What causes unilateral facial numbness in a patient with Systemic Lupus Erythematosus (SLE) on plaquenil (hydroxychloroquine)?

Unilateral Facial Numbness in SLE Patients on Plaquenil

Unilateral facial numbness in an SLE patient on plaquenil most likely represents neuropsychiatric lupus (NPSLE) affecting the trigeminal nerve, though stroke, peripheral neuropathy, and non-SLE causes must be urgently excluded through MRI imaging and clinical assessment. 1, 2, 3

Primary Differential Diagnosis

Neuropsychiatric SLE (Most Common)

• Peripheral neuropathy from SLE frequently affects cranial nerves and often co-exists with other neuropsychiatric manifestations, diagnosed with electromyography and nerve conduction studies 1
• The trigeminal nerve can be affected by inflammatory mechanisms in NPSLE, causing unilateral facial sensory deficits 3
• Attribution to SLE requires neuroimaging, cerebrospinal fluid analysis, and exclusion of confounding factors 3

Cerebrovascular Disease (Critical to Exclude)

• Atherosclerotic/thrombotic/embolic cerebrovascular disease is common in SLE patients, particularly those with antiphospholipid antibodies 1
• Ischemic optic neuropathy is usually unilateral, especially in patients with antiphospholipid antibodies 1
• Stroke affecting the brainstem (particularly pontine tegmentum) can present with unilateral facial numbness 4

Non-SLE Causes Requiring Exclusion

• Lumbar puncture for CSF analysis and MRI should be considered to exclude non-SLE causes, especially infection 1, 3
• Bell's palsy can present with facial numbness and requires assessment for Lyme disease in endemic areas 2
• Multiple sclerosis can cause unilateral facial numbness with pontine lesions 4

Immediate Diagnostic Workup

Imaging (First Priority)

• MRI of brain, orbit, face, and neck with and without contrast is the imaging test of choice for facial numbness 2
• Brain MRI has modest sensitivity (50-70%) for neuropsychiatric lupus but should be performed when neurological symptoms are present 3
• Advanced MRI techniques should be considered when standard MRI findings are normal or don't correlate with clinical syndrome 3

Clinical Assessment

• Assess onset timing: acute onset (<72 hours) suggests stroke or Bell's palsy, while gradual progression suggests neoplasm or infection 2
• Examine for associated symptoms requiring urgent evaluation including visual changes, eye pain, and other cranial nerve involvement 2
• Check for antiphospholipid antibodies, as these increase thrombotic risk 1

Laboratory and Neurophysiological Testing

• Consider laboratory testing including Lyme serology and ESR/CRP 2
• Trigeminal somatosensory evoked potentials (TSEP) and blink reflex testing can localize lesions and complement MRI findings 4
• Electromyography and nerve conduction studies diagnose peripheral neuropathy 1

Treatment Based on Underlying Mechanism

For Inflammatory NPSLE

• First-line therapy combines high-dose glucocorticoids with immunosuppressive agents, achieving response rates up to 70% 3
• Combination therapy with glucocorticoids and immunosuppressive agents should be considered in severe peripheral neuropathy cases 1
• Cyclophosphamide is recommended for severe organ-threatening neuropsychiatric manifestations 3
• Azathioprine or mycophenolate mofetil should be used for maintenance therapy after initial control 3

For Thrombotic/Antiphospholipid-Related Disease

• Antiplatelet and/or anticoagulation therapy is recommended for NPSLE related to antiphospholipid antibodies 1, 3
• Anticoagulation may be superior to antiplatelet therapy for secondary prevention of arterial events in antiphospholipid antibody syndrome 1, 3
• Antiplatelet agents may be considered for primary prevention in SLE patients with persistently positive, moderate or high, antiphospholipid antibody titres 1

If Bell's Palsy Confirmed

• Prescribe oral corticosteroids within 72 hours of symptom onset, with evidence showing 83% recovery at 3 months versus 63.6% with placebo 2

Critical Pitfalls to Avoid

• Do not assume plaquenil is causing the facial numbness - while plaquenil can rarely cause neuromyotoxicity, it is protective in SLE and associated with delayed disease onset and improved outcomes 5, 6
• Distinguish between primary neuropsychiatric lupus and secondary causes - infection, metabolic abnormalities, and hypertension must be excluded 1, 3
• Do not order CT of the head/brain initially - it provides no useful information for initial management and exposes patients to unnecessary radiation 1
• Corticosteroid-induced psychiatric disease occurs in 10% of patients treated with prednisone ≥1 mg/kg, manifesting primarily as mood disorder rather than neurological symptoms 3

Follow-Up Requirements

• Reassess or refer to a specialist if there are new or worsening neurologic findings, no improvement within 2-3 weeks, incomplete recovery at 3 months, or development of ocular symptoms 2
• Relapses may occur in up to 50% of NPSLE cases and may require maintenance immunosuppressive therapy 3