Diagnostics
at the meeting were equally unsure if they were the best specialism to care for fibromyalgia patients. “They said, if this is an autoimmune disease, these patients should probably not be with us, but at the rheumatology clinic.” From Svensson’s perspective, the answer to where fibromyalgia patients belong is unlikely to be binary, and that is not surprising. “Doctors and researchers haven’t yet fully grasped fibromyalgia, and when there is no consensus on the definite causes and few medications to try, it is difficult to determine which clinic is best suited for diagnosis and care,” she says.
She uses rheumatoid arthritis as an example of a disease for which the peripheral components could be sustaining its symptoms, much like IgG antibodies could be doing in fibromyalgia patients. “If you look at the population of [rheumatoid arthritis] patients that are successfully treated with anti-rheumatic drugs, you get a really good response from a disease activity perspective, but 30% to 50% of those individuals will still have pain.” In practice, this means the biomarkers of inflammation, like C-reactive protein levels, as well as the more obvious symptom, swollen joints, reduce – but the pain remains. If the idea of patients experiencing pain without any clear physiological reason is sounding familiar, that is because these patients are, for all intents and purposes, exhibiting fibromyalgia symptoms.
“Doctors and researchers haven’t yet fully grasped fibromyalgia, and when there is no consensus on the definite causes and few medications to try, it is difficult to determine which clinic is best suited for diagnosis and care.”
Dr Camilla Svensson, Karolinska Institutet
Even less surprising then is that of the 2–4% of people estimated to be fibromyalgia sufferers, researchers have indicated the comorbidity rate with rheumatoid arthritis to vary between 10% and 30%, depending on the region examined. For Svensson, this begs an important question regarding rheumatoid arthritis patients with persistent pain after effective treatment: “Is this fibromyalgia? Or is it just a central nervous system consequence of an autoimmune condition where patients have had long-lasting activity in the pain fibres, which has led to changes at the level of the spinal cord and brain?” This latter theory is based on the idea of centralised pain or centralised sensitisation, essentially meaning that the mechanisms behind the body’s pain signals are somehow impaired – although the cause of this impairment is unknown.
Potential treatments
The centralised pain explanation has been the dominant theory for a while now, which is why the
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research of Svensson, along with her colleagues Dr David Andersson and Professor Stuart Bevan of KCL, was so groundbreaking. In the study, the researchers injected mice with either IgG antibodies from fibromyalgia patients, or from healthy control subjects. The result was significant differences on tests designed to evaluate mechanical and cold hypersensitivity, muscular strength, and fatigue, with the negative consequences exhibited only by those given fibromyalgia IgG. The researchers also administered IgG-depleted serum as an extra control measure and found no significant differences on the tests. These results raise an interesting question: if the human IgG of fibromyalgia sufferers is pathogenic, can immunomodulation therapy eliminate the symptoms? With strong moral and ethical reasons not to try and replicate the research using healthy humans instead of mice, Andersson and Bevan believe this could be the most definitive way to test their hypothesis that fibromyalgia is sustained by IgG antibodies in the immune system.
“If we can transfer symptoms from patients to mice using the antibodies, we would also expect removing these antibodies from patients to at least give symptomatic relief,” says Andersson. “You either need to stop the production [of antibodies] in the patient, or remove them from circulation.” Perhaps one reason the likes of Andersson, Bevan and Svensson believe fibromyalgia could have an autoimmune cause is that such a treatment would be similar to that of other diseases in this category, like systemic lupus erythematosus, Sjogren’s syndrome and autoimmune forms of encephalitis – all of which tend to be managed using immunomodulatory treatments. The first port of call tends to be lowering the number of immune cells using drugs like corticosteroids, but in severe cases that fail to respond adequately to a pharmacological approach, plasmapheresis – a therapy that separates plasma from the blood – has been used to remove them altogether. Plasmapheresis is time-consuming, expensive and carries inherent risks (although, so does long-term corticosteroid use), but due to the absolute reduction of IgG, Andersson and Bevan see it as the natural litmus test in humans for their theory that fibromyalgia is autoimmune.
“The next step will be for clinical investigators to run clinical trials with plasmapheresis to see how that impacts their symptoms,” says Bevan. “It’s something we would dearly like to see done,” adds Andersson.
Cerebrospinal fluid pressure If plasmapheresis is shown to improve fibromyalgia symptoms, the case for an autoimmune basis to the disease will be stronger, and patients will continue to be sent to the rheumatology department. But another branch of researchers have been advancing a different theory for a while now. Dr Mieke Hulens, working at
Practical Patient Care /
www.practical-patient-care.com
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