Can stopping methotrexate (methotrexate) trigger urticaria?

Methotrexate Discontinuation and Urticaria

There is no evidence in the medical literature that stopping methotrexate can trigger urticaria, though methotrexate has been used as a treatment for chronic urticaria in patients not responding to conventional therapy.

Methotrexate and Urticaria: The Connection

• Methotrexate is primarily used in inflammatory conditions including atopic dermatitis, psoriasis, and rheumatoid arthritis as an immunomodulator 1
• Rather than causing urticaria upon discontinuation, methotrexate has actually been used as a treatment for chronic urticaria that is resistant to antihistamines 1, 2
• In a retrospective study, methotrexate showed effectiveness in treating chronic urticaria with a complete response achieved in 7 out of 8 patients (87%) who were not responding to high-dose antihistamines 2
• A randomized placebo-controlled trial, however, did not show significant additional benefit of methotrexate over H1 antihistamines alone in chronic spontaneous urticaria 3

Methotrexate Discontinuation: Known Effects

• When methotrexate is discontinued, the primary concern is disease flare of the condition being treated, rather than development of new symptoms like urticaria 4
• Guidelines recommend tapering or discontinuing methotrexate once clearance or near-clearance of the treated condition is achieved and maintained 1
• Non-responding patients on a sufficient dose (15mg per week or greater) may consider discontinuing therapy after a 12 to 16 week trial 1

Methotrexate and Hypersensitivity Reactions

• While not related to discontinuation, it's worth noting that methotrexate itself can occasionally cause hypersensitivity reactions:
• Anaphylactoid reactions including urticaria have been reported during methotrexate administration, though these are rare 5
• These reactions typically occur during administration rather than after discontinuation 5
• In rare cases, methotrexate can cause cutaneous ulceration, but this is different from urticaria 6

Management Considerations

• If a patient develops urticaria after stopping methotrexate, consider other potential causes:

  • New medication started to replace methotrexate 1
  • Underlying condition flare that manifests with urticarial symptoms 4
  • Coincidental development of chronic spontaneous urticaria 1

• For management of urticaria regardless of cause:

  • First-line treatment includes non-sedating H1 antihistamines 1
  • For refractory cases, options include higher doses of antihistamines, adding H2 antihistamines, or considering immunomodulatory agents 1
  • Ironically, methotrexate itself may be considered for treatment of chronic urticaria not responding to antihistamines 2, 7

Clinical Pearls and Pitfalls

• Methotrexate has a well-documented side effect profile, but urticaria upon discontinuation is not among the recognized effects 1
• When discontinuing methotrexate, monitor for disease flare of the original condition rather than new-onset urticaria 4
• If urticaria develops after methotrexate discontinuation, consider it coincidental and treat according to standard urticaria management protocols 1
• Remember that methotrexate has actually been used as a treatment for chronic urticaria in some cases 2, 7