Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis

Rheumatol Int. 2016 Jul;36(7):1027-32. doi: 10.1007/s00296-016-3489-0. Epub 2016 May 7.


Granulomatosis with polyangiitis (GPA), an autoimmune disease characterized by inflammatory granulomas and necrotizing small-vessel vasculitis, primarily affects the respiratory tract and kidneys. Azathioprine (AZA) is a purine analog that is commonly used for maintaining GPA remission after induction therapy with cyclophosphamide. While the dose-dependent side effects of AZA are common and well known, hypersensitivity reactions such as pulmonary toxicity are rare. Here, we describe a case involving a 38-year-old man with GPA-associated pauci-immune crescentic glomerulonephritis who developed subacute hypersensitivity pneumonitis (HP) during AZA maintenance therapy. Five months after the initiation of AZA administration (100 mg/day), the patient was admitted with a 7-day history of cough, dyspnea, and fever. High-resolution computed tomography of the chest showed ill-defined centrilobular nodules and diffuse ground-glass opacities in both lung fields. Bronchoscopy with bronchoalveolar lavage was negative for infectious etiologies. A transbronchial lung biopsy specimen revealed poorly formed non-necrotizing granulomas. A chest radiograph obtained at 2 weeks after discontinuation of AZA showed normal findings. The findings from this case suggest that AZA-induced HP should be considered as a differential diagnosis when a patient with GPA exhibits fresh pulmonary lesions accompanied by respiratory symptoms during AZA therapy.

Keywords: Azathioprine; Granulomatosis with polyangiitis; Hypersensitivity pneumonitis; Wegener’s granulomatosis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alveolitis, Extrinsic Allergic / chemically induced*
  • Alveolitis, Extrinsic Allergic / diagnosis
  • Alveolitis, Extrinsic Allergic / immunology
  • Azathioprine / adverse effects*
  • Biopsy
  • Bronchoscopy
  • Drug Hypersensitivity / diagnosis
  • Drug Hypersensitivity / etiology*
  • Drug Hypersensitivity / immunology
  • Granulomatosis with Polyangiitis / diagnosis
  • Granulomatosis with Polyangiitis / drug therapy*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Male
  • Predictive Value of Tests
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Immunosuppressive Agents
  • Azathioprine