What is the first-line treatment for a child with seizures, high Anti-double-stranded Deoxyribonucleic Acid (Anti-dsDNA) and normal Antinuclear Antibody (ANA) levels?

Treatment for Pediatric Seizures with Elevated Anti-dsDNA and Normal ANA

Corticosteroids (Option D) are the first-line treatment for this child presenting with seizures and elevated anti-dsDNA antibodies, as this clinical picture suggests CNS lupus (neuropsychiatric SLE) requiring immediate immunosuppression to prevent irreversible neurological damage.

Clinical Context and Diagnosis

This presentation is highly concerning for CNS lupus with neuropsychiatric manifestations, specifically seizures as the presenting feature:

• Elevated anti-dsDNA antibodies are highly specific for SLE (>95% specificity), even when ANA is normal, which can occur in approximately 5% of SLE cases 1
• Anti-dsDNA antibodies have been identified in epilepsy patients as part of autoimmune-mediated seizure disorders, representing approximately 16% of certain epilepsy populations 2
• Seizures in the context of positive anti-dsDNA suggest active autoimmune CNS inflammation requiring urgent immunosuppression 3

Why Corticosteroids First

Corticosteroids provide immediate, broad immunosuppression that is critical for acute neuropsychiatric lupus:

• Intravenous methylprednisolone is the standard acute treatment for CNS lupus manifestations, including seizures 3
• Early immunotherapy initiation (median 4 months from seizure onset) is associated with significantly better outcomes compared to delayed treatment (22 months for non-responders, P<0.05) 3
• In autoimmune epilepsy studies, 81% of patients reported improvement with immunotherapy, with 18 achieving seizure freedom 3
• Corticosteroids work rapidly to suppress CNS inflammation and can prevent progression to refractory seizures 4, 5

Why Not the Other Options Initially

Hydroxychloroquine (Option A) is important for long-term SLE management but:

• Takes 3-6 months to achieve therapeutic effect, making it inadequate for acute seizure control 1
• Should be added as maintenance therapy after acute control is achieved 1
• Dose is 6.5 mg/kg/day or 400 mg/day (whichever is lower) with annual ophthalmological screening after 5 years 1

Cyclophosphamide (Option B) is reserved for:

• Severe, refractory lupus nephritis or life-threatening organ involvement 1
• Cases that fail to respond to corticosteroids 3
• Not first-line for isolated CNS manifestations without other severe organ involvement 1

Mycophenolate mofetil (Option C) is:

• A steroid-sparing maintenance agent for lupus nephritis 1
• Not appropriate for acute neuropsychiatric presentations requiring immediate immunosuppression 1

Treatment Algorithm

Immediate management:

1. Intravenous methylprednisolone (typically 1000 mg/day for 3-5 days for acute CNS lupus) 3
2. Concurrent antiepileptic drug (levetiracetam is preferred due to minimal drug interactions) 6
3. Seizure precautions: position on side, protect airway, remove harmful objects 6

If seizures persist >5 minutes:

• Lorazepam 0.05-0.1 mg/kg IV (maximum 4 mg) at 2 mg/min 6

After acute control (within days to weeks):

1. Transition to oral prednisone with gradual taper over months 1
2. Add hydroxychloroquine 6.5 mg/kg/day for long-term disease control 1
3. Consider steroid-sparing agents (mycophenolate or azathioprine) if prolonged immunosuppression needed 1

Monitoring requirements:

• Serial anti-dsDNA and complement levels (C3/C4) monthly initially 1
• MRI brain with contrast to assess for CNS inflammation 6
• EEG to monitor seizure activity 6
• Complete blood count, metabolic panel, and urinalysis to screen for other organ involvement 1

Critical Pitfalls to Avoid

• Do not delay immunotherapy while waiting for complete autoantibody panels or neuroimaging—early treatment (within 4 months) is associated with significantly better seizure outcomes 3
• Do not treat as simple epilepsy alone—antiepileptic drugs without immunosuppression will likely fail in autoimmune-mediated seizures 3, 5
• Do not assume normal ANA excludes SLE—anti-dsDNA can be positive with negative ANA in approximately 5% of SLE cases 1
• Do not use antipyretics alone if febrile—they do not prevent seizures and this presentation suggests autoimmune etiology, not simple febrile seizures 6

Expected Outcomes

With prompt corticosteroid therapy:

• 81% of patients with autoimmune epilepsy show improvement with immunotherapy 3
• Many achieve complete seizure freedom, particularly when treatment is initiated early 3
• Delayed immunotherapy (>22 months) is associated with poor response 3
• Long-term prognosis depends on controlling underlying SLE activity 1