Methotrexate (MTX) is a powerful medication used to treat a variety of conditions, including rheumatoid arthritis (RA), psoriasis, and certain types of cancer. As an immunosuppressant, it works by inhibiting cell proliferation, which is effective for managing these diseases but can also lead to a range of side effects. For many patients, skin-related problems are a notable concern. While most are manageable, it is crucial to recognize both common and severe reactions to ensure patient safety.
Common Skin Side Effects
Photosensitivity
One of the most frequently reported skin issues is photosensitivity, where the skin becomes highly sensitive to sunlight. This can result in a severe, exaggerated sunburn reaction, even after minimal sun exposure. Patients taking methotrexate should take precautions against intense sunlight and ultraviolet (UV) light, including avoiding sunbeds, wearing protective clothing, and using high-factor sunscreen.
Rashes and Hives
Many individuals may experience milder skin reactions, such as a rash, itchy skin (pruritus), or hives (urticaria). While typically not serious, any new or persistent rash should be reported to a healthcare provider. A rash that is swollen, blistering, or peeling could indicate a more severe issue.
Mouth Sores and Mucositis
Mouth sores, or stomatitis, are a common and dose-related side effect of methotrexate. This involves ulcers or erosions on the gums, cheeks, tongue, and lips. The appearance of these sores can be an early sign of toxicity and should be monitored closely. Regular folic acid supplementation, often prescribed alongside methotrexate, can help reduce the incidence of mouth sores.
Hair Loss
Temporary hair thinning and loss (alopecia) can occur with methotrexate use, though it is a less common side effect, especially with lower doses. For some, it can be a dose-related issue that may lessen with folic acid supplementation or dose adjustment. Hair growth typically returns to normal once the medication is stopped.
Skin Discoloration and Other Minor Issues
Less frequently, methotrexate can cause changes in skin pigmentation, particularly in sun-exposed areas. Some patients may also report feeling a burning sensation on the skin or bruising more easily.
Severe but Rare Cutaneous Complications
Cutaneous Ulceration
In rare cases, methotrexate toxicity can manifest as severe cutaneous ulceration, often appearing as painful, necrotic lesions. This is particularly noted in patients with pre-existing skin conditions like psoriasis, where existing psoriatic plaques may erode or ulcerate. However, it can also occur in non-psoriatic patients. The appearance of these ulcers can be a herald for impending systemic toxicity and requires immediate medical attention.
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
These are extremely rare but potentially fatal skin reactions. SJS and TEN are characterized by widespread blistering, peeling, and loosening of the skin, including the mucous membranes. Symptoms often begin with a flu-like illness followed by a painful, blistering rash that spreads rapidly. This is a medical emergency.
Vasculitis
Methotrexate has been reported to induce cutaneous leukocytoclastic vasculitis (LCV) in very rare instances. LCV is an inflammation of the small blood vessels in the skin, which can cause a rash of small, purplish spots (palpable purpura), sometimes accompanied by blisters or ulcers. Paradoxically, methotrexate is sometimes used to treat vasculitis, making this a complex and infrequent adverse event.
Nail Changes
In more severe cases, methotrexate can cause significant nail changes, including the separation of the nail from the nail bed (onycholysis), discoloration, or inflammation around the nail folds (paronychia). These changes often resolve after stopping the medication.
Risk Factors for Methotrexate-Induced Skin Problems
Several factors can increase a patient's risk of developing skin issues while on methotrexate:
- Incorrect Dosing: Taking the medication daily instead of weekly due to a misunderstanding is a major cause of acute toxicity.
- Renal Impairment: Impaired kidney function can lead to higher levels of methotrexate in the blood, increasing toxicity.
- Folate Deficiency: Inadequate or absent folic acid supplementation increases the risk of side effects, including mouth sores.
- Older Age: Patients over 55 may be more susceptible to adverse effects.
- Drug Interactions: Concurrent use of certain medications, such as some NSAIDs or antibiotics, can increase methotrexate levels.
Comparison of Common vs. Severe Methotrexate Skin Reactions
| Feature | Common Reactions (e.g., Photosensitivity, Mild Rash) | Severe Reactions (e.g., Ulceration, SJS/TEN) |
|---|---|---|
| Incidence | Fairly common | Rare to very rare |
| Appearance | Sunburn-like rash, itchiness, hives, or mild redness | Deep, painful erosions; severe blistering and peeling skin; palpable purpura |
| Underlying Mechanism | Phototoxicity, hypersensitivity | Direct cell toxicity due to inhibited cell division or immune-mediated reactions |
| Associated Symptoms | Possible mild mouth sores, fatigue | May precede or occur with other systemic toxicity, such as pancytopenia or fever |
| Management | Sun protection, symptomatic relief, dose adjustment | Immediate discontinuation of methotrexate; potential use of folinic acid; supportive care |
Managing Skin Issues from Methotrexate
Management depends on the severity of the reaction. For mild issues like photosensitivity or minor rashes, the doctor may recommend precautionary measures and topical treatments. However, any signs of severe toxicity, such as blistering, ulceration, or fever, necessitate immediate medical evaluation. Early recognition and communication with a healthcare provider are key to preventing more serious outcomes.
Read more about methotrexate side effects from the NHS
Conclusion
In summary, methotrexate can indeed cause a range of skin problems, from relatively common issues like photosensitivity and mouth sores to rare but serious complications such as cutaneous ulcers and SJS/TEN. The severity of these reactions can depend on various factors, including dosage, kidney function, and concomitant medications. By understanding these potential risks, patients can work with their healthcare providers to monitor for signs of toxicity and take appropriate preventive and management steps. Always report any new or worsening skin symptoms to your doctor immediately to ensure safe treatment.
