Chapter 4 ● Flight Over ME/CFS

Keep a looking glass in your own heart, and the more carefully you scan your own frailties, the more tender you are for those of your fellow-creatures.

– Sir William Osler, M.D.

Medical science occasionally experiences breakthroughs that challenge and replace established knowledge on a particular subject. Sometimes, the latest information reveals an irrefutable truth. Innovations often impact those who have lived with an outdated understanding. For instance, the discovery that Campylobacter pylori (later known as Helicobacter pylori) causes gastritis and gastric ulcers led to the treatment with antibiotics and cimetidine, replacing surgical treatments for these conditions.

Despite its significance, the internet is rife with conspiracy theories challenging the discovery of this etiological agent. Today, we know that this pathogen infects over 65% of the global population, and its discovery earned Barry J. Marshall and J. Robin Warren the 2005 Nobel Prize in Medicine and Physiology. Their remarkable work exemplifies scientific determination, as they infected themselves to prove their hypothesis.

Currently, a similar revolution is unfolding concerning fibromyalgia, ME|CFS, and associated syndromes. This transformation began with Dr. Marian Dix Lemle's proposal of a core pathophysiology pathway, further investigated by Belgian and Australian scientists.

ME|CFS is a prevalent emerging clinical disorder of unknown cause, characterized by numerous somatic and psychological symptoms and chronic disability.

The condition is also referred to as FMS (fibromyalgia syndrome), CFS (chronic fatigue syndrome), fibromyalgic encephalopathy, fibrositis, CFIDS (chronic fatigue with immune dysfunction syndrome), muscular hardening, Iceland disease, MCS (multiple chemical sensitivities), and a plethora of other names, reflecting its poorly understood nature.

Inexperienced physicians may find these clinical syndromes perplexing, but after evaluating a sufficient number of patients, ME|CFS becomes a recognizable condition. The disease presents as a chronic, multi-symptom condition with cycles of exacerbation and mild improvement, progressively worsening over time. Ultimately, neurocognitive impairment disables most of its victims.

Over the past 50 years, physicians worldwide have observed an uncontrolled rise in this clinical disorder, particularly in major cities. Its primary symptoms include unexplained fatigue, headaches, depression, pain, insomnia, and other conditions, often accompanied by hypersensitivity. In the last two decades, the disease has become quite better defined. Research using diagnostic criteria for chronic fatigue syndrome reveals a significant increase in prevalence, and when fibromyalgia patients are included, the numbers soar. By 1990, some experts suspected that the disease incidence was rising too rapidly.

The disease manifests in sporadic and epidemic forms, resulting in outbreaks. Clinical cases within these outbreaks are more homogeneous than isolated ME|CFS patients, as if each surge exhibits a distinct clinical pattern. Additionally, the varying perspectives of different medical specialists treating ME|CFS patients may contribute to the observed variation in clinical descriptions, diagnostic criteria, and disease nomenclature.

The rise in new cases during the 1980s could have been anticipated, but medical scientists were initially baffled by its pathology. ME|CFS has expanded since the early 20th century, following an extended logarithmic growth curve. If not an artifact, this curve showed a brief attenuation in the mid-1990s, followed by sustainable growth, continuing to rise today. Our research suggests that the steep increase in new patients is just the tip of a vast iceberg. Outbreaks and endemic ME|CFS are hiding in plain sight, and nothing has been done to stop it. This pandemic has taken hold worldwide, particularly in regions with higher socioeconomic standards. Our data indicates that the worst is yet to come, exacerbated by COVID-19.

One disease, many illnesses?– ME|CFS, fibromyalgia, or whichever names we give to the disease, presents features of neurological, endocrine, and musculoskeletal affections, autoimmune conditions, elements of psychological disturbs, exposure to stressors and exhaustion, hypersensitivity, such as allergies, and intolerance to physical stimuli and multiple substances. This spectrum of diseases is associated with digestive tract problems, infections, dizziness, orthostatic intolerance, widespread pain in bones, muscles, tendons, and joints, abnormal body temperature, impotence, dysmenorrhea, and abnormal hemostasis. This disorder does not fit known disease definitions – it configures a new distinct nosological entity.

Disease in Children?– To date, no comprehensive studies have been published addressing ME/CFS, fibromyalgia, and related diseases in pediatrics. Nevertheless, children and teenagers are also affected, being challenging to recognize. The NICE Guidelines for CFS/ME Diagnosis and Management (updated 2014) include diagnostic criteria for children. Symptoms such as sadness, school phobia, depressive states, headaches, body pain, and fatigue should be carefully evaluated in young patients. ME/CFS can be particularly devastating for children, potentially causing significant impairment in learning and development. I have diagnosed several children and teenagers with severe ME/CFS; some have achieved remission, while others remain under follow-up, with most doing well today. In some cases, the disease was first suspected by the patient or a relative living in the same household. One case in my series involved a child who was bullied at school and whose mother had been diagnosed with fibromyalgia three years earlier.

A review of the literature reveals that fibromyalgia is distinct from M.E., ME/CFS, and related illnesses, despite some confusion among GWI patients, advocates, and physicians. From an etiogenic perspective, these conditions share a common origin and exhibit similar clinical findings. However, the variability in symptom prevalence and severity among patients leads to different clinical presentations, categorizing them into groups that fit specific diagnostic definitions and guiding them to various specialists. These complexities create a multifaceted disease spectrum with numerous denominations across medical specialties. For instance, when musculoskeletal pain predominates over fatigue and other symptoms, the condition is often managed by rheumatologists, algologists, and orthopaedists and is labeled as fibromyalgia or FMS. On the other hand, neurologists typically see the most severely affected patients when symptoms such as ataxia, speech problems, seizures, and other neurological signs are present, initially diagnosing them as multiple sclerosis or atypical polio, eventually evolving to myalgic encephalomyelitis or, less frequently, ME/CFS.

When patients exhibit extreme fatigue, depression, dizziness, emotional lability, and other symptoms, they are often diagnosed with chronic fatigue syndrome (CFS) or ME/CFS. Patients with severe fatigue and infections may be labeled as having CFIDS, indicating immune dysfunction within CFS. A significant medical stream and several research teams focus on these patients and advocate that CFS is a distinct clinical entity separate from most pain syndromes.

Immunologists, allergists, and general practitioners frequently encounter patients exhibiting multiple chemical sensitivities but rarely diagnose them with ME/CFS. Symptoms such as sleep disturbances, cognitive impairments, and pain are common across all related diseases.

Many physicians see patients with memory problems, headaches, insomnia, and body pain but seldom diagnose them with ME/CFS. Similarly, patients with severe inflammatory bowel disease are often evaluated by gastroenterologists, who rarely associate the conditions with this clinical spectrum.

Rheumatology periodicals publish articles on fibromyalgia or FMS; neurology literature addresses M.E. or myalgic encephalomyelitis, and there are scientific journals dedicated to ME/CFS and chronic fatigue syndrome.

Psychiatrists and psychologists publish and read papers on CFS and have deliberately inverted the letters to create CFS/ME, which they adopt. Immunologists focus on atopic conditions, multiple chemical sensitivities (MCS), and autoimmune conditions. Internists who study all these syndromes may sometimes get lost in the complexity.

Naming the condition is a significant challenge. In England, according to M.E. Research U.K., a foundation promoting research on the disease, the ME/CFS label has been split: M.E. is used by patients as a lay term, while CFS is adopted by doctors and medical and scientific journals.

A similar confusing history has occurred with fibromyalgia or FMS, once referred to as muscular rheumatism, psychogenic rheumatism, myofascial pain syndrome, chronic pain, and other names. Some designate ME/CFS and related syndromes as NEI or NEID (neuroendocrine-immune diseases). Interestingly, the condition has also been named E.I. (environmental illness). In a paper by H. Newbold and co-workers published in 1973, MCS was included among ecological mental diseases.

A few years ago, a committee convened by the Institute of Medicine of the National Academies examined the evidence base for ME/CFS. Sponsored by the Department of Health and Human Services, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, the Food and Drug Administration, and the Social Security Administration, the experts released their report on February 10, 2015.

In their report, titled "Beyond Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Redefining an Illness," the committee proposed new diagnostic criteria and a new designation for ME/CFS. They claimed that this would improve timely diagnosis, care, and knowledge among healthcare providers, patients, and the public. However, at the same time, they suggested the new designation SEID (Systemic Exertion Intolerance Disease), which they argued more accurately captures the central characteristics of the illness: the fact that exertion of any sort—physical, cognitive, or emotional—adversely affects patients in many organ systems and aspects of their lives.

The committee aligned with those who see chronic fatigue syndrome as a distinct disease. They grouped five of the seven most frequent ME/CFS symptoms: fatigue (worsened by exertion, labeled malaise), insomnia (referred to as unrefreshing sleep), cognitive dysfunction (termed mental affection), dizziness (attributed to orthostatic intolerance), and created, once again, a subgroup of ME/CFS patients under a new name. While not explicitly stated, the committee acknowledged the separate existence of fibromyalgia, GWI, and related conditions. However, they seemed to overlook pain and depression.

Although the new SEID diagnostic criteria, along with the efforts of its powerful sponsors, might facilitate the diagnosis of many new chronic fatigue patients, it is clear that the criteria are far from perfect—they exclude too many patients. Who was SEID created for? Is it a 'cease fire' tool for ME/CFS and fibromyalgia advocates, for instance?

In this study, I choose to disregard the new and experimental designations and primarily use M.E., ME/CFS, fibromyalgia, or FMS to refer to the illness. These terms are the most widespread and widely accepted names for this polymorphic entity today. Some researchers propose the term myalgic encephalopathy, as no unequivocal evidence of myelitis has been demonstrated, and it remains unclear whether inflammation is part of the disease process. Encephalopathy, however, can be demonstrated through autopsy, SPECT scans, QEEG, PET scans, and MRI.

In the future, the disease may be renamed EME (environmental myalgic encephalopathy), a designation that best fits the explanations provided throughout this work. This focus on the disease's origin allows for distinguishing ME/CFS from other encephalomyelitides, adjusting the classification to a less inflammatory condition.

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