Sim 3. Testing diagnostic hypotheses

Although expert clinicians gather much less data than novices, their diagnoses are more likely to be accurate.  Experts’ knowledge and experience allow them to target questions, exam maneuvers, and testing to the problem at hand.  As a novice, you rely on the comprehensive H&P to uncover important details – experts gather less data but their experience allows them to target better data.

To confirm their diagnostic hypotheses, clinicians can test them with questions about specific symptoms or risk factors for the diseases they’re considering.  They may look for an exam finding or perform labs or x-rays.  The results of each of these investigations – focused questions, hypothesis-driven physical exam, and diagnostic testing – can support or argue against diseases that are on the differential. Comparing illness scripts can help you identify the signs and symptoms that are most useful in differentiating between diagnoses.

Compare the three causes of acute pharyngitis below.  Some features, like acute onset and fever, are common to all three, but there are also important differences.  Most patients with a viral URI have cough or rhinorrhea while those with streptococcal pharyngitis do not.  Exposure to children makes streptococcal pharyngitis more likely in adults.  And cervical lymphadenopathy is common in strep pharyngitis and mono but uncommon in routine viral URI.

A novice would learn about the absence of cough, exposure to children and the presence of cervical adenopathy during a complete H&P.   Experts, on the other hand, would target their focused questions to uncover these differences, which are diagnostically useful in sore throat.  Symptoms or risk factors that change the likelihood of a diagnosis (like cough or rhinorrhea) would be added to your problem representation.

Sometimes, a specific symptom or risk factor is required to make a diagnosis.  For example, if a patient with fever has never travelled outside the Northwest, they cannot have malaria.  Focused question can also target red flags that require additional investigation, like severe pain with jaw opening in a patient with sore throat. An expert who elicited that red flag would examine and test for an abscess.

Diagnostic utility of clinical findings

Symptoms and physical exam signs can be considered ‘diagnostic tests’, just like a lab test or x-rays.  Their validity (or accuracy) refers to their ability to distinguish between people who have and those who do not have a disease. Just as with lab testing, not all positive results are true positives.  Some patients with crushing substernal chest pain have a diagnosis other than acute coronary syndrome.  A yes or no answer to a focused question usually doesn’t ‘rule in’ or ‘rule out’ a disease, it just changes the probability.

As you learn about the ‘classic’ symptoms of diseases, consider how much each changes the probability of the diagnosis.  For some diseases, the sensitivity and specificity of different signs and symptoms have been studied.  The JAMA Rational Clinical Exam series and “The Patient History: An Evidence-Based Approach to Differential Diagnosis” summarize the available data on the accuracy symptoms and risk factor in predicting specific diagnoses.  As your clinical experience grows, you’ll get a sense of how much certain symptoms change the probability in the patient population that you see.

Likelihood ratios

The utility of a clinical feature can be reported as a likelihood ratio (LR), a number calculated from the finding’s sensitivity and specificity.  Likelihood ratios can range from 0 to ∞.

Findings with LRs greater than 1 increase the probability of disease – the higher the LR, the more strongly the feature supports the disease.

Findings with LRs less than 1 decrease the probability of disease – the closer the LR is to zero, the more strongly it argues against the disease.  Findings with an LR right around 1 aren’t useful – they don’t meaningfully change the probability of disease.

Here’s an example, from a JAMA Rational Clinical Exam article on lumbar spinal stenosis, a common cause of back pain in older adults.

The authors identified three symptoms that strongly support spinal stenosis if present, with a positive LRs > 5: absence of pain when seated, improvement in symptoms when bending forward, and bilateral buttock or leg pain.  A ‘no’ to any of these questions argues only weakly against spinal stenosis because the negative likelihood ratios are ~ 0.5.

Neurogenic claudication – leg pain that develops with standing or walking – supports a diagnosis of spinal stenosis less strongly. The positive LR for this question is lower.  But with a negative LR of 0.2, the absence of neurogenic claudication argues more strongly against spinal stenosis.

Knowing this, you can ask each of these focused questions when seeing patients with chronic back pain.

Testing hypotheses with physical exam

A century ago, the gold standard for most diagnoses was, out of necessity, the physical exam.   But even with today’s technology, the physical exam is still essential.

Some diagnoses, such as cellulitis, are still made based on physical exam findings – there is no diagnostic test that performs better.  Sometimes the exam suggests a possibility that you hadn’t considered – unilateral throat swelling suggests peritonsillar abscess in a patient that you thought had plain old strep throat.

Having diagnostic hypotheses as you start your physical can focus your attention on the most helpful findings.  You are much more likely to notice a soft heart murmur if you’re thinking about pulmonary hypertension than if you are just going through a ‘complete’ PE. Your diagnostic hypothesis can also add specific maneuvers to your exam, those with findings that change the probability of the diagnoses on your differential.

Physical exam findings can move the probability of a diagnosis up or down.  That might be enough to forego a lab or imaging study because the likelihood of a diagnosis is now so low – or to justify expensive testing because the likelihood is now higher.  In this workshop, we’ll discuss some exam findings that are helpful in patients with chest pain, and we’ll return to the hypothesis driven exam in future sims.

Evidence-Based Physical Diagnosis, available full text through the Health Sciences Library, is an excellent summary of the evidence supporting physical exam.   For some exam maneuvers, there isn’t any evidence – it has not been formally studied.  Sometimes the evidence is just what you’d expect, and sometimes the evidence is surprising.

Resources & references

The Patient History: An Evidence Based Approach to Differential Diagnosis. Henderson, Mark et al. Lange, 2012. LINK

Evidence Based Physical Diagnosis, 5th ed. McGee, Steven R. Elsevier, 2022.  LINK

JAMA Rational Clinical Exam Series LINK