What is the appropriate management for a patient with Systemic Lupus Erythematosus (SLE) experiencing progressive leg weakness?

Progressive Leg Weakness in SLE: Management Approach

For an SLE patient presenting with progressive leg weakness, immediately pursue urgent spinal cord MRI with contrast and exclude infection before escalating immunosuppression, as this presentation most likely represents SLE myelopathy requiring prompt high-dose intravenous methylprednisolone combined with cyclophosphamide within hours of diagnosis to prevent permanent neurological deficit. 1

Immediate Diagnostic Workup

Obtain contrast-enhanced spinal cord MRI urgently to detect T2-weighted hyperintense lesions (present in 70-93% of SLE myelopathy cases) and assess for longitudinal myelopathy (involvement of >3 spinal cord segments). 1 Simultaneously perform brain MRI when other neuropsychiatric symptoms coexist to evaluate for additional NPSLE manifestations. 1

Perform lumbar puncture with comprehensive CSF analysis including cell count, protein, glucose, microbiological studies (bacterial cultures, fungal cultures, viral PCR panel), and cytology to aggressively exclude CNS infection before initiating immunosuppressive therapy. 1, 2 Mild-to-moderate CSF abnormalities (elevated protein, lymphocytic pleocytosis) occur in 50-70% of SLE myelopathy but are non-specific. 1

Assess for concurrent neuropsychiatric manifestations: One-third of SLE myelopathy patients have other major NPSLE features, with optic neuritis being most common (21-48%). 1 If longitudinal myelopathy is present, send serum NMO IgG (aquaporin-4) antibodies to diagnose co-existing neuromyelitis optica. 1

Determine the underlying mechanism: SLE myelopathy presents as either inflammatory transverse myelitis or ischemic/thrombotic myelopathy. 1 Check antiphospholipid antibodies, as their presence suggests thrombotic mechanism and predicts worse prognosis. 1 Signs of grey matter dysfunction (flaccidity, hyporeflexia) versus white matter dysfunction (spasticity, hyperreflexia) help distinguish pathophysiology. 1

Critical Pitfall to Avoid

Never escalate immunosuppression in a febrile SLE patient with neurological symptoms without first excluding infection—this is a potentially fatal error. 2 The differential diagnosis includes opportunistic infections (Pneumocystis jirovecii, cytomegalovirus, fungal infections) particularly in patients on chronic glucocorticoids >7.5 mg/day and immunosuppressive agents like mycophenolate mofetil. 2

Immediate Treatment Protocol (Once Infection Excluded)

Initiate combination therapy with intravenous methylprednisolone PLUS intravenous cyclophosphamide within the first few hours of diagnosis. 1 This combination is effective in SLE myelitis when used promptly, with neurological response paralleled by MRI improvement occurring within days to 3 weeks. 1

The EULAR guidelines emphasize that delay >2 weeks in initiating therapy is associated with severe neurological deficit and poor outcomes. 1 Other poor prognostic factors include extensive spinal cord MRI lesions, reduced muscle strength or sphincter dysfunction at presentation, and presence of antiphospholipid antibodies. 1

For antiphospholipid-positive myelopathy with thrombotic mechanism: Add anticoagulation therapy with warfarin (target INR 2.0-3.0 for venous thrombosis, 3.0-4.0 for arterial or recurrent thrombosis) in addition to immunosuppression, as this combination has shown good results. 1, 3

Maintenance Therapy and Relapse Prevention

Relapses occur in 50-60% of patients during corticosteroid dose reduction, underscoring the absolute need for maintenance immunosuppressive therapy. 1 Options include:

• Azathioprine for maintenance therapy, particularly suitable for women contemplating pregnancy 3
• Mycophenolate mofetil for maintenance of non-renal and renal manifestations 3

Taper glucocorticoids aggressively to <7.5 mg/day prednisone equivalent and withdraw when possible to prevent organ damage and reduce infection risk. 3, 2

Refractory Cases

For severe cases not responding to standard therapy: Plasma exchange therapy synchronized with intravenous cyclophosphamide has been used successfully. 1 Rituximab may be considered for organ-threatening disease refractory to standard immunosuppressive agents. 3

Peripheral Neuropathy Considerations

If the presentation is peripheral rather than central (polyneuropathy, mononeuropathy multiplex, or Guillain-Barré-like syndrome), the approach differs. 1, 4 Peripheral nervous system disorders in SLE present with altered sensation, pain, and muscle weakness (2-3% prevalence). 1 These typically respond to glucocorticoids combined with immunosuppressive agents (azathioprine, cyclophosphamide, or mycophenolate mofetil). 1

Monitoring and Long-Term Management

All SLE patients require hydroxychloroquine ≤5 mg/kg real body weight as foundational therapy unless contraindicated, as it reduces disease activity, prevents flares, and improves survival. 3, 5 Continue this throughout treatment of myelopathy.

Monitor for treatment complications: SLE patients have 5-fold increased mortality risk, requiring aggressive screening for infections, cardiovascular disease, osteoporosis, and malignancies. 3 Patients on chronic immunosuppression need vigilant infection surveillance. 2