Abstract
Background.
Flares in dermatomyositis (DM) are associated with increased disability, health care utilization, and reduced quality of life. We aim to determine the characteristics and risk factors of flares in patients with DM.
Methods.
Patients were included if seen at The Johns Hopkins Myositis Center and fulfilled the 2017 EULAR/ACR Classification Criteria for DM. Two authors reviewed all notes and recorded patient symptoms, exams, labs, imaging findings, and medication changes. Objective flare was defined as active disease on exam or ancillary testing that resulted in an increase in immunosuppressive therapy. Characteristics of patients and flares were summarized using descriptive statistics. We assessed the association between patient characteristics and time to first flare using Cox proportional hazards models.
Results.
In this study with 637 patients with DM, rash was the most common finding of flare (75.7%), followed by muscle weakness (58.4%), new/worsening findings on lung function tests and/or imaging (19.0%) and arthritis (12.4%). Over 85% of the patients who reported rash, weakness, dyspnea, joint swelling, dysphagia or fever met the definition of objective flare. Black race and shorter time to diagnosis were associated with increased flare risk. Among patients with DM who experienced an objective flare, only 2–5% had a cancer diagnosis within 6–24-months of flare. In a subset of newly diagnosed patients, 26% had ≥1 flare during follow-up. The incidence rate of flares was 5.1 per 100 person-years. The average time between diagnosis and the first flare was 2.9 years (SD 2.3) ranging between 6.2 months and 10.8 years.
Conclusion.
In this tertiary care center cohort of DM patients, patient-reported symptoms of increased disease activity were often indicative of objective flare. We identified Black race and shorter time to diagnosis as risk factors for flare. Understanding these factors can inform clinicians about monitoring strategies and improved patient outcomes.
INTRODUCTION
Dermatomyositis (DM) is a chronic systemic inflammatory myopathy which can affect multiple organ systems including the muscle, skin, lungs, joints, and heart. The clinical course of patients with inflammatory myopathies is highly heterogenous. Approximately 60–80% of patients experience polycyclic or chronic persistent disease despite treatment, while a minority of patients follow a monocyclic course with a single episode of active disease [1–6]. Polycyclic disease course is generally defined as relapsing remitting disease with flares and quiescent periods of disease activity. The extent and severity of damage that accrue over time as well as mortality rates are higher in patients with a polycyclic or chronic persistent course compared to those with monocyclic course [1, 7, 8]. The timing and extent of flares define and distinguish these different disease courses from each other. Higher flare frequency is associated with increased morbidity with more disability and pain, higher health care utilization including emergency department visits and hospitalizations, absenteeism and work productivity loss among patients with DM [9–11]. Therefore, understanding the characteristics and risk factors of flares is critical, as it can inform individualized therapeutic and monitoring strategies in patients with inflammatory myopathies, and serve as meaningful clinical outcomes in therapeutic trials.
Studying flares in DM has been hampered by a lack of a validated definition of flare. A group of myositis experts through the International Myositis Assessment and Clinical Studies Group (IMACS) developed a consensus derived preliminary criteria for flare as following: i) worsening of the patient’s global condition, as assessed by the physician, by ≥2 cm on a 10-cm visual analog scale (VAS) and worsening of findings of manual muscle testing by 20%, or ii) worsening of global extra-muscular organ disease activity (a composite of constitutional, cutaneous, skeletal, gastrointestinal, pulmonary, and cardiac activity) by ≥2 cm on a 10-cm VAS, or 3) worsening of any 3 of 6 IMACS core set activity measures by ≥30% [12]. However, this definition has not been validated and a new flare definition has not been developed even though data driven definitions of flare was agreed to be a priority for myositis field more than two decades ago [12]. Furthermore, these measures are not often collected in the routine clinical care of patients with DM.
In this study, our goals are (i) to report the characteristics of DM flare with a broader goal of informing the development of a standardized flare definition (particularly by examining the relationship between patient symptoms and objective findings on physical exam and/or ancillary studies) and ii) to identify the risk factors for objective flares in patients with DM.
METHODS
Patients
The Johns Hopkins Myositis Cohort was retrospectively reviewed from 2003–2020 for patients who had all required data and met any of the following criteria: Diagnosis of dermatomyositis by 2017 EULAR/ACR Classification Criteria for IIM OR patients with a classic DM rash (Gottron’s or heliotrope) and consistent histopathology on skin biopsy to capture those with amyopathic disease [13]. All patients were ≥18 years old at the time of their first DM symptom. Symptom onset was defined as the first DM symptom documented in the electronic medical record by the patient limited to the following: arthralgia, dyspnea, myalgia, weakness, or rash consistent with DM. Asymptomatic hyperCKemia was not considered a symptom.
Systematic Review of Records
Two authors (CM and YW) manually reviewed all notes to ascertain any increase in disease activity over longitudinal follow-up and the context in which it occurred (i.e., medication changes, infectious complications, ultraviolet light, malignancy, idiopathic, etc.). The Johns Hopkins IRB approved the protocol, and all patients provided informed consent.
Definitions of Flare
Given the absence of a validated definition for flare in patients with DM, a flare was defined as i) objective evidence of active disease on physical exam or ancillary testing for any of the following manifestations that are new or worse: weakness, skin rash consistent with DM, inflammatory arthritis, pulmonary function test or lung imaging findings concerning for worsening or new myositis-related lung disease, and ii) an increased in immunosuppressive/immunomodulatory therapy. The thresholds for determining worsening weakness or lung function/extent of lung disease warranting escalation of therapy were determined by the clinician.
Episodes of increased disease activity were not counted as a flare if they occurred within 3 months of tapering/discontinuation/starting of immunosuppressive or immunomodulatory medications. Only the patients who were stable on immunosuppressive regimen were eligible to flare. Given the pharmacokinetics and dynamics of intravenous immunoglobulin (IVIG) and rituximab (RTX), we did not count the increase in disease activity as flares if they occurred < 3 months or < 6 months from last IVIG or RTX infusion, respectively. Additionally, an increase in disease activity within 6-months of diagnosis date was not counted as a flare.
Statistical Analyses
Patient characteristics, signs and symptoms were summarized using descriptive statistics. We assessed the association between individual characteristics of interest and risk of a first flare using univariate Cox proportional hazards models. We selected the following individual characteristics: sex, race (considered as Black, White, and other races), age at diagnosis, time to diagnosis from symptom onset, and autoantibodies (anti-Jo-1, PL-12, PL-7, EJ, OJ, TIF1γ, NXP2, SAE, Mi2, SAE, PM/Scl, and Ku). For multivariable models, we included all individual characteristics in a single model. Since certain autoantibodies were relatively rare, for the multi-variable model, we collapsed autoantibody results into anti-synthetase (ASyS) (anti-EJ, Jo-1, OJ, PL-12, PL-7) and DM (anti-MDA5, Mi2, NXP2, SAE, TIF1γ). In secondary analyses, we allowed for multiple flare events using Andersen Gill models for recurrent events adjusted for a similar set of characteristics as above. All analyses were performed using R version 4.2.2.
RESULTS
i. Participant characteristics
There was a total of 637 patients with DM (75.4% female; 77.1% White, 12.9% Black) with an average age at diagnosis of 48.7 years (SD ± 13.7) (Table 1). The patients had an average of 1.2 years (± 1.9 years) between symptom onset and diagnosis and had a follow up duration of 7.9 years (± 4.6 years) at the Johns Hopkins Myositis Center. The most common autoantibody in the cohort was anti-TIF1γ (30.1%) followed by anti-Jo-1 autoantibody (13.2%). Overall, 35.5% of the patients (226 of 637) had at least one objective flare over the follow-up period. Patients with an objective flare had a shorter interval from symptom onset to diagnosis date and were more likely to be of Black race (Table 1). In a subset of patients who were seen at the Johns Hopkins Myositis Center within 6-months of their physician diagnosis (n=367), 26.4% of the patients (n=97) had at least one objective flare during their follow-up. The incidence rate of flares was 5.1 per 100 person-years. The average time between diagnosis and the first flare was 2.9 years (SD 2.3) ranging between 6.2 months and 10.8 years.
Table 1.
Baseline demographic and disease related characteristics of all DM patients, those who had flare and those who did not have flare during follow-up.
| All patients (n=637) | Patients with objective flare (n=226) | Patients without objective flare (n=411) | ||||
|---|---|---|---|---|---|---|
| n or mean | % or SD | n or mean | % or SD | n or mean | % or SD | |
| Age at diagnosis | 48.7 | 13.7 | 46.5 | 13.2 | 50.0 | 13.9 |
| Time to diagnosis (yrs) | 1.2 | 1.9 | 1.0 | 1.6 | 1.4 | 2.1 |
| Follow-up duration (yrs) | 7.9 | 4.6 | 8.8 | 4.8 | 10.3 | 4.7 |
| Sex (Female) | 480 | 75.4% | 175 | 77.4% | 305 | 74.2% |
| Race | ||||||
| Asian | 19 | 2.9% | 5 | 2.2% | 14 | 3.4% |
| Black | 82 | 12.9% | 40 | 17.7% | 42 | 10.2% |
| Other | 45 | 7.1% | 10 | 4.4% | 35 | 8.5% |
| White | 491 | 77.1% | 171 | 75.7% | 320 | 77.9% |
| Autoantibodies | ||||||
| Anti-MDA5 | 45 | 7.1% | 17 | 7.5% | 28 | 6.8% |
| Anti-Mi-2 | 64 | 10.0% | 16 | 7.1% | 48 | 11.7% |
| Anti-TIF1γ | 192 | 30.1% | 69 | 30.5% | 123 | 29.9% |
| Anti-NXP-2 | 67 | 10.5% | 20 | 8.8% | 45 | 11.8% |
| Anti-SAE | 19 | 2.9% | 3 | 1.3% | 16 | 3.9% |
| Anti-Jo-1 | 84 | 13.2% | 37 | 16.4% | 47 | 11.4% |
| Anti-PL-7 | 12 | 1.9% | 7 | 3.1% | 5 | 1.2% |
| Anti-PL-12 | 15 | 2.4% | 10 | 4.4% | 5 | 1.2% |
| Anti-EJ | 5 | 0.8% | 1 | 0.4% | 4 | 0.9% |
| Anti-OJ | 17 | 2.7% | 5 | 2.2% | 12 | 2.9% |
| Anti-PM-Scl | 28 | 4.4% | 11 | 4.9% | 17 | 4.1% |
| Anti-Ku | 6 | 0.9% | 2 | 0.9% | 4 | 0.9% |
ii. Signs and symptoms of objective flare
Among patients with objective flare (n=226), DM-attributable rash documented on physical examination was the most common finding (n=171, 75.7%), followed by muscle weakness on exam (n=132, 58.4%), new or worsening findings on PFTs and/or HRCT (n=43, 19.0%) and inflammatory arthritis (n=28, 12.4%). A total of 86 patients (38.1%) had ‘other’ objective findings including elevation in muscle enzymes (n=63), abnormal muscle imaging (n=4), electromyography (EMG) (n=7) or skin or muscle biopsy findings concerning for active disease (n=4), or new or worsening oxygen requirement (n=1).
The patient reported symptoms of patients with objective flare included rash (n=158, 70.5%), muscle weakness (n=139, 62.1%), dyspnea (n=72, 32.1%), fatigue (n=55, 24.6%), joint swelling (n=33, 14.7%), dysphagia (n=32, 14.3%) and fever (n=12, 5.4%). A total of 95 patients (42.4%) experienced ‘other’ symptoms including myalgias (n=46; 20.5%), joint pain (n=28, 12.5%), itching (n=11; 4.9%), joint stiffness (n=5; 2.2%), decreased muscle endurance (n=3, 1.3%) and hair loss (n=1; 0.4%).
iii. Relationship between patient-reported symptoms and meeting the definition of objective flare
Approximately 90% of the patients who self-reported rash had objective evidence of rash attributable to DM on physical exam by a myositis specialist (Figure 1). Symptoms of weakness, joint swelling, and dyspnea had appreciable physical exam findings or lung imaging/pulmonary function study findings in 80.5%, 37.1% and 53.9% of the patients, respectively.
Figure 1.
Frequency of symptoms (A) and percentage of patients who met the objective flare criteria among patients with DM (B).
The majority of the patients who reported symptoms met the definition of objective flare. Patients who have self-reported dyspnea were most likely to meet the definition of objective flare (94.7%), followed by symptoms of joint swelling (94.3%), weakness (93.3%), rash (91.9%), fatigue (91.7%), dysphagia (91.4%), and fever (85.7%) (Figure 1).
iv. Determinants of objective flare
In univariate Cox proportional hazards model, Black race, ASYS autoantibody (particularly anti-PL-12) and shorter time to diagnosis were significantly associated with increased risk for objective flare (Table 2). In the multivariable model, Black race and time to diagnosis remained significantly associated with the risk of objective flare, while the presence of ASyS autoantibody lost its significant association with flare. Similar results were seen in models incorporating a recurrent events model (Supplementary Table 1).
Table 2.
Risk factors for flare in patients with DM on univariate and multivariable Cox proportional hazards models.
| Univariate Cox proportional hazards model | Multivariable Cox proportional hazards model | |||||
|---|---|---|---|---|---|---|
| Hazard ratio | CI | p value | Hazard ratio | CI | p value | |
| Age at diagnosis | 0.99 | 0.99, 1.00 | 0.3 | 0.99 | 0.98, 1.00 | 0.3 |
| Time to diagnosis | 0.90 | 0.83, 0.99 | 0.03* | 0.89 | 0.81, 0.99 | 0.02* |
| Sex (male) | 0.82 | 0.60, 1.12 | 0.2 | 0.91 | 0.66, 1.25 | 0.6 |
| Race | ||||||
| White | 1.00 | - | - | 1.00 | - | - |
| Black | 1.63 | 1.15, 2.30 | 0.006* | 1.55 | 1.07, 2.24 | 0.02* |
| Asian | 0.63 | 0.26, 1.54 | 0.3 | 0.59 | 0.24, 1.44 | 0.3 |
| Other | 0.72 | 0.37, 1.40 | 0.3 | 0.55 | 0.26, 1.19 | 0.1 |
| Autoantibodies | ||||||
| Anti-MDA-5 | 1.15 | 0.70, 1.88 | 0.6 | - | - | - |
| Anti-Mi-2 | 0.62 | 0.37, 1.05 | 0.08 | - | - | - |
| Anti-TIF1γ | 0.97 | 0.73, 1.29 | 0.8 | - | - | - |
| Anti-NXP-2 | 0.98 | 0.63, 1.53 | 0.9 | - | - | - |
| Anti-SAE | 0.45 | 0.14, 1.41 | 0.2 | - | - | - |
| Anti-Jo-1 | 1.24 | 0.87, 1.78 | 0.2 | - | - | - |
| Anti-PL-7 | 1.88 | 0.89, 4.01 | 0.1 | - | - | - |
| Anti-PL-12 | 2.59 | 1.37, 4.89 | 0.003* | - | - | - |
| Anti-EJ | 0.53 | 0.07, 3.78 | 0.5 | - | - | - |
| Anti-OJ | 0.94 | 0.39, 2.29 | 0.9 | - | - | - |
| Anti-PM/Scl | 1.10 | 0.60, 2.02 | 0.8 | - | - | - |
| Anti-Ku | 1.43 | 0.46, 4.48 | 0.5 | - | - | - |
| Autoantibodies (categorical) | ||||||
| ASYS | 1.44 | 1.07, 1.95 | 0.02* | 1.37 | 0.99, 1.88 | 0.06 |
| DM | 0.86 | 0.63, 1.17 | 0.3 | 0.93 | 0.67, 1.28 | 0.7 |
Abbreviations: ASYS: Anti-synthetase syndrome, DM: Dermatomyositis
On multivariable models stratified by race, ASYS autoantibody had no significant association with flare risk (Supplementary Table 2). Time to diagnosis remained significantly associated with higher flare risk in patients with White race, while it was not significantly associated with flare risk in patients with Black race.
Among patients with DM who experienced an objective flare (n=227), the prevalence of cancer was notably low. Only 2.2% had a cancer diagnosis within 6 months of flare, 3.5% within 12 months, and 4.8% within 24 months. Overall, 14.9% of patients with a flare had a history of cancer at any time suggesting fewer observed cancer cases, particularly in close temporal proximity, than expected (Table 3).
Table 3.
Prevalence of history of cancer among patients with DM who had flare.
| Time frame | No. cancers | OR (95% CI) | p value |
|---|---|---|---|
| Cancer within 6 months | 5 (2.2%) | 0.02 (0.01, 0.06) | <0.001 |
| Cancer within 12 months | 8 (3.5%) | 0.04 (0.02, 0.08) | <0.001 |
| Cancer within 24 months | 11 (4.8%) | 0.04 (0.02, 0.08) | <0.001 |
| Any history of cancer | 34 (14.9%) | 0.18 (0.12, 0.25) | <0.001 |
Of the 135 patients with a history of cancer of the whole cohort, 64 (47.4%) were diagnosed with cancer prior to their myositis diagnosis, while 71 (52.6%) were diagnosed after. Among those with cancer after myositis, the average interval between myositis and cancer diagnosis was 3.9 years (±5.0). Most of these cancers (64.8%, n=46) occurred within 3 years of the myositis diagnosis, whereas 35.2% (n=25) were diagnosed more than 3 years later. Within the subgroup of patients who developed cancer after myositis (n=71), 19 (26.8%) experienced at least one objective flare. Among them, 5 patients (7.0%) had a flare within 6 months of their cancer diagnosis, 8 (11.3%) within 12 months, and 10 (14.1%) within 24 months. These 19 patients were nearly evenly split between those with early cancer (≤3 years after myositis diagnosis, n=10) and late cancer (>3 years, n=9). On average, the time between flare and cancer diagnosis was 1.9 years (±2.3) in the early cancer group and 3.7 years (±2.7) in the late cancer group (p=0.1).
DISCUSSION
In this tertiary care center cohort, approximately one third of the patients with DM experienced at least one objective flare. The majority of patient-reported symptoms of increased disease activity were associated with objective findings on exam or ancillary studies and prompted an increase in immunosuppressive therapy. Black race and shorter time to diagnosis were associated with increased risk of flares. Most flares did not herald a cancer diagnosis.
The most common patient reported symptoms of DM flare in this study were rash and muscle weakness in approximately 60–70% of the those who had objective flare. The majority of the patients who self-reported rash and weakness had evidence of rash and weakness attributable to DM on physical examination and met the definition of objective flare in over 90% of the patients. A survey study with 524 patients with DM and polymyositis (PM) showed that the most common symptoms of flare were muscle weakness seen in approximately 80% of the patients followed by rash in 45% of the patients [9]. This difference between prevalence of rash between studies is likely due to the survey study including patients with PM, while our study solely included patients with DM. The survey study also showed fatigue and myalgias as common symptoms of flare in 78% and 64% of the patients, respectively [9]. Qualitative interviews with patients living with myositis also highlight fatigue, myalgias and generalized pains (not limited to muscles) as symptoms associated with flares [14]. However, nearly 25% of patients had myalgias and fatigue as reported flare symptoms in our study. This significant difference between rates of fatigue and myalgia between these studies is likely due to differences in study design. The symptoms reported in our study were derived from retrospective chart review of the physician notes. Since patients were not systematically asked about their symptoms at each visit, lower rate of fatigue and myalgias could be expected. However, this can also potentially suggest that myalgias and fatigue are less frequently reported by physicians in their notes since they are relatively non-specific symptoms and could be less commonly attributed to a potential DM flare by physicians. In our study, over 90% of patients who reported fatigue met the definition of objective flare. Therefore, patient-reported fatigue and myalgias should raise suspicion for a potential flare.
The flare rate among patients with DM was 26.4%, which is considerably low compared to other studies reporting flare rates of 64–72% [11, 15]. This could be explained by a number of factors. First, our study did not include patients who had flares due to medication tapering (as tapering strategies may differ among physicians) as well as those who had increased disease activity within 6 months of their diagnosis. Further, the flare definition used in our study was stringent and was based on physical examination and/or additional tests along with an increase in immunosuppression compared to other studies in which the flares were patient reported. In one study which included a daily symptom tracker, patient-reported flares were seen to occur at an average of once every 3 weeks while symptom-reported flares resolve within 3 days [14]. This finding likely reflects day-to-day fluctuations on disease activity that patients frequently report on qualitative interviews rather than true flare [16]. Although it is critically important to include patient reported symptoms in flare definition, as they were also often indicative of objective flare in our study, the degree of change or persistence in patient reported symptoms for this definition needs to be cautiously determined.
Black race was associated with increased risk of DM flare in both univariate and multivariable regression models. Autoantibody status, particularly the presence of ASyS antibodies which are more commonly seen in Black individuals in these patients could explain these findings; however, the results were independent of the autoantibody status. Given that the flares related to medication discontinuation/non-adherence were excluded in this study, these results also could not be explained by medication use. Although this is the first study to show increased risk of flare in Black individuals with DM, a few prior studies suggested that Black race is likely a poor prognostic factor in inflammatory myopathies with lower survival rates [17]. In one study, Black individuals with ASyS demonstrated more severe interstitial lung disease than White individuals [18]. Another study showed that Black individuals with juvenile DM had worse disability, disease activity, and health related quality of life, and were more likely to have calcinosis than non-Black individuals [19].
A shorter time to diagnosis was associated with an increased risk of DM flare. This could be due to patients with earlier diagnoses experiencing a more severe clinical presentation at onset and potentially increased risk of flare during the disease course. It could also indicate that these patients with earlier diagnoses may have easier access to health care or may be more engaged in their care, which allows them to report their symptoms to their providers in a timelier manner. We did not have variables that could provide information about the disease activity or access to health care of the patients to further examine the role of these potential factors in flare risk.
Among DM patients with objective flare, only 2–4% had cancer within 6–12 months of the flare. Among DM patients who had cancer after their myositis diagnosis, only 7–11% had flares within 6–12 months of their cancer diagnosis. Even though the association between DM diagnosis and contemporaneous cancer is well known, to our knowledge, the relationship between DM flare and cancer diagnosis has not been previously studied [20, 21]. Our findings suggest that the majority of DM flares did not have a close temporal association with cancer diagnosis and the majority of patients with DM who were diagnosed with cancer did not experience a DM flare. These results suggest that many cancers diagnosed in patients with DM may not be biologically related to DM and could be related to other risk factors or chronic immunosuppression.
Other risk factors for flares reported in prior studies include environmental factors such as sun exposure and non-steroidal anti-inflammatory drug use and were not examined in this study [15]. Presence of anti-EJ/anti-Jo1 autoantibodies were found to be significantly associated with flare in a recent study with patients with ASyS [22], our study did not find any myositis specific autoantibodies to be a significant risk factor for flare on multivariable models.
The main limitation of this study is its retrospective design with data extracted from the patient charts. Therefore, patient symptoms were not systemically asked or reported, and physical examination and ancillary study findings were not standardized. Further, the participants were followed at a tertiary care specialized myositis center; therefore, the results, particularly in regard to flare rates, may not be generalizable to the whole DM population. In addition, the duration of flare was not captured, which should be a focus for future research. Limitations withstanding, the study represents one of the few studies on flare in patients with DM and includes a large, well described cohort with systematic serotyping of autoantibodies and a comprehensive assessment of symptoms and objective findings.
CONCLUSION
One third of the adults with DM in a specialized tertiary care center cohort met the objective definition of flare. Patient-reported symptoms are highly suggestive of an objective flare. Rash and muscle weakness were the most common patient-reported symptoms of flare, while myalgia and fatigue could be underrecognized symptoms of DM flare. Importantly, in contrast to a widely held belief among clinicians, the majority of the flares do not herald a cancer diagnosis. The results of the study highlight the symptoms and risk factors of objective flares in patients with DM and can inform development of a standardized flare definition of myositis in the future.
Supplementary Material
Funding support:
DS is supported by the Rheumatology Research Foundation Scientist Development Award, Rukel Foundation, C-COMP Pilot Grant, and RUSH to Progress Pilot Award. CM is supported by the Jerome L Greene Foundation and R01 AR083912 and ET by K08-AR0777732. LCS is supported by the Zhang Myositis Discovery Fund. This project was also supported, in part, by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.
Footnotes
Conflicts of interest: Authors report no conflict of interest relevant to this study.
REFERENCES
- 1.Rider LG, Lachenbruch PA, Monroe JB, et al. Damage extent and predictors in adult and juvenile dermatomyositis and polymyositis as determined with the myositis damage index. Arthritis Rheum 2009;60(11):3425–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Bronner IM, van der Meulen MF, de Visser M, et al. Long-term outcome in polymyositis and dermatomyositis. Ann Rheum Dis 2006;65(11):1456–61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Shu XM, Lu X, Xie Y, Wang GC. Clinical characteristics and favorable long-term outcomes for patients with idiopathic inflammatory myopathies: a retrospective single center study in China. BMC Neurol 2011;11:143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Marie I, Hachulla E, Hatron PY, et al. Polymyositis and dermatomyositis: short term and longterm outcome, and predictive factors of prognosis. J Rheumatol 2001;28(10):2230–7. [PubMed] [Google Scholar]
- 5.Taborda AL, Azevedo P, Isenberg DA. Retrospective analysis of the outcome of patients with idiopathic inflammatory myopathy: a long-term follow-up study. Clin Exp Rheumatol 2014;32(2):188–93. [PubMed] [Google Scholar]
- 6.van de Vlekkert J, Hoogendijk JE, de Visser M. Long-term follow-up of 62 patients with myositis. J Neurol 2014;261(5):992–8. [DOI] [PubMed] [Google Scholar]
- 7.Danieli MG, Gambini S, Pettinari L, Logullo F, Veronesi G, Gabrielli A. Impact of treatment on survival in polymyositis and dermatomyositis. A single-centre long-term follow-up study. Autoimmunity reviews 2014;13(10):1048–54. [DOI] [PubMed] [Google Scholar]
- 8.Amaral Silva M, Cogollo E, Isenberg DA. Why do patients with myositis die? A retrospective analysis of a single-centre cohort. Clin Exp Rheumatol 2016;34(5):820–6. [PubMed] [Google Scholar]
- 9.Christopher-Stine L, Wan GJ, Kelly W, McGowan M, Bostic R, Reed ML. Patient-reported dermatomyositis and polymyositis flare symptoms are associated with disability, productivity loss, and health care resource use. J Manag Care Spec Pharm 2020;26(11):1424–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Williams J, Verstappen SMM, Krogh NS, Dixon WG, Chinoy H, Oldroyd AGS. Remotely collected patient-reported data characterises the impact of idiopathic inflammatory myopathy flares upon work productivity. Rheumatology (Oxford) 2024;63(6):e168–e9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Christopher-Stine L, Wan GJ, Kelly W, McGowan M, Bostic R, Reed ML. Patient-reported dermatomyositis and polymyositis flare symptoms are associated with disability, productivity loss, and health care resource use. Journal of Managed Care & Specialty Pharmacy 2020;26(11):1424–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Oddis CV, Rider LG, Reed AM, et al. International consensus guidelines for trials of therapies in the idiopathic inflammatory myopathies. Arthritis Rheum 2005;52(9):2607–15. [DOI] [PubMed] [Google Scholar]
- 13.Lundberg IE, Tjarnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 2017;76(12):1955–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Oldroyd AGS, Krogh NS, Dixon WG, Chinoy H. Investigating characteristics of idiopathic inflammatory myopathy flares using daily symptom data collected via a smartphone app. Rheumatology (Oxford) 2022;61(12):4845–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Mamyrova G, Rider LG, Ehrlich A, et al. Environmental factors associated with disease flare in juvenile and adult dermatomyositis. Rheumatology (Oxford) 2017;56(8):1342–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Oldroyd A, Dixon W, Chinoy H, Howells K. Patient insights on living with idiopathic inflammatory myopathy and the limitations of disease activity measurement methods - a qualitative study. BMC Rheumatol 2020;4:47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Schiopu E, Phillips K, MacDonald PM, Crofford LJ, Somers EC. Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine. Arthritis Res Ther 2012;14(1):R22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Pinal-Fernandez I, Casal-Dominguez M, Huapaya JA, et al. A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies. Rheumatology (Oxford) 2017;56(6):999–1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Phillippi K, Hoeltzel M, Byun Robinson A, Kim S. Race, Income, and Disease Outcomes in Juvenile Dermatomyositis. J Pediatr 2017;184:38–44.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Sigurgeirsson B, Lindelöf B, Edhag O, Allander E. Risk of cancer in patients with dermatomyositis or polymyositis. A population-based study. N Engl J Med 1992;326(6):363–7. [DOI] [PubMed] [Google Scholar]
- 21.Mecoli CA, Igusa T, Chen M, et al. Subsets of Idiopathic Inflammatory Myositis Enriched for Contemporaneous Cancer Relative to the General Population. Arthritis Rheumatol 2023;75(4):620–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Hasegawa A, Kurasawa K, Koike R, et al. Clinical features and risk factors of flare in anti-synthetase syndrome. Clin Rheumatol 2025. [DOI] [PubMed] [Google Scholar]
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