Understanding drug-induced oral ulcers
Drug-induced oral ulcers, also known as stomatitis or oral mucositis, are a side effect of certain medications that manifest as painful sores in the mouth. These can range from minor irritations to severe, debilitating ulcerations that impact a person's ability to eat and speak. The precise mechanism can vary widely depending on the drug in question, but often involves direct cellular damage, immune system overreaction, or inflammatory pathways.
While some drug-induced sores can be confused with common aphthous ulcers, they are often larger, more persistent, and may not respond to conventional treatments. A careful medical history is essential for determining if a medication is the cause, particularly when dealing with patients on multiple drugs. Discontinuation or dose reduction of the implicated medication often leads to resolution, confirming its role.
Chemotherapy and targeted cancer therapies
Chemotherapy-induced mucositis is one of the most well-known causes of drug-induced oral ulceration. These cytotoxic drugs target rapidly dividing cells, which includes not only cancer cells but also the healthy, fast-regenerating cells of the oral mucosal lining. The resulting inflammation and breakdown of the mucosal lining leads to painful sores, which can increase the risk of bleeding and infection.
- Methotrexate (MTX): A widely used antimetabolite, MTX can cause significant oral mucositis, particularly in the high-dose regimens used for cancer or at lower doses for rheumatoid arthritis.
- 5-Fluorouracil (5-FU): This antimetabolite is known to have a high incidence of stomatitis, especially in continuous infusion regimens.
- mTOR inhibitors (e.g., Everolimus, Sirolimus): These newer, targeted cancer therapies can cause aphthous-like ulcers through a different, immune-mediated mechanism, often referred to as mTOR inhibitor-associated stomatitis (mIAS).
Cardiovascular medications
A number of drugs prescribed for heart conditions and blood pressure have been linked to oral ulcers or lichenoid reactions, an inflammatory condition resembling oral lichen planus.
- Beta-blockers (e.g., Bisoprolol, Metoprolol): These can trigger oral lichenoid drug eruptions in some patients. Discontinuation of the medication typically leads to resolution of the lesions.
- Nicorandil: Used to treat angina, this potassium-channel activator is particularly notorious for causing deep, painful, and persistent oral and anal ulcerations. These ulcers are often resistant to topical steroids and require cessation or dose reduction of the drug to heal.
- Angiotensin-Converting Enzyme (ACE) Inhibitors (e.g., Captopril, Enalapril): While less common, these blood pressure medications have been reported to cause oral lichenoid reactions.
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs, a class of drugs widely available over-the-counter and by prescription, can also be a culprit. Their mechanism may involve localized irritation or a systemic immune reaction.
- Ibuprofen, Naproxen, Diclofenac, Aspirin: Case reports and studies have linked these common NSAIDs to the development of oral ulcerations. Some cases are due to localized irritation from holding the tablet in the mouth, while others are systemic.
- Diclofenac Sodium: Specific cases of drug-induced erythema multiforme, a reaction causing blistering and ulceration of the skin and mucous membranes, have been linked to diclofenac.
Other medications linked to oral ulcers
- Antibiotics: Certain antibiotics, including penicillins, cephalosporins, and tetracyclines, have been reported to cause oral sores. This can be due to a hypersensitivity reaction or an overgrowth of candida (thrush) in some instances.
- Immunosuppressants: Besides cancer-related treatments, immunosuppressants like mycophenolate used for organ transplant recipients can cause cold sores or open mouth sores.
- Bisphosphonates (e.g., Alendronate): Primarily used for osteoporosis, incorrect use—such as sucking the tablet—can cause localized ulceration due to direct irritation.
- Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: These newer diabetes medications, such as sitagliptin, have been linked to oral ulcerations in some cases.
- Phenytoin: This anti-seizure medication has been associated with oral ulcers and other gum issues.
Comparison table of drugs causing oral ulcers
| Drug Class | Specific Examples | Mechanism | Clinical Features |
|---|---|---|---|
| Chemotherapy | Methotrexate, 5-Fluorouracil | Direct cytotoxicity to rapidly dividing mucosal cells, inflammation. | Widespread, painful mucositis often developing 5-14 days post-treatment. |
| mTOR Inhibitors | Everolimus, Sirolimus | Immune-mediated aphthous-like ulcers via innate immune response activation. | Discrete, ovoid ulcers with erythematous halo, mimicking aphthous stomatitis. |
| Beta-blockers | Bisoprolol, Metoprolol | Immune-mediated lichenoid drug eruption via β-adrenoreceptor blockade. | White striae, erosions, and ulcerations, often bilateral on buccal mucosa. |
| Nicorandil | Nicorandil | Unclear; possibly direct toxic effect or hypersensitivity reaction. | Deep, painful, persistent ulcers; often poorly responsive to topical steroids. |
| NSAIDs | Ibuprofen, Diclofenac | Local irritation, allergic hypersensitivity, or systemic immune response. | Varied, from localized sores to widespread erythema multiforme-like lesions. |
Management and treatment strategies
If a drug is suspected of causing oral ulcers, the first and most critical step is to consult the prescribing physician to discuss potential alternatives or a dose reduction. Do not stop a prescribed medication without medical advice. In many cases, ulcers resolve completely within weeks of discontinuing the offending agent.
Palliative care is often necessary to manage symptoms and improve quality of life while the ulcers heal. Management strategies include:
- Topical corticosteroids: For immune-mediated ulcers like lichenoid reactions or mIAS, high-potency topical steroids may be effective, though they often fail for nicorandil-induced ulcers.
- Topical anesthetics: Viscous lidocaine or benzocaine preparations can provide temporary pain relief, especially before eating.
- Oral hygiene: Maintaining excellent oral hygiene is paramount to prevent secondary infections. This includes gentle brushing and rinsing with salt water or a baking soda solution.
- Magic mouthwash: Compounded solutions containing various combinations of topical anesthetics, antacids, and antifungals can be effective for pain relief.
- Dietary adjustments: Avoiding hot, spicy, or acidic foods, and opting for soft, bland foods can minimize irritation and pain.
- Oral cryotherapy: For some chemotherapy regimens, swishing ice chips in the mouth during infusion can help prevent mucositis.
Conclusion
While many medications offer significant health benefits, the potential for adverse effects like oral ulcers cannot be ignored. The list of which drugs can cause mouth ulcers is extensive, ranging from potent chemotherapy agents to common over-the-counter NSAIDs. For patients experiencing persistent or unusual oral sores, a review of their medication list by a healthcare professional is essential. The most effective approach involves identifying and, if appropriate, discontinuing the causative drug, combined with targeted palliative care. Given the complexity of different drug mechanisms and patient comorbidities, working closely with your healthcare team is key to managing drug-induced oral ulcers safely and effectively. For specific information on managing drug-induced complications, resources like the Oral Cancer Foundation offer valuable support and guidance, particularly for cancer patients.
