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Indices of the Scleroderma Assessment Questionnaire (SAQ) can be used to demonstrate change in patients with systemic sclerosis over time
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Joint Bone Spine 75 (2008) 286e290 http://france.elsevier.com/direct/BONSOI/
Original article
Indices of the Scleroderma Assessment Questionnaire (SAQ) can be used to demonstrate change in patients with systemic sclerosis over time Predrag Ostojic*, Nemanja Damjanov Clinical Rheumatology III, Institute of Rheumatology, School of Medicine, University of Belgrade, Serbia Accepted 6 June 2007 Available online 2 April 2008
Abstract Objective: This study aims to estimate the value of the Scleroderma Assessment Questionnaire (SAQ) to demonstrate change in patients (pts) with systemic sclerosis (SSc) over time. Methods: Sixty pts with SSc were evaluated at two occasions, 12 months apart. Pts were divided into three subgroups according to criteria of improved, unchanged or deteriorated status of vascular, respiratory, gastrointestinal and musculosceletal system. All pts filled in the SAQ as part of both evaluations, and the Index of Vascular Status (IVS), Index of Respiratory Status (IRS), Index of Gastrointestinal status (IGS) and Index of Musculoskeletal Status (IMSS) were calculated. Average index scores for particular organ system at the beginning and after the follow-up period in all subgroups of pts were compared. Results: The mean value of IVS decreased significantly in pts with objectively improved vascular status (1.91 vs. 1.29, p ¼ 0.01), but increased in pts with deteriorated status (1.54 vs. 2.13, p ¼ 0.003). In the subgroup of pts with unchanged vascular morphology or function, the IVS did not change significantly either (1.84 vs. 1.77, p ¼ 0.36). The mean value of IRS decreased significantly in pts with objectively improved lung function (1.08 vs. 0.62, p ¼ 0.027), and increased in pts with deteriorated function (0.69 vs. 1.12, p ¼ 0.012). In the subgroup of pts with unchanged pulmonary function, the IRS did not change significantly (0.13 vs. 0.14, p ¼ 0.18). A statistically significant decrease in mean IGS value was found in pts who were treated with prokinetics (1.20 vs. 0.70, p < 0.001). In pts who were not treated with prokinetics, an increase of IGS was observed (0.58 vs. 0.76, p ¼ 0.002). Differences between mean values of the IMSS were statistically significant in subgroups of pts with improved (1.28 vs. 0.90, p ¼ 0.004) or deteriorated musculoskeletal status (0.98 vs. 1.44, p ¼ 0.012), but not in pts with unchanged condition of this organ system (0.72 vs. 0.68, p ¼ 0.498). Conclusion: The SAQ is a sensitive measurement to demonstrate change in patients with SSc over time. Ó 2008 Elsevier Masson SAS. All rights reserved. Keywords: Systemic sclerosis; Questionnaire; Functional ability; Disease status
1. Introduction Systemic sclerosis (SSc) is a clinically heterogeneous generalized disorder which affects the connective tissue of the skin and internal organs such as gastrointestinal tract, lungs, heart and kidneys. It is characterized by alterations of the
* Corresponding author. Institute of Rheumatology, Clinical Rheumatology III, School of Medicine, University of Belgrade, Resavska 69, 11000 Belgrade, Serbia. E-mail address: [email protected] (P. Ostojic).
microvasculature, disturbances of the immune system and by massive deposition of collagen. SSc is a chronic disease with usually slow progression of damage. In many patients it is almost impossible to differentiate exacerbation and remission of the disease, since inflammation is very mild and laboratory parameters, like C-reactive protein or erythrocyte sedimentation rate, are usually normal. For these reasons, it is very difficult to follow disease activity and functional ability in patients with SSc. However, criteria of disease activity in SSc have been recently defined by Valentini and coworkers, and the value of the test has been assessed in a multicenter study [1]. On the other hand, a severity scale
1297-319X/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2007.06.014
P. Ostojic, N. Damjanov / Joint Bone Spine 75 (2008) 286e290
for individual organ involvement, based on objective signs of damage, has been developed and tested by Medsger et al. [2]. Some questionnaires, which are developed to assess disease severity and functional ability in SSc, based on patient’s subjective complaints, are also published. The Health Assessment Questionnaire Disability Index (HAQ-DI), at first created for patients with rheumatoid arthritis, correlates with some parameters of functional ability also in patients with SSc, but not with objective signs of lung, heart or kidney involvement [3,4]. Steen and Medsger added special-generated Visual Analogue Scales (VAS) to the HAQ, in order to evaluate specific organ symptoms, like Raynaud’s phenomenon, gastrointestinal and lung involvement, pain, and overall disease severity [5]. This questionnaire is known as the Scleroderma Health Assessment Questionnaire (SHAQ). Rouf and coworkers [6] developed and tested the Systemic Sclerosis Questionnaire (SySQ), whereas Silman et al. [7] published the Scleroderma Functional Assessment Questionnaire (SFAQ). The SHAQ draws most attention, and a French version of the questionnaire is already validated [8]. But until now none of these questionnaires is widely in use. We have recently published a new questionnaire for SSc patients, the Scleroderma Assessment Questionnaire (SAQ). In a previous article [9], we have assessed face validity, reproducibility and content validity of the test. This study aims to estimate the value of the SAQ to demonstrate change in patients with SSc over time.
Table 1 Structure and the contents of the Scleroderma Assessment Questionnaire (SAQ) Subgroup of questions
Questions (English version)
Answering category
Vascular dysfunction
Do you feel pain in fingers when they are exposed to a cold environment? Do your fingers change colour (turn white or blue) when they are exposed to a cold environment? Do you feel pain in chest when the weather is cold?? Do you feel pain in your fingers when touching or holding objects
B
Do you feel you are short of breath while climbing twenty stairs? Do you feel you are short of breath when walking on the flat ground? Do you feel you are short of breath when dressing? Do you feel you are short of breath when sitting? Do you cough? Do you cough up phlegm?
A
Does a bite of a firm food (for example bread) lag behind your breastbone when you swallow? Does a sip of liquid (for example water or tea) lag behind your breastbone when you swallow? Do you have heartburn?? Do you feel pain when swallowing? Do you have constipation or diarrhea
B
Respiratory dysfunction
Gastrointestinal dysfunction
2. Methods Development of the SAQ, item generation and selection, structure and contents of the questionnaire, are systematically described in our previous paper [9]. Briefly, the SAQ consists of 23 questions divided into four subgroups: four items related to vascular dysfunction, six items to respiratory, five items to gastrointestinal and eight items to musculoskeletal dysfunction. Some items are derived from the SySQ questionnaire, with permission of authors. An English translation of the original Serbian language questionnaire, which is validated in this study, is shown in Table 1. There is a multiple choice of four answers to each question. As in HAQ, the answers are assessed on a 0e3 scale: answers referring to the intensity of symptoms (no ¼ 0, some ¼ 1, moderate ¼ 2, very intensive ¼ 3), answers referring to the frequency of symptoms (never ¼ 0, sometimes ¼ 1, frequently ¼ 2, always ¼ 3) and answers referring to the ability to perform activities (without difficulty ¼ 0, with some difficulty ¼ 1, with much difficulty ¼ 2, not able to do ¼ 3). The Index of Vascular Status (IVS), Index of Respiratory Status (IRS), Index of Gastrointestinal status (IGS) and Index of Musculoskeletal Status (IMSS) are calculated, dividing the total score for particular group by number of questions for that group. The range of all indices is from 0 to 3. A higher index value indicates more severe damage of particular organ system. Sixty consecutive SSc patients were included in this study. The characteristics of patients are shown in Table 2. At the start and after 12 months, established indicators of vascular, respiratory, gastrointestinal and musculoskeletal damage were assessed as follows: capillaroscopic findings, presence
287
Musculosceletal dysfunction
Do you drop objects frequently when holding them (for example a bar of soap, a glass or a pack of cigarettes)? Are you able to open your mouth wide enough to bite an apple? Are you able to hold a pen and write? Are you able to do and undo your shirt buttons? Are you able to hold a knife and cut bread? Are you able to get out of bed without someone’s help? Are you able to dry your entire body with a towel? Are you able to make your bed?
A
A A
A A A B B
B
B A B B
C C C C C C C
Bold items are derived from the SySQ with permission of authors. All items are scored from 0 to 3. Answering categories: A. intensity of symptoms (no ¼ 0, some ¼ 1, moderate ¼ 2, very intensive ¼ 3), B. frequency of symptoms (never ¼ 0, sometimes ¼ 1, frequently ¼ 2, always ¼ 3), C. ability to perform activities (without difficulty ¼ 0, with some difficulty ¼ 1, with much difficulty ¼ 2, no able to do ¼ 3).
of finger-tip ulcers, finger-tip osteolysis (estimated by hand radiography), interstitial lung fibrosis (estimated by chest radiography), forced vital capacity (FVC), carbon-monoxide diffusing capacity (DLCO), modified Rodnan skin score, finger-to-palm distance (distance between the tip of the third finger and the distal palmar crease), muscle weakness and arthritis (estimated by physical examination). At this two
P. Ostojic, N. Damjanov / Joint Bone Spine 75 (2008) 286e290
288 Table 2 Characteristics of patients
3. Results
Number of patients Mean age (minemax) (years) Gender M F
60 52 (25e76) 8 (13.3%) 52 (86.7%)
Disease subset lcSSc dcSSc
27 (45%) 33 (55%)
Mean disease duration (years) Pitting scars or digital ulcers Finger-tip osteolysis Telagiectasias Esophageal hypomotility Lung fibrosis (chest X-ray) FVC < 80% DLCO < 70% Tendon friction rubs Joint contractures Muscle weakness Arthralgia Arthritis
3.8 34/60 (56.6%) 13/60 (21.6%) 30/60 (50.0%) 45/60 (75.0%) 22/60 (36.6%) 16/60 (26.6%) 43/60 (71.6%) 9/60 (15.0%) 29/60 (48.3%) 19/60 (31.6%) 29/60 (48.3%) 9/60 (15.0%)
time points, all patients filled in the SAQ as part of their evaluation. After the follow-up period, patients were divided into three subgroups according to criteria of improved, deteriorated or unchanged status of each organ system (vascular, respiratory and musculoskeletal system). There are no validated decisive factors of improved or deteriorated disease status in SSc. For this reason, we used the same criteria applied by Steen and Medsger in the validation process of the SHAQ [5], with some modifications. These criteria are shown in Table 3. Because none of the usual diagnostic procedures is sensitive enough to detect changes in gastrointestinal function in SSc, patients were divided into two subgroups: patients treated and patients not treated with prokinetics (metoclopramide) during the follow-up period. The results of several functional studies [10e12] show that metoclopramide improves lower esophageal sphincter pressure, esophageal contraction amplitudes and reduces the gastric emptying delay. We used the Wilcoxon’s statistical test to compare the mean values of IVS, IRS, IGS and IMMS before and after follow-up, in subgroups of patients with improved, deteriorated or unchanged status of particular organ system.
Mean values of each index at the beginning and after 12 months in subgroups of patients with improved, deteriorated or unchanged status of particular organ system are shown in Table 4. According to previous established criteria, an objectively improved vascular status was observed in 14 patients (23.3%), a deteriorated status in 17 (28.3%) patients, while in 29 (48.4%) patients no significant change in vascular morphology or function was noticed. The mean value of IVS decreased significantly in patients with objectively improved vascular status (1.91 vs. 1.29, p ¼ 0.01), but increased in patients with deteriorated status (1.54 vs. 2.13, p ¼ 0.003). In the subgroup of patients with unchanged vascular morphology or function, the IVS did not change significantly either (1.84 vs. 1.77, p ¼ 0.36). Lung function tests were performed at both time points in only 28 of 60 patients, because of some technical troubles. In 10/28 (35.7%) patients, we have noticed an improvement (8 of them improved just DLCO), but in 13/28 (46.4%) patients we noticed a decline in lung function parameters after the follow-up. In 5/58 (17.9%) patients, the lung function did not change significantly. The mean value of IRS decreased significantly in patients with objectively improved lung function (1.08 vs. 0.62, p ¼ 0.027), and increased in patients with deteriorated function (0.69 vs. 1.12, p ¼ 0.012). In the subgroup of patients with unchanged pulmonary function, the IRS did not change significantly (0.13 vs. 0.14, p ¼ 0.18). Thirty-six patients were treated with prokinetics during the follow-up period, while 24 patients did not take these drugs. We have found a statistically significant decrease in mean IGS value in patients who were treated with prokinetics (1.20 vs. 0.70, p < 0.001). In patients who were not treated with prokinetics, an increase of IGS was observed (0.58 vs. 0.76, p ¼ 0.002). An objectively improved condition of the musculoskeletal system was observed in 30 (50.0%) patients, a deteriorated status in 20 (33.3%) patients, while in 10 (16.7%) patients no significant change was noticed. Differences between values of the IMSS were statistically significant in subgroups of patients with improved or deteriorated musculoskeletal status, but not in patients with unchanged condition of this organ system.
Table 3 Criteria of improved, deteriorated and unchanged status of particular organ system Organ system
Criteria of improved status
Criteria of deteriorated status
Criteria of unchanged status
Vascular system
1 Healed finger-tip ulcers, or 2 Improved capillaroscopic finding
1 No changes related to ulcers, capillaroscopic finding or osteolysis
Respiratory system
1 FVC increased for 15%, or 2 DLCO increased for 10%
1 2 3 1 2 3
Musculoskeletal system
1 2 3 4
Skin score decreased 20%, or FTP decreased 10%, or Improved muscle strength, or Remission of arthritis
1 2 3 4
Development of new ulcers, or Deteriorated capillaroscopic finding, or Development of finger-tip osteolysis FVC decreased 15%, or DLCO decreased 10%, or Development of interstitial fibrosis on chest radiography Skin score increased 20%, or FTP increased 10%, or Worsen muscle weakness, or Exacerbation of arthritis
1 FVC remain stable (15%), and 2 DLCO remain stable (10%) 1 2 3 4
Skin score remain stable ( 20%), and FTP remain stable (10%), and No change in muscle strength, and No change in arthritis
P. Ostojic, N. Damjanov / Joint Bone Spine 75 (2008) 286e290 Table 4 Differences among values of indices, calculated using the SAQ, at baseline and after 12 months for each patient subgroup Objective status change
Number of patients
Test
IVS
Improved status of vascular system Wilcoxon’s test
14/60
baseline 12 months
1.91 0.61 1.29 0.77 z ¼ 2.56, p ¼ 0.011
Deteriorated status of vascular system Wilcoxon’s test
17/60
baseline 12 months
1.54 0.63 2.13 0.62 z ¼ 2.97, p ¼ 0.003
Unchanged status of vascular system Wilcoxon’s test
29/60
baseline 12 months
1.84 0.63 1.77 0.69 z ¼ 0.92, p ¼ 0.36
Objective status change
Number of patients
Test
IRS
Improved status of respiratory system Wilcoxon’s test
10/28
baseline 12 months
1.08 0.61 0.62 0.77 z ¼ 2.21, p ¼ 0.027
Deteriorated status of respiratory system Wilcoxon’s test
12/28
baseline 12 months
0.69 0.58 1.12 0.58 z ¼ 2.52, p ¼ 0.012
Unchanged status of respiratory system Wilcoxon’s test
5/28
baseline 12 months
0.13 0.11 0.14 0.17 z ¼ 1.34, p ¼ 0.18
Objective status change
Number of patients
Test
IGS
Patients treated with prokinetics Wilcoxon’s test
36/60
baseline 12 months
1.20 0.54 0.70 0.39 z ¼ 4.03, p < 0.001
Patients not treated with prokinetics Wilcoxon’s test
24/60
baseline 12 months
0.58 0.40 0.76 0.42 z ¼ 3.15, p ¼ 0.002
Objective status change
Number of patients
Test
IMSS
Improved status of musculoskeletal syst. Wilcoxon’s test
30/60
baseline 12 months
1.28 0.68 0.90 0.68 z ¼ 2.87, p ¼ 0.004
Deteriorated status of musculoskeletal syst. Wilcoxon’s test
20/60
baseline 12 months
0.98 0.60 1.44 0.74 z ¼ 3.16, p ¼ 0.012
Unchanged status of musculoskeletal syst. Wilcoxon’s test
10/60
baseline 12 months
0.72 0.75 0.68 0.76 z ¼ 0.68, p ¼ 0.498
IVS e index of vascular status, IRS e index of respiratory status, IGS e index of gastrointestinal status, IMSS e index of musculoskeletal status.
4. Discussion It is difficult to follow changes in disease status and functional ability in patients with SSc. The inflammatory process is very mild, and organ damage develops often insidiously and slowly. Mostly used diagnostic procedures are not sensitive enough to detect organ damage in the early phase, and to notice minimal change in damage or function over time. Symptoms and patient’s subjective complaints are very important in evaluation of disease status in SSc, and physicians
289
often ask patients to guess, did their disease status changed over time or not. As in most other chronic rheumatic diseases, the self-assessment questionnaire is a very important tool for evaluation of patients with SSc. Since 1997, few selfassessment questionnaires for SSc patients are developed. Steen and Medsger have added visual analogue scales (VAS) to the Health Assessment Questionnaire (HAQ) [5], to cover typical organ symptoms. Nevertheless, the HAQ contains questions concerning functions that in systemic sclerosis usually are not limited (such as walking or arising), but questions concerning functional limitations which are result of skin thickening or fibrinous tenosynovitis are not included. Furthermore, no relationship was found between the HAQ-disability index and parameters of heart, lung and kidney involvement [3,4]. The proposed Visual analogue scales (VAS) to measure vascular and internal organ involvement in systemic sclerosis do not cover the whole spectrum of systemic sclerosis symptoms and the reliability of individual VAS is somewhat limited, which was shown by other authors [13,14]. The Systemic Sclerosis Questionnaire (SySQ) consists of 32 questions related to different organ symptoms, and its validity in evaluation of functional and morphological impairments in patients with systemic sclerosis is already established. Until now, no results have been published about its applicability to measure change in clinical trials. Silman et al. [7] recently published an 11-item disability assessment questionnaire for measurement of musculosceletal impairment in patients with systemic sclerosis. Until now none of these questionnaires is widely in use. We have recently published the SAQ, a new self-assessment questionnaire for patients with SSc, and assessed face validity, reproducibility and content validity of the test [9]. The SAQ was build up as a result of major input from patients and rheumatologist familiar with systemic sclerosis. Instead to use VAS, we developed specific questions related to vascular, respiratory, gastrointestinal and musculosceletal symptoms, to assess involvement of those organ systems. We noticed a significant correlation between the IVS and various indicators of vascular damage and dysfunction (capillary damage, finger-tip ulcers and finger-tip osteolysis). Values of the IRS were higher in patients with lung fibrosis, restrictive lung dysfunction and/ or decreased lung diffusing capacity, than in patients with normal pulmonary function. Higher values of the IGS were associated with esophageal hypomotility, while higher values of the IMMS were associated with reduced hand motility, joint contractures, muscle weakness and arthralgia or arthritis [9]. The present study documents usefulness of the SAQ to demonstrate change in disease status and functional ability in SSc patients over time. Values of the IVS correlated significantly with objective improvement or deterioration of vascular function, but did not change in patients with stable vascular function. In scientific clinical work, as well as in routine clinical practice, the IVS could be very useful in assessment of frequency, severity and pain during attacks of Raynaud’s phenomenon. Because of some technical troubles, lung function tests were performed at both time points in only 28 of 60 patients.
290
P. Ostojic, N. Damjanov / Joint Bone Spine 75 (2008) 286e290
Surprisingly, we have noticed improvement of lung function in even ten patients. Most of them improved in lung diffusing capacity, whilst vital capacity did not change significantly. One should be careful in making conclusions, because results of lung function tests depend on patient’s cooperation. Both, low number of re-evaluated patients and questionable reproducibility of lung function tests, may be a significant limitation of the validation process of IRS. However, at the end of the follow up, we noticed significantly higher values of IRS in patients with deteriorated lung function, and lower values in patients with improved lung function. The IGS could be very useful to assess dysfunction at different levels of the gastrointestinal tract. Some items in the subgroup of questions related to gastrointestinal dysfunction are linked to upper gastrointestinal symptoms (like dysphagia and heartburn), while others are linked to lower gastrointestinal symptoms (like diarrhea and constipation). In this study, IGS decreased significantly in patients who were treated with prokinetics, but increased in patients without therapy. Similarly, the IMMS correlated well with objective improvement or deterioration of musculosceletal damage and function. In conclusion, the Scleroderma Assessment Questionnaire (SAQ) is a sensitive measurement to demonstrate change in patients with SSc over time. In addition to previous estimated face validity, reproducibility and content validity of the test, our present results confirm the overall accuracy of the SAQ for assessment of disease status in SSc. References [1] Valentini G, Della Rosa A, Bombardieri S, et al. European multicentre study to define disease activity criteria for systemic sclerosis.* II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis 2001;60:592e8.
[2] Medsger Jr TA, Silman AJ, Steen VD, et al. A disease severity scale for systemic sclerosis: development and testing. J Rheumatol 1999;26: 2159e67. [3] Clements PJ, Weng KW, Hurwitz EL, et al. Correlates of the disability index of the Health Assessment Questionnaire: a measure of functional impairment in systemic sclerosis. Arthritis Rheum 1999;42:2372e80. [4] Poole JL, Steen VD. The use of the Health Assessment Questionnaire (HAQ) to determine physical disability in systemic sclerosis. Arthritis Care Res 1991;4:27e31. [5] Steen V, Medsger Jr TA. The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time. Arthritis Rheum 1997;40:1984e91. [6] Rouf J, Bru¨hlmann P, Michel A, et al. Development and validation of a self-administered systemic sclerosis questionnaire (SySQ). Rheumatology 1999;38:535e42. [7] Silman A, Akesson A, Newman J, et al. Assessment of functional ability in patients with scleroderma: a proposed new disability assessment instrument. J Rheumatol 1988;25:79e83. [8] Georges C, Chassany O, Mouthon L, et al. Validation of French Version of the Scleroderma Health Assessment Questionnaire (SSc HAQ). Clin Rheumatol 2005;24:3e10. [9] Ostojic P, Damjanov N. The Scleroderma Assessment Questionnaire (SAQ): a new self-assessment questionnaire for evaluation of disease status in patients with systemic sclerosis. Z Rheumatol 2006;65:168e75. [10] Mercado U, Arroyo de Anda R, Avenduo L, et al. Metoclopramide response in patients with early diffuse systemic sclerosis. Effect on esophageal motility abnormalities. Clin Exp Rheumatol 2005;23:685e8. [11] Johnson DA, Drane WE, Curran J, et al. Metoclopramide response in patients with progressive systemic sclerosis. Effect on esophageal and gastric abnormalities. Arch Intern Med 1987;147:1597e601. [12] Drane WE, Karvelis K, Johnson DA, et al. Scintigraphic detection of metoclopramide esophageal stimulation in progressive systemic sclerosis. J Nucl Med 1987;28:1040. [13] Ferraz MB, Quaresma MR, Aquino LR, et al. Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. J Rheumatol 1990;17:1022e4. [14] Zivkovic N, Petrovic R, Miliv V. Assessment of the value of different pain measurement scales in rheumatoid arthritis patients. Acta Rheum Belgrad 1996;26(2):49e52.
Joint Bone Spine 75 (2008) 286e290 http://france.elsevier.com/direct/BONSOI/
Original article
Indices of the Scleroderma Assessment Questionnaire (SAQ) can be used to demonstrate change in patients with systemic sclerosis over time Predrag Ostojic*, Nemanja Damjanov Clinical Rheumatology III, Institute of Rheumatology, School of Medicine, University of Belgrade, Serbia Accepted 6 June 2007 Available online 2 April 2008
Abstract Objective: This study aims to estimate the value of the Scleroderma Assessment Questionnaire (SAQ) to demonstrate change in patients (pts) with systemic sclerosis (SSc) over time. Methods: Sixty pts with SSc were evaluated at two occasions, 12 months apart. Pts were divided into three subgroups according to criteria of improved, unchanged or deteriorated status of vascular, respiratory, gastrointestinal and musculosceletal system. All pts filled in the SAQ as part of both evaluations, and the Index of Vascular Status (IVS), Index of Respiratory Status (IRS), Index of Gastrointestinal status (IGS) and Index of Musculoskeletal Status (IMSS) were calculated. Average index scores for particular organ system at the beginning and after the follow-up period in all subgroups of pts were compared. Results: The mean value of IVS decreased significantly in pts with objectively improved vascular status (1.91 vs. 1.29, p ¼ 0.01), but increased in pts with deteriorated status (1.54 vs. 2.13, p ¼ 0.003). In the subgroup of pts with unchanged vascular morphology or function, the IVS did not change significantly either (1.84 vs. 1.77, p ¼ 0.36). The mean value of IRS decreased significantly in pts with objectively improved lung function (1.08 vs. 0.62, p ¼ 0.027), and increased in pts with deteriorated function (0.69 vs. 1.12, p ¼ 0.012). In the subgroup of pts with unchanged pulmonary function, the IRS did not change significantly (0.13 vs. 0.14, p ¼ 0.18). A statistically significant decrease in mean IGS value was found in pts who were treated with prokinetics (1.20 vs. 0.70, p < 0.001). In pts who were not treated with prokinetics, an increase of IGS was observed (0.58 vs. 0.76, p ¼ 0.002). Differences between mean values of the IMSS were statistically significant in subgroups of pts with improved (1.28 vs. 0.90, p ¼ 0.004) or deteriorated musculoskeletal status (0.98 vs. 1.44, p ¼ 0.012), but not in pts with unchanged condition of this organ system (0.72 vs. 0.68, p ¼ 0.498). Conclusion: The SAQ is a sensitive measurement to demonstrate change in patients with SSc over time. Ó 2008 Elsevier Masson SAS. All rights reserved. Keywords: Systemic sclerosis; Questionnaire; Functional ability; Disease status
1. Introduction Systemic sclerosis (SSc) is a clinically heterogeneous generalized disorder which affects the connective tissue of the skin and internal organs such as gastrointestinal tract, lungs, heart and kidneys. It is characterized by alterations of the
* Corresponding author. Institute of Rheumatology, Clinical Rheumatology III, School of Medicine, University of Belgrade, Resavska 69, 11000 Belgrade, Serbia. E-mail address: [email protected] (P. Ostojic).
microvasculature, disturbances of the immune system and by massive deposition of collagen. SSc is a chronic disease with usually slow progression of damage. In many patients it is almost impossible to differentiate exacerbation and remission of the disease, since inflammation is very mild and laboratory parameters, like C-reactive protein or erythrocyte sedimentation rate, are usually normal. For these reasons, it is very difficult to follow disease activity and functional ability in patients with SSc. However, criteria of disease activity in SSc have been recently defined by Valentini and coworkers, and the value of the test has been assessed in a multicenter study [1]. On the other hand, a severity scale
1297-319X/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2007.06.014
P. Ostojic, N. Damjanov / Joint Bone Spine 75 (2008) 286e290
for individual organ involvement, based on objective signs of damage, has been developed and tested by Medsger et al. [2]. Some questionnaires, which are developed to assess disease severity and functional ability in SSc, based on patient’s subjective complaints, are also published. The Health Assessment Questionnaire Disability Index (HAQ-DI), at first created for patients with rheumatoid arthritis, correlates with some parameters of functional ability also in patients with SSc, but not with objective signs of lung, heart or kidney involvement [3,4]. Steen and Medsger added special-generated Visual Analogue Scales (VAS) to the HAQ, in order to evaluate specific organ symptoms, like Raynaud’s phenomenon, gastrointestinal and lung involvement, pain, and overall disease severity [5]. This questionnaire is known as the Scleroderma Health Assessment Questionnaire (SHAQ). Rouf and coworkers [6] developed and tested the Systemic Sclerosis Questionnaire (SySQ), whereas Silman et al. [7] published the Scleroderma Functional Assessment Questionnaire (SFAQ). The SHAQ draws most attention, and a French version of the questionnaire is already validated [8]. But until now none of these questionnaires is widely in use. We have recently published a new questionnaire for SSc patients, the Scleroderma Assessment Questionnaire (SAQ). In a previous article [9], we have assessed face validity, reproducibility and content validity of the test. This study aims to estimate the value of the SAQ to demonstrate change in patients with SSc over time.
Table 1 Structure and the contents of the Scleroderma Assessment Questionnaire (SAQ) Subgroup of questions
Questions (English version)
Answering category
Vascular dysfunction
Do you feel pain in fingers when they are exposed to a cold environment? Do your fingers change colour (turn white or blue) when they are exposed to a cold environment? Do you feel pain in chest when the weather is cold?? Do you feel pain in your fingers when touching or holding objects
B
Do you feel you are short of breath while climbing twenty stairs? Do you feel you are short of breath when walking on the flat ground? Do you feel you are short of breath when dressing? Do you feel you are short of breath when sitting? Do you cough? Do you cough up phlegm?
A
Does a bite of a firm food (for example bread) lag behind your breastbone when you swallow? Does a sip of liquid (for example water or tea) lag behind your breastbone when you swallow? Do you have heartburn?? Do you feel pain when swallowing? Do you have constipation or diarrhea
B
Respiratory dysfunction
Gastrointestinal dysfunction
2. Methods Development of the SAQ, item generation and selection, structure and contents of the questionnaire, are systematically described in our previous paper [9]. Briefly, the SAQ consists of 23 questions divided into four subgroups: four items related to vascular dysfunction, six items to respiratory, five items to gastrointestinal and eight items to musculoskeletal dysfunction. Some items are derived from the SySQ questionnaire, with permission of authors. An English translation of the original Serbian language questionnaire, which is validated in this study, is shown in Table 1. There is a multiple choice of four answers to each question. As in HAQ, the answers are assessed on a 0e3 scale: answers referring to the intensity of symptoms (no ¼ 0, some ¼ 1, moderate ¼ 2, very intensive ¼ 3), answers referring to the frequency of symptoms (never ¼ 0, sometimes ¼ 1, frequently ¼ 2, always ¼ 3) and answers referring to the ability to perform activities (without difficulty ¼ 0, with some difficulty ¼ 1, with much difficulty ¼ 2, not able to do ¼ 3). The Index of Vascular Status (IVS), Index of Respiratory Status (IRS), Index of Gastrointestinal status (IGS) and Index of Musculoskeletal Status (IMSS) are calculated, dividing the total score for particular group by number of questions for that group. The range of all indices is from 0 to 3. A higher index value indicates more severe damage of particular organ system. Sixty consecutive SSc patients were included in this study. The characteristics of patients are shown in Table 2. At the start and after 12 months, established indicators of vascular, respiratory, gastrointestinal and musculoskeletal damage were assessed as follows: capillaroscopic findings, presence
287
Musculosceletal dysfunction
Do you drop objects frequently when holding them (for example a bar of soap, a glass or a pack of cigarettes)? Are you able to open your mouth wide enough to bite an apple? Are you able to hold a pen and write? Are you able to do and undo your shirt buttons? Are you able to hold a knife and cut bread? Are you able to get out of bed without someone’s help? Are you able to dry your entire body with a towel? Are you able to make your bed?
A
A A
A A A B B
B
B A B B
C C C C C C C
Bold items are derived from the SySQ with permission of authors. All items are scored from 0 to 3. Answering categories: A. intensity of symptoms (no ¼ 0, some ¼ 1, moderate ¼ 2, very intensive ¼ 3), B. frequency of symptoms (never ¼ 0, sometimes ¼ 1, frequently ¼ 2, always ¼ 3), C. ability to perform activities (without difficulty ¼ 0, with some difficulty ¼ 1, with much difficulty ¼ 2, no able to do ¼ 3).
of finger-tip ulcers, finger-tip osteolysis (estimated by hand radiography), interstitial lung fibrosis (estimated by chest radiography), forced vital capacity (FVC), carbon-monoxide diffusing capacity (DLCO), modified Rodnan skin score, finger-to-palm distance (distance between the tip of the third finger and the distal palmar crease), muscle weakness and arthritis (estimated by physical examination). At this two
P. Ostojic, N. Damjanov / Joint Bone Spine 75 (2008) 286e290
288 Table 2 Characteristics of patients
3. Results
Number of patients Mean age (minemax) (years) Gender M F
60 52 (25e76) 8 (13.3%) 52 (86.7%)
Disease subset lcSSc dcSSc
27 (45%) 33 (55%)
Mean disease duration (years) Pitting scars or digital ulcers Finger-tip osteolysis Telagiectasias Esophageal hypomotility Lung fibrosis (chest X-ray) FVC < 80% DLCO < 70% Tendon friction rubs Joint contractures Muscle weakness Arthralgia Arthritis
3.8 34/60 (56.6%) 13/60 (21.6%) 30/60 (50.0%) 45/60 (75.0%) 22/60 (36.6%) 16/60 (26.6%) 43/60 (71.6%) 9/60 (15.0%) 29/60 (48.3%) 19/60 (31.6%) 29/60 (48.3%) 9/60 (15.0%)
time points, all patients filled in the SAQ as part of their evaluation. After the follow-up period, patients were divided into three subgroups according to criteria of improved, deteriorated or unchanged status of each organ system (vascular, respiratory and musculoskeletal system). There are no validated decisive factors of improved or deteriorated disease status in SSc. For this reason, we used the same criteria applied by Steen and Medsger in the validation process of the SHAQ [5], with some modifications. These criteria are shown in Table 3. Because none of the usual diagnostic procedures is sensitive enough to detect changes in gastrointestinal function in SSc, patients were divided into two subgroups: patients treated and patients not treated with prokinetics (metoclopramide) during the follow-up period. The results of several functional studies [10e12] show that metoclopramide improves lower esophageal sphincter pressure, esophageal contraction amplitudes and reduces the gastric emptying delay. We used the Wilcoxon’s statistical test to compare the mean values of IVS, IRS, IGS and IMMS before and after follow-up, in subgroups of patients with improved, deteriorated or unchanged status of particular organ system.
Mean values of each index at the beginning and after 12 months in subgroups of patients with improved, deteriorated or unchanged status of particular organ system are shown in Table 4. According to previous established criteria, an objectively improved vascular status was observed in 14 patients (23.3%), a deteriorated status in 17 (28.3%) patients, while in 29 (48.4%) patients no significant change in vascular morphology or function was noticed. The mean value of IVS decreased significantly in patients with objectively improved vascular status (1.91 vs. 1.29, p ¼ 0.01), but increased in patients with deteriorated status (1.54 vs. 2.13, p ¼ 0.003). In the subgroup of patients with unchanged vascular morphology or function, the IVS did not change significantly either (1.84 vs. 1.77, p ¼ 0.36). Lung function tests were performed at both time points in only 28 of 60 patients, because of some technical troubles. In 10/28 (35.7%) patients, we have noticed an improvement (8 of them improved just DLCO), but in 13/28 (46.4%) patients we noticed a decline in lung function parameters after the follow-up. In 5/58 (17.9%) patients, the lung function did not change significantly. The mean value of IRS decreased significantly in patients with objectively improved lung function (1.08 vs. 0.62, p ¼ 0.027), and increased in patients with deteriorated function (0.69 vs. 1.12, p ¼ 0.012). In the subgroup of patients with unchanged pulmonary function, the IRS did not change significantly (0.13 vs. 0.14, p ¼ 0.18). Thirty-six patients were treated with prokinetics during the follow-up period, while 24 patients did not take these drugs. We have found a statistically significant decrease in mean IGS value in patients who were treated with prokinetics (1.20 vs. 0.70, p < 0.001). In patients who were not treated with prokinetics, an increase of IGS was observed (0.58 vs. 0.76, p ¼ 0.002). An objectively improved condition of the musculoskeletal system was observed in 30 (50.0%) patients, a deteriorated status in 20 (33.3%) patients, while in 10 (16.7%) patients no significant change was noticed. Differences between values of the IMSS were statistically significant in subgroups of patients with improved or deteriorated musculoskeletal status, but not in patients with unchanged condition of this organ system.
Table 3 Criteria of improved, deteriorated and unchanged status of particular organ system Organ system
Criteria of improved status
Criteria of deteriorated status
Criteria of unchanged status
Vascular system
1 Healed finger-tip ulcers, or 2 Improved capillaroscopic finding
1 No changes related to ulcers, capillaroscopic finding or osteolysis
Respiratory system
1 FVC increased for 15%, or 2 DLCO increased for 10%
1 2 3 1 2 3
Musculoskeletal system
1 2 3 4
Skin score decreased 20%, or FTP decreased 10%, or Improved muscle strength, or Remission of arthritis
1 2 3 4
Development of new ulcers, or Deteriorated capillaroscopic finding, or Development of finger-tip osteolysis FVC decreased 15%, or DLCO decreased 10%, or Development of interstitial fibrosis on chest radiography Skin score increased 20%, or FTP increased 10%, or Worsen muscle weakness, or Exacerbation of arthritis
1 FVC remain stable (15%), and 2 DLCO remain stable (10%) 1 2 3 4
Skin score remain stable ( 20%), and FTP remain stable (10%), and No change in muscle strength, and No change in arthritis
P. Ostojic, N. Damjanov / Joint Bone Spine 75 (2008) 286e290 Table 4 Differences among values of indices, calculated using the SAQ, at baseline and after 12 months for each patient subgroup Objective status change
Number of patients
Test
IVS
Improved status of vascular system Wilcoxon’s test
14/60
baseline 12 months
1.91 0.61 1.29 0.77 z ¼ 2.56, p ¼ 0.011
Deteriorated status of vascular system Wilcoxon’s test
17/60
baseline 12 months
1.54 0.63 2.13 0.62 z ¼ 2.97, p ¼ 0.003
Unchanged status of vascular system Wilcoxon’s test
29/60
baseline 12 months
1.84 0.63 1.77 0.69 z ¼ 0.92, p ¼ 0.36
Objective status change
Number of patients
Test
IRS
Improved status of respiratory system Wilcoxon’s test
10/28
baseline 12 months
1.08 0.61 0.62 0.77 z ¼ 2.21, p ¼ 0.027
Deteriorated status of respiratory system Wilcoxon’s test
12/28
baseline 12 months
0.69 0.58 1.12 0.58 z ¼ 2.52, p ¼ 0.012
Unchanged status of respiratory system Wilcoxon’s test
5/28
baseline 12 months
0.13 0.11 0.14 0.17 z ¼ 1.34, p ¼ 0.18
Objective status change
Number of patients
Test
IGS
Patients treated with prokinetics Wilcoxon’s test
36/60
baseline 12 months
1.20 0.54 0.70 0.39 z ¼ 4.03, p < 0.001
Patients not treated with prokinetics Wilcoxon’s test
24/60
baseline 12 months
0.58 0.40 0.76 0.42 z ¼ 3.15, p ¼ 0.002
Objective status change
Number of patients
Test
IMSS
Improved status of musculoskeletal syst. Wilcoxon’s test
30/60
baseline 12 months
1.28 0.68 0.90 0.68 z ¼ 2.87, p ¼ 0.004
Deteriorated status of musculoskeletal syst. Wilcoxon’s test
20/60
baseline 12 months
0.98 0.60 1.44 0.74 z ¼ 3.16, p ¼ 0.012
Unchanged status of musculoskeletal syst. Wilcoxon’s test
10/60
baseline 12 months
0.72 0.75 0.68 0.76 z ¼ 0.68, p ¼ 0.498
IVS e index of vascular status, IRS e index of respiratory status, IGS e index of gastrointestinal status, IMSS e index of musculoskeletal status.
4. Discussion It is difficult to follow changes in disease status and functional ability in patients with SSc. The inflammatory process is very mild, and organ damage develops often insidiously and slowly. Mostly used diagnostic procedures are not sensitive enough to detect organ damage in the early phase, and to notice minimal change in damage or function over time. Symptoms and patient’s subjective complaints are very important in evaluation of disease status in SSc, and physicians
289
often ask patients to guess, did their disease status changed over time or not. As in most other chronic rheumatic diseases, the self-assessment questionnaire is a very important tool for evaluation of patients with SSc. Since 1997, few selfassessment questionnaires for SSc patients are developed. Steen and Medsger have added visual analogue scales (VAS) to the Health Assessment Questionnaire (HAQ) [5], to cover typical organ symptoms. Nevertheless, the HAQ contains questions concerning functions that in systemic sclerosis usually are not limited (such as walking or arising), but questions concerning functional limitations which are result of skin thickening or fibrinous tenosynovitis are not included. Furthermore, no relationship was found between the HAQ-disability index and parameters of heart, lung and kidney involvement [3,4]. The proposed Visual analogue scales (VAS) to measure vascular and internal organ involvement in systemic sclerosis do not cover the whole spectrum of systemic sclerosis symptoms and the reliability of individual VAS is somewhat limited, which was shown by other authors [13,14]. The Systemic Sclerosis Questionnaire (SySQ) consists of 32 questions related to different organ symptoms, and its validity in evaluation of functional and morphological impairments in patients with systemic sclerosis is already established. Until now, no results have been published about its applicability to measure change in clinical trials. Silman et al. [7] recently published an 11-item disability assessment questionnaire for measurement of musculosceletal impairment in patients with systemic sclerosis. Until now none of these questionnaires is widely in use. We have recently published the SAQ, a new self-assessment questionnaire for patients with SSc, and assessed face validity, reproducibility and content validity of the test [9]. The SAQ was build up as a result of major input from patients and rheumatologist familiar with systemic sclerosis. Instead to use VAS, we developed specific questions related to vascular, respiratory, gastrointestinal and musculosceletal symptoms, to assess involvement of those organ systems. We noticed a significant correlation between the IVS and various indicators of vascular damage and dysfunction (capillary damage, finger-tip ulcers and finger-tip osteolysis). Values of the IRS were higher in patients with lung fibrosis, restrictive lung dysfunction and/ or decreased lung diffusing capacity, than in patients with normal pulmonary function. Higher values of the IGS were associated with esophageal hypomotility, while higher values of the IMMS were associated with reduced hand motility, joint contractures, muscle weakness and arthralgia or arthritis [9]. The present study documents usefulness of the SAQ to demonstrate change in disease status and functional ability in SSc patients over time. Values of the IVS correlated significantly with objective improvement or deterioration of vascular function, but did not change in patients with stable vascular function. In scientific clinical work, as well as in routine clinical practice, the IVS could be very useful in assessment of frequency, severity and pain during attacks of Raynaud’s phenomenon. Because of some technical troubles, lung function tests were performed at both time points in only 28 of 60 patients.
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Surprisingly, we have noticed improvement of lung function in even ten patients. Most of them improved in lung diffusing capacity, whilst vital capacity did not change significantly. One should be careful in making conclusions, because results of lung function tests depend on patient’s cooperation. Both, low number of re-evaluated patients and questionable reproducibility of lung function tests, may be a significant limitation of the validation process of IRS. However, at the end of the follow up, we noticed significantly higher values of IRS in patients with deteriorated lung function, and lower values in patients with improved lung function. The IGS could be very useful to assess dysfunction at different levels of the gastrointestinal tract. Some items in the subgroup of questions related to gastrointestinal dysfunction are linked to upper gastrointestinal symptoms (like dysphagia and heartburn), while others are linked to lower gastrointestinal symptoms (like diarrhea and constipation). In this study, IGS decreased significantly in patients who were treated with prokinetics, but increased in patients without therapy. Similarly, the IMMS correlated well with objective improvement or deterioration of musculosceletal damage and function. In conclusion, the Scleroderma Assessment Questionnaire (SAQ) is a sensitive measurement to demonstrate change in patients with SSc over time. In addition to previous estimated face validity, reproducibility and content validity of the test, our present results confirm the overall accuracy of the SAQ for assessment of disease status in SSc. References [1] Valentini G, Della Rosa A, Bombardieri S, et al. European multicentre study to define disease activity criteria for systemic sclerosis.* II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis 2001;60:592e8.
[2] Medsger Jr TA, Silman AJ, Steen VD, et al. A disease severity scale for systemic sclerosis: development and testing. J Rheumatol 1999;26: 2159e67. [3] Clements PJ, Weng KW, Hurwitz EL, et al. Correlates of the disability index of the Health Assessment Questionnaire: a measure of functional impairment in systemic sclerosis. Arthritis Rheum 1999;42:2372e80. [4] Poole JL, Steen VD. The use of the Health Assessment Questionnaire (HAQ) to determine physical disability in systemic sclerosis. Arthritis Care Res 1991;4:27e31. [5] Steen V, Medsger Jr TA. The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time. Arthritis Rheum 1997;40:1984e91. [6] Rouf J, Bru¨hlmann P, Michel A, et al. Development and validation of a self-administered systemic sclerosis questionnaire (SySQ). Rheumatology 1999;38:535e42. [7] Silman A, Akesson A, Newman J, et al. Assessment of functional ability in patients with scleroderma: a proposed new disability assessment instrument. J Rheumatol 1988;25:79e83. [8] Georges C, Chassany O, Mouthon L, et al. Validation of French Version of the Scleroderma Health Assessment Questionnaire (SSc HAQ). Clin Rheumatol 2005;24:3e10. [9] Ostojic P, Damjanov N. The Scleroderma Assessment Questionnaire (SAQ): a new self-assessment questionnaire for evaluation of disease status in patients with systemic sclerosis. Z Rheumatol 2006;65:168e75. [10] Mercado U, Arroyo de Anda R, Avenduo L, et al. Metoclopramide response in patients with early diffuse systemic sclerosis. Effect on esophageal motility abnormalities. Clin Exp Rheumatol 2005;23:685e8. [11] Johnson DA, Drane WE, Curran J, et al. Metoclopramide response in patients with progressive systemic sclerosis. Effect on esophageal and gastric abnormalities. Arch Intern Med 1987;147:1597e601. [12] Drane WE, Karvelis K, Johnson DA, et al. Scintigraphic detection of metoclopramide esophageal stimulation in progressive systemic sclerosis. J Nucl Med 1987;28:1040. [13] Ferraz MB, Quaresma MR, Aquino LR, et al. Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. J Rheumatol 1990;17:1022e4. [14] Zivkovic N, Petrovic R, Miliv V. Assessment of the value of different pain measurement scales in rheumatoid arthritis patients. Acta Rheum Belgrad 1996;26(2):49e52.