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Methotrexate associated photosensitivity

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Methotrexate associated photosensitivity

  • photosensitivity reactions are established side effects of methotrexate treatment and are currently listed in the product information, including the Patient Information Leaflet (1)

  • photosensitivity reactions often look and feel like sunburn
    • can leave sun-exposed skin with a rash, redness, swelling, blisters, red bumps or oozing lesions
    • severe cases can cause secondary skin infection
    • photosensitivity reactions fall into two categories
      • phototoxic reactions
        • a drug is activated by exposure to UV light and causes damage to the skin that can look and feel like a sunburn or a rash
        • reactions can happen within minutes or after hours of exposure and are usually limited to the skin that has been exposed
        • exposure to methotrexate and UV radiation can result in the typical phototoxic exaggerated sunburn response, characterized by erythema and oedema, and often accompanied by pain, tenderness, and pruritus (2)
          • blistering and desquamation may also occur in severe cases
          • the sites most frequently involved are sun-exposed areas on the face, chest, arms, and legs, as well as the dorsa of the hands and posterior region of the neck
          • hyperpigmentation is also common after the acute reaction has resolved, and may persist for several months (2)
      • photoallergic reactions
        • occur when UV rays interact with the ingredients in medicines or other products applied directly to the skin
        • the body's immune system recognizes changes caused by sun exposure as a foreign threat
        • body produces antibodies and attacks, causing a reaction
        • note that these reactions are distinct from "recall" reactions where radiation-induced dermatitis and sunburn can reappear on re-exposure to radiation and sunlight while on methotrexate therapy
          • UV recall is an exceptional inflammatory phototoxic reaction that occurs after administration of a systemic therapy and strictly affects areas of skin that have been involved in a prior episode of UV-induced solar erythema (2)

Advice for healthcare professionals (1):

  • photosensitivity reactions (which include phototoxicity, where a drug is activated by exposure to UV light and causes damage to the skin that can look and feel like a sunburn or a rash) are known side effects of methotrexate treatment and can occur with both low-dose and high-dose treatment
  • reactions manifest as severe sunburn such as rashes with papules or blistering, with some patients reporting swelling; rarely, photosensitivity reactions have contributed to deaths from secondary infections
  • healthcare professionals, including those prescribing and dispensing methotrexate, should remind patients to take precautions to protect themselves from the sun and UV rays
  • report suspected adverse drug reactions associated with methotrexate on a Yellow Card


  • Drug Safety Update volume 17, issue 1: August 2023: 2.
  • Sibaud V. Anticancer treatments and photosensitivity. J Eur Acad Dermatol Venereol. 2022 Jun;36 Suppl 6(Suppl 6):51-58. doi: 10.1111/jdv.18200. PMID: 35738806; PMCID: PMC9328141

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