In 1996, Judith Curren, 42, took her own life with help from Jack Kevorkian, MD.

Curren was thought to have chronic fatigue syndrome (CFS), an illness associated with immune and neurologic symptoms that remains difficult to diagnose. A medical examiner questioned whether Curren was ever sick, according to the New York Times.

Myalgic encephalomyelitis (ME/CFS) is the preferred term for patients suffering from what has historically been called CFS. Advocates and patients say "chronic fatigue" is too fluffy a term for a disease so crippling.

Leonard "Len" Jason, PhD, director of the Center for Community Research at DePaul University in Chicago, told MedPage Today, "In our society energy, stamina, and endurance are probably more valued than anything else, including even money. And if you don't have [those commodities], you are really not participating in the 'American dream.'"

Lily Chu, MD, an ME/CFS researcher, explained the difference between general fatigue and what patients experience. A person who runs a marathon may have general fatigue, but it isn't an all-over body pain, their lymph nodes aren't swollen, and they don't have difficulty sleeping or problems concentrating.

"Those aren't things you normally see with healthy people after exertion," said Chu, a community advisory board member at the ME/CFS Initiative at Stanford University in Stanford, Calif. A third to a quarter of patients are bedbound or homebound because of their ME/CFS, she added.

Yet 85% of healthcare providers believe ME/CFS is fully or partly a psychiatric condition, according to a 2011 study by Elizabeth Unger, MD, PhD, and colleagues from the CDC in Atlanta.

Lucinda Bateman, MD, founder of the Fatigue Consultation Clinic in Salt Lake City told MedPage Today,"The reason doctors stigmatize the patients is because they don't understand the illness."

A condition as complex as ME/CFS requires observation time and strong communication; patients with cognitive symptoms have difficulty communicating, and doctors have less and less time, so the disease became "an annoyance," she said.

Carol Head, MBA, president of the Los Angeles-based Solve ME/CFS Initiative, a patient-centered research organization, told MedPage Today, "I can think of few things that would do more to lighten the burden for [ME/CFS] patients than to have every physician believe it's real."

For decades, the ME/CFS medical community have battled for recognition for a misunderstood condition. But within the last year, healthcare agencies have taken the first key steps towards giving the disease more attention.

A Turning Point

In February 2015, the Institute of Medicine (IOM) published a report that offered clinicians a better definition for ME/CFS. Bateman and Chu were members of the IOM expert and review committees, respectively.

The report presented streamlined diagnostic criteria for ME/CFS and highlighted "post-exertional malaise," or increased difficulty functioning after even minimal cognitive or physical activity as a hallmark symptom, that should persist for at least 6 months.

More importantly, the IOM report validated the message patient and advocacy groups had been pushing for decades -- that ME/CFS is a debilitating, multisystemic, medical illness.

It also noted that as many as 2.5 million people in the U.S. may have the disease, but 84% to 91% of patients go undiagnosed.

While Bateman said "the IOM report is gold," Robert Miller, a patient of 30 years from Reno, Nev., described it as "a call to action and a blueprint for research."

In addition to describing the disease's core characteristics, the panel chose a new name: Systemic Exertion Intolerance Disease (SEID) for the disease. The panel felt the new name better characterized the systemic nature of the illness while alluding to its core symptom of post-exertion malaise.

Expert Response

At a meeting in August, the Chronic Fatigue Syndrome Advisory Committee (CFSAC) to the Department of Health and Human Services (HHS) met to discuss the IOM report, and a report from an NIH working group, and made 16 recommendation to HHS Secretary Sylvia Burwell. They included:

Prioritize the development of biomarkers and objective diagnostics tests

Address gaps in basic translational, clinical, and epidemiological research

Advance treatments and therapeutics

Provide funding commensurate with the burden of the disease

Use the diagnostic criteria to educate and inform

The advisory committee voted on whether to recommend SEID as the new name for the condition, but ultimately suggested use of the disease's historical name, myalgic encephalomyelitis.

Funding a Priority

Both the IOM report and the CFSAC recommendations emphasized the dearth of federal investment in the disease.

The economic burden of ME/CFS to society -- based on lost productivity and medical expenses -- stands somewhere from $17 to 24 billion annually, according to the IOM.

Yet NIH spent only $5 million on the disease in fiscal year 2015. An agency report ranks funding for the condition at 231 out of 244 disease research categories, noted a patient's open letter to Francis Collins, MD, PhD, director of the NIH, in the Washington Post.

Moreover, NIH's grant review process leaves little room for optimism. Only 12% of grants are approved each year, Head said. It takes only takes one of 10 experts reviewers to doubt the validity of the illness and "that's the end of the game," she said.

Head, a member of the CFSAC committee, has urged the NIH to create an independent set of funds to be earmarked for ME/CFS, "so we have a shot."

Currently, ME/CFS researchers compete for funding against better-known diseases. The NIH prefers to invest in disease research that has preliminary results from smaller studies, so ME/CFS researchers continue to have "a chicken and egg problem."

Head would also hope for less turnover on review panels, as having to explain ME/CFS to even one new committee member increases the chance that the condition will not be given serious consideration, she explained.

Head estimates that $250 million is needed annually to match the burden of the disease with its research needs. Some advocates -- including MEAction, an online platform and nonprofit based in New Jersey -- are lobbying Congress to add an ME/CFS funding provision to the 21st Century Cures Act.

CFSAC recommended that the disease be assigned a home at the National Institute of Neurological Disorders and Stroke, arguing that such a move would increase accountability for research.

Pathology Unknown

Research on the cause of ME/CFS has been challenging. "There are more gaps than substance," Head said.

One current theory is that the disease is caused by an immune system malfunction following an infection of Epstein Barre Virus (EBV). However, the IOM noted "there is insufficient evidence to conclude that all cases of ME/CFS (SEID) are caused by EBV or that ME/CFS (SEID) is sustained by ongoing EBV infection."

Mady Hornig, MD, professor of epidemiology and director of translational research at Mailman School of Public Health at Columbia University in New York City, recently led a study on biomarkers associated with the illness. If the disease is a post-infection disorder, Hornig's group theorized that an infection may rev up the body's immune system, but then has a tough time shutting down the response for some unknown reason.

Hornig said more research on patients in the early stages of the disease will help researchers understand how it evolves.

"We think that this could have implications for how you should treat ME/CFS, early on as opposed to later in the illness," she said.

Future Research

Studies of ME/CFS have been criticized for their small sample sizes, but this is often because they are poorly funded. Recruiting patients, many of whom are homebound, is difficult. Also, participating in a study can mean days and weeks of worsened symptoms, even in patients who are not severely ill.

ME/CFS study populations often include more women then men -- usually middle-age white women -- so the results may not be generalizable to other groups.

Generalizability was a limitation in a study by Jason's group that found suicide among the top three causes of death in patients with ME/CFS, along with cancer and heart disease. His group also found that ME/CFS patients who died from cancer were "considerably younger" than those who died from cancer in the general population. But the group used a memorial list from an ME/CFS foundation as its main data source so the results did not have wide application.

Despite these barriers, there is a pressing need for more research, such as longitudinal studies to understand the course of the disease over time; treatment trials, to see if the care being provided is actually helping patients; and biomarker-based studies, Bateman said.

Treatment

There are currently no FDA-approved drugs for ME/CFS so patients must pay out-of-pocket for medications that offer some relief. Most patients follow a trial-and-error approach to treatment, testing off-label options, and alternative-complementary therapies.

In 2013, the FDA rejected a new drug application for rintatolimod (Ampligen) from Philadelphia-based Hemispherx, after the Arthritis Advisory committee voted against recommending approval for ME/CFS. However many patients, including Miller, take rintatolimod off-label for ME/CFS symptoms.

Another treatment option under consideration is the monoclonal antibody rituximab (Rituxan). A small 2011 trial found that two-thirds of ME/CFS patients who received the drug showed improvements in their symptoms. Eleven of the 29 subjects were still in remission 3 years after treatment, reported New Scientist.

There are currently six open new drug applications for the treatment of ME/CFS under review at the FDA, according to an FDA representative who spoke at the CFSAC meeting.

Education

Only one in three medical schools include ME/CFS information in their curriculum and only 40% of medical textbooks include material related to the disease, according to the IOM.

The IOM report recommended that ME/CFS be included on medical licensure exams, and that workshops be sponsored at major medical conferences focused on the condition. It also urged collaboration with large healthcare systems.

"To me, the biggest need in the field is for all doctors to be trained about this illness and to fold it into what they do everyday," Bateman said.