Differential Diagnosis
The cornerstone of
Western medicine
Initial thoughts. . .
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Each question asked during the patient
interview reflects a sign, symptom, or risk
factor for a disease that we feel may
explain the patient’s presentation.
Differential diagnosis directs our patient
encounter from the very beginning.
Static Process
Patient encounter
History
Physical
Differential Diagnosis
Diagnostic testing
Final diagnosis
Dynamic Process
HISTORY
PHYSICAL
DIFFERENTIAL
Where do we begin?
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Use available information
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Age
Gender
Chief complaint
Vital Signs
Chart Review (as applicable)
Thought process. . .
Epidemiology, Chief complaint, Vital signs
Differential diagnosis
Focused history and physical
Problem List
Refine differential diagnosis
Final diagnosis
Further history or physical
Diagnostic testing
Studying is important!
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Understanding of epidemiology
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Knowledge of disease presentation
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Age, gender, race
Which diseases present with cough, which with
fever, acute versus chronic symptoms, etc.
Ability to recognize abnormal vital signs
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Is the patient hypertensive? Tachycardic? Febrile?
Diagnosis may be made simply. . .
Or not so simply. . .
Formal Differential
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Not needed:
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Classic presentation of common disease
Risk of acute mortality
Needed:
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Atypical disease presentation
Examination or testing does not confirm suspected
diagnosis
Multiple signs and symptoms with no obvious
connection
When you hear hoof beats. . .
think horses
Occam’s Razor
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A principle attributed to the 14th century
logistician and Franciscan friar, William of
Ockham
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“Pluralitas non est ponenda sine neccesitate”
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Plurality (numerous ideas) should not be posited
(considered) without necessity
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That is. . . Keep it SIMPLE!!
Intuitive Postulates
Consider each sign or symptom individually
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Generate a separate differential for each of the
patient’s issues
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Compare the problem-specific differentials
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Include diagnoses that appear frequently
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Those which explain all pertinent positive findings.
Exclude diagnoses that appear infrequently
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Diagnoses that do not explain a majority of findings are
unlikely candidates.
O/W healthy patient with. . .
“cough, fever, headache, tired”
Cough
Fever
Headache
Fatigue
infection
autoimmune
vascular
nutrition
trauma
infection
exposure
metabolic
congenital
inflammation
neoplasm
infection
exposure
endocrine
neurologic
endocrine
meds/drugs
neoplasm
psychogenic
meds/drugs
neoplasm
meds/drugs
infection
exposure
neurologic
metabolic
meds/drugs
neoplasm
psychogenic
exposure
trauma
autoimmune
How to proceed. . .
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Infection, neoplasm, meds/drugs, and exposure
are the most likely categories
Neoplasm, trauma, meds/drugs can be ruled-out
convincingly by further history alone
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Exposure may be difficult – is the patient aware?
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DIRECT questioning – specific possibilities
Proceeding. . .
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After ranking categories – begin to think
about specific diagnoses
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In this case – infection is most probable
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List out specific infectious etiologies
INFECTION
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Infectious Mononucleosis (Epstein Barr - EBV)
Upper respiratory infection (rhinovirus,
paramyxovirus, etc.)
Sinusitis
Measles
Varicella
Pneumonia
Bronchitis
Making the diagnosis
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Using epidemiological data, history, and
physical we attempt to discover the
correct diagnosis
If our working diagnosis proves
inadequate, we return to the differential
and start anew
Streamlined Process
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Utilizing this more fluid thought process, as each
category is considered, specific diagnoses are
postulated simultaneously
As you develop the differential, more than one
diagnosis may be plausible
In this case the final differential is comprised of
the top possibilities in each of medical category
As illustrated here 
INFECTION
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EXPOSURE
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upper respiratory infection, sinusitis, EBV
insecticides, petroleum based chemicals or fumes
MEDICATION/DRUGS
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inhalant abuse, medication overdose (aspirin)
Epidemiology
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The study of disease in a specific population
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Disease prevalence varies tremendously in different
patient populations
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Students should become familiar with age, gender, and
race-related disease risk
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In clinical study, understanding disease-specific
epidemiology is equally important to knowledge of
diagnosis and treatment
Epidemiology is essential
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Sinusitis remains the most probable diagnosis in lieu of
any further information
Young child who had not received standard
immunizations consider other infectious etiologies such
as varicella or measles, along with sinusitis
If this same young child had a history of exposure to
someone with either of these illnesses, consideration of
these diagnoses would be moved ahead of sinusitis
altogether
Epidemiology is essential
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Furthermore, the likelihood of pulmonary malignancy in
a child would be infinitesimally small
16-year-old male who had recently spent numerous
sleepless nights studying for final examinations, we
would strongly consider EBV infection
A 65 year old male with a life-long history of
construction work involving asbestos, then asbestosis or
pulmonary malignancy might be considered before
sinusitis or EBV
Developing a Thorough Differential
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First review categories or areas of medicine
Once you had identified categories that are
plausible, then proceed to specific diagnoses
within those categories
This ensures that you consider ALL possible
areas of medicine and do not just focus on the
most common
VINDICATES
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Vascular
Infectious, Inflammatory
Neoplastic
Drugs
Iatrogenic, Idiopathic/psychogenic
Congenital
Autoimmune (allergic)
Trauma
Endocrine (metabolic/nutrition), Exposure
Systems
Rank-listing the differential
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Ranking of differential makes the list of
diagnoses more useful
Assuming that the diagnoses considered
adequately explain the patient’s symptoms, the
final order is based on two concepts –
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Most common/most likely diagnosis
Diseases that are associated with high mortality or
morbidity
But what do we do with the
zebras?
Move uncommon disorders higher?
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The diagnosis is plausible in our patient
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The diagnosis can be eliminated by additional history,
physical examination, or non-invasive testing
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Nearly impossible in our patient? Not necessary to consider it
from the outset – regardless of lethality.
Diagnosis requires invasive study, specialized laboratory eval. or
expensive testing? It should remain toward the bottom of our
differential list
The diagnosis is associated with acute mortality
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Diagnosis is associated with mortality only after a prolonged
period of time? Consideration following further evaluation of
more common disorders is advisable
Sample case:
Adolescent patient with chest pain
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Common causes include pleurisy, costochondritis, benign
overuse myalgia, or anxiety/stress
As such, these diagnoses should appear at the top of the
differential – with specific historical and physical data
influencing the final order
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Myocardial infarction (MI), while plausible, would be
highly unlikely in an otherwise healthy child
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Therefore, MI would be placed lower on the list of
possible etiologies
Myocardial infarction?
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Using the criteria outlined above, eliminating the
possibility of MI prior to final diagnosis is a
reasonable approach
The diagnosis is plausible, is associated with
acute mortality, and can be ruled-out with a
minimally invasive test  Electrocardiogram
Enzymes (CKMB/Troponin) are rarely needed in
this scenario
Teaching Points
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If the patient’s presentation is consistent with a rare
diagnosis, then further evaluation by whatever means
necessary is compulsory
The point is not to limit our evaluation in order to save
money or time – instead, diagnostic evaluation should be
driven by clinical indication
What is emphasized herein is that you must THINK
through the process of deciding which diagnoses are
considered first, and which can wait.
The doctor as an artist
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Each disease process does not present in exactly the
same way every time. Medicine is more than pure
scientific study – it is an art form
One cannot simply memorize key facts about a diagnosis
and limit consideration of this disease to the fulfillment
of all necessary criteria alone
An astute physician recognizes the possibility of disease
presenting atypically – thereby not explaining every sign
or symptom
Test of time. . .
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Having made a final diagnosis, continued observation of
the patient will allow us to determine if our suspicion
was correct
Students should recognize that uncovering the etiology
of disease may require time
Early on in the course of an individual disease, limited
historical data and newly emerging physical findings may
make accurate diagnosis difficult
Following the patient’s clinical course or response to
therapy may allow time for the disease to declare itself
Don’t be afraid to RE-THINK
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If the clinical course or therapeutic response is not
consistent with the original diagnosis, then that
diagnosis must be questioned
For example, if the disease worsens unexpectedly or the
patient’s symptoms persist despite adequate medical
therapy, the physician must not persist in their
presumption that the original diagnosis was correct
Western physicians will turn to the medical literature or
their colleagues for another opinion
Student Intern Resident Staff
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As they are just beginning their medical training,
students have a less exhaustive understanding
of disease presentation, and so cannot narrow
their history and physical to only the most
relevant topics
With time and experience the student becomes
more adept at the process of obtaining a
relevant, focused history, performing a directed
physical examination, and the like
Student Intern Resident Staff
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With time, students learn to incorporate a
dynamic approach to the differential
diagnosis
This allows them to reassess diagnostic
possibilities throughout the entire process
– not just after the basic information has
been obtained
Dynamic Process
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This intuitive style of thinking has been ingrained into the minds of
Western physicians
The process begins at the onset of the patient’s presentation and
then drives the entire patient encounter – directing further
questioning, examination, and diagnostic testing
In cases where clinical course or response to therapy is inconsistent
with the original diagnosis, return to the differential leads the
physician in a new direction
In every sense of the word, differential diagnosis is a dynamic
process.
Dynamic Process
DIFFERENTIAL
FOLLOW-UP
H&P
DIAGNOSIS
TREATMENT