Fatal toxoplasmic encephalitis triggered by anti-TNF therapy

Area of Science:

• Infectious Diseases
• Immunology
• Neurology

Background:

• Reactivation of latent Toxoplasma gondii infection can cause severe neurological disease, particularly in immunocompromised individuals.
• While anti-tumor necrosis factor-alpha (TNF-α) therapy is known to trigger T. gondii reactivation in mouse models, this is rare in humans despite widespread use.
• Serological evidence of latent T. gondii infection is common globally, yet the reasons for infrequent reactivation with TNF-α blockade remain unclear.

Observation:

• A 74-year-old woman with rheumatoid arthritis developed fatal cerebral toxoplasmosis following anti-TNF-α therapy.
• Initial symptoms of confusion and cognitive decline were misdiagnosed, leading to delayed diagnosis and treatment.
• Brain imaging revealed characteristic ring-enhancing lesions, confirmed by biopsy showing T. gondii parasites.

Findings:

• The patient's condition deteriorated despite standard toxoplasmosis treatment, suggesting potential contributing factors like immune resilience loss and virulent T. gondii strains.
• Post-mortem analysis of cerebrospinal fluid identified T. gondii peptides.
• A literature review indicated that the risks of anti-TNF-α therapy in T. gondii seropositive individuals are underestimated.

Implications:

• This case underscores the potential for severe neurological complications from T. gondii reactivation in patients receiving anti-TNF-α therapy.
• Routine screening for T. gondii seropositivity before and after initiating anti-TNF-α therapy is recommended, similar to protocols for tuberculosis.
• Increased awareness and proactive screening can mitigate the risk of fatal toxoplasmosis in susceptible patients undergoing immunosuppressive therapy.