Systematic reviews look at diagnosis, treatment of myalgic encephalomyelitis/chronic fatigue syndrome

Two systematic reviews published this week examine the diagnosis and treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

The reviews were performed to provide background for a National Institutes of Health Pathways to Prevention workshop. The first review examined trials published from January 1998 to September 2014 that described diagnostic methods for ME/CFS and their accuracy. A total of 44 studies met inclusion criteria. The authors found that 8 case definitions have been used for ME/CFS and noted that a ninth case definition has recently been proposed by the Institute of Medicine. In general, the authors said, patients who meet ME criteria appear to make up a more symptomatic subset of the ME/CFS population. Self-reported symptom scales appear to be effective in detecting ME/CFS in clinical trial settings, but their validity and generalizability in broad spectrums of undiagnosed patients have not yet been determined, the authors said.

The authors noted that their findings were limited by study heterogeneity and highly selected patient populations but concluded that none of the existing 9 sets of clinical criteria for ME/CFS have been proven adequate in cases of diagnostic uncertainty. “More definitive studies in broader populations are needed to address these research gaps,” the authors wrote.

The second review examined trials published between January 1998 and September 2014 that studied effectiveness and adverse effects of ME/CFS treatments. Thirty-five trials enrolled participants who met the 1994 CDC and Oxford definitions of CFS. Of these, 2 trials found some improvement in exercise measures with rintatolimod versus placebo (low strength of evidence), while trials that looked at galantamine, hydrocortisone, immunoglobulin G (IgG), valganciclovir, isoprinosine, fluoxetine, and complementary medicines yielded inconclusive results due to insufficient evidence. (Rintatolimod, an immunomodulatory drug with an unclear mechanism for treating ME/CFS, is not currently approved in the U.S. for this indication; isoprinosine, an immunomodulatory drug used primarily as an antiviral agent, is not available in the U.S.) Improvements in fatigue, function, and work impairment as well as global improvement were seen in some trials with counseling and graded exercise therapy versus no treatment, relaxation, or support, and counseling was also seen to improve quality of life (low to moderate strength of evidence).

The authors noted that the included trials were heterogeneous and had other limitations. However, they concluded that rintatolimod, counseling, and graded exercise therapy may benefit some patients who meet CFS case definitions. “More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps,” the authors wrote.

Based on these reviews, the resulting NIH Pathways to Prevention Workshop recommended overarching research strategies, which were published in a separate position paper.

An accompanying editorial noted that ME/CFS is estimated to affect 836,000 to 2.5 million Americans and said that the recent case definition proposed by the Institute of Medicine may help discriminate between those who have the disease and those who do not, although further testing of the definition is necessary. He acknowledged that much remains unknown about the disease but stressed that its existence as a “real” illness should no longer be questioned.

“When skeptical physicians, many of whom are unaware of [supporting] literature, tell patients with ME/CFS that ‘there is nothing wrong,’ they not only commit a diagnostic error: They also compound the patients' suffering,” the editorialist wrote.

The reviews, position paper, and editorial were published in the June 16 Annals of Internal Medicine.

Read more about the Institute of Medicine's newly proposed ME/CFS definition in the June ACP Internist.