Management and successful desensitization in methotrexate‐induced anaphylaxis

Abstract

Anaphylactic/anaphylactoid reactions to methotrexate are rare. In patients with methotrexate-induced anaphylaxis, discontinuation of treatment may increase the risk of death due to cancer progression. In such patients, desensitization may enable the patient to continue treatment with methotrexate. We report the case of a child with metastatic osteosarcoma, who experienced an anaphylactic/anaphylactoid reaction to methotrexate. Skin tests with methotrexate were not performed because their diagnostic value is controversial. Desensitization with methotrexate was successful and allowed the patient to complete 12 additional courses of chemotherapy. Thus, we confirm that desensitization may be a safe procedure in patients with cancer who experience methotrexate-induced anaphylaxis.

Hypersensitivity reaction to high-dose methotrexate and successful rechallenge in a pediatric patient with osteosarcoma

“…Rechallenging pediatric oncology patients with high‐dose methotrexate following hypersensitivity reactions has also been reported in the literature . In osteosarcoma patients, these case reports have often used extended infusions (e.g., infusion times of up to 27 hours) to desensitize patients to methotrexate . Data suggest that attainment of adequate peak methotrexate plasma concentrations (≥700–1,000 µmol/L) is important for successful outcomes in osteosarcoma patients .…”

Anaphylaxis during the first course of high-dose methotrexate: a case report and literature review

“…Most of the reviewed cases occurred after repeated courses of MTX 6–15 . In contrast, only five patients (four from PubMed search plus ours) experienced anaphylactic reaction during the first MTX infusion, 2–5 as shown by our case and the literature search.…”

Clinical practice

“…Intravenous desensitization for methrotrexate is started at 1/1,000 of the full dose in 1.5 h followed by 1/100 in 1.5 h, 1/10 in 6 h and the remaining dose in 24 h every therapeutic cycle [3, 7]. This procedure may necessitate a dose reduction due to increased toxicity as a result of prolonged exposure to methotrexate [3].…”

“…This procedure may necessitate a dose reduction due to increased toxicity as a result of prolonged exposure to methotrexate [3]. …”

“…From 0.01 mg twofold increases every 15 minKim [11]♀, 7, tuberculosisRifampicin and isoniazideDyspnea, rash, pruritusPositiveOralYesStarting dose 0.1 mg, twofold increase every 15 minMorgan [18]♀, 4, astrocytomaCarboplatinFlushing, urticaria, facial edema, coughNDIVYes1–2.5–5–7.5–10–10–25–50-remaining mg. Dose repeated if symptoms occurredBroome [5]♂, 3, astrocytomaCarboplatinCough, congestion, flushing,NegativeIVYes♂, 7, astrocytomaAbdominal pain, erythemaNegative1–2.5–5–10–25 mg iv push q15 min followed by 25–50 mg infusion q15 min, followed by 331 mg 200 mg/hr continuous infusionOgle [19]♀, 3, neurofibromatosisCarboplatinAbdominal discomfort, flushing, increased respiratory effortNRIVYes0.01–0.1–0.5–1.0–2.5–5–10–22.5 mg push q15 min followed by 66 mg over 44 min.Soyer [21]8, ALL E. coli l -asparaginaseAnaphylaxisNRIVYes in 3 casesStarting dose 1 IU, dose doubling every 10 min doseFive uneventful (3 due to anaphylactic reaction during desensitization)Bouchireb [3]♀, 9, astrocytomaMethotrexateUrticariaNDIVYes1/1,000 of full dose in 1.5 h followed by 1/100 in 1.5 h, 1/10 in 6 h and the remaining dose in 24 hCaldeira [7]♂, 9, ALLMethotrexateUrticariaNDIVYes1/1,000 of full dose in 1.5 h followed by 1/100 in 1.5 h, 1/10 in 6 h and the remaining dose in 24 h CF cystic fibrosis, ALL acute lymphatic leukemia, PPL penicilloyl-poly- l -lysine, NR not reported, ND not done…”