Chronic fatigue syndrome/myalgic encephalomyelitis is a serious and disabling disorder of children and adults. It affects millions of individuals in the United States (U.S.) and globally leading in significant disability, morbidity and occasionally mortality. Skeptical about the optimal care of affected patients, experts at the Institute of Medicine (IOM) were commissioned to create an authoritative report addressing nearly all aspects of the disorder in a report entitled, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness (https://www.ncbi.nlm.nih.gov/books/NBK274235/).
BACKGROUND AND OVERVIEW
A series of outbreaks resembling poliomyelitis reported around the globe at the Royal Free Hospital in London included patients with malaise, tender lymph nodes, sore throat, pain, and encephalomyelitis. The term “benign myalgic encephalomyelitis (EM)” reflected the absent mortality. Two psychiatrists in the United Kingdom (U.K.) who reviewed the reports of 15 outbreaks and concluded them to be psychosocial phenomena caused by mass hysteria on the part of the patients or altered medical perception of the community. By 1986, the prefix “benign” was dropped, and the first diagnostic criteria for ME characterized the disorder as a unique form of muscle fatigability that lasted up the 3 days following minor physical effort before normal muscle function returned. At the same time, two large outbreaks of an illness in the U.S. characterized by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgia attracted attention because of its association with Epstein-Barr virus (EBV). Later investigations at the Centers for Disease Control and Prevention (CDC) reached a consensus on the clinical features of the illness, choosing the term “chronic fatigue syndrome (CFS)” noting that it not only was it more neutral and inclusive, but that EBV infection did not predate all cases.
Over time, it became evident that the term CFS trivialized the seriousness of the disorder while ME was often inaccurate as there was inconsistent proof of central nervous system inflammation or muscle pain in all cases. Coded identically by the World Health Organization's (WHO) International Classification of Diseases, Tenth Revision (ICD-10) as disorders of the nervous system (ICD G93.3), clinicians and researchers applied differing criteria and case definitions for ME and CFS, while “fatigue syndrome”, the hallmark of the combined disorder, was coded separately (ICD F48.0) under mental and behavioral disorders. These inconsistencies added to the confusion in unifying ME/CFS under a single diagnostic rubric.
The IOM report recommends an alternative terminology, renaming EM/CFS “systemic exertion intolerance disease” (SEID) emphasizing the central characteristic of the disorder, that exertion of any sort whether physical, cognitive or emotional, adversely affects patients in different parts of their body and in diverse aspects of their lives.
EPIDEMIOLOGY AND RECENT TRENDS
ME/CFS affects an estimated 836,000 to 2.5 million individual in the U.S. There are an estimated 84% to 91% of affected individuals yet to be diagnosed due to barriers in accessing clinical services or a consequence of referral pathways. Adult women are affected more often than men with an average age at onset of 33 years, although the disorder occurs in those under age 10 and above age 70. The Avon Longitudinal Study of Parent and Children (ALSPAC) birth cohort of chronic disabling fatigue lasting 6 months or more affected 1.3% of 13-year-olds and was equally common in boys and girls. CFS affected 1.9% of 16-year-olds in this U.K. birth cohort with a risk factor of gender not seen in the 13-year-olds or in 16-year-olds without high levels of depressive symptoms. Pediatricians need to recognize that children with ME/CFS present differently from adults, with more equal gender balance, and greater likelihood of sore throat and headaches and usual absence of cognitive symptoms, tender lymph nodes, palpitations, dizziness, general malaise and pain. The latter findings in a suspected child with ME/CFS may be a clue to the presence of a coexisting disease or alternative disorder.
The pathology of ME/CFS remains unknown and there is no diagnostic test for the disorder. Existing diagnostic criteria for ME/CFS have been developed through the consensus of experts notably, the 1994 CDC definition by Fukada; the 2003 Canadian Consensus Criteria (CCC), the 2007 Clinical Guidelines for CFS/ME of the British National Institute for Health and Clinical Excellence (NICE), the 2010 Revised CCC, and the 2011 International Consensus Criteria for ME (ME-ICC), with some exceptions for pediatric case definitions. These existing diagnostic criteria focused on similar sets of symptoms, but differed in the number of symptoms required and how those symptoms were defined. With most diagnostic criteria developed for adults, they were used to diagnose children and adolescents in both clinical and research settings. The Royal College of Pediatrics developed one case definition, while the CCC, NICE guidelines, and ME-ICC included guidelines for diagnosing ME/CFS in children.
The panel of experts of the IOM report a diagnosis of EM/CFS is highly suspected in those with chronic fatigue with a substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities for 6 months with post-exertional malaise and unrefreshing sleep, and either cognitive impairment or orthostatic intolerance.
Notwithstanding mental fatigue, there may be frank cognitive symptoms identified as memory and concentration impairments, and confusion. Post-exertional malaise is an exacerbation of symptoms or fatigue triggered by physical or mental exertion that lasts for 24 hours. Unrefreshing sleep is typically due to concomitant sleep dysfunction or frank sleep disturbances. Orthostatic intolerance may be a manifestation of autonomic disease and associated with cardiovascular, gastrointestinal and genitourinary impairments. Immune manifestations typically lead to sore throat in children and painful adenopathy in adults, both with associated laboratory humoral and cell-mediated immune system laboratory abnormalities. Notwithstanding true myalgia, there may be headaches and arthralgia. There are available questionnaires and tools useful in the assessment of fatigue, impairments in function, post-exertional malaise, sleep problems, neurocognitive symptoms, orthostatic intolerance and pain.
The challenge of improving the diagnosis and care of patients with ME/CFS is in determining with certainty the cause of ME/CFS as well as the mechanisms associated with the development and progression of the illness. While most studies have compared affected patients to healthy controls, there are a paucity of studies focused on distinguishing subgroups of ME/CFS. Determining the most effective means of treatment will likely take into account recognition of the natural history of the disease and its temporal progression with or without various empiric treatment regimens, and recognition of subsets of patients with shared disturbances in response to physical and emotional stressors, infection, immune dysfunction, and the expression of associated genetic, epigenetic and environmental triggers.