We are still discovering new diseases

Center for Undetected and Rare Diseases: Last Hope Marburg

The University Clinic Gießen-Marburg is the point of contact for patients who have already left a lot of traces in the health system - and for whom doctors rarely find answers.

Prof. Dr. med. Jürgen Schäfer, Head of the Center for Undetected and Rare Diseases, prepares the flood of files for a sleepless night. Photos: Jan Haas / picture alliance for Deutsches Ärzteblatt

On the table in front of Dr. med. Yulia Sharkova is lying in a bulging green folder. While the doctor speaks, she keeps leafing through the thick pile of paper. In just a few minutes, she gives her colleagues who are present the quintessence of what is in front of her on almost 100 pages: framework data on the patient, key facts of the medical history, central symptoms, previous diagnostics. And then the thought ping-pong starts in the conference room on level +2 of the interior department. "Can that be lupus?", "Has tuberculosis been excluded?", "Is there any joint pain noted?" Internist Sharkova is questioned in a friendly manner. She can parry some of the objections thanks to her knowledge of the files, others she gratefully accepts. Change. Lateral thinking. Brooding together. Weighing up. That is the purpose of this open brainstorming session. While Sharkova lets what he hears rattle through in his head, colleague Dr. med. Tobias Müller enters the relevant facts in the digital data record, visible to everyone on the wall thanks to a laptop and projector. After a good quarter of an hour everything is said about case 4223, the next file of the day changes - and the thought-ping-pong starts all over again.

Medical detective work

This scenario is repeated every Tuesday from 2 p.m. to 3:30 p.m. Then the 15-person team from the Center for Unrecognized and Rare Diseases of the University Hospital Gießen-Marburg (ZusE) will meet at the horseshoe table in the bright room for discussion. Doctors from various fields are present: almost all areas of specialization in internal medicine, general medicine, laboratory medicine, neurology, psychosomatics, radiology, and pharmacology. Even a veterinarian and parasitologist sometimes comes along. The experts from the center's own laboratory are also there. They are specialists in discovering traces that have gone undetected in a number of previous laboratory tests. In addition: freelancers - for example a resident internist in Marburg - who volunteer their time here. What the collective does is “not rocket science”, as Prof. Dr. med. Jürgen Schäfer, head of the center founded in 2013, emphasizes. It is simply meticulous medical detective work, for which the luxury commodity par excellence in today's medicine is available: time. The most complex, urgent and bizarre cases that land on the table with the Hessians are discussed. It is precisely those patient stories that a resident does not want any more than the devil wishes for holy water.

Doctor's letters, findings, laboratory reports, personal notes from patients: before Marburg comes into play, those affected often have to go through up to 40 stations in the health system. Sometimes the folders are so thick that the stapler can barely hold the paper. The silent paper files tell the medical histories of people who have been looking for one thing for years, sometimes decades: help. You suffer from diffuse symptoms: paralysis, permanent fever, inexplicable tooth loss, chronic fatigue, unexplained joint pain. And so on and so on. Their story has one thing in common: a coherent diagnosis is missing. "These patients have had a real odyssey across our health system," says cardiologist Schäfer, who shows great compassion for the patients. "The suffering of those affected is enormous".

The workload that the Marburg troops have to work through is also enormous because of the many patients who have not been diagnosed by the health system. More than 6,000 patient files have fluttered onto the Hessians' desks since the center was founded. They are stored in an office room on the first floor of the hospital, neatly filed and numbered in loose-leaf binders and folders. Two shelves are already full of it up to the top. Years have passed before a file can be pulled from the shelf for editing.

Prioritize tough

In order to be able to master the mountain of files at all, the ZusE team has developed a strict approach. It is - by necessity - selected and prioritized in a tough way. The Marburg refer all cases involving children to other centers. They do not yet have any expertise here. Patients who have been diagnosed and who contact the center are also rejected. What is then left is divided into two groups: doctor referrals and individual patient contacts.

Hospital referrals are treated primarily, first and foremost those from in-house. This is followed by the patient cases in which colleagues from external institutions or residents turn to the Marburg team with a request for help. In last place come patients who are proactive. The center only accepts patients in exceptional cases. Schäfer says the flood of files is giving him sleepless nights. It torments him that the cry for help from so many patients remains unheard of. Schäfer and his colleagues don't even manage 1,000 inquiries a year - although he and three other team members now mainly work as medical detectives. "I could have ten more people, we wouldn't make it," says Schäfer. It sometimes takes several days for a doctor to rummage through one of the thick files and conduct cross-research. Then the case is discussed - in a large or small circle. This is followed by the writing of a letter of up to four pages for the doctor treating the person concerned. In it: key facts for the search for traces of the Marburgers and recommendations for further diagnostics.

For laboratory manager Dr. Muhidin Soufi, the good and close cooperation with the clinicians is an important component of successful work.

In particularly tricky cases, ZusE's own laboratory is even used. It's in the basement of the hospital - a blessing as everyone on the team is. The short distances are one of the big pluses of Marburg. "Laboratory employees and clinicians are in close, direct communication with one another," says laboratory manager Dr. Muhidin Soufi, human biologist. Schäfer drop by himself every day. And it's not just him who can be seen: Sometimes patients even turned up in the laboratory, longingly waiting for results or directly delivering their samples themselves. Doing research for the ivory tower? Not in Marburg.

Problem flat rate per case

The laboratory is equipped with the most modern equipment. Urine, blood and stool samples as well as complex genetic tests are processed here. In addition to access to state-of-the-art equipment, laboratory employees and their medical colleagues benefit from the magic word time. "It can sometimes take months before a clear result is established," says Soufi. This time is also taken in the laboratory. The high effort is worthwhile, nobody doubts it here: "When you find out that a patient is fine again after years of suffering because we have found something, then that is the greatest joy."

The result of the meticulous detective work in Marburg is often exciting: vomiting over months, caused by parasites, brought in by a dog. Life-threatening cobalt poisoning from a defective metal femoral head prosthesis. A tropical worm that has taken root in the body - invaded by a rare fish in the home aquarium. In addition: wandering kidney, sepsis through tooth roots, Sheehan's syndrome. In Marburg there is nothing that does not exist.

The center does not work profitably - that should be clear to everyone. Schäfer doesn't really want to talk about money. However, he does not deny that the annual costs for the ZusE are in the higher six-digit range. The owner of the center, the Rhön-Klinikum AG, accepts that the center is not economical.

Elsewhere, Schäfer is not at a loss for clear words: “The flat rate system is a huge problem for all houses with maximum care. In the past, the patients stayed until we knew what was going on. That's how I grew up in medicine. Today doctors have to make a diagnosis after a short period of time. ”This repeatedly leads to incorrect assessments - or the clinical picture simply remains undetected. The DRG system is not made for rare diseases.

Thought ping pong every Tuesday in the conference room of the Center for Rare Diseases.

In Schäfer's mind, it is crystal clear how to deal with patient cases. He has been calling for "carer wards" at Germany's university hospitals for years. It has to be part of the care mandate to take care of the tricky patient cases and not depend on the “goodwill of a carrier”, he says. After all: the attention is growing. There are now 27 centers for rare diseases in Germany. They are supposed to be the point of contact for the approximately four million Germans who suffer from one of the 7,000 to 8,000 rare diseases. However, funding remains a challenge.

Marburg not only takes care of the rare, but also of the unrecognized diseases. Schäfer describes the restriction of centers to the rare as a "wasted opportunity". He says, “Patients with unrecognized diseases have just as difficult times. The resources and diagnostic processes required to track down the cause of the complaints are basically no different. ”The number of cases of undetected diseases in Marburg is greater than that of the rare ones.

That's how easy it can be

Schäfer can tell plenty of examples of how easy it is sometimes to end patient suffering. Like this one: A patient suffered from severe, inexplicable depression for almost five years. Schäfer stumbled upon a statement from the husband that the woman was doing well during the pregnancy and that an IUD was used as contraception afterwards. “The doorbell rang,” says Schäfer, who is now naturally sensitized to such statements. The depression was a side effect of the hormonal IUD. One that was even described in the warning notices. It can be that simple sometimes.

System error knowledge deficit

The Marburger does not want to understand this as a reproach to his colleagues in outpatient care, rather he speaks of a "system error". "The attending gynecologist knows nothing about the depression, the attending psychologist knows nothing about the spiral." The lack of networking and knowledge transfer, along with the problem of remuneration, is a major part of the dilemma. Schäfer is clear: The “actually excellent German health system” is not only leaving the patients in the lurch, but also the resident colleagues. In the current care structure, it is very difficult for them to devote themselves to patients who fall out of the norm. No resident could care for a patient for hours during his consultation.

They have great hopes in Marburg in new digital opportunities. The team makes use of IT wherever it can. When looking for the right diagnosis, doctors are increasingly turning to medical databases and diagnostic tools. “The human eye cannot do what technology can do,” says Müller. He is a doctor and computer scientist at the same time - a stroke of luck for Marburg. There will be even more technology in the future: the ZusE is working with the IT giant IBM. IBM's supercomputer Watson is now helping to solve the puzzling patient stories. The good reputation of the Marburg center made the prestigious cooperation possible.

How it works? The patients fill out a digital questionnaire drawn up by the Marburg medical team. From this, IBM Watson extracts the information relevant to the doctors and creates a list of hypotheses. From these, the doctors can derive their diagnosis much faster than before. There is no need to go through the files manually. The pilot phase with Watson has been successfully completed - and Schäfer breathes a sigh of relief. “We are up to our necks. Without technical support, we would never have a chance to work through the mountains of files. Now I hope that we will see some land again from the middle of this year. ”Perhaps Watson will then also solve the cases in which the Marburgers have not made any progress so far: Despite all their efforts, medical detectives are currently only finding half to two thirds of all Cases a solution.

Until the supercomputers eventually start working across the board, Schäfer appeals to his medical colleagues: listen. Think outside the box. Do not automatically put the psychosomatic stamp on the patient as an "embarrassment diagnosis" that can be found in almost every medical record. Simple: Don't leave the patient alone. Schäfer says: Above all, he learns one thing over and over again in his work: humility. "We know a lot, but we still don't know everything by a long way."

Nora Schmitt-Sausen