Case Presentation: A 66-year-old gentleman presented to the ER with complaints of worsening right lower extremity pain and weakness for two weeks. Vital signs were notable for fever, tachycardia, and hypotension. Initial laboratory data was significant for leukocytosis with a chest radiograph suggesting right lower lobe pneumonia. Patient was treated for sepsis with broad-spectrum antibiotics (vancomycin, ceftazidime, and flagyl) and resuscitated with four liters of normal saline. His mean arterial blood pressures remained <50 despite fluid resuscitation, so low-dose norepinephrine was started and he was admitted to the ICU with a presumed diagnosis of septic shock secondary to pneumonia. The patient had also undergone a CT scan of his chest, abdomen, and pelvis in the ER with results available the following morning. The CT of his chest showed multiple, tiny lung nodules bilaterally and CT of his abdomen showed a subtle, enhancing lesion in the right hepatic lobe. He showed significant clinical improvement the following morning, so norepinephrine was stopped and he was downgraded to the step-down unit. Hepatology was consulted due to the new hepatic lesion in the setting of a known history of hepatitis C. Initial assessment was probable hepatocellular carcinoma with a plan for transcatheter arterial chemoembolization after resolution of sepsis. Pulmonology was consulted in the setting of multiple new pulmonary nodules with concern for metastatic disease. Initial impression was that his symptoms were likely due to post-obstructive pneumonia and he would be a good candidate for bronchoscopy once his sepsis resolved. He was continued on broad-spectrum antibiotics, although he had recurrent fevers up to 103°F over the next five days. Infectious Diseases was consulted and the impression was that his recurrent fevers were likely secondary to his underlying hepatocellular carcinoma and it was reasonable to discontinue antibiotics as a full infectious work-up, including fungal etiologies, was negative. Patient began to develop a worsening mental status with a rising eosinophilia, so the suspicion for a fungal infection became high. A repeat fungal infectious work-up was significant for a positive coccidioides serology (previous result was indeterminant) and fungal culture positive for coccidioides. A lumbar puncture was performed and confirmed coccidioidal meningitis. He was started on high-dose fluconazole with a resolution of his fevers and stabilization of his mental status.

Discussion: Coccidioidomycosis is a fungal disease that is prevalent across the Southwestern United States. The initial, nonspecific symptoms following infection and ability to widely disseminate throughout the human body makes this a challenging diagnosis. This case highlights the importance of repeating fungal serologies if there is a high suspicion for infection. With regard to coccidioides specifically, an indeterminate result can indicate either a false-positive or low level of coccidioides antibodies.

Conclusions: Fungal infections often have atypical clinical presentations, yet can cause devastating disease. Antibody titers and fungal blood cultures often take many weeks to fully result, so a high clinical suspicion should prompt further investigation. An initial, negative fungal serology or blood culture does not rule out a fungal infection.