Methotrexate in Dermatology
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Direct answer
Methotrexate is a folate antagonist that inhibits dihydrofolate reductase, slowing the proliferation of keratinocytes and activated T cells, and it is a standard systemic drug for psoriasis and several autoimmune blistering and connective tissue diseases. It is given once weekly, never daily, with folic acid to reduce toxicity. Hepatitis, tuberculosis, renal and liver screening and a pregnancy test precede starting, and blood counts and liver function are monitored throughout treatment.
What you must remember
- Mechanism: inhibits dihydrofolate reductase, reducing purine and thymidylate synthesis, and promotes adenosine release, which contributes to its anti-inflammatory effect.
- Indications: moderate-to-severe psoriasis, psoriatic arthritis, pemphigus, bullous pemphigoid, dermatomyositis and cutaneous sarcoidosis.
- Dosing: usually 7.5 to 25 mg once weekly, given orally or by subcutaneous injection and titrated to response.
- Folic acid: given to reduce gastrointestinal and haematological toxicity, typically on a day other than the methotrexate dose, as set by local protocol.
- Weekly, not daily: daily dosing errors have caused fatal toxicity, so the weekly schedule is stressed to every patient.
- Pre-treatment screening: hepatitis B and C serology, tuberculosis assessment, full blood count, renal and liver function and pregnancy status.
- Major toxicities: bone marrow suppression, hepatotoxicity with fibrosis, hypersensitivity pneumonitis, mucositis and teratogenicity.
- Interactions: trimethoprim-sulphamethoxazole increases marrow toxicity, and alcohol should be avoided.
A safe sequence for methotrexate
Methotrexate is safe in dermatology when screening, dosing and monitoring are followed in order, and each step below addresses a known source of serious harm.
- Screen before starting: test for hepatitis B and C, assess tuberculosis status, check renal and liver function and blood counts, and confirm pregnancy status.
- Choose the dose: start within the usual range of 7.5 to 25 mg weekly, given once a week and titrated by response.
- Prescribe folic acid: give folic acid according to the local protocol, typically on a day other than the methotrexate dose.
- Counsel the patient: explain that methotrexate is taken once a week and never daily, and advise avoiding alcohol and interacting drugs.
- Monitor regularly: check blood counts and liver and renal function every few weeks at first and then at intervals, with liver assessment during long-term therapy.
- Recognise toxicity: withhold the drug for falling counts, abnormal liver tests, new cough or breathlessness, or mouth ulcers, and seek specialist advice.
- Plan for pregnancy: methotrexate is teratogenic, so it is stopped before conception, with the interval set by current guidance.
Dose-related toxicity is best prevented rather than treated, so the schedule and counselling matter as much as the prescription. Patients should carry a card that lists the weekly dose and the monitoring plan.
Where the exam tries to catch you
Methotrexate questions test the weekly schedule, the screening and the interactions.
- Trap: prescribing methotrexate as a daily dose Correct: it is given once weekly, because daily dosing has caused fatal toxicity.
- Trap: starting without hepatitis and tuberculosis screening Correct: these infections change the risk and must be assessed before therapy begins.
- Trap: combining methotrexate with trimethoprim-sulphamethoxazole Correct: the combination raises the risk of bone marrow suppression and should be avoided.
- Trap: assuming folic acid replaces monitoring Correct: folic acid reduces some side effects but does not prevent hepatotoxicity or marrow suppression, so monitoring continues.
Frequently asked questions
What is the standard weekly dose of methotrexate in dermatology?
Methotrexate in dermatology is usually given at 7.5 to 25 mg once a week, orally or by subcutaneous injection. The dose is titrated according to response and tolerability. Daily dosing is never used, because it has caused fatal toxicity.
Why is folic acid given with methotrexate?
Folic acid is given with methotrexate to reduce gastrointestinal and haematological toxicity. It is not thought to reduce the therapeutic benefit of methotrexate in psoriasis. The schedule of folic acid is set by the local protocol.
Which tests are needed before starting methotrexate?
Hepatitis B and C serology, tuberculosis screening, full blood count, renal and liver function and pregnancy status are assessed before methotrexate starts. A baseline chest radiograph is useful. These tests identify patients at higher risk of serious toxicity.
What is the most serious toxicity of methotrexate?
Bone marrow suppression, hepatotoxicity and hypersensitivity pneumonitis are among the most serious toxicities of methotrexate, and any of them needs prompt review. Daily dosing errors can cause fatal pancytopenia. Regular blood counts and liver tests are the main safeguards.