A recent study published online in a supplement to Arthritis & Rheumatology looked at the prevalence of fibromyalgia among patients with ankylosing spondylitis, finding a high prevalence, at 43%. Lead investigator Marina N. Magrey, MD, of Case Western Reserve University and MetroHealth Medical Center in Cleveland here describes the study findings. Click here to download a detailed abstract of this study.
Further discussion of fibromyalgia in the context of other chronic disease is provided by Carmen Gota, MD, of Cleveland Clinic.
Magrey: We did this study to answer a very important clinical question, whether tools of disease activity in ankylosing spondylitis measure just the inflammatory pain or do they even measure fibromyalgia pain?
Ankylosing spondylitis is … it’s a chronic inflammatory disease that predominantly involves axial skeleton and is associated with human leukocytic antigen B27. It’s characterized by inflammation in the spine, peripheral joints, and entheses, resulting in pain, fatigue, and stiffness.
So despite significant progress made in the treatment of ankylosing spondylitis, there are many patients who continue to have persistent pain, and this pain may be related to their disease activity or may be unrelated to their disease activity, and in those patients, we think the pain may be coming from this chronic, nonarticular fibromyalgia syndrome.
It’s very important for the clinician to actually be able to detect fibromyalgia in these patients, because based on that, they could decide whether they want to continue treating these patients or de-escalate these patients.
Tools for Measurement
Now we do have two very reliable tools of disease activity in ankylosing spondylitis called Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASDAS. Both of these are patient-reported outcomes. ASDAS is an improved version of BASDAI, because it not only incorporates the patient-reported outcomes, but it also includes in it ESR and CRP, which is … values, which are more objectively reflecting inflammation.
Both of these tools measure fatigue, stiffness, back pain, tenderness, and peripheral joint pain. There have been some studies in the past which have actually shown that the Bath Ankylosing Spondylitis Disease Activity Index may not be specifically measuring inflammatory pain and may actually be measuring fibromyalgia pain. So we were kind of quite intrigued since we routinely use these tools in our clinical practice to assess disease activity to test whether they were really measuring fibromyalgia pain or not.
So we can hypothesize that these patient-reported outcome disease activity tools in AS, actually not only measure inflammatory pain, but were also measuring fibromyalgia pain and severity. So based on this hypothesis, we decided to test this in a proper study.
It was a cross-sectional prospective study. We prospectively enrolled 62 patients with ankylosing spondylitis from our arthritis clinic. In order to get included in the study, the patient should have been at least 18 years of age and had to fulfill New York classification criteria for ankylosing spondylitis and had to have grade 3 or grade 4 sacroiliitis. We wanted to make sure that the patients had established ankylosing spondylitis.
Then we administered these patient-reported outcome tools such as disease activity to these patients. We also measured their ESR and CRP, which are routinely used to assess disease activity by rheumatologists. To measure the frequency of fibromyalgia in these patients, we based it on 2010 ACR diagnostic criteria for fibromyalgia and asked the patients to record their widespread pain index scores and symptom severity scores.
The Study Results
So the results of the study were quite surprising. So we found about 27 out of the 62 patients fulfilled the 2010 diagnostic criteria for fibromyalgia, the ACR diagnostic criteria for fibromyalgia. So the estimated prevalence based on this was pretty high. It was much higher than we had seen in … has been seen in previous studies.
The two groups of patients with fibromyalgia and without fibromyalgia were not much different, at least in terms of age. The median age was about 49 years, and there was no difference in gender. There was no difference in use of biologics between the two groups. The only significant difference that we found between the two groups was that African Americans were more likely to have fibromyalgia compared to Caucasians.
Our main aim of the study was to test the relationship between BASDAI and ASDAS scores with that of widespread pain index and symptom severity scores using logistic regression analysis. We did not find any significant association between these two scores. We did not even find any association between ESR and CRP and widespread pain index and symptom severity scores, so we were unable to prove our hypothesis.
We do acknowledge some limitations of the study. The limitations are that, firstly, it was a small cohort of patients. Another, that our patients who were included in the study had very high disease activity index and which may have caused some kind of bias. Hence, the prevalence … estimated prevalence of fibromyalgia, which we detected, was very high.
So to … for practical purposes, the study helped us 1) that those patients with ankylosing spondylitis with a very high disease activity scores, the clinicians should look for fibromyalgia symptoms in these patients because we found those patients who had very high disease activity scores tend to have more fibromyalgia than patients whose disease activity scores were low. And there’s a plausible explanation for that, because these are the patients who are in pain, and when they’re in pain, they may not be sleeping well. They may not be able to do enough physical activity.
Another thing is that we found that both BASDAI and ASDAS are useful, reliable tools of disease activity in AS, hence, should be routinely used in the clinical practice to gauge treatment.
Gota: Fibromyalgia is a biopsychosocial disorder and it can be associated with a lot of other medical conditions. Patients with fibromyalgia have widespread pain, have nocturnal pain, have a lot of morning stiffness, have fatigue, and a lot of other symptoms like neurological symptoms, neurologic type pain, difficulty with memory and concentration, and oftentimes they have associated depression and anxiety or other mood disorders.
The symptoms of autoimmune disorders and other inflammatory diseases can also be those of chronic pain. They can also be associated with nocturnal pain, morning stiffness, and fatigue. The presence of pain can affect how people will sleep. So sometimes for the clinician it’s difficult to differentiate which one is the reason for the patient’s complaints.
If you look at people with chronic conditions, for instance rheumatoid arthritis, about 20% of those patients probably have fibromyalgia. The percentage depends on the study and the way fibromyalgia was assessed. If you look at the literature in ankylosing spondylitis or psoriatic arthritis — the seronegative spondyloarthropathies — it’s about 15%, but there’s one study that shows a higher percentage. This was a study of ankylosing spondylitis in females, and they reported about 50% of those patients also had fibromyalgia. So in patients with chronic illnesses the prevalence of fibromyalgia is higher. We believe that’s happening at least partially because these are chronic stressors.
You can diagnose fibromyalgia in several ways. The most important thing is by discussion with the patient. At the time of the clinical encounter when you listen to the patient, how the patient describes the pain and the associated symptoms, you get a sense that the fibromyalgia may be an issue. The most important aspects that make you think somebody has fibromyalgia are as follows. One, the pain is going on for a long period of time. Also the pain is generally widespread. It affects the back, the upper extremities, lower extremities, sometimes chest, abdomen. And there are features of the pain that are very suggestive of fibromyalgia. The pain occurs with rest. It’s worse after exertion but has some degree of improvement with activity.
It’s also strongly associated … when the patients describe the pain they use a lot of color. They describe it oftentimes in dramatic terms — stabbing, burning, unbearable, and often they use what we call neuropathic characteristics for the pain. So patients will say it’s burning, tingling, which is a little different from other conditions like rheumatoid arthritis where these kinds of neuropathic aspects are missing.
Also the pain is almost always associated with fatigue. These patients have a lot of fatigue, they have nonrestorative sleep, and they also describe, which untrained clinicians are not aware of, a lot of stiffness. In our patient population at the Cleveland Clinic, we found that about 60% of patients with fibromyalgia reported morning stiffness of more than an hour. So that can sometimes be confusing because we usually associate morning stiffness with inflammatory conditions.
This Study’s Findings
Well their results are surprising if you look at several other papers. There is one recently that was published in September from France, where they looked at patients with ankylosing spondylitis, they looked at patients with psoriatic arthritis, and the prevalence was about 15% of comorbidity between fibromyalgia and spondyloarthropathy. I don’t know why this study found such a high prevalence. It is well known that women who have ankylosing spondylitis have a higher prevalence of fibromyalgia than men with ankylosing spondylitis, but that was not what this study showed. This was just an abstract that was published and we are awaiting the more detailed publication about how the patients were recruited.
From what I read in the abstract, the criteria for fibromyalgia were the American College of Rheumatology 2010 criteria. If you look at these criteria, it’s composed of two subsets. One is the widespread pain index. That measures pain in different body parts. They’re supposed to be nonarticular but sometimes patients cannot make that differentiation. And the areas involve the upper neck, upper back, lower back, upper extremities, lower extremities, and those are also areas that hurt in ankylosing spondylitis. The other part of the American College of Rheumatology criteria includes the symptom severity score and that has four questions that grade the severity of fatigue, the severity of cognitive problems, the difficulty with sleep, and then a set of other somatic symptoms.
You can see that fatigue can occur in both patients with ankylosing spondylitis but also in fibromyalgia. A lot of the pain in ankylosing spondylitis is nocturnal so it’s imaginable that a lot of these patients don’t sleep well even if they do not have fibromyalgia. So my personal opinion, what I think in this study, is that probably the American College of Rheumatology 2010 criteria for fibromyalgia may be difficult to apply as a diagnostic tool for fibromyalgia in this subset of patients with ankylosing spondylitis because of the similarity of symptoms. So I’m not sure that these criteria correctly identify patients with fibromyalgia.
If you look at the data, patients who had ankylosing spondylitis and fibromyalgia also had higher C-reactive protein and higher sedimentation rates than the ones who didn’t, which is hard to interpret and definitely cannot be attributed to fibromyalgia. And if you look at prior studies, what they found was that actually using the CRP as a measure of disease activity was helpful in differentiating ankylosing spondylitis from fibromyalgia.
There was a very nice editorial in the Journal of Rheumatology that was associated with the article I mentioned previously from France looking at the prevalence of fibromyalgia and spondyloarthropathy. They used the term ‘contextual factors.’ So you always have to look at the whole patient. Fibromyalgia patients usually have pain for a long time, but they don’t only have pain. They also have a lot of other issues. They usually have a lot of stress in their lives. A lot of these patients have prior traumatic events. A lot of patients endure depressive symptoms, they do not sleep well, they report a lot of stiffness.
It’s very important when we consider fibromyalgia to take into consideration other factors that we may call contextual factors. Patients with fibromyalgia oftentimes have a lot of stress, their symptoms have been going on for a long time, they have disturbed sleep, and they often endure depressive and anxiety symptoms. And they have other manifestations such as symptoms of irritable bowel syndrome, migraine, which can be very helpful in understanding that this is probably fibromyalgia.
I think that patients who have both fibromyalgia and ankylosing spondylitis or other inflammatory diseases can pose a challenge for the clinician. I think the most important thing is to take a good history, listen carefully to the patient, do a complete physical examination, and oftentimes that is very helpful in differentiating the two or being able to recognize that there is more than one mechanism at play.