“Maureen’s Story”: Diagnosing a Case of Mold Toxicity

Reprinted with the kind permission of ProHealth: 9/14/11

Dr. Neil Nathan, a specialist in treatment of complex medical illnesses, practices with Gordan Medical Associates near Mendocino, CA.

This information is excerpted with kind permission from his book On Hope and Healing for Those Who Have Fallen Through the Medical Cracks ©2010 Neil Nathan, MD, all rights reserved. These excerpts provide a general introduction to biotoxicity as one cause of unexplained illness; but a detailed discussion of biotoxicity’s many agents, symptoms, diagnosis, and treatment can be found in the book.

________________________________

Mold and Biotoxicity: There’s a Fungus Among Us

When it comes to understanding the different components of chronic illness, the concept of toxicity has received a good deal of recent attention. With the publication of Dr. Richie Shoemaker’s brilliant book, Mold Warriors, we now have some new tools to both evaluate and treat toxicity in its different forms.

It is fairly obvious that a microbe (bacteria, virus, fungus, parasite, or other infective agent) makes us sick by infecting us, and it is equally clear that treating these disease-causing microbes will make us better. But what is just becoming clear to us is that not only do these microbes make us sick by causing an infection, but some of these microbes can, in the process of being killed by our immune system, release toxins into our bodies that make us even sicker. Because these toxins are made by microbes, which are living biological systems, we call them biotoxins.

For most, the immune system recognizes these toxins and uses its defense mechanisms to destroy them. Unfortunately, about 25% of people are genetically unable to make an antibody to these toxins, and these patients may get progressively sicker as the toxins accumulate within their bodies.

What specific microbes are we talking about? The most common offenders are molds, especially the black mold Stachybotrys, but several other mold species such as Cladosporium and Fusarium can play a role in toxin formation. Harmful toxins can also be produced by certain viruses, especially those in the Herpes family, such as Epstein-Barr virus, which is the agent of mononucleosis; Cytomegalovirus; and Human Herpes Virus 6 (HHV-6), which is the agent of roseola infection.

A new and particularly toxic strain of HHV-6 has recently been discovered and has now been linked to chronic fatigue [ME/CFS] and fibromyalgia. Lyme bacteria can also produce these toxins, as can infections with the mycoplasmas, which are infective particles between viruses and bacteria in size. The atypical pneumonias (walking pneumonia) and Gulf War syndrome are examples of these infective agents.

Symptoms

So what are the symptoms of biotoxicity? Patients with this problem may experience a surprisingly wide range of symptoms related to many different organ systems. These symptoms sound a lot like fibromyalgia or chronic fatigue or depression. In children, it might appear like ADHD.

Diagnosis

The first order of business is to even consider the diagnosis.

Treatment

Several treatments for biotoxicity are currently in use. Dr. Shoemaker provides a combination of medications based on his testing. In its simplest form, this consists of using “Cholestyramine” the binding resin cholestyramine (trade name, Questran) or its cousin, Welchol.

Maureen’s Story

Maureen was a 28-year-old woman whom I saw for the first time in March of 2006. Her symptoms had begun three years previously, when she was working in a building with a very leaky roof.

She had also experienced several traumatic events at the same time, including a difficult divorce, which complicated both our evaluation and her perceptions about what may have triggered her illness.

In August of 2005, Maureen began to violently throw up on a daily basis, and this went on for months. She saw multiple physicians, including several gastrointestinal specialists, and underwent extensive testing, which showed no obvious cause for her symptoms.

She was diagnosed by various physicians as having bipolar disorder, irritable bowel syndrome, and hypochondriasis (meaning it was all in her head or psychosomatic).

Since her initial exposure to the mold, Maureen had gained 35 pounds and had developed sensitivities to all sorts of chemicals and perfumes (which we call multiple chemical sensitivities). This is actually a common event following untreated biotoxin exposure.

She continued to experience daily nausea and vomiting, regular headaches, and an inability to think clearly. She described her poor decision making in very simple terms: It’s like I’m inept.

She also reported blurred vision and bouts of chest tightness with wheezing.

When Maureen came to me, she had just lost her job of 14 years, at which she had been previously quite competent, and she was trying to live a normal life and raise her three children.

But she could hardly function.

Her energy level was very low, and she reported difficulty staying asleep and waking up unrefreshed each morning. She described joint pains in her neck, shoulder, and upper back, and she displayed the classical irritable bowel symptoms of gas bloating, distention and diarrhea alternating with constipation.

When I tested her vision with the Functional Acuity Contrast Test (FACT),a test of ability to detect contrasts that can indicate poor retinal function and has been closely related to biotoxicity], the results strongly suggested biotoxin exposure.

Her DHEA test was a little low, as was her progesterone level. I started her on natural progesterone cream, ¼ tsp daily, applied to her skin. I also put her on a small dose of DHEA.

And we started cholestyramine in the form of Questran Light, one scoop mixed with water three times daily, which is the best immediate treatment for mold toxicity.

When Maureen returned in April, just six weeks later, she reported that she was already 80% better. Her energy was markedly improved despite the fact that she was still living in her home, which had obvious mold exposure.

She had a new job, was successfully working again, but noticed that when she missed even a single day of her Questran, she became lethargic again.

She planned to remediate her home to clean up the mold, and she was thrilled that she had her life back; she was no longer plagued by nausea, vomiting, chest pain, and joint pain.

She was so impressed with her improvement in just a short period of time, that she bought a copy of Mold Warriors to give to her family physician, who had essentially told her she was a hypochondriac.

Her physician refused to even look at the book or to take Maureen’s story seriously.

It has been my experience that most of our mold-toxic patients have had a similar experience to Maureen’s. Their symptoms are usually misunderstood as representing psychological imbalances, particularly depression, but they do not respond well to antidepressant and anti-anxiety medications. That should be the tip-off that we need to look deeper for a cause of these symptoms.

Recalling that only 25% of patients are genetically unable to make the antibodies they need to these toxins, these patients may live in a home with others who have no symptoms or work in a mold-laden environment where others are not sick.

***

* Neil Nathan, MD, is perhaps best known to ProHealth readers for his recent trial of “A simplified Methylation Protocol for Treatment of ME/CFS and Fibromyalgia,” conducted in collaboration with Drs. Amy Yasko, Rich Van Konynenburg, and Jacob Teitelbaum.

Note: This information has not been reviewed by the FDA. It is general information and is not meant to take the place of a physician’s attention or to prevent, diagnose, treat or cure any illness, condition or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS

Abstract:

Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute-onset neuropsychiatric syndrome (PANS)/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. Increasing evidence suggests that immune dysregulation-including persistent inflammation, autoantibody production, and cellular immune dysfunction-may underlie these conditions.

This narrative review synthesizes peer-reviewed literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). Evidence supporting immune-targeted treatment strategies is strongest in subsets of patients with identifiable immunologic abnormalities. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification. TPE functions by removing circulating immune complexes, autoantibodies, and inflammatory mediators, and observational data suggest benefit in patients with demonstrable autoantibody burden. Further controlled studies incorporating immunologic phenotyping and early intervention are needed to define the therapeutic role of immune-directed interventions across these conditions.

Source: Kaplan G. Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS. Transfus Apher Sci. 2026 Jun 26;65(4):104482. doi: 10.1016/j.transci.2026.104482. Epub ahead of print. PMID: 42391726.  https://pubmed.ncbi.nlm.nih.gov/42391726/

Designing studies for post-treatment Lyme disease and other infection-associated chronic illnesses

Abstract:

Infection-associated chronic illnesses (IACIs) encompass a spectrum of poorly understood syndromes often marked by significant neurologic and multisystem symptoms following an infectious event. This review focuses on several diseases representative of the IACI spectrum. These are post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). Their clinical and biological complexity, combined with a lack of clear diagnostic criteria and objective available laboratory biomarkers, makes them difficult to distinguish from conditions with overlapping features.

This presents challenges for research studies, as well as diagnosis and clinical management. This diagnostic ambiguity, coupled with heterogeneous patient presentations, has led to challenges in research, including misclassification of study participants and inconsistent or irreproducible findings. Some PTLDS research exemplifies these issues, which also extend to other IACIs.

To advance the field, we highlight key methodological refinements and approaches for studying IACIs, including rigorous participant selection, standardized sample collection protocols, and the use of appropriate control groups, including those with microbiologic proof of the initial infection when known and technologically feasible. We also address broader influences on research quality, such as stigma, historical neglect, and the urgency to find treatments, which have contributed to the proliferation of poorly controlled studies and questionable practices. Drawing lessons from past challenges, we propose a path forward grounded in fit-for-purpose methodological rigour to improve scientific understanding and support evidence-based therapeutic development for IACIs.

Source: Arnaboldi PM, Becker J, Nath A, Coyle PK, Handel A, Sellati TJ, Gomes-Solecki M, Garcet S, Henderson MK, Mullins P, Cowan E, McCombie WR, Wellins AM, Allegretta M, Bergquist J, Schutzer SE. Designing studies for post-treatment Lyme disease and other infection-associated chronic illnesses. Brain. 2026 May 18:awag016. doi: 10.1093/brain/awag016. Epub ahead of print. PMID: 42148664. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awag016/8586348 (Full text)

Making Invisible Illnesses Visible: Recognizing and Responding to Infection Associated Chronic Conditions

Abstract:

The emergence of post-COVID conditions (PCC) has renewed attention to infection-associated chronic conditions and illnesses (IACCI), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Lyme disease-associated chronic symptoms. Millions of Americans are affected by these debilitating, misunderstood conditions, which share symptom profiles and pathophysiologic abnormalities. IACCI have received insufficient clinical attention and research investment.

We outline elements of a patient-centered approach to care, emphasizing validation of patients’ experiences, multidisciplinary management, and symptom-focused treatment. Opportunities to strengthen clinical practice include a new CMS code for chronic condition management, extended visits, and creation of welcoming care environments. Advances in PCC and ME/CFS research provide a foundation for exploring shared mechanisms and developing targeted therapies. Improved surveillance, harmonized research, and inclusive trial designs are needed to define disease burden and accelerate therapeutic progress. Coordinated action by clinicians, researchers, and policymakers can help address longstanding gaps and improve outcomes for all individuals with IACCI

Source: Iskander JK, Haridopolos S. Making Invisible Illnesses Visible: Recognizing and Responding to Infection Associated Chronic Conditions. Clin Infect Dis. 2026 Apr 9:ciag240. doi: 10.1093/cid/ciag240. Epub ahead of print. PMID: 41967005. https://pubmed.ncbi.nlm.nih.gov/41967005/

Long COVID as an Infection-Associated Chronic Condition: Implications

In-Brief:

A link between infection and chronic illness has been recognized, along with the complexities of interactions between pathogen, environment, host genetics, route of exposure, and timing of outcomes. The COVID-19 pandemic has brought this issue to the forefront and Long COVID is recognized to be an infection associated chronic condition. However, given the wide range of Long COVID presentations, the singular expression gives a false sense of simplicity. Long COVID is best considered as a group of infection associated conditions requiring developing research studies and treatment trials that address the inherent heterogeneity.
Source: Unger ER. Long COVID as an Infection-Associated Chronic Condition: Implications. Am J Health Promot. 2025 Jul;39(6):960-965. doi: 10.1177/08901171241308066b. Epub 2025 Jun 8. PMID: 40485158. https://journals.sagepub.com/doi/10.1177/08901171241308066b (Full text)

Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies

Abstract:

The intersection of psychiatry and medicine presents unique diagnostic and ethical challenges, particularly for conditions involving significant brain-body interactions, such as psychosomatic, somatopsychic, and complex systemic disorders. This article explores the historical and contemporary issues in diagnosing such conditions, emphasizing the fragmentation of medical and psychiatric knowledge, biases in clinical guidelines, and the mismanagement of complex illnesses.

Diagnostic errors often arise from insufficient integration between general medicine and psychiatry, compounded by the reliance on population-based guidelines that neglect individual patient needs. Misclassification of conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, and fibromyalgia as psychosomatic or psychogenic has led to stigmatization and delayed care. While these conditions are referenced as emblematic examples of misclassified and poorly understood disorders, the five clinical cases discussed in this article do not directly illustrate these diseases. Instead, they exemplify shared diagnostic and ethical dilemmas at the medicine–psychiatry interface, including uncertainty, fragmentation, and the risk of epistemic injustice.

The article critically examines terms like medically unexplained symptoms and functional disorders, highlighting their limitations and potential for misuse. Case examples underscore the consequences of diagnostic inaccuracies and the urgent need for improved approaches. Ethical considerations are also explored, emphasizing respecting patient experiences, promoting individualized care, and acknowledging the inherent uncertainties in medical diagnosis.

Advances in technologies such as brain imaging and molecular diagnostics offer hope for bridging the gap between psychiatry and medicine, enabling more accurate assessments and better patient outcomes. The article concludes by advocating comprehensive training at the medicine-psychiatry interface and a patient-centered approach that integrates clinical observation, research insights, and a nuanced understanding of mind-body dynamics.

Source: Monaco F, Vignapiano A, D’Angelo M, Raffone F, Di Stefano V, Boccia A, Longobardi A, Gruttola BD, Fornaro M, Corrivetti G, Martino I, Steardo L, Steardo L Jr. Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies. Front Psychiatry. 2025 Apr 22;16:1576179. doi: 10.3389/fpsyt.2025.1576179. PMID: 40330647; PMCID: PMC12053010. https://pmc.ncbi.nlm.nih.gov/articles/PMC12053010/ (Full text)

A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis – chronic fatigue syndrome

Abstract:

Background: Up to 20% of Lyme disease cases experience post-treatment Lyme disease syndrome (PTLDS). The biological basis for PTLDS is poorly understood and no evidence-based treatment has been identified. Genetic studies have the potential to elucidate PTLDS pathophysiology and identify treatment targets.

Methods: We used electronic health record data (EHR) and genetic data from a linked biorepository to conduct a genome-wide association study (GWAS) for PTLDS among patients from a Pennsylvania health system. We evaluated the validity of the GWAS results in two separate conditions that have hypothesized overlapping pathophysiology, fibromyalgia and myalgic encephalomyelitis – chronic fatigue syndrome (ME/CFS). GWAS analyses were performed using logistic regression in SUGEN, assuming an additive genetic model, and adjusting for age, sex, array, and the first 10 principal components calculated from whole genome genotyping to adjust for ancestry, and accounting for relatedness including all 1st degree relationships. The functional mapping and annotation analysis (FUMA) tool was used to explore top findings from our GWAS.

Results: Among the 161,875 eligible MyCode participants with genotyping, there were 3,585 who met the criteria for treated Lyme disease. A subset of 695 (19.4%) of these patients met the criteria for PTLDS and the remaining 2890 were classified as controls. We identified two PTLDS loci that reached the suggestive significance threshold (P < 5 × 10– 7), with lead variants rs77857587, near IRX1, and rs10833979, near GAS2. Our top index single nucleotide polymorphism (SNP), rs77857587, is in high linkage disequilibrium with a long-range protein quantitative locus SNP, rs111774530, for the MARC2 (Mitochondrial Amidoxime Reducing Component 2) protein. We identified 5,041 cases of fibromyalgia (150,599 controls) and 2,268 cases of ME/CFS (151,594 controls) among the MyCode participants. Neither of the two suggestively significant loci were associated with fibromyalgia or ME/CFS.

Conclusion: We identified two PTLDS loci that reached a suggestive significance threshold. Our top index SNP is associated with the MARC2 protein, a protein that has been linked to multiple immune checkpoints. Further study is needed in a larger population to evaluate whether there is genetic evidence of the role of immune response in the occurrence of PTLDS.

Source: Hirsch AG, Justice AE, Poissant A, Nordberg CM, Josyula NS, Aucott J, Rebman AW, Schwartz BS. A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis – chronic fatigue syndrome. BMC Infect Dis. 2025 Feb 24;25(1):265. doi: 10.1186/s12879-024-10238-x. PMID: 39994562; PMCID: PMC11853495. https://pmc.ncbi.nlm.nih.gov/articles/PMC11853495/ (Full text)

Fibroblast growth factor receptor inhibitors mitigate the neuropathogenicity of Borrelia burgdorferi or its remnants ex vivo

Abstract:

In previous studies, we showed that fibroblast growth factor receptors (FGFRs) contribute to inflammatory mediator output from primary rhesus microglia in response to live Borrelia burgdorferi. We also demonstrated that non-viable B. burgdorferi can be as pathogenic as live bacteria, if not more so, in both CNS and PNS tissues.

In this study we assessed the effect of live and non-viable B. burgdorferi in inducing FGFR expression from rhesus frontal cortex (FC) and dorsal root ganglion (DRG) tissue explants as well as their neuronal/astrocyte localization. Specific FGFR inhibitors were also tested for their ability to attenuate inflammatory output and apoptosis in response to either live or non-viable organisms.

Results show that in the FC, FGFR2 was the most abundantly expressed receptor followed by FGFR3 and FGFR1. Non-viable B. burgdorferi significantly upregulated FGFR3 more often than live bacteria, while the latter had a similar effect on FGFR1, although both treatments did affect the expressions of both receptors. FGFR2 was the least modulated in the FC tissues by the two treatments. FGFR1 expression was more prevalent in astrocytes while FGFR2 and FGFR3 showed higher expression in neurons.

In the DRG, all three receptor expressions were also seen, but could not be distinguished from medium controls by immunofluorescence. Inhibition of FGFR1 by PD166866 downregulated both inflammation and apoptosis in both FC and DRG in response to either treatment in all the tissues tested.

Inhibition of FGFR1-3 by AZD4547 similarly downregulated both inflammation and apoptosis in both FC and DRG in response to live bacteria, while with sonicated remnants, this effect was seen in one of the two FC tissues and 2 of 3 DRG tissues tested. CCL2 and IL-6 were the most downregulated mediators in the FC, while in the DRG it was CXCL8 and IL-6 in response to FGFR inhibition. Downregulation of at least two of these three mediators was observed to downregulate apoptosis levels in general.

We show here that FGFR inhibition can be an effective anti-inflammatory treatment in antibiotic refractive neurological Lyme. Alternatively, two biologics may be needed to effectively curb neuroinflammation and pathology in the CNS and PNS.

Source: Parthasarathy G. Fibroblast growth factor receptor inhibitors mitigate the neuropathogenicity of Borrelia burgdorferi or its remnants ex vivo. Front Immunol. 2024 Apr 4;15:1327416. doi: 10.3389/fimmu.2024.1327416. PMID: 38638441; PMCID: PMC11024320. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11024320/ (Full study)

Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome?

Abstract:

Dysautonomia, or dysfunction of the autonomic nervous system (ANS), may occur following an infectious insult and can result in a variety of debilitating, widespread, and often poorly recognized symptoms. Dysautonomia is now widely accepted as a complication of COVID-19 and is an important component of Post-Acute Sequelae of COVID-19 (PASC or long COVID).

PASC shares many overlapping clinical features with other infection-associated chronic illnesses including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Treatment Lyme Disease Syndrome (PTLDS), suggesting that they may share common underlying mechanisms including autonomic dysfunction.

Despite the recognition of this complication of Lyme disease in the care of patients with PTLD, there has been a scarcity of research in this field and dysautonomia has not yet been established as a complication of Lyme disease in the medical literature.

In this review, we discuss the evidence implicating Borrelia burgdorferi as a cause of dysautonomia and the related symptoms, propose potential pathogenic mechanisms given our knowledge of Lyme disease and mechanisms of PASC and ME/CFS, and discuss the diagnostic evaluation and treatments of dysautonomia. We also outline gaps in the literature and priorities for future research.

Source: Adler BL, Chung T, Rowe PC, Aucott J. Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome? Front Neurol. 2024 Feb 8;15:1344862. doi: 10.3389/fneur.2024.1344862. PMID: 38390594; PMCID: PMC10883079. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883079/ (Full text)

Long COVID Diagnostic with Differentiation from Chronic Lyme Disease using Machine Learning and Cytokine Hubs

Abstract:

The absence of a diagnostic for long COVID (LC) or post-acute sequelae of COVID-19 (PASC) has profound implications for research and potential therapeutics. Further, symptom-based identification of patients with long-term COVID-19 lacks the specificity to serve as a diagnostic because of the overlap of symptoms with other chronic inflammatory conditions like chronic Lymedisease (CLD), myalgic encephalomyelitis-chronic fatigue syndrome (ME-CFS), and others. Here, we report a machine-learning approach to long COVID diagnosis using cytokine hubs that are also capable of differentiating long COVID from chronic Lyme.

We constructed three tree-based classifiers: decision tree, random forest, and gradient-boosting machine (GBM) and compared their diagnostic capabilities. A 223 patient dataset was partitioned into training (178 patients) and evaluation (45 patients) sets. The GBM model was selected based on performance (89% Sensitivity and 96% Specificity for LC) with no evidence of overfitting.

We tested the GBM on a random dataset of 124 individuals (106 PASC and 18 Lyme), resulting in high sensitivity (97%) and specificity 90% for LC). A Lyme Index composed of two features ((TNF-alpha +IL-4)/(IFN-gamma + IL-2) and (TNF-alpha *IL-4)/(IFN-gamma + IL-2 + CCL3) was constructed as a confirmatory algorithm to discriminate between LC and CLD.

Source: Bruce Patterson, Jose Guevara-Coto, Javier Mora et al. Long COVID Diagnostic with Differentiation from Chronic Lyme Disease using Machine Learning and Cytokine Hubs, 18 January 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3873244/v1] https://www.researchsquare.com/article/rs-3873244/v1 (Full text)