What is the management of Posterior Reversible Encephalopathy Syndrome (PRES) associated with tacrolimus (FK506) use?

Management of Posterior Reversible Encephalopathy Syndrome (PRES) Associated with Tacrolimus

The management of tacrolimus-associated PRES requires immediate discontinuation of tacrolimus and switching to an alternative immunosuppressant, along with aggressive blood pressure control and seizure management.

Clinical Presentation of Tacrolimus-Associated PRES

PRES is a neurological disorder characterized by:

• Altered mental status (78.9% of patients)
• Seizures (52.6% of patients)
• Visual disturbances (31.5% of patients)
• Headaches
• Hypertension (significant increase in mean arterial pressure) 1

Diagnostic Approach

1. Neuroimaging:

   • MRI is the gold standard showing characteristic gray and white matter abnormalities in temporal, parietal, and occipital lobes 2
   • Look for subcortical fluid attenuation inversion recovery (FLAIR) hyperintensity signals 3

2. Laboratory Assessment:

   • Check tacrolimus blood levels (although PRES can occur with therapeutic levels) 1
   • Monitor serum creatinine (often elevated) 1
   • Check serum magnesium (hypomagnesemia may contribute) 4

Management Algorithm

Step 1: Immediate Interventions

• Discontinue tacrolimus or switch to an alternative immunosuppressant 4, 3
• Control hypertension with antihypertensive medications 4, 1
• Administer anticonvulsants for seizure management 4
• Magnesium supplementation if deficient 4

Step 2: Alternative Immunosuppression Options

1. Switch to cyclosporine:

   • Demonstrated success in heart transplant recipients 3
   • Monitor closely as cyclosporine can also cause PRES

2. Combined tacrolimus and sirolimus at reduced doses:

   • Allows for lower tacrolimus doses while maintaining immunosuppression
   • Shown to result in rapid clinical improvement and resolution of PRES 5
   • Effective in maintaining allograft function without rejection 5

3. Switch to another agent entirely:

   • Consider in severe cases or recurrent PRES 1

Step 3: Monitoring and Follow-up

• Follow-up MRI at 2-6 weeks to confirm resolution of brain lesions 5
• Seizure prophylaxis for short term until radiological findings resolve 3
• Blood pressure monitoring to ensure adequate control 1
• Allograft function assessment to ensure no rejection with new immunosuppression regimen 5

Outcomes and Prognosis

• PRES is generally reversible when managed promptly
• Symptoms typically resolve within days of tacrolimus discontinuation 4
• MRI abnormalities usually resolve within 2 weeks 4
• Survival rates vary based on management strategy:
  • 40% when tacrolimus is continued
  • 40% when tacrolimus is temporarily held then resumed
  • 50% when switched to another agent 1

Important Considerations and Caveats

• PRES can occur as early as 5 days after starting tacrolimus 3
• Hemorrhagic complications (intracerebral and subarachnoid) can occur with tacrolimus-associated PRES, increasing morbidity 2
• Elevated tacrolimus levels are not always present at PRES onset 1
• Hypertension is a significant contributing factor and must be aggressively controlled 1
• Early recognition and management are crucial to prevent permanent neurological sequelae 3

Prevention Strategies

• Targeted prevention for high-risk patients:
  • Magnesium supplementation
  • Strict blood pressure control
  • Serial monitoring of tacrolimus blood concentrations 4