What is the initial treatment for lupus cerebritis?

Initial Treatment for Lupus Cerebritis

For lupus cerebritis (severe acute neuropsychiatric SLE with inflammatory mechanisms), initiate high-dose glucocorticoids combined with cyclophosphamide as first-line therapy. 1, 2

Immediate Therapeutic Approach

Glucocorticoid Regimen

• Administer intravenous methylprednisolone pulse therapy at 250-1000 mg daily for 1-3 consecutive days to provide rapid therapeutic effect 1, 2, 3
• Follow with oral prednisone at 0.5-1 mg/kg/day (maximum 60 mg/day), as doses exceeding this threshold do not improve outcomes and accelerate damage accrual 2
• Taper aggressively with a goal of <7.5 mg/day for maintenance therapy 2, 3

Immunosuppressive Therapy

• Add cyclophosphamide to glucocorticoids for severe acute neurologic manifestations including seizures, psychosis, myelitis, peripheral neuropathy, brain stem disease, or optic neuritis 1, 2
• Cyclophosphamide is favored due to better certainty of evidence and lower cost compared to alternatives 2
• Rituximab may be considered as an alternative for refractory cases, though it has lower quality evidence and was primarily evaluated in treatment-resistant patients 1, 2

Critical Diagnostic Distinction

Attribution to SLE-related versus non-SLE neuropsychiatric manifestations is essential before initiating immunosuppressive therapy 1

Diagnostic Workup Required

• Neuroimaging to identify inflammatory versus thrombotic processes 1
• Cerebrospinal fluid investigation 1
• Assessment of risk factors: type and timing of manifestation relative to lupus onset, patient age, non-neurological lupus activity, presence of antiphospholipid antibodies 1
• Exclude infection aggressively—obtain cultures before initiating immunosuppression when infection cannot be ruled out 3

Treatment Algorithm Based on Mechanism

• For inflammatory/immune-mediated mechanisms: Glucocorticoids plus immunosuppressive agents (cyclophosphamide preferred) 1, 2, 3
• For atherothrombotic/antiphospholipid-related manifestations: Antiplatelet agents or anticoagulation 1, 3
• When both mechanisms coexist: Combination of immunosuppressive and anticoagulant/antithrombotic therapy 1

Adjunctive and Rescue Therapies

Additional Treatment Options for Severe or Refractory Cases

• Intravenous immunoglobulin (IVIG) at 400 mg/kg/day for 4 days can be added in cases of inadequate response to glucocorticoids or to avoid glucocorticoid-related infectious complications 4
• Therapeutic plasma exchange may be considered for severe refractory cases 2, 4
• The combination of cyclophosphamide, IVIG, and plasmapheresis has been used successfully in fulminant cerebritis 4

Maintenance Therapy After Initial Response

• Continue monthly intravenous pulse cyclophosphamide for 6 months, followed by maintenance infusions every 3 months for up to 2 years 4
• If cyclophosphamide must be discontinued due to toxicity, switch to mycophenolate mofetil (3000 mg/day) with or without calcineurin inhibitors 4

Foundational Therapy

All patients must receive hydroxychloroquine at ≤5 mg/kg real body weight unless contraindicated, as it reduces disease activity, prevents flares, and improves survival even in severe disease 2, 3

Critical Pitfalls to Avoid

• Never delay immunosuppressive therapy—glucocorticoids alone are insufficient for crisis management and lead to prolonged high-dose steroid exposure 2
• Do not use prednisone >1 mg/kg/day or >60 mg/day, as higher doses provide no additional benefit 2
• Distinguish lupus cerebritis from opportunistic infections (particularly toxoplasmosis, which can mimic cerebritis in immunosuppressed patients) before escalating immunosuppression 5
• Consider gonadal toxicity when using cyclophosphamide in reproductive-age patients and counsel about fertility preservation options 2
• Maintain high suspicion for infection throughout treatment, as immunosuppressed SLE patients have substantially elevated infection risk 3