Azathioprine hypersensitivity syndrome in a cohort of ANCA-associated vasculitis patients

Publication date: Available online 24 October 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Arno C. Hessels, Jan Stephan F. Sanders, Annick A.J.M. van de Ven, Bart-Jan Kroesen, Annechien J.A. Lambeck, Abraham Rutgers, Coen A. Stegeman

Abstract

Background

Azathioprine hypersensitivity syndrome is a rare complication of azathioprine therapy. Its symptoms resemble infection or relapse of inflammatory disease, hindering correct diagnosis. Current literature is limited to sporadic case reports and reviews.

Objective

To estimate the incidence of azathioprine hypersensitivity syndrome and describe its characteristics in the context of an observational cohort of ANCA-associated vasculitis patients. Also, to facilitate early recognition and awareness among clinicians.

Methods

Within a cohort of 290 ANCA-associated vasculitis patients receiving azathioprine maintenance therapy, frequency of azathioprine hypersensitivity was described and characteristics were compared between hypersensitive and non-hypersensitive patients. Clinical picture, laboratory abnormalities and concurrent medication of patients with azathioprine hypersensitivity were described.

Results

Of 290 patients, 25 (9%) experienced azathioprine hypersensitivity after a median of 14 (IQR 12-18) days. Frequent symptoms were fever (100%), malaise (60%), arthralgia (36%) and rash (32%). All patients used prednisolone (median 10mg/d, IQR 9.4-16.3mg/d) at the time of the hypersensitivity reaction. Most patients had a rise in CRP, leukocyte counts and neutrophil counts, but no eosinophilia. Thiopurine S-methyltransferase (TPMT) activity was significantly lower in hypersensitive patients (median 74.4 [IQR 58.0-80.1]nmol/gHb/l) compared to controls (median 81.4 [71.9-90.5] nmol/gHb/l), P=0.01. Hypersensitive patients had a higher risk of relapse (HR 2.2, 95% CI 1.2-4.2; P=0.01).

Conclusion

Azathioprine hypersensitivity syndrome is strikingly common in ANCA-associated vasculitis, might be associated with reduced TPMT activity, is accompanied by an increase in neutrophil counts and may occur even during concomitant prednisolone therapy. Proper recognition may prevent unnecessary hospital procedures and damage to the patient.