Differential Diagnosis

Reminder

Start with the most likely diagnosis —
but do not stop thinking.

CTAC still applies Common things are common. Your most likely diagnosis is still the horse. But the differential is the structured process of ruling others in and out.

The obligation Every diagnosis on your list requires justification, evaluation, and a decision. If you cannot justify it — it does not belong on the list.

The skill A differential is not a memory test. It is a reasoning exercise. The student who balances evidence outperforms the student who memorises lists.

Definition

"A differential diagnosis is a list of diseases that you cannot confidently exclude after history and examination."

If a diagnosis is on your list, you must

Justify it — what feature supports its inclusion?

Evaluate it — what does the evidence actually say?

Act on it — what investigation or decision follows?

A differential is not a random list. It is a ranked list — and ranking requires balancing the evidence for and against each possibility.

The Method

Balancing a Diagnosis — for each possibility, ask two questions

＋

Positively Relevant Points

For

Symptom typical of this disease
Sign characteristic of this disease
Known risk factor present
Epidemiology fits (age, sex, background)

−

Negatively Relevant Points

Against

Absence of a key expected symptom
Presence of a contradictory sign
Epidemiology inconsistent
Response contradicts expected pattern

Key insight Negative findings are often more powerful than positive ones.
The absence of an expected feature can significantly lower the probability of a diagnosis — sometimes more convincingly than the presence of any single positive finding.
A student who ignores negative findings is reasoning with half the evidence.

Examples

Balancing in practice — the evidence does the ranking

Example 01 Respiratory · Paediatrics

Child with Wheeze

Scenario: An 8-year-child presents with wheeze. The leading diagnosis is asthma (CTAC). But certain features must be actively balanced — the goal is to confirm the horse while not missing a dangerous alternative.

Balancing Asthma vs. Foreign Body Aspiration

For Asthma

Recurrent episodes of wheeze

Triggered by cold or exercise

Family history of atopy

Bilateral expiratory wheeze

Responds to bronchodilator

Against Asthma — Raise Suspicion

First sudden-onset episode

Unilateral reduced air entry

History of choking on food or object

No family or personal atopy history

No response to bronchodilator

Verdict — how to balance Many strong FOR points with no AGAINST: asthma becomes most likely — treat accordingly. Strong AGAINST points present (especially unilateral signs + choking history): reconsider urgently.
A Foreign body aspiration requires bronchoscopy, not more salbutamol.

The "against" points are not there to confuse you — they are there to protect your patient. One strong negative finding can outweigh several positive ones.

Example 02 Haematology · Paediatrics

Child with Anaemia

Scenario: A child presents with anaemia. CTAC tells you iron deficiency is the horse. This example is not about doubting that diagnosis — it is about the separate and essential question of ruling out a dangerous alternative. Acute lymphoblastic leukaemia must be considered and then actively excluded or retained based on the evidence.

Screening for Leukaemia (ALL) — retain or exclude?

Features that raise concern for ALL

Unexplained fever

Bone pain or limb pain

Hepatosplenomegaly

Unexplained bruising or bleeding

Pancytopenia on FBC

Features that make ALL unlikely

Isolated microcytic anaemia only

Normal white cell count

Normal platelet count

No organomegaly on examination

Dietary iron deficiency risk factor present

Verdict — two separate questions The balancing here does two jobs simultaneously: it confirms iron deficiency as the working diagnosis AND it screens for a diagnosis that must not be missed.
If all the "against ALL" points are present and none of the "for ALL" points — treat iron deficiency.
If any "for ALL" features are present — investigate before assuming dietary anaemia.

Ruling in the horse and ruling out the dangerous zebra are two different tasks — and both must be done, not just one.

Ranking

Prioritising Differentials — in this order, every time

The three-tier hierarchy

How to rank your differential list

Most Likely

Based on the balance of evidence and CTAC. This is your provisional diagnosis. It has the most supporting points and the fewest contradictory ones. You will treat this first.

Most Dangerous — Must Not Miss

The diagnosis that, if missed, would cause serious or irreversible harm. Even if unlikely, it must be actively excluded. This is where a single strong negative finding does powerful work.

Less Likely but Possible

Diagnoses with partial evidence support but insufficient to rank higher. Keep them on the list only if you can justify them. They drive your investigation plan, not your immediate management.

This hierarchy prevents two opposite errors: missing emergencies by focusing only on the likely, and over-investigating trivial causes by treating everything as equally urgent.

Presentation

How to present a differential — mature clinical reasoning

Compare these two approaches

What separates a student from a clinician

Immature — do not say this

"My differential diagnosis includes asthma, foreign body, bronchiolitis, cardiac failure, and tracheomalacia."

Mature — say this instead

"My provisional diagnosis is asthma, supported by recurrent wheeze, exercise trigger, and family atopy. However, I cannot exclude foreign body aspiration because of the unilateral air entry reduction — I would want a chest X-ray to evaluate this. Cardiac failure is unlikely given the absence of any cardiac signs and the bronchodilator response."

The mature presentation demonstrates three things simultaneously: a working diagnosis with justification, a dangerous alternative actively considered, and an unlikely diagnosis explicitly excluded with reasoning. That is clinical thinking.

Bedside & Viva Tool

The 4-Question Balance

Apply this to every diagnosis on your list — at the bedside, in the viva, on the ward.

Why it fits

What features of this patient support this diagnosis? Be specific — name the findings.

Why it does not fit

What features argue against it? What expected finding is absent? This question is equally important.

How sure am I?

Given the balance of evidence — is this most likely, possible, or unlikely? Where does it rank?

What next?

What investigation or clinical decision follows from this diagnosis being on the list?

Use this tool before you speak in a viva or write in a case note. If you cannot answer all four questions for a diagnosis — either remove it from your list or investigate until you can.

Common Student Errors

What poor differential reasoning looks like

Listing diseases without justification If you cannot say why it is there, it should not be there.

Ignoring negative findings Absence of expected features is evidence — often powerful evidence against a diagnosis.

Not ranking differentials An unranked list does not guide management. Ranking is the clinical decision.

Treating absence of expected findings as unimportant A missing key feature often lowers probability more than any positive finding raises it.

Final Take-Home Message

"Differential diagnosis is not a list.
It is a balance."

Medicine is weighing evidence — For. Against. Probability. Risk.
If you cannot explain why a diagnosis is on your list, remove it.

Think logically Balance carefully Act responsibly

Start with the most likely diagnosis —but do not stop thinking.