Complex Disease Service seeks to solve mystery cases

Operating under the formal name of the Complex Disease Service, Dr. Zuhair Ballas and his colleagues aim to be the hotline for practitioners caring for puzzling patients. Serving in a consultative capacity, the service specializes in diagnosing patients who present with an usual combination of symptoms, who might have rare diseases, or who might have rare manifestations of a not-so-rare disease.

BallasZuhairDr. Ballas—a Professor of Medicine who calls himself a clinical immunologist—has worked on such cases independently for years, with beginnings in the 1980s. His first patient with a rare presentation of a usual reaction, he said, was a woman who was referred to him to rule out immunodeficiency because she had “recurrent toxic shock syndrome.” After an extensive review of her history, Dr. Ballas and his colleagues discovered that most of her symptoms occurred shortly after coming down with a cold, and taking over-the-counter cold medications. After much sleuthing, they found one common ingredient in all these cold medications: pseudoephedrine. They did an oral challenge with pseudoephedrine and were able to reproduce her symptoms. “That was early on in my youth, showing me the value of taking a detailed history, keeping an open mind, and realizing that common diseases can always present in uncommon manifestations,” said Dr. Ballas.

His reasoning for putting his skills and experience toward the Complex Disease Service are straightforward: “Some of them are easy to solve by just taking history, some of them are easy to solve because of a rare drug reaction. But the others are really very complicated, and so the reason I’m involved is because most diseases, I believe, have some kind of inflammatory or immunological element,” Dr. Ballas said. “My bias is that almost all inflammation—if it’s not infectious-related—is immune-mediated. Since we’re Immunology, we’re the perfect people to look at that.”

Even so, Dr. Ballas acknowledges the highly collaborative nature of the service. “Knowing there is no one person who can do this, obviously, the idea is to identify other experts in other departments and other disciplines that I can call upon. We have a lot of rich resources on our faculty and in the institution at large, so I can kind of tap into that expertise as well,” he said.

The organized service started gaining momentum in the last few years, after Dr. Ballas stepped down as Division Director of the Division of Immunology and has had more time to devote to the project. “You need somebody who has been around for a while, because I’ve seen the evolution of many diseases and therapies,” he said. “Usually, the primary practitioners are busy trying to fix the day-to-day abnormalities, so we figured they occasionally might need somebody who is not worried about the daily potassium or sodium level, for example, that can try to see the big picture.”

Dr. Ballas also mentors younger faculty and fellows on how to see the big picture. “We go through a thinking process. It really helps me to figure out what’s going on when I’m trying to explain to residents, fellows, and students as to why I’m thinking that. To me, I don’t think the service can be successful without our trainees. Absolutely, they keep me on my toes because I have to explain what I’m thinking. I have to convince them I’m not totally crazy,” he said, laughing.

Particularly helpful, he anticipates, is the dual-track fellowship pathway that allows fellows to get certification in both Rheumatology and Allergy/Immunology. “Because they are just different aspects of the immune system, it helps to have someone who can see both. The fellowship track has been another impetus for me to really get going on the service,” Dr. Ballas said, noting that Dr. Svjetlana Dolovcak, the first dual-certification graduate, will be joining as a faculty member in October.

Given their complicated nature, such clinical cases take time, however, and Dr. Ballas admits it often takes a day or two until he can come to a conjecture by employing the true scientific method. Even then, sometimes the diagnosis is uncertain and only confirmed by the patient’s response to the treatment. “Very rarely am I one-hundred percent sure of what’s going on. So, you have to keep an open mind. You develop a working diagnosis; if it doesn’t fit everything, you have to change your thinking. It helps to have a flood of ideas, but really more important is trying to do pattern recognition, come up with various possibilities, arrange priorities, and proceed to examine them one by one.”

Another challenge comes in negotiating treatment options. Most of the therapies are off-label, and therefore not often covered by insurance agencies, with whom Dr. Ballas spends a substantial amount of time talking. “But the most gratifying thing in the world is when you actually are right and the patient responds,” he said. “That’s the built-in reward. That’s what makes it all worthwhile.”

The Complex Disease Service mostly serves inpatients throughout the UIHC system, including in pediatrics. However, Dr. Ballas is hoping to expand the resource to outside-referring physicians once UIHC finishes the development of an online web portal. In light of these hopes, he notes that he’s going to need more hands on deck: “We’re open to anybody who is interested to come work.”

“People ask me, ‘when should I call you?’” Dr. Ballas said. “Well, if you see a patient and you say, ‘I have no idea what’s going on,’ that’s my phone number. [laughs] Because that’s what we like to do.”

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