Scleroderma (systemic sclerosis) is a rare autoimmune connective tissue disease that can damage multiple organs and reduce quality of life. Patient-reported outcome measures capture the patient’s perspective. Some measures are specific to systemic sclerosis and others are general. Patient-reported outcomes in systemic sclerosis are important to aid in understanding the impact of systemic sclerosis on patients.
Key points
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Systemic sclerosis (scleroderma) is a rare, chronic, connective tissue disease with fibrosis of the skin and many organs, vascular damage, and production of autoantibodies leading to many heterogeneous signs and symptoms.
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Systemic sclerosis is one of the most severe connective tissue diseases with disability; altered appearance; organ damage of skin, gastrointestinal tract, lungs, pulmonary arteries, kidneys, and other organs; digital ulcers; and amputation, with significant emotional and social impact.
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Patient-reported outcome measures provide a patient-centered method of assessing the impact of various problems in systemic sclerosis.
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Patient-reported outcome measures in systemic sclerosis can be general measures or tools that are unique to SSc.
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Commonly used patient-reported outcome measures include the Health Assessment Questionnaire Disability Index, Scleroderma Health Assessment Questionnaire, pain assessments, patient global assessments, Raynaud’s Condition Score, and University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale 2.0.
Introduction
Systemic sclerosis (SSc), also known as scleroderma, is a chronic, rare autoimmune disease involving the connective tissues of several organs in a progressive manner. SSc classically is associated with fibrosis of the skin and internal organs, the production of autoantibodies, and vascular disruption and damage. Depending on the severity of the disease and the organs affected, patients with SSc have different clinical features. Scleroderma is considered one of the most severe of the connective tissue diseases with significant morbidity and mortality.
SSc is classified according to the amount of skin involvement. In limited cutaneous SSc, the skin distal to the elbows and knees is involved, but the skin of the face and neck may also be fibrosed. In the more severe diffuse cutaneous SSc (dcSSc) subset, skin fibrosis occurs both proximally and distally. The diffuse form is more progressive and has earlier visceral organ involvement.
SSc usually causes fibrosis of the tissues of the face and hands, leading to disability and disfigurement. However, many other manifestations of SSc can affect a patient’s quality of life (QoL) and prognosis. For example, SSc patients often experience pain from many features of their disease, including Raynaud’s phenomenon, digital ulcers, gastrointestinal tract involvement, and inflammatory arthritis. Moreover, SSc patients may experience severe pruritus, which can interfere with function and sleep. Pulmonary involvement can include pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), resulting in symptoms such as dyspnea, fatigue, cough, and chest pain. Chest pain in SSc may also be related to cardiac involvement and pleural and pericardial effusions. Gastrointestinal tract fibrosis can lead to dysmotility, severe gastroesophageal reflux disorder (GERD), early satiety, cramps, bloating, diarrhea and incontinence. Scleroderma may affect the kidneys, leading to scleroderma renal crisis, or the heart, leading to cardiomyopathy, arrhythmias, and constrictive pericarditis.
One of the most common symptoms in SSc is fatigue, which occurs in 90% of patients. Other symptoms, including depressive symptoms, sexual dysfunction, fear of disease progression and death, issues with body image, and work disability all affect the QoL of patients with SSc. Approximately half become work disabled. Altered facial appearance and abnormal hands disfigure SSc patients, affecting self-esteem. Moreover, SSc patients suffer psychologically because of the progressive nature of SSc and lack of a cure. There may be reduced oral opening and dry mouth, and combined with reflux this can result in problems eating, halitosis, and poor oral hygiene.
Treatment of SSc is generally complicated, including a combination of symptomatic treatment and disease- or organ-specific treatment. There are scant guidelines for nonpharmacologic management of SSc. Patient-reported outcome (PRO) measurements (PROMs) give patients the opportunity to express the effects of their disease experience. PROMs are unique in that they do not measure the same thing as biologic parameters and physician-assessed outcomes, even though there can be correlations between various measurements.
Although objective measurements of disease characteristics related to SSc exist, such as pulmonary function tests or digital ulcer counts, which may overlap with PROS, they do not fully quantify the patient’s experience. Physicians may view major internal organ involvement as extremely important, whereas patients may be more concerned with symptoms that reduce their QoL, such as intense pain, pruritus, or fatigue. PROs allow for the measurement of health outcomes according to the patient, which reflect the goal of improving their QoL and health care. Most trials in SSc include outcomes reflecting laboratory, physician, and patient measures.
Introduction
Systemic sclerosis (SSc), also known as scleroderma, is a chronic, rare autoimmune disease involving the connective tissues of several organs in a progressive manner. SSc classically is associated with fibrosis of the skin and internal organs, the production of autoantibodies, and vascular disruption and damage. Depending on the severity of the disease and the organs affected, patients with SSc have different clinical features. Scleroderma is considered one of the most severe of the connective tissue diseases with significant morbidity and mortality.
SSc is classified according to the amount of skin involvement. In limited cutaneous SSc, the skin distal to the elbows and knees is involved, but the skin of the face and neck may also be fibrosed. In the more severe diffuse cutaneous SSc (dcSSc) subset, skin fibrosis occurs both proximally and distally. The diffuse form is more progressive and has earlier visceral organ involvement.
SSc usually causes fibrosis of the tissues of the face and hands, leading to disability and disfigurement. However, many other manifestations of SSc can affect a patient’s quality of life (QoL) and prognosis. For example, SSc patients often experience pain from many features of their disease, including Raynaud’s phenomenon, digital ulcers, gastrointestinal tract involvement, and inflammatory arthritis. Moreover, SSc patients may experience severe pruritus, which can interfere with function and sleep. Pulmonary involvement can include pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), resulting in symptoms such as dyspnea, fatigue, cough, and chest pain. Chest pain in SSc may also be related to cardiac involvement and pleural and pericardial effusions. Gastrointestinal tract fibrosis can lead to dysmotility, severe gastroesophageal reflux disorder (GERD), early satiety, cramps, bloating, diarrhea and incontinence. Scleroderma may affect the kidneys, leading to scleroderma renal crisis, or the heart, leading to cardiomyopathy, arrhythmias, and constrictive pericarditis.
One of the most common symptoms in SSc is fatigue, which occurs in 90% of patients. Other symptoms, including depressive symptoms, sexual dysfunction, fear of disease progression and death, issues with body image, and work disability all affect the QoL of patients with SSc. Approximately half become work disabled. Altered facial appearance and abnormal hands disfigure SSc patients, affecting self-esteem. Moreover, SSc patients suffer psychologically because of the progressive nature of SSc and lack of a cure. There may be reduced oral opening and dry mouth, and combined with reflux this can result in problems eating, halitosis, and poor oral hygiene.
Treatment of SSc is generally complicated, including a combination of symptomatic treatment and disease- or organ-specific treatment. There are scant guidelines for nonpharmacologic management of SSc. Patient-reported outcome (PRO) measurements (PROMs) give patients the opportunity to express the effects of their disease experience. PROMs are unique in that they do not measure the same thing as biologic parameters and physician-assessed outcomes, even though there can be correlations between various measurements.
Although objective measurements of disease characteristics related to SSc exist, such as pulmonary function tests or digital ulcer counts, which may overlap with PROS, they do not fully quantify the patient’s experience. Physicians may view major internal organ involvement as extremely important, whereas patients may be more concerned with symptoms that reduce their QoL, such as intense pain, pruritus, or fatigue. PROs allow for the measurement of health outcomes according to the patient, which reflect the goal of improving their QoL and health care. Most trials in SSc include outcomes reflecting laboratory, physician, and patient measures.
Key elements of patient-reported outcome measurements in Systemic sclerosis
Performing a physical examination to assess skin disease or obtaining blood work to measure hemoglobin, renal function, and pulmonary function are well established and relatively easy ways to measure some aspects of SSc. However, it is not as simple to capture the patient experience. PROMs are tools that attempt to address this issue. The development and validation of these patient-centered instruments requires a rigorous process.
SSc is heterogeneous and can involve nearly every organ system. Accordingly, patients may be affected in every domain of their life, so a variety of tools are required to capture their experience. PROMs need to be reliable, valid, accurate, and ideally responsive to change. SSc has unique traits compared with other chronic illnesses, so some tools may be specific to SSc.
PROMs should be accessible, easy to use and score, relevant, and meaningful to the population in question. SSc affects individuals with varying levels of education, languages, and backgrounds, so PROMs should be straightforward and easily understood by patients. Many rheumatologists operate busy clinics, so for tools to gain widespread acceptance in practice, they should be easily integrated into daily routine. This fact is true for the Health Assessment Questionnaire (HAQ) and patient global assessments of overall disease, pain, and fatigue. On the other hand, some PROMs are solely used in clinical trials in which specific research is addressed (such as performing a Raynaud’s Condition Score [RCS] daily during a Raynaud’s phenomenon trial).
The most commonly used PROs in SSc are the HAQ, the Scleroderma HAQ (SHAQ), pain assessments, patient global assessments, the RCS, and the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale 2.0 (UCLA SCTC GIT 2.0). Tools that are newly being applied to SSc such as the Patient Reported Outcomes Measurement Information System (PROMIS) are also of interest. These instruments are the focus of this article, but there are numerous other PROMs that have been developed for or are used in SSc. Fig. 1 illustrates the multitude of symptoms that frequently occur in SSc.
General Measures
Health Assessment Questionnaire
One of the earliest PROs used in rheumatic disease, the HAQ is a quick, easy, and inexpensive way to assess a patient’s health status. Originally published in 1980, the HAQ focuses on 5 core domains: death, discomfort, disability, drug toxicity, and cost. Items in the HAQ are scored from 0 to 3, with 3 indicating greater disability. An overall average score is then calculated using the totals for completed sections. Although the HAQ was originally used in rheumatoid arthritis (RA), the disability section of the HAQ (HAQ-DI) is one of the most commonly used assessments of function in SSc. The HAQ-DI focuses on daily activities including eating, arising, hygiene, gripping, walking, and dressing. The tool is reliable and responsive to change; has good predictive, concurrent, and construct validity; and predicts mortality in early dcSSc. The HAQ-DI does, however, have limitations. For example, the HAQ-DI focuses mainly on musculoskeletal disability rather than other forms of disability that patients with SSc may encounter, such as dyspnea, fatigue, and gastrointestinal complaints. Moreover, it was suggested that including assistive devices in the scoring may overestimate the disability of the respondent. Because the HAQ was published in 1980, there are also concerns that it may be outdated and may have certain items only applicable to some patients, such as opening a carton of milk. It does not include current hand function such as keyboarding or using a cell phone.
Scleroderma Health Assessment Questionnaire
To make a more SSc-specific measurement than the generic HAQ, Steen and Medsger published the SHAQ in 1997. The SHAQ is the HAQ-DI and also includes visual analog scales (VAS) for pain, digital ulcers, vascular problems, gastrointestinal symptoms, lung symptoms, and overall disease severity ; thus, it has features beyond function that commonly affect SSc patients. For each VAS symptom, a patient indicates on a 15-cm line how much the symptom interferes with their function. Each centimeter indicated is converted to 0.2 points, or the total distance in centimeters is measured and divided by 5 to give a score from 0 to 3. Each VAS score is displayed individually in addition to the HAQ-DI score.
The SHAQ is also fast and easy to use with better face validity in SSc than the HAQ-DI. Moreover, the SHAQ is responsive to change and is found to have reliability and convergent, predictive and concurrent validity. The HAQ-DI is still more widely used than the SHAQ, and the SHAQ is sometimes improperly scored by those using it, as each VAS scale is to be scored separately.
Global assessments
Global assessments are fast, easy-to-score tools that can be completed by a patient or others (eg, physicians or blinded assessor in trials). As with many other PRO measures, global assessments are useful because they allow patients to express their disease impact through one or more measures. Several different questions can be used in various global assessments. Global assessments may have one representative score or they may consist of a variety of subscales. Because physicians and patients rate disease differently, there are often differences in their individual global assessments. For example, patients often rate their disease severity higher than their physicians do. Global assessments have been found to be valid and sensitive to change. There is no standard question that is asked, and often scales are numerical or continuous. Global assessments may be for overall SSc disease activity, severity, and damage or be organ/symptom specific, such as for the impact of gastrointestinal problems, Raynaud’s Phenomenon, pain, or fatigue. It is important to note that a single question may give enough information compared with a longer questionnaire, and it depends on what one wants to measure. A long questionnaire may be more comprehensive, but a visual analog scale may be just as sensitive to change when health status improves or worsens.
Other general measures
A variety of other PROs have been used as measures of health-related QoL (HRQoL) in SSc. The EuroQol-5D (EQ-5D) is one of the earliest of these PROs, developed in 1987. The EQ-5D is found to correlate with the HAQ-DI, SHAQ, and the Short Form-6D (SF-6D) and is valid for patients with SSc.
The Short-Form Health Survey (SF-36) is another PROM that has been applied to assess the HRQoL of patients with SSc. The SF-36 strongly correlates to the HAQ-DI for SSc and has adequate validity, although reliability of this tool in SSc has yet to be determined. The importance of general QoL measures is that they can potentially compare the impact of various diseases, but they may not be completely relevant or may not capture the totality of a specific disease.
General measures of well-being and HRQoL developed specifically for SSc include the Symptom Burden Index (SBI) and the United Kingdom SSc Functional Score (UKFS). Neither, however, is widely used in SSc studies. Table 1 compares general and SSc-specific common PROMs.
| Score | Features | Specific to SSc? | |
|---|---|---|---|
| HRQoL and general measures | Health Assessment Questionnaire (HAQ) |
| — |
| SHAQ |
| ✓ | |
| EQ-5D |
| — | |
| SF-36 |
| — | |
| SBI |
| ✓ | |
| UKFS |
| ✓ | |
| Health status in chronic disease | FACIT |
| — |
| PROMIS |
| — | |
| Pulmonary involvement | Borg Dyspnea Index |
| — |
| Baseline Dyspnea Index and Transition Dyspnea Index |
| — | |
| CAMPHOR |
| — | |
| Hand involvement and disability | Cochin Hand Function Scale/Duruoz Hand Index |
| — |
| HAQ and HAQ-DI |
| — | |
| DASH |
| — | |
| ABILHAND |
| — | |
| Michigan Hand Questionnaire | — | — | |
| Gastrointestinal involvement | SSc-GIT 1.0 |
| ✓ |
| UCLA SCTC GIT 2.0 |
| ✓ | |
| Mouth disability | MHISS |
| ✓ |
| Raynaud’s phenomenon | RCS |
| — |
Related posts:
Patient Reported Outcomes in Rheumatic Diseases
Patient-Reported Outcomes in Rheumatoid Arthritis
Patient-Reported Outcomes in Systemic Lupus Erythematosus
Patient-Reported Outcomes in Psoriatic Arthritis
Challenges and Opportunities in Using Patient-reported Outcomes in Quality Measurement in Rheumatology
The Promise of Patient-Reported Outcomes Measurement Information System—Turning Theory into Reality
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