Cyclophosphamide Induces False-Positive Results in Detection of Aspergillus Antigen in Urine

Abstract

Pulmonary aspergillosis, especially invasive pulmonary aspergillosis (IPA) is a common life-threatening complication among immunocompromised patients.1Spearing RL Pamphilon DH Prentice AG. Pulmonary aspergillosis in immunosuppressed patients with haematological malignancies.QJM. 1986; 59: 611-625PubMed Google Scholar Early diagnosis and intensive antifungal chemotherapy with amphotericin B is the only way to save such patients who contract this disease. The detection of circulating Aspergillus galactomannan antigen is one promising method for early diagnosis of IPA.2Yu B Niki Y Armstrong D. Use of immunoblotting to detect Aspergillus fumigatus antigen in sera and urines of rats with experimental invasive aspergillosis.J Clin Microbiol. 1990; 28: 1575-1579PubMed Google Scholar,3Burnie JP. Antigen detection in invasive aspergillosis.J Immunol Methods. 1991; 143: 187-195Crossref PubMed Scopus (8) Google Scholar Recently, a kit for Aspergillus antigen detection (Pastorex Aspergillus, Diagnostics Pasteur, Marnes-la-Coquette, France) has become commercially available.4Van Cutsem J Meulemans L Van Gerven F Stynen D. Detection of circulating galactomannan by Pastorex Aspergillus in experimental invasive aspergillosis.Mycoses. 1990; 33: 61-69PubMed Google Scholar Some retrospective studies indicated that the positive rates of the kit were not high enough,5Hashiguchi K Wada H Yamada O Yawata Y Yoshida K Okimoto N et al.A case of chronic myelogenous leukemia with pulmonary aspergillosis diagnosed by the detection of circulating Aspergillus antigen.Assoc Infect Dis. 1992; 66: 1592-1596PubMed Google Scholar but other prospective studies have shown satisfactory results for the detection of antigen in not only the serum but also the urine of patients. We have been using the kit to detect Aspergillus antigen in the serum and urine of rats with IPA. We have already reported on our animal models of IPA.6Niki Y Bernard EM Edwards FF Schmitt HJ Yu B Armstrong D. Model of recurrent pulmonary aspergillosis in rats.J Clin Microbiol. 1991; 29: 1317-1322Crossref PubMed Google Scholar In our recurrent IPA model, corticosteroid or cyclophosphamide was administered to rats with chronic stable Aspergillus lesions in their lungs to induce aggravation of the infection. When the steroid was administered, it took a relatively long time (4 to 7 weeks) to detect antigen in their serum and urine. However, when reinduction therapy with cyclophosphamide was begun the next day, the urine, but not the serum, of all the animals was antigen positive. We continued the experiment and found that almost all urine samples showed positive results until 18 days after the start of 3 days of cyclophosphamide treatment. We could not believe these results, so we injected cyclophosphamide into noninfectious rats. We found that the urine of all rats was antigen positive. Although Pastorex Aspergillus is considered to be a useful kit for the early diagnosis of IPA, the possibility of false-negative results should be considered when the kit is used to detect antigen in the urine of patients treated with cyclophosphamide.