Azathioprine Hypersensitivity Syndrome – Two Case Reports of Autoimmune Bullous Dermatoses

Abstract

Azathioprine is a widely used immunosuppressant for autoimmune bullous dermatoses, valued for its steroid-sparing properties. However, it can rarely precipitate azathioprine hypersensitivity syndrome, an idiosyncratic reaction presenting with fever, malaise, exanthema, and arthralgia within two to four weeks of therapy. Because its systemic manifestations often mimic infection or disease exacerbation, Azathioprine hypersensitivity syndrome is frequently under-recognized. We report two cases of azathioprine hypersensitivity syndrome in patients with autoimmune bullous dermatoses. The first involved a 63-year-old male with pemphigus foliaceus who developed fever, myalgia, and hypotension 14 days after initiating azathioprine, with recurrence and multi-organ involvement – including acute kidney injury – upon re-exposure. The second case concerned a 92-year-old male with bullous pemphigoid who developed fever and marked systemic inflammation within three days of treatment initiation. Both patients demonstrated rapid resolution of symptoms after azathioprine withdrawal. These cases highlight the potential severity of azathioprine hypersensitivity syndrome, including multi-organ involvement and sepsis-like presentation. Dermatologists must maintain a high index of suspicion for azathioprine hyper-sensitivity syndrome during the early weeks of azathioprine therapy, as prompt recognition and cessation are critical for favorable outcomes.