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Decoding Differential Diagnosis: How to Think Like a UK…
Decoding Differential Diagnosis: How to Think Like a UK Clinician
A real-world, example-rich guide for PLAB, UKMLA, PRES candidates and new NHS doctors.
Differential diagnosis is one of the most important thinking skills you will ever develop as a clinician. Not because exams demand it, but because real patients need it. UK medical practice—both in hospitals and general practice—relies heavily on calm, logical, safety-focused reasoning.
Many IMGs discover quickly that the UK’s clinical thought process feels different from what they are used to. It isn’t about memorising endless lists or jumping to exotic diagnoses. Instead, it’s about probability, pattern recognition, red flags, guidelines and structured thinking.
The good news?
This way of reasoning is learnable, and you’ll start to enjoy medicine more once it “clicks.”
Below is a practical guide to help you think like a UK clinician, filled with real examples for every step.
The NHS Approach: What Makes It Different?
UK clinicians approach cases with a specific mindset. It’s not magic—it’s method.
They start with probability, not possibility.
Example:
A 20-year-old student with chest pain after lifting a suitcase → MSK pain is far more likely than aortic dissection.
A UK clinician starts there.
They scan for danger early.
Example:
Headache + fever + photophobia → meningitis needs urgent consideration
even if the final diagnosis turns out to be viral illness.
They follow national guidelines.
NICE pathways guide decisions from chest pain to headache to depression.
Example:
Suspected PE → apply Wells score → determines whether you order D-dimer or go straight to CTPA.
They document and safety-net.
This protects patients and clinicians.
Example:
Tension headache diagnosis → advise red flags (“come back if vomiting, confusion or sudden severe pain”).
This entire system is built on calm, rational, structured thinking.
The Six-Step Method UK Clinicians Use
Every experienced NHS doctor uses this framework subconsciously.
Here it is, made visible—with examples.
Identify the main complaint clearly.
Strip the story to one core symptom before analysing.
Examples:
- Patient with fever, vomiting and abdominal pain → main complaint = abdominal pain
- Patient with dizziness, palpitations, and sweating → main complaint = palpitations
- Patient with fatigue, weight gain, constipation → main complaint = fatigue
A clear starting point reduces confusion.
Sort the symptom into broad systems.
This narrows your thinking dramatically.
Examples by system:
Chest Pain
- Cardiac (ACS, pericarditis)
- Pulmonary (PE, pneumonia)
- GI (GERD, oesophageal spasm)
- MSK (costochondritis)
Headache
- Primary (migraine, tension)
- Infective (meningitis)
- Vascular (SAH, temporal arteritis)
Abdominal Pain
- Upper GI (ulcer, pancreatitis)
- Lower GI (appendicitis)
- Hepatobiliary (cholecystitis)
- Renal (stones)
Fatigue
- Endocrine (hypothyroidism)
- Haematological (anaemia)
- Psychological (depression, burnout)
- Chronic disease (CKD, HF)
Just grouping the symptom into a system removes half the confusion.
Identify red flags FIRST.
Red flags trump everything else.
This is core to NHS reasoning.
Examples of red flags (with explanation):
Chest Pain
- Sweating + radiation → possible ACS
- Sudden tearing pain → aortic dissection
- Dyspnea + pleuritic pain → PE
Headache
- Thunderclap onset → SAH
- Neck stiffness → meningitis
- Jaw claudication + age >50 → temporal arteritis
Abdominal Pain
- Rebound tenderness → peritonitis
- Hypotension → sepsis/bleeding
- Persistent vomiting → obstruction
Shortness of Breath
- SpO₂ < 92% → acute respiratory compromise
- Unilateral leg swelling → possible PE
Back Pain
- Urinary incontinence → Cauda equina
- Night pain + weight loss → malignancy
- Fever + back pain → spinal infection
UK clinicians immediately check for these because missing them leads to catastrophic outcomes.
Think of the most common and most likely causes.
This is a huge differentiator between UK practice and many other countries.
Examples of “most likely” reasoning:
Chest Pain in a 25-year-old
- Most likely: MSK pain or anxiety
- Less likely: GERD
- Unlikely but dangerous: PE
Headache in a 30-year-old woman
- Most likely: migraine
- Less likely: tension headache
- Unlikely but serious: meningitis
Fatigue in a 40-year-old
- Most likely: lifestyle stress, sleep deficit
- Common medical causes: iron deficiency anaemia, hypothyroidism
Abdominal pain in RLQ
- Most likely: appendicitis
- Other possibilities: ovarian torsion, renal stone
Probability protects patients from unnecessary tests and panic.
Recognise clinical patterns (“signature clusters”).
This is where experience shines.
Here are some commonly tested and clinically relevant signature patterns:
ACS Pattern
- Crushing chest pain
- Sweating
- Radiates to jaw/arm
- Worse on exertion
PE Pattern
- Sudden dyspnea
- Pleuritic pain
- Tachycardia
- Recent surgery/immobility
Pancreatitis Pattern
- Severe epigastric pain
- Radiates to back
- Worse after alcohol
- ↑ Amylase/Lipase
Appendicitis Pattern
- Periumbilical pain → RLQ shift
- Fever
- Loss of appetite
Migraine Pattern
- Unilateral throbbing
- Photophobia
- Nausea
- Visual aura
Kidney Stone Pattern
- Loin-to-groin pain
- Haematuria
- Severe colicky pain
NHS clinicians rely on these patterns instinctively.
Choose investigations that answer a clear question.
Don’t scattershot-test.
Test with intention.
Examples of targeted investigations:
Suspected ACS
- ECG + Troponin
Purpose: rule out MI
Suspected PE
- Wells score → D-dimer or CTPA
Purpose: risk stratification
Suspected UTI
- Dipstick → culture
Purpose: confirm infection
Suspected appendicitis
- Clinical exam → ultrasound/CT if unclear
Purpose: confirm diagnosis, avoid perforation
Suspected hypothyroidism
- TSH → free T4
Purpose: confirm severity
Suspected pneumonia
- CXR
Purpose: identify consolidation
Every test answers a question—not creates more.
Expanded Real-Life Scenarios (With Deep Reasoning)
Chest Pain on a Busy Morning
A 58-year-old man arrives with central chest pain, sweating, and nausea.
Differentials:
- ACS (HIGH probability)
- PE
- Aortic dissection
- GERD
- MSK pain
Analyzing the case (NHS style):
- Red flags? Yes → sweating + central pain
- High-risk age → 58
- Description fits “classic ACS”
Safest next step:
Urgent ECG
Not antacid.
Not D-dimer.
Not “observe.”
The NHS is safety-first.
Headache After a Long Work Week
A 29-year-old woman reports unilateral throbbing headaches with photophobia.
Differentials:
- Migraine (most likely)
- Tension headache
- Cluster headache
- Early meningitis (serious but unlikely)
Reasoning:
- No fever, neck stiffness
- History of similar episodes
- Lights make it worse
- Nausea present
Next step:
Treat as migraine (NSAID + triptan).
No CT scan needed.
Abdominal Pain After Dinner
A 42-year-old woman with severe RUQ pain radiating to the shoulder, after a fatty meal.
Differentials:
- Biliary colic
- Cholecystitis
- Pancreatitis
- Peptic ulcer
- Hepatitis
Reasoning:
- Pain after fatty meal → biliary origin
- RUQ tenderness → gallbladder
- Fever? Tenderness? Murphy’s sign?
Next step:
- Ultrasound (first-line)
- FBC, LFTs
- Consider antibiotics if cholecystitis
Shortness of Breath After a Flight
A 34-year-old woman, suddenly breathless after a long flight.
Differentials:
- PE (must rule out)
- Anxiety
- Asthma
- Pneumonia
Reasoning:
- Long flight → risk factor
- Sudden onset → PE
- Tachycardia → supports PE
Next step:
Wells score → determine D-dimer or CTPA.
Common Pitfalls (With Examples)
Jumping to rare diseases.
Example:
Joint pain + rash → thinking “lupus” instead of post-viral or reactive arthritis.
Over-investigating.
Example:
Ordering CT brain for a clear migraine history.
Ignoring red flags.
Example:
Back pain with urinary incontinence → MUST rule out cauda equina urgently.
Relying on memory instead of structure.
Memorising lists leads to confusion under pressure.
Frameworks lead to clarity.
Simple Frameworks to Train Your Brain (With Examples)
OLD CARTS for pain
Onset, Location, Duration, Character, Aggravating factors, Relieving factors, Timing, Severity
Example:
Sudden sharp pain worsened by inspiration → pleuritic → think PE.
Systems-based sorting
Heart → Lungs → GI → MSK → Psych
Example:
Chest pain evaluation →
- ACS?
- PE/pneumothorax?
- GERD?
- Costochondritis?
- Anxiety?
VINDICATE for differentials
Vascular, Infection, Neoplastic, Drugs, Inflammatory, Congenital, Autoimmune, Trauma, Endocrine
Helpful for complex presentations like confusion or weakness.
Final Thoughts: Differential Diagnosis Is a Skill You Build
Differential diagnosis in the NHS is not a test of memory.
It is a test of:
- Calm thinking
- Prioritising safety
- Following patterns
- Understanding probability
- Using guidelines sensibly
- Asking the right questions
- Choosing smart investigations
You don’t need to know everything.
You just need a framework that makes the chaos make sense.
Once this reasoning becomes familiar, you will find cases less stressful, decisions more confident, and exams far easier.
Thinking like a UK clinician is a journey—but with structured practice, it becomes second nature.