Methotrexate

Methotrexate is a relatively old treatment which has been used in psoriasis since the late 1960s. There are relatively few randomised controlled trials looking at its efficacy; however, it is considered to be a very useful drug for the management of severe psoriasis. Its downsides are the degree to which it has adverse systemic effects.

It is an anti-proliferative drug, that is it affects cell DNA and stops psoriatic skin cells from developing. It does this by inhibiting folic acid, thus natural levels of folic acid in patients on methotrexate are likely to be lower. For patients with psoriasis, the dosage is kept low and given once a week at the same time. It is usually taken orally (starting at a low dose of 2.5 or 5 mg working up to a maximum dose of 20–25 mg depending on blood results and effect), but can also be given as an intramuscular injection. This latter technique is useful if the patient is particularly affected by nausea. Before commencing a patient on methotrexate, they must be counselled as to the potential side effects (listed in Table 8.5) and the likely impact it will have on their lifestyle (e.g. need to reduce alcohol intake). Subsequently regular blood monitoring is needed, particularly to ascertain kidney and liver function. Kidney function is important as the drug is secreted through the kidneys and any decrease in function could increase the likelihood of toxicity.

Table 8.5 Potential side effects of methotrexate.   Side effects Notes   Leukopenia and thrombocytopenia Falling white blood cell and platelet counts indicate bone marrow toxicity and the treatment should be discontinued. Generally occurs 8–11 days after commencement of treatment.   Oral and plaque ulceration Can indicate toxicity.   Lower levels of folic acid Can lead to decreases in red blood cells and possible megaloblastic anaemia. A dose of 1–5 mg of folic acid is usually given daily (except on the day when the methotrexate is taken). This does not seem to compromise the therapeutic efficacy of the methotrexate.   Teratogenicity Some evidence to suggest this, sexually active fertile individuals should take birth control precautions.   Hepatotoxicity This is a major clinical concern as it is known that prolonged use of methotrexate increases the risk of fibrosis and eventual cirrhosis of the liver. This is made more likely there is a high alcohol intake. Blood tests are helpful to indicate liver function, but they do not indicate fibrosis. For this a liver biopsy is needed which itself carries risks.   Pulmonary toxicity Is unusual and can present as a non-productive cough with or without fever.