Folic acid antagonist used in the treatment of several neoplasms and inflammatory disorders.
Anaphylactic shock: fewer than 20 cases reported.
Clinical manifestations
General: anaphylactic shock.
Cutaneous: pruritus, urticaria, angioedema, cutaneous vasculitis, severe epidermal toxicity.
Respiratory: acute pneumonitis, bronchospasm.
Hematological: pancytopenia, agranulocytosis, hemolytic anemia.
Diagnostic methods
Cutaneous testing.
Skin prick-test: with methotrexate 10 mg/ ml. One positive case (anaphylactic shock).
Intradermal test: 0,1 ml of 25 mg/ ml solution of methotrexate. One case positive complicated by syndromic reaction (anaphylactic shock).
No specific IgE found.
No specific histamine release shown.
Drug induced lymphocyte stimulation test (DLST): positive in 2 cases of pancytopenia, and one case of agranulocytosis.
IgG3 antibody in a case of hemolytic anemia.
Type I reactions: anaphylaxis, urticaria, angioedema.
Type II reactions: hemolytic anemia.
Type III reactions: acute pneumonitis, cutaneous vasculitis.
If no alternative therapy exists and there is a non life-threatening hypersensitivity reaction, re-challenge may be considered.
Most of the time (92%) there are recurrent symptoms despite premedication.
Desensitization is sometimes used (one successful case beginning with 0.1 mg up to 25 mg in 60 hours).


  1. Alkins S.A, Byrd J.G, Morgan S.K, Ward F.T, Weiss R.B, "Anaphylactoid reactions to methotrexate", Cancer. 1996; 77 (10): 2123-6
  2. Vega A, Cabanas R, Contreras J, Lopez-Casana J, Lopez-Serrano C, Pascual C, Martinez-Alzamora F, "Anaphylaxis to methotrexate: a possible IgE-mediated mechanism", J. Allergy. Clin. Immunol., 1994; 94 (2.1): 268-70
  3. Cohn J.R, Cohn J.B, Fellin F, Cantor R, "Systemic anaphylaxis from low dose methotrexate", Ann.Allergy., 1993; 70 (5): 384-5
  4. Gluck-Kuyt I, Irwin L.E, "Anaphylactic reaction to high dose methotrexate", Cancer. Treat. Rep., 1979; 63: 797-8

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.