Methotrexate and Its Use for Psoriasis and Other Skin Conditions

What Is Methotrexate?

Methotrexate (formerly known as amethopterin) is a medication used to treat a wide range of medical conditions including blood and solid organ cancers, autoimmune conditions, ectopic pregnancy, and in some cases, medical abortions.^[1] 

Brand names that are associated with this medication are:

Trexall

Rasuvo

How Does Methotrexate Work?

Methotrexate works by inhibiting dihydrofolate acid reductase, an enzyme that makes folic acid and is required for cells to divide, as well as make, recycle and repair their DNA.^[2] This enzyme is especially important for the survival of rapidly dividing cells like cancer cells and certain immune cells such as T-cells and B-cells. Therefore, methotrexate can treat cancers, as well as autoimmune and autoinflammatory conditions where the immune system is dysregulated and working abnormally.

What Conditions Does Methotrexate Treat? 

Methotrexate is FDA-approved to treat psoriasis (both skin and joint diseases), rheumatoid arthritis, Sezary Syndrome (a blood cancer that originates from the skin lymphoma called cutaneous T-cell lymphoma), lung cancer (particularly squamous cell and small cell types), Non-Hodgkin’s lymphoma, and cancers related to pregnancy (gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole).^[3]

Methotrexate is often used off-label by physicians for a large number of other skin conditions including immunobullous diseases, autoimmune connective tissue diseases, vasculitis, (inflammation of the blood vessels) and eczema.^[1]

How Is Methotrexate Given?

Methotrexate tablets can be taken orally, or solution forms can be administered intravenously (into veins), intramuscularly (into the muscle), or subcutaneously (under skin).^[1] When taken orally, it must first be absorbed by the intestines, then passed through the liver before reaching the bloodstream. Therefore, the bioavailability of the drug is lowered.^[3] However, when administered by injection, the entire dose of methotrexate is absorbed directly into the blood, which is called 100% bioavailability.

Methotrexate is often administered once weekly. Since methotrexate inhibits the synthesis of folate, an important vitamin for cellular function, folic acid supplementation is usually taken daily, except on the day that the methotrexate dose is taken.^[1]

What Are Potential Side Effects and Risks of Methotrexate?

• Methotrexate may cause liver damage in certain people if taken long term. This is especially true in patients who have certain underlying medical conditions, such as diabetes, obesity, hepatitis C, psoriasis, and in those who do not take folic acid supplementation during methotrexate course.^[1,4]

• Methotrexate may rarely cause injury to the lungs, such as acute pneumonitis (inflammation of the lung tissue) and lung fibrosis (thickening of the lung tissue).^[1,5]

• The most life-threatening side effect of methotrexate is pancytopenia, a deficiency of all three types of blood cells (red cells, white cells, and platelets). Pancytopenia due to methotrexate is most commonly caused by drug interactions (especially when taken together with sulfamethoxazole/trimethoprim^[6] or nonsteroidal anti-inflammatory medications)^[7], kidney disease, or when folic acid supplementation is not taken.^[8]

• Methotrexate can cause an abortion and interfere with the development of the fetus. Therefore, methotrexate should be avoided in women of potential child-bearing age unless they are using reliable birth control.^[1] It is considered pregnancy category X, which means animal or human studies have shown abnormalities in babies when females take this medication during pregnancy.

• There are rare reports of methotrexate causing lymphoma.^[10]

• Because methotrexate is excreted in the urine, high dose methotrexate can precipitate in the urinary tract and cause kidney damage.^[1]

• Certain medications can interact with methotrexate and increase its toxicity to blood cells, causing bone marrow failure and liver injuries.^[1]

• Dizziness and fatigue are also potential adverse reactions from methotrexate, so one should exercise caution when driving or operating machinery while taking this medication.^[3]

• Methotrexate can cause nausea and a decrease in appetite. Rarely it can also cause diarrhea, vomiting and mouth ulcers. Folic acid supplementation may help to reduce these side effects.^[9] 

A practitioner should periodically monitor liver, kidneys, and blood count of a patient who is taking methotrexate.