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Abstract
Background Pain is considered a priority for research by adult patients with autoimmune inflammatory myopathy (AIM) and their families. Our aim was to review the literature for studies reporting on pain in adult AIM and to summarise their findings.
Methods A scoping review was conducted searching for studies in PubMed and MEDLINE including more than five adult patients with AIM and assessing pain using a patient-reported outcome measure. Study population characteristics, pain measurement and clinical correlates of pain were extracted using a standardised protocol.
Results The search strategy identified 2831 studies with 33 meeting inclusion criteria. Most studies used visual analogue scales (n=14) and/or the Medical Outcomes Study 36-Item Short Form Bodily Pain Scale (n=17). Frequency of pain and/or myalgias ranged from 64% to 100%. Subjects with AIM had significantly more pain than the general population and comparable pain to other chronic rheumatic diseases. Insufficient results were available to identify significant clinical correlates of pain in AIM.
Conclusion This review suggests that the burden of pain in AIM is considerable. Still, due to the heterogeneity and low quality of the evidence, significant knowledge gaps persist. Studies are needed to characterise pain trajectories of patients with AIM.
- dermatomyositis
- polymyositis
- patient reported outcome measures
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What is already known on this topic?
Pain in autoimmune inflammatory myopathy (AIM) is considered a high priority for research by patients and their families. However, little is known about the pain experience in AIM.
What this study adds?
Based on patient-reported outcomes measures, the burden of pain in AIM is considerable. Important gaps in the literature were identified notably concerning clinical correlates of pain in AIM.
How this study might affect research, practice or policy?
Longitudinal studies are needed to characterise the pain experience in AIM including predictors of severity and clinical correlates to identify possible pain mechanisms and offer targeted management to patients.
Introduction
Autoimmune inflammatory myopathies (AIMs) are rare chronic autoimmune diseases characterised by muscle inflammation and weakness. Major AIM subsets are dermatomyositis (DM), antisynthetase syndrome, overlap myositis, immune-mediated necrotising myositis, sporadic inclusion body myositis and polymyositis (PM).1 2 AIM in adults is rare, with an estimated incidence of 20 cases per million per year and a prevalence of 30 cases per 100 000 individuals.3 AIMs are functionally impairing and, when compared with other systemic autoimmune rheumatic diseases, associated with greater impairment in health-related quality of life.4 After conducting multiple surveys with patients, their families and physicians, the Outcome Measures in Rheumatology Myositis Special Interest Group listed pain as one of five highest priorities for research in AIM while emphasising the paucity of data on the subject.5–8 With the aim to better characterise the pain experience in AIM, we searched the literature for studies reporting on pain in adult AIM and summarised their findings in this scoping review.
Methods
This review was conducted using the Arksey and O’Malley framework9 and guided by the methodology from recent scoping reviews.10 It included the following five key phases: (1) research question identification; (2) relevant studies identification; (3) study selection; (4) data charting; and (5) collating, summarising and reporting results. The following question guided the review: what is known about the burden of pain in adult AIM? The comprehensive search was implemented on 15 February 2022, in PubMed and MEDLINE with limitation to English and French languages and human studies. No limits were placed on date or type of studies. The search query was built to capture articles that addressed the specific topics of pain, patient-reported outcome measures (PROMs), and autoimmune inflammatory myopathies or idiopathic inflammatory myopathies.
The reference lists of included studies were manually searched to identify any further studies not captured by the search. A ‘snowball’ technique was adopted in which citations within articles were searched if they appeared relevant to the review.10 Papers were eligible for inclusion if they were full-length articles in English or French language including (1) pain assessment by at least one PROM and (2) more than five adult subjects with AIM. Titles and abstracts were reviewed for eligibility. Titles for which an abstract was not available and/or for which the screening decision was uncertain were reviewed via a search for keywords in their full text.
Data from included papers were extracted including author(s), year of publication, publication type, main topic of the study and data relevant to the specific objectives of this scoping review, that is, (1) characteristics of study population included, (2) pain measurement using a PROM and (3) clinical correlates of pain if included in the study. Data were compiled in a tabular format and qualitatively summarised. A quantitative meta-analysis was not planned as it was anticipated that the data collected would be too heterogenous for this type of analysis.
Results
Studies characteristics
The search strategy identified 2831 studies and, after exclusion of duplicates and ineligible papers, 33 studies including pain measures in adult subjects with AIM were included in this review (see flowchart in online supplemental figure 1).11–43 The characteristics of the studies included are summarised in online supplemental table 1. The papers included originated from Europe (n=24),11–17 19 20 24–26 28–32 35–38 40 USA (n=7),18 21–23 33 41 42 South America (n=1)34 and Australia (n=1)43 with years of publication ranging from 1999 to 2021. Most of the studies were cross-sectional (n=11) or cohort (n=9) studies. One study had a case–control design (n=1)36 and one was prospective (n=1).13 There were five open-label studies,11 12 14 24 34 five randomised controlled trials (RCTs)15 20 29 30 37 and one randomised single-blinded trial39 using pain as an outcome measure. Almost half of studies used unidimensional pain intensity measurement, namely, visual analogue scale (VAS) or numerical rating scale (n=15).11 13 17 23–25 27 30 31 36–39 41 42 The rest of the studies used multidimensional pain measurements including the Medical Outcomes Study 36-Item Short Form Bodily Pain (SF-36 BP) or 12-Item Short Form Bodily Pain (n=17),11 12 16 21–23 26–30 32 34–37 40 the Borg Rate of Perceived Pain Scale (n=1),14 the Health Assessment Questionnaire–Pain Index (n=1),18 the Individualised Neuromuscular Quality of Life Questionnaire (INQOL, n=1),33 the Nottingham Health Profile (NHP, n=3)15 19 and the Short Form McGill Pain Questionnaire (n=1).20
Supplemental material
Supplemental material
Frequency of pain
Few of the studies included in the review provided estimates of the frequency of pain in their population. In a 2010 RCT including 62 patients with early AIM, 81% of the participants had myalgias at baseline.44 In a small cohort study of eight patients newly diagnosed with AIM, 100% had pain at baseline.25 In a 2020 US survey-based study (n=381), myalgias were reported in 64% of participants, being more frequent with increased numbers of flares per year.18 A German study reporting on cross-sectional clinical characteristics of patients with AIM from 1997 to 2017 showed a decreasing frequency of moderate to severe pain (53% in 1997 compared with 25% in 2017).13 However, the patient populations were quite different between those two time points with the 2017 cohort having a longer disease duration and lower disease activity compared with the 1997 cohort, making it difficult to draw meaningful conclusions.
Comparisons with the general population
Comparisons of pain measures with the general population were done in 11 studies (table 1). In nine of those, subjects with AIM had significantly more pain than the general population.19 21 22 26 28 32 35 36 43 Subjects included in those studies generally had established stable disease except for one RCT comparing the use of high-dose prednisone to dexamethasone in early disease (<6 months disease duration) where SF-36 BP scores in untreated subjects with AIM at study entry were severely impaired.35 In seven studies using an additive scoring of the SF-36 BP, the mean or median bodily pain (BP) scores in the subjects with AIM ranged from 42 to 78 compared with 70 to 100 in the general population (with lower numbers indicating more pain).21 26 28 32 35 36 43
Pain measures in AIM compared with the general population
Comparisons with other rheumatic or neuromuscular diseases
Comparisons of pain measures with other neuromuscular or rheumatic diseases were reported in five studies (table 2).19 22 23 29 33 In a large survey-based study including 1715 patients with AIM with a median disease duration of 9.2 (IQR 5–14) years, the burden of pain using the SF-36 BP was comparable to rheumatoid arthritis.22 A study including only female patients with DM/PM (n=113) recruited through a national support group with a mean (range) disease duration of 7 (1–27) years reported less pain in AIM using the NHP compared with female patients with rheumatoid arthritis and osteoarthritis.19 In a cross-sectional study using the INQOL, patients with DM/PM reported more pain compared with various other neuromuscular diseases.33 In that study, patients with inclusion body myositis (IBM) had burden of pain similar to other neuromuscular diseases, which was also the case in an RCT in IBM (n=60) where prerandomisation SF-36 BP scores were comparable to previously published scores in facioscapulohumeral dystrophy, myotonic dystrophy and Charcot-Marie-Tooth type 1.29 45 46
Pain measures in AIM compared with other neuromuscular or rheumatic diseases
Clinical characteristics and disease course
Studies reporting on age, sex, AIM subsets, disease activity/course and pain are summarised in table 3. Sex differences were assessed in three studies.28 32 43 In a cross-sectional study assessing grip strength and health-related quality of life in established DM/PM (n=31), women had lower mean SF-36 BP scores (more pain) compared with men (52 vs 65) although not reaching statistical significance.32 In a cohort study of patients with DM, PM and overlap myositis (OM) (n=87), being female was a predictor of lower SF-36 BP scores (more pain; β −15.5, p=0.000).28 A cross-sectional study including patients with DM, PM, immune-mediated necrotising myopathy (IMNM), IBM and non-specific myositis (n=50) found no sex differences in SF-36 BP scores.43 Two studies reported no difference in SF-36 BP scores based on age, although results were not shown.29 43
Studies reporting on age, sex, AIM subsets, disease activity/course and pain
Pain measures were stratified by AIM subsets in six studies,19 28 32 33 38 40 and comparison of pain measures by AIM subsets were reported in six studies.28 32 35 38 40 43 While most of these studies reported no statistically significant difference in pain measures between AIM subsets, a survey-based study showed lower mean±SD pain intensity using VAS in IBM (22±27, p<0.05) compared with DM (37±28), PM (39±29) and OM (38±33).38 Similarly, in a cross-sectional study on health-related quality of life in chronic neuromuscular diseases, pain measured using the INQOL score was lower in IBM compared with DM/PM (46±29 vs 70±19).33 In a cohort study assessing physical activity in AIM, although non-significant, baseline mean±SD SF-36 BP scores were lower in DM (more pain, 55±24) than in IMNM (71±24) or OM (63±28).40
Few studies reported pain measures in patients with early active AIM.15 25 30 Baseline pain scores in an RCT comparing high-dose prednisone to dexamethasone in early AIM reported very low median SF-36 BP scores in untreated subjects with AIM with improvement at 18 months (32 vs 72).35 This contrasts with the results of a cross-sectional study that found disease duration more than 5 years to be a predictor of lower BP scores (more pain; β= −14.2, p=0.001). Of note, this study specifically included subjects with a follow-up of at least 3 years introducing a survivorship bias that may explain this discrepancy. In IBM, no correlation between pain and disease duration was reported by Sadjadi et al.29 As for the impact of disease activity on pain, vague or broad inclusion criteria and heterogenous populations made interpretation of the results, and comparison of the studies difficult. Nonetheless, some studies suggested that uncontrolled disease (progressive course or frequent flares within 1 year) was associated with more pain.18 26 Interestingly, a cross-sectional study found SF-36 BP scores to be correlated with Patient Global Assessment (r=−0.62, p<0.001) but not with Physician Global Assessment (r=−0.14, p=0.35).43 Finally, a cross-sectional study explored associations between different domains of the NHP and found that low levels of energy were associated with more pain (β=0.2, p=0.03). Similarly, SF-36 BP scores were moderately correlated with Beck Depression Inventory scores in IBM.29 These results align with those of Rose et al, who reported that pain in neuromuscular diseases including AIM correlated with anxiety, depression and illness perception.33
Muscle strength, endurance, functional disability and physical activity
Studies reporting on muscle strength, endurance and functional disability are summarised in table 4. Studies assessing pain in relation to muscle strength and endurance showed weak or no correlations.16 24 28 32 36 43 Functional disability measured using the Health Assessment Questionnaire–Disability Index was moderately correlated with pain in two cross-sectional studies.28 42 Similarly, lower SF-36 BP scores were reported in patients with AIM with higher disability scores measured by the modified Rankin score.35
Studies reporting on muscle strength, endurance and functional disability and pain
Twelve studies reporting pain measures in physical activity interventions (n=10)11 12 14 15 20 24 27 34 37 39 or monitoring (n=2)40 41 are summarised in table 5. For most of the physical activity interventions, there was no significant change in pain preintervention and postintervention. However, two studies noted improvement of pain after physical activity interventions.12 34 An open-label study of 13 patients with mildly active DM/PM following a 12-week low-intensity resistance exercise programme showed improvement in mean±SD SF-36 BP scores after the intervention (59±11 vs 87±15, p=0.002).34 Interestingly, different pain measures generated conflicting results in some of those studies. In an RCT randomising participants to a 4-week standardised hospital-based exercise programme or standard or care, no significant differences in SF-36 BP scores at 3, 6 or 12 months were reported, while pain intensity measured with a VAS was significantly improved at 12 months in the intervention group (mean VAS±SD 36±37 vs 5± 11) while remaining stable in the control group.37 In a small study of 10 patients with AIM following a home exercise programme for a 12-week period, median SF-36 BP scores worsened at 12 weeks (88 (range 25–100) vs 51 (range 31–100)), while the VAS for pain intensity remained stable.11
Studies assessing pain severity in relation with physical activity
Discussion
This scoping review of 33 studies reporting on pain measures in AIM indicates that the burden of pain in subjects with AIM is greater than that of the general population and comparable to other chronic rheumatic diseases such as rheumatoid arthritis. However, it is important to note that pain was rarely the primary focus of the studies included. In addition, the studies were mostly small, single-centre studies with ill-defined populations and methodology that were at high risk of bias. This review highlights areas where research could help better characterise the pain experience in AIM.
None of the studies included in this review formally explored the relationship between disease activity and pain in AIM using comprehensive disease activity measures. Potential non-inflammatory pain contributors such as comorbidities (eg, fibromyalgia) or disease damage (eg, muscle dysfunction/atrophy) are often overlooked and can complicate disease activity assessment. Correlations between pain and biological markers of disease activity would be helpful to generate hypotheses about the possible mechanisms of pain in AIM. For example, a histopathological study by Noda et al showed that fasciitis rather than myositis was associated with myalgia in their cohort of 54 Japanese patients with AIM.47 Additionally, patients who present with pain and myopathic features should be carefully assessed for AIM mimickers such as toxic, infectious and metabolic myopathies. Future studies on structural abnormalities including, but not limited to, the muscle (eg, joint, skin, nerves, Raynaud’s disease) would be important to identify possible structures involved in pain generation in AIM.
Interestingly, some of the data reported in this review suggest sex differences in the AIM pain experience. This aligns with the literature in inflammatory arthritis such as rheumatoid arthritis and spondyloarthropathies, where female patients consistently report higher levels of pain than male patients.48 Animal studies have also shown that there are important sex differences in pain processing.49 50 This notion should be kept in mind when planning future epidemiological or mechanistic studies on pain in AIM as ignoring the possibility of sex differences could lead to inconclusive or misleading results. Similarly, some of the studies included in this review suggested differences in pain measures when populations were stratified by AIM subsets. Disease subset classification in AIM is challenging and the subject of considerable debate in the field. However, as AIM phenotypes differ significantly based on clinical features and serological profiles, pain mechanisms and characteristics could as well. The studies included in this review in majority overlooked extramuscular features and their possible association with pain, and none considered autoantibody profiles. Some of the included studies also showed that muscle strength and endurance are not parameters that correlate well with pain.16 24 28 32 36 43 Thus, researchers interested in pain in AIM should carefully select their study subjects and plan their analyses, paying particular attention to possible sex differences and heterogeneity in clinical phenotypes.
Finally, several of the studies included in this review used VAS as pain measure. The use of unidimensional scales for pain measurement has some limitations as it mostly reflects the sensory pain dimension and not the affective aspect of pain. On the other hand, multidimensional tools that are more comprehensive take longer to administer. Moreover, as there is currently no consensus on how to measure pain in AIM, different tools are used, and their results are difficult to compare. As shown in this review, discordance is possible between unidimensional and multidimensional measures, and it is imperative that future studies address this important issue. There is a pressing need for systematic and standardised pain assessment in AIM to facilitate research and improve management of patients with AIM.
Conclusion
The burden of pain in AIM is considerable. However, due to the heterogeneity and low quality of the evidence available, significant knowledge gaps persist. Studies are needed to longitudinally characterise the pain experience in AIM, including predictors of severity and clinical correlates to identify possible pain mechanisms and offer targeted management to patients.
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References
Supplementary materials
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Footnotes
Contributors All authors have contributed to study conception, data collection, data analysis and interpretation, drafting of the article, critical revision of the article and final approval of the submitted version.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.