What is the best treatment approach for a patient with one-sided scalp pain that is unresponsive to anti-inflammatory medication (NSAIDs)?

Unilateral Scalp Pain Unresponsive to NSAIDs: Differential Diagnosis and Treatment Approach

For unilateral scalp pain that fails to respond to anti-inflammatory medications, the most critical step is to distinguish between primary headache disorders (particularly migraine), neuropathic conditions (scalp dysesthesia), and secondary causes requiring urgent evaluation.

Differential Diagnosis

Primary Headache Disorders

• Migraine: Unilateral headache is characteristic of migraine, which affects 12% of the population and is the most disabling primary headache disorder 1
• Trigeminal autonomic cephalalgias: These can present with strictly unilateral pain and autonomic features 1
• Tension-type headache: Though typically bilateral, can occasionally be unilateral 1

Neuropathic/Dysesthetic Conditions

• Scalp dysesthesia: Characterized by burning, tingling, or pain in the scalp without visible skin changes; frequently misdiagnosed as seborrheic dermatitis 2
• Associated with cervical spinal changes, psychiatric disorders, and environmental factors 2

Secondary Causes Requiring Urgent Evaluation

Evaluate immediately for "red flags" including 1:

• Abrupt onset (thunderclap headache suggesting subarachnoid hemorrhage)
• Neurologic signs (suggesting mass lesion, stroke)
• Age ≥50 years (temporal arteritis risk)
• Cancer or immunosuppression (metastases, infection)
• Provocation by Valsalva or postural changes (increased intracranial pressure)

Treatment Algorithm

Step 1: If Red Flags Present

• Immediate neuroimaging and specialist consultation 1
• Consider temporal artery biopsy if age ≥50 with new-onset unilateral headache

Step 2: If Migraine Suspected (Unilateral, Pulsating, Moderate-Severe Intensity)

First-line acute treatment (since NSAIDs already failed):

• Triptans (sumatriptan, rizatriptan, zolmitriptan): Eliminate pain in 20-30% of patients at 2 hours 3, 1
• Avoid in patients with cardiovascular disease due to vasoconstrictive properties 1

Second-line acute treatment if triptans fail or contraindicated:

• CGRP antagonists (gepants): Rimegepant or ubrogepant eliminate headache in 20% at 2 hours with nausea/dry mouth in 1-4% 3, 1
• Lasmiditan (5-HT1F agonist): Safe in cardiovascular risk factors 3, 1
• Dihydroergotamine (DHE): Particularly intranasal formulation 3

For status migrainosus (continuous severe migraine >72 hours):

• Systemic corticosteroids (prednisone) may be appropriate 3

Critical caveat: Limit acute treatments to ≤2 times per week to prevent medication-overuse headache 3

Step 3: If Neuropathic/Dysesthetic Pain Suspected (Burning, Tingling, No Response to Standard Analgesics)

First-line treatment:

• Oral pregabalin (low dose): Demonstrated benefit in scalp dysesthesia case series 2
• Topical compound: Amitriptyline + lidocaine + ketamine applied to affected area 2

Adjunctive therapy:

• Oral antihistamines and topical corticosteroids add value when combined with analgesic agents but insufficient alone 2

Evaluate for associated conditions:

• Cervical spine imaging for degenerative changes 2
• Screen for psychiatric comorbidities (depression, anxiety) 2

Step 4: If Inflammatory Scalp Condition Present (Visible Erythema, Scaling)

For seborrheic dermatitis or scalp dermatomyositis:

• Topical corticosteroids: More effective than placebo for total clearance (RR 3.76,95% CI 1.22-11.56) 4
• Mild (class I-II) and strong (class III-IV) steroids are comparable in short-term efficacy 4
• Alternative: Topical calcineurin inhibitors comparable to steroids but with more adverse effects 4

For refractory scalp dermatomyositis:

• Consider intravenous immunoglobulin, rituximab, or apremilast 5
• Low-dose naltrexone or platelet-rich plasma show promise 5

Common Pitfalls to Avoid

• Do not assume all scalp pain is inflammatory: Scalp dysesthesia is frequently misdiagnosed as seborrheic dermatitis, leading to ineffective topical steroid treatment 2
• Do not use opioids or butalbital routinely: These lead to dependency, rebound headaches, and loss of efficacy 6, 3
• Do not overlook medication-overuse headache: Occurs with ≥15 days/month of most analgesics or ≥10 days/month of triptans 3
• Do not miss temporal arteritis: New-onset unilateral headache in patients ≥50 requires urgent evaluation 1

When to Refer

• Neurology: Refractory headache despite first and second-line treatments, concern for secondary headache 3
• Dermatology: Visible scalp changes unresponsive to initial treatment 5, 4
• Pain management: Neuropathic pain requiring complex medication regimens 2