Abstract Central nervous system (CNS) infections in systemic lupus erythematosus (SLE) are uncommon, representing approximately 3% of all infectious complications. Among these, cryptococcal meningitis (CM) remains one of the most fatal, particularly in immunocompromised individuals, with global mortality rates ranging from 25% to 50%. The prevalence of CM in SLE patients is less than 1%. Mycophenolate mofetil and glucocorticoids, frequently used in lupus nephritis management, are well-known contributors to opportunistic fungal infections through suppression of humoral and cell-mediated immunity. Co-infection with Cryptococcus neoformans and reactivated varicella-zoster virus (VZV) is exceedingly rare, and even fewer cases involve VZV vasculopathy leading to cerebral infarction or hemorrhage.We report a case of disseminated cryptococcosis with cryptococcal meningitis and concurrent VZV meningitis in an immunosuppressed 41-year-old man receiving high-dose corticosteroids and mycophenolate for biopsy-proven lupus nephritis. The patient presented with a two-week history of intractable hiccups prior to hospitalization. He had been lost to follow-up after his initial SLE diagnosis and continued high-dose immunosuppression independently for six months. One month prior to admission, he developed shingles and completed antiviral therapy. Initial workup revealed a CD4 count 15 cells/µL and positive cryptococcal blood cultures. Despite initiation of antifungal therapy, his mental status worsened. Lumbar puncture demonstrated an opening pressure of 34 cm H2O, and cerebrospinal fluid (CSF) analysis confirmed C. neoformans by PCR. Persistent encephalopathy required external ventricular drain placement, later supplemented with a lumbar drain for pressures ranging from 30 to 50 cm H2O.His clinical course was marked by obstructive hydrocephalus, new-onset seizures, and intraparenchymal hemorrhage. Serial CSF remained PCR-positive for C. neoformans and later detected reactivated VZV, coinciding with sudden hemodynamic decline. Repeat neuroimaging demonstrated multiple cerebral hemorrhages consistent with VZV-associated vasculopathy. Despite aggressive antifungal, antiviral, and intracranial pressure–directed therapy, the patient remained comatose and was transitioned to hospice care.This case underscores the devastating interplay of severe immunosuppression, dual opportunistic infections, and catastrophic CNS injury. High-dose prednisone with mycophenolate induces profound T- and B-cell suppression, increasing mortality tenfold. A nationwide Swedish study found the incidence of reactivated VZV in CSF ∼0.002% annually, with vasculitic/hemorrhagic complications occurring in 0.007% cases. The combination of cryptococcal meningeal inflammation and VZV-mediated vasculitis synergistically worsens intracranial hypertension and vascular injury, driving mortality 50%. This case highlights the need for early neurological assessment, vigilant monitoring of intracranial pressure, prompt dual-pathogen screening, and judicious immunosuppressive management in SLE patients presenting with atypical neurological symptoms such as persistent hiccups. This abstract is funded by: none
Meruva et al. (Fri,) studied this question.