Diagnosing Complex and Mystery Conditions

Posted By Donna Alvarado, Medical Editor

Presented by
Justin Lotfi, MD, Clinical Assistant Professor of Medicine
Linda Geng, MD, PhD, Clinical Assistant Professor of Medicine

September 5, 2019

On popular TV programs, hospital patients with a rare illness always get diagnosed within 60 minutes. The doctor is a hero(ine). The patient is grateful.

In real life, it’s not so fast or easy. That’s where Stanford’s Consultative Medicine Clinic comes in. Doctors there specialize in pursuing the diagnosis of patients with the most complex medical conditions.

Often these patients have seen other doctors who couldn’t help. Sometimes they’ve struggled through months or even years without knowing what’s wrong.

“Everyone’s going to be frustrated if you can’t figure out a mystery diagnosis,” said Justin Lotfi, MD,  an internal medicine doctor, in a presentation to the Stanford Health Library.  “It’s frustrating for the patient. They don’t feel good, they’re suffering, they feel helpless.”

Recognizing a need

Doctors at Stanford saw the need for helping people with complicated “mystery” medical problems. About 5 years ago, they started the Stanford Consultative Medicine Clinic for those who hadn’t been helped elsewhere.

Some patients may have multiple symptoms that appear to affect different parts of the body that don’t fit any known illness. Other patients may have a symptom of a common illness that turns out to be something else.

One patient came to Stanford’s consultative clinic with a sharp shooting pain down his leg. That’s the classic sign of a nerve problem called sciatica. But the problem kept coming back.

Doctors did a careful exam and medical history that eventually turned up a different cause: shingles. That’s a painful condition that shows up in adults, caused by the same virus that gave them chickenpox as children.

In many cases, shingles causes pain in a patient’s trunk or arms. The leg pain had led doctors at first to diagnose sciatica. “You can be fooled,” Dr. Lotfi said.

Challenges to diagnosis

Coming up with the correct diagnosis for a complicated illness can be difficult, Dr. Lotfi said. There are multiple reasons:

  • Lack of time
    Most patients get about 15 to 20 minutes for their appointments with a doctor. That’s not enough time for a complicated case.
    Doctors get as frustrated as patients when they don’t have enough time to figure out what’s going on, Dr. Lotfi said. “The clock’s ticking. You have to see your next patient.”

        When doctors feel rushed, they may interrupt patients who are trying to explain complicated symptoms. “A lot of        the clues to these patients are the elements of a mystery,” Dr. Lotfi said. “So once you interrupt them,        whatever story was coming out is kind of lost forever.”

        Patients coming to Stanford’s consultative clinic get more time. Their first visit may be 60 minutes. If necessary,         they may return for more appointments over time. Even if a patient comes in with a shoebox of medical records,         they Dr. Lotfi said, “I go through those.”

  • Lack of knowledge
    Symptoms that appear to be a common ailment may turn out to be something else: a rare condition that few doctors have seen. Even specialists can miss a diagnosis.
    A rare diagnosis is, by definition, rare. Even doctors may not have seen it in training or in medical practice.
  • Biases and expectations
    Based on early cues, a doctor sometimes expects to find a particular diagnosis. That can interfere with staying open-minded to the cause of an illness.
    If he’s not careful, Dr. Lotfi said, “I ignore a lot of other symptoms and signs that come up later. It’s a very common pitfall.”
    The bias can also be caused by:
    • Other recent cases: Doctors often judge a case based on what’s most recent in their memories.
    • Ascertainment bias: this is similar to stereotyping. After seeing symptoms, a doctor may also notice the patient’s age, gender, and other qualities that suggest a condition. “You come up with an assumption without even getting a history or exam,” Dr. Lotfi said.

        “There are dozens of biases,” Dr. Lotfi said. Doctors try to set aside these influences to stay open to new         information.

  • Data and red herrings
    Sometimes data from lab tests or medical imaging scans turn out to be false or wrong. This is sometimes called “a red herring.”
    MRI scans may show degeneration of the spine or knee, for example. But that’s not necessarily what’s causing pain. As people age, “We all kind of have degeneration,” Dr. Lotfi said.
    Similarly, even lab tests can have an error in results. About 10% of lab results have some kind of error, according to studies, Dr. Lotfi said.
  • Unknown conditions
    Sometimes patients have symptoms that don’t fit any known medical condition or syndrome. That’s when doctors face especially difficult decisions.
    “If they don’t fit the criteria, we don’t do treatment,” Dr. Lotfi said. “Because some treatment has some pretty harsh effects.”
    In some cases, the best doctors can do is continue to monitor the patients over time, watching and waiting for new clues to emerge.

Getting a fresh look

When a patient comes to the consultative clinic, doctors take a step back from any previous diagnoses. Their goal is to take a fresh look at what might be causing the illness.

This usually means listening carefully to the patient’s story to get a full medical history. It also includes a thorough physical exam, followed by any tests that might help.

If those steps still don’t any clear answers, the doctor may decide to wait and repeat the patient’s evaluation again in a few months. Sometimes new clues emerge over time.

Rare causes

In one case, a patient came to the clinic with a painful ear after camping. The painful area had some red dots that looked like a spider bite, and his previous doctor had given him an antibiotic for that.

By the time he got to the clinic, his ear was swollen. The front of his face looked uneven, with one side sagging. After careful reevaluation, the clinic doctor diagnosed a rare condition called Ramsay Hunt Syndrome that is caused by a common virus, varicella zoster. After getting antiviral medicine, the patient improved.

Many times, a complex diagnosis from consultative medicine takes time and repeat visits. Among the questions doctors may face are:

  • Have the results of previous lab testing been false or misleading?
  • Is this a rare illness masquerading as a common disease?
  • Have the symptoms evolved over time?

In one case, a patient with abdominal pain and vomiting had been previously seen by specialists. They had given her a diagnostic test for a gallbladder disorder that showed normal results. They couldn’t give her a diagnosis.

Consultative medicine doctors determined that the gallbladder test had been wrong. After studying the results, they found the test had been done without a key chemical. Without that, the test wasn’t sensitive enough to pick up evidence of gallbladder problems.

The patient had surgery to remove her gallbladder and recovered fully. Her symptoms were gone.

Difficult to wait

In some cases, it takes a long time to find the correct diagnosis. Dr. Lotfi said he is honest with patients when he hasn’t come up with a clear answer. “I don’t want to give you a misdiagnosis,” he said. “It’s better to give an ‘I don’t know’ answer than a wrong answer.”

The wrong diagnosis can lead to the wrong treatment—which can have bad results. Doctors have all seen patients getting worse from “medically induced harm” caused by wrong treatments.

“It’s such a humbling process,” Dr. Lotfi said. He spends time “hearing patient stories, acknowledging how patients are hurt, and feeling frustrated myself. I realize how there is so much I – and any one person – can’t know.”

Having a team of doctors work together at the consultative clinic helps a lot, he said. They can discuss cases together, forming a kind of “collective intelligence.”

Patient options

Stanford’s consultative clinic isn’t the only option for patients who are struggling to get a correct diagnosis. Depending on their needs, patients can seek help from 3 different Stanford Health Care programs:

  • Stanford Medicine Online Second Opinion, an online service. Patients who have seen doctors outside Stanford can send their medical records and supporting information. Their cases are sent to the appropriate Stanford specialist, who reviews the information and responds with a written second opinion.
    When should a patient seek a second opinion?
    • If it’s a serious illness.
    • If it’s a complex illness with multiple symptoms.
    • If it’s a rare or uncertain diagnosis.

         A patient can be anywhere in the world and get a second opinion from Stanford Health Care, Dr. Geng said.         “This is all digital.”

  • Stanford Consultative Medicine Clinic. “This is really about in-person, in-depth” evaluation, Dr. Geng said.
    This can require multiple visits. Doctors can get advanced lab testing, specialist review, genetic consultations, and other resources. They also run extensive online searches for relevant information and use artificial intelligence programs to dig up clues.
  • Stanford Center for Undiagnosed Diseases. This program can offer help to patients who have exhausted most other options for getting a diagnosis. This center is part of a nationwide network of top medical centers that pool information on unsolved illnesses.

For more information:

Justin Lotfi, MD

Linda Geng, MD, PhD

Stanford Consultative Medicine Clinic

Stanford Medicine Online Second Opinion

Stanford Center for Undiagnosed Diseases

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