The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome

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.

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

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.

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.

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

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.