By Paul Nicolaus
July 9, 2019 | Researchers from The Ohio State University have identified potential biomarkers of fibromyalgia and have differentiated the condition from several other related illnesses. They believe the discovery could be a turning point that leads to a blood test.
Fibromyalgia is a chronic condition characterized by muscle pain and fatigue throughout the body. Currently, diagnosis relies on patient history and patient-reported information as well as physical examination, X-rays, and blood work.
Without reliable biomarkers, however, diagnosis and treatment remain a challenge, and the disease is frequently misdiagnosed or left undiagnosed. It is estimated, for example, that it has taken a person with fibromyalgia five years, on average, to receive an accurate diagnosis, according to the National Fibromyalgia and Chronic Pain Association.
One notable difficulty is that many of the symptoms overlap those of other conditions. Moreover, the presence of other diseases, such as rheumatoid arthritis or lupus, does not necessarily rule out a fibromyalgia diagnosis.
The Ohio State researchers believe their work may offer new hope, however. Their study, published in the Journal of Biological Chemistry (doi: 10.1074/jbc.RA118.005816), examined 50 people diagnosed with fibromyalgia, 29 with rheumatoid arthritis, 19 with osteoarthritis, and 23 with lupus.
The work relied on a technique called vibrational spectroscopy to measure the energy level of molecules within the blood samples taken from participants. When a laser contacts certain biochemicals in the blood, it causes a vibration, said Kevin Hackshaw, a professor in Ohio State's College of Medicine and a rheumatologist at the university's Wexner Medical Center.
When that vibration is at a certain level of frequency, that frequency is conveyed on a graph as some form of curve. "We can tell by the characteristics of the curve what specific molecules have been contacted by the laser," he told Diagnostics World.
Initially, they analyzed samples from participants whose disease status was known in order to come up with a baseline pattern for each diagnosis. From there, they evaluated the remainder of the samples blindly and were able to group participants into disease categories based on a molecular signature.
What they discovered is that there are characteristic proteins, sugars, or nucleic acids that are present in blood samples of fibromyalgia patients, and that particular combination of compounds is distinct from the compounds of other conditions.
"That's why we call it a fingerprint," he explained. It is not a specific chemical but rather a specific range of chemicals that determines whether or not an individual has fibromyalgia.
The researchers concluded that vibrational spectroscopy could provide a reliable diagnostic test for differentiating fibromyalgia from other disorders and for establishing blood-based biomarkers of fibromyalgia-related pain.
In addition, they indicated that the metabolic fingerprinting technique has the potential to determine the severity of the disorder, which could help lead to improved treatment for patients.
Diagnosis Could Impact Costs and Crisis
Even though this has dissipated in recent years, Hackshaw explained that there has traditionally been some skepticism about the genuineness of this condition and about the pain of fibromyalgia patients. While most physicians no longer question whether the condition is real, he noted that there are still doubters out there.
This skepticism occurs, he said, because from a physical standpoint most patients look fine, but then they continue to complain of pain. Because fibromyalgia is often associated with a number of overlapping conditions, patients tend to have a variety of complaints. "That multiplicity of complaints becomes time-consuming," he said, "and many physicians don’t want to spend that amount of time for that particular type of condition."
The result is that patients get shuffled around and are seen by a select few physicians who may have the patience to work with them. Another typical result, he added, is that patients with fibromyalgia tend to spend plenty of healthcare dollars getting spinal taps, MRIs, and repeated blood tests for ANA or rheumatoid factor during the search for a diagnosis.
Even when the diagnosis seems clear from a clinical standpoint, many patients are not satisfied because they look okay even though they feel terrible. Coming up with a test that can lead to a definitive diagnosis, therefore, may drive healthcare costs down.
It could also factor into the opioid crisis, considering how many patients with fibromyalgia complain of chronic pain. "If you were to survey or evaluate patients who were seen in chronic pain clinics," he pointed out, "upwards of 40% of those individuals actually meet criteria for fibromyalgia."
The majority of patients in chronic pain clinics are treated with opioids. The problem, according to Hackshaw, is that fibromyalgia stems from a derangement in nerve signals and is not a condition that should be treated with opioids.
"So being able to come up with a specific diagnosis can dissuade a lot of those practitioners from prescribing opioids for these individuals who clearly have fibromyalgia," he said, "and that can help to cut into the opioid crisis."
Excitement Tempered by Caveats
Lucinda Bateman, founder and medical director of Bateman Horne Center, which focuses on fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome, told Diagnostics World that she sees the study as a novel, creative approach and views the findings as a significant development in this realm of research.
"Everything we do that shows a scientific basis for these illnesses brings them out of the shadows and into mainstream medicine where they can get an earlier diagnosis and better treatment," she said.
Along with her enthusiasm came several caveats, however. The grouping of participants into a fibromyalgia cohort is a subjective one. "It was made by rheumatologists, so I would assume that it's a good diagnosis," she explained, but there's a bit of trust involved in that element of the study.
Study participants were on their regular medications, she added, which may or may not alter the results, and there was no healthy control group included in the study.
Under the umbrella of fibromyalgia and chronic fatigue syndrome, there are many different subsets and patterns, she explained. Patients may have small fiber neuropathy, for example, or underlying metabolic syndrome. "There are these overlapping conditions threaded through," she said, "which is why it's hard to make any strong conclusions from a sample size of 50."
"I think this area of research is very promising," Bateman added, "and I hope they can do more studies" using bigger sample sizes and comparisons.
Dan Clauw, director of the University of Michigan's Chronic Pain and Fatigue Research Center, also pointed to the study's reliance on a small sample. The results have not yet been replicated, he explained, and he is skeptical that they will be.
Even if the results are replicated, it isn't known if this fingerprint pertains to fibromyalgia or a common co-morbidity such as stress or obesity. This research is "simply the first step in identifying a potential biomarker," he noted, but there's still much work to be done.
In Pursuit of a Blood Test
Hackshaw pointed out that an original study in 2013 looked at 20 patients, which preceded the recently published study that examined 50 subjects. "Now we want to do the same type of study and look at 500 patients," he said.
"There's never a shortage of subjects with fibromyalgia," he added. "We've got hundreds of patients that we don't see normally at the university who've volunteered." Within a couple of years, Hackshaw estimates that he and colleagues will be able to look at that type of data.
Within three or four years, he predicts they should have a blood test that could be easily transferable to the clinic or the bedside.
His team's recent findings, along with other findings (such as elevated levels of substance P in cerebral spinal fluid and changes in neurochemistry) have helped to document that fibromyalgia is a real condition, he noted.
"We're hopeful that having a documented, reliable blood test will help patients further along the line to where they realize that their symptoms are being taken seriously and they can have some peace about knowing what it is that they're suffering from," he said.
The advantage of a blood test is that it is cheaper and less invasive than other methods, he added. Functional magnetic resonance imaging costs thousands of dollars, for example, and spinal taps are invasive procedures. "That's why we're very excited about our study and where it could go."
The implications of this research extend beyond diagnostics, according to Hackshaw, who said there could be new hope on the treatment side as well.
"In terms of therapeutics, we recognize that fibromyalgia is not one closely clustered set of individuals with one set of characteristics," he explained. Fibromyalgia is part of a set of conditions called central sensitivity syndrome, which are all pain disorders thought to be caused by abnormal nerve responses.
Fibromyalgia is the most common, but there are several conditions within this spectrum. Individuals can be impacted by issues such as chronic migraines, temporal mandibular joint dysfunction, low back pain, or irritable bowel syndrome, among others.
These conditions are commonly overlapping, but Hackshaw believes they are all distinct. For example, there are patients with fibromyalgia whose primary concern may be pain but also deal with depression. On the other hand, some patients with fibromyalgia have pain as well as a sleep disturbance. Still others with fibromyalgia have pain and experience fatigue.
"What our research has shown, at least in preliminary stages, is that those distinct fibromyalgia subsets have differences in terms of their fingerprint," Hackshaw said, and he speculates that it is possible to determine a specific metabolic fingerprint for all of these conditions.
As his team's work moves forward, they want to identify the specific chemicals that make up the fingerprint, he said, and if these are chemicals that are not being targeted by current therapeutics, "then further studies will be aimed at targeting those particular new sites."
The ability to come up with specific fibromyalgia clinical phenotypes could help guide practitioners toward a therapy that would be most beneficial depending on that individual's symptoms.
A cluster of individuals with fibromyalgia and a sleep disturbance might be treated with a tricyclic agent, for example, to help treat pain and induce sleep. Alternatively, a patient with fibromyalgia whose major issue is cognitive slowing might best benefit from using a serotonin-norepinephrine reuptake inhibitor.
"These could be new therapeutic opportunities," he added, "that might help these patients forever."
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.