Toward Characterization and Definition of Fibromyalgia Severity
From: BMC Musculoskelet Disord. 2010 Apr 8;11(1):66. [Epub ahead of print]
Fibromyalgia is a disorder of unknown etiology that is generally diagnosed according to the American College of Rheumatology (ACR) criteria, which include chronic, widespread pain for at least 3 months, and the presence of 11 out of 18 tender points. Prevalence estimates for the United States suggest that approximately 5 million individuals have this condition, with a higher prevalence among women (3.4%) than men (0.5%). Although chronic widespread pain is the hallmark of fibromyalgia, core symptoms of fibromyalgia also include sleep disturbance, fatigue, mood disorders, and localized pain (headache, back and/or neck pain). These core symptoms are included among the domains that have been identified and recognized by OMERACT (Outcomes Measures in Rheumatology) as important for assessment in fibromyalgia.
Fibromyalgia has a substantial negative impact on quality of life, resulting in health status that is poorer than other chronic pain conditions such as rheumatoid arthritis and osteoarthritis. The burden imposed by core fibromyalgia symptoms translates into limitations of productivity, personal and family life, as well as a reduced ability to complete simple activities of daily living.
This multidimensional nature of fibromyalgia has made it difficult to define and assess the severity of fibromyalgia as a condition. The indeterminate etiology and lack of specific disease markers exacerbate the problem of assessing fibromyalgia severity. While several studies investigated the potential use of biologic markers for fibromyalgia (e.g. cytokines, antipolymer antibodies), correlation of these markers with symptoms was equivocal at best, rendering them ineffective as indicators of severity. Similarly, although tender points and a total myalgic score have been evaluated as measures of severity, they demonstrate inherent variability over time, show little correlation with other outcome measures, and importantly, neither is of clinical relevance to patients. A recent comprehensive review of potential fibromyalgia biomarkers highlighted the lack of appropriate evaluation of objective biomarkers of fibromyalgia, although limited data from a longitudinal study suggested that the results obtained during experimental pain testing were associated with clinical status improvements. However, it should be noted that in addition to sensitivity to change with clinical improvement, biomarkers need to demonstrate change with worsening disease if they are to be considered indicators of disease severity.
The ability to evaluate and measure the severity of fibromyalgia as a condition is likely to provide several benefits including identification of treatment responders in clinical trials and clinical practice. Characterization of severity levels may also be used as a marker for disease progression. Treatment approaches may be specifically targeted to patients at different levels of severity, with the potential for determining if early treatment may slow or prevent disease progression. There have been few published studies on severity or progression of fibromyalgia as a disease state, and what little has been reported about the natural history of fibromyalgia is inconsistent. Although a longitudinal study by Wolfe et al. reported no change in the severity of specific symptoms over time, a review of the few published studies suggested no clear pattern of progression or remission.
Chronic pain is the symptom of fibromyalgia that is of primary importance to patients and clinicians and is routinely evaluated as an endpoint in clinical trials and clinical practice. Although pain can be quantitatively evaluated from the patient’s perspective, it may not be an adequate surrogate of disease severity, since it may display intrapatient variability in intensity which does not necessarily correlate with the presence or severity of other fibromyalgia symptoms. A patient-reported instrument frequently used to assess fibromyalgia is the Fibromyalgia Impact Questionnaire (FIQ). Although the FIQ is sensitive to treatment effects, it evaluates the impact of fibromyalgia on various activities which may be related to, but does not actually measure, disease severity. Furthermore, the FIQ appears to have low sensitivity to clinical worsening, and it is unlikely to be an accurate indicator of disease severity.
In trying to develop a model of fibromyalgia severity, Goldenberg et al. evaluated 15 potential explanatory factors in a regression analysis. Several of the items evaluated, including pain and psychological distress, may relate to severity as contributory factors. However, others such as employment status, pending litigation, and education level, may be associated with severity in terms of impact but are not adequate for providing a definition of fibromyalgia severity as a disease state.
A study by Giesecke et al. used cluster analysis to classify patients with fibromyalgia into subgroups based on levels of mood, catastrophizing, perceived control over pain, and tenderness. While this attempt at categorization demonstrated an ability to place patients into one of three groups (moderate mood, catastrophizing and perceived pain control with low tenderness; elevated mood assessment, catastrophizing, and tenderness with low control over pain; and normal mood and catastrophizing with high pain control but extreme tenderness), these results were not placed in the overall context of disease severity.
The purpose of the current study was to initially characterize fibromyalgia severity from the perspective of individuals with fibromyalgia and to determine if patients’ perception of fibromyalgia severity is more than simply their pain. We utilized data from a larger fibromyalgia patient study to conduct a post-hoc exploratory analysis of symptom severity. Data were collected on several self-reported parameters including patient-rated disease severity and the presence of core comorbid conditions, we report here the preliminary evaluation of whether patient self-reported severity of fibromyalgia is associated with corresponding severity of pain and sleep interference and the presence of core co-morbidities. This patient perspective is also complemented with the results of a small physician survey designed to understand the physicians’ perspective by capturing information on what characteristics the physicians use to assess fibromyalgia severity in their daily clinical practice.
This study suggests that the association of fibromyalgia severity with symptoms that have been identified as being of clinical importance by patients and physicians, and are considered by OMERACT to be among the core fibromyalgia symptoms for evaluation, may be useful for the characterization and assessment of the severity of fibromyalgia as a condition. In particular, with higher self-reported fibromyalgia severity, i.e. from mild to moderate to severe, an associated increase was observed in pain, sleep disturbance, and depressive symptoms, as well as the use of medications for fibromyalgia and the presence of comorbid conditions including back and neck pain. Therefore, these characteristics may contribute to the patient’s overall perception of disease severity.
Determining a definition of fibromyalgia severity could be helpful for disease management. A definition based on the patient’s perspective may be especially useful, since in the absence of objective disease biomarkers it relies on readily available information of clinical relevance to the patient that can be used by physicians for patient classification and management. The only other study that attempted to develop a severity model also used a patient-reported outcome, global VAS, as the anchor for fibromyalgia severity [20]. While the current study did not use a validated measure, the anchor for fibromyalgia severity was a question specifically addressing fibromyalgia rather than a global assessment.
The use of patient self-report is increasingly being accepted and applied as a method to evaluate disease states and management strategies in clinical trials, especially for chronic pain conditions [25]. This has been true for the rheumatic diseases including fibromyalgia, for which most of the core domains considered by OMERACT as being essential for evaluation, are patient-centric. The top five of these domains include pain, fatigue, patient global, sleep, and multidimensional function. These domains are generally the same as those identified as being important by patients, i.e. pain or physical discomfort, aching joints or pain, lack of energy or fatigue, effects on sleep, and problems with attention or concentration. Patients may have a better sense of their condition than can be obtained using objective clinical criteria, and at least in some rheumatic conditions, patient-centered outcomes may also discriminate between placebo and active treatment as well as or better than objective clinical measures.
While two factors identified in this exploratory analysis, i.e. pain and depression, were previously identified by Goldenberg et al. as having a potential relationship with fibromyalgia severity, the results reported here also suggest that overall, patients with longer fibromyalgia duration tended to report greater fibromyalgia severity. However, it should be noted that there was a small increase in the proportion of patients reporting mild severity among the patients with fibromyalgia duration > 10 years relative to those having a shorter duration. Although the reason for this increase was not explored, it could potentially be due to adaptation or a greater ability to cope with a chronic condition among some patients. This is consistent with what was reported by Kennedy et al. in one of the few long-term (10-year) follow-up of patients with fibromyalgia; at 10 years, despite the presence of symptoms that showed little change from the initial survey and continued use of medication, a substantial proportion of patients reported that they felt better in terms of fibromyalgia symptoms.
The observed relationship between fibromyalgia severity and duration is in contrast to Goldenberg et al. who reported that there was no relationship between these variables. Their observation may potentially result from use of a global assessment rather than a more specific fibromyalgia assessment. Similarly, the results reported here diverge from a previous study which reported that symptom severity does not change over time. However, that study used more compressed assessment scales for sleep disturbance and pain (0-3 visual analogue scales) than the current study (0-10 NRS) and did not stratify patients by fibromyalgia duration. If such an association between duration and severity can be confirmed, it may provide an opportunity to identify patients early in the disease continuum and eventually modify or delay disease progression through the use of pharmacological and/or non-pharmacological interventions.
The observation that the NRS scores for sleep disturbance were higher than NRS pain scores across all levels of fibromyalgia severity appears to be consistent with a recent analysis showing that sleep problems were predictive of pain, although it is unlikely that the relationship between sleep and pain is unidirectional. However, the data do suggest that these two variables may be central, although not exclusive, components for defining severity of fibromyalgia, and that management of both pain and sleep problems are integral to the treatment of fibromyalgia.
In contrast to the patient survey, which was closed-ended and elicited severity information based on specific symptoms and comorbidities, the physician survey was open-ended. This physician survey demonstrated that, consistent with the absence of an adequate definition of fibromyalgia severity, there was a general lack of consensus regarding criteria that physicians use as an indicator of fibromyalgia severity. That pain was the most frequently used criterion of severity was not surprising considering that pain is often the primary complaint of patients with fibromyalgia. However, despite being ranked first as an indicator of severity, only 61% of the physicians considered pain the primary criterion. There was little concordance on the use of other criteria, including several of the factors that demonstrated a relationship with higher levels of self-reported fibromyalgia severity, i.e. sleep interference and the presence of comorbidities, which were identified by only 43% and 32% of physicians, respectively. The small sample size (N = 28) may have contributed to this lack of concordance.
Although functional disability was ranked second and fatigue was ranked third, these criteria were used overall by 54% and 39% of physicians, respectively. These particular criteria, although identified by physicians, were not assessed in patients as part of the patient survey, and may be considered a limitation of the study, especially since fatigue is a frequent complaint among patients with fibromyalgia. Indeed, while the patient and physician surveys provide complementary information regarding perceptions of fibromyalgia severity, the different manner in which the surveys were performed precludes comparison of these surveys, since patients were asked to rate severity but were not asked to rank symptoms.
Since physicians identified and ranked criteria in response to a question (“When you assess the severity of fibromyalgia as a condition in your patients, what are the top 5 items [specific symptoms, specific physical findings, specific abnormal lab findings, etc.] that influence your decision-making?”), physicians were not specifically queried as to how these assessments are made. It should be noted that objective clinical assessment using tender points was cited by only 18% of the physicians, and that nearly all the other criteria were patient-centric. The variety of criteria that these physicians, who routinely treat fibromyalgia patients, reported using and the lack of concordance on their use, reinforces the need to define what constitutes an adequate measure of fibromyalgia severity. Being able to define and measure fibromyalgia severity may have practical benefits in terms of understanding disease progression and evaluating treatment approaches for their potential ability to slow progression. The ability to slow progression is likely to have a broader clinical and economic impact by reducing health resource utilization and associated costs.
This study explored the patient and physician perspective of fibromyalgia severity. With greater patient reported fibromyalgia severity, there was an increase in other patient reported variables including pain and sleep interference, presence of comorbid conditions and use of medications for fibromyalgia. This study also suggests that physicians use different domains to rank fibromyalgia severity. Both these findings need to be validated in further studies. When evaluating severity of fibromyalgia, physicians should consider the patient perspective.
Source: Toward Characterization and Definition of Fibromyalgia Severity
