To recognize role of immunomodulatory therapies in reactivation of CNS Toxoplasmosis in HIV-negative patients.

Toxoplasma Gondii is a protozoan parasite that causes asymptomatic or mild systemic infections (fevers, chills, myalgias, lymphadenopathy) in immunocompetent patients. Toxoplasmosis can reactivate in immunocompromised states, particularly HIV with CD4 counts <100, presenting as Toxoplasmosis encephalitis (TE). However, few cases of TE have been reported in the setting of immunomodulatory agents.

We report a 21-year-old female with history of Crohn’s colitis on infliximab and recent COVID-19 infection treated with baricitinib who presented with one week of progressive left arm weakness (strength 3/5) and left leg weakness (4/5) and was found to have TE.

MRI demonstrated a single right thalamocapsular 2 cm rim-enhancing mass with concentric inner ring, internal diffusion restriction, and hemosiderin deposits and surrounding vasogenic edema causing 2.7 mm midline shift. Lumbar puncture revealed six nucleated cells (95% lymphocytes), 105 protein, 35 glucose (68 serum). CSF demonstrated positive toxoplasmosis PCR (IgG+, IgM+), but negative gram stain. Flow cytometry demonstrated CD4 count 1080 (40%), CD19 count 135 (5%), and negative HIV antibodies. Patient was started on pyrimethamine and sulfadiazine for treatment of TE. However, worsening lethargy due to edema and increased 4 mm midline shift, required steroids before observing clinical improvement. By discharge, patient was at baseline mental status and improving strength on treatment.

While rare case reports describe TE in HIV-negative patients, role of immunomodulatory therapies in reactivation has not been well described. While this patient was chronically on infliximab, its inhibition of TNF-alpha, which is produced by CD4+ lymphocytes, qualitatively dampened her robust immune system. Adding JAK1/2 inhibitors, Baricitinib, likely altered downstream production of cytokines, shifting balance from asymptomatic to active disease. This case supports existing literature that TE should be considered in patients with recent changes in immunomodulatory therapies, regardless of HIV status.