Functional outcome and quality of life in adult patients with idiopathic inflammatory myositis

A. Ponyi1,2, G. Borgulya2, T. Constantin2, A. Váncsa1, L. Gergely1 and K. Dankó1

1 Division of Clinical Immunology, Third Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen and 2 Second Department of Pediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary.

Correspondence to: A. Ponyi, Third Department of Internal Medicine, Division of Clinical Immunology, Medical and Health Science Center, University of Debrecen, 4004 Debrecen, Móricz Zs Krt 22, Hungary. E-mail: ponyi{at}gyer2.sote.hu


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objectives. To present the outcome of patients with idiopathic inflammatory myositis, focusing on functional ability and quality of life.

Methods. Analysis was performed using data from 105 adult patients with definitive polymyositis, dermatomyositis or overlap myositis, who were followed up at a single centre. The diagnosis was made between 1979 and 2000 based on Bohan and Peter's criteria. Functional ability was assessed after a minimum follow-up of 3 yr with the Health Assessment Questionnaire Disability Index (HAQDI) and quality of life was measured with the Short Form 36-item questionnaire (SF-36).

Results. Fifteen patients in our cohort died and 87 participated in the evaluation of functional outcome. Functional ability after a median follow-up of 107.1 months (range 36.4–273.3) was heterogeneous. The median HAQDI score was 0.875 (range 0–2.875). Polyphasic or chronic–progressive disease course, osteoporosis and long-term follow-up were predictive of higher HAQDI scores. In terms of quality of life, significant differences from population norms were shown in all domains of the SF-36. There were no significant differences in the SF-36 scores among the patients according to clinicopathological subset or disease course.

Conclusions. Although the mortality of our cohort was favourable, myositis continues to have a great impact on life in the medium and long term. The present work indicates that myositis patients have a significantly poorer quality of life than the normal population, but there was no difference among the patients according to clinicopathological subsets.

KEY WORDS: Dermatomyositis, Outcome, Overlap myositis, Polymyositis, Quality of life


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by chronic muscle inflammation leading to progressive weakness of the proximal muscles. The frequent extraskeletal and extramuscular involvement contributes greatly to the morbidity and mortality of the disease. Survival has progressively improved worldwide in recent decades [1, 2], but IIMs continue to have a long-term impact on life.

Outcome can be evaluated based on survival rate, disease activity and damage, as well as from the perspective of the individual patient. For a complete assessment of the outcome in patients with IIM, it is essential to evaluate the broader impact of illness and treatment on patients.

Various instruments are available to assess health status. The International Myositis Outcome Assessment Collaborative Study Group (IMACS) recommends [3] the Stanford Health Assessment Questionnaire (HAQ) [4] for the evaluation of physical function in myositis patients. The HAQ is a comprehensive measure assessing cumulative functional abnormalities in performing activities of daily living. The widely used generic quality of life (QoL) measure, the Short Form 36-item questionnaire (SF-36), is also recommended by the IMACS for myositis patients [3].

In this study, we describe the outcome of 105 adult patients with different subsets of IIM who have been followed-up longitudinally by a single clinical immunology centre. Physical function, as measured by HAQ, and QoL, as measured by SF-36, were investigated as primary outcomes. Secondary outcomes were work status and the development of glucocorticoid-related complications.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patient selection and study design
One hundred and five adult patients with definitive IIM, who were diagnosed, treated and longitudinally followed up for a minimum of 3 yr by the Third Department of Internal Medicine, University of Debrecen, Hungary, were enrolled from our myositis database.

Diagnosis of IIM was based in all cases upon the criteria defined by Bohan and Peter [5]. The diagnosis was made between 1979 and 2000. All the patients were Caucasian. Patients were classified into clinicopathological subsets: (i) primary, adult polymyositis (PM); (ii) primary, adult dermatomyositis (DM); and (iii) overlap myositis (OM) (myositis in association with all or some clinical and immunological features of another systemic autoimmune disease). Patients with OM met the classification criteria for IIM as well as for the respective disease overlapping with myositis: the revised criteria of the American Rheumatism Association for rheumatoid arthritis (RA) [6], systemic lupus erythematosus (SLE) [7], systemic sclerosis (SSc) [8] or the European criteria for Sjögren syndrome [9]. Patients with juvenile DM/PM or OM and patients with cancer-associated myositis were excluded.

We analysed the following data: the time of diagnosis, age, sex, duration of symptoms before the diagnosis was made, presence of Raynaud's phenomenon, presence of polyarthritis, presence of myositis-specific anti-Jo-1 antibody (measured by enzyme-linked immunoassay), initial treatment (glucocorticoid or glucocorticoid with other second-line immunosuppressive drugs, including methotrexate, cyclosporin A, azathioprine, cyclophosphamide and intravenous immunoglobulin) and the date of death or the end of follow-up.

Evaluation of primary and secondary outcomes was performed on all patients between 1 February 2003 and 31 August 2003. Written informed consent was obtained for participation in all cases. The study conformed to the ethical standards currently applied in Hungary. Of the surviving 90 patients, only two (2%) dropped out and 87 agreed to participate in the study. At the same time as the administration of the HAQ and SF-36 questionnaires, a detailed evaluation of disease activity, disease course and secondary outcomes was performed. The reference time for the HAQ and the SF-36 was the week preceding the administration of the questionnaires.

Evaluation of disease activity and disease course
To evaluate muscle power, the UK Medical Research Council System scale (0–5) was used to test muscle strength of the following manoeuvres on each side: shoulder abduction; elbow flexion; elbow extension; finger strength; hip flexion; hip abduction; knee extension; foot dorsiflexion; and neck flexion (manual muscle strength testing, MMT). Zero is the lowest and 5 is the highest score indicating the level of muscle power; the maximum score is 85 points, which refers to normal muscle power.

Disease activity was defined based upon (i) constant or progressive reduction in muscle strength (measured by MMT), (ii) elevation of serum creatinine kinase (CK) and/or lactate acid dehydrogenase (LDH) activity [measured with an Integra 700 automated analyser (Roche)], and (iii) the presence of the characteristic rash in patients with DM. Remission was defined as (i) stable improvement or normalization of muscle strength (measured by MMT), (ii) normalization of serum CK and/or LDH activity, and (iii) the disappearance of cutaneous changes. By definition, patients were in the inactive phase of the disease when remission was achieved. In some patients, moderate and stable doses of immunosuppressive drugs were used to maintain remission.

Patients were classified into three groups based on their clinical course: (i) monophasic; (ii) relapsing–remitting; and (iii) chronic–progressive. The disease course was considered to be monophasic if a single episode of the disease occurred and then recovery from active disease was achieved and the patient remained free of symptoms and laboratory changes of disease activity 24 months after diagnosis. The disease course was regarded as relapsing–remitting if the patient had more than a single episode and remission occurred between relapses. A relapse was defined as disease reactivation after remission lasting 6 months or more. A chronic–progressive course was defined as failure to achieve remission by 24 months after diagnosis.

Evaluation of functional outcome by HAQ and QoL by SF-36
Functional ability was assessed using a translated and validated Hungarian version of the Stanford HAQ disability index (HAQDI) [4, 10, 11]. The HAQ was self-administered. HAQ examines disability in eight categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip and activities. The range of the final HAQDI score is 0.0–3.0. Patients were classified as mildly disabled with a score of 0.1–1.0, moderately disabled with a score of 1.01–2.0 and severely disabled with a score of 2.01–3.0. Eighty-seven questionnaires were completed from a possible 90, and 80 were assessable.

The SF-36 is a self-administered questionnaire containing 36 items which represent eight domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. The SF-36 scores are calculated on a scale in which 0 represents the worst and 100 the best. SF-36 has been translated and validated for Hungarian conditions [12]. Eighty-seven questionnaires were completed from the possible 90.

Secondary outcomes
In addition, we investigated glucocorticoid-related complications: osteoporosis, osteoporotic compression fracture (CF) of the spine and avascular necrosis (AVN). These outcomes were evaluated on the basis of the clinical records available. Osteoporosis was defined as a significantly reduced bone mineral density (BMD) according to the WHO classification (T score ≤2.5 S.D.). BMD was measured by dual energy X-ray absorptiometry at the lumbar spine and femoral neck. Work status was also investigated with a self-reported questionnaire.

Statistical analysis
All data were analysed using the SPSS for Windows 10.0 statistics software (SPSS Inc., Chicago, IL, USA). Characteristics of the patients were described with simple descriptive statistics. Medians were used rather than means when non-Gaussian distribution occurred. As a univariate analysis, Kruskal–Wallis and Mann–Whitney tests were used to compare HAQDI scores or SF-36-scores in different domains among groups of myositis patients.

The Z-test was used to determine the statistical significance of the observed differences in SF-36 scores between patient groups and the normal population. To take the age and sex effect into account in the SF-36, the data were grouped by gender and decade of age; the mean difference from population values [4] was calculated, then standardized by the standard deviation of the population to produce a Z-score for each domain.

Correlation analyses were performed to assess the correlation structure of the variables (Pearson's correlation or Spearman's rank correlation, as appropriate). Multiple linear regression models were applied to try to find variables that best predicted the value of the HAQ or SF-36 scores. The models contained a constant term, which represented the average response. The coefficient in the regression model can be interpreted as the increase in the outcome value when the corresponding predictor condition is present. A backward selection strategy was applied, using the F statistic with P = 0.05 as the criterion entering predictor variables and P = 0.1 as removal threshold. The independent variables entered in the regression models were: sex, age at the time of diagnosis, clinicopathological subset, delay in diagnosis, initial CK value, anti-Jo-1 status, Raynaud's, arthralgia or arthritis, initial treatment, duration of follow-up, disease course and secondary outcomes: osteoporosis, compression fracture or avascular necrosis, and work status. For the duration of follow-up, multiple categories were created as follows: category 1, 36–60 months; category 2, 61–84 months; category 3, 85–120 months; category 4, 121–160 months; category 5, longer than 161 months. Follow-up time categories were treated as one block in the model variable selection procedure.

P values equal or less than 0.05 were considered significant.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patient characteristics
Clinical characteristics of our cohort of IIM patients at the time of diagnosis and at the time of present study are summarized in Table 1. The most frequent clinicopathological subset was PM. The mean age at diagnosis did not differ among the subsets. DM patients were diagnosed after a significantly shorter duration of symptoms than PM and OM patients (P = 0.003 and P = 0.008 respectively). The observed female:male ratio was characteristic of the disease; however, among OM patients there was a female predominance. Anti-Jo-1 antibodies detected at the time of diagnosis were positive in 15% of the patients (anti-Jo-1 test were available only in 40 patients at the time of diagnosis). Fifteen patients died in our cohort, with 13 disease-specific deaths, mainly due to pulmonary and cardiac complications. Six out of 13 disease-specific deaths occurred within the first year after the diagnosis, with a cumulative mortality rate of 5.7% during the first year of the disease.


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TABLE 1. Characteristics of patients with IIM

 
Eighty-seven patients agreed to participate in the evaluation of functional outcome. There were 52 patients (60%) with PM and 21 patients with DM (24%). Fourteen patients had OM (16%), of whom seven had Sjögren syndrome, three had RA, two had SSc and two had SLE. At the time of the study, most of the patients were in the inactive phase (Table 1). Half of these patients still required medication, mainly low-dose glucocorticoids (2–20 mg/day, mean 7.85 mg/day), to maintain remission. In some cases, additional second-line agents were also needed (methotrexate in three patients, azathioprine in two patients and cyclophosphamide in two patients). At the time of the study, some patients still had active disease and were treated with glucocorticoids and second-line immunosuppressive agents (methotrexate, azathioprine or cyclosporin in three cases each, and cyclophosphamide in two cases). Based upon the disease course, approximately half of the patients were monophasic, and the chronic–progressive type was the least common. At the time of the study, the mean MMT score was 79±6.8 in monophasic patients, 73±5.7 in polyphasic patients, and 63±6.0 in chronic patients. Completely normal muscle power (when the MMT score was 85) was achieved in 21/45 (46.7%) monophasic patients and in 4/33 (12.1%) polyphasic patients, while no chronic patients had normal muscle power.

Functional outcome
The median HAQDI score was 0.875 (range 0–2.875). The distribution of HAQDI scores for the patients is presented in Fig. 1. As measured by the HAQ, 14 patients (17.5%) had no disability (HAQDI = 0), 31 patients (38.8%) were mildly disabled, 25 (31.2%) were moderately disabled and 10 (12.5%) were severely disabled. There were no significant differences in HAQDI scores among PM, DM and OM patients, but the disease course had a significant effect on functional ability. Patients with relapsing–remitting and chronic–progressive disease course had significantly higher HAQDI scores than monophasic patients (P = 0.029 and P = 0.013). Disease activity and muscle power measured by MMT were correlated with HAQDI (r = 0.28, P = 0.009 and r = –0.61, P<0.001). We also investigated a variety of factors predicting higher HAQDI scores with a multiple regression analysis (Table 2). Female gender, a polyphasic and chronic disease course, and osteoporosis were significant predictors of higher HAQDI scores. Furthermore, we found that patients who were followed up longer than 5 yr tended to have higher scores.



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FIG. 1. Distribution of HAQDI scores in patients with IIM.

 

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TABLE 2. Predicting factors for disability measured by HAQDI

 
Quality of life
Significant differences from population norms were shown in all domains of the SF-36 (P<0.001) (Fig. 2). There were no significant differences among PM, DM and OM patients in the scores for the SF-36 domains. Interestingly, there was also no difference according to the disease course. Disease activity at the time of the study did not correlate with SF-36 domains, but MMT scores correlated with physical functioning (r = –0.57, P<0.001), role functioning (r = –0.34, P = 0.001) and bodily pain (r = –0.27, P = 0.01) domains. Predictor variables of impaired QoL in different SF-36 domains are presented in Table 3.



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FIG. 2. SF-36 scores in different domains: patients with idiopathic inflammatory myositis compared with population means.

 

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TABLE 3. Predicting factors for QoL measured by SF-36

 


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FIG. 3. SF-36 scores in different domains: patients with idiopathic inflammatory myositis according to different disease courses.

 
Considering that the measured indices may evaluate some similar aspects of functional outcome, we examined possible relationships among them. Some domains of the SF-36 were correlated with HAQDI. Significant relationships were revealed between HAQDI and (i) the physical functioning domain (r = –0.71, P<0.001), (ii) HAQDI and the role functioning domain (r = –0.52, P<0.001), (iii) HAQDI and the bodily pain domain (r = –0.52, P<0.001) and (iv) HAQDI and the role emotional domain (r = –0.42, P<0.001).

Secondary outcomes
In the evaluation of glucocorticoid-related morbidity, we focused on investigating long-term side-effects. Glucocorticoid-induced osteoporosis affected 22 (25%) patients, two of whom had a CF and two had an AVN. We found no relationship between HAQDI score and these complications, although all patients with CF and AVN were mildly disabled based upon the HAQDI score (1.00–2.00). Patients with any one of these glucocorticoid-related complications had significantly lower SF-36 scores in physical functioning and role emotional domains (P = 0.003 and P = 0.011) compared with patients without these complications.

Work status was also examined. We evaluated the ability to work with respect to past and current employment in our cohort of patients. Thirty-seven out of 87 patients (42%) were not able to work at any point in life due to IIM. The proportion of disabled patients was not different among PM, DM and OM subsets. Interestingly, there was no significant relationship between work status and QoL.


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
In this study, our objective was to investigate the functional outcome of patients with myositis who were longitudinally followed up by a single centre in Hungary. As survival rates have increased since the introduction of glucocorticoids and immunosuppressive agents [1, 2, 13], the functional outcome has become an exciting field for observational studies. From the view of the patients, one of the most important aspects of health is the ability to perform activities of daily living.

The distribution of HAQDI scores revealed that only 17.5% of the patients had no disability and 12.5% were severely disabled. The majority of patients (70%) were mildly to moderately disabled. Therefore, there was an unfavourable functional outcome, taking into consideration that only 13% of the patients had active disease at the time of the study. As clinicopathological and serological subsets differ from each other in prognosis [14], we compared the functional outcomes of PM, DM, OM and anti-Jo-1 patients. There were no differences among them, though our cohort contained relatively few OM and anti-Jo-1-positive patients. Patients, who had a polyphasic or chronic–progressive disease course or had a longer duration of the disease tended to have higher HAQDI scores. Drouet et al. found that 30% of their 28 adult patients with PM/DM had a poor or very poor functional outcome, as measured by the Arthritis Impact Measurement Scales [15]. Functional prognosis of a cohort of 39 patients was found to be fairly well assessed by a four-stage grading system by Maugars et al.; 84.6% of patients experienced insignificant muscular disability at a minimum of 7-yr follow-up [13]. Clarke et al. analysed longitudinal changes in HAQDI scores in a national cohort of patients (n = 257) and found that disability increased with disease duration [16]. Disease damage derived from glucocorticoid treatment also contributed to disability. They suggested that more severe disease after diagnosis could be a factor contributing to functional disability. Marie et al. also had a longitudinal series of 77 patients with PM/DM [17] with a high morbidity. Functional course was measured with the HAQ; the median initial HAQDI score was 1.0 and the final HAQ score was 0.25. Moreover, only 52% of patients who achieved remission experienced a return to normal previous activities, and functional outcome was also poor in non-remitting patients. It should be mentioned that cancer-associated myositis patients were included in this study, and this contributed to the poor outcome. In contrast with adult patients, juvenile DM patients had a favourable functional outcome [18], as measured by the Childhood HAQ, as most of the 65 patients had scores of 0 (72%) and only 8% had a score ≥1.0 after a medium- or long-term follow-up.

Our patients had a marked impairment of QoL, as significant differences from Hungarian population norms were found in all domains of the SF-36. We found no difference among clinicopathological subsets, as also found by Sultan et al. [1]. There was no difference according to disease course in SF-36 scores. We also tried to analyse broader aspects of impaired QoL in myositis patients. Except for polyarthritis and Raynaud's phenomenon, no significant relationships were found between SF-36 scores and extramuscular features; therefore we did not investigate their effects. The multivariate regression analysis showed that the most important predictors were gender, the duration of follow-up and the presence of polyarthritis or osteoporosis. Being female was a predictor of poorer QoL in the domains of physical functioning, role functioning and bodily pain. Interestingly, in the domain of general health, being a female was a predictor of better QoL. Better QoL was measured in most of the domains with shorter duration of disease. Categorization of follow-up times suggests that the impairment of QoL is marked during the first 60 months of disease course, and later it stalls. Normal daily activities of living were affected by the presence of polyarthritis or osteoporosis, as these variables were predictors of physical and role functioning. Disease course was a predictor only in the physical functioning domain: chronic patients had a worse QoL in this domain. Furthermore, the effect of the clinicopathological subset appeared only in one domain: OM patients had poorer health status. The vitality, social functioning, role emotional and mental health domains seemed not to be influenced by the variables we examined. After all, these results can be interpreted as an effect of remarkable disease damage, which contributes to poor QoL even in patients with inactive disease.

Glucocorticoid-related morbidity also contributes to poorer patient-reported functional outcome. Because a significant predictive factor of impaired functional outcome was disease damage derived from the side-effects of long-term glucocorticoid treatment, the use of second-line agents should be encouraged. Recently, many authors have promoted the use of second-line drugs early in the disease course along with glucocorticoids [19], especially when the prognosis is considered to be poor. Prevention of osteoporosis and osteoporotic complications should be emphasized in the follow-up of myositis patients. It should be also mentioned that the poor functional outcome of our cohort may be overestimated because 14 patients, who were in remission, were lost to follow-up before a minimum follow-up of 3 yr (12% of the whole group).

In summary, our study indicates that, in the majority of patients, myositis continues to have a great impact on functional ability and on many aspects of QoL, in both the medium and the long term. The present work confirms that myositis patients have a significantly poorer QoL than the normal population, even if they are in remission. These results can be explained as a consequence of disease damage caused by disease activity and by its treatment as well.


    Acknowledgments
 
This work was supported by a grant from the Hungarian Scientific Research Fund (T: 030336).

The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 6 February 2004; revised version accepted 10 August 2004.