In today’s medical landscape, we have diagnostic labels for nearly everything—chronic fatigue, autoimmune disease, depression, IBS, anxiety, fibromyalgia. But when you peel back the layers, these labels often don’t explain why the symptoms began in the first place. That question—why is this happening?—is at the heart of what I now call IACIRS: Infection-Associated Chronic Inflammatory Response Syndrome.
What Is IACIRS?
IACIRS is a term I coined to describe a common yet poorly understood pattern I see in many patients with chronic, complex illness. It merges two established concepts:
- IACI (Infection-Associated Chronic Illness) refers to long-term, multi-system symptoms triggered by infectious exposures. These could be bacterial, viral, or fungal in origin. Think post-treatment Lyme disease, ME/CFS, Long COVID, or other post-infectious syndromes. The core idea is that the infection sets off a process that the body fails to resolve.
- CIRS (Chronic Inflammatory Response Syndrome), developed by Dr. Ritchie Shoemaker, originally described an illness driven by exposure to biotoxins—most commonly from mold but also from organisms like Borrelia or Babesia. CIRS is characterized by persistent, dysregulated inflammation, even after the original exposure has ended. Shoemaker also mapped out biomarker profiles (e.g., C4a, MMP-9, TGF-beta1) and genetic predispositions (HLA haplotypes) to help identify these patients.
But here’s what I see in practice: CIRS almost always includes microbial triggers. In fact, I rarely see a true mold-only case. Instead, mold often opens the door to deeper immune dysfunction—but it’s usually microbial biotoxins that keep the fire burning.
Primary Microbial Drivers
Not all infections are created equal. Some microbes seem to be especially good at hijacking the immune system, impairing detox pathways, and leaving the body in a state of chronic immune confusion. These are what I refer to as primary microbial drivers, and the list includes:
- Candida albicans and other fungal species
- Aspergillus (particularly in mold-exposed individuals)
- Borrelia burgdorferi (Lyme disease)
- Babesia and Bartonella (vector-borne coinfections)
- Possibly SARS-CoV-2 spike protein, which appears to act similarly to other biotoxins in some individuals
These microbes and toxins don’t just cause localized symptoms—they produce byproducts and biotoxins that throw the immune system off course. The result is a cascade of midstream immune dysfunction that translates downstream into a wide array of inflammatory and degenerative conditions.
Downstream Consequences of Immune Imbalance
What happens when the immune system gets stuck in overdrive—or worse, loses its ability to distinguish self from other? We begin to see a full-body breakdown of regulation, which can look like:
- Psychiatric symptoms like anxiety, panic, depression, OCD, and mood swings, often linked to elevated pro-inflammatory cytokines like IL-6 and TNF-alpha (Miller & Raison, 2016; Dantzer et al., 2008)
- Fatigue and brain fog from mitochondrial dysfunction and neuroinflammation (Naviaux, 2016)
- Metabolic disruption, including insulin resistance, leptin resistance, and thyroid dysfunction, as inflammation hijacks hormonal feedback loops (Hotamisligil, 2006)
- Allergies and chemical sensitivities, as the limbic system and mast cells remain in a hypersensitized state
- Autoimmune conditions, as persistent immune activation leads to tissue-targeting antibodies
- Immune suppression, which allows for the reactivation of latent viruses like EBV, HHV-6, and shingles—and for acute infections like sinusitis or UTIs to recur more frequently
This is the real story behind most chronic illness: it’s not just about the infection itself—it’s about what the infection does to your immune system.
Parainfectious vs. Post-Infectious: It’s Both
This leads to the million-dollar question: Are the symptoms of IACIRS due to an active infection still causing harm (parainfectious) or are they the result of immune dysfunction that continues after the infection is gone (post-infectious)?
In my experience, the answer is: both.
- Parainfectious illness refers to immune dysfunction that occurs while the pathogen is still present. The symptoms come from the direct damage of the organism as well as from the immune system’s response to it—neuroinflammation, cytokine storms, oxidative stress.
- Post-infectious illness describes a situation where the pathogen may be gone or largely suppressed, but the immune system remains in an inflammatory loop—continuing to generate symptoms long after the trigger has disappeared.
The truth is, most patients fall somewhere in the middle. This is why testing matters. Direct detection of microbial DNA, antigens, or biotoxins is critical. Antibody tests and immune markers alone can’t tell us whether the organism is still there or whether the immune system is just stuck.
And this is where clinical response becomes a diagnostic tool. If someone improves with antimicrobials, we may be dealing with ongoing infection. If symptoms improve with immune modulation then we’re likely dealing with a post-infectious response.
What’s the Path Forward?
You don’t have to choose between treating the infection and regulating the immune system. You often have to do both. In my practice, we follow a Root Cause Triad approach:
- Stress + Nervous System: calming the threat response, supporting sleep, and retraining the limbic system
- Toxins + Biotoxins: reducing exposure, binding and clearing mycotoxins, supporting detox pathways
- Microbes: identifying and targeting the primary microbial drivers while rebuilding immune tolerance
This layered, root cause method allows us to address IACIRS at every level—from the spark that started it to the fire that continues to burn.
IACIRS is not just another acronym—it’s a more accurate map of what’s actually going on in many patients who’ve been told they’re fine when they’re anything but. By recognizing both the infectious triggers and the immune aftermath, we can offer a path forward that’s rooted in biology—not blame.
And that’s the start of real healing.