What are the likely causes and recommended evaluation and management for a 38‑year‑old man with loss of his left upper eyelashes?

Unilateral Upper Eyelash Loss in a 38-Year-Old Man

This patient requires urgent evaluation to exclude sebaceous cell carcinoma, which commonly masquerades as chronic unilateral blepharitis with focal lash loss (madarosis). 1, 2

Immediate Diagnostic Priority: Rule Out Malignancy

The unilateral presentation with eyelash loss is a critical red flag that demands immediate attention. Proceed directly to full-thickness eyelid biopsy if the presentation is truly isolated to one eyelid, as this is atypical for benign inflammatory conditions and highly concerning for malignancy. 2

Key Warning Signs to Assess

Examine the affected left upper eyelid carefully for these concerning features that mandate biopsy: 1, 2

• Focal lash loss (ciliary madarosis) in the affected area
• Loss of normal eyelid margin anatomy, including nodular masses or ulceration
• Unifocal recurrent chalazia that do not respond to therapy
• Conjunctival cicatricial changes in the affected eye
• Marked asymmetry or resistance to standard therapy

Before obtaining the biopsy, consult with a pathologist regarding the potential need for frozen sections and mapping of the conjunctiva to search for pagetoid spread, as fresh tissue may be needed to detect lipids using special dyes such as oil red-O. 1

Systematic Examination Protocol

Bilateral Four-Lid Margin Examination

Despite the unilateral presentation, examine all four eyelid margins (both upper and lower lids bilaterally) systematically using slit-lamp biomicroscopy to look for subtle bilateral involvement that may have been missed. 1, 2 This is critical because:

• Demodex blepharitis characteristically affects all four eyelid margins bilaterally, as mites colonize lash follicles and meibomian glands 2
• True localization to only one upper lid is atypical for benign inflammatory conditions 2
• Finding bilateral disease would support a benign diagnosis like Demodex or seborrheic blepharitis 2

Specific Features to Document

Look for these findings on all lid margins: 1

• Cylindrical dandruff or collarettes at the eyelash base (pathognomonic for Demodex)
• Abnormal deposits at the base of remaining eyelashes
• Vascularization or hyperemia of eyelid margins
• Ulceration or vesicles
• Scaling, hyperkeratosis
• Abnormalities of meibomian orifices (capping, pouting, retroplacement)
• Character of meibomian secretions (expressibility, thickness, turbidity)

Ancillary Diagnostic Testing

Perform microscopic evaluation of epilated lashes from the affected left upper lid by placing them on a glass slide with a drop of fluorescein and a cover slip to look for Demodex mites. 1, 2 This can help confirm or exclude Demodex as the etiology.

Differential Diagnosis Framework

Malignant Causes (Must Exclude First)

Sebaceous cell carcinoma is the most critical diagnosis to exclude: 1, 2

• Often presents with chronic unilateral blepharitis unresponsive to therapy
• Causes focal lash loss (madarosis)
• May have conjunctival cicatricial changes in the affected eye
• Can masquerade as recurrent chalazion or chronic blepharitis
• Has high metastatic potential if diagnosis is delayed 3

Infectious Causes

If malignancy is excluded, consider: 4, 5

• Fungal blepharitis (e.g., Microsporum species): Rare but can cause unilateral madarosis with erythematous squamous lesions; requires mycological examination of palpebral scales and eyelashes 4
• Staphylococcal blepharitis: Severe cases may lead to eyelash loss and eyelid scarring, though typically bilateral 1
• Pediculosis palpebrarum (Phthirus pubis): Can cause lash loss; look for adult lice and nits on examination 1

Inflammatory/Dermatologic Causes

Consider these if bilateral involvement is found: 1, 5

• Demodex blepharitis: Look for cylindrical dandruff on multiple lid margins
• Seborrheic blepharitis: Associated with seborrheic dermatitis
• Ocular rosacea: Look for facial telangiectasia, history of facial flushing
• Discoid lupus or scleroderma: Can cause scarring madarosis 5

Medication-Induced Causes

Ask about recent medication use: 1, 6

• Isotretinoin: Associated with blepharitis and disruption in tear function 1
• Dupilumab: Associated with conjunctivitis, keratitis, and blepharitis in 32-55% of patients 1
• Chemotherapy agents (bortezomib, cetuximab, TNFα inhibitors): Can cause blepharitis as a side effect 6

Critical Pitfalls to Avoid

The most critical error is dismissing unilateral or highly localized presentation without proper malignancy workup—this can be vision-threatening and life-threatening. 2 Do not:

• Assume all eyelash loss is benign inflammatory blepharitis 2
• Fail to examine all four eyelid margins systematically, which may miss subtle bilateral involvement 2
• Delay biopsy in cases with recurrence, atypical features, or resistance to standard therapy 1, 3
• Initiate empiric treatment for blepharitis without first excluding malignancy in unilateral presentations 2

Management Algorithm

Step 1: Perform comprehensive bilateral four-lid margin examination with slit-lamp biomicroscopy 1, 2

Step 2: If truly unilateral with any warning signs (focal madarosis, margin distortion, resistance to therapy), proceed directly to biopsy 1, 2

Step 3: If bilateral involvement is found, perform lash epilation for Demodex examination and consider cultures if severe inflammation present 1

Step 4: Only after malignancy is excluded should empiric treatment for inflammatory blepharitis be initiated 2