Much Can Be Done to Ease 'Chronic Fatigue Syndrome' Symptoms

Miriam E. Tucker

March 12, 2018

SALT LAKE CITY, UT — The illness commonly known as chronic fatigue syndrome is complex and currently incurable, but clinicians can still do a great deal to manage symptoms and improve patients' quality of life, experts agree.

In a 2-day meeting held March 2 and 3, 2018, specialists in the condition, now termed myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), met to discuss their assessment and treatment approaches. The aim of the "summit," organized by Lucinda Bateman, MD, and held at her Bateman-Horne Center facility here, was to initiate development of expert consensus ME/CFS guidance for primary care and specialist clinicians, and to identify research priorities to address major knowledge gaps.

"One of the messages I'd like to send to physicians is not to have an all-or-nothing approach to this illness, but to break it down into its parts, and see what you can get hold of with the history, objective markers, and clinical intuition. And then, it's not unreasonable to try some things that are not harmful or expensive," Bateman told Medscape Medical News.

The 13 panelists, who hail from primary care, infectious disease, immunology, neurology, endocrinology, pediatrics, and integrative medicine, discussed and prioritized elements of history-taking, physical exam findings, diagnostic tests, and treatment approaches for each of the illness' major components. The core features include fatigue, impaired function, postexertional malaise, sleep dysregulation, neurocognitive impairment, and orthostatic intolerance; other commonly reported features are widespread pain, immune dysregulation, and infection.

Panel members focused on approaches they have found to be most helpful and that can be accomplished in primary care, as well as more advanced modalities that would be more feasible in specialty practices.

Assessing the Illness

The document the group produces will endorse the 2015 Institute of Medicine diagnostic criteria, which define ME/CFS as 6 months of unexplained fatigue with substantial functional impairment, postexertional malaise, unrefreshing sleep, and either cognitive dysfunction or orthostatic intolerance. The symptoms must be moderate to severe and present at least 50% of the time. (Five summit participants, including Bateman, were on the writing committee for that report, and three others served as reviewers for it.)

Assessing functional capacity is key, Bateman said. "It's an illness that impairs people's ability to function in their daily lives. Clinicians need to ask about function, and what happens when people exert themselves both physically and cognitively."

One revealing question is, "What would you be doing now if you weren't ill?" Typically, as opposed to depressed patients, those with ME/CFS will have a laundry list. "Our patients are trapped in bodies that don't work," Bateman said. "They're desperate to do more."

Laboratory tests such as complete blood count with differential, complete metabolic panel, erythrocyte sedimentation rate and C-reactive protein, antinuclear antibody, rheumatoid factor, lipid panel, thyroid-stimulating hormone, and celiac screen should all be performed to investigate symptoms, but are often unhelpful. (As reported previously by Medscape Medical News, evidence suggests that the inflammatory cytokines involved in ME/CFS are different from those that induce C-reactive protein.)

In contrast, assessments that often yield valuable information in patients with ME/CFS include evaluation for orthostatic intolerance and autonomic dysregulation (ideally via tilt-table, but also can be accomplished with the 10-minute "Lean" test), and laboratory tests for Lyme immunoglobulin G (IgG) and IgM; lymphocyte subsets; IgG subclasses; Epstein-Barr virus, including early antigen antibody; herpes viruses; urine or serum markers of mast cell activation syndrome; small intestinal bacterial overgrowth; and natural killer cell function (almost universally low in patients with ME/CFS).

Brain imaging with magnetic resonance imaging or electroencephalography may be indicated in patients who exhibit "brain fog," headaches, or other neurocognitive symptoms.

"A lot of the testing we do is the differential diagnosis, and we're looking for comorbid conditions, treatment targets, and subgroups, like people with [small intestinal bacterial overgrowth] or mast cell activation. In the clinical setting, we don't have to make sense of it all. We just have to identify it, and see if the patient responds to treatment," Bateman said.

Panel member Charles W. Lapp, MD, who recently retired from his ME/CFS and fibromyalgia practice in Charlotte, North Carolina, told Medscape Medical News, "We use most tests for exclusionary purposes. We don't want to miss something that's treatable."

But, he added, some tests are for conditions that often accompany ME/CFS and exacerbate the symptoms. For example, for patients with high Epstein-Barr virus early antigen antibody titer, "if we can reduce that viral load, it might make the patient feel better. We don't know if its treating ME/CFS per se, but it's reducing the perpetuators, and that might make a difference."

Treatments Aimed at Symptom Relief

There is currently no US Food and Drug Administration-approved drug for ME/CFS, so treatments need to be individualized and directed toward the patient's most troubling illness manifestations and symptoms.

Medications that were endorsed by a majority of the panel include low-dose naltrexone for patients with pain and cognitive dysfunction, low-dose beta blockers or fludrocortisone for those exhibiting orthostatic intolerance, and intravenous Ig for patients with a variety of immune dysfunction indications including low IgG or IgA or recurrent infections.

Also universally viewed as critical for primary management of ME/CFS is the concept of adaptive pacing. With it, patients learn to conserve their limited energy by carefully adapting their activity so as not to exceed their anaerobic thresholds and thereby precipitate a "crash." One helpful website to offer patients is the CFIDS & Fibromyalgia Self-Help Program website.

There was also some endorsement among panel members for, but less agreement about the optimal use of, interventions such as antivirals or antibiotics, methyl folate for patients with methylenetetrahydrofolate reductase mutations, and immune modulators for low natural killer cell activity and other identified immune dysfunctions.

In general, much of the approach involves thinking outside the box, and sometimes borrowing from other fields, Bateman said. For example, she points to data suggesting that amantadine may improve fatigue and cognition in multiple sclerosis. "There's no reason we can't give [patients with ME/CFS] a trial of amantadine. Just making these cross-connections is very helpful."

Panel to Call for Randomized Trials of Biological Treatments

Panel members are well aware that not only are the products they use not approved by the US Food and Drug Administration for ME/CFS, but many are supplements that aren't even regulated by the administration. Part of the summit's deliverables will be a call for addressing that deficiency via randomized controlled clinical trials, according to the organizers.

"Very few treatments have been rigorously studied in ME/CFS," summit comoderator Anthony Komaroff, MD, professor of medicine at Harvard Medical School in Cambridge, Massachusetts, told Medscape Medical News. "For one thing, with drugs that are off patent, it is hard to find funding to test off-label use. And with drugs still on patent, pharma needs some empirical evidence of benefit before investing in pursuing a new indication for use, and collecting such evidence takes money.... So clinicians are left to trying treatments that are unproven, but for which there is a plausible rationale for their use, and little chance of harm."

Notably missing from the recommended treatment list are cognitive behavioral therapy aimed at overcoming "false illness beliefs" and "graded exercise." (A trial published in 2011 suggested those interventions were helpful, but it has since been faulted by the ME/CFS community because of its patient selection criteria and methodological issues.) The summit panel voted unanimously to include a statement rejecting those modalities as inappropriate and potentially harmful.

What Does the Patient Need?

In addition to treatments, patients with ME/CFS very often have other critical needs. Some will require disability verification, for which 2-day cardiopulmonary exercise testing may be necessary to prove impairment in function and postexertional malaise. Patients with ME/CFS will show distinct abnormalities on the second day of 2-day cardiopulmonary exercise testing, but several panelists said they believe that it's too taxing for patients to be used in routine clinical assessment.

Other patient needs may include disability parking permits, home healthcare, equipment such as canes or wheelchairs, and social services such as Meals on Wheels for those living alone.

Several panel members expressed concern about the future for patients who lack sufficient social support, and for adult bedbound patients being cared for by aging parents. One physician described a Munchausen case in which a healthy school-aged child was faking illness to stay home and care for her mother, who was disabled with the real illness ME/CFS.

Validating the Patient's Experience

Of course, all of this requires that the clinician accept and communicate to the patient that ME/CFS is real, despite the lack of clarity about its etiology, Komaroff noted. "There is a literature of over 9000 publications that says this has a biological underpinning. It's not imaginary, and it's not fabrication."

He continued, "People don't understand how devastating it can be to be really sick and for people to not believe you. The personal invalidation that people with this illness have experienced...the spouse, the parent, the employer who at first are sympathetic, but when three doctors in a row say there's nothing wrong, patients begin to see their support systems in danger."

And, Komaroff added, "The importance of clinical validation to the patients, in my experience, has been enormous, even when you follow it by 'I'm going to do everything I can, but I can't promise that I'm going to be able to make you feel better.' "

Indeed, Bateman said of the panel's work, "I want to take the knowledge that we have and make it impossible for people to turn away from this disease."

Komaroff is a section editor for UpToDate. Bateman and Lapp have disclosed no relevant financial relationships.

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