Azathioprine is an imidazole analogue of 6-mercaptopurine. This immunosuppressive agent has become the mainstay of therapy for rheumatological and dermatological conditions, and inflammatory bowel diseases.
Hypersensitivity reactions to azathioprine: more than 50 patients reported (up to 1998) in English medical literature.
Risk factors
Presence of fever, gastrointestinal symptoms, or exacerbation of the underlying disease upon initiation of the drug are risk factors for a hypersensitivity reaction.
Concomitant use of corticosteroids (hypotension).
Clinical manifestations
(within 4 weeks of initiation of the treatment)
General: fever (38/49), hypotension (4/49), tachycardia (2/49).
Cutaneous: urticaria (8/49), maculopapular eruption (3/49), erythema multiforme, erythema nodosum, purpura, petechiae.
Respiratory: dyspnea (5/49), pneumonitis (3/49), cough (1/49).
Gastrointestinal: nausea (21/49), vomiting (21/49), diarrhea (10/49), jaundice (3/49), pancreatitis (3/49), hepatitis (3/49).
Musculoskeletal: arthralgia (7/49), myalgia (6/49), rhabdomyolysis (1/49).
Neurological: headache (7/49), meningismus (3/49), peripheral neuropathy (2/49), seizure (1/49).
Renal: oliguria (3/49), acute interstitial nephritis (1/49).
Diagnostic methods
No antibodies to azathioprine or its metabolites have been found.
Recurrence of symptoms with drug re-challenge (to be performed with extreme caution).
Role of the imidazole side-chain?
Avoidance, especially if the initial dose of the medication elicits a febrile or systemic response.


  1. Fields C.L, Robinson J.W, Roy T.M, Ossorio M.A, Byrd R.P Jr, "Hypersensitivity reaction to azathioprine", South. Med. J., 1998; 91 (5): 471-4
  2. Jones J.J, Ashworth J, " Azathioprine-induced shock in dermatology patients", J. Am. Acad. Dermatol., 1993; 29 (5.1): 795-6
  3. Rosenthal E, "Azathioprine shock", Postgrad. Med. J., 1986; 62 (729):

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