From the Journals

Chronic Fatigue Syndrome and Fibromyalgia: A Single Disease Entity?


 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

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