Can methotrexate cause angioedema, nausea and vomiting three days after administration?/nA 23-year-

Fråga: Can methotrexate cause angioedema, nausea and vomiting three days after administration? A 23-year-old woman with psoriasis had been treated with methotrexate 10 mg/week for two weeks. Three days after the second dose, she felt nauseous and vomited. Later, her lips, face and neck swelled and her throat was itching. She was treated with adrenaline and prednisolone with good effect. As she had also eaten a chocolate bar, she was allergy tested for milk, cacao and various nuts, with negative result. She has no other diseases and no other drugs.

Sammanfattning: There are a few cases of methotrexate hypersensitivity reported in the literature, and it cannot be ruled out that methotrexate was the cause of angioedema in the present case.

Svar: A PubMed search on methotrexate and drug hypersensitivity revealed two case reports on angioedema as a possible side-effect of methotrexate. The first report describes a 53-year-old woman with rheumatoid arthritis, who during a second treatment period with methotrexate had several episodes of pharyngeal and facial edema. The treatment was discontinued and she had no more episodes (1). The second report describes a 30-year-old man, who developed facial and pharyngeal edema 10 minutes after intravenous treatment with high dose methotrexate (2).

There are two reports on angioedema related to methotrexate in the Swedish side effect register (Swedis). A 36-year old man with psoriasis-arthritis developed recurrent episodes of tongue swelling and swallowing difficulties during methotrexate-treatment, which disappeared upon discontinuation. A 60-year-old woman with reumathoid arthritis experienced a swelling of half her tongue and breathing difficulties, less than an hour after methotrexate intake. She had, at the occasion, been treated with low dose methotrexate for at least half a year. There are also 14 reports on nausea and four on vomiting, related to methotrexate (3). Nausea and vomiting are common side effects of methotrexate, according to the manufacturer (4).

Urticaria, angioedema and/or anaphylaxia may be caused by type 1, IgE-mediated, hypersensitivity reactions, but may also be anaphylactoid, i.e. not IgE-mediated. There are case reports of patients, who has reacted with urticaria due to methotrexate, but who has tolerated high-dose methotrexate after desensitisation (5, 6).

In the present case, it cannot be ruled out that methotrexate was the cause of angioedema, and allergy testing may be of value. We recommend that the present case be reported to the regional side effect centre.