissue may be needed for oil red-O staining 5

Other Neoplastic Considerations

• Conjunctival lymphoma: Painless, pink "salmon patch" lesion with fleshy swelling, most mobile and nonlobulated 5
• Ocular surface squamous neoplasia: Papillomatous or sessile nodules, may be leukoplakic, associated with HPV and UV exposure 5

Non-Infectious Inflammatory Causes

Floppy Eyelid Syndrome

• Upper eyelid edema with easily everted upper lid and horizontal lid laxity 1
• Associated with obesity, sleep apnea, and thyroid disease 1

Giant Papillary Conjunctivitis

• Papillary hypertrophy of superior tarsal conjunctiva with mucoid discharge in contact lens wearers 1
• Treatment includes discontinuing contact lens wear, switching to daily disposables, and using preservative-free solutions 1

Molluscum Contagiosum

• Shiny, dome-shaped umbilicated lesion(s) on eyelid skin or margin with associated follicular conjunctivitis 5
• More common in immunocompromised patients 5

Infectious Causes Beyond Bacterial

Herpes Zoster Ophthalmicus

• Vesicular dermatomal rash or ulceration of eyelids with severe pain 5
• May have pseudodendritic epithelial keratitis 5

Pediculosis Palpebrarum

• Adult lice at eyelash base with nits adherent to lash shafts 1
• Associated follicular conjunctivitis 1

Clinical Algorithm for Evaluation

1. First: Rule out orbital cellulitis - Check vision, extraocular movements, proptosis, fever 1
2. Second: Assess for localized pustule or nodule - Suggests hordeolum 1
3. Third: Evaluate for diffuse lid swelling - Consider preseptal cellulitis vs. inflammatory causes 1
4. Fourth: Check for chronicity and unilateral presentation - If chronic and unresponsive to therapy, strongly consider biopsy for sebaceous carcinoma 5, 1
5. Fifth: Look for associated systemic signs - Sinusitis symptoms, immunocompromised state, contact lens wear 1

Common Pitfalls to Avoid

• Do not dismiss chronic unilateral blepharoconjunctivitis as benign - This is a classic presentation of sebaceous carcinoma 5, 1
• Do not confuse preseptal with orbital cellulitis - Vision and extraocular movements are the key distinguishing features 2
• Do not overlook cicatricial changes - May indicate ocular mucous membrane pemphigoid requiring immunofluorescence studies 5
• Consider emerging pathogens - Community-acquired MRSA is increasingly common in periocular infections 7