The differential diagnosis, used appropriately, can serve as one of the most powerful de-biasing tools. When we interview a patient, review records, perform physical exam, etc., we begin to focus on certain areas and eliminate other things from our consideration. Much of this is due to inappropriate bias. For example:

• Framing effect: The patient tells us initially that her ovary is hurting, and that the pain is similar to when she had an ovarian cyst before. The patient (or family member, referring physician, etc.) has framed the condition for us and potentially made us blind to other possibilities.
• Triage cueing: Since the patient was referred for her pelvic pain by her primary care doctor to a gynecologist, we tend to focus only on gynecologic sources of pain (or a GI doctor only on GI causes of pain, etc.).
• Anchoring: The patient tell us in her first few sentences that she has right lower quadrant pain, low-grade temperature, and nausea; we immediately become worried about appendicitis even after we learn that she does not have anorexia and has a three day history of diarrhea. Anchoring is the tendency to lock onto the salient features of a diagnosis too early and not modify our theory as new data arrives.

There are many other types of bias that could be cited. One tool to avoid these and other biases is the differential diagnosis. Traditionally, the differential diagnosis is developed after the history has been obtained, records reviewed, and perhaps even after the physical exam has been performed; then the differential is narrowed down with further testing. But this approach opens the door to a great deal of bias that can lead to an incorrect diagnosis (or no diagnosis). However, if the differential diagnosis is made at the earliest opportunity, there is less chance that we will be biased by what we learn. Practically speaking, this means making the differential diagnosis after learning of the chief complaint, then using history, physical, etc., to arrange the differential in order of most likely to least likely. If you have never done this consciously, you will find that if you do then you will ask different (and more meaningful) questions when taking the history than when you form your differential diagnosis later in the process.

(Note that in some cases a differential diagnosis may be arranged in order of most dangerous to least dangerous rather than most likely to least likely; we will debate the merits of this approach at a later time).

Our biased thought processes (or System 1 thinking in Dual Process Theory) serves us well for most patients. “Common things are common and rare things are rare.” “When you hear hoofbeats, think horses, not zebras.” But as nicely sounding as those axioms are, it doesn’t mean that rare things don’t exist or that there is no such thing as a zebra. Our System 1 thinking fails the patients who are outliers because they tend to get misdiagnosed and potentially harmed in the process. We won’t diagnose something that we never think of, so we need to think broadly and then hone in on the most probable diagnoses as new information becomes available. Therefore, we should think of a broad differential before you learn more about the patient.

There are many different ways to make a differential diagnosis, and there is no one way that is always appropriate. Here are some tips:

• Think about the anatomy or physiology of the problem. Indeed, a good differential diagnosis actually starts with what you already know is right, that is, the normal function of the body. Think about how to disrupt this normalcy to cause the symptom. You don’t even need to know the name of the disease or process. For pelvic pain, for example, ask yourself some basic questions:
• What are the mechanisms that cause us to feel pain? Think about, for example, how a noxious stimulus in the pelvis is transmitted to the brain. Thinking this way will lead you to consider problems in other places, like the spinal cord or brain.
• What anatomy is located in the place where the pain is? For the pelvis, you need to consider each organ (or system) in the vicinity: uterus, ovary, fallopian tube, large and small bowel, bladder, ureter, pelvic floor muscles, abdominal wall muscles, ligaments, etc. And since pain has to be transmitted through nerves to the brain, consider the pathways of those nerves all the way to the brain, as well as issues that affect the perception of pain, such as psychiatric problems.
• What types of processes might affect those organs to cause pain? Pick an organ and apply a process: inflammation, infection, neoplasm, vascular, mass effects, etc. So for example: you consider the fallopian tube and then you go through the systems and consider perhaps salpingitis, hydrosalpinx, pyosalpinx, tuboovarian abscess, tuboovarian complex, tubal cancer, tubal torsion, etc. A useful mnemonic for remembering the relevant processes is VINDICATE’M:
  • Vascular
  • Inflammatory/Infectious
  • Neoplastic
  • Degenerative/Deficiency/Drugs
  • Idiopathic/Intoxicant/Iatrogenic
  • Congenital
  • Autoimmune/Allergic/Anatomic
  • Traumatic
  • Endocrine/Environmental
  • Metabolic/Mass effect
• Consider each symptom independently at first. If a patient presents with right lower quadrant pain, nausea, fever, and anorexia, consider the differential for each of those things. Then investigate the diagnoses that are on each list.

When you start to ask more questions of the patient, you will learn a lot very quickly that will make your list narrow down. For example,

• What is the timing of the process? Divide symptoms into acute, subacute or chronic. There will be some overlap in the lists, but there will be lots of differences too.
• Is the patient pregnant or not?
• What is the nature of the pain? Crampy, sharp, dull? Crampy pain for example implies the contraction of a viscus hollow, e.g., bowel, bladder, ureter, uterus. Learn what these different types of pain mean.
• What are associated or alleviating factors?
• Is the pain associated with menses?

A mnemonic like SOCRATES can be helpful for you to remember the types of questions to ask:

• Site: Where is it located?
• Onset: When did it start? Was the onset gradual or abrupt?
• Character: What does it feel like? Sharp, dull, crampy, throbbing, tearing, burning, etc.
• Radiation: Has it moved? Does it radiate to anywhere?
• Associations:  Nausa, fever, pain during sex, loss of appetite, changes in bowel or bladder habits, etc.
• Timing: Has it gotten better or worse since onset? Does it come and go? How often does it happen? Etc.
• Exacerbating/Alleviating factors: What makes it better or worse? What remedies/medicines have been tried? What limitations does the pain cause?
• Severity: Rate the pain on a scale of 0-10.

When we first learn about a complaint (e.g. pelvic pain), it is part of the learning process to be as exhaustive as possible in making a differential diagnosis. If you have never thought about a condition, you will never diagnosis it. This is a System 2 cognitive process. In real life, you will simplify this differential down to include the most common issues for speed and efficiency (System 1 thinking); in the back of your mind, however, you will still think about zebras when the data do not fit the diagnosis you are pursuing. Our speedy System 1 heuristics will work better if we take the time in the beginning, when learning, to be comprehensive and analytical. We also need to understand how common or rare the diseases on our list are, and how to diagnosis them. Don’t worry about treatments; you can (and should) look that up when you make the diagnosis.

Below I will give two differentials. First, the practical differential diagnosis that I use everyday that reflects common and likely things and which helps me keep perspective of the most likely diagnoses. I also go through this gestalt with the patient to educate her about my thinking. This is a heuristic, or a System 1 Differential Diagnosis. Then I will give a more exhaustive differential of things that are still in the back of my mind (System 2 Differential Diagnosis).

System 1 Differential Diagnosis for chronic pain in a non-pregnant woman

I think of five domains:

1. Gastrointestinal (about 1/3 of all causes of female “pelvic pain”)
   1. Constipation
   2. Irritable Bowel Syndrome
   3. Diverticular Disease
   4. Celiac Disease
2. Urologic (about 1/4 of causes)
   1. Interstitial cystitis/Painful Bladder Syndrome
   2. Chronic UTI
3. Gynecologic (about 1/5 of causes)
   1. Endometriosis
   2. Ovarian cysts
   3. Adhesions
   4. Dysmenorrhea
   5. Adenomyosis
   6. Fibroids
4. Peripheral nervous system/musculoskeletal
   1. Abdominal wall hernia
   2. Myofascial pain syndrome
   3. Pudendal Neuralgia
   4. Piriformis syndrome
5. Central nervous system/psychiatric
   1. Untreated depression
   2. History of sexual abuse

If you take a history with these five domains in mind, you can quickly focus on one area with a few specific questions; namely:

• What are your bowel habits like?
• How many times a day do you urinate? Do you urinate at night?
• Does it hurt to have sex? If so, with insertion or penetration?
• Is the pain present only when you menstruate? Does it worsen with menses?
• Do you have a history of abuse? Have you felt depressed recently?
• Is the pain worse with exercise or other specific physical activities?

If the answers to any of these questions are positive, then further questions will quickly help focus the work-up. Here is the longer differential diagnosis:

System 2 Differential Diagnosis for chronic pain in a non-pregnant woman (the laundry list)

• Extrauterine causes
  • Adhesions
  • Adnexal cysts
  • Chronic ectopic
  • Chronic PID
  • Endometriosis
  • Endosalpingiosis
  • Ovarian Neoplasia
  • Ovarian remnant syndrome
  • Ovarian dystrophy
  • Pelvic congestion
  • Peritoneal cysts
  • Residual accessory ovary
  • Salpingitis
• Intrauterine causes
  • Adenomyosis
  • Dysmenorrhea
  • Cervical stenosis
  • Chronic endometritis
  • Uterine/cervical polyps
  • Leiomyomata
  • Pelvic organ prolapse
  • Embedded or malpositioned IUD
  • Congenital uterine abnormality (such as a noncommunicating horn)
• Urinary Tract
  • Bladder neoplasm
  • Chronic UTI
  • Interstitial cystitis
  • Radiation cystitis
  • Urolithiasis
  • Destrusor dyssynergia
  • Urethral diverticulum
  • Urethral syndrome
  • Urethral caruncle
• Gastrointestinal
  • Colon cancer
  • Chronic intermittent bowel obstruction
  • Colitis
  • Constipation
  • Diverticular disease
  • Hernia
  • Inflammatory bowel disease
  • Irritable bowel syndrome
  • Celiac disease
  • Gas colic
  • Lactose intolerance
• Musculoskeletal
  • Abdominal wall myofascial pain
  • Chronic coccygeal pain
  • Compression of lumbar vertebrae
  • Degenerative joint disease
  • Disk herniation/rupture
  • Fibromyositis
  • Muscle strains/sprains
  • Neuralgia of iliohypogastric, ilioinguinal, and/or genitofemoral nerves
  • Pelvic floor myalgia
  • Piriformis syndrome
  • Rectus tendon strain
  • Spondylosis
• Other
  • Abdominal epilepsy
  • Abdominal migraine
  • Bipolar Disease
  • Depression
  • Malingering
  • Conversion Disorder
  • Familial Mediterranean fever
  • Porphyria
  • Shingles
  • Somatic referral
  • Diabetic ketoacidosis

Don’t be satisfied with your diagnosis unless it satisfies all of the patient’s symptoms. Try to disprove your theory. Always ask, What else could it be?