Mystery Illnesses | Part 2
The Great Imitators
When Infection Doesn’t Look Like Infection
Aaron Hartman MD
March 11, 2026
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When Symptoms Won’t Stay In Their Lane…
For many patients with chronic illness, the story rarely begins with a single clear diagnosis.
Symptoms move.
Fatigue appears first. Then digestive issues. Joint pain follows. Brain fog arrives months later. Sometimes the symptoms fade for a while, only to return somewhere else in the body.
Each new symptom tends to send the patient to a different specialist. Neurology. Rheumatology. Gastroenterology. Endocrinology.
Each specialist evaluates their own system carefully. Tests are ordered. Imaging is performed. Panels come back normal … or close enough to normal that nothing clearly explains what the patient is experiencing.
From the patient’s perspective…
The experience is disorienting. The illness refuses to stay inside a single category.
From the clinician’s perspective…
The case begins to look increasingly complex.
And eventually a different question begins to emerge:
What if something more systemic is driving all of this?
The Reluctant Discovery
One of the surprising realities of complex chronic illness is that clinicians often arrive at certain explanations slowly.
Not because we’re uninterested in helping patients. Because we’re human, and some possibilities initially feel too complicated, too controversial, or too poorly understood to pursue.
Dr. Jenski describes this dynamic in his own clinical work.
“There was a point where I was like, I’m not going to deal with mold. It’s too complicated. And then it’s like, I can’t help my patients unless I figure it out. And then the same thing happened with Lyme. I was going to ignore Lyme…then you realize: I guess I have to learn how to deal with tick-borne illnesses as well. And then you start wondering: is this everywhere?”
For the best doctors, what understandably begins as reluctance eventually gives way to curiosity.
When enough patients present with similar patterns—unexplained fatigue, neurological symptoms, inflammatory complaints—good clinicians eventually start asking whether something common might be hiding underneath those cases.
The Great Imitators
As I mentioned to Dr. Jenski, we’ve actually been here before.
Historically, certain diseases earned the nickname “the great imitators.” Conditions like syphilis and tuberculosis could mimic a remarkable range of other illnesses. Patients might present with neurological symptoms, joint pain, psychiatric changes, or inflammatory problems in different parts of the body. The underlying disease stayed the same, but the presentation kept changing.
And before those patterns were understood, physicians also treated the symptoms in isolation. Only later did it become clear that a single underlying cause could move through multiple systems and appear to be something different each time.
In other words, history offers us another reason to be cautious with so-called “mystery illnesses.” What appears confusing at first may simply be another example of an illness that unfolds across systems, revealing itself slowly.
Once clinicians begin thinking in those terms, the investigation changes. Instead of asking only which symptoms are present, they begin asking a different question entirely:
Where did the story begin?
Following the Trigger
Dr. Jenski explains that identifying the trigger event can often be more informative than analyzing symptoms in isolation.
“Finding out when someone’s trigger was … was it a hike with a tick bite, or was it moving into a new house with new carpet? Or moving into an old house that you renovated? … Because treating the mast cells can help calm symptoms down, but if you don’t identify what started the whole cascade, you’re going to miss the bigger picture.”
In some cases the trigger is obvious: A tick bite. Getting shingles. COVID.
In other cases the trigger is environmental: changes in living conditions, building exposures, or other stressors that gradually affect the body’s systems.
Whatever the origin, the timeline of events often reveals connections that symptom checklists alone cannot.
When the Immune System Is Stressed
As clinicians follow these timelines, another pattern sometimes emerges.
The immune system itself may have been under prolonged strain long before the illness became obvious.
Dr. Jenski describes how this kind of sustained immune stress can eventually reveal infections that were previously dormant or controlled.
“Autoimmunity is par for the course in these patients. The innate immune system is working overdrive all the time and it then activates the adaptive. Eventually it can deplete itself. … And now you see that drop in white count, that drop in that natural killer cell count, and now maybe indolent infections get unleashed.
And suddenly the presentation becomes Lyme or Epstein-Barr reactivation. But when you track it back, it was mold that did it. It was the house. It was the environment stressing the immune system long enough for those other things to show up.”
From this perspective, infections may not always be the first domino to fall. Sometimes they appear later in the process. They emerge only after the immune system has been pushed beyond its ability to keep certain pathogens in check.
This can make the illness difficult to interpret. Specialists may see only the final presentation, not the sequence of events that led there.
The Logic of Dormancy
Another complicating factor is that infections don’t always behave in simple, binary ways. They’re not always either fully present or fully gone.
Instead, the immune system may contain certain pathogens for long periods of time, keeping them in a “controlled” state, or dormancy.
Dr. Jenski explains this dynamic when discussing autoimmune illness and infection.
“You can’t cure autoimmunity. Once your body sees self as foreign it will continue to make those antibodies until you teach the immune system how to go into remission. That’s what we attempt to do by removing triggers—by healing infections, by reversing leaky gut—and then those chronic infections can go dormant.
If you understand how you got there and live accordingly, you can keep that system in remission for years. But you can flare, and that’s something patients need to understand.”
This perspective helps explain why some patients experience cycles of improvement and relapse. When the immune system regains stability, symptoms may recede. But when new stressors emerge (illness, environmental exposures, major life stress) the balance can shift again.
A Pattern Begins to Appear
Viewed this way, infections aren’t always isolated events.
They’re often part of a larger biological pattern involving immune stress, environmental exposures, and the body’s ongoing attempts to maintain balance.
That doesn’t mean infection explains every complex illness. Nor does it mean every patient with chronic symptoms is dealing with a hidden pathogen. But for clinicians who treat these patients regularly, the pattern appears often enough to raise an important possibility:
Some of the illnesses that appear mysterious at first may not be mysteries at all. They may simply be conditions that unfold across multiple systems, revealing their causes slowly over time.
And in many of those stories, infection turns out to be one piece of a much larger puzzle.
The remaining articles in this series will explore several of those pieces: environmental illness, mast cell activation, and nervous system dysfunction.
When understood together, the patterns finally begin to surface.
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