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
b
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
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-IVaxis 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
(FEV
1
), 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-
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 cross-
sectional 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
Available online at www.sciencedirect.com
General Hospital Psychiatry 30 (2008) 441445

Corresponding author. Tel.: +39 0577 586275; fax: +39 0577 233451.
E-mail address: goracci3@unisi.it (A. Goracci).
0163-8343/$ see front matter 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.genhosppsych.2008.04.010
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 involve-
ment, 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 relation-
ship 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 character-
istics 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 Ques-
tionnaire (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 integra-
tion (MasterScreen Pneumotachograph - Jaeger, Wuerzburg
- Germany). Forced expiratory volume in the first second
(FEV
1
) 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
Table 1
Demographic characteristics (n=80)
Variable N or *mean % or *S.D.
Age 46* 9.8*
Gender
Male 36 45%
Female 44 55%
Race
White 80 100%
Education
University Degree 8 10%
High School 37 46.3%
Secondary School 26 32.5%
Primary School 9 11.3%
Employment status
Full-time 53 66%
Part-time 15 18,7%
Homemaker 6 7,5%
Disabled
Retired
Unemployed 3 3.8%
Other 3 3,8%
Marital status
Married or living as married 58 72.5%
Widowed 1 1.3%
Separated or divorced 6 7.5%
Never married 15 18.8%
442 A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441445
Volume in the first second (FEV
1
) 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 meanstandard deviation (MSD)
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 one-
way 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 469,8 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 3,280,8 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 44,9219 (ref.: 18-55 UI/
min.ml.). The mean FEV
1
was 10019.1% and the mean
FVC was 10523.3% of predicted values. Only 10 patients
(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-IVaxis 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 FEV
1
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 (QLES-
Q). 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 multi-
systemic involvement (57,9327,84 vs, 70,6319,46, 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 (49,3321,18 vs. 63,5616,76, Pb.001), feelings
[63,2822,65 vs. 80,0015,62, Pb.0001], leisure time
activities [55,8328,79 vs. 68,1821,39, Pb.032) and
general activity [47,9116,43 vs. 62,9116,52, Pb.0001)
scales (Table 5).
Table 2
Psychiatric DSM-IVaxis I diagnosis
Major Depressive Disorder 25%
Panic Disorder 6,3%
Bipolar Disorder 6,3%
Generalized Anxiety Disorder 5%
Obsessive Compulsive Disorder 1,3%
Table 3
Relationship between Q-LES-Q and FEV1%, FVC %, and ACE
Q-LES-Q domains Pearson Coefficients
FEV1% FVC % ACE
Physical Health 0.23

0.29

0.09
Feelings 0.16 0.24

0.01
Work 0.23 0.23 0.16
Household duties 0.04 0.06 0.02
Leisure time activities 0.20 0.17 0.05
Social Relations 0.06 0.09 0.17
General Activities 0.27

0.32

0.01

Pb.05.

Pb.01.
Table 4
Q- LES-Q and multi-systemic involvement
Q-LES-Q
domains
Multi-systemic
involvment (N=61)
No Multi-systemic
involvment (N=19)
Physical Health 53 (20.3) 62.9 (19.8)
Feelings 68.7 (21.8) 75.7 (19.5)
Work 73.9 (18.7) 81.3 (13.5)
Household duites 66.9 (23.4) 66.3 (19.4)
Leisure time activites 57.9 (27.8)

70.6 (19.4)
Social Relations 69 (15.7) 70.6 (19.1)
General Activities 52.18 (18.5) 60.4 (14.5)

Pb.03 Data are expressed as means (SD).

443 A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441445
Subjects reporting dyspnea endorsed significantly worse
scores than subjects without dyspnea on the physical health/
activities (44,5822,51 vs. 60,0017,98, Pb.002), feelings
[61,4623,48 vs 74,2119,45, Pb.014), leisure time acti-
vities [49,9126,92 vs. 65,5425,21, Pb.016)] and general
activities [41,4814,84 vs. 59,39 16,58 , Pb.0001] scales.
Subjects receiving steroids endorsed lower scores on the
physical health/activities (47,2519,49 vs. 65,3117,42,
Pb.001), feelings ( 63,9823,37 vs. 78,2215,79, Pb.002)
and general activities (48,5818,09 vs. 60,8615,59, 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 [43,7518,84 vs 63,0014,65, Pb.010), work
[65,2317,44 vs. 78,7514,59, Pb.049] and general activity
[45,2316,78 vs. 63,2517,11, Pb.009)] scales.
Subjects with a comorbid psychiatric disorder endorsed
significantly lower scores than subjects without psychiatric
comorbidities on the physical health/activities (45,9721,37
vs 62,6916,78, Pb.0001), leisure time activities (51,66
28,07 vs 68,4122,93, pb0,0001), feelings (57,4922,55 vs
80,4213,96, Pb.022), work (70,4020,11 vs 80,0914,56,
Pb.0001) and general activities (46,2919,84 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-LESQsubscales.
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% [13]. 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 pub-
lished 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 socio-
economical 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 5
Q- Les-Q and asthenia
Q-LES-Q domains Asthenia (N=46) No Asthenia (N=34)
Physical Health 49.3 (21.1) 63.5 (16.7)

Feelings 63.2 (22.6) 80 (15.6)

Work 73 (20.2) 79.6 (13.1)

Household duites 65.2 (24.1) 69 (19.5)
Leisure time activites 55.8 (28.7) 68.1 (21.3)

Social Relations 67.3 (16.3) 72.3 (16.5)

General Activities 47.9 (16.4) 62.9 (16.5)

Pb.001.

Pb.0001.

Pb.032 Data are expressed as means (SD).

Table 6
Q- Les-Q and steroids use
Q-LES-Q domains Steroids (N=44) No Steroids (N=36)
Physical Health 47.2 (19.4) 65.3 (17.4)

Feelings 63.9 (23.3) 78.2 (15.7)

Work 73.1 (20.3) 78.9 (14.0)

Household duties 65.9 (23.7) 67.8 (20.8)
Leisure time activites 58.3 (27.6) 64.1 (25.1)
Social Relations 67.7 (17.6) 71.4 (15.0)
General Activities 48.5 (18.0) 60.8 (15.5)

Data are expressed as means (SD).

Pb.001.

Pb.002.
444 A. Goracci et al. / General Hospital Psychiatry 30 (2008) 441445
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 Day-
Hospital 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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