What medications can cause lichenoid reactions in the mouth?

Medications That Can Cause Lichenoid Reactions in the Mouth

Numerous medications can cause oral lichenoid reactions, with the most common culprits being thiazide diuretics, anti-hypertensives, anti-malarials, immune checkpoint inhibitors, beta-blockers, and NSAIDs. 1, 2, 3

Common Medication Classes Associated with Oral Lichenoid Reactions

Cardiovascular Medications

• Beta-blockers (strong evidence) 3
• Angiotensin-converting enzyme (ACE) inhibitors including ramipril, enalapril, and quinapril 4
• Angiotensin receptor blockers (ARBs) including candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan 4
• Anti-arrhythmic drugs particularly amiodarone and dronedarone 4
• Methyldopa (one of the most frequently reported - 20.37% of cases) 5, 3
• Thiazide diuretics including hydrochlorothiazide (can trigger various photosensitive eruptions including lichenoid reactions) 4

Immunomodulatory Medications

• Immune checkpoint inhibitors (ICIs) - PD-1 inhibitors (pembrolizumab, nivolumab) and PD-L1 inhibitors (atezolizumab) 4
• Interferon-alpha (11.11% of reported cases) 5
• Imatinib and Infliximab (9.26% of reported cases) 5
• TNF antagonists (tumor necrosis factor antagonists) 2
• Gold compounds 2, 3
• Penicillamine 3

Other Medications

• Antimalarial drugs 2
• Quinidine and quinine 3
• NSAIDs (nonsteroidal anti-inflammatory drugs) 3
• Antihistamines (rare cases reported with cetirizine and loratadine) 6
• Corticosteroids (rare cases reported with methylprednisolone) 6

Clinical Presentation and Diagnosis

Oral lichenoid reactions typically present with:

• White lacy patterns (Wickham's striae)
• Erythematous and erosive lesions
• Violaceous papules and plaques
• Erosions and striae in oral mucosa 1

These reactions can be difficult to distinguish from idiopathic oral lichen planus. Key differentiating factors include:

• Asymmetric distribution (unlike the typically symmetric pattern of oral lichen planus)
• Temporal relationship to medication initiation
• Resolution upon medication withdrawal (partial or complete) 5, 7

Management Approach

1. Identify and withdraw the suspected medication when possible (achieved in 68.5% of reported cases) 5
2. Monitor for resolution - partial or complete resolution may occur in 44.4% of cases after withdrawal (16.7% without additional treatment, 27.7% with treatment) 5
3. Symptomatic treatment:
   • High-potency topical corticosteroids (first-line): clobetasol propionate 0.05% gel or fluocinonide 0.05% gel applied 2-3 times daily 1
   • Topical calcineurin inhibitors: tacrolimus 0.1% ointment for patients who cannot tolerate corticosteroids 1
   • Intralesional triamcinolone (10-20 mg) for resistant hyperkeratotic areas 1

Important Considerations

• The causality relationship between medications and oral lichenoid lesions is often difficult to establish definitively 5
• Formal causality assessment using validated algorithms (like Naranjo or C-D-R protocol) is rarely performed in clinical practice (only 14.8% of cases) 5
• Photosensitivity may play a role in some medication-induced lichenoid reactions, particularly with thiazide diuretics and amiodarone 4
• Patients on medications known to cause lichenoid reactions should be advised to seek shade when outside, wear protective clothing, and use broad-spectrum sunscreens 4
• Persistent ulcerations should be biopsied to rule out malignant transformation, as there is a small risk of squamous cell carcinoma in long-standing oral lichenoid lesions 1