Pain, functional disability, and their Association in Juvenile Fibromyalgia Compared to other pediatric rheumatic diseases

Juvenile primary fibromyalgia syndrome (JPFS) affects up to 6% of otherwise healthy children and commonly leads to subspecialty evaluation with a pediatric rheumatology provider [1‐3]. The primary symptom of JPFS is widespread musculoskeletal pain that persists in the absence of an underlying inflammatory disease or other medical condition. In at least a subset of youth with JPFS, pain is associated with significant and enduring impairment in the ability to participate in usual activities and maintain positive well-being [4‐7]. Reducing this functional impairment often is regarded as a primary goal of treatment for JPFS. This treatment goal is based in part on the clinical tenet that the perception of pain often improves once functional ability is optimized [8]. Thus, a strong association between severity of functional disability and pain in JPFS is assumed in treatment and has been partly borne out in extant research.

For other medical conditions commonly managed in pediatric rheumatology, levels of impairment in functioning and well-being also can be substantial. For example, children with juvenile dermatomyositis (JDM), systemic lupus erythematosus (SLE), or juvenile idiopathic arthritis (JIA) have significantly reduced scores on measures of health-related quality of life (HRQOL) relative to healthy peers [9‐12]. The prevalence and severity of pain in most pediatric rheumatic diseases, however, rarely has been systematically studied [13]. Consequently, the extent to which pain is associated with indices of functioning across pediatric rheumatic diseases is largely unknown. Determining this would help inform the conceptualization and comprehensive treatment of JPFS and other pediatric rheumatic diseases.

Multi-site patient registries offer an optimal means of comparing clinical data across conditions. Registries use observational study methods to collect high quality data in naturalistic clinical settings [14]. Data elements typically are specified consistently, captured uniformly across sites, and are considered to accurately represent the clinical status of patients. For diseases with relatively low prevalence in particular, multi-site registries can be instrumental in ensuring sufficient sample sizes to make generalizable inferences from comparative observational research.

For the current study, we used data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry to achieve the following aims: (a) to quantify the occurrence and intensity of pain across a representative sample of pediatric patients diagnosed either with a chronic idiopathic musculoskeletal pain condition (JPFS) or another rheumatic disease; and (b) to determine if the strength of relationship between pain and functioning is unique to JPFS or comparable across diseases seen in pediatric rheumatology. We hypothesized that levels of pain and disability, and the magnitude of their association, would be uniquely high among youth with JPFS relative to youth with other rheumatic diseases.

Patients with JPFS were found in this study to reliably report both higher levels of pain and more impairment in functioning than children with any other rheumatic disease. The degree to which pain is associated with impairment in functioning and well-being, however, was found to be variable across rheumatic conditions. Results suggested in particular that the occurrence and level of pain in patients with JIA, JDM, SLE, and MCTD is robustly linked to indicators of greater impairments in functioning.

This study further confirms that severe pain and impairment in functioning is typical in youth with JPFS who are seen in pediatric rheumatology clinics. This is a common observation in research on youth with idiopathic chronic musculoskeletal pain [4, 6, 25, 26]. A distinguishing feature of the current study, however, is that uniformly collected data were aggregated into a registry from multiple sites across North America. Thus, results are likely generalizable beyond the idiosyncrasies of a particular region or practice. Further, we were able to compare identical measures of pain and functioning across conditions managed in pediatric rheumatology. To our knowledge, such comparison has not been previously done. Results of these analyses suggest that levels of pain and functional impairment on average are more severe in JPFS than other conditions encountered in pediatric rheumatology. Similar findings were reported in a recent adult study comparing indices of HRQOL across rheumatic diseases; fibromyalgia was second only to rheumatoid arthritis in its impact on functioning [27]. There are multiple potential reasons for these findings. Youth with JPFS often are likely to have comorbid symptoms of anxiety and depression, which can further augment pain perception and problems with functioning and quality of life [6]. Pain in JPFS also is partly a function of “amplification” (or disordered regulation) of nociceptive input and is the primary symptom affecting youth with JPFS; this is not necessarily the case in other pediatric rheumatic diseases. Pain and impairments in functioning in JPFS may also be difficult to significantly modify with the resources available to most pediatric rheumatologists. Alternatively, children with a rheumatic disease may be more likely than youth with JPFS to downplay or underreport problems with pain and functioning to their care team out of concern that reporting such problems could lead to increased bothersome medical treatment.

The ability to compare the relationship between pain and indicators of functioning in the current study facilitated some unique findings. Pain in JPFS has a relatively well-established moderate association with functional limitations [4]. Patients with inflammatory rheumatic disease and connective tissue disorders (JIA, JDM, SLE, and MCTD), however, were observed in our study to have a comparatively stronger relationship between pain and functional disability. Identifying similarities in the manifestation of the disease process in these particular rheumatic diseases may help explain this finding. For example, it may be that the quality and/or location of pain experienced with these conditions is especially limiting for participating in the physical activities typically enjoyed by children and adolescents. Pain in these conditions, when high or enduring, may also result in aggressive disease-modifying treatments that have adverse consequences for functioning. Alternatively, pain may work synergistically with other disease symptoms (e.g., muscle weakness, arthritis) common in these conditions to further augment existing functional impairment. In the absence of further research, possible explanations remain speculative. Nevertheless, the results further establish the unique importance for assessing and treating pain in pediatric rheumatology. Managing disease activity understandably is the central focus in treating rheumatic disease [28]. Regardless of disease activity level, however, we observed a relatively robust relationship between pain and functional disability across most pediatric rheumatic diseases.

Use of data from the CARRA Legacy Registry enabled an evaluation of clinically relevant research questions that otherwise would have been difficult and costly to conduct. This registry provided the infrastructure for secure collection, storage, and sharing of uniformly collected data from multiple informants for over 9000 pediatric rheumatology patients [29]. Cross-condition comparisons were made possible by having included common data elements in the registry, supplemented by data collection forms specific to each disease. Despite these advantages, there also were limitations associated with use of registry data for the current study. Measures used to evaluate pain and functioning sacrificed comprehensiveness for efficiency and universality. The selected measures (e.g., the CHAQ) unlikely fully captures the nuances of pain and functional impairment for all conditions evaluated in the study. Patients enrolled in the registry also were a “convenience sample” being treated in pediatric rheumatology and were able to speak and read English. Further, not all 56 clinical sites contributed data on each condition in the registry; for example, fewer than half of sites contributed data on patients with JPFS. Patients in the fibromyalgia sample also were required to meet classification criteria commonly used in research (American College of Rheumatology criteria if > = 18 years old or Yunus and Masi diagnostic criteria if < 18 years). Thus, although use of the registry facilitated access to data from representative cohorts of patients, there may still be limits on the generalizability of findings. Data for the current study also were collected at a single occasion during any point of a patient’s disease course. Levels and associations of the variables studied may have varied had we evaluated them prospectively.

Results of the current study further confirm that pain and impairment in indicators of functioning often are severe in youth with JPFS but may be even more connected with one another in patients with other rheumatic diseases including JIA, JDM, SLE, and MCTD. Pain appears to reliably relate to perceived impairments in typical daily functioning and overall well-being across these conditions. Historically pain has been less routinely assessed or targeted for treatment in many pediatric rheumatic disease relative to more objective indicators of disease activity. Pain and optimal approaches to minimize its impact also have been rarely studied in several of the pediatric rheumatic diseases. However, more routine incorporation of pain and other patient-reported outcomes into patient registries in part is helping to address this [29‐31]. Our findings emphasize that pain across conditions commonly managed in pediatric rheumatology would benefit from continued increased prioritization in assessment, treatment and research.