Azathioprine-Associated Hypersensitivity Reaction in a Patient With Churg Strauss Vasculitis

Abstract

A zathioprine (AZA) has been used since the beginnings of immunosuppressive therapy in organ transplantation, and later, to treat various autoimmune diseases. We report a case of a patient with an AZA-induced hypersensitivity reaction, a rare but potentially harmful side effect. CASEA 59-year-old male patient presented with elevated systemic inflammatory markers, blood eosinophilia of 53%, clinical and laboratory signs of myositis, bilateral pulmonary infiltrates, and peripheral polyneuropathy with rapid onset and progression. He had been suffering from asthma and chronic rhinitis for years. Antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, and antisynthetase-antibodies were negative, and complement levels were found to be within the normal range. Sarcoidosis, hematologic disorders, malignant, and allergic causes were excluded. A clinical diagnosis of a Churg Strauss vasculitis was made. After prednisone pulse and intravenous cyclophosphamide therapy, the patient improved rapidly, eosinophils returned within the normal range, pulmonary infiltrates vanished, and the polyneuropathy remained stable. After remission induction, a maintenance therapy with AZA was initiated with the patient, and the dose tapered to 200 mg/d. Initially, the drug was well tolerated. However, after 2 weeks of AZA treatment, the patient was presented to our emergency department with an acute onset of fever of up to 39°C, nausea, vomiting, and diarrhea. Laboratory tests showed an elevated C-reactive protein concentration of 74 mg/L, and a normal white blood count with relative neutrophilia of 92% and lymphopenia of 1.5%. Level of eosinophils was not elevated (0.7%). Liver function tests were normal. Urine analysis, chest x-ray, and abdominal ultrasound revealed no bacterial focus. AZA was stopped, and the patient was discharged with antibiotic treatment, as he refused to be admitted to the hospital. The patient recovered completely within a couple of days, and blood tests showed inflammatory markers and differential blood count within the normal range; therefore, AZA treatment was resumed about 3 weeks later. After 1 dose of AZA (50 mg), he developed the same symptoms and laboratory changes as those seen before. AZA hypersensitivity was now suspected, and the medication was stopped. Without any antibiotic treatment, the patient again recovered within days. C-reactive protein and differential blood count returned within the normal range. Immunosuppressive therapy was then switched to methotrexate without any sign of relapse of the apparent Churg Strauss vasculitis.

Der rheumatologische Patient auf der Intensivstation

“…Azathioprin kann auch nach mehreren Therapiemonaten, i.d.R. jedoch innerhalb der ersten Wochen Hypersensitivitätsreaktionen auslösen, die bis zu systemischen Schockzuständen führen können [8]. Des Weiteren ist bei abdominellen Beschwerden an die Azathioprin-induzierte Pankreatitis zu denken.…”