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Quality of life, anxiety and depression in Sarcoidosis
Available online at www.sciencedirect.com
General Hospital Psychiatry 30 (2008) 441 – 445
Quality of life, anxiety and depression in Sarcoidosis Arianna Goracci, M.D. a,⁎, Andrea Fagiolini, M.D. a,b , Mirko Martinucci, M.D. c , Sara Calossi, M.D. a , Serena Rossi, M.D. a , Tonino Santomauro, M.D. a , Angela Mazzi, M.D. d , Francesco Penza, M.D. d , Antonella Fossi, M.D. d , Elena Bargagli, M.D. d , Maria Grazia Pieroni, M.D. d , Paola Rottoli, M.D. d , Paolo Castrogiovanni, M.D. a a
Psychiatry Division, Department of Neuroscience, University of Siena School of Medicine, Viale Bracci 1, 53100 Siena, Italy Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA c Psychiatry Division, Versilia Hospital, 55041 Lido di Camaiore (LU), Italy d Department of Clinical Medicine and Immunological Sciences, Respiratory Diseases Section, University of Siena School of Medicine Viale Bracci 1, 53100 Siena, Italy Received 22 November 2007; accepted 25 April 2008 b
Abstract Objectives: This study sought to evaluate the quality of life and the presence of psychiatric disorders in patients with sarcoidosis. Methods: Data were collected from 80 consecutive outpatients with sarcoidosis presenting to the Sarcoidosis Center of the Respiratory Diseases Division at the University of Siena, Italy. Results: Forty-four percent of the subjects endorsed at least one psychiatric DSM-IV axis I diagnosis. Specifically, 25% of subjects met the criteria for Major Depressive Disorder, 6.3% for Panic Disorder, 6.3% for Bipolar Disorder, 5% for Generalized Anxiety Disorder and 1.3% for Obsessive Compulsive Disorder. Statistically significant correlations were found between Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC) and several domains of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) questionnaire. Subjects with multi-systemic involvement, with asthenia and with a more severe radiographic stage and subjects receiving steroids, reported a poorer quality of life. Conclusions: Sarcoidosis is associated with a high rate of psychiatric comorbidity and may contribute to a poorer quality of life. A referral for a psychiatric or psychological evaluation and counseling should be considered for many of the sarcoidosis patients. © 2008 Elsevier Inc. All rights reserved. Keywords: Sarcoidosis; Quality of life; Depression; Anxiety; Comorbidity
1. Introduction Sarcoidosis is an inflammatory disease of unknown etiology that may involve several systems and impair the quality of life. Cox and colleagues [1] recently evaluated the health-related quality of life (HRQL) and mental health of persons with sarcoidosis and found that outpatients with sarcoidosis had global reductions in HRQL and mental health indeces. Similar results were found by Drent and colleagues (1998) [2,3] who evaluated sixty-four patients with sarcoi-
⁎ Corresponding author. Tel.: +39 0577 586275; fax: +39 0577 233451. E-mail address: [email protected] (A. Goracci). 0163-8343/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2008.04.010
dosis and found a correlation between sarcoidosis, quality of life and depressive symptoms. Many authors have also suggested an association between sarcoidosis and mental well-being in general and certain psychiatric illnesses, such as depression and anxiety. For instance, Chang and colleagues [4] conducted a crosssectional study and examined sociodemographic and disease morbidity factors associated with depression in patients with sarcoidosis and reported a prevalence of depression as high as 60%. Female gender, low income, decreased access to medical care, dyspnea on exertion and number of systems involved were associated with depression. Klonoff and Kleinhenz assessed anxiety, depression, life stress and symptoms of agoraphobia and/or panic in
442
A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441–445
Table 1 Demographic characteristics (n=80) Variable
N or *mean
% or *S.D.
Age Gender Male Female Race White Education University Degree High School Secondary School Primary School Employment status Full-time Part-time Homemaker Disabled Retired Unemployed Other Marital status Married or living as married Widowed Separated or divorced Never married
46*
±9.8*
36 44
45% 55%
80
100%
8 37 26 9
10% 46.3% 32.5% 11.3%
53 15 6
66% 18,7% 7,5%
3 3
3.8% 3,8%
58 1 6 15
72.5% 1.3% 7.5% 18.8%
seventeen patients with sarcoidosis and found a relationship between increased life stress and impairment in lung function, thus pointing to the potential benefits of stress reduction treatment as an adjunctive therapy for patients with sarcoidosis [5]. Yamada and colleagues [6] evaluated the influence of stressful life events on the onset of sarcoidosis and found that the magnitude of stressful life events was significantly higher in patients with sarcoidosis compared with healthy controls. In addition, capacity for coping with stress was found to be inferior in sarcoidosis patients compared with that in the control groups. Yeager et al. [7] assessed the association of demographic and psychosocial factors with respiratory health in 736 persons with sarcoidosis and found that 46% of cases reported significant symptoms of depression (vs. 27% of controls), which were associated with decreased FVC and greater dyspnea. Moreover impaired spirometry and greater dyspnea were associated with poorer quality of life. The authors concluded that a “global approach to the sarcoidosis patient, including careful assessment of dyspnea and health related quality of life, as well as of lung function and radiographic changes, and any extrathoracic involvement, is important, not only in management of the individual patient, but should also prove beneficial in assessing outcomes in clinical trials in the future.” Although most of the existing studies point to a relationship between sarcoidosis and poorer quality of life and to a high prevalence of psychiatric illness in subjects with sarcoidosis, the interest in the mental well being and quality of life of these patients has risen only recently and the number of studies on this topic is still limited. Also, many
studies did not evaluate the prevalence of psychiatric illnesses via a structured clinical interview and limited their assessments to major depressive [1,2,4] and anxiety (5) disorders. Moreover, to our knowledge, no study has ever evaluated the HRQL in Italian patients. To this end, we decided to evaluate the prevalence of psychiatric illness via the administration of the Mini International Neuropsychiatric Interview to a group of 80 Italian subjects with sarcoidosis and to evaluate the relationship between specific characteristics of sarcoidosis and several areas of quality of life.
2. Methods The Institutional Review Board (Ethical Committee) at the University of Siena reviewed and approved all the procedures described in this protocol and all subjects gave written informed consent prior to participating in the study. Subjects were 80 consecutive outpatients presenting between November 2004 and September 2005 to the Sarcoidosis Center of the Respiratory Diseases Division at the University of Siena. Sixty patients had biopsy-proven sarcoidosis. The diagnosis in the other 20 patients the diagnosis was done based on a bronchoalveolar lavage findings and a compatible clinical-radiological pattern according to the ATS and ERS Statement on Sarcoidosis [8]. Patient radiological stage (0-I, II, III and IV), duration of ilness, serum angiotensin converting enzyme (ACE) and presence of extrathoracic involvement were recorded at the entry in the study. All patients participated in a research diagnostic interview using the Mini International Neuropsychiatric Interview (MINI-PLUS) [9] and completed the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [10]. The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a self-report instrument used to assess the degree of enjoyment and satisfaction experienced by subjects in eight areas, including: physical health/activities (13 items), feelings (14 items), work (13 items), household duties (10 items), school/course work (10 items), leisure time activities (6 items), social relations (11 items), and general activities (14 items). The three areas of work, household duties, and school/course work are filled out by the respondent only if applicable. Items are rated on a 5-point scale. Higher scores denote higher levels of satisfaction. There are two additional items which explore medication satisfaction and life satisfaction and contentment over the last week. The Italian version of the Q-LES-Q has recently been validated by Rossi et al. [11]. Pulmonary function tests (PFTs) were performed on all patients using a pneumotachograph with electronic integration (MasterScreen Pneumotachograph - Jaeger, Wuerzburg - Germany). Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) data were also obtained. Consistent with the American Thoracic Society guidelines, we recorded the highest value of three technically acceptable forced expiratory manouvres. Forced Expiratory
A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441–445 Table 2 Psychiatric DSM-IV axis I diagnosis Major Depressive Disorder Panic Disorder Bipolar Disorder Generalized Anxiety Disorder Obsessive Compulsive Disorder
25% 6,3% 6,3% 5% 1,3%
Volume in the first second (FEV1) and Forced Vital Capacity (FVC) were expressed as percentage of predicted value adjusted for age, gender and height (CECA 83). 2.1. Statistical analyses The study analyses were performed using SPSS 11.0 for Windows software (SPSS, Inc., Chicago, IL). Descriptive statistics were reported as mean±standard deviation (M±SD) for continuous variables that were normally distributed. For comparison between two groups, a Student's t test was performed. If the data was not normally distributed, then the Mann-Whitney rank test was employed. A one-way analysis of variance (ANOVA), followed by the Kruskal-Wallis oneway ANOVA on ranks if the data were not normally distributed, were performed as appropriate. Correlations between FEV1 and quality of life scores were performed using Pearson's coefficient of correlation. P values b .05 were considered significant. 3. Results Table 1 shows the demographical characteristics of the study sample. Mean age at the diagnosis of Sarcoidosis patients was 46±9,8 years. Thirty-two percent of patients were in radiological stage 0, 16% in stage I, 26% in stage II, 21% in stage III, and 5% in stage IV. The duration of illness at entry in our study was 3,28±0,8 years, with 79% of the patients with a duration of disease greater than 2 years. Twenty-five percent of our sample did not have any extra thoracic manifestation, 56% had one, 13% two, 5% three and 1% four. Mean ACE concentration was 44,92±19 (ref.: 18-55 UI/ min.ml.). The mean FEV1 was 100±19.1% and the mean FVC was 105±23.3% of predicted values. Only 10 patients
Table 3 Relationship between Q-LES-Q and FEV1%, FVC %, and ACE Q-LES-Q domains
Physical Health Feelings Work Household duties Leisure time activities Social Relations General Activities ⁎ Pb.05. ⁎⁎ Pb.01.
443
(8%) showed impairment in lung function. Of these, 7 showed a restrictive pattern while 3 had an obstructive pattern. Fifty-seven percent of the subjects reported asthenia and 30% reported dyspnea. Fifty-five percent of study subjects were receiving steroids (82% orally, 18% inhaled). Of these, 28% were on steroid treatment for 1 year or less, 58 % for 1 to 5 years and 14% for more than 5 years. Three patients were receiving cytotoxic agents (e.g. Methotrexate, Azathioprine). Of the 45% of the patients who were not on steroids at study entry, 30% had used steroids in past. Forty-four percent of our subjects with a diagnosis of sarcoidosis endorsed at least one psychiatric DSM-IV axis I diagnosis. Specifically, 25% of subjects met the criteria for Major Depressive Disorder, 6,3% for Panic Disorder, 6,3% for Bipolar Disorder, 5% for Generalized Anxiety Disorder and 1,3% for Obsessive Compulsive Disorder (Table 2). Significant correlations were found between FEV1 and the physical health/activities (Pearson coefficient 0,23, Pb.05) and the general activities (Pearson coefficient 0,27; Pb.05) domains of the quality of life instrument (QLESQ). Also, significant correlations were found between FVC and the physical health/activities (Pearson coefficient 0,29; 95% Pb.01), feelings (Pearson coefficient 0,24; Pb.05) and general activities (Pearson coefficient 0,32; 95% Pb.05) QLES-Q subscales (Table 3). Subjects with multi-systemic involvement endorsed significantly lower scores (worse quality of life) on the leisure time activities sub scale than subjects with no multisystemic involvement (57,93±27,84 vs, 70,63±19,46, Pb.03) (Table 4). Subjects with a more severe radiographic stage showed significantly worse ratings on the QLES-Q general activities scale (Pb.007), with Duncan Post Hoc Test showing significantly worse scores for subjects at stage 4 compared to subjects with a lower stage (stage 4=31,7; stage 3=49,7; stage 2=51,6; stage 1=54,5, stage 0=62,7; 4N3,2,1,0; Pb.05). Subjects reporting asthenia endorsed significantly worse score than subjects without asthenia on the “physical health/ activities” (49,33±21,18 vs. 63,56±16,76, Pb.001), feelings [63,28±22,65 vs. 80,00±15,62, Pb.0001], leisure time activities [55,83±28,79 vs. 68,18±21,39, Pb.032) and general activity [47,91±16,43 vs. 62,91±16,52, Pb.0001) scales (Table 5). Table 4 Q- LES-Q and multi-systemic involvement
Pearson Coefficients FEV1%
FVC %
ACE
0.23 ⁎ 0.16 0.23 −0.04 0.20 0.06 0.27 ⁎
0.29 ⁎⁎ 0.24 ⁎ 0.23 −0.06 0.17 0.09 0.32 ⁎⁎
0.09 0.01 0.16 −0.02 −0.05 0.17 0.01
Q-LES-Q domains
Multi-systemic involvment (N=61)
No Multi-systemic involvment (N=19)
Physical Health Feelings Work Household duites Leisure time activites Social Relations General Activities
53 (20.3) 68.7 (21.8) 73.9 (18.7) 66.9 (23.4) 57.9 (27.8) ⁎ 69 (15.7) 52.18 (18.5)
62.9 (19.8) 75.7 (19.5) 81.3 (13.5) 66.3 (19.4) 70.6 (19.4) 70.6 (19.1) 60.4 (14.5)
⁎ Pb.03 Data are expressed as means (SD).
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A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441–445
Table 5 Q- Les-Q and asthenia Q-LES-Q domains
Asthenia (N=46)
No Asthenia (N=34)
Physical Health Feelings Work Household duites Leisure time activites Social Relations General Activities
49.3 (21.1) 63.2 (22.6) 73 (20.2) 65.2 (24.1) 55.8 (28.7) 67.3 (16.3) 47.9 (16.4)
63.5 (16.7) ⁎ 80 (15.6) ⁎⁎ 79.6 (13.1) 69 (19.5) 68.1 (21.3) ⁎⁎⁎ 72.3 (16.5) 62.9 (16.5) ⁎⁎
⁎ Pb.001. ⁎⁎ Pb.0001. ⁎⁎⁎ Pb.032 Data are expressed as means (SD).
Subjects reporting dyspnea endorsed significantly worse scores than subjects without dyspnea on the “physical health/ activities” (44,58±22,51 vs. 60,00±17,98, Pb.002), feelings [61,46±23,48 vs 74,21±19,45, Pb.014), leisure time activities [49,91±26,92 vs. 65,54±25,21, Pb.016)] and general activities [41,48±14,84 vs. 59,39± 16,58 , Pb.0001] scales. Subjects receiving steroids endorsed lower scores on the physical health/activities (47,25±19,49 vs. 65,31±17,42, Pb.001), feelings ( 63,98±23,37 vs. 78,22±15,79, Pb.002) and general activities (48,58±18,09 vs. 60,86±15,59, Pb.002) scales (Table 6). Significant differences were also found between subjects that were receiving oral steroids and subjects who were taking inhaled steroids, with the former endorsing lower scores (worse quality of life) on the “physical health/ activities” [43,75±18,84 vs 63,00±14,65, Pb.010), work [65,23±17,44 vs. 78,75±14,59, Pb.049] and general activity [45,23±16,78 vs. 63,25±17,11, Pb.009)] scales. Subjects with a comorbid psychiatric disorder endorsed significantly lower scores than subjects without psychiatric comorbidities on the physical health/activities (45,97±21,37 vs 62,69±16,78, Pb.0001), leisure time activities (51,66± 28,07 vs 68,41±22,93, pb0,0001), feelings (57,49±22,55 vs 80,42±13,96, Pb.022), work (70,40±20,11 vs 80,09±14,56, Pb.0001) and general activities (46,29±19,84 vs 60,45± 13,56, Pb.0001) Q-LES Q subscales. Comparing subjects (post-hoc Duncan test) with mood disorders (m), subjects with anxiety disorders (a) and subjects without a psychiatric comorbidity (n), we found significant differences in the scores on the physical health/activities (m=43.28, a= 52.70, n= 62.69; uba,n Pb.001), feelings (m=55.20, a= 63.20, n= 80.42; u,abn; Pb.001), leisure time activities (m=47.44; a=62,20; n=68,41, uba,n; Pb.005) and general activities (m=43.92; a=52,20; n=60,45, uba,n;Pb.001) Q-LES Q subscales. 4. Discussion This study found significant relationship between specific clinical characteristics of sarcoidosis and poorer quality of life with special reference to the domains of physical health/ activities, leisure time activities, general activities and feelings.
The study also confirmed the high rate of psychiatric comorbidity in subjects with sarcoidosis and its relationship with a poorer quality of life. The prevalence of comorbid psychiatric illness that we found is much higher than the prevalence in the general population but it is lower than previously reported by other authors. For instance, we found a 25% prevalence of major depressive disorder whereas other authors have reported a prevalence of up to 66% [1–3]. This may be at least in part due to the fact that the presence of psychiatric illnesses in our study was assessed via a rigorous structured diagnostic interview (MINI PLUS) [9], whereas most of the other studies have used less rigorous assessment instruments. For instance, Cox et al (1) and Chang et al. (4) limited their diagnostic assessment to the Center for Epidemiologic Studies depression scale and Drent et al (2) used the Beck Depression Inventory. Other factors that may explain the difference between our research and the previously published studies include ethnicity and socioeconomic status. For instance, the study that reported the highest prevalence of depression (1), was conducted in the USA and included a high percentage of African Americans (80%), whereas our study was conducted in Italy and included only white subjects. Clearly, the possible influence of race and socioeconomical status on the association between sarcoidosis and psychiatric illnesses is worth of further studies. The relationship among sarcoidosis, psychiatric illness and poorer quality of life is likely mediated by multiple factors. Although the cross sectional design of this study does not permit to evaluate how much of the reduction in quality of life is mediated by the development of comorbid psychiatric illnesses, it is well possible that sarcoidosis contributes to a poorer quality of life also via mechanisms that are not exclusively correlated with the presence of a psychiatric illness. First, patients may experience symptoms such as body pain, low energy and asthenia that can well contribute to depression, anxiety and poorer quality of life. Second, they have to face a relatively unpredictable multisystemic disease, which may be characterized by a distressing alternation between periods of remission and relapses. Third, medications that are used to treat sarcoi-
Table 6 Q- Les-Q and steroids use Q-LES-Q domains
Steroids (N=44)
No Steroids (N=36)
Physical Health Feelings Work Household duties Leisure time activites Social Relations General Activities
47.2 (19.4) 63.9 (23.3) 73.1 (20.3) 65.9 (23.7) 58.3 (27.6) 67.7 (17.6) 48.5 (18.0)
65.3 (17.4) ⁎ 78.2 (15.7) ⁎⁎ 78.9 (14.0) 67.8 (20.8) 64.1 (25.1) 71.4 (15.0) 60.8 (15.5) ⁎⁎
Data are expressed as means (SD). ⁎ Pb.001. ⁎⁎ Pb.002.
A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441–445
dosis, such as the steroid, are not free of significant physical and mental side effects [1]. For instance, in our study, subjects receiving steroids endorsed lower scores on the physical health/activities, feelings, and general activities Q-LES-Q scales. These observations are consistent with the Chronic Obstructive Pulmonary Disease (COPD) literature, which points to the relationship between depression and certain symptoms and consequences of COPD such as fatigue, insomnia, reduced appetite, medication side effects, reduced self esteem and social embarrassment because of the need of oxygen or because of the chronic cough [12,13]. Among the limitations of this study, we would like to acknowledge its cross sectional design, which did not permit to evaluate the direction of causality between sarcoidosis, psychiatric illness and quality of life. Moreover, it is important to acknowledge that all patients were recruited in a DayHospital Sarcoidosis Center and that therefore the results cannot be generalized to the hospitalized subjects with more severe exacerbations of sarcoidosis or to subjects with less severe forms, which are generally untreated or which are not sent to a tertiary Center. Notwithstanding the limitations, our results show a relatively high rate of psychiatric comorbidity and a high impact of specific sarcoidosis features on very important areas of quality of life, which call for adequate attention to these aspects in all patients with sarcoidosis. For instance, we believe that a brief psychiatric or psychological evaluation be indicated in all patients with sarcoidosis and that the possibility of a more extensive and specialistic evaluation and counseling should be considered for those patients who screen positively for the presence of psychiatric illnesses and for a poor quality of life.
445
References [1] Cox CE, Donohue JF, Brown CD, et al. Health-related quality of life of persons with sarcoidosis. Chest 2004;125:997–1004. [2] Drent M, Wirnsberger RM, Breteler MH, et al. Quality of life and depressive symptoms in patients suffering from sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 1998;15(1):59–66. [3] De Vries J, Drent M, Van Heck GL, et al. Quality of life in sarcoidosis: a comparison between members of a patient organisation and a random sample. Sarcoidosis Vasc Diffuse Lung Dis 1998;15:183–8. [4] Chang B, Steimel J, Moller DR, et al. Depression in sarcoidosis. Am J Respir Crit Care Med 2001;163:329–34. [5] Klonoff EA, Kleinhenz ME. Psychological factors in sarcoidosis: the relationship between life stress and pulmonary function. Sarcoidosis 1993;10(2):118–24. [6] Yamada Y, Tatsumi K, Yamaguchi T, et al. Influence of stressful life events on the onset of sarcoidosis. Respirology 2003;8(2):186–91. [7] Yeager H, Rossman MD, Baughman RP, et al. Pulmonary and psychosocial findings at enrollment in the ACCESS study. Sarcoidosis Vasc Diffuse Lung Dis 2005;22(2):147–53. [8] American Thoracic Society, the European Respiratory Society, and the World Association of Sarcoidosis and Other Granulomatous Disorders. Statement on sarcoidosis: joint statement of the American Thoracic Society, the European Respiratory Society, and the World Association of Sarcoidosis and Other Granulomatous Disorders. Am J Respir Crit Care Med 1999;160:736–55. [9] Sheehan DV, Lecrubier Y, et al. The Mini International Neuropsychiatric Interview (M.I.N.I.). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry 1997;12:224. [10] Endicott J, Nee J, et al. Quality of Life enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull 1993;29:321. [11] Rossi A, Rucci P, Mauri M, et al. Validity and reliability of the Italian version of the Quality of Life, Enjoyment and Satisfaction Questionnaire. Qual Life Res 2005;14(10):2323–8. [12] Van Ede L, Yzermans CJ. Prevalence of depression in patients with COPD: a systematic review. Thorax 1999;54:688–92. [13] Mikkelsen RL, Middelboe T, et al. Anxiety and depression in patients with chronic obstructive pulmonary disease (COPD). A review. Nord J Psychiatry 2004;58(1):65–70.
General Hospital Psychiatry 30 (2008) 441 – 445
Quality of life, anxiety and depression in Sarcoidosis Arianna Goracci, M.D. a,⁎, Andrea Fagiolini, M.D. a,b , Mirko Martinucci, M.D. c , Sara Calossi, M.D. a , Serena Rossi, M.D. a , Tonino Santomauro, M.D. a , Angela Mazzi, M.D. d , Francesco Penza, M.D. d , Antonella Fossi, M.D. d , Elena Bargagli, M.D. d , Maria Grazia Pieroni, M.D. d , Paola Rottoli, M.D. d , Paolo Castrogiovanni, M.D. a a
Psychiatry Division, Department of Neuroscience, University of Siena School of Medicine, Viale Bracci 1, 53100 Siena, Italy Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA c Psychiatry Division, Versilia Hospital, 55041 Lido di Camaiore (LU), Italy d Department of Clinical Medicine and Immunological Sciences, Respiratory Diseases Section, University of Siena School of Medicine Viale Bracci 1, 53100 Siena, Italy Received 22 November 2007; accepted 25 April 2008 b
Abstract Objectives: This study sought to evaluate the quality of life and the presence of psychiatric disorders in patients with sarcoidosis. Methods: Data were collected from 80 consecutive outpatients with sarcoidosis presenting to the Sarcoidosis Center of the Respiratory Diseases Division at the University of Siena, Italy. Results: Forty-four percent of the subjects endorsed at least one psychiatric DSM-IV axis I diagnosis. Specifically, 25% of subjects met the criteria for Major Depressive Disorder, 6.3% for Panic Disorder, 6.3% for Bipolar Disorder, 5% for Generalized Anxiety Disorder and 1.3% for Obsessive Compulsive Disorder. Statistically significant correlations were found between Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC) and several domains of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) questionnaire. Subjects with multi-systemic involvement, with asthenia and with a more severe radiographic stage and subjects receiving steroids, reported a poorer quality of life. Conclusions: Sarcoidosis is associated with a high rate of psychiatric comorbidity and may contribute to a poorer quality of life. A referral for a psychiatric or psychological evaluation and counseling should be considered for many of the sarcoidosis patients. © 2008 Elsevier Inc. All rights reserved. Keywords: Sarcoidosis; Quality of life; Depression; Anxiety; Comorbidity
1. Introduction Sarcoidosis is an inflammatory disease of unknown etiology that may involve several systems and impair the quality of life. Cox and colleagues [1] recently evaluated the health-related quality of life (HRQL) and mental health of persons with sarcoidosis and found that outpatients with sarcoidosis had global reductions in HRQL and mental health indeces. Similar results were found by Drent and colleagues (1998) [2,3] who evaluated sixty-four patients with sarcoi-
⁎ Corresponding author. Tel.: +39 0577 586275; fax: +39 0577 233451. E-mail address: [email protected] (A. Goracci). 0163-8343/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2008.04.010
dosis and found a correlation between sarcoidosis, quality of life and depressive symptoms. Many authors have also suggested an association between sarcoidosis and mental well-being in general and certain psychiatric illnesses, such as depression and anxiety. For instance, Chang and colleagues [4] conducted a crosssectional study and examined sociodemographic and disease morbidity factors associated with depression in patients with sarcoidosis and reported a prevalence of depression as high as 60%. Female gender, low income, decreased access to medical care, dyspnea on exertion and number of systems involved were associated with depression. Klonoff and Kleinhenz assessed anxiety, depression, life stress and symptoms of agoraphobia and/or panic in
442
A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441–445
Table 1 Demographic characteristics (n=80) Variable
N or *mean
% or *S.D.
Age Gender Male Female Race White Education University Degree High School Secondary School Primary School Employment status Full-time Part-time Homemaker Disabled Retired Unemployed Other Marital status Married or living as married Widowed Separated or divorced Never married
46*
±9.8*
36 44
45% 55%
80
100%
8 37 26 9
10% 46.3% 32.5% 11.3%
53 15 6
66% 18,7% 7,5%
3 3
3.8% 3,8%
58 1 6 15
72.5% 1.3% 7.5% 18.8%
seventeen patients with sarcoidosis and found a relationship between increased life stress and impairment in lung function, thus pointing to the potential benefits of stress reduction treatment as an adjunctive therapy for patients with sarcoidosis [5]. Yamada and colleagues [6] evaluated the influence of stressful life events on the onset of sarcoidosis and found that the magnitude of stressful life events was significantly higher in patients with sarcoidosis compared with healthy controls. In addition, capacity for coping with stress was found to be inferior in sarcoidosis patients compared with that in the control groups. Yeager et al. [7] assessed the association of demographic and psychosocial factors with respiratory health in 736 persons with sarcoidosis and found that 46% of cases reported significant symptoms of depression (vs. 27% of controls), which were associated with decreased FVC and greater dyspnea. Moreover impaired spirometry and greater dyspnea were associated with poorer quality of life. The authors concluded that a “global approach to the sarcoidosis patient, including careful assessment of dyspnea and health related quality of life, as well as of lung function and radiographic changes, and any extrathoracic involvement, is important, not only in management of the individual patient, but should also prove beneficial in assessing outcomes in clinical trials in the future.” Although most of the existing studies point to a relationship between sarcoidosis and poorer quality of life and to a high prevalence of psychiatric illness in subjects with sarcoidosis, the interest in the mental well being and quality of life of these patients has risen only recently and the number of studies on this topic is still limited. Also, many
studies did not evaluate the prevalence of psychiatric illnesses via a structured clinical interview and limited their assessments to major depressive [1,2,4] and anxiety (5) disorders. Moreover, to our knowledge, no study has ever evaluated the HRQL in Italian patients. To this end, we decided to evaluate the prevalence of psychiatric illness via the administration of the Mini International Neuropsychiatric Interview to a group of 80 Italian subjects with sarcoidosis and to evaluate the relationship between specific characteristics of sarcoidosis and several areas of quality of life.
2. Methods The Institutional Review Board (Ethical Committee) at the University of Siena reviewed and approved all the procedures described in this protocol and all subjects gave written informed consent prior to participating in the study. Subjects were 80 consecutive outpatients presenting between November 2004 and September 2005 to the Sarcoidosis Center of the Respiratory Diseases Division at the University of Siena. Sixty patients had biopsy-proven sarcoidosis. The diagnosis in the other 20 patients the diagnosis was done based on a bronchoalveolar lavage findings and a compatible clinical-radiological pattern according to the ATS and ERS Statement on Sarcoidosis [8]. Patient radiological stage (0-I, II, III and IV), duration of ilness, serum angiotensin converting enzyme (ACE) and presence of extrathoracic involvement were recorded at the entry in the study. All patients participated in a research diagnostic interview using the Mini International Neuropsychiatric Interview (MINI-PLUS) [9] and completed the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [10]. The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a self-report instrument used to assess the degree of enjoyment and satisfaction experienced by subjects in eight areas, including: physical health/activities (13 items), feelings (14 items), work (13 items), household duties (10 items), school/course work (10 items), leisure time activities (6 items), social relations (11 items), and general activities (14 items). The three areas of work, household duties, and school/course work are filled out by the respondent only if applicable. Items are rated on a 5-point scale. Higher scores denote higher levels of satisfaction. There are two additional items which explore medication satisfaction and life satisfaction and contentment over the last week. The Italian version of the Q-LES-Q has recently been validated by Rossi et al. [11]. Pulmonary function tests (PFTs) were performed on all patients using a pneumotachograph with electronic integration (MasterScreen Pneumotachograph - Jaeger, Wuerzburg - Germany). Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) data were also obtained. Consistent with the American Thoracic Society guidelines, we recorded the highest value of three technically acceptable forced expiratory manouvres. Forced Expiratory
A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441–445 Table 2 Psychiatric DSM-IV axis I diagnosis Major Depressive Disorder Panic Disorder Bipolar Disorder Generalized Anxiety Disorder Obsessive Compulsive Disorder
25% 6,3% 6,3% 5% 1,3%
Volume in the first second (FEV1) and Forced Vital Capacity (FVC) were expressed as percentage of predicted value adjusted for age, gender and height (CECA 83). 2.1. Statistical analyses The study analyses were performed using SPSS 11.0 for Windows software (SPSS, Inc., Chicago, IL). Descriptive statistics were reported as mean±standard deviation (M±SD) for continuous variables that were normally distributed. For comparison between two groups, a Student's t test was performed. If the data was not normally distributed, then the Mann-Whitney rank test was employed. A one-way analysis of variance (ANOVA), followed by the Kruskal-Wallis oneway ANOVA on ranks if the data were not normally distributed, were performed as appropriate. Correlations between FEV1 and quality of life scores were performed using Pearson's coefficient of correlation. P values b .05 were considered significant. 3. Results Table 1 shows the demographical characteristics of the study sample. Mean age at the diagnosis of Sarcoidosis patients was 46±9,8 years. Thirty-two percent of patients were in radiological stage 0, 16% in stage I, 26% in stage II, 21% in stage III, and 5% in stage IV. The duration of illness at entry in our study was 3,28±0,8 years, with 79% of the patients with a duration of disease greater than 2 years. Twenty-five percent of our sample did not have any extra thoracic manifestation, 56% had one, 13% two, 5% three and 1% four. Mean ACE concentration was 44,92±19 (ref.: 18-55 UI/ min.ml.). The mean FEV1 was 100±19.1% and the mean FVC was 105±23.3% of predicted values. Only 10 patients
Table 3 Relationship between Q-LES-Q and FEV1%, FVC %, and ACE Q-LES-Q domains
Physical Health Feelings Work Household duties Leisure time activities Social Relations General Activities ⁎ Pb.05. ⁎⁎ Pb.01.
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(8%) showed impairment in lung function. Of these, 7 showed a restrictive pattern while 3 had an obstructive pattern. Fifty-seven percent of the subjects reported asthenia and 30% reported dyspnea. Fifty-five percent of study subjects were receiving steroids (82% orally, 18% inhaled). Of these, 28% were on steroid treatment for 1 year or less, 58 % for 1 to 5 years and 14% for more than 5 years. Three patients were receiving cytotoxic agents (e.g. Methotrexate, Azathioprine). Of the 45% of the patients who were not on steroids at study entry, 30% had used steroids in past. Forty-four percent of our subjects with a diagnosis of sarcoidosis endorsed at least one psychiatric DSM-IV axis I diagnosis. Specifically, 25% of subjects met the criteria for Major Depressive Disorder, 6,3% for Panic Disorder, 6,3% for Bipolar Disorder, 5% for Generalized Anxiety Disorder and 1,3% for Obsessive Compulsive Disorder (Table 2). Significant correlations were found between FEV1 and the physical health/activities (Pearson coefficient 0,23, Pb.05) and the general activities (Pearson coefficient 0,27; Pb.05) domains of the quality of life instrument (QLESQ). Also, significant correlations were found between FVC and the physical health/activities (Pearson coefficient 0,29; 95% Pb.01), feelings (Pearson coefficient 0,24; Pb.05) and general activities (Pearson coefficient 0,32; 95% Pb.05) QLES-Q subscales (Table 3). Subjects with multi-systemic involvement endorsed significantly lower scores (worse quality of life) on the leisure time activities sub scale than subjects with no multisystemic involvement (57,93±27,84 vs, 70,63±19,46, Pb.03) (Table 4). Subjects with a more severe radiographic stage showed significantly worse ratings on the QLES-Q general activities scale (Pb.007), with Duncan Post Hoc Test showing significantly worse scores for subjects at stage 4 compared to subjects with a lower stage (stage 4=31,7; stage 3=49,7; stage 2=51,6; stage 1=54,5, stage 0=62,7; 4N3,2,1,0; Pb.05). Subjects reporting asthenia endorsed significantly worse score than subjects without asthenia on the “physical health/ activities” (49,33±21,18 vs. 63,56±16,76, Pb.001), feelings [63,28±22,65 vs. 80,00±15,62, Pb.0001], leisure time activities [55,83±28,79 vs. 68,18±21,39, Pb.032) and general activity [47,91±16,43 vs. 62,91±16,52, Pb.0001) scales (Table 5). Table 4 Q- LES-Q and multi-systemic involvement
Pearson Coefficients FEV1%
FVC %
ACE
0.23 ⁎ 0.16 0.23 −0.04 0.20 0.06 0.27 ⁎
0.29 ⁎⁎ 0.24 ⁎ 0.23 −0.06 0.17 0.09 0.32 ⁎⁎
0.09 0.01 0.16 −0.02 −0.05 0.17 0.01
Q-LES-Q domains
Multi-systemic involvment (N=61)
No Multi-systemic involvment (N=19)
Physical Health Feelings Work Household duites Leisure time activites Social Relations General Activities
53 (20.3) 68.7 (21.8) 73.9 (18.7) 66.9 (23.4) 57.9 (27.8) ⁎ 69 (15.7) 52.18 (18.5)
62.9 (19.8) 75.7 (19.5) 81.3 (13.5) 66.3 (19.4) 70.6 (19.4) 70.6 (19.1) 60.4 (14.5)
⁎ Pb.03 Data are expressed as means (SD).
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Table 5 Q- Les-Q and asthenia Q-LES-Q domains
Asthenia (N=46)
No Asthenia (N=34)
Physical Health Feelings Work Household duites Leisure time activites Social Relations General Activities
49.3 (21.1) 63.2 (22.6) 73 (20.2) 65.2 (24.1) 55.8 (28.7) 67.3 (16.3) 47.9 (16.4)
63.5 (16.7) ⁎ 80 (15.6) ⁎⁎ 79.6 (13.1) 69 (19.5) 68.1 (21.3) ⁎⁎⁎ 72.3 (16.5) 62.9 (16.5) ⁎⁎
⁎ Pb.001. ⁎⁎ Pb.0001. ⁎⁎⁎ Pb.032 Data are expressed as means (SD).
Subjects reporting dyspnea endorsed significantly worse scores than subjects without dyspnea on the “physical health/ activities” (44,58±22,51 vs. 60,00±17,98, Pb.002), feelings [61,46±23,48 vs 74,21±19,45, Pb.014), leisure time activities [49,91±26,92 vs. 65,54±25,21, Pb.016)] and general activities [41,48±14,84 vs. 59,39± 16,58 , Pb.0001] scales. Subjects receiving steroids endorsed lower scores on the physical health/activities (47,25±19,49 vs. 65,31±17,42, Pb.001), feelings ( 63,98±23,37 vs. 78,22±15,79, Pb.002) and general activities (48,58±18,09 vs. 60,86±15,59, Pb.002) scales (Table 6). Significant differences were also found between subjects that were receiving oral steroids and subjects who were taking inhaled steroids, with the former endorsing lower scores (worse quality of life) on the “physical health/ activities” [43,75±18,84 vs 63,00±14,65, Pb.010), work [65,23±17,44 vs. 78,75±14,59, Pb.049] and general activity [45,23±16,78 vs. 63,25±17,11, Pb.009)] scales. Subjects with a comorbid psychiatric disorder endorsed significantly lower scores than subjects without psychiatric comorbidities on the physical health/activities (45,97±21,37 vs 62,69±16,78, Pb.0001), leisure time activities (51,66± 28,07 vs 68,41±22,93, pb0,0001), feelings (57,49±22,55 vs 80,42±13,96, Pb.022), work (70,40±20,11 vs 80,09±14,56, Pb.0001) and general activities (46,29±19,84 vs 60,45± 13,56, Pb.0001) Q-LES Q subscales. Comparing subjects (post-hoc Duncan test) with mood disorders (m), subjects with anxiety disorders (a) and subjects without a psychiatric comorbidity (n), we found significant differences in the scores on the physical health/activities (m=43.28, a= 52.70, n= 62.69; uba,n Pb.001), feelings (m=55.20, a= 63.20, n= 80.42; u,abn; Pb.001), leisure time activities (m=47.44; a=62,20; n=68,41, uba,n; Pb.005) and general activities (m=43.92; a=52,20; n=60,45, uba,n;Pb.001) Q-LES Q subscales. 4. Discussion This study found significant relationship between specific clinical characteristics of sarcoidosis and poorer quality of life with special reference to the domains of physical health/ activities, leisure time activities, general activities and feelings.
The study also confirmed the high rate of psychiatric comorbidity in subjects with sarcoidosis and its relationship with a poorer quality of life. The prevalence of comorbid psychiatric illness that we found is much higher than the prevalence in the general population but it is lower than previously reported by other authors. For instance, we found a 25% prevalence of major depressive disorder whereas other authors have reported a prevalence of up to 66% [1–3]. This may be at least in part due to the fact that the presence of psychiatric illnesses in our study was assessed via a rigorous structured diagnostic interview (MINI PLUS) [9], whereas most of the other studies have used less rigorous assessment instruments. For instance, Cox et al (1) and Chang et al. (4) limited their diagnostic assessment to the Center for Epidemiologic Studies depression scale and Drent et al (2) used the Beck Depression Inventory. Other factors that may explain the difference between our research and the previously published studies include ethnicity and socioeconomic status. For instance, the study that reported the highest prevalence of depression (1), was conducted in the USA and included a high percentage of African Americans (80%), whereas our study was conducted in Italy and included only white subjects. Clearly, the possible influence of race and socioeconomical status on the association between sarcoidosis and psychiatric illnesses is worth of further studies. The relationship among sarcoidosis, psychiatric illness and poorer quality of life is likely mediated by multiple factors. Although the cross sectional design of this study does not permit to evaluate how much of the reduction in quality of life is mediated by the development of comorbid psychiatric illnesses, it is well possible that sarcoidosis contributes to a poorer quality of life also via mechanisms that are not exclusively correlated with the presence of a psychiatric illness. First, patients may experience symptoms such as body pain, low energy and asthenia that can well contribute to depression, anxiety and poorer quality of life. Second, they have to face a relatively unpredictable multisystemic disease, which may be characterized by a distressing alternation between periods of remission and relapses. Third, medications that are used to treat sarcoi-
Table 6 Q- Les-Q and steroids use Q-LES-Q domains
Steroids (N=44)
No Steroids (N=36)
Physical Health Feelings Work Household duties Leisure time activites Social Relations General Activities
47.2 (19.4) 63.9 (23.3) 73.1 (20.3) 65.9 (23.7) 58.3 (27.6) 67.7 (17.6) 48.5 (18.0)
65.3 (17.4) ⁎ 78.2 (15.7) ⁎⁎ 78.9 (14.0) 67.8 (20.8) 64.1 (25.1) 71.4 (15.0) 60.8 (15.5) ⁎⁎
Data are expressed as means (SD). ⁎ Pb.001. ⁎⁎ Pb.002.
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dosis, such as the steroid, are not free of significant physical and mental side effects [1]. For instance, in our study, subjects receiving steroids endorsed lower scores on the physical health/activities, feelings, and general activities Q-LES-Q scales. These observations are consistent with the Chronic Obstructive Pulmonary Disease (COPD) literature, which points to the relationship between depression and certain symptoms and consequences of COPD such as fatigue, insomnia, reduced appetite, medication side effects, reduced self esteem and social embarrassment because of the need of oxygen or because of the chronic cough [12,13]. Among the limitations of this study, we would like to acknowledge its cross sectional design, which did not permit to evaluate the direction of causality between sarcoidosis, psychiatric illness and quality of life. Moreover, it is important to acknowledge that all patients were recruited in a DayHospital Sarcoidosis Center and that therefore the results cannot be generalized to the hospitalized subjects with more severe exacerbations of sarcoidosis or to subjects with less severe forms, which are generally untreated or which are not sent to a tertiary Center. Notwithstanding the limitations, our results show a relatively high rate of psychiatric comorbidity and a high impact of specific sarcoidosis features on very important areas of quality of life, which call for adequate attention to these aspects in all patients with sarcoidosis. For instance, we believe that a brief psychiatric or psychological evaluation be indicated in all patients with sarcoidosis and that the possibility of a more extensive and specialistic evaluation and counseling should be considered for those patients who screen positively for the presence of psychiatric illnesses and for a poor quality of life.
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