Mystery Illnesses
The Myth of “Mystery Illness”
Aaron Hartman MD
March 4, 2026
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There is a question that shows up again and again in exam rooms and inboxes:
Why can’t anyone figure out what’s wrong with me?
By the time someone asks that question, they’ve usually seen more than one specialist. Their thyroid panel is “within range.” Their symptoms move (fatigue one month, gut issues the next, joint pain after that). The file thickens. The certainty thins.
And eventually, the phrase appears: “Mystery illness.”
But when Dr. Christian Jenski hears the phrase, he doesn’t accept the premise.
“I think it’s because we don’t really see them as mysteries. To me, the term ‘mystery illness’ is a bit of a misnomer. It’s common in our practice … it’s ‘mysterious’ elsewhere. And it’s because there’s not a definitive way to diagnose it … or there is a constellation of symptoms that overlaps with another constellation. … So when there’s not clear black and white clarity, it’s often befuddling to conventional medicine.
If you have to do a therapeutic or diagnostic trial of intervention. … If you have to look at a constellation of symptoms combined with some screening tools combined with this lab and maybe this lab and then have a conversation with the patient. That’s NOT really where conventional medicine shines.
But it is kind of where we do.”
Dr. Jenski and I have been thinking a lot about these so called ‘mysteries.’
If something is common in one setting and mysterious in another, the illness itself may not be the unstable variable. It could be the framework.
When “I Don’t Know” Becomes the End of the Road
Patients rarely describe a single dramatic dismissal. What they describe is erosion: A normal scan. A normal panel. A referral. Another referral. A suggestion that stress might be the issue. Eventually, the subtle implication that nothing measurable means nothing meaningful.
Dr. Jenski describes a different posture:
“There has to be a degree of intellectual medical curiosity.
There has to be clinical acumen, there has to be the willingness to do something that is (safe, not harmful, something you’d be willing to do yourself) … but not necessarily the standard of care, not necessarily FDA approved. The whole goal is do SOMETHING. Don’t say ‘I don’t know,’ don’t say ‘I have no options for you.’
Just try to figure it out. I think that’s really why they wind up on our doorstep … they’re just kind of gaslit until they eventually find us.”
That word—gaslit—lands heavily.
It’s not an accusation against individual physicians. It is a description of what it feels like when symptoms persist but the system has no container for them. When the model requires black and white, anything gray starts to look imaginary.
The Specialty Between the Specialties
Because of all this, I’ve started answering a common question a bit differently.
What do you do?
It’s a question we all need an answer for (even doctors). Here’s what I tried out on Dr. Jenski:
You see your cardiologist for your heart. You see your GI doctor for your gut. You see your rheumatologist for your autoimmune issue. But who talks about the gut issue being related to the rheumatoid and the heart stuff? Who talks about the autoimmune disease in your arteries … called cardiovascular disease?
That led us to the analogy of interstitium (we are doctors after all).
In anatomy, the interstitium is the fluid-filled space between everything else: cell membranes, organs, muscles, whole systems. That’s us — Dr. Jenski and I — not another specialty you refer to. We’re the space between referrals.
Modern medicine is extraordinarily good at organs. It’s less comfortable with overlap.
Autoimmune disease becomes rheumatology. Gut dysfunction becomes gastroenterology. Cardiovascular risk becomes cardiology. Each domain advances. Each domain refines. But if inflammation, immune signaling, barrier function, and infection cross those boundaries, the patient becomes the only place the full picture exists.
The System Behind ‘Autoimmune’
What happens when a patient has rheumatoid … inflammatory bowel disease … hashimotos … celiac? All of these are systemic autoimmune illnesses. It’s not just your joints or thyroid.
In order to have an autoimmune disease, you have to have four things:
– Genetic predisposition
– Leaky gut
– Chronic infection
– A triggering event
So all of a sudden, we have three basic things we should look for in every, absolutely every autoimmune case. And yet, in most exam rooms, the joint is treated as THE problem … or the thyroid … or the colon. The immune system becomes a rheumatology issue. The gut becomes a gastroenterology issue. The infection (if anyone looks for it at all) belongs to someone else.
Systemic illness treated as isolated parts will eventually look confusing. Not because it’s unknowable. Because it’s being asked the wrong question.
The “Poster Child” of the Not-So-Mysterious
When our conversation turned (as it often does) to chronic inflammatory response syndrome (CIRS), Dr. Jenski pushes the argument further.
“It’s ubiquitous. It is the poster child of what we’re talking about, as far as ‘mysterious illnesses’ that aren’t as mysterious as you think. The complex, system-wide, symptom wide, biological disarray that ensues. It is immune dysregulation. It is inflammation. It is mitochondrial dysfunction.
It is all these things happening concurrently. And it’s set up by someone who has a genetic predisposition, an environmental exposure, and then a scale that tips. It’s the shortest way to say it.”
What appears random or ‘complex’ begins to look patterned when viewed at the level of systems instead of symptoms.
Immune dysregulation doesn’t stay politely confined to one organ. Mitochondrial dysfunction doesn’t announce itself with a single lab value. Environmental exposures do not always produce immediate disease. But layered together, they form a story.
Where the Mystery Actually Lives
If these illnesses are common in one practice and confounding in another, if patients circulate between experts yet never feel seen as whole, if inflammation crosses organs while specialties do not—then the mystery might not live in the biology at all.
It might live in the fragmentation.
This article doesn’t attempt to diagnose what is happening in any individual case. And it doesn’t outline treatment protocols or testing strategies. For now, however, I just want to ask the question of whether the word mystery belongs to the illness … or to the model used to interpret it.
For readers who recognize themselves in the gray zones between specialties, the next step is an investigation. The word journey is overused, but it’s still appropriate. One way to begin is by looking at the core systems that tend to link these stories together—gut function, stress physiology, and sleep architecture—and asking where imbalance might first appear.
Not as a diagnosis. As a starting point for clarity.
The mystery, it turns out, may be less about whether something is wrong—and more about whether we are looking in the right way.
Start the Investigation
If you recognize yourself in the gray zones between specialties, begin by looking at three foundational systems that often shape how people feel day to day: gut function, stress physiology, and sleep.