Complementary Health Approach Use Among Adults Reporting a Clinician Diagnosis of Chronic Fatigue Syndrome in a US Online Quota Sample

Abstract:

Background/Objectives: We compared reported complementary health approach (CHA) use by self-reported clinician diagnosis of chronic fatigue syndrome (CFS), with favorability and expected helpfulness as additional exploratory outcomes.

Methods: This secondary analysis included 3022 adults from a 2024 US nonprobability online quota sample. Diagnoses were not clinically verified, and formal ME/CFS criteria were not assessed. Logistic models adjusted for ten covariates, using Firth regression for sparse or unstable estimates. Revision-time Benjamini-Hochberg correction defined nine question-based families by outcome and approach grouping.

Results: Among 167 respondents reporting CFS, adjusted odds of use were higher for physical (aOR 2.22, 95% CI 1.60-3.07), nutritional (2.25, 1.34-3.80), combined (1.89, 1.24-2.88), and systems approaches (1.99, 1.32-3.01); all q < 0.05. Nineteen individual CHAs and all seven conventional approaches met q < 0.05 for use. Any-CHA use was 98.2% versus 94.6% (aOR 2.46, 95% CI 0.97-8.91; q = 0.065). Adding the count of other self-reported clinician diagnoses attenuated category-use associations; their CIs included 1. Psychological-category favorability was lower using a mean >3.5 cutoff, but its FDR threshold status depended on midpoint handling. No expectancy association met q < 0.05.

Conclusions: Respondents reporting CFS reported greater use of multiple approaches. Additional-diagnosis adjustment changed the estimates, but the count cannot distinguish morbidity from healthcare contact or diagnosis ascertainment. The findings do not establish CFS-specific treatment use, substitution, or effectiveness.

Source: Agostini K, Heims AN, DiCristo J, Bond AD, Agnello RN, Motyka TM. Complementary Health Approach Use Among Adults Reporting a Clinician Diagnosis of Chronic Fatigue Syndrome in a US Online Quota Sample. J Clin Med. 2026 Oct 29;15(21):8425. doi: 10.3390/jcm15218425. PMID: 43030569. https://www.mdpi.com/2077-0383/15/21/8425 (Full text)

Treg and Oxidative Stress Biomarker Profiles in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Chronic immune dysregulation is the possible pathophysiological mechanism in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long coronavirus infectious disease (long COVID, LC). However, a detailed characterization of regulatory and effector T-cell subsets in these conditions remains limited. To assess and compare T-cell subsets in relation to serum biomarkers of chronic activation and oxidative/nitrosative stress in an attempt to differentiate between LC and ME/CFS patients.

Peripheral blood mononuclear cells (PMNC) from LC patients (n = 89), ME/CFS patients (n = 125), and healthy controls (HC, n = 80) were analyzed using multiparameter flow cytometry. The frequencies of naïve (CD45RA+), effector (CD45RA-), CD31+, CD39+, CD73+, GARP+, PI16+, CD15s/CD161+, and CD147+ Treg subsets were determined in relation to CD4+ and CD8+ T-cell differentiation, activation, and effector subsets. Catalase (CAT), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), malondialdehyde (MDA), nitric oxide synthase 1 and 3 (NOS1, NOS3), zonulin, lipopolysaccharide (LPS), immunoglobulin G (IgG) against lipopolysaccharide (IgG-LPS), Toll-like receptor 4 (TLR4), indoleamine 2,3-dioxygenase (IDO), and Dickkopf-related protein 1 (DKK1) were measured in serum by ELISA. Clinical symptom scores (HAMA, HAMD, FF, dePol) were additionally assessed.

The immune-serum biomarkers distinguishing LC, ME/CFS, and HC comprised Th17, CD15s+CD161-eTreg, and CD161+ Treg. The five-marker signature retained significance after adjustment for age, BMI, and sex. Altered T-cell subsets were strongly associated with markers of oxidative (GPX1) and nitrosative (NOS3) stress but not directly with symptom severity. ME/CFS showed a strong separation from HC across Random Forest (AUC = 0.907) and logistic regression (AUC = 0.924).

The modest distinction of LC from HC (AUC = 0.727 and 0.577 respectively) possibly reflected important endotypic diversity, though differences in disease duration, vaccination history, biomarker selection, and other cohort characteristics might add to it. MDA was an independent predictor for three-class classification, ME/CFS vs. HC, and LC vs. HC pairwise comparisons, while GPX1 discriminated between ME/CFS and LC.

In spite of shared biomarkers of oxidative stress and T-cell response dysregulation, our results support the hypothesis that LC and ME/CFS differ in the extent of cellular damage and the exhaustion of compensatory mechanisms.

Source: Todorova Y, Dimitrova R, Kalfova T, Petrov S, Bozhkova M, Ivanovska M, Dudova D, Murdjeva M, Taskov H, Maes M, Nikolova M. Treg and Oxidative Stress Biomarker Profiles in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci. 2026 Oct 22;27(21):9422. doi: 10.3390/ijms27219422. PMID: 43027675. https://www.mdpi.com/1422-0067/27/21/9422 (Full text)

Pyridostigmine and low-dose naltrexone for ME/CFS: study protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic disease with no FDA-approved treatments. This report describes a protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial investigating the impact of low-dose naltrexone (LDN) and pyridostigmine (Mestinon) on physiological response, symptoms, and functionality of ME/CFS patients.

Methods: Participants (target n = 160) are recruited through clinics at Massachusetts General Hospital and Brigham and Women’s Hospital, and through Open Medicine Foundation’s StudyME registry. They are then randomized into one of four arms: LDN/pyridostigmine, LDN/placebo, placebo/pyridostigmine, placebo/placebo. Treatment is administered for 13 weeks after an initial screening period of up to 4 weeks. Primary outcomes are FUNCAP-55 score, peak oxygen utilization, heart rate recovery, and oxygen uptake efficiency slope. Secondary outcomes are scores from DSQ-PEM and PROMIS-29 surveys, DANA Brain Vital score, step count, heart rate, and heart rate variability.

Discussion: The results of this trial will provide novel insights into the efficacy of and predictors of response to LDN and pyridostigmine in ME/CFS. This may inform future treatment strategies for ME/CFS. The trial will also validate what primary and secondary outcomes to use in similar clinical trials.

Trial registration: This trial was registered on clinicaltrials.gov (NCT06366724) on April 16, 2024.

Source: Meadows D, Squires J, Dibble J, Palwayi S, Felsenstein D, Tannenbaum L, Li P, Xiao W, Bergquist J, Systrom D. Pyridostigmine and low-dose naltrexone for ME/CFS: study protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial. Trials. 2026 Aug 12;27(1):654. doi: 10.1186/s13063-026-09943-6. PMID: 43000413; PMCID: PMC13746464. https://pmc.ncbi.nlm.nih.gov/articles/PMC13746464/ (Full text)

Development and initial content validation of the Vienna post-exertional malaise questionnaire: an iterative mixed-methods study

Abstract:

Objectives: Post-exertional malaise (PEM) is a multidimensional exertion-response pattern involving diverse triggers, variable onset, and prolonged recovery. This study developed and content-validated the Vienna Post-Exertional Malaise (VPEM) Questionnaire, a patient-reported outcome measure assessing functional decline, recovery, crash-associated symptoms, and pacing adaptations in ME/CFS.

Methods: An iterative mixed-methods instrument-development study combined quantitative ratings and qualitative feedback across sequential evaluation cycles. An initial 13-item draft, informed by existing PEM, fatigue, and functional-capacity instruments and consensus literature, was evaluated by individuals with ME/CFS or Post-COVID-19 syndrome (PCS) using Likert ratings, open-ended feedback, and interviews. Quantitative data were summarised descriptively, and qualitative data were analysed using deductive-inductive structuring content analysis. Revisions were documented in revision matrices. The revised instrument was evaluated by an interdisciplinary expert panel using domain-level and item-level ratings of relevance and clarity.

Results: Twelve individuals with ME/CFS and one individual with PCS fulfilling ME/CFS criteria evaluated the questionnaire. Ratings showed high approval for length (92.3%) and terminology (76.9%), while completeness and clarity were more heterogeneous. Qualitative findings identified ambiguities in distinguishing PEM from non-specific fatigue, missing trigger domains, and insufficient representation of intra-individual variability. After revision, the expert panel (n = 11) rated PEM coverage as complete or largely complete (100%) and the multidimensional structure as suitable or very suitable (90.9%). Item-level ratings showed high relevance (S-CVI/Ave = 0.96), whereas clarity ratings were more variable (S-CVI/Ave = 0.82).

Conclusions: The VPEM Questionnaire operationalises PEM as multidimensional post-exertional deterioration. Findings support initial content and face validity, warranting further psychometric validation.

Source: Pimminger T, Ahrens-Schwabe A, Fragner T, Brandl T, Kotzian ST, Wüst RCI, Waldhoer T, Kapan A. Development and initial content validation of the Vienna post-exertional malaise questionnaire: an iterative mixed-methods study. Qual Life Res. 2026 Nov 7;35(12):327. doi: 10.1007/s11136-026-04434-2. PMID: 42998183; PMCID: PMC13744550. https://pmc.ncbi.nlm.nih.gov/articles/PMC13744550/ (Full text)

Fibromyalgia, Chronic Fatigue Syndrome, and Multiple Sclerosis are associated with lower translocator protein binding affinity genotypes

Abstract:

Introduction: Neuroinflammation is a known pathophysiologic mechanism in multiple sclerosis and a proposed mechanism in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Positron Emission Tomography (PET) imaging of the translocator protein (TSPO) has been widely used to measure neuroinflammation, though second-generation ligands are highly sensitive to a single nucleotide polymorphism, rs6971, resulting in high, mixed, and low affinity binders. It is unknown whether this polymorphism is associated with neuroinflammatory disorders.

Materials and methods: Eighty-six total participant genotypes for TSPO binding affinity were identified through Sanger sequencing (30 fibromyalgia, 21 ME/CFS, 11 multiple sclerosis, and 24 healthy controls). Associations between patient group and genotype were assessed with Fisher’s Exact test. Associations between genotype and symptom severity from self-report questionnaires were assessed with Kruskal-Wallis tests.

Results: In the present study individuals with fibromyalgia, (ME/CFS), or multiple sclerosis were more likely to have a mixed- or low-affinity genotypes compared to healthy controls. Presence of the low or mixed genotypes were also associated with greater self-reported fatigue severity and depressive symptoms.

Discussion: These findings should be confirmed in larger samples but suggest functional consequences of rs6971 polymorphism that may be related to the pathophysiology of pain and fatigue illnesses.

Source: Jones C, Younger J. Fibromyalgia, Chronic Fatigue Syndrome, and Multiple Sclerosis are associated with lower translocator protein binding affinity genotypes. medRxiv [Preprint]. 2026 Oct 21:2026.10.19.26365953. doi: 10.64898/2026.10.19.26365953. PMID: 42996068; PMCID: PMC13738865. https://pmc.ncbi.nlm.nih.gov/articles/PMC13738865/ (Full text)

More common than we thought: Hypermobile Ehlers-Danlos Syndrome, comorbidity burden, and long COVID risk in a national cohort

Abstract:

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a complex, underdiagnosed connective tissue disorder characterized by widespread symptoms affecting multiple organ systems. Recent clinical observations suggest that individuals with hEDS may be at increased risk for persistent symptoms following COVID-19, commonly referred to as Long COVID.

Using data from over 19 million patients across the United States, we examined associations between hEDS, COVID-19 infection, Long COVID, and related chronic conditions. We identified just over 25,000 individuals with hEDS and estimated a prevalence of approximately 1 in 800, which is higher than previously recognized.

Despite similar rates of COVID-19 infection between patients with hEDS and matched controls, patients with hEDS were nearly three times more likely to develop Long COVID. This risk was concentrated among patients with hEDS who also had overlapping conditions commonly seen in post-viral syndromes, including autonomic dysfunction (POTS), immune dysregulation (MCAS), and chronic fatigue (ME/CFS). Patients with hEDS also exhibited higher odds of having additional risk factors for severe or prolonged illness, including chronic lung and autoimmune conditions, depression, and cerebrovascular disease.

A subgroup of patients received their hEDS diagnosis only after a COVID-19 or Long COVID diagnosis, and this subgroup was highly enriched for multimorbidity, particularly POTS and MCAS.

These findings establish hEDS as more prevalent than previously recognized and identify a substantially elevated, comorbidity-driven risk of Long COVID in this population. Improved screening, earlier diagnosis, and integrated care pathways are urgently needed to support this complex and underserved patient group.

Source: Pearson ML, Laraway BJ, Elias ER, Bilousova G, Haendel MA. More common than we thought: Hypermobile Ehlers-Danlos Syndrome, comorbidity burden, and long COVID risk in a national cohort. PLOS Digit Health. 2026 Nov 5;5(11):e0001707. doi: 10.1371/journal.pdig.0001707. PMID: 42986813; PMCID: PMC13739140. https://pmc.ncbi.nlm.nih.gov/articles/PMC13739140/ (Full text)

A Woman With Multiple Neuropathic Symptoms, Hypersensitivity to Heat, Peppers, and Alcohol, With a Variant in the TRPV1 Capsaicin Receptor Gene: Possible Implications to ME/CFS

Abstract:

Transient receptor potential vanilloid 1 (TRPV1) is a ligand and heat-gated ion channel expressed on nociceptors that plays a central role in thermal and chemical pain signaling. Loss-of-function variants in TRPV1 have been associated with reduced nociception. We report a 65-year-old woman with disabling polyneurofunctional/neuropathic symptomatology including migraine, functional gastrointestinal disorders, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Diagnostic evaluation revealed sensory polyneuropathy and autonomic instability. Whole genome sequencing reanalysis identified a heterozygous TRPV1 c.2174A > T (p.Lys725Met) Likely Pathogenic variant that is very rare and highly conserved.

Our patient reports consistent, longstanding, marked hypersensitivity to heat, capsaicin, and alcohol, all of which are known TRPV1 agonists, supporting a gain-of-function mechanism for this variant. Furthermore, prior studies have implicated TRPV1 hyperactivity in migraine, nociceptive sensitization, and ME/CFS. Despite the excellent clinical correlation, causality of the variant cannot be definitively established without functional studies.

This case expands the potential phenotypic spectrum associated with TRPV1, and highlights a possible role for TRPV1-mediated channelopathies in complex neurofunctional disorders including ME/CFS.

Source: Zimmermann PM, Boles RG. A Woman With Multiple Neuropathic Symptoms, Hypersensitivity to Heat, Peppers, and Alcohol, With a Variant in the TRPV1 Capsaicin Receptor Gene: Possible Implications to ME/CFS. Case Rep Genet. 2026 Nov 3;2026:1920171. doi: 10.1155/crig/1920171. PMID: 42979319; PMCID: PMC13729082. https://pmc.ncbi.nlm.nih.gov/articles/PMC13729082/ (Full text)

“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.

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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.

Post-acute infection: before we forget it again

Abstract:

Long COVID did not invent the post-acute phase of infection; it made it impossible to ignore. Acute infections are still often framed as time-limited events that end in recovery, deterioration or death, but this view fails to capture patients who remain biologically and clinically unwell after the acute infection has passed. The problem extends beyond SARS-CoV-2. Post-acute morbidity has been described after influenza, Epstein-Barr virus infection, Q fever, sepsis, and other infections, yet definitions, coding systems, and clinical pathways remain fragmented.

We argue that post-acute infection should not be organized only by the initiating pathogen. Such pathogen-centric labels may be clinically tidy, but they risk producing heterogeneous cohorts, diluted biomarker signals, and disease-specific silos that obscure shared mechanisms of incomplete recovery. Instead, the field needs a second axis: the host-recovery state.

Persistent inflammation, immune remodelling, loss of tolerance, antigenic stimulation, endothelial dysfunction, mitochondrial impairment, and tissue injury may represent overlapping immunometabolic failure modes across infections. Defining these states over time could help transform post-acute infection from a residual clinical label into a mechanism-informed framework for research, biomarkers, and care.

Source: Madsen HB, Desler C. Post-acute infection: before we forget it again. Clin Exp Immunol. 2026 Jan 6;220(1):uxag061. doi: 10.1093/cei/uxag061. PMID: 42931812; PMCID: PMC13701074. https://pmc.ncbi.nlm.nih.gov/articles/PMC13701074/ (Full text)

Dr. Lapp on CFS versus FM: Twins, Cousins, or Just Acquaintances?

by Charles W. Lapp, MD
September 6, 2011

Ed Note: This article is reproduced with kind permission from Bruce Campbell’s CFIDS & Fibromyalgia Self-Help website (https://cfsselfhelp.org/). Dr. Lapp directed the Hunter-Hopkins Center in Charlotte, NC, one of the few medical practices in the US specializing in the treatment of ME/CFS and FM. [Dr. Lapp is now retired.]

Reprinted with the kind permission of Prohealth: 9/6/11

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Chronic Fatigue Syndrome is a disorder characterized by debilitating fatigue and recurrent flulike symptoms, such as muscle and joint aches, sore throat, swollen glands, and difficulty thinking. Fibromyalgia Syndrome is a disorder characterized by widespread muscle pain.

Can such different descriptions share anything in common?

Siamese Twins

Most experts agree that the symptoms of CFS and FM are so close that they are – for all intents – the same disorder. It’s a bit like Jekyll and Hyde, or perhaps like Chang and Eng Bunker, the Siamese twins made famous by P.T. Barnum. They were both the same “person” but had two different names, two similar but different personalities.

Assigning a Diagnosis

Patients who present to their primary care providers frequently relate a litany of complaints such as fatigue, vague aching, and trouble with memory or concentration.

Based on these complaints, the primary care doctor will most likely diagnose Chronic Fatigue Syndrome using the 1994 international case definition published by the Centers for Disease Control.

On the other hand,  the patient whose major complaint is pain will likely consult a rheumatologist who will ask, “Where does it hurt?” When it is determined that the patient hurts at the classical “tenderpoints” defined by the ACR [American College of Rheumatology] in 1990, the likely diagnosis will be Fibromyalgia.

Overlaps and Shadows

So one diagnosis is frequently given by primary care physicians and the other by rheumatologists. Both diagnoses have several features in common: exertional malaise [activity intensifying symptoms], cognitive difficulties, muscle pain (or myalgias) and a sleep disorder.

Both are frequently associated with “overlap disorders” or “shadow syndromes,” as I like to call them. The most common “shadow syndromes” are irritable bowel syndrome, irritable bladder, temperomandibular dysfunction, and mitral valve prolapse.

Others include premenstrual syndrome, primary dysmenorrhea, migraine, restless legs or periodic leg movements, Myofascial Pain Syndrome (MPS), chemical sensitivities, autonomic dysfunction (Neurally Mediated Hypotension and Postural Orthostatic Tachycardia Syndrome), Gulf War Syndrome, and possibly hyperextensibility, acne rosacea, Raynaud’s phenomenon, sicca complex (dry eyes and mouth) and vasomotor rhinitis (constant runny nose and congestion).

Note that the shadow syndromes occur predominantly in females, are defined clinically rather than by physical or laboratory findings, and many are associated with either pain or fatigue. It is likely that these disorders occur concurrently because they share a common biophysiological thread.

Fibromyalgia & CFS Compared

The symptoms are similar for both syndromes, including debilitating fatigue, post-exertional malaise, feverishness, sore throat, headache, joint aches, a feeling of generalized weakness, subjective swelling, non-radicular paresthesias (numbness or tingling that does not follow typical nerve patterns), memory loss, forgetfulness, confusion, irritability, and depressed mood.

There are some subtle differences, however. (See Table 1 at end of article.)  Historically, CFS is frequently triggered by a flulike or infectious illness, but sometimes occurs after trauma or surgery. FM, on the other hand, is frequently triggered by trauma, less often by an infectious process.

While there is a preponderance of women in both disorders, women are more likely to have FM (9:1) than CFS (7:3). The median age for both disorders is about 40 years, although all age groups are vulnerable, including children and seniors. Familial aggregations and overlapping HLA haplotypes are described for both disorders.

Physiologically, both disorders have in common reduced midbrain and cortical blood flow; autonomic dysfunction such as symptomatic orthostatic tachycardia and neurally mediated hypotension;  suppression of the hypothalamic pituitary axis; disturbed Stage 4 sleep; reduced serum or CSF serotonin levels; and suppression of growth hormone, somatomedin C, or IGF1. (Similarities are summarized in Table 2.)

Substance P, a neurotransmitter responsible for the transmission of pain is elevated in persons with FM (but not CFS); and RNaseL, a cellular antiviral enzyme is frequently elevated in CFS (but not in FM). These differences may reflect why pain is a key symptom in FM, and viral symptoms predominate in CFS.

Treatment

The treatment of CFS and FM is hampered by the absence of a known cause and pathophysiology. In such instances, treatment is generally limited to supportive care and symptomatic therapy. Thus a prudent diet, basic supplementation, and traditional management of sleep disruption, pain, and autonomic symptoms are the standard course.

Counseling is helpful in coping with chronic illness and stress, and study after study has extolled the virtues of low level progressive exercise. Activity must be approached cautiously, however.

“Pure cases” of FM seem to respond with increased endurance and improved well-being to a progressive exercise program, while “pure cases” of CFS are more likely to respond with increased cognitive and flulike symptoms to a similar regimen. Thus, persons with CFS may have to start at a lower level and progress more slowly.

Pure Cases

There are certainly cases of “pure CFS” or “pure FM.” When there is no significant complaint of muscle pain, the patient would be diagnosed as having “pure CFS,” mostly characterized by fatigue, cognitive dysfunction, sleep disruption, and flu-like symptoms including vague muscular aching during relapses.

When cognitive symptoms are minimal and widespread muscle pain is the major complaint, the patient is thought to have “pure FM.” These make up a minority of the cases,  however, since about 70% of persons with CFS meet criteria for FM, and about 70% of persons with FM also meet criteria for CFS.

In most aspects Fibromyalgia and CFS are almost identical. There are subtle differences in biochemistry, prevalence, and perhaps response to exercise that separate them ever so slightly. CFS and FM may represent the extreme ends of a spectrum of multisystem disorders characterized by fatigue, pain, and female predominance.

* * * *

Table 1: Differences
CFS                                 FM
Trigger                    Flulike > trauma        Trauma > flulike

Female to Male      7 to 3                          9 to 1
Predominance

Prevalence             400-800 per 100K    2,000 per 100K

Substance P           Normal                       Increased

RNaseL                  Increased                     Normal

Exercise
Intolerance              +++                            +

Table 2: Similarities

• Reduced cerebral blood flow in cortex and midbrain
• HPG Axis suppression
• Non-restorative sleep
• Reduced serum and/or CSF serotonin
• Low growth hormone
• Familial aggregation / haplotypes

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ProHealth Note – have you visited:

The Treating CFS & FM website (www.treatcfsfm.org). Dr. Lapp and Dr. Campbell are long-time collaborators who have also pooled their knowledge to create this website. It is a guide that can take you step-by-step through creation of a personal treatment plan.

Disclaimer: This material is posted for informational and educational purposes only and is not intended to substitute for medical or other professional advice. Consult your physician or other health care provider regarding your symptoms and medical needs.