What are the differential diagnoses for a patient presenting with migraine attacks and recurrent episodes of fever?

Differential Diagnosis for Migraine Attacks with Recurrent Fever

When a patient presents with both migraine attacks and recurrent fever, the fever is NOT a feature of primary migraine and mandates investigation for secondary causes, particularly infectious, inflammatory, or autoimmune conditions that can mimic or coexist with migraine. 1, 2

Primary Migraine Does NOT Cause Fever

• Migraine without aura presents with recurrent headaches lasting 4-72 hours with unilateral, pulsating, moderate-to-severe pain aggravated by activity, accompanied by nausea/vomiting, photophobia, and phonophobia—but fever is explicitly NOT part of the diagnostic criteria 1
• Migraine with aura adds transient focal neurological symptoms (visual, sensory, speech) lasting 5-60 minutes before or during headache, but again, fever is absent from the clinical picture 1
• The presence of recurrent fever alongside migraine-like headaches should immediately trigger consideration of secondary headache disorders 2

Critical Secondary Causes to Exclude

Infectious Etiologies

• Meningitis presents with headache, neck stiffness, and unexplained fever—this is a medical emergency requiring immediate evaluation with lumbar puncture after neuroimaging 2
• Encephalitis can present with headache, fever, and altered mental status or personality changes 2
• Chronic or recurrent sinusitis may cause facial pain/headache with low-grade fever, though this typically has different pain characteristics than migraine 2

Inflammatory and Autoimmune Conditions

• Systemic lupus erythematosus (SLE) commonly presents with both migraine-like headaches and recurrent fevers, along with other systemic manifestations
• Vasculitis syndromes can cause headache and fever, particularly in younger patients
• Behçet's disease presents with recurrent fever, headache, and other systemic features including oral/genital ulcers
• Adult-onset Still's disease characteristically presents with quotidian (daily spiking) fevers and headache

Other Important Considerations

• Giant cell arteritis in patients >50 years presents with new-onset headache, scalp tenderness, jaw claudication, and may have low-grade fever—requires immediate ESR/CRP and temporal artery evaluation 2
• Brain abscess or subdural empyema presents with progressive headache, fever, and focal neurological signs 2
• Medication-overuse headache can complicate chronic migraine but does not explain fever 3

Diagnostic Approach

Red Flags Requiring Urgent Investigation

• Unexplained fever with headache is itself a red flag mandating further workup 2
• Neck stiffness or limited neck flexion suggests meningitis 2
• Altered consciousness, memory, or personality changes indicate CNS infection or inflammation 2
• Progressive worsening of headache pattern over weeks to months 2
• Focal neurological symptoms or signs beyond typical migraine aura 2

Essential Investigations

• Complete blood count with differential to assess for infection or inflammatory process
• ESR and CRP to screen for inflammatory conditions; note that ESR can be normal in 10-36% of giant cell arteritis cases 2
• Blood cultures if systemic infection suspected
• Lumbar puncture after neuroimaging if meningitis/encephalitis considered—this is mandatory when fever and headache coexist with meningeal signs 2
• MRI brain with and without contrast is the preferred neuroimaging modality for subacute presentations or suspected inflammatory/infectious process 2
• Autoimmune serologies (ANA, anti-dsDNA, complement levels) if systemic autoimmune disease suspected

When to Image Emergently

• CT head immediately if acute presentation with fever, headache, and altered mental status 2
• MRI brain with contrast if subacute fever and headache to evaluate for abscess, meningitis, or inflammatory conditions 2

Management Algorithm

1. Immediate triage: Any patient with headache plus fever plus neck stiffness or altered consciousness requires emergency admission 2
2. Urgent evaluation within 48 hours: Recurrent fever with migraine-like headaches but no meningeal signs warrants urgent neurology referral and infectious disease consultation 2
3. Do NOT attribute fever to migraine: This is a dangerous assumption that can delay diagnosis of life-threatening conditions 2, 4
4. Treat the underlying cause: Once secondary causes are identified, treatment targets the specific etiology rather than symptomatic migraine management

Common Pitfall to Avoid

The most critical error is assuming the headaches are "just migraine" and dismissing the fever as coincidental or unrelated. Fever is never a feature of primary migraine, and its presence demands thorough investigation for secondary causes that may be life-threatening if missed. 1, 2, 4