Cyclophosphamide


Nitrogen mustard derivative widely used in the treatment of various malignancies and auto-immune disorders.
 
Incidence
Low. Fewer than 25 cases reported.
 
Clinical manifestations
(higher with intravenous than oral route)
 
Urticaria (+++) immediate or delayed.
 
Anaphylactic shock +/- bronchospasm (+++).
 
Angioedema.
 
Vasculitis.
 
Diagnostic methods
Cutaneous testing with cyclophosphamide, ifosfamide, and cyclophosphamide metabolites: 4 hydroperoxycyclophosphamide and phosphoramide mustard.
Prick-tests and intradermal tests: cyclophosphamide and ifosfamide 1 mg/ ml and 10 mg/ ml; cyclophosphamide metabolites 1 µg/ml to 10 mg/ ml.
 
A few cases with positive skin-tests to cyclophosphamide, ifosfamide, or metabolites.
 
No specific IgE.
 
Mechanisms
Possible IgE-mediated allergy. Cyclophosphamide is a low molecular weight compound able to form an immunogenic complex with a carrier protein.
 
Phosphoramide mustard contains the bischlorethylamine group common to the nitrogen mustards leading to potential cross-reactivity with other nitrogen mustards (melphalan, chlorambucil, ifosfamide).
 
Management
Avoidance.
 
Use of an other nitrogen mustard (ifosfamide) is sometimes possible under strict medical supervision.

References

  1. Popescu N.A, Sheehan M.G, Kouides P.A, Loughner J.E, Condemi J.J, Looney R.J, Leddy J.P, "Allergic reactions to cyclophosphamide: delayed clinical expression associated with positive immediate skin-tests to drug metabolites in five patients", J. Allergy. Clin. Immunol., 1996; 97: 26-33
  2. Knysak D.J, Mc Lean J.A, Solomon W.R, Fox D.A, Mc Cune W.J, "Immediate hypersensitivity reaction to cyclophosphamide", Arthritis. Rheum., 1994; 37 (7): 1101-4
  3. Cromar B.W, Colvin M, Casale T.B, "Validity of skin tests to cyclophosphamide and metabolites", J. Allergy Clin. Immunol., 1991; 88: 965-7
  4. Kim H.C, Kesarwala H.H, Colvin M, Saidi P, "Hypersensitivity reaction to a metabolite of cyclophosphamide", J. Allergy Clin. Immunol., 1985; 76 (4): 591–4.

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