The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome

J Am Acad Dermatol. 2011 Jul;65(1):184-91. doi: 10.1016/j.jaad.2010.04.041. Epub 2011 Apr 15.


Background: Azathioprine (AZA) hypersensitivity syndrome is a rare side effect that typically occurs early in the initiation of therapy and may include a cutaneous eruption. It is often under-recognized because it mimics infection or disease exacerbation. Until recently, the cutaneous findings associated with AZA hypersensitivity have been reported using nonspecific, descriptive terms without a supportive diagnostic biopsy.

Objective: To characterize the cutaneous and histologic findings associated with AZA hypersensitivity syndrome.

Methods: We conducted a retrospective analysis of two cases of AZA hypersensitivity syndrome and describe the cutaneous manifestations and histological findings of each case. A review of the English literature for cases of AZA hypersensitivity or allergic or adverse reactions associated with AZA was performed.

Results: Sixty-seven cases of AZA hypersensitivity were reviewed; 49% (33/67) had cutaneous manifestations. Of those cases presenting with cutaneous findings, 76% (25/33) had biopsy results or clinical features consistent with a neutrophilic dermatosis, whereas the other 24% (8/33) were reported as a nonspecific cutaneous eruption.

Limitations: Only case reports in which the skin findings could be classified were reviewed.

Conclusions: The predominant cutaneous reaction reported in the literature and observed in the present case series is a neutrophilic dermatosis. Hypersensitivity to AZA can manifest along a wide clinical spectrum from local neutrophilic disease to a systemic syndrome. Skin findings may be an important early clue to the diagnosis of AZA hypersensitivity and aid in prompt recognition and treatment of this potentially life-threatening adverse drug effect.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Aged
  • Azathioprine / adverse effects*
  • Azathioprine / therapeutic use
  • Biopsy, Needle
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Eruptions / epidemiology
  • Drug Eruptions / etiology*
  • Drug Eruptions / physiopathology
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / epidemiology
  • Female
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Sweet Syndrome / epidemiology
  • Sweet Syndrome / etiology*
  • Sweet Syndrome / physiopathology


  • Immunosuppressive Agents
  • Azathioprine