Sim 5. Prioritize the differential

Intro (1).  Today we’ll talk about prioritizing a differential diagnosis.  After defining the problem, you’ve come up with diagnostic hypotheses, and tested them using focused questions and the physical exam.  How do you decide which diagnosis is most likely?

Recap of pattern recognition versus analytic thinking (2).  Remember there are two ways doctors can arrive at a working diagnosis.  The first is pattern recognition.  The doctor using system 1 thinking intuitively and rapidly recognizes the problem.  A few focused questions and the exam confirm the diagnosis and maybe exclude dangerous alternatives, and that’s that.

The second approach is analytic.  The doctor using system 2 consciously and explicitly analyzes information, attempting to match the patient’s problem to the illness scripts she’s built over the years.

Expert clinicians seeing a patient with a familiar problem often use pattern recognition.  Even experts fall back on analytic thinking when a patient has an uncommon, atypical, or high risk presentation.  We don’t want to rely on our gut instincts alone if the problem’s tough or the consequences of a mistake are bad.

As a novice diagnostician, you should practice using system 2, analytic thinking for any patient with a new concern – at least until you’re a resident, you’re really not allowed to NOT have a differential diagnosis for a patient’s problem.  As your clinical experience grows, you’ll find yourself using more pattern recognition.

Differential diagnosis (3).  Your goal: a differential diagnosis that includes the most likely and in some cases, the most lethal, causes of your patient’s problem.  Our brains can handle only so much cognitive load – we can’t realistically consider more than 5 or 6 diagnoses at once.  So how do we figure out which should be on our differential?

A good place to start is with the pretest probability – the relative likelihood of different diagnoses in patients presenting with the same problem.  You may have heard the old saying “When you hear hoofbeats, think horses not zebras” (at least in the United States).  In general, a common illness is much more likely than a rare one, though the rare ones are sometimes the ones that come to mind.

As you learn about illnesses, pay attention to whether they’re common or rare.  Look up the frequency of different causes of your patients’ chief concerns.  Over time, you’ll develop a sense of how common each is in your patient population.

An example (4).   Let’s say you’re seeing a 42 year old man with difficult to control hypertension.  He is on maximum doses of 3 medications – a diuretic, a beta blocker, and an ACE inhibitor.  Despite the excellent regimen, his BP in the office is still consistently in the 160-170’s/90s.  Take a minute and come up with your differential diagnosis as you walk in the door to see him.

I bet you came up with diagnoses like these. (pheochromocytoma (< 1%), hyperaldosteronism (~10%), Cushings’s (<1%), coarctation of the aorta(<1%)

It turns out that these are all rare causes of resistant hypertension.  By far the most common is poor medication adherence.  The exact prevalence is hard to pin down, but in one study that used chromatography to measure drug levels, almost 50% of patients with resistant hypertension seemed to have a significant problem with adherence.  Sleep apnea, excess salt intake, and kidney disease are also more common than the ‘zebras’ that jump quickly to mind.

Hypothesis testing (5).  So walking in the door, maybe your differential diagnosis looked like this.

You test your hypotheses with focused questions.  Each answer has the potential to change your differential: to move the probability of a diagnosis up or down, or sometimes, eliminate it completely.

You start with questions about adherence.  You remember a Rational clinical exam article  – a ‘yes’ answer to one question – have you missed any pills in the last week – supports nonadherence if the answer is yes, and argues against it if the answer is no.   (+ LR of 4.3, – LR of 0.5).  Your patient is vague about medication names and doses, and says he has missed doses this week.  Now nonadherence is even more likely.

You might ask more focused questions about the other items on your differential, to make sure there’s not another diagnosis you SHOULD be considering now.

You perform an exam, again testing your hypotheses.  You might check weight and neck circumference to assess sleep apnea risk, or check for striae or hirsutism that might indicate Cushing’s.  Assuming you don’t find anything that supports these, you’re left with medication nonadherence and renal disease at the top of your differential.  You can check a creatinine and focus on adherence rather than spend many thousands of dollars testing for a whole list of very unlikely possibilities.  You might hear this referred to as ‘shotgun’ testing.  Hoping to hit the target, but not knowing quite what it is, you aims in a lot of directions at once.  The expert shoots right at the target.

Flip the script (6).  What if your patient with difficult to control hypertension said yes, he does have intermittent pounding headaches, the most common feature of symptomatic pheos after hypertension.  And yes, he does have palpitations associated with his headaches.  These ‘yeses’ move the probability of pheochromocytoma up enough to test for it, which is expensive, inconvenient, and often falsely positive.  Given the low prevalence of pheo, other diagnoses are still more likely even with headaches and palpitations, but your focused questions have moved you above the testing threshold – it’s a diagnosis you wouldn’t want to miss.

Changing probability (7):  As you gather information from the history and exam, the probability of the diagnoses on your differential changes.  The more features of your patient’s illness match the typical presentation of the disease, the more likely it is.  If your patient with resistant hypertension, headaches, and palpitations also has episodic pallor and diaphoresis, a family history of pheo, and orthostatic hypotension, you really need to get cracking on working it up.

The more common features your patient lacks, the less likely it is.  Sometimes, the lack of a single clinical finding will actually rule out a diagnosis – it’s a must have feature.  For example, if your patient with fever of unknown origin reports that she’s never left the state of Washington, you can pretty much rule out malaria as a cause.  But remember, usually the presence or absence of a features just changes  probability rather than ruling a diagnosis in or out.