Can Fibromyalgia be Detected Through Blood Tests?

Is There a New Blood Test on the Horizon for Difficult to Diagnose Fibromyalgia?

The race is on for a diagnostic test for Fibromyalgia. Whoever discovers the first reliable test will help millions of people have their health complaints validated and will become very famous and likely make a lot of money if the test can be patented. As a result authors of new but still preliminary findings are suggesting that their work could lead to a diagnostic test. Authors and journals are putting early results into the media and generating interest on FM websites and blogs. While any one of three recent findings discussed below may be valid, it is a bit early to get too excited. I have been in the field long enough to see many new exciting ideas come and go. Usually, this is because researchers make an observation in a small group of patients/participants which doesn’t turn out to be generally true for all patients with Fibromyalgia. 

Since Fibromyalgia is a total body condition it undoubtedly affects more than one system and more than one test in more than one body system may turn out to be useful. As well, there may be subsets of patients who differ from each other. This is very useful to know as treatment approaches may differ among testable subsets. Knowledge is power. So read on… to see three different approaches being researched.

How Could a Blood Test Work for FM? Will Cytokines be the answer?

Behm, F.G., Gavin, I.M., Karpenko, O., Lindgren, V., Gaitonde, S., Gashkoff, P.A., & Gillis, B.S. (2012) Unique immunologic patterns in fibromyalgia. BMC.Clin Pathol., 12, 25.

In this study, conducted at the University of Illinois at Chicago, the researchers compared blood samples of 110 patients with FM and 91 healthy controls. The Fibromyalgia patients had an average age of 53 years and had been ill on average for 16 years. The blood of each participant was drawn and the peripheral blood mononucleocytes (PBMCs), which includes most of the immune cells, were separated and grown (cultured) in a petri dish. The level of immune chemicals (cytokines) they produced was measured before and after the cells were exposed to molecules that they interpret as an immune threat. In healthy immune cells, the level of immune chemicals increases significantly after such an exposure – the immune system is ramping up to fight the threat. The PBMC stimulation test is a very standard one in research and some advanced clinical labs and measures the functional capacity of immune cells – do they respond to threats appropriately?

Before the immune stimulation, the levels of cytokines in the cell cultures were very low in both groups. This is what one would expect. In the healthy group, the cytokine levels increased as expected after stimulation.  In the Fibromyalgia group, the cytokine levels increased far less. Although mixed, the body of research seems to be growing that patients with FM and other chronic pain conditions show decreased production of the cytokines IL-6, IL-8, IL-10 and IFN-gamma under stimulation conditions. Regular blood cytokine tests don’t reliably show an FM profile. The reaction to the stress of antigenic stimulation seems necessary to see a difference in immune function between FM and other groups. As I have noted in previous newsletters, most of these cytokines are both elevated and easily stimulated in patients with ME/CFS.

The authors conclude that FM is not a rheumatologic, neurologic or psychiatric condition but an immune condition. Only 9 of the FM group suffered from depression at the time of the study and their results were not different from the rest of the group “proving that depression by itself had an extremely limited impact on the cytokine profiles in FM patients”.

What About a Molecular Signature?

Hackshaw, K.V., Rodriguez-Saona, L., Plans, M., Bell, L.N., & Buffington, C.A. (2013) A bloodspot-based diagnostic test for fibromyalgia syndrome and related disorders. Analyst, 138, 4453-4462.

This study recently published by researchers at the Ohio State University compared the substances present in the blood of small groups of patients with Fibromyalgia (14), Osteoarthritis (12) and Rheumatoid Arthritis (14). They used two strategies to identify the molecules present in the blood.

Infrared spectroscopy measures the vibration of molecules after they are exposed to infrared light. Using this method each molecule has its own fingerprint. Using this test no single molecule differentiated the blood of the FM group from the blood of the two arthritis groups. Therefore the researchers used complicated statistics to identify variations in the profiles of the two groups. Using a strategy called SIMCA they were able to identify the blood from FM patients with 100% accuracy. This high level of accuracy is rare in medicine. However, one must remember the sample sizes are very small and replication will be critical to see if the test is as accurate in larger samples.

The group also compared blood samples using metabolomics analysis. This strategy uses mass spectrometry to identify molecules present in human blood. Each molecule present has a unique fingerprint and many of the fingerprints are identified (ie. we know which molecule they refer to).  For this part of the study, there were 10 participants in each of the three groups. About 30 molecules had different profiles in the FM, OA and RA groups. However, the diagnostic accuracy using this approach was only 75% (in other words they would predict the wrong disorder in 25% of cases). For a test to be useful in clinical practice the accuracy should be 99% or higher. Otherwise too many people will be harmed by receiving inaccurate results.  The molecules that differentiated between the groups included several amino acids, molecules involved in tryptophan metabolism, molecules associated with oxidative stress, glucose utilization and with hemoglobin synthesis.

Is Fibromyalgia a Neuropthy?

Albrecht, P.J., Hou, Q., Argoff, C.E., Storey, J.R., Wymer, J.P., & Rice, F.L. (2013) Excessive Peptidergic Sensory Innervation of Cutaneous Arteriole-Venule Shunts (AVS) in the Palmar Glabrous Skin of Fibromyalgia Patients: Implications for Widespread Deep Tissue Pain and Fatigue. Pain Med., 14, 895-915.

This is the most complicated of the three studies to understand in detail but the punch line is clear and important. In this study, the research team from upstate New York were challenging the now widely accepted belief that Fibromyalgia is a “central” pain disorder. It is now accepted that the source of pain in FM comes from the pain volume regulators in the brain and spinal cord and not from the peripheral tissues of the hands, arms and legs that appear sore. There have been a few dissenting voices to this central pain theory, one published a year ago by Calgary neurologist Cory Toth who found abnormalities in skin biopsies in FM patients. The New York group took tissue biopsies from the thumb side of the palm of the hand of women with FM and compared these biopsies with those from age, gender-matched healthy individuals.

The tissues were stained and examined under a microscope to identify the types and prevalence of nerve fibres in the biopsy samples. In the samples from the participants with FM, they found abnormal types and numbers of nerves at the place where the arterioles become venules ... the place where blood flow to the tissues occurs.

The authors found more small sensory nerve fibres in the palms of the FM group than in the healthy group. They hypothesize that this may account for increased hand tenderness in FM. As well, since this area is important for the control of blood flow, the nerve changes could lead to decreased circulation and insufficient oxygen in the deep tissues ... maybe explaining the sensation often expressed by patients with FM of “poor circulation”. They also noted that women have twice the sensory innervation to this arteriole-venule region than men. Thus women may be more prone to pain or circulation changes from increased nerve growth than men. The research group is now extending their study to men to see if it is the same or different.

This study is interesting as it broadens the scope of FM pathology to peripheral tissues and suggests it may not be “all in the head” after all. Or it may be that central changes cause peripheral changes or vice versa. In any event, the media reporting from this study that “Fibromyalgia has finally been explained” seems premature. Many aspects of the findings need to be replicated and the interpretations are complex and far from clear (at least to me).

Author: Eleanor (Ellie) Stein MD FRCP(C)

I am a psychiatrist with a small private practice in Calgary and am an assistant clinical professor in the faculty of medicine at the University of Calgary. Since 2000, I have worked with over 1000 patients, all with ME/CFS, FM and ES. My passion for this field comes from my own struggle with these diseases, my desire to improve my health and then pass on what I learn. My goal is for every patient in Canada to have access to respectful, effective health care within the publicly funded system. 

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