Coccidioidomycosis in patients with various inflammatory disorders treated with tumor necrosis factor α inhibitors

Abstract

Coccidioides fungi are found primarily in the southwestern United States and are the cause of coccidioidomycosis. Tumor necrosis factor α inhibitors (TNFIs) are therapies for autoimmune and inflammatory conditions; their association with coccidioidomycosis is not well characterized. We aimed to determine the prevalence and characteristics of coccidioidomycosis among TNFI recipients with different inflammatory disorders at a tertiary care center. We retrospectively reviewed the electronic health records of patients at our institution from April 4, 2010 to December 17, 2017, who received TNFIs (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab) and had positive culture, pathologic, and/or serologic results for coccidioidomycosis. Among 1770 patients identified who received TNFIs, 49 (2.8%) had proven or probable coccidioidomycosis. Of these 49, 28 (57%) were men, 47 (96%) were White, and 42 (86%) had pulmonary coccidioidomycosis. The most common TNFIs used were adalimumab, infliximab, and etanercept. Coccidioidomycosis was identified in 25 of 794 patients with rheumatologic disorders (3.1%), 18 of 783 patients with inflammatory bowel disease (IBD) (2.3%), and six of 193 patients with dermatologic disorders (3.1%) (P = .34). There was no difference in coccidioidal infections among recipients of any particular TNFI agents. A minority of patients (7/49, 14%) had an extrapulmonary infection, and the majority of these (6/7) had IBD. Our study shows a low prevalence of coccidioidomycosis in TNFI recipients, even within the Coccidioides-endemic area. Persons with IBD were disproportionately represented among those with extrapulmonary coccidioidomycosis. Treatment with azoles was effective. Lay Summary Among 1770 patients who received tumor necrosis factor α inhibitors, 49 (2.8%) had newly acquired coccidioidomycosis over a 7-year period. Dissemination occurred in 14.3%, but disproportionately among those with underlying inflammatory bowel disease. All patients recovered with medical management.

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

“…The reported studies have either centered on TNFi [38] or grouped all BRMs together [15,39]. In one review, Blair et al [40] reviewed reports of coccidioidomycosis with various BRMs.…”

“…In one review, Blair et al [40] reviewed reports of coccidioidomycosis with various BRMs. In one study of TNFi recipients within the endemic region [38], 49/1770 (2.8%) had proven or probable coccidioidomycosis, a >10-fold increase compared with reported infections in Arizona during the same time (0.26% (2011) to 0.1% (2017)) [41]. While the increased incidence may in part be due to increased surveillance [42], there were 7 cases of DCM (7/1770, 0.4%), 3 receiving infliximab and 4 receiving adalimumab.…”

“…While the increased incidence may in part be due to increased surveillance [42], there were 7 cases of DCM (7/1770, 0.4%), 3 receiving infliximab and 4 receiving adalimumab. There was no difference in incidence of infection between patients receiving etanercept, a soluble TNF receptor, versus other TNF antibodies [38]. There has been one case report of DCM in a patient receiving vedolizumab (α4β7 integrin) for Crohn's disease [43] and one diagnosed with a pulmonary nodule while receiving abatacept (CTLA4) [39].…”