title: Increased rates of early adverse reaction to azathioprine in patients with Crohn's disease compared to autoimmune hepatitis: a tertiary referral center experience.
abstract: OBJECTIVE
  Idiosyncratic drug hypersensitivity may occur at increased rates in specific patient populations. Azathioprine has a significant early adverse reaction (EAR) profile, which includes an acute syndrome of constitutional symptoms, fever, rash, and acute pancreatitis and often requires discontinuation of drug. EAR precludes azathioprine use in patients with Crohn's disease (CD) and autoimmune hepatitis (AIH). Our aims were to investigate differential rates of EAR to azathioprine in CD compared to AIH in a tertiary referral center population.
  
  
  METHODS
  Retrospective chart review of consecutive CD and AIH patients who were initiated on azathioprine in our inflammatory bowel disease (IBD) and hepatology centers was performed. EAR (fevers and constitutional symptoms, severe arthralgias, nausea, and vomiting) were defined as those occurring within 1 month of initiation. EAR rates between AIH and CD patients were compared using the Fisher's exact test.
  
  
  RESULTS
  One hundred and forty-three CD (88F/55M; age 39.2 +/- 13 yr) and 40 AIH (35F/5M; age 53.1 +/- 14 yr) patients were studied. All patients were initiated with equivalent azathioprine dosage (50 mg qd). All AIH patients were on prednisone (mean daily dose 7.5 mg) compared to 51% of CD patients (median daily dose 20 mg). EAR rates were significantly higher in CD patients (42/143; 29%) compared to AIH (2/40; 5%) (Fisher's exact test; p= 0.008). EAR excluding nausea and vomiting were still significantly higher in CD patients (27/143; 19%) compared to AIH (1/40; 2.5%) (Fisher's exact test; p= 0.01). All patients with EAR required drug discontinuation and 7% of CD patients required hospitalization for management of these complications.
  
  
  CONCLUSIONS
  CD patients represent a unique subgroup at increased risk of EAR to azathioprine. Mechanisms behind these reactions need to be further defined.
authors.affiliation: Division of Gastroenterology and Hepatology; Division of Allergy and Immunology, Department of Medicine, Digestive Disease Center, Froedtert Memorial Lutheran Hospital, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
authors.forename: Kia
authors.initials: K
authors.lastname: Saeian
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Varma
authors.forename: Jose
authors.initials: J
authors.lastname: Franco
authors.forename: Joshua F
authors.initials: JF
authors.lastname: Knox
authors.forename: Judy
authors.initials: J
authors.lastname: Podoll
authors.forename: Jeanne
authors.initials: J
authors.lastname: Emmons
authors.forename: Michael
authors.initials: M
authors.lastname: Levy
authors.forename: David G
authors.initials: DG
authors.lastname: Binion
mesh_terms: D000208:Acute Disease; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018771:Arthralgia / Q000139:chemically induced; D001379:Azathioprine / Q000009:adverse effects*; D003424:Crohn Disease / Q000188:drug therapy*; D004198:Disease Susceptibility; D004342:Drug Hypersensitivity / Q000209:etiology*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D019693:Hepatitis, Autoimmune / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010195:Pancreatitis / Q000139:chemically induced; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D001379:Azathioprine; D011241:Prednisone