A Case of Cryptococcal Meningitis and Fungemia With Relapse in an HIV-Negative, Non-transplant Patient on Azathioprine Therapy for Mixed Connective Tissue Disorder

Cryptococcal meningitis typically occurs in immunocompromised patients. Approximately 80% of cryptococcal infections occur in HIV patients. Non-HIV, non-transplant recipient patients are the least numerous population groups affected by cryptococcal infections. While this group includes patients on biologics and corticosteroids, very few cases have been reported in patients on azathioprine. Cryptococcal meningitis requires antifungal therapy, the duration of which varies among different population groups. Inadequate duration of antibiotics among these groups is one of the most common reasons for relapse; therefore, it is crucial to consider patient demographic when determining antifungal duration. Here, we report a 68-year-old male with a history of mixed connective tissue disease on azathioprine for six years, who was admitted to the hospital with worsening lethargy. Several days into admission, the patient developed low-grade fevers. Subsequent blood cultures grew Cryptococcus neoformans. He was started on liposomal amphotericin B. Lumbar puncture (LP) was done, which demonstrated positive cryptococcal antigen, and flucytosine was added to the treatment regimen. Repeat CSF culture demonstrated no fungal organisms. Amphotericin B was discontinued after 20 days of therapy. Following clinical improvement, he was subsequently discharged on oral fluconazole. One week following discharge, the patient was readmitted with worsening fevers and altered mental status. CSF studies demonstrated the growth of Cryptococcus on culture. Liposomal amphotericin B was reinitiated, and fluconazole was continued. Imaging showed hydrocephalus, which worsened despite ventriculoperitoneal shunt. The patient expired following transition to comfort care. In conclusion, cryptococcal meningitis should be considered as a differential in non-HIV, non-transplant patients on azathioprine presenting with fever and worsening lethargy, and 4-6 weeks of induction therapy is required in this patient group to prevent relapse.