Originally published in Mayo Clinic Proceedings on August 25, 2021 By Lucinda Bateman, MD et al.
Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.
Abbreviations and Acronyms:
CBT (cognitive behavioral therapy), GET (graded exercise therapy), ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), NAM (National Academy of Medicine), PEM (post-exertional malaise)Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, multi-system disease affecting millions of people worldwide. Despite its high prevalence and disabling nature, medical education programs rarely cover ME/CFS and guidance for practicing clinicians is often outdated and inappropriate.1,2 Standard tests typically return normal results, and some clinicians are wholly unaware of or question the legitimacy of ME/CFS.1,3 Consequently, up to 91% of affected people are undiagnosed or misdiagnosed with other conditions, such as depression.1 To obtain a diagnosis, patients frequently have had to see multiple clinicians over a number of years. Even after diagnosis, patients struggle to obtain appropriate care and have often been prescribed treatments, such as cognitive-behavioral therapy (CBT) and graded exercise therapy (GET), that could worsen their condition.1,2,4In 2015, the US National Academy of Medicine (NAM, previously the Institute of Medicine) created new ME/CFS clinical diagnostic criteria that required the hallmark symptom of post-exertional malaise (PEM).1 The US Centers for Disease Control and Prevention have adopted these new criteria, have removed recommendations for CBT and GET, and have begun to incorporate the best clinical practices of ME/CFS experts. These steps will help improve the speed and accuracy of diagnosis and the quality of clinical care.Lingering symptoms including fatigue follow various types of infectious illnesses.5 These “postinfectious” fatigue syndromes resemble ME/CFS.6 Moreover, ME/CFS itself often follows an infectious-like illness.1 On occasion, the infectious illness preceding ME/CFS, such as infectious mononucleosis,1Coxiella burnetii infection,7 giardiasis,8 or severe acute respiratory syndrome (caused by a coronavirus similar to the etiologic agent of COVID-19),9,10 has been well documented, but often, no attempt has been made to diagnose the infectious agent.Following acute COVID-19, whether hospitalized or not, many patients continue to experience debility and symptoms for many months.6,11, 12, 13 Some of these “long haulers” may have symptoms reflecting organ damage, such as to the lungs or heart, from the acute disease.13 Other long haulers are symptomatic despite having no clear evidence of such organ damage.13 A study of patients ill 6 months after mild or moderate acute COVID-19 found that about half met criteria for ME/CFS.14 One review suggested that the number of cases of ME/CFS could double as a result of the pandemic.6 Like ME/CFS patients, those with post-COVID conditions have recounted being dismissed by health care professionals.15This article provides essential information about how to diagnose and care for adults with ME/CFS and echoes other recent ME/CFS guidance.16, 17, 18 Accurately and expeditiously diagnosing ME/CFS is important. There are many steps a clinician can take to improve the health, function, and quality of life of these patients. Even if they do not go on to develop ME/CFS, some patients with post-COVID conditions may also benefit from approaches such as pacing.
Myalgic encephalomyelitis/chronic fatigue syndrome affects between 836,000 and 2.5 million Americans of all ages, ethnicities, genders, and socioeconomic backgrounds.1 Some groups are disproportionately affected:
- •Women are affected at a rate 3 times that of men.1
- •Onset often occurs between the ages of 10 to 19 years and 30 to 39 years.18,19 The average age at onset is 33 years, but ME/CFS can develop in people as old as 77 years and as young as 2 years.1,18
- •Blacks and Latinxs may be affected at a higher rate and with greater severity than other groups.20, 21, 22
- •An infectious episode near the onset of ME/CFS is recounted by 80% or more of patients.23 In prospective studies, 5% to 13% of people infected with certain pathogens developed ME/CFS in later months.7 Cases have occurred both sporadically and in clusters.1
Historically, premorbid mood disorders, personality issues, and childhood adversity have been linked to the development of ME/CFS. However, study limitations, such as use of overly broad criteria that included people with depression but not ME/CFS, could confound those findings.1 Mental health after the onset of ME/CFS is similar to that in other medical conditions and better than that seen in depression.24,25 The prevalence of depression and anxiety in ME/CFS is similar to that in other disabling, chronic illnesses.26,27
Impact and Prognosis of ME/CFS
Myalgic encephalomyelitis/chronic fatigue syndrome substantially impairs occupational, educational, social, and personal activities. The degree of impairment can exceed that of rheumatoid arthritis, multiple sclerosis, depression, heart disease, cancer, and lung disease.24,28,29 There is a wide spectrum of severity30 ranging from mild to very severe:
- •Mild: mobile and self-caring; may continue working but will have reduced other activities
- •Moderate: reduced mobility, restricted in instrumental activities of daily living, needs frequent periods of rest; usually not working
- •Severe: mostly housebound; limited to minimal activities of daily living (eg, face washing, showering); severe cognitive difficulties; may be wheelchair dependent
- •Very severe: mostly bedridden; unable to independently carry out most activities of daily living; often experience extreme sensitivity to light, sound, and other sensory input
Up to 75% are unable to work, and an estimated 25% are consistently housebound or bedbound.31,32 The level of severity can fluctuate, with 61% reporting being bedbound on their worst days.33Although it is known that patients can be ill for years or even decades, no definitive study of prognosis exists. Studies are limited by small sample sizes, high dropout rates, short follow-up times, inclusion of patients with other conditions, and inappropriate definitions of recovery.34,35 A systematic review concluded that the chance of full recovery is only 5%.36 One ME/CFS-focused clinical practice estimated that 50% of its patients were still ill after 2 decades whereas a second estimated 93% (oral communication, US ME/CFS Clinician Coalition, March 2019). Temporary remission is reported, but relapses often occur. Patients most commonly report a fluctuating illness pattern in which symptoms wax and wane but are always present.37, 38, 39 Specialty clinics for ME/CFS reported that 84% of 960 patients observed long term developed at least 1 comorbid condition. Additional comorbidities were associated with worsened health.40