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Q&A: Dr. Leon Fine Talks About Cedars-Sinai's Center for the Undiagnosed Patient

Analysis  |  By Eric Wicklund  
   June 24, 2022

The Center for the Undiagnosed Patient at Cedars-Sinai takes on healthcare's most perplexing cases, and has helped several patients get their lives back.

Healthcare is complex, and not without its mysteries. Sometimes healthcare providers have to be detectives to figure out a diagnosis and treatment.

At Cedars-Sinai, a team of clinicians from a wide range of specialties gathers every week to tackle one particular mystery. They're part of the Center for the Undiagnosed Patient, a specialty clinic launched in 2017 to help patients whose conditions defy identification.

HeralthLeaders recently sat down (virtually) with Leon Fine, MD, a professor of medicine and biomedical sciences at Cedars-Sinai and medical director of the center, to talk about the center's mission. This interview has been edited for length and clarity.

Q. How was the Center for the Undiagnosed Patient launched?

Leon Fine: There was a sense that existing medical diagnostic systems, even in academic medicine, were failing to address a segment of the patient population that was left undiagnosed, frustrated [and] uncertain. There was a substantial level of underlying anxiety [with patients] about their condition due to its chronicity and the inability of the medical community to solve the problem.

So we set up something, and were careful about naming it. We called it the Center for the Undiagnosed Patient, singular, rather than Center for Undiagnosed Patients, plural. There was something quite specific in deciding that, in the sense that each prospective patient would have to have a good sense that we were really interested in them personally, and that we were about to address their problem.

Dr. Leon Fine, medical director of the Center for the Undiagnosed Patient at Cedars-Sinai. Photo courtesy Cedars-Sinai.

Who are these patients? Many have what would be broadly called rare diseases, very infrequent diseases that most doctors haven't encountered. Another group of patients has more traditional diseases: heart failure, lupus, atherosclerotic heart disease, etc., but present in atypical ways. There are also patients with multiple diseases involving multiple organs, called comorbidities. They may have had a presenting symptom that is a single thing, such as chest pain or shortness of breath, but behind that there is a series of diseases which actually could have contributed and have to be taken into consideration.

These are all long-term patients. Many have seen multiple specialists; it's not unusual for patients to have seen more than a dozen doctors, sometimes many more, each one bringing to the table their specific area of knowledge [but not] seeing the whole patient.

The question was, if we were to set up a new entity called the Center for the Undiagnosed Patient, why would any patient want to come and see us? Because we would just be the 12th doctor. Why would they have any more confidence in coming to see us, because they'd already seen so many doctors. That to me was a very central question to be answered.

The answer came with a notion that the only way we could do it was to bring a so-called team approach to the patient. Number one, the patient would access our center, and it was absolutely essential in this age of online medicine that the patient be seen personally. Number two, the leadership team at the center was constituted of generalists and not specialists.

Every patient who was presented would first be considered by a team of at least a half a dozen doctors [who ask] 'Can we possibly help this patient and could the weight of opinion of six talented and capable people have more impact on the patient's belief than just seeing yet another doctor?'

Q. How are the patients screened?

Fine: A patient can access the center online or by picking up the phone and talking to someone. We require that the patient's background information be made available to us. Nowadays that's much easier, because a lot of this information is in the electronic medical record, but in many cases it's not. And in many, many cases, the narrative of what happened to the patient and the timeline was missing. You get soundbites, as it were, of information, and getting the story becomes that much more difficult.

We require a referral from a doctor, because it's much more convincing if the doctor is the person who's providing the information, but we do open the door to patients accessing us directly. The reason is we are not a treating center. We are a diagnostic center. So if we are able to come up with some useful answers, we want to feed them back to someone who can then take that patient by the hand and lead the patient through a whole series of therapeutic options and therapeutic trials.

We have a very talented nurse practitioner (Jennifer Elad, DNP, ACNP) who spends hours, literally, going through the patient's records. There are often hundreds of pages of records that have to be screened. We've even had a patient with a thousand pages of records. It requires many hours to sift through these records, and it's even more difficult to put them into some sort of context, like a three- or four-page summary, which can then be presented to our leadership team.

Along with that summary, [Elad] has also spoken to the patient. A presentation is then made to the group, which consists now of three lead internists, a lead pediatrician, myself, and the associate director, another generalist who has a specialty in pulmonary medicine.

The first question to be asked is, do we think we can be helpful by taking on this patient? If the sense is not really, we don't waste the time of the patient or our own time in pretending or hoping that we can do something. There's a small number of applicants who we tell, "We are terribly sorry, but we do not think we can be help with you."

I should point out that in order to cover the cost of the hour spent going through the record, we do require that the patient pays $500. That hardly covers, but certainly contributes to the patient's commitment to us as it were.

If we decide that this is a patient that we want to take on, we then [ask] how are we going to approach this case? Which of our lead internists will take the case?. We also have approximately 25 specialist consultants. And we have a psychiatrist on our team. [Similar] centers that have sprung up around the country have chosen to deflect the psychiatric case from their interest, because they don't feel that this is part of what they're all about. We have recognized that there's no patient we have seen that doesn't have a psychological overlay to the problem. We can then refer the patient to a psychiatrist if we feel that was a dominant component of the problem.

We assign the case to one of our lead internists or pediatrician, who then sees the patient face-to-face. With COVID, we had a number of patients that we couldn't do the face-to-face, but we were not prepared to compromise on that. We must see the patient, because medicine is about taking a very comprehensive history. Looking at a patient and talking to a patient gives you an immense amount of information that you simply could not get online.

We try not to duplicate some of the specialists the patient has already seen. If someone has an issue relating to rheumatology, they've already seen three rheumatologists, each with a different twist. We're very careful about that, because this is not going to really enhance anything.

Once the patient has been seen by a selected group of specialists, it goes back to the original generalist to summarize the case, which then is represented to the group, and that closes the loop.

We've been going now for a few years. The number of cases we see, because of the time commitment, is not large enough to do any statistical analysis. But off the top of my head, I can roughly say that we make a new diagnosis with a name in about a third of our cases.

Another third of patients gain substantially from the encounter because we're able to confidently tell them that they don't have all the awful diseases they thought they had. You do not have cancer. You do not have a heart that is failing. You do not have blood vessels that are not working. Most patients believe us, but of course some still don't believe us, and we know when they leave us, they'll go to the 13th doctor. Nothing we can do there.

The other third of patients, we simply don't know. We've gone the whole route, and we honestly say, 'We simply cannot solve your problem.' We do say to them, 'We'd be very happy to see you again, let's say in six months' time, to see if something has evolved, and we'll be able to see whether we can add anything.'

Q. How long does it take for you to come to a conclusion on a patient, whether it's a diagnosis or you can't diagnose?

Fine: In most cases, we make an opening for this person within two weeks. The initial evaluation takes maybe a week or two. It takes us another week or two to get an appointment for the person to see the generalists, and we try and make sure that the consultants are available around that time.

I'd say that it probably takes a couple of months, but there are some patients who take much longer. Patients who come from afar, from out of state. It does not happen in our center the way it does in some institutions where the patient comes in, and two days later they get a printout. We cannot do it that way, and we don't pretend to do it that way. We are being very thorough.

Q. What about the patients that you can't do anything for? What's the next step for a patient like that?

Fine: That's one of the most frustrating and disappointing parts of diagnostic medicine. We can see they are flailing around looking for a doctor who can help them, so the referring physician is a very important element in the whole cycle.

If the patient says, 'Well, can you make a suggestion?,' we try not to make suggestions about doctors in our own institution, because that could be self-serving. Our function is to help with the diagnosis We can confidently say that we don't think the patient has this, that, or the other. It's just possible that something will emerge later, where we can be of help.

Q. You mentioned about a third of the patients you are able to find a diagnosis for. How does it feel to be able to help someone who's been looking for help for so long?

Fine: That's the reason we do it. There was a woman in her 70s who suddenly started getting frequent episodes of abdominal pain. Every time it occurred it was slightly different, in a different point in the abdomen, for a different [length] of time, and it started getting worse and worse. She goes on pain killers. Some work sometimes, some don't. This went on for a number of years.

We took the history, and we presented to the group all the CT scans that had been done with the abdomen that were negative. There was nothing there that we could see. Then one of our group said, 'Has the patient ever had a CT scan of the abdomen during an episode of pain?' We looked through the record, and the answer was no. And he told the patient, 'When you next have an episode, we would like to see you and do a CT scan on you while that happens.' The patient had an episode that lasted a day or two, came to see us, we did the CT scan on the abdomen, and guess what? We found that she had a partial bowel obstruction in the abdomen.

Our surgeon went in, found that the piece of bowel was adherent to this little opening, freed it under laparoscopy, and closed the little opening through which the bowel was protruding. The patient has never had pain since then.

That was remarkable. And all that we did was to ask a single question. Had we not done that we wouldn't have seen the distension of the bowel due to obstruction, we couldn't have made the diagnosis. That was just an interesting case. I'm not suggesting that all of our cases are like that, but that it certainly illustrates how a single insight can be a key insight in some cases.

Q Are diagnoses confusing or complex, or are they unusual?

Fine: They tend to not be unusual. They tend to be diseases which present in a complex way and which we simplify because of our breadth of expertise. We say, 'Let's not focus on that particular symptom that would seem to be peripheral.' If you see a problem list for patients, there are at least a dozen things on that problem list, and each one has value. We try to prioritize what we think the most important or the second most important is.

These are [usually] relatively common diseases. But there are also a number of new ones. Every time you open the New England Journal of Medicine, there's a new genetic disease that has been described. So we do genotyping on our patients. We analyze the genome when we think there may be a genetic explanation. We get the report, and anything that looks like it may be a mutation or an unusual polymorphism of the gene, we look in. Data analysts look at the record to see whether there are any other cases which are linked to that particular abnormality.

We have had cases where we discovered something which didn't make any sense, and we went out into the international community and said, 'Has anybody else seen a patient like this' Sure enough, some have, and eventually there is a whole network of doctors who've seen one case.

You could say, if there's nothing you could do for the patient, what good is it for the patient? The answer is, patients do feel comforted that a name can be applied to their condition, that other people have it, and maybe someone now will start looking for a solution to the problem. That's where publishing in an academic setting comes in. The group publishes together, the disease gets a name and an understanding, and that often opens the door to someone saying let's try this. It works for them.

Q: the resources you have at your disposal, you pretty much can go anywhere for help on these types of cases.

Fine: We do have a broad range of consultants. Cedars-Sinai is one the leading academic medical centers in the country. We're proud of that. And I must say that the reputational value of the Center for the Undiagnosed Patient is appreciated by its leadership.

Think about this: The practice of medicine today is very much dependent on income generation. What doctor can spend a few hours with a patient and legitimately bill that patient for the time they spent? Are we generating large amounts of money for the institution? Absolutely not. Is the institution proud of this entity and does it believe that it is something that enhances their reputation in a very positive way? Absolutely yes.

There are two dimensions to this. One is the training of younger doctors, which we haven't yet done but we want to do. We would like to bring in medical residents in training, to listen in and participate and see how we analyze things.

We are also now starting to build a strong research arm at the center. We're very lucky to have some very talented people who study the biochemical components of diseases. So we will get a patient in and we will take some blood samples and urine samples and various things, send them to these biochemists, and they analyze the genome, they analyze the patient's lipids, they analyze the patient's metabolic products. They see a pattern for the patient which can be looked at side by side with the patient's physical and clinical presentation.

Now, you can't make much of one or two cases, but when you have 20 or 30 cases of someone presenting, let's say, with an irritable bladder, you might see patterns of expression of various genes and various proteins that are different amongst that group of patients. Some present this way, some present that way. And then you say, maybe our description of this as cystitis is oversimplistic. These patients seem to have three different diseases, all presenting in the same way, but if that's the case biochemically, then clearly the diagnostic and treatment should go along with that.

Q: What does it feel like to finally solve a riddle, to be able to give a patient the answer to a question that may have evaded everybody else, and they finally got an answer that they've been so long waiting for?

Fine: We do have a sense of triumph. My God, look at it, something so simple, and we solved it. We are known as a group that tries to tackle medical mysteries. I don't think that sense of triumph happens as often as you think it might. Sometimes the contribution is only partial, not complete. And I can remember where we actually made the specific diagnosis and it was clear that it was a rare diagnosis and we were very happy that we made it, but the patient's symptoms didn't get better as a result. We said, 'Who knows, maybe we haven't solved it yet.' So we're very cautious and I hope modest about not overplaying what we've achieved.

“We do have a sense of triumph. My God, look at it, something so simple, and we solved it. We are known as a group that tries to tackle medical mysteries. ”

Eric Wicklund is the Innovation and Technology Editor for HealthLeaders.


KEY TAKEAWAYS

The Center for the Undiagnosed Patient at Cedars-Sinai helps patients who have debilitating health conditions that haven't been diagnosed.

These patients may have previously undefined diseases, they may have chronic conditions that present differently, or they may have multiple chronic health concerns that haven't been properly treated.

The center takes a team approach to tackling these mysteries, and succeeds roughly 30% of the time in making a diagnosis. In other cases they help the patient better understand his or her health concern by ruling out certain diseases.


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