SSc is a heterogeneous disease with a variable clinical course. In limited cutaneous (lc) SSc, skin changes are restricted to distal to the elbows and/or knees, but may involve the face and neck regions, compared to diffuse cutaneous (dc) SSc in which skin thickening also occurs proximally. The disease course is more progressive and worse overall in dcSSc [1, 2]. Hand function may be an important determinant of functional disability in SSc. The hand deformity most observed in SSc is the disabling 'claw’ type deformity, which manifests as a loss of flexion at the metacarpophalangeal joint (MCP) and contracture at the proximal interphalangeal joint (PIP). Hand deformity in SSc is distinct from that of RA, where RA may result in subluxations and ulnar drift at MCPs, and malalignment at the wrists. In 115 SSc patients, at least moderate functional disability was present in 37.5% with lcSSc and 64% with dcSSc [3].

Although WD in SSc is not described in the literature, the prevalence and factors associated with WD in RA are well researched. RA is a logical parallel comparison group for this study of WD in SSc because: 1) it is a chronic autoimmune disease that affects people of similar age and sex as SSc, 2) the frequency of WD is known to be high in RA [4-9], and 3) a substantial body of research on factors predictive of WD in RA exists. Prevalence (or frequency) estimates of WD in RA have ranged from 9-67% (average disease duration ranged from 0.5-20 years) in cross-sectional studies and 22-90% (average disease duration ranged from 1-30 years) in longitudinal studies [4-9]. Reasons for WD in RA can vary with disease duration. Some with longstanding RA have joint damage but in early RA, there may be a decreased ability to work due to pain, fatigue, acute joint swelling and lack of adaptation to the chronicity of RA [30]. Disability in RA is often measured using the Health Assessment Questionnaire Disability Index (HAQ-DI) [31, 32] as an outcome measure. Disability appears to increase slowly at a relatively constant rate over the course of the disease after an initial dramatic improvement just following diagnosis (likely due to the onset of treatment) [33]. However, the course of disability for an individual cannot be predicted by disease duration [33]. There may be reversible and irreversible disability in RA - the former from disease activity and the latter from damage. In RA, gender appears to have little influence over functional outcome [34].

The Health Assessment Questionnaire Disability Index (HAQ-DI) measures functional disability and is widely used in rheumatologic diseases. HAQ-DI scores range from 0-3, where zero is no functional disability (or pain) and 3 is extreme disability (or pain). There is consensus in the RA literature that high HAQ-DI scores are associated with WD, as all studies that have investigated the HAQ-DI have confirmed the association with WD [6, 8-13, 15-29]. A large study (n=823) reported a baseline mean HAQ-DI score of 1.0 in those with WD; high HAQ-DI scores and baseline pain were the most significant predictors of subsequent WD [19]. Other studies have confirmed that high baseline HAQ-DI scores (at least ≥ 1.0) were among the most important predictors of WD within the 2-year to 20-year follow-up periods [17, 23, 26, 28, 29]. Cross-sectional studies have also shown higher HAQ-DI scores in work disabled (compared to working) patients [13, 24]. Table 1 summarizes the association between selected factors and WD in SSc vs RA.

The HAQ-DI has been validated for use in SSc and has demonstrated sensitivity over time [35, 36]. Functional disability (assessed by HAQ-DI) may be similar in SSc and RA; however, studies that combine dcSSc and lcSSc may mask an effect modification by disease subtype. For example, one study reported that SSc (n=24 dcSSc, 52 lcSSc) had less severe HAQ-DI scores compared to an age- and sex-matched RA cohort, but patients with dcSSc had the highest HAQ-DI scores of all three groups (dcSSc, lcSSc and RA) [37]. Thus, patients with dcSSc may have worse functional disability compared to lcSSc and RA.

Functional disability (often defined as HAQ-DI scores ≥ 1.0) has been a significantly important determinant of WD in every one of the RA studies reviewed that assessed functional disability [6, 8-13, 15-26]. High baseline HAQ scores (often defined as ≥1.0) have been shown to predict the development of WD [8, 22, 23]. Another study found that the mean HAQ scores over the course of the follow-up period were predictive of WD [19]. Thus, there is strong evidence for the predictive value of the HAQ in determining RA-related WD.

A survey assessed demographic and other personal factors, including work status, education level, and disease duration. The questionnaire was validated in a study of accuracy of self-report of medical history in rheumatologic patients [38]. The questionnaire was mailed to all patients with SSc (n=129) who had been seen at the same rheumatology practice over 2 years, and a sample of RA controls (n=230), frequency-matched with SSc for age and sex. Subjects were blinded to the hypothesis. SSc patients met the ACR diagnostic criteria for SSc, or if they did not, they met diagnostic criteria for CREST. That is to say that patients who had limited SSc and did not have digital pits or resorption and no pulmonary fibrosis were included if they met criteria for CREST [39, 40]. We then divided them into limited or diffuse disease (those being diagnosed with CREST were included in the limited group as in the Leroy criteria [40]). RA patients met the ACR criteria for RA [41].

After two mailings the response rates were 61% for SSc (n=28 dcSSc, n=51 lcSSc), and 67% for RA (n=155). Respondents to the questionnaire were of similar age and sex distributions as non-respondents. In the SSc group only, respondents had a longer mean disease duration compared to non-respondents (12 y vs 7.2 years, p=0.01). Subjects were asked “Do you work?” with multiple choice options: 1) Yes, 2) Yes, in the home, 3) Retired - not now but used to, 4) Had to stop work due to illness, 5) Never worked. All respondents who answered the question were considered for eligibility in the WD study. Subjects who chose multiple choice option # 4 (Had to stop due to illness) were considered work disabled. Subjects who had chosen either of option # 1 (Yes, ie. working) or # 2 (Yes, working in the home) were considered to not be work disabled and were included in the study. All subjects who reported that they were retired (option # 3) or that they had never worked (option #5) were excluded from the WD study. Fig. (1) describes participant selection and inclusion/exclusion criteria. N=61 SSc and n=104 RA patients were included in the WD SSc final database.

The same questionnaire used to collect WD status also included a question that asked if a subject’s job was physically demanding. The decision was made to include this exploratory variable in analyses as it was relevant to the research question but had been subject to item non-response (10 observations were missing in RA, 2 in dcSSc, and 4 in lcSSc).

As part of the ongoing clinical research initiative at St. Joseph’s Health Care London, the HAQ-DI and HAQ pain scales are collected at each clinic visit for all patients. The HAQ-DI that was completed at the clinic visit dated closest to the questionnaire timing was obtained from each subject’s medical chart. Consistent with both the SSc and RA literature, a dichotomized HAQ-DI score ≥ 1.0 vs <1.0 was used. HAQ-DI scores were calculated using the Standard Disability Index Scoring method which takes into account the use of aids and devices (available online at http://aramis.stanford. edu/downloads/HAQ%20Instructions.pdf). Scores <1.0 indicated less functional disability, and scores ≥ 1.0 indicated functional disability (captures any individual whose activities of daily living (ADLs) can only be carried out ‘with some difficulty’). However, the results of the bivariate analyses demonstrated that dichotomizing scores as <1.0 vs ≥ 1.0 resulted in a loss of information, and the decision to use continuous variables in the analyses was made. All data were entered into a JMP Version 4 database (SAS Institute, Cary, NC, USA, 2000).

The estimate of WD in SSc we observed (as well as the Moser estimate) was relatively high and is comparable to (or higher than) WD in RA, where the large majority of RA studies have reported WD in at least 30% of subjects by 10 years disease duration (range 27-62%). We compared WD in SSc with our internal RA reference group, and the proportions were significantly different (56% vs 35%, p=0.009) (Table 1). This difference in frequency may be partially due to the availability of more effective disease-modifying treatments in RA compared to SSc.

Despite the fact that this study used secondary data, the definition of WD was fairly consistent with those of several studies of WD in RA. This suggests that the measurement tool was accurate enough to adequately capture the relative impact of WD in SSc.

HAQ-DI scores were the most important independent factors associated with WD in both SSc and in RA. This is the first study to examine the relationship between HAQ-DI scores and WD in SSc; however, it is not surprising that this strong relationship exists, given that in the literature the HAQ-DI is strongly associated with WD in every RA study that assesses HAQ-DI [6, 9-13, 15-29].

Logistic regression analyses demonstrated that longer disease duration was marginally important in determining WD (β_dur = 0.043, OR=1.044, p=0.042); however, the effect of disease duration may be modified by disease extent.

Several studies have described more WD in women with RA than men [19, 20, 26], whereas others have not [13, 43]. Education has been associated with WD in RA. Highest level of education is often used as a proxy measure of SES [13, 17, 19, 20]. Disease duration of RA may affect WD but not in all literature [13].

High job demands, autonomy and control over work-related factors, and support in the work place are recognized factors associated with WD. RA patients often need to decrease their hours and/or change jobs, although this may not prevent subsequent WD [44-46].High physical requirements have been associated with WD in some studies [4, 6, 7, 9, 13, 15, 19, 22] but not in others [16, 17]. Anxiety and depression have been associated with current and subsequent WD in RA [10, 19, 20]. Danieli et al. reported that people with SSc in their cohort had more depressive symptoms compared to those with RA [37]. Thus, it is feasible that the psychological burden of SSc is substantial and may be associated with WD, although these factors were not addressed in this study.

One study of psychological adjustmentin SSc reported proportions of work disabled study participants [42]. Of 94 respondents to a mailed questionnaire (64% response rate), 23 (24.5%) were work disabled, 24 (25.5%) were working part-time or full-time outside the home, 17 (18.1%) were homemakers, and 27 (28.7%) were retired [42].

The population of southwestern Ontario has unique characteristics compared to other regions in Ontario. London is an urban center in which households may tend to have moderate-high SES (a common proxy measure for SES, having at least a high school education, was common in both SSc [83.6%] and RA [90.3%] respondents). Rural areas in the region may have less high SES households and different practices with respect to occupations, and some patients with SSc travel from remote geographic locations to receive care at the London clinic. Due to the unique catchment area serviced by the London rheumatology clinic, the results of this study may not be generalizable beyond southwestern Ontario, or even the study rheumatologist’s cohort. However, it is likely that results were representative of SSc and RA patients referred to rheumatology services in southwestern Ontario. Additional research would improve the certainty of this statement.

A limitation to this study is that it is cross-sectional (involving the analysis of data collected for another study with linkage to HAQs completed around the same time). Thus, there is a lack of information about the temporal association of potential risk factors (including disease/symptom onset and time of earliest high HAQ-DI scores) and the outcome. The distinction between the proportion with WD and the risk of developing WD is important. An additional limitation to this research was that subset analyses conducted between dcSSc and lcSSc subsets were underpowered, and thus no conclusions can be drawn based on these data. Strengths of this study include that the participants were well characterized (who met criteria for dcSSc, lcSSc, or RA), comparison groups were used appropriately, and the HAQ-DI was used as the outcome measure, which is standardized and validated in SSc.