Case Presentation: Coccidioidomycosis is a fungal infection caused by the dimorphic organism Coccidioides commonly reported in the Southwest of the United States. Tumor necrosis factors inhibitors (TNFi) have become widely used to treat autoimmune and inflammatory conditions. But patients using TNFi are at increased risk of developing several infections, including coccidioidomycosis in endemic areas. Nevertheless, there has been a scarcity in the literature on management guidelines for those on active TNFi treatment with coccidioidomycosis.A 67-year-old male with significant past medical history for hypertension, hyperlipidemia, and Crohn’s disease was undergoing treatment with infliximab and methotrexate. He was initially asymptomatic; a few months later noted a loss of appetite, weight loss (15 pounds), generalized fatigue, subjective fever, headache, and night sweats. He reported frequent travel history to Southern Arizona. He was undergoing workup for increased prostate-specific antigen (PSA). An incidental finding of bilateral pulmonary nodules was noted per a computed tomography (CT) scan. This prompted further evaluation with a positron emission tomography (PET) scan, which demonstrated increased uptake in mediastinal, perihilar, and supraclavicular lymph nodes. Supraclavicular biopsy was aborted due to difficult vascular access. The patient underwent an endobronchial biopsy of a lymph node. Subsequently, tissue samples demonstrated caseating granulomas. All bacterial, fungal tissue cultures and acid-fast bacilli (AFB) stains were negative.Complete blood count (CBC) was remarkable for eosinophilia. Inflammatory markers were elevated, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serological testing as vasculitis biomarkers, human immunodeficiency virus (HIV), interferon-gamma release assay (IGRA) for tuberculosis returned negative. Coccidioidomycosis complement fixation (CF) came back at 1:32, consistent with active disease. The patient was started on a fluconazole 400 mg once-daily regimen. His overall symptoms ameliorated in five months since the initiation of the antifungal therapy. His exercise tolerance, CT chest findings, and PSA levels markedly improved. Magnetic resonance imaging (MRI) of the brain was unremarkable. The patient declined the lumbar puncture since his headache episodes subsided. The clinical decision regarding TNFi was discussed and coordinated with the gastroenterology team to hold infliximab until the coccidioidomycosis CF titers declined to < 1:4. Also, vedolizumab was started per gastroenterology service, and the patient’s Crohn’s disease was controlled. He was followed up closely in the outpatient clinic.

Discussion: This case is an example of disseminated coccidioidomycosis in the setting of TNFi use. The patient presented with pulmonary lymph nodes and possible prostate involvement as suggestive by the improvement of his PSA levels following the initiation of fluconazole. Unfortunately, we could not prove neurological involvement with meningitis as the patient refused lumbar puncture.

Conclusions: This case highlights the significance of considering disseminated coccidioidomycosis in the differential diagnosis in patients on TNFi. Suspicion and early diagnosis are essential. There may be a role for routine serological monitoring in endemic areas. Per recent literature, holding TNFi, and treating with fluconazole until coccidioidomycosis CF titers < 1:4 may help control the disease.