Can an 11-year-old patient with a 4-year history of systemic lupus erythematosus (SLE) experience sudden weakness, headache, and vomiting after physical activity, which was previously well-tolerated, over the past 6 months?

Neurological Lupus Complications Must Be Ruled Out Urgently

This 11-year-old with 4-year SLE history presenting with new-onset exercise-induced headache, vomiting, and weakness over 6 months requires immediate evaluation for CNS lupus involvement, particularly cerebrovascular disease and antiphospholipid syndrome (APS), as these manifestations commonly occur with high disease activity and can present insidiously in pediatric patients. 1

Critical Red Flag Assessment

This presentation demands urgent neurological evaluation because:

• Cerebrovascular disease occurs in 50-60% of SLE-APS patients in the context of high disease activity, and ischemic stroke/TIA comprises over 80% of these cases 1
• Cognitive dysfunction (attention deficits, memory impairment, executive dysfunction) are the most commonly affected domains in SLE-APS patients, and these can manifest as exercise intolerance and "weakness" 1
• Normal laboratory values do not exclude active CNS lupus, as neurological involvement can occur independently of systemic disease activity—this is the most dangerous diagnostic pitfall 1

The 6-month progressive course with exercise-triggered symptoms distinguishes this from benign exercise-induced anaphylaxis (which presents acutely with urticaria and preserved mental status) 2 or typical post-concussion syndrome 2.

Immediate Diagnostic Workup Required

Neuroimaging (Highest Priority)

• Obtain urgent non-contrast head CT immediately to exclude intracranial hemorrhage, space-occupying lesions, or acute stroke 3, 4
• MRI brain with and without contrast is the diagnostic test of choice for detecting subtle ischemic changes, vasculitis, or demyelinating lesions in CNS lupus 5
• Headache brought on by exertion or Valsalva maneuver specifically indicates need for neuroimaging to exclude increased intracranial pressure 3, 5

Antiphospholipid Antibody Testing

• Test for lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies 1
• Triple antibody positivity indicates highest risk for thrombotic events and would mandate anticoagulation consideration 1
• Persistently positive moderate-to-high titers represent strong risk factors for cerebrovascular disease 1

Additional Laboratory Evaluation

• Complete blood count, comprehensive metabolic panel, ESR, CRP, complement levels (C3, C4), anti-dsDNA antibodies to assess lupus disease activity 2, 6
• Urinalysis to monitor for new-onset proteinuria (lupus nephritis can develop in 40% of SLE patients) 6

Alternative Diagnoses to Consider

Cyclic Vomiting Syndrome (CVS)

The pattern could represent CVS, which presents with:

• Stereotypical episodes of acute-onset vomiting lasting less than 7 days, at least 3 discrete episodes per year 3
• Prodromal symptoms (fatigue, mental fog, headache) occurring in 65% of patients, lasting median 1 hour before vomiting 3
• However, the exercise-specific triggering and 6-month progressive course make this less likely than CNS lupus

Migraine Without Aura

• Recurrent moderate-to-severe unilateral/pulsating headache with photophobia, phonophobia, nausea, vomiting 3
• Duration 4-72 hours when untreated, family history common 3
• Exercise can trigger migraine, but the consistent pattern with physical activity over 6 months in an established SLE patient raises concern for secondary causes

Cerebral Aneurysm (Less Likely But Must Exclude)

• Sentinel headaches occur in up to 43% of patients with aneurysmal SAH within 2-8 weeks before major rupture 4
• The 6-month timeline makes unruptured aneurysm less likely, but headache with exertion is a red flag requiring neuroimaging 4, 5

Management Algorithm

If Neuroimaging Shows Acute Pathology

• Immediate neurology/neurosurgery consultation for stroke, hemorrhage, or mass lesions 4
• Pulse methylprednisolone 1000mg IV daily for 3-5 days if CNS vasculitis confirmed 7
• Consider cyclophosphamide for severe CNS lupus (intravenous pulse regimen safer than oral) 7

If Neuroimaging Normal But High Clinical Suspicion

• Lumbar puncture to evaluate for aseptic meningitis (common in CNS lupus) 2, 5
• MRI with contrast and MRA/MRV to detect subtle vasculitis or venous thrombosis 5
• The most dangerous error is attributing symptoms to lupus without adequately ruling out infection, particularly in immunosuppressed patients 1

Acute Symptom Management

• Ondansetron 4-8mg sublingual/oral every 4-6 hours for nausea/vomiting 3
• Avoid NSAIDs if renal involvement suspected (can worsen lupus nephritis) 6
• Sumatriptan plus antiemetics during prodromal phase if migraine component confirmed 3

Critical Pitfalls to Avoid

• Never dismiss exercise-induced symptoms in SLE patients as deconditioning—this can be the presenting manifestation of cerebrovascular disease 1
• Failure to obtain neuroimaging is the most common diagnostic error in patients with concerning headache patterns 4, 5
• Do not wait for systemic lupus activity markers to be abnormal before investigating CNS symptoms, as CNS lupus can occur independently 1
• Generalized tonic-clonic seizures occur in 67-88% of SLE patients with seizure disorder—if any seizure-like activity reported, this requires immediate evaluation 1

Disease Activity Monitoring Going Forward

• Monitor for constitutional symptoms (fatigue, nausea, headache, cognitive development) at each visit 2
• Urinalysis every 6-12 months to monitor for proteinuria (AA amyloidosis risk) 2
• Hydroxychloroquine is standard of care and has been associated with significant reduction in mortality—ensure compliance 6
• Immunosuppressive agents (azathioprine, mycophenolate mofetil, cyclophosphamide) typically used for moderate-to-severe disease 6, 7