Successful Treatment of Refractory Disseminated Coccidioidomycosis with Adjunctive Interferon-γ

Background Coccidioidomycosis (CM) is an infection caused by the Coccidioides ssp., which are endemic to the southwestern United States and Mexico. Most cases of CM are asymptomatic or cause mild respiratory illness, but 1% progress to extrapulmonary multi-organ dissemination, which can be severe or even fatal. When standard antifungal treatment regimens are inadequate, immunomodulatory interventions may be required. Here we present a case of refractory disseminated CM (DCM) that achieved remission with the addition of recombinant IFNγ. Case Presentation A previously healthy 19-year-old African American male was referred to the NIH with refractory DCM, complicated by a paraspinal phlegmon and a T10 compression fracture. His infection failed to respond to treatment with itraconazole and amphotericin B. The patient had no history of recurrent or severe infections and no family history of immune deficiency or autoimmunity. He lived for a year in Arizona prior to diagnosis, where he was likely exposed to the pathogen. CT imaging revealed severe disseminated infection in the lungs and pleural space, with lytic lesions in several thoracic spine vertebrae, as well as a pathologic T10 fracture. Lung biopsies and serum testing confirmed DCM without secondary infection. Upon admission, the patient’s CRP was elevated (65.3 mg/l). Despite initiating treatment with amphotericin B, caspofungin, and posaconazole, the infection continued to progress. Amphotericin B was discontinued due to side effects, and IFNγ therapy was initiated subcutaneously at 50 mcg/m 2-3 times weekly. The patient showed rapid improvement and was discharged on posaconazole and IFNγ alone, with reduced pain and normalizing CRP levels (2.2 mg/L) within one month. A follow-up CT scan at two months showed a marked reduction in measurable disease. Discussion We present a case where adjunctive IFNγ led to successful and significant symptom improvement when no other treatments were effective. Treating DCM with IFNγ could be effective in enhancing immune responses in treatment-resistant cases, leading to improved clearance of refractory fungal infections, even in patients with no clearly defined immunodeficiency.