Differential Diagnosis (or How to Know It’s Not Lupus)

  • /Reviewed by: Amy Rontal, MD
  • Differential diagnosis is one of the most important skills that medical students need to learn, whether they are studying specifically for the boards or for their future careers. The reason for this is that, if you don’t even consider a diagnosis as a possibility, you will never be able to actually make the diagnosis, much less treat the problem. When it comes to treating patients in the real world, you can always look up a specific detail: like a drug dose or which antibody you should be testing for when working up a patient for a specific disease. However, you cannot look up a test or treatment for a disease you have not even thought of.

    On board exams, it’s also important to be able to think of possibilities as you read the question stem before even reading the answer choices. There are a few reasons for this. The first is time. You are very limited on time when taking the USMLE or COMLEX and it makes sense to have a few likely possibilities (and a most likely possibility) before you even look at the answer choices. The second reason is actually quite similar to real medical practice. Board style questions often require you to make 2-3 steps to get to the correct answer. If you haven’t been able to construct a differential diagnosis, it’s often difficult to take the required steps to get to the right answer. Lastly, reading the answer choices before creating a list of possibilities in your mind will often trip you up, because the answer choices are often designed so that they all fit with some of the clues in the question stem. With that in mind, let’s get to an example to see how to do this with an exam question I made up. 

    The Question Stem 

    A 58-year-old female presents to the emergency department with her husband complaining of left sided chest pain for 3 hours. She complains of shortness of breath and she appears to be very anxious. Her medications include conjugate estrogen/medroxyprogesterone 0.3mmg/1.5mg and fluoxetine 40mg daily. She had a laparoscopic cholecystectomy 16 years ago and an appendectomy in her 20s. She does not smoke and drinks a glass of wine with dinner most nights. On physical exam, her vital signs include a pulse of 102, respiratory rate of 22, blood pressure of 100/65, temperature of 37.6 (99.7), and O2 saturation of 93% on room air. On auscultation she is slightly tachycardic with no murmurs, her lungs are clear to auscultation, but she takes shallow breaths due to pain, and there is no jugular venous distention. She has no pedal edema and there is no digital clubbing. ECG shows nonspecific T wave changes in the lateral leads. Laboratory studies show the following: 

    Hemoglobin: 12.8

    Hematocrit: 37%

    Platelets: 200,000

    White blood cells: 11,000

    BUN: 16

    Creatinine: 0.9

    Sodium: 138

    Potassium: 4.1

    Calcium: 9.6

    CO2: 28

    Glucose: 110

    pH: 7.48

    PCO2: 27

    PO2: 70

    The first troponin level is not available yet. What is the next best step in management?

    1. Prep the lab for a cardiac catheterization
    2. CT angiogram of the coronary arteries
    3. Ventilation Perfusion Scan
    4. CT angiogram of the chest
    5. Sputum cultures
    6. Plain chest radiography
    7. D Dimer


    So this may be a lot easier than most of your test questions, but the point is that the USMLE (or COMLEX) often requires you to know the differential diagnosis of non-traumatic chest pain and apply it to arrive at the correct answer. Let’s go through the most important diagnoses for non-traumatic acute onset chest pain. The list includes:

    1. Acute coronary syndromes
    2. Aortic dissection
    3. Pulmonary embolism
    4. Pneumothorax
    5. Pericarditis
    6. Pneumonia

    This is not an absolutely complete list, but these are relatively common diseases that you will see on the board exams and in real life. If you can come up with these quickly and order them from most to least likely, it will be much easier to get to the correct answer. So let’s look at each one and some of it’s main features to try to figure this out.

    • Acute coronary syndromes are often described as crushing chest pain or pressure accompanied by nausea and diaphoresis. The pain can radiate to the neck, jaw and either or both arms. Often comes with risk factors such as diabetes, hypercholesterolemia, hypertension, smoking, and family history. It is more common in women > 65 and men > 55 and diagnosed with ECG and cardiac enzymes.
    • Aortic dissection is usually described as pain that is tearing, maximal at onset, and radiates to the back. It can feature unequal blood pressure in the arms, elevated troponins, or focal neurological findings due to stroke. The main risk factor is hypertension. It also occurs with connective tissue disorders like Marfan Syndrome.
    • Pulmonary embolism is usually described as pleuritic chest pain that is often accompanied by tachypnea, tachycardia, or both. ECG findings are usually non-specific and chest x ray is often normal. Arterial blood gases classically show hypoxia with hypocapnia and respiratory alkalosis. Risk factors include smoking, inherited thrombophilias, autoimmune thrombophilias, malignancies, surgery, trauma, and immobility.
    • Pneumothorax is usually described as pleuritic chest pain often accompanied by tachypnea and/or tachycardia. There may be hypoxia, hypocapnia, and respiratory alkalosis. It can be caused by emphysema, congenital blebs, and connective tissue disorders such as Marfan Syndrome. Diagnosis is typically made by chest x-ray.
    • Pericarditis is usually described as pleuritic chest pain that is worse when supine. It has many etiologies. ECG shows diffuse ST segment elevation and PR depression. Troponins may be elevated. If it is constrictive, there may be jugular venous distention. Chest auscultation may reveal a friction rub. Diagnosis is clinical and includes history and physical, ECG findings, echocardiography, and lab testing.
    • Pneumonia can be accompanied by pleuritic chest pain but often causes no pain. Typical findings include some combination of cough, fever, leukocytosis, tachycardia, tachypnea, and hypoxia. Physical exam will often reveal rales, bronchophany and/or egophany.

    So let’s take a look at our patient. Her chest pain is pleuritic, she’s tachypnic, tachycardic, and slightly hypotensive. Her ABG shows respiratory alkalosis with mild hypoxemia. She’s also taking exogenous estrogen, which increases the risks for thromboembolic disease, but also increases the risk for acute coronary syndromes. She does not have fever, pain radiation, diaphoresis, nausea, other cardiac risk factors, jugular venous distention, ST elevation or depression, or any specific medical history that would point to a diagnosis. The most likely diagnosis is pulmonary embolism. The best test in patients with moderate or high probability of pulmonary embolism is CT angiography of the pulmonary vessels as long as there are no contraindications like severe renal disease or allergy to intravenous contrast in which case ventilation perfusion scan can be done. In this patient with a creatinine of 0.9 CT angiography is the next best step in management.

    I hope you can see how coming up with the differential diagnosis prior to reading the answer choices can help. As an exercise, I would recommend doing this with every question you do during exam prep. It may be difficult in the beginning, but the long-term benefits on exams and in practice will be well worth it.