The Impact of Psychological Functioning upon Systemic Sclerosis Patients’ Quality of Life Thomas N. Hyphantis, MD, PhD,* Niki Tsifetaki, MD, PhD,† Vassiliki Siafaka, PhD,‡ Paraskevi V. Voulgari, MD, PhD,§ Christina Pappa, MD, MSc,¶ Marina Bai, MSc,¶ Kalliopi Palieraki, MSc,¶ Aliki Venetsanopoulou, MD,储 Venetsanos Mavreas, MD, PhD,** and Alexandros A. Drosos, MD, FACR††
Objective: To access health-related quality of life (HRQOL) in systemic sclerosis (SSc) patients using the World Health Organization Quality of Life Instrument, Short-Form (WHOQOLBREF), and to identify the association between clinical, psychopathological, and personality parameters and SSc patients’ HRQOL. Methods: Fifty-six patients with SSc were compared with 72 patients with rheumatoid arthritis (RA), 43 with systemic lupus erythematosus (SLE), 34 with Sjögren syndrome (SS), and 74 healthy controls. A wide range of clinical information was collected and the following self-report instruments were used: the WHOQOL-BREF, the General Health Questionnaire, the Symptom Distress Check List, the Hostility and Direction of Hostility Questionnaire, the Defense Style Questionnaire, and the Sense of Coherence scale. Results: HRQOL perceived by SSc patients was significantly impaired compared with healthy controls. Initial examination of HRQOL across groups of rheumatology patients revealed similar HRQOL, but when age, pain, psychopathology, and coping strategies were taken into account, SSc patients had impaired physical health QOL in comparison with RA, SLE, and SS patients. Arthritis-related pain was closely associated with SSc patients’ HRQOL. Elevated psychological distress symptoms as well as certain personality traits, such as maladaptive defenses and lower sense of coherence, were also associated with diminished HRQOL. Conclusions: Impaired psychological functioning is associated with diminished HRQOL in SSc, and consequently, treatment of depressive symptoms should be considered a priority. Moreover, assessment of HRQOL should only be used in conjunction with specific psychological distress measurements, to detect the influence of psychopathology on HRQOL. © 2007 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 37:81-92 Keywords: systemic sclerosis, quality of life, psychological distress, personality, sense of coherence, ego mechanisms of defense
*Assistant Professor of Psychiatry, Department of Psychiatry, Medical School, University of Ioannina, Ioannina, Greece. †Rheumatologist, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. ‡Psychologist, Department of Psychiatry, Medical School, University of Ioannina, Ioannina, Greece. §Assistant Professor of Rheumatology, Rheumatology Clinic Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. ¶Fellow in Psychiatry, Department of Psychiatry, Medical School, University of Ioannina, Ioannina, Greece. 储Fellow in Rheumatology, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. **Professor of Psychiatry, Department of Psychiatry, Medical School, University of Ioannina, Ioannina, Greece. ††Professor of Rheumatology, Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. The authors have no conflicts of interest to disclose. Address reprint requests to: Alexandros A. Drosos, MD, FACR, Professor of Medicine/Rheumatology, Department of Internal Medicine, Medical School, University of Ioannina, 45,110 Ioannina, Greece. E-mail: [email protected]
0049-0172/07/$-see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2007.03.008
ystemic sclerosis (SSc) is a connective tissue disease characterized by excessive fibrosis of the skin, vascular changes, and variable internal organ involvement, including the lungs, heart, kidney, and gastrointestinal tract (GI) (1). Skin changes, pain of various causes, and certain internal organ involvement may lead to impairment of functional status and severe limitations in work and social activities (2). These alterations of one’s general health perceptions may adversely affect a patient’s perceived physical health and ultimately health-related quality of life (HRQOL) (3,4). In the last decade, a limited number of studies have investigated HRQOL in SSc patients, suggesting that SSc patients have impaired HRQOL compared with healthy controls, but similar to that of patients with other rheumatic diseases (4-7). These studies have been performed using the Medical Outcome Study Short-Form Questionnaire (SF-36) to evaluate general HRQOL, which has been regarded as an appropriate outcome measurement for many chronic diseases. However, the meaning of quality of life (QOL) and the most appropriate way to measure this construct are uncertain (8). Although generic measures of HRQOL permit valid comparison of HRQOL among different groups of people or different diseases, the conceptual limitations of many measures purporting to address general HRQOL seriously restrict their value (8,9). In an effort to overcome such problems, the World Health Organization (WHO) introduced the WHOQOL-100 instrument, a cross-culturally valid assessment that is available in several culture-specific and language-specific versions (10). A short form of this instrument, the WHOQOL-BREF, was developed for use in situations where time is restricted and when respondent burden must be minimized (11). WHOQOL-BREF has been shown to have similar psychometric properties to the WHOQOL-100, while a noteworthy feature is the inclusion of social and environment domains for assessment (11,12). Although the usefulness of the WHOQOL-BREF in assessing HRQOL in patients with rheumatic diseases has been recently addressed (8,13), it is not known if any studies to date have used it among SSc patients. On the other hand, a major concern in assessing general HRQOL is that psychological distress symptoms, especially depressive symptoms, are highly but negatively correlated with many aspects of HRQOL (14,15). For this reason, it has been suggested that psychopathological symptoms should always be considered thoroughly when assessing HRQOL to take the measurement overlap into account (15). Although it is well documented that approximately half of SSc patients experience mild to severe depressive symptoms (16-18), studies investigating the impact of various psychopathological conditions on SSc patients’ HRQOL are limited (7). In addition, although recent evidence supports the protective impact of various personality factors such as sense of coherence (19), hostility (18), and defensive styles (20) in rheumatic diseases,
Systemic sclerosis patients’ quality of life
little attention has been given to the impact of these parameters on SSc patients HRQOL. Therefore, the aim of the present study was first to access HRQOL in SSc patients, using the WHOQOL-BREF, compared with other rheumatic diseases as well as healthy controls, and, second, to identify the association between clinical parameters, various forms of psychopathology, as well as certain personality traits with SSc patients’ HRQOL. PATIENTS AND METHODS Participants A consecutive sample of 56 SSc outpatients with years of attendance at the outpatient clinic of the Rheumatology Department of Ioannina Medical School Hospital, Greece, participated in the study. HRQOL of SSc patients was compared with HRQOL of 149 patients suffering from other rheumatic diseases with years of attendance at the same Rheumatology Department, which served as “disease controls.” This sample consisted of 72 patients with rheumatoid arthritis (RA), 43 with systemic lupus erythematosus (SLE), and 34 with Sjögren syndrome (SS). These diseases were chosen because they share many similarities with SSc (7) and have been used for comparison in other studies evaluating HRQOL in rheumatic diseases (21). Diagnoses of SSc, RA, SLE, and SS were confirmed based on the respectively recommended criteria (22-26), and the diagnosis of scleroderma subtypes was confirmed via LeRoy’s criteria (27). Patients with localized scleroderma such as morphea or linear scleroderma were excluded from the study. Finally, another sample of 74 voluntary participants randomly selected from the hospital’s staff list and patients’ relatives served as “healthy” controls. The demographic profiles of patients and controls are presented in Table 1. All participants were able to read and write in Greek, and none had a history of psychotic illness, current alcohol and/or drug abuse, or dementia. Procedure and Study Instruments All the procedures that followed were in accordance with the ethical standards on human experimentation (World Medical Association Helsinki Declaration) and with the local hospital’s Ethics Committee. All patients with the aforementioned diseases that were followed up regularly at our Rheumatology outpatient department within a 6-month period were asked to participate in the study. After the participants received a complete description of the study, the voluntary nature of their participation, and the confidentiality of the survey, all agreed to participate and written informed consent was obtained. This high participation rate may be due to a good doctor–patient relationship, taking into consideration that all patients had been followed up by the same experienced rheumatologist throughout the duration of the disease. A series of self-report measurements was administered along with a
T.N. Hyphantis et al.
Table 1 Demographic Profiles of Patients and Controls Variables
Number of participants Female:Male Age (years) Range mean ⫾ SD Family status: married (n, %) Years of education (mean ⫾ SD) Disease duration (y) (mean ⫾ SD)
25–70 52.6 ⫾ 12.4 38 (68) 8.7 ⫾ 4.2 15.5 ⫾ 12.2
20–72 53.3 ⫾ 12.6 56 (78) 7.7 ⫾ 3.1 15.9 ⫾ 8.5
21–73 44.9 ⫾ 12.1** 35 (81) 10.6 ⫾ 3.8* 13.7 ⫾ 8.3
21–69 53.4 ⫾ 10.9 25 (74) 7.1 ⫾ 3.3 9.0 ⫾ 5.8**
23–72 49.8 ⫾ 10.9 57 (78) 12.4 ⫾ 3.3*** NA
NA, not applicable. *P ⬍ 0.001. **P ⬍ 0.01. ***P ⬍ 0.05. Statistically significant differences between SSc patients and healthy controls, RA, SLE, or SS patients (2-tailed t-test).
request for demographic information, whereas additional clinical data and laboratory results were obtained by reviewing patients’ records using a standardized data collection form. The following self-report instruments were used: 1. Quality of life instrument. The World Health Organization Quality of Life Instrument, Short-Form (WHOQOL-BREF), was used (11,12), which is a 26item version of the WHOQOL-100 and covers a broad range of facets that was agreed on international consensus. It was developed in the context of 4 domains of HRQOL: physical health, psychological health, social relationships, and environment. It also includes facets on overall quality of life (ie, “How would you rate your quality of life?”) and satisfaction with general health (ie, “How satisfied are you with your health?”). Each item is rated on a 5-point Likert interval scale and the scores are transformed on a scale from 0 to 100 to enable comparisons to be made between domains composed of unequal numbers of items. A higher score indicates better HRQOL. The Greek version of the WHOQOL-BREF was used (11,28,29). 2. Psychopathology instruments. a. The General Health Questionnaire (GHQ-28) (30) is a screening instrument that estimates the likelihood of participants being assessed of having a psychiatric diagnosis or disease at interview. The GHQ-28 consists of 28 items belonging to 4 clusters: (a) somatic symptoms of depression; (b) anxiety and insomnia; (c) social dysfunction; and (d) depressive feelings. According to the standardization of GHQ-28 for the Greek population, the best cutoff point of the Greek version is 5, as found by receiver-operating characteristics analysis (31). GHQ-28 has been widely used in rheumatic diseases, and studies have shown that it may be used as an instrument for screening as well as for assessing the impact of illness on these kinds of diseases (32).
b. The Symptom Distress Checklist-90-R (SCL90-R) is a 90-item multidimensional self-report symptom inventory designed to measure psychopathological symptoms in psychiatric and medical patients (33). It also estimates the Global Severity Index (GSI) designed to measure overall psychological distress, which can be used as a summary of the test. The utility of SCL-90-R as a psychological screening instrument in rheumatic disease patients has been well documented (34); also, it has been standardized for the Greek population (35). 3. Personality instruments. a. The Defense Style Questionnaire (DSQ) is a rating scale that is designed to estimate behavior suggestive of 25 ego defense mechanisms, which are psychodynamic in origin, and 4 defense styles, namely, “maladaptive action,” “image distorting,” “self-sacrificing,” and “adaptive” styles (36). Maladaptive action style indicates the participants’ inability to deal with their impulses by taking constructive action on their own behalf. The essence of image distorting style is the splitting of the image of self and other into good and bad and into strong and weak. Self-sacrificing style reflects a need to perceive one’s self as being kind, helpful to others, and never angry, and adaptive style is associated with good coping (36). DSQ was translated into Greek with Dr. Bond’s permission, and its application to the Greek population is now under investigation by our research team. DSQ has been used with Greek medical patients (37,38), and the standardization results so far indicate that the Greek version of DSQ shares for the most part the same properties as the original (38). b. The Hostility and Direction of Hostility Questionnaire (HDHQ) (39) provides a measure of hostility manifestation that reflects an attitudinal personality trait and shows the participant’s reaction to frustrating occurrences. The HDHQ has been
Systemic sclerosis patients’ quality of life
used within the general Greek population as well as with medical patients (37,38,40). c. The Sense of Coherence (SOC) Scale—a 29-item questionnaire based on Aaron Antonovsky’s salutogenic theory, which postulates that “sense of coherence” is a global orientation to view the world and the individual environment as comprehensible, manageable, and meaningful, claims that the way people view their life has a positive influence on their health (41). It is considered to be a measure of an individual’s capacity to cope with stress (41,42). A growing body of research has used SOC in rheumatic diseases (19,42) and, recently, in SSc patients (43). SOC-29 has been translated and standardized for the Greek population (44). Clinical Feature Estimations Patients were examined by experienced rheumatologists (N.T. and A.A.D.), and medical data were collected, including SSc clinical features and laboratory data. Skin thickness was estimated using the Modified Rodnan Skin Thickness Score technique (45). A 100-mm visual analog pain scale was used to assess the severity of pain. Each patient was asked to place a mark that corresponds to their current level of pain intensity between terminal points designated either “no pain” or “worst possible pain.” The pain scale is designed to evaluate the presence or absence of arthritis-related pain and to obtain information from patients on how their pain has been most often over the past week, although pain may be reported to vary over the course of a day or from day to day (46). The assessment of internal organ involvement was based on clinical and laboratory evidence over time. More specifically, assessment of lung involvement was based on the occurrence of interstitial and/or vascular lung disease: ●
Interstitial lung disease was diagnosed if dyspnea was present according to (1) the New York Heart Association (NYHA) classification; (2) pulmonary function tests ⬍80% of the predicted value [forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), DLCO/alveolar volume (VA)]; and (3) bilateral basilar fibrosis presence in chest radiography. ● Pulmonary hypertension was diagnosed in the presence of (1) dyspnea according to the NYHA classification; (2) isolated reduction of DLCO (FVC/DLCO ratio ⬎1.4); and (3) abnormal estimated systolic pulmonary artery pressure (⬎30 mm Hg). ● Lung involvement was documented by (1) chest radiography; (2) computed tomography (CT); (3) echocardiography with Doppler study; and (4) pulmonary function tests (47). ● Esophageal involvement was diagnosed by (1) the presence of symptoms of dysphagia and heartburn; and (2) abnormal manometry, endoscopy, or cine-video barium esophagram (48).
Lower GI tract involvement was diagnosed by (1) symptoms of diarrhea, constipation, intestinal distension, or fecal incontinence and (2) abnormal manometry, plain abdominal radiograph films, abdominal CT; and (3) endoscopy (48). ● The diagnosis of cardiac involvement was assisted by electrocardiography, echocardiography, and/or chest radiograph with (1) dyspnea, according to the NYHA classification; (2) palpitations, chest pain, dizziness, presyncope, syncope, heart rate; (3) conduction defects, arrhythmias; (4) edema/venous congestion; (5) pericardial effusion; (6) ejection fraction, peak E/peak A ratio and pulmonary artery pressure by echocardiography with echo-Doppler study (49). ● Renal involvement was assessed using (1) arterial blood pressure (systolic and diastolic); (2) serum creatinine; and (3) urinalysis (dipstick and microscopic) (50). STATISTICAL ANALYSIS Statistical analysis was performed using the Statistical Package for the Social Sciences 10.0 (SPSS Inc., Chicago, IL) for Windows. Univariate comparisons were first conducted between SSc patients and controls to investigate differences in WHOQOL-BREF domains, using ANOVA and 2-tailed t-tests. 2 analyses for categorical data and 2-tailed t-tests for continuous data were performed to investigate demographic differences between patients and controls. Four independently produced multiple regression analyses were next performed on the entire sample of patients with rheumatic disease to examine the factors that are most closely associated with patients’ HRQOL. In these analyses, each rheumatic disease was treated as an independent variable, along with the major demographic, psychiatric, and psychological variables studied as well as the clinical factors that were common in all groups of patients (ie, disease duration and pain); whereas dependent variables were the 4 domains of the WHOQOL-BREF. Because the variables of individual items from the questionnaires were ordinal, nonparametric correlation coefficients were calculated next to determine the strength of the relationship between clinical as well as psychological parameters and HRQOL domains among SSc patients. Spearmann’s rank correlation and Kendall’s tau-b correlation were used when appropriate (51). Subsequently, separate multiple regression analyses among the SSc patients were performed to determine the independent associations between various clinical parameters, psychological factors, and certain domains of the HRQOL. Six analyses were performed, with dependent variables, the WHOQOL-BREF domains, and independent variables, the statistically significant factors, based on the results of the univariate correlation analyses. Taking into consideration the relatively small number of participants and the great number of questionnaires, independent variables were entered into the model when
T.N. Hyphantis et al.
Figure 1 Health-related quality of life rates of each World Health Organization Quality of Life-Short Form domains (ie, physical health, psychological, social relationships, and environment) for various rheumatic diseases, in comparison to healthy controls (mean ⫾ 95% confidence interval). The samples consisted of the present study’s SSc patients (n ⫽ 56), RA (n ⫽ 72), SLE patients (n ⫽ 43), SS patients (n ⫽ 34), and HC (n ⫽ 72). Data for the Greek (GGP) and International (IS) general population were derived from ref. 16. ⴱⴱⴱP ⬍ 0.001; ⴱP ⬍ 0.05; statistically significant differences between SSc patients and healthy controls, RA, SLE, or SS patients (2-tailed t-test).
P ⬍ 0.01, to prevent problems raised from multicollinearity. In addition, only the most statistically significant clinical and psychological variables were entered into the multiple regression analyses. When appropriate, F values are included. These represent the statistical significant results of ANOVA in regression analyses, whereas the subsets of numbers in parentheses represent the degrees of freedom in each analysis (which are also an index of the sample size, after controlling for the missing values). RESULTS Patient Characteristics SSc patients and healthy controls were not significantly different in age, sex, and marital status, whereas SLE patients were younger than SSc patients (P ⬍ 0.01). SSc, RA, and SS patients were less educated than SLE patients and healthy controls (F4,272 ⫽ 22.2, P ⬍ 0.001). SSc patients had longer disease duration than SS patients (P ⬍ 0.01) and similar disease duration with RA and SLE patients (Table 1). Among the SSc patients, 39 (70%) had limited and 17 (30%) had diffuse scleroderma. Rodnan scleroderma skin score ranged from 2 to 34 [mean (⫾SD) ⫽ 11.1 ⫾ 10.1]. SSc patients’ assessment of arthritis-related pain ranged from 20 to 80 [mean (⫾SD) ⫽ 43.4 ⫾ 14.5]. Thirty-one patients (55%) had pulmonary involvement. Clinical evidence of esophageal involvement was present in 32 patients (57%). Fourteen patients (25%) had evidence of lower GI tract involvement, and 1 patient had renal involvement.
HRQOL Measurements SSc patients had significantly reduced HRQOL in physical, psychological, and social relationships WHOQOLBREF domains, compared with healthy controls (Fig. 1). To confirm if our healthy control sample was similar to that of the general population, we verified that WHOQOL-BREF scores of our controls were in the range of the Greek population normative data (11,28). WHOQOL-BREF domain scores were also compared with the respective scores obtained from the international adult sample from the general population (N ⫽ 11,830) of the WHO survey (11). Although a formal statistical test was not performed due to the different sampling methods, certain differences relevant to most domains of the WHOQOL-BREF were also observed between SSc patients and the general population (Fig. 1). The HRQOL perceived by patients with diffuse cutaneous SSc (dcSSc) was not significantly different from that of patients with limited cutaneous SSc (lcSSc) (data not shown). The HRQOL of SSc patients was not significantly different from HRQOL of the other rheumatologic patients in the univariate analyses (Fig. 1). Multiple Regression Analyses on the Sample of Patients with Rheumatic Diseases Multiple regression analyses performed on the whole sample of patients with rheumatic diseases revealed that, when all major parameters studied were taken into account, having SSc was closely associated with reduced physical health QOL (P ⬍ 0.03). In addition, general
Systemic sclerosis patients’ quality of life
Table 2 Demographic, Clinical, Psychiatric, and Psychological Parameters Associated with the Four WHO-QOL-BREF Domains in the Whole Sample of patients with Rheumatic Diseases (n ⫽ 205) Dependent Variables Physical Health Independent Variables Demographic Age Sex Educational level Living alone Clinical Disease duration Pain Psychiatric SCL-90-R GSI Psychological Maladaptive action Image distorting Self-sacrificing Adaptive style Total hostility Rheumatic Disease Systemic sclerosis Lupus Rheumatoid arthritis Sjogren’s syndrome Cumulative R2 Adj. ANOVA
⫺0.178 ⫺0.039 0.063 ⫺0.028
0.004 NS NS NS
⫺0.076 0.013 0.070 ⫺0.011
NS NS NS NS
⫺0.136 ⫺0.100 0.008 0.095
0.038 NS NS NS
⫺0.082 0.033 0.102 ⫺0.034
NS NS NS NS
⫺0.059 ⫺0.048 0.025 0.142 ⫺0.003
NS NS NS 0.021 NS
⫺0.050 ⫺0.054 0.170 0.069 ⫺0.140
NS NS 0.010 NS NS
⫺0.023 ⫺0.089 0.202 0.026 ⫺0.032
NS NS 0.003 NS NS
⫺0.029 ⫺0.028 0.195 0.069 ⫺0.032
NS NS 0.007 NS NS
⫺0.136 0.013 ⫺0.035 0.025 0.403 F(5,192) ⫽ 23.6, P ⬍ 0.001
0.030 NS NS NS
⫺0.017 ⫺0.025 ⫺0.049 0.015 0.342 F(2,198) ⫽ 44.3, P ⬍ 0.001
NS NS NS NS
⫺0.034 0.093 ⫺0.074 ⫺0.049 0.293 F(3,198) ⫽ 24.1, P ⬍ 0.001
NS NS NS NS
⫺0.019 0.028 ⫺0.086 0.056 0.210 F(2,196) ⫽ 23.2, P ⬍ 0.001
NS NS NS NS
NS, nonsignificant. Note: Four independently produced multiple regression analyses with dependent variables the WHOQOL-BREF domains and independent variables the major demographic, clinical, psychiatric and psychological variables studied. In these analyses each rheumatic disease was treated as an independent variable.
psychological distress, as measured by the SCL-90-R GSI, was the variable most significantly associated with all domains of the WHOQOL-BREF. Pain, older age, and lower rates of self-sacrificing and adaptive defense styles were also associated with reduced rates in several aspects of HRQOL (Table 2). Demographic, Clinical, Psychiatric, and Personality Factors Associated with SSc Patients’ HRQOL Age was negatively correlated with physical health (P ⬍ 0.03) and the longer the disease duration, the lower the satisfaction with general HRQOL and physical health (P ⬍ 0.05 and P ⬍ 0.04, respectively). Living alone (ie, singles, widowed, or divorced) was also negatively correlated with physical health (P ⬍ 0.05), whereas sex and education level did not correlate with any of the WHOQOL-BREF domains (Tables 3-5). Arthritis-related pain was negatively correlated with most aspects of HRQOL, namely, general QOL (P ⬍ 0.01), physical health (P ⬍ 0.001), psychological health (P ⬍ 0.01), and social relationships (P ⬍ 0.01). Total skin score was negatively correlated with general health
(P ⬍ 0.04) and environment (P ⬍ 0.05); pulmonary involvement was negatively correlated with general health (P ⬍ 0.05) and the social relationships domain (P ⬍ 0.05). Likewise, esophageal involvement was negatively correlated with psychological health (P ⬍ 0.05) and the social relationships domain (P ⬍ 0.05) (Tables 3-5). Interestingly, all psychiatric and personality factors studied were strongly but negatively correlated with all the WHOQOL-BREF domains. The strength of these correlations was much higher than the strength of the correlations between all demographic and clinical variables studied and WHOQOL-BREF domains (Tables 3-5). Six separate multiple regression analyses among the patients with SSc were conducted next, with dependent variables the WHOQOL-BREF domains and independent variables the statistically significant demographic, clinical, and psychological variables, based on the results of the univariate correlation analyses. These analyses revealed the following: Arthritis-related pain and elevated rates on the SCL-90-R GSI were the variables most closely associated with decreased general HRQOL. Higher GSI rates and maladaptive action defense style were closely associated
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Table 3 Demographic, Clinical, and Psychological Parameters Associated with General Quality of Life and General Health in Systemic Sclerosis Patients (n ⫽ 56) Dependent Variables General Quality of Life Multiple Regression Analysis1
Univariate Analyses Independent Variables Demographic Age Sex3 Educational level Living alone3 Clinical Disease duration Age of disease onset Total skin score Lung involvement3,4 Esophagus involvement3 Arthritis related pain Psychiatric SCL-90-R GSI5 Physical symptoms of depression6 Depressive feelings6 Anxiety6 Social disability6 Psychological Maladaptive action Image distorting Self-sacrificing Adaptive style HDHQ total Hostility SOC
0.023 ⫺0.142 0.125 ⫺0.071
Multiple Regression Analysis1
Univariate Analyses c2
0.871 0.299 0.313 0.607
0.047 ⫺0.104 0.084 ⫺0.225
0.739 0.419 0.470 0.083
0.125 ⫺0.108 0.061 ⫺0.259 ⫺0.171 ⫺0.358
0.381 0.452 0.672 0.050 0.211 0.009
⫺0.263 ⫺0.100 ⫺0.278 ⫺0.180 ⫺0.164 ⫺0.218
0.048 0.481 0.039 0.162 0.200 0.121
⫺0.453 ⫺0.547 ⫺0.523 ⫺0.442 ⫺0.420 ⫺0.432 ⫺0.447 0.070 0.004 ⫺0.604 0.508
0.001 0.001 0.001 0.001 0.002
⫺0.655 ⫺0.647 ⫺0.417 ⫺0.563 ⫺0.669
0.001 0.001 0.002 0.001 0.001
0.002 0.001 0.626 0.976 0.001 0.001
0.001 0.001 0.861 0.844 0.001 0.001
⫺0.581 ⫺0.564 0.025 0.028 ⫺0.639 0.618
NS, nonsignificant. Note: 1: Two independently produced multiple regression analyses with dependent variables, the General Quality of Life and General Health, as measured by WHOQOL-BREF. Selection of independent variables was based on the results of univariate comparisons and the strongest statistically significant variables of univariate comparisons were chosen as independent variables. Due to the small number of patients, from all psychiatric variables studied, only GSI has been selected, since it represents a summary of psychological distress symptoms. 2: Spearman’s correlation coefficients. 3: Kendall’s tau-b correlation coefficient. 4: Thirty-one patients (55%) had lung involvement. Interstitial lung disease was present in 25 patients (45%) and pulmonary hypertension was present in 6 patients (11%). 5: SCL-90-R Global Severity Index. 6: GHQ-28 subscales—alternative Likert scoring method (“0123”).
with decreased satisfaction with general health (Table 3). The final models were significant, accounting for 34% (F(2,49) ⫽ 24.9, P ⬍ 0.001) and 42% (F(2,49) ⫽ 26.1, P ⬍ 0.001) of the variance in general HRQOL and general health scores, respectively. Arthritis-related pain, higher hostility rates, and elevated GSI rates were closely associated with decreased physical health, while higher total hostility rates and arthritis-related pain were closely associated with reduced psychological health (Table 4). The final models were also significant, accounting for 63% (F(3,47) ⫽ 26.3, P ⬍ 0.001) and 36% (F(2,50) ⫽ 15.49, P ⬍ 0.001) of the variance in the physical and psychological domains scores, respectively.
Finally, higher rates on SOC and arthritis-related pain scores were closely associated with reduced social relationships domain rates, while lower rates on SOC and higher rates on total hostility were closely associated with diminished environment domain rates. The final models accounted for 35% (F(2,49) ⫽ 14.7, P ⬍ 0.001) and 38% (F(2,49) ⫽ 31.7, P ⬍ 0.001) of the variance in the social relationships and environment domains scores, respectively. DISCUSSION The results of the present study revealed that the HRQOL perceived by SSc patients was significantly impaired com-
Systemic sclerosis patients’ quality of life
Table 4 Demographic, Clinical, and Psychological Parameters Associated with “Physical Health” and “Psychological Health” Domains of WHO-QOL-BREF in Systemic Sclerosis Patients (n ⫽ 56) Dependent Variables Physical Health Multiple Regression Analysis1
Univariate Analyses Independent Variables Demographic Age Sex3 Educational level Living alone3 Clinical Disease duration Age of disease onset Total skin score Lung involvement3,4 Esophagus involvement3 Arthritis related pain Psychiatric SCL-90-R GSI5 Physical symptoms of depression6 Depressive feelings6 Anxiety6 Social disability6 Psychological Maladaptive action Image distorting Self-sacrificing Adaptive style HDHQ Total Hostility SOC
⫺0.295 ⫺0.052 0.155 ⫺0.228
Multiple Regression Analysis1
Univariate Analyses c2
0.034 0.658 0.141 0.044
⫺0.065 ⫺0.042 0.184 ⫺0.195
0.604 0.666 0.082 0.078
⫺0.019 ⫺0.290 ⫺0.064 ⫺0.070 ⫺0.115 ⫺0.417
0.842 0.038 0.528 0.551 0.324 0.001
⫺0.087 ⫺0.255 ⫺0.071 ⫺0.072 ⫺0.236 ⫺0.322
0.372 0.043 0.483 0.538 0.046 0.008
⫺0.690 ⫺0.613 ⫺0.489 ⫺0.573 ⫺0.651 ⫺0.629 ⫺0.641 ⫺0.023 0.002 ⫺0.660 0.536
0.001 0.001 0.001 0.001 0.001
⫺0.587 ⫺0.501 ⫺0.478 ⫺0.514 ⫺0.513
0.001 0.001 0.001 0.001 0.001
0.001 0.001 0.817 0.988 0.001 0.001
0.001 0.001 0.694 0.787 0.001 0.001
⫺0.630 ⫺0.463 0.039 0.027 ⫺0.660 0.578
NS, nonsignificant. Note: 1: Two independently produced multiple regression analyses with dependent variables the “Physical health” and “Psychological health” domains of WHO-QOL-BREF. Selection of independent variables was based on the results of univariate comparisons and the strongest statistically significant variables of univariate comparisons were chosen as independent variables. Due to the small number of patients, from all psychiatric variables studied, only GSI has been selected, since it represents a summary of psychological distress symptoms. 2: Spearman’s correlation coefficients. 3: Kendall’s tau-b correlation coefficient. 4: Thirty-one patients (55%) had lung involvement. Interstitial lung disease was present in 25 patients (45%) and pulmonary hypertension was present in 6 patients (11%). 5: SCL-90-R Global Severity Index. 6: GHQ-28 subscales—alternative Likert scoring method (“0123”).
pared with healthy controls. This finding is consistent with the results of previous studies that reported reduced HRQOL in SSc patients as compared with healthy controls (5,6). Initial examination of HRQOL across groups of rheumatology patients showed similar HRQOL between SSc patients and patients with various rheumatic diseases, in line with the results of previous studies (4,7). However, when other demographic, psychological, or clinical parameters were taken into account, SSc patients showed reduced physical health QOL as compared with patients with other rheumatic diseases. Thus, the present findings show that when age, pain, psychopathology, and coping strategies were considered, SSc patients had impaired physical health QOL
in comparison with RA, SLE, and SS patients. However, our sample consisted of SSc patients with very long disease duration. Organ structure changes occur predominantly in late disease (52), and internal and external physical changes and organ involvement result in severe limitations in work, social activities, and everyday life and subsequently lead to decreased HRQOL (5,6,53). Thus, the present findings may not be generalizable to all SSc patients, but may be limited to patients with late disease. Comparisons between SSc subtypes revealed that HRQOL of patients with dcSSc did not differ with that of patients with lcSSc. Danieli and coworkers (7) also found that HRQOL did not differ significantly between dcSSc
T.N. Hyphantis et al.
Table 5 Demographic, Clinical, and Psychological Parameters Associated with “Social Relationships” and “Environment” Domains of WHO-QOL-BREF in Systemic Sclerosis Patients (n ⫽ 56) Dependent Variables Social Relationships Multiple Regression Analysis1
Univariate Analyses Independent Variables Demographic Age Sex3 Educational Level Living alone3 Clinical Disease duration Age of disease onset Total skin score Lung involvement3,4 Esophagus involvement3 Arthritis related pain Psychiatric SCL-90-R GSI5 Physical symptoms of depression6 Depressive feelings6 Anxiety6 Social disability6 Psychological Maladaptive action Image distorting Self-sacrificing Adaptive style HDHQ total hostility SOC
0.031 ⫺0.099 0.037 ⫺0.024
Multiple Regression Analysis1
Univariate Analyses c2
0.757 0.408 0.734 0.839
⫺0.045 0.034 0.195 ⫺0.079
0.751 0.772 0.065 0.504
⫺0.041 ⫺0.027 ⫺0.020 ⫺0.254 ⫺0.238 ⫺0.275
0.682 0.786 0.857 0.039 0.044 0.016
⫺0.034 ⫺0.057 ⫺0.263 ⫺0.074 ⫺0.125 ⫺0.157
0.723 0.558 0.042 0.526 0.285 0.231
⫺0.532 ⫺0.409 ⫺0.295 ⫺0.391 ⫺0.390 ⫺0.347 ⫺0.346 0.148 0.057 ⫺0.479 0.531
0.001 0.007 0.023 0.009 0.008
⫺0.593 ⫺0.601 ⫺0.597 ⫺0.608 ⫺0.435
0.001 0.001 0.001 0.001 0.003
0.032 0.032 0.291 0.686 0.002 0.001
0.001 0.001 0.803 0.770 0.001 0.001
⫺0.613 ⫺0.465 ⫺0.035 ⫺0.041 ⫺0.693 0.560
NS, nonsignificant. Note: 1: Two independently produced multiple regression analyses with dependent variables the “Social relationships” and “Environment” domains of WHO-QOL-BREF. Selection of independent variables was based on the results of univariate comparisons and the strongest statistically significant variables of univariate comparisons were chosen as independent variables. Due to the small number of patients, from all psychiatric variables studied, only GSI has been selected, since it represents a summary of psychological distress symptoms. 2: Spearman’s correlation coefficients. 3: Kendall’s tau-b correlation coefficient. 4: Thirty-one patients (55%) had lung involvement. Interstitial lung disease was present in 25 patients (45%) and pulmonary hypertension was present in 6 patients (11%). 5: SCL-90-R Global Severity Index. 6: GHQ-28 subscales—alternative Likert scoring method (“0123”).
and lcSSc, but other studies have reported that many HRQOL components were lower in dcSSc than in lcSSc (4,6). Although these differences could be explained by the differences in the total number of patients and the respective ratio of limited and diffuse forms, disease duration may be also of particular significance for HRQOL of dcSSc and lcSSc patients. The natural history of SSc is best understood by dividing dcSSc and lcSSc patients into those who have early or late disease, since each of these 4 stages has characteristic clinical and laboratory features (52). Since the duration of SSc in our population was long, these findings may also be restricted to late dcSSc and lcSSc patients. Thus, further investigation is needed to detect differences in HRQOL between early dcSSc and
early lcSSc, as well as between late dcSSc and late lcSSc patients. Among the clinical parameters studied, arthritis-related pain had the highest association with HRQOL. The higher the levels of arthritis-related pain, the lower the general, physical, psychological, and social relationships HRQOL. These findings are in accordance with the results of Georges and coworkers (6), who reported a high correlation between pain and several aspects of HRQOL in SSc patients. Our findings further confirm this relationship between pain and SSc patients’ HRQOL, suggesting that effective control of pain should constitute 1 of the primary therapeutic goals in SSc-treated patients.
The present findings showed that all psychiatric manifestations studied were strongly but negatively correlated with all aspects of HRQOL. Similarly, distinct personality traits, namely higher hostility rates, adoption of a maladaptive action defense style, and lower rates of SOC, were also associated with decreased HRQOL. The impact of psychological functioning on SSc patients’ HRQOL has not received much attention. Danieli and coworkers (7) have reported that a reduced HRQOL was associated with depressive symptoms. Del Rosso and coworkers (5) highlighted the role of SSc patients’ psychological functioning, although an independent evaluation of psychological distress was lacking. Available data (16-17,40,43,54) and a previous report of our team based on the same cohort of patients (18) suggest that SSc patients experience elevated depressive symptoms. In addition, Altman and coworkers (55) reported a high suicide rate among the 264 SSc patients studied over a prolonged period of time. A review of the mortality of 63 medical disorders provided initial evidence of an increased risk for suicide among SSc patients (56). These findings should alert physicians and health providers to pay attention to the psychological profile of SSc patients. The results of the present study indicate that psychopathology is strongly but negatively associated with SSc patients’ HRQOL. The patients’ inability to deal with their impulses by taking constructive action on their own behalf, and their low capacity to overcome stressors, were also strongly associated with impaired HRQOL. Thus, since modifiable appraisal and coping variables appear to play an important role in predicting adjustment to SSc (57), early evaluation of psychological distress symptoms and maladaptive personality traits could provide information that would aid the treatment of psychological difficulties that interfere with several aspects of SSc patients’ HRQOL. However, in depth evaluation of psychological parameters may be not practical for use in the everyday clinical setting, since it takes a considerable amount of time (1-1.5 hours). As our results have shown, however, the use of the GHQ-28 and/or the DSQ may be a useful and time-efficient method for detecting major psychiatric symptoms and personality traits that warrant attention and intervention in SSc patients. There are a number of limitations to our study. The sample size and use of self-reported measures of psychological distress prevent us from generalizing the findings. A second limitation is in the number of variables assessed as predictors of HRQOL. Since only a few of the potential important predictors were assessed, our conclusions are limited by the number of variables studied. Moreover, the sample size of SSc patients was too small to develop regression models that involve more than 5 or 6 independent variables, further reducing the potential important predictors of patients’ HRQOL. Another limitation is in the validity of using the WHOQOL-BREF in SSc patients. The WHOQOL-BREF has been used in patients with other rheumatic diseases (8,13), and it is regarded as
Systemic sclerosis patients’ quality of life
a reliable and valid instrument in assessing HRQOL in RA patients (8); however, its use in SSc patients has not yet been formally validated. Although our study provides initial evidence of its validity in SSc patients, since predicted relationships among WHOQOL-BREF domains and several measurements were confirmed, more studies on the validity of the WHOQOL-BREF in SSc patients are needed. In conclusion, the present study, using a new instrument in the field, the WHOQOL-BREF, confirmed previous findings reporting that SSc patients have a reduced HRQOL compared with healthy controls. In addition, we showed that when the overall physical and psychological burden was taken into account, SSc patients had impaired physical health QOL as compared with patients with other rheumatic diseases. Treatment of arthritisrelated pain and proper therapeutic intervention of depressive symptoms should be considered a priority. Personality features also warrant attention in the clinical management of SSc patients since some of these traits can be modified by proper psychotherapeutic approaches. Moreover, assessment of HRQOL should only be used in conjunction with specific psychological distress measurements to detect the influence of psychopathology on HRQOL. Finally, future longitudinal studies comparing both generic and disease-specific measurements of HRQOL with psychological distress are needed to confirm the impact of overall psychological functioning on SSc patients’ HRQOL. ACKNOWLEDGMENT The authors thank Dr. Katerina Antoniou, Lecturer of Pharmacology, Medical School, University of Ioannina, for important comments and helpful criticism. REFERENCES 1. Silver RM, Medsger TA Jr, Bolster MB. Systemic sclerosis and scleroderma variants: clinical aspects. In: Koopman WJ, Moreland LW, editors. Arthritis and Allied Conditions: A Textbook of Rheumatology. 15th ed. Philadelphia: Lippincott Williams & Wilkins, 2005, p. 1633-705. 2. Baron M, Lee P, Keystone EC. The articular manifestations of progressive systemic sclerosis (scleroderma). Ann Rheum Dis 1982;41:147-52. 3. Wilson IB, Cleary PD. Linking clinical variables with healthrelated quality of life. A conceptual model of patient outcomes. JAMA 1995;273:59-65. 4. Johnson SR, Gladman DD, Schentag CT, Lee P. Quality of life and functional status in systemic sclerosis compared to other rheumatic diseases. J Rheumatol 2006;33:1117-22. 5. Del Rosso A, Boldrini M, D’Agostino D, Placidi GP, Scarpato A, Pignone A, et al. Health-related quality of life in systemic sclerosis as measured by the Short Form 36: relationship with clinical and biologic markers. Arthritis Rheum 2004;15:51(3):475-81. 6. Georges C, Chassany O, Toledano C, Mouthon L, Tiev K, Meyer O, et al. Impact of pain in health related quality of life of patients with systemic sclerosis. Rheumatology (Oxford) 2006;45(10):1298-302. 7. Danieli E, Airo P, Bettoni L, Cinquini M, Antonioli Ch, Cavazzana I, et al. Health-related quality of life measured by the Short
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