What is the recommended evaluation and treatment plan for a 29‑year‑old woman with 3‑4 bilateral migraine‑type headaches per week accompanied by phonophobia and facial flushing (acetaminophen ineffective, currently taking naproxen), a new pruritic rash localized to the right breast possibly related to naproxen, and stable vitreous floaters?

Evaluation and Management of Frequent Bilateral Headaches with Naproxen-Associated Pruritic Rash

Immediate Discontinuation of Naproxen and Dermatologic Assessment

Stop naproxen immediately and evaluate the pruritic right breast rash for drug hypersensitivity reaction, contact dermatitis, or unrelated dermatologic pathology. A localized pruritic rash appearing after naproxen initiation raises concern for NSAID hypersensitivity, though the unilateral breast distribution is atypical and warrants dermatologic examination to exclude other causes (e.g., contact dermatitis, fungal infection, inflammatory dermatoses). 1

• Document the temporal relationship between naproxen initiation and rash onset, distribution, morphology, and any systemic symptoms (fever, angioedema, respiratory symptoms). 2
• If the rash resolves after naproxen discontinuation, avoid all NSAIDs in this class and consider selective COX-2 inhibitors only after allergist evaluation if future NSAID therapy is required. 1

---

Headache Diagnosis: Probable Migraine Without Aura

This patient meets criteria for migraine without aura based on bilateral distribution, phonophobia, facial flushing (autonomic feature), frequency of 3–4 episodes per week, and failure of acetaminophen. 2, 3 The absence of photophobia does not exclude migraine, as the International Headache Society requires only one of photophobia or phonophobia. 2

• Red-flag exclusion: Confirm absence of thunderclap onset, progressive worsening, fever, focal neurologic deficits, new onset after age 50, or headache worsened by Valsalva maneuver. 2 Neuroimaging is not indicated if the neurologic examination is normal and the headache pattern is consistent with primary migraine. 2
• The stable vitreous floaters are unrelated to migraine and require no acute intervention unless accompanied by flashes, visual field defects, or sudden increase in floater density (which would mandate urgent ophthalmologic evaluation for retinal detachment). 2

---

Acute Migraine Treatment Algorithm

First-Line Acute Therapy: Triptan + NSAID Combination

Initiate combination therapy with sumatriptan 50–100 mg PLUS naproxen sodium 500 mg at headache onset, as this combination is superior to either agent alone and represents the strongest evidence-based recommendation for moderate-to-severe migraine. 1, 4 However, because naproxen caused a suspected hypersensitivity reaction, substitute an alternative NSAID.

• Alternative NSAID options (in order of preference):

  • Ibuprofen 400–800 mg combined with sumatriptan 50–100 mg. 1, 5
  • Aspirin 1000 mg combined with sumatriptan 50–100 mg. 1, 5
  • Diclofenac 50–100 mg combined with sumatriptan 50–100 mg. 4

• Dosing strategy: Take medication at the earliest sign of headache onset (while pain is still mild) to maximize efficacy. 2, 1, 6 Delaying treatment until pain is severe reduces response rates. 2, 1

• If one triptan fails after 2–3 headache episodes, switch to a different triptan (e.g., rizatriptan 10 mg, eletriptan 40 mg, or zolmitriptan 2.5–5 mg), as failure of one triptan does not predict failure of others. 1, 7, 8

Second-Line Acute Therapy: Gepants (CGRP Antagonists)

If triptans are contraindicated (cardiovascular disease, uncontrolled hypertension) or ineffective after trials of multiple triptans, escalate to ubrogepant 50–100 mg or rimegepant 75 mg. 1, 3 Gepants have no vasoconstrictive properties and are safe in patients with cardiovascular risk factors. 1, 3

Rescue Therapy for Severe Attacks

For severe attacks unresponsive to oral therapy, use intravenous metoclopramide 10 mg PLUS ketorolac 30 mg IV (if NSAID hypersensitivity is excluded) or dihydroergotamine (DHE) 0.5–1.0 mg IV as an alternative. 1 Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes. 1, 6

• Avoid opioids (hydromorphone, oxycodone, codeine) and butalbital-containing compounds due to limited efficacy, high risk of medication-overuse headache, dependency, and rebound headaches. 2, 1, 4

---

Critical Medication-Overuse Headache Prevention

Limit all acute migraine medications to no more than 2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 2, 1, 4 This patient's frequency of 3–4 headaches per week mandates immediate initiation of preventive therapy rather than relying solely on acute treatment. 2, 1

---

Preventive Therapy: Mandatory for Frequent Migraine

Initiate preventive therapy immediately because this patient has more than 2 headaches per week, which meets criteria for prophylaxis. 2, 1 Preventive therapy reduces attack frequency by ≥50%, restores responsiveness to acute treatments, and prevents progression to chronic migraine. 1

First-Line Preventive Medications

• Propranolol 80–240 mg/day (FDA-approved, strong evidence from multiple RCTs). 1, 9 Start at 40 mg twice daily and titrate every 1–2 weeks to effect or maximum tolerated dose. 9

  • Contraindications: Asthma, bradycardia, heart block, hypotension, diabetes with hypoglycemia unawareness. 9
  • Alternative beta-blockers: Timolol 20–30 mg/day, metoprolol 100–200 mg/day. 1

• Topiramate 50–200 mg/day (strong evidence for episodic and chronic migraine). 1 Start at 25 mg nightly and increase by 25 mg weekly to minimize adverse effects (paresthesias, cognitive slowing, weight loss). 1

  • Contraindications: Pregnancy (teratogenic), nephrolithiasis, glaucoma. 1

• Amitriptyline 30–150 mg/day (preferred if comorbid depression, anxiety, or insomnia). 1 Start at 10–25 mg nightly and titrate by 10–25 mg every 1–2 weeks. 1

Second-Line Preventive Options

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) if oral preventives fail or are contraindicated. 1 Efficacy requires 3–6 months of treatment. 1
• OnabotulinumtoxinA (Botox) 155–195 U every 12 weeks is FDA-approved for chronic migraine (≥15 headache days/month) and should be considered if three oral preventives fail. 1

---

Behavioral and Lifestyle Modifications

• Maintain a headache diary (paper or smartphone app) to track attack frequency, triggers, medication use, and response. 2 This improves accuracy of reporting and identifies modifiable triggers. 2
• Identify and mitigate triggers: Sleep deprivation, stress, missed meals, alcohol, caffeine overuse, hormonal fluctuations. 2, 1
• Limit caffeine intake to <200 mg/day to prevent caffeine-withdrawal headaches. 1

---

Follow-Up and Monitoring

• Reassess in 4–6 weeks to evaluate acute treatment efficacy, preventive medication tolerability, and headache frequency. 2, 1
• Preventive therapy requires 2–3 months for oral agents to demonstrate efficacy; do not abandon therapy prematurely. 1
• If headaches persist despite optimized acute and preventive therapy, refer to a neurologist or headache specialist for consideration of advanced therapies (CGRP antibodies, Botox, neuromodulation devices). 1

---

Management of Vitreous Floaters

• Stable vitreous floaters require no intervention unless accompanied by new flashes, sudden increase in floater density, or visual field defects, which mandate urgent ophthalmologic evaluation for retinal detachment. 2
• Reassure the patient that stable floaters are benign and unrelated to migraine. 2