Methotrexate and psoriasis: what should we know?

Methotrexate, also known as4-amino-10-methylfolic acid, is a treatment used in cases of psoriasis or psoriatic arthritis. Since the 1960s, it has been widely used to treat severe psoriasis. It exerts various actions, varying according to the dose used. Its anti-proliferative effect slows down the multiplication of cells. It is thus used in the treatment of psoriasis, where the skin cells multiply excessively. Its anti-inflammatory action and its ability to modulate the immune response are also exploited to counter the chronic skin inflammation observed in psoriasis.

How does methotrexate act on psoriasis?

The action of methotrexate can be explained by its ability to inhibit the intracellular enzyme dihydrofolate reductase, reducing the supply of reduced folate cofactors necessary for the synthesis of nucleic acids and proteins, and thus directly interfering with epidermal cell division.

Another mechanism has also been suggested. Methotrexate treatment would eliminate CD8+ T lymphocytes, which would consequently suppress the activity signal of macrophages. This would reduce the production of prostaglandins, affecting the activation and proliferation of CD4+ T lymphocytes. Thus, by generally reducing the activity of T lymphocytes, this results in limiting the proliferation of keratinocytes, leading to the onset of psoriasis symptoms.

Before initiating the treatment, the doctor must ensure that there are no contraindications. A blood test is carried out to assess the functioning of the kidneys, liver, blood cells and to screen for any potential infections. For women of childbearing age, a pregnancy test is conducted. A chest X-ray is performed in certain cases.

If the results are normal, the treatment is prescribed in the form of tablets or subcutaneous injections, to be taken or administered once a week. The dose of methotrexate typically varies between 7.5 and 25 mg per week, with an average of 15 mg per week. The tablets can be taken all at once or divided between the morning and evening, on the specified day of the week for the treatment. They are swallowed during meals.

In order to monitor your tolerance to the treatment, blood tests are carried out after 7 days, then every 15 days during the first month, followed by once a month every 2 to 3 months. If necessary, your doctor can adjust the dose of methotrexate by increasing or decreasing it. In some cases, the treatment follow-up may include regular check-ups.

In the case of psoriasis, a chronic disease, the duration of treatment with methotrexate can extend from several months to several years, provided it is tolerated and effective. This is a suspension treatment that does not cure the disease but allows for the control of its progression throughout the duration of the treatment.

The results of the treatment vary from one individual to another, but in approximately 70% of cases, an improvement in psoriasis is observed. Some people may notice an improvement as early as the first month of treatment, but the maximum effect is typically achieved after about 3 to 4 months of treatment.

There are certain contraindications to the use of methotrexate:

• Pregnancy and breastfeeding.

It is crucial not to contemplate pregnancy during methotrexate treatment, in the month or ovulatory cycle following its cessation for women, or within 3 months for men. Pregnancy is strongly discouraged during the treatment. If a pregnancy occurs, it is important to immediately stop the treatment and inform your doctor. Indeed, methotrexate is a teratogenic drug that can lead to foetal death, miscarriage, or congenital abnormalities. Similarly, breastfeeding is contraindicated during treatment as methotrexate can pass into breast milk and be toxic to the baby.

• Use of other medications.

Some drug combinations are forbidden with methotrexate as they could potentially increase its concentration in the blood and render it toxic. Before taking a new medication, it is crucial to check with your doctor if it is compatible with methotrexate.

• Vaccines.

Most vaccines can be administered during treatment with methotrexate, with the exception of "live" vaccines such as the yellow fever vaccine. Indeed, methotrexate is an immunosuppressant associated with a risk of severe infections. Vaccination in these patients could pose a risk of developing a disease. If necessary, live vaccines should be administered at least three weeks before starting the treatment.

Note: It is essential to maintain regular follow-ups with your doctor and dermatologist throughout the duration of the treatment, not forgetting to carry out the prescribed blood tests.

Adverse effects are rare, but it is important that you are informed about them. Among the possible adverse effects are:

• A decrease in red blood cells, white blood cells, or platelets.

• A liver condition, manifesting in individuals with a liver weakened by alcohol consumption, overweight or a history of viral infections.

• Rarely, symptoms such as coughing, fever, or shortness of breath may occur.

• Nausea and abdominal heaviness can occur, typically in a moderate manner.

• Aphthous-like erosions can form in the mouth or on the skin.

• At times, one may experience feelings of fatigue or a decrease in libido.

WEINSTEIN G. D. & al. Cytotoxic and Immunologic Effects of Methotrexate in Psoriasis. The Society for Investigate Dermatology (1990).

BOFFA M. J. & al. Methotrexate for psoriasis. Clinical and Experimental Dermatology (1996).

KALB R. E. & al. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. Journal of the American Academy of Dermatology (2009).