False-Positive IgM Serology in Coccidioidomycosis

Abstract

The clinical observation has been made that there might be an unacceptable number of false-positive enzyme immunoassay (EIA) test results for IgM among persons suspected of having coccidioidomycosis. Patients with a positive result for IgM by EIA are thought to have a diagnosis of acute coccidioidomycosis. However, this study found that 82% of patients with an IgM-positive and IgG-negative EIA result did not have coccidioidomycosis.The Premier Coccidioides enzyme immunoassay (EIA; Meridian Bioscience, Inc., Cincinnati, OH) is a commercially available test used for the serological diagnosis of coccidioidomycosis. Clinical laboratories use that EIA for the detection of both IgM and IgG antibodies directed against Coccidioides. A positive EIA result for IgM is believed to be associated with the initial antibody response seen in an acute Coccidioides infection (3). The EIA test is also used to determine the presence of IgG antibody, which is diagnostic of an infection with Coccidioides. Clinicians use the various IgM and IgG antibody responses to determine the presence or the absence of an acute or a chronic Coccidioides infection (5).The Premier assay may be subject to false-positive results for IgM, as suggested by prior studies (2, 3). In contrast, those clinical and serological studies found a good correlation between a positive result for IgG by the Premier assay and infection with Coccidioides.A false-positive EIA result for IgM occurs when patients are thought to be experiencing acute coccidioidomycosis but do not have a Coccidioides infection. Clinical observations have raised concern that there may be an unacceptable number of false-positive IgM results with the Premier assay. A false-positive serological result can create clinical problems, resulting in the treatment of patients for a disease that they do not have or thinking that the patient has coccidioidomycosis and missing another medical condition. The study described here was done to correlate clinical findings and serological results for patients who had a positive result for IgM and a negative result for IgG by the Premier Coccidioides EIA. CASE REPORTA man with chronic lung disease and an aortic valve replacement who was receiving warfarin was admitted for hemoptysis. A month previously he had been diagnosed as having acute pulmonary coccidioidomycosis on the basis of positive results for IgM and negative results for IgG by EIA. He was placed on oral fluconazole at 400 mg daily. Fluconazole is known to alter the metabolism of warfarin. The fluconazole caused an increase in the anticoagulation effect of warfarin, which led to bleeding and hemoptysis. The problem resolved following discontinuation of the fluconazole and the finding of no confirmatory evidence for coccidioidomycosis. MATERIALS AND METHODSThe laboratories at John C. Lincoln Hospitals (the clinical laboratory) have routinely used the Premier EIA kit since 1995 for the detection of IgM and IgG antibodies in patients suspected of having an infection due to Coccidioides. The EIAs were per...

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

“…In contrast, Kuberski et al identified 17 patients with positive EIA IgM and negative EIA IgG tests and determined that only 3 of them "may have had coccidioidomycosis," giving a false-positive rate of 82% (150). The inclusion/exclusion criteria were not specified, nor was it stated whether there was any additional serologic testing.…”

Immunoglobulin M for Acute Infection: True or False?

“…Although the cases focus on virology due to the nature (4,5), Toxoplasma gondii (6)(7)(8), the Coccidioides spp. causing coccidiomycosis (9), and Borrelia burgdorferi (10).…”

Clinical Specificity of the Enzyme Immunoassay Test for Coccidioidomycosis Varies According to the Reason for Its Performance

“…One retrospective study demonstrated that 86% of patients with this test result had positive serologic findings by other methods (5), a finding echoed in the present study of 102 patients, in which 80 (78%) had either positive culture or histology or positive serologic findings by other methods. The demonstration of both IgM and IgG by EIA has been repeatedly shown to correlate well with other diagnostic assays in reference laboratories (6,7,13), but the finding of the IgM ϩ /IgG Ϫ remains problematic. Such problems with the IgM resolve when the serology is repeated (5), and seroconversion from isolated EIA IgM reactivity to EIA IgG reactivity occurs.…”

“…However, the EIA has generated some controversy, especially as it pertains to the particular finding of immunoglobulin M (IgM) reactivity in the absence of any immunoglobulin G (IgG) detected (EIA IgM ϩ /IgG Ϫ ). The few publications on this subject have been mixed: 1 study showed no falsepositive results on EIA IgM ϩ /IgG Ϫ for patients symptomatic for coccidioidomycosis (5), another demonstrated 2.2% (6), and a third study demonstrated an 82% false-positive rate (7). The finding of IgM reactivity in the absence of IgG by EIA is therefore difficult to interpret.…”