What are the possible causes and recommended management for white patches inside the lips?

White Patches Inside the Lips: Differential Diagnosis and Management

White patches inside the lips require immediate clinical evaluation to distinguish benign conditions from oral leukoplakia, which carries a 4-16% malignant transformation risk, with erythroplakia (red patches) carrying even higher risk and requiring prompt removal. 1, 2, 3

Initial Clinical Assessment

The first step is determining whether the white patch can be wiped away:

• If the patch wipes off easily: This suggests oral candidiasis (thrush) requiring antifungal treatment with nystatin oral suspension (100,000 units four times daily for 1 week) or miconazole oral gel (5-10 mL held in mouth after food four times daily for 1 week). 4

• If the patch cannot be removed: Proceed with differential diagnosis below. 1, 5

Differential Diagnosis of Non-Removable White Patches

Benign Infectious Causes

HPV-related lesions (squamous papilloma, condyloma acuminatum, verruca vulgaris):

• Appear as exophytic, sessile, or pedunculated growths with papillary projections 1
• May appear pink or white depending on keratinization degree 1
• Treatment: Surgical excision is recommended, as approximately 1% can harbor dysplasia, particularly in immunosuppressed individuals 1
• Recurrence is unusual and suggests incomplete removal 1

Traumatic Lesions

Morsicatio labiorum (chronic cheek/lip biting):

• Presents as white, shaggy patches from chronic trauma 6
• May have grey covering if secondarily infected 6
• Treatment approach:
  • Apply white soft paraffin ointment every 2 hours for surface protection 6
  • Use 0.2% chlorhexidine digluconate mouthwash (10 mL twice daily) to reduce bacterial colonization 6
  • Apply benzydamine hydrochloride oral rinse or spray every 3 hours for pain control 6
  • Eliminate irritating foods (citrus, tomatoes, spicy/hot foods) 6

Premalignant Lesions (Highest Priority)

Oral leukoplakia (OLK):

• Defined as a white patch/plaque that cannot be wiped away and cannot be characterized as any other definable disorder 1, 5
• Represents 85% of all precancerous oral lesions 2
• Malignant transformation risk: 4% overall, but up to 16% for lesions with dysplasia 2, 3

Clinical subtypes with different risk profiles:

• Homogeneous leukoplakia: Lower malignant potential 1
• Non-homogeneous leukoplakia: Higher risk of malignant transformation 1
• Erythroplakia (red patches) or erythroleukoplakia (mixed red-white): Considerably higher malignant risk than pure white lesions and should always be removed 5, 3

Mandatory Evaluation for Persistent White Patches

Any white patch that persists beyond 2 weeks requires biopsy with histopathological examination to rule out dysplasia or malignancy. 1, 5, 3

Histopathological Features to Assess

The biopsy evaluates for:

• Hyperkeratosis (ortho- or parakeratotic) 2
• Acanthosis of epithelium 2
• Epithelial dysplasia severity (loss of basal cell polarity, increased nuclear-cytoplasmic ratio, abnormal mitoses, cellular pleomorphism) 2
• Chronic inflammatory infiltrates in lamina propria 2

Management Algorithm for Confirmed Oral Leukoplakia

Step 1: Eliminate Causative Factors

• Smoking cessation 1, 3
• Alcohol cessation 1, 3
• Remove sources of chronic trauma (ill-fitting dentures, fractured teeth) 1

Step 2: Treatment Selection Based on Lesion Characteristics

For localized, accessible lesions:

• Traditional surgical excision, CO2 laser ablation, or cryosurgery 1
• Photodynamic therapy (ALA-PDT): Emerging as fourth-line alternative for its minimally invasive nature, efficacy, and low risk of disfigurement 1

For extensive lesions or those at difficult anatomical sites:

• Photodynamic therapy is preferred over invasive surgery due to reduced postoperative pain, edema, and scarring 1

Step 3: Long-Term Surveillance

All patients with oral leukoplakia require lifelong follow-up at 6-12 month intervals, regardless of whether the lesion was treated or observed, to detect recurrences or new malignant transformation early. 3

Special Considerations

Angular Cheilitis (Corners of Mouth)

If white patches are specifically at the lip commissures with cracking/fissuring:

• First-line treatment: Combination therapy with hydrocortisone 1% plus miconazole 2% or clotrimazole 1%, applied 2-3 times daily for 1-2 weeks 4
• Address mechanical factors (ill-fitting dentures, loss of vertical dimension) 4
• For resistant cases: Systemic fluconazole 100 mg daily for 7-14 days 4

Oral Aphthous Ulcers

If lesions are ulcerated rather than purely white patches:

• First-line: Betamethasone sodium phosphate 0.5 mg dissolved in 10 mL water as rinse-and-spit solution 1-4 times daily 7
• Alternative: Clobetasol 0.05% ointment mixed in 50% Orabase applied twice weekly to dried mucosa 7

Critical Red Flags Requiring Urgent Referral

• Erythroplakia or mixed red-white lesions: Always remove due to high malignant potential 3
• Rapid growth or change in appearance 5
• Ulceration that doesn't heal within 2 weeks 6
• Pain disproportionate to clinical appearance 6
• Associated lymphadenopathy 6

Common Pitfalls to Avoid

• Do not assume all white patches are benign: Biopsy is mandatory for persistent lesions 1, 5, 3
• Do not use petroleum-based products chronically on lips: They promote mucosal dehydration and increase secondary infection risk 1, 4, 6
• Do not rely on chemoprevention alone for leukoplakia: Randomized trials show no promising evidence for preventing malignant transformation 1
• Do not discharge patients after successful treatment: Lifelong surveillance is required due to recurrence and field cancerization risk 3