Case-based learning: differentiating migraine in a patient with sickle cell disease

Introduction

Migraine is a common neurological disorder that remains underestimated, under-recognised and undertreated^​1–4​. The World Health Organization estimates that headache disorders affect around 40% of the global population, with migraine among the leading causes of neurological disability worldwide^​2​.

Despite this burden, migraine is still commonly described as “just a headache”. In reality, an attack may include nausea, vomiting, photophobia, phonophobia, dizziness, visual disturbance, cognitive difficulty, fatigue and substantial functional impairment^​2,3,5​.

This creates a diagnostic challenge. Patients do not always present asking for help with “migraine”. They may describe sinus pain, stress headache, pressure behind the eyes, dizziness, a banging sensation in the head or simply ask for another analgesic^​5–8​.

Diagnosis is clinical. There is no routine biomarker, blood test or scan that confirms migraine in a typical presentation. The National Institute for Health and Care Excellence (NICE) and the International Classification of Headache Disorders recommend diagnosis according to the pattern and characteristics of attacks while remaining alert to features suggesting a secondary cause^​3,9​. Migraine without aura involves recurrent 4–72-hour headache attacks with moderate-to-severe pain, nausea, light or sound sensitivity, and worsening with activity^​9​.

Migraine is a high-variance condition. Pain does not have to be unilateral, while non-pain symptoms may dominate the presentation. Vestibular migraine adds further complexity. It involves recurrent moderate-to-severe dizziness or vertigo lasting between 5 minutes and 72 hours in a person with a history of migraine, together with migraine features during at least some episodes^​10​. Patients may describe imbalance, dizziness, nausea, head-motion sensitivity or visual and sensory sensitivity rather than classic spinning vertigo^​10,11​.

Recognition may be particularly difficult in people already living with chronic pain or complex conditions such as sickle cell disease. Headache and dizziness may be attributed to anaemia, dehydration, infection, medication use or sickle cell disease itself. Conversely, attributing a new presentation too quickly to migraine risks missing serious complications including stroke or infection^{​12–14​}.

Medicines use adds another diagnostic layer. NICE recommends combination acute treatment with an oral triptan and either a non-steroidal anti-inflammatory drugs (NSAID) or paracetamol where appropriate, with antiemetic treatment considered according to symptoms^​3​. Opioids and ergots are not recommended for acute migraine. Frequent use of acute medicines can also contribute to medication-overuse headache (MOH), making an accurate history of both headache days and medicine-use days essential^​3,9​.

The following composite case illustrates how a pharmacist can use structured history-taking to recognise migraine features while avoiding diagnostic anchoring, assessing medication use and identifying when escalation is required. Details have been changed to protect patient confidentiality.

Case scenario: a 27-year-old woman with sickle cell disease and possible vestibular migraine

A 27-year-old woman living with sickle cell disease presents for a pharmacy-led consultation because of severe head symptoms that have become increasingly difficult to manage at home. The consultation is undertaken by a clinical pharmacist independent prescriber with postgraduate prescribing training and a clinical interest in headache disorders, working within an agreed scope of practice.

The patient describes a “heavy burden” in the centre of her forehead, with a banging sensation that sometimes feels as though she has been hit. Movement makes the pain worse. Light and sound are difficult to tolerate, and she describes buzzing or ringing sensations, with surrounding sounds appearing unusually loud or echoing. The patient is nauseated, dizzy, exhausted and unable to sleep properly. She does not describe clear spinning vertigo.

The pharmacist first establishes whether urgent secondary causes need to be excluded. The patient is questioned about sudden thunderclap onset, neurological deficit, confusion, collapse, seizure, persistent visual loss, fever, neck stiffness, recent head injury and pregnancy or postpartum status. In view of her sickle cell disease, the pharmacist also asks specifically about chest pain, breathlessness, worsening dehydration and whether the presentation resembles her usual sickle cell episodes^{​3,12–14​}. She reports no weakness, facial droop, speech disturbance, collapse, seizure, fever, neck stiffness or chest symptoms and is not pregnant or postpartum. However, she emphasises that this episode feels different from her usual sickle cell pain. Dizziness, sensory sensitivity and worsening with head movement are particularly prominent.

Further history establishes that the head symptoms developed over several days, with the first two days being particularly severe. Previous episodes of head pain had occurred, but this episode has persisted and has had a greater effect on normal activities.

The pharmacist then uses the PIN domains — photophobia, incapacitation and nausea — as a rapid screening aid. The patient confirms all three: light bothers her during the headache; she feels nauseated; and the symptoms have prevented her from working and functioning normally^​15,16​. PIN alone does not establish the diagnosis, but the responses increase the likelihood of migraine and prompt a fuller headache assessment. Her dizziness, nausea, motion sensitivity and sensory sensitivity also raise the possibility of vestibular migraine. However, a diagnosis is not made on these features alone because established vestibular migraine criteria require recurrent qualifying episodes and exclusion of alternative vestibular or neurological disorders^​10,11​.

Medicine use is explored separately from the symptom history. The patient has used paracetamol, a triptan and an opioid prescribed for sickle cell pain. She reports taking analgesic medicines several times per day on many days during the previous three months because the head pain has persisted. None have provided sustained relief.

The pharmacist asks which medicines are used specifically for sickle cell pain, which are being taken for headache and on how many days per month each is used. The patient cannot provide a sufficiently reliable monthly total. MOH therefore cannot be confirmed from this consultation alone; although, the pattern creates significant concern about medication overuse and warrants further assessment^​3,9​.

The differential diagnosis remains deliberately broad. It includes migraine, possible vestibular migraine, MOH, sickle-cell-related neurological complications, dehydration, anaemia-related symptoms, infection, adverse effects from medicines and vestibular disorders. Tension-type headache, cluster headache and sinus disease are also considered.

The pharmacist explains that the presentation contains several migraine features. However, the new headache pattern in a patient with sickle cell disease warrants same-day medical assessment to exclude an acute secondary cause. The patient is given explicit safety-netting and advised to seek emergency help for sudden severe deterioration, weakness, speech or persistent visual disturbance, collapse, seizure, fever with neck stiffness, chest symptoms, severe dehydration or rapidly progressive symptoms.

The pharmacist also addresses medicine use. Opioids are not recommended for acute migraine, and the patient is advised not to use her sickle cell opioid as a treatment for migraine^​3​. Its appropriate use within her established sickle cell pain plan is distinguished from repeated use for headache.

Potential NICE-recommended acute migraine options are discussed, including an oral triptan with paracetamol or, where suitable, an NSAID, with an antiemetic if required. Aspirin 900mg may also be considered as monotherapy^​3​. Renal and gastrointestinal risks are considered before NSAID or aspirin use, particularly because sickle cell disease may be associated with renal complications and dehydration. Cardiovascular history is checked when considering triptan suitability.

As repeated acute medicine use is a concern, further unsupervised escalation of analgesia is discouraged, and a structured review of medicine-use days is agreed. Any withdrawal strategy must also take account of the legitimate need for analgesia within the patient’s sickle cell pain plan.

The pharmacist asks the patient to keep a headache and medicine diary recording headache days, dizziness, nausea, photophobia and phonophobia, sickle cell pain days, medicines used, sleep, hydration, menstrual pattern and functional impairment.

The assessment, working diagnosis, medicine history, safety-netting and follow-up plan are documented and communicated through the appropriate clinical pathway. Follow up is arranged to review the diary, treatment response and whether further diagnostic assessment or preventive migraine treatment is required.

Discussion

Differentiating migraine from overlapping symptoms

Several features in this case support migraine: moderate-to-severe head pain, aggravation by movement, nausea, photophobia, phonophobia and significant functional impairment^​3,9​. The additional dizziness and head-motion sensitivity make vestibular migraine an important differential. However, the distinction between possible and confirmed vestibular migraine matters. A single presentation containing dizziness and migraine symptoms does not fulfil recognised diagnostic criteria without the required pattern of recurrent vestibular episodes^​10,11​.

The case also illustrates why relying on the patient’s diagnostic label can lead to missed migraine. The patient did not initially say: “I have migraine.” Instead, she described banging head pain, dizziness, buzzing, sensory sensitivity and an inability to function.

PIN provides a useful rapid screen in this situation. It assesses disability, nausea and photophobia. In its original primary care validation study, the three-item ID Migraine screen demonstrated a sensitivity of 0.81 and specificity of 0.75, while subsequent meta-analysis reported similar diagnostic performance^​15,16​.

PIN should therefore prompt further assessment rather than replace it.

For pharmacists, the important question is not simply: “How bad is the pain?” — it is: “What pattern are these symptoms following?”

The presence of sickle cell disease is central to the assessment but should not predetermine the diagnosis.

NICE advises healthcare professionals to regard people with sickle cell disease as experts in their own condition and to consider alternative diagnoses when an episode is atypical^​12​. In this case, the patient’s statement that the headache felt different from her usual sickle cell pain was clinically important.

The pharmacist must therefore avoid two potential mistakes: anchoring everything to sickle cell disease or anchoring everything to migraine. Both can harm the patient.

Prescribing and management considerations

A structured red-flag screen (e.g. a SNOOP-based approach, see Box) can help identify systemic symptoms, neurological deficit, sudden onset, pattern change and other features associated with secondary headache^​17​. In a patient with sickle cell disease, the threshold for escalation should also reflect the increased relevance of neurological, infective, dehydration and cardiopulmonary complications^{​12–14​}.

The value of the framework is not in mechanically reciting an acronym — it is in ensuring that important questions are not omitted when a complex history makes the consultation noisy.

Medicine history is particularly important in people living with more than one painful condition.

Asking simply, “What painkillers do you take?” is insufficient.

The pharmacist needs to establish:

• Which medicine is taken;
• What condition it is being taken for;
• How many days per month it is used;
• Whether medicine use has increased;
• Whether the patient is treating separate pain conditions with the same medicine;
• Whether treatment provides meaningful relief.

This distinction is particularly important in sickle cell disease. An opioid may have a legitimate role within an agreed sickle cell acute pain plan but still be inappropriate for treating migraine^​3,12​.

MOH also requires more than the observation that a patient is “taking a lot of pain-relief”. Diagnostic criteria take account of headache frequency, duration of overuse and the number of days per month that particular acute medicines are used^​9​.

In this case, the history raises concern because repeated acute medicine use has occurred over approximately three months. However, the patient cannot reliably quantify medicine-use days or headache days. The pharmacist should therefore document suspected medication overuse or risk of MOH, rather than prematurely recording a confirmed diagnosis.

A diary can turn an unclear medicine history into clinically useful information at follow up.

Acute treatment and prescribing within competence

Once serious secondary causes have been appropriately considered, treatment decisions should follow the likely headache diagnosis and the patient’s individual risk factors.

NICE recommends combination acute treatment with an oral triptan and either an NSAID or paracetamol. Monotherapy with a triptan, NSAID, aspirin 900mg or paracetamol may also be considered according to patient preference, comorbidities and risk^​3​. An antiemetic can be considered even where nausea or vomiting is not prominent.

In a patient with sickle cell disease, selection of an NSAID warrants particular attention to renal function, dehydration and gastrointestinal risk. Current medicines, anticoagulant use, asthma or NSAID sensitivity and previous response should also be assessed where relevant. Triptan prescribing requires consideration of cardiovascular contraindications and precautions.

This is an example of prescribing within competence rather than prescribing simply because authority to prescribe exists. The case was undertaken by an independent prescriber with relevant postgraduate training and a defined clinical interest in headache disorders. Pharmacists who assess and manage migraine should similarly work within their own competence, local governance arrangements and access to appropriate escalation pathways.

However, migraine should not automatically sit outside routine pharmacy practice. The Pharmaceutical Journal‘s 2025 migraine roundtable survey found that 56% of pharmacist respondents described themselves as only “somewhat confident” in recommending appropriate migraine treatment, while 34% were confident or very confident^​18​. The same report identified gaps in differentiating headache types and in knowledge of current migraine treatments.

These findings support greater education and clearer pharmacy pathways rather than routine referral of every uncomplicated migraine presentation.

Documentation and follow up are part of treatment

The consultation should not end when a medicine is supplied or prescribed.

Accurate documentation is particularly valuable where migraine has previously been hidden within broad terms such as “headache” or “pain”. Recording the clinical features, working diagnosis, medicine use, red-flag assessment, safety-netting and follow-up plan creates continuity between pharmacy, primary care and specialist services.

Follow up also provides information that the first consultation cannot.

A headache diary can establish:

• Total headache days;
• Days with migraine features;
• Dizziness or vestibular-symptom days;
• Acute medicine-use days;
• Sickle cell pain days;
• Treatment response;
• Functional impact.

This allows the clinician to determine whether acute treatment is effective, whether medication overuse is occurring and whether the pattern is progressing.

Risk of chronification

A main objective is not only to manage the current attack but to reduce the risk of progression.

Chronic migraine is defined as headache on at least 15 days per month for more than three months, with migraine features on at least eight days per month^​9​. It is associated with greater disability and poorer quality of life than episodic migraine^{​19–21​}. Factors associated with migraine chronification include high baseline headache frequency, ineffective acute treatment, medication overuse, psychological distress, obesity and other comorbidities^{​19–21​}.

The patient in this case has several reasons to warrant structured follow up: chronic pain, disrupted sleep, repeated acute medicine use and significant functional impairment.

If migraine remains recurrent, disabling or inadequately controlled despite optimised acute treatment, preventive treatment should be considered in accordance with NICE guidance^​3​. Options include propranolol, topiramate and amitriptyline, where clinically suitable. Topiramate requires particular attention because it is contraindicated for migraine prevention during pregnancy and is subject to Pregnancy Prevention Programme requirements in people who can become pregnant^​22​.

Patients who do not respond to, cannot tolerate or cannot use conventional treatments may meet NICE criteria for newer migraine-specific options. These include rimegepant for acute treatment in defined circumstances and preventive treatments including gepants, calcitonin gene-related peptide monoclonal antibodies and botulinum toxin type A, according to individual NICE technology appraisal criteria^{​23–30​}.

Pharmacists do not necessarily need to initiate every stage of this pathway. They do need to recognise when treatment has failed and know where the patient should go next.

This case demonstrates that effective migraine care is not only about choosing a medicine. It is about listening well, recognising patterns, avoiding diagnostic anchoring, managing risk and supporting the patient with a clear plan that will allow them to achieve long term control of their condition.