Azathioprine hypersensitivity syndrome (AHS) is a rare yet life-threatening clinical phenomenon seen in about 2% of patients within weeks of initiating therapy. Clinical features include constitutional symptoms with or without a cutaneous reaction, and a high index of suspicion is required to avoid a delay in diagnosis1,2. Less commonly, liver and renal dysfunction, hypotension, and shock may occur1. Laboratory abnormalities include neutrophilia, leukocytosis, anemia, elevated inflammatory markers, and rarely, positive antineutrophilic cytoplasmic antibodies2,3.
A woman in her 20s with systemic lupus erythematosus presented with a 3-week history of rash. The eruption started with scattered nontender, pruritic pustules on the right leg and then generalized to the torso and extremities (Figure 1). The patient reported concurrent fevers, fatigue, nausea, myalgias, and arthralgias. Laboratory evaluation revealed neutrophilia, mild anemia, stable proteinuria, and normal comprehensive metabolic panel. Six weeks prior to presentation, azathioprine (AZA) was started. Biopsy showed subcorneal collection of neutrophils with diffuse dermal neutrophilic infiltrate without evidence of vasculitis (Figure 2). A diagnosis of AHS was made. AZA was substituted with mycophenolate mofetil, resulting in complete resolution on Day 10 followup.
Multiple erythematous pustules and nodules on the right leg.
Histopathologic image showing a subcorneal collection of neutrophils with diffuse dermal neutrophilic infiltrate (H&E, original magnification × 10).
While the exact etiology of AHS remains unknown, current studies have suggested a type III or IV immune-mediated reaction1,2. Given the mortality associated with AHS, for patients who present with systemic and cutaneous symptoms while taking AZA, the safest course is to stop taking it. Upon AZA cessation, complete resolution typically occurs within a week2,4. Rechallenge is not recommended because of an increased risk of morbidity and mortality4.
