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Coccidioidal Hepatic Abscess in a Patient With Disseminated Coccidioidomycosis: A Case Report

Coccidioidomycosis is an infection caused by inhalation of arthroconidia of Coccidioides. Forty percent of patients will develop mild and self-limited respiratory infection, and a small fraction of these individuals will develop extrapulmonary disseminated disease. This is the case of a patient with a known history of disseminated coccidioidomycosis, who initially presented for symptoms of persistent pneumonia. On evaluation, the patient was found to have a hepatic abscess for which he underwent percutaneous drainage. Culture grew Coccidioides immitis, and the patient was treated with systemic antifungal. This is a rare case of disseminated coccidioidomycosis in the liver.


Introduction
Coccidioidomycosis is a fungal infection that is endemic to the Southwestern region of the United States. It is caused by inhalation of spores of Coccidioides immitis and Coccidioides posadasii. It has a wide clinical manifestation, from asymptomatic to fatal disease. It presents as flu-like symptoms and pneumonia. In minority of cases, extrapulmonary dissemination occurs to skin, joints, bones, and the central nervous system (CNS). [1][2][3][4][5] Dissemination to liver frequency is unknown and is only limited to a few published case reports presenting as granulomatous hepatitis. 6

Methods
A literature search was conducted to evaluate whether similar cases have reported previously. The search included databases PubMed, Google Scholar, and Infectious Disease society of America's (IDSA) Clinical Infectious Disease Journal database. The following search terms were applied: coccidioidomycosis, disseminated coccidioidomycosis, hepatic abscess, coccidioidomycosis involving liver.

Case Presentation
The patient was a 50-year-old male with type 1 diabetes mellitus, end-stage renal disease (ESRD) on hemodialysis.
He was originally diagnosed with pulmonary coccidioidomycosis in 2005, and in 2007, he was found to have disseminated tibial osseous and coccidioidomycosis meningitis. Patient was previously treated with amphotericin B that was transitioned to voriconazole.
In 2020, the patient was experiencing subjective intermittent fevers, cough, and dyspnea for 2 months and received 2 courses of treatment for community-acquired pneumonia (CAP) without improvement. He presented to our emergency department (ED) with low-grade fever and leukocytosis of 15.5 × 10 3 /µL with neutrophilia. Liver tests showed alkaline phosphatase of 219, aspartate aminotransferase (AST) of 99, alanine aminotransferase (ALT) of 45, albumin 1.9, and total protein 6.5, and viral hepatitis workup was negative. Coccidioides immunodiffusion IgG and IgM assays were both reactive with complement fixation of >1:512. Chest X-ray in the ED showed diffuse patchy and confluent right greater than left airspace disease with consolidation and micronodular densities ( Figure 1).
Computed tomography (CT) scan of chest revealed diffuse patchy right lung airspace disease with ground glass opacities. As the patient presented during SARS 2 COVID-19 pandemic, COVID-19 testing was performed and returned negative. CT chest also showed an accidental collection in the liver ( Figure 2). As a result, then CT scan of abdomen was obtained and demonstrated a rim enhancing hepatic septate collection measuring 7.3 × 6.8 × 5.4 cm (Figure 3).
Patient underwent an ultrasound-guided percutaneous drainage and sampling of the hepatic collection with placement of a percutaneous drain. Periodic acid-Schiff (PAS) staining of the fluid showed multiple spherules with endosporulation resembling coccidioidomycosis with no bacteria isolated. Gram stain showed spherules resembling Coccidioides sp (Figure 4). Fungal culture eventually grew and was sent to reference fungal laboratory (University of Texas at San Antonio) where growth of Coccidioides immitis was confirmed. Antifungal susceptibility testing at the same reference fungal laboratory for amphotericin B, 5-flurocytosine, fluconazole, itraconazole, and voriconazole minimum inhibitory concentrations were ≤0.03, >64, 8, 0.06, and 0.125 µg/mL, respectively.    Parental treatment with liposomal amphotericin B was discussed with the patient, but he deferred. Therefore, he was switched from oral voriconazole to oral isavuconazonium 372 mg daily and discharged with close follow-up with the infectious disease clinic.

Discussion
Hepatic abscess is usually bacterial, less commonly parasitic, rarely fungal. When faced with HA, one should seek advice from a multispecialty team including an interventional radiologist, a hepatobiliary surgeon, and an infectious disease specialist. Needle aspiration and microbiology is a valuable approach.
Coccidioidomycosis is usually self-limiting in most immunocompetent hosts. It is estimated that more than 60% of infections are asymptomatic. 7 Involvement of the liver in disseminated coccidioidomycosis is probably common. In most instances, this is subclinical and suspected 5′-nucleotidase and alkaline phosphatase are elevated. Symptomatic hepatic involvement in coccidioidomycosis is rare. 8 There is limited literature regarding symptomatic liver involvement, those reported are typically immunocompromised and have long-standing systemic coccidioidomycosis. This patient suffered lifelong diabetes, ESRD, as well as his 15-year history of disseminated coccidioidomycosis.
Coccidioidal hepatic abscess is clearly rare, and this is the first case report to the best of our knowledge. The literature regarding therapy of other fungal liver abscess may have some insight to offer how to treat coccidioidomycosis liver abscess. Cases of hepatosplenic candidiasis that were successfully treated with fluconazole have been reported by Kauffman et al. 9 Our treatment approach should be modeled after treatment of disseminated coccidioidomycosis, which is initial use of liposomal amphotericin B with transition to azoles. 10

Conclusion
This case report demonstrates that it is paramount for clinicians to maintain a high clinical suspicion to include disseminated coccidioidomycosis in the differential diagnosis of patients with exposure to endemic regions, particularly for those who are immunocompromised and had coccidioidomycosis in the past. This case demonstrates a rare manifestation of disseminated coccidioidomycosis to the liver with abscess formation. As per our literature search as well as many years of treating coccidioidomycosis in an endemic area, this seems to be a unique case. Furthermore, we are fairly certain that this is the first such case to be reported.