Ethylenediamine is used as a binding agent (creams, eye drops, aminophylline, enema) conferring greater solubility and reducing the alkalinity of the drug. Aminophylline is a complex of 2 theophylline molecules to one ethylenediamine molecule.
Ethylenediamine sensitivity: 13% in patients with contact dermatitis.
Clinical manifestations
(allergic reaction may occur with intravenous aminophylline and oral formulations or suppositories).
Manifestations usually appear 24 to 48 hours after intake of the drug, but delays of 6 to 8 hours have also been reported.
General: anaphylactic shock, fever, headache, myalgia.
Respiratory: bronchospasm, occupational asthma in exposed subjects to ethylenediamine vapors.
Cutaneous: pruritus, urticaria, maculopapular rash, angioedema, periorbital edema, exfoliative dermatitis, erythroderma, contact dermatitis (occupational in pharmacists).
Diagnostic methods
Cutaneous testing.
Intradermal skin-tests: aminophylline 1%, ethylenediamine 0.1% and 1%.
Patch-tests: aminophylline 1% pet. , ethylenediamine 1% pet.
No specific IgE found.
Specific histamine-release positive in one case.
Possible IgE-mediated hypersensitivity in few cases
Type IV cellular reaction. Sensitization to ethylenediamine is particularly common with topical drugs.
Acetylation is one of the major metabolic pathways for ethylenediamine.
Ethylenediamine-sensitive patients can develop allergy to piperazine (antihelminthic agent); to ethanolamine group antihistamines (clemastine, carbinoxamine, diphenhydramine, hydroxyzine); to triethanolamine containing creams and to ethylenediamine antihistamines (tripelennamine hydrochloride, antazoline phosphate).
Use an ethylenediamine-free theophylline.


  1. Urbani C.E, "Urticarial reaction to ethylenediamine in aminophylline following mesotherapy", Contact. Dermatitis, 1994; 31 (3): 198-9
  2. Eedy D.J, "Angioneurotic oedema following piperazine ingestion in an ethylenediamine-sensitive subject", Contact. Dermatitis, 1993; 28 (1): 48-9
  3. de la Hoz B, Perez C, Tejedor M.A, Lazaro M, Salazar F, Cuevas M, "Immediate adverse reaction to aminophylline", Ann. Allergy., 1993; 71 (5): 452-4
  4. Thompson P.J, Gibb W.R.G, Cole P, Citron K.M, " Generalized allergic reactions to aminophylline", Thorax, 1984; 39 (8):600-3.
  5. Elias J.A, Levinson A.I, "Hypersensitivity reactions to ethylenediamine in aminophylline", Am. Rev. Respir. Dis., 1981; 123 (5): 550-2.

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