Quality of Life of Couples Living with Sarcoidosis

Sarcoidosis is a multisystem inflammatory disorder of unknown cause(s) that imposes a burden on patients’ lives [1]. It affects men and women all over the world, at a relatively young age [2]. In addition to the specific organ-related symptoms, less specific disabling symptoms, including fatigue, cognitive failure, symptoms associated with small fiber neuropathy (SFN), and physical impairments, may have a major influence on the daily activities and the social and professional lives of the patients. These symptoms can lead to stress, anxiety, depression, and social and physical limitations [3-8]. Moreover, sarcoidosis patients experience reduced work ability [9-11].

The impact of any disease depends on the patient’s disease perception and coping strategies. Various aspects of sarcoidosis, such as the often unpredictable and chronic nature of the disease [2], the uncertainty about the cause, and the broad range of frequently persistent symptoms may result in an aggravating influence on patients’ lives. Hence, living with a long-term disease like sarcoidosis significantly affects patients’ quality of life (QoL), with negative consequences for general health and social and psychosocial well-being. QoL is a concept that concerns someone’s evaluation of their functioning in a wide range of domains but always includes the physical, psychological, and social domains. Anxiety and depressive symptoms are also common in patients with sarcoidosis and are associated with disease severity [6, 7]. Previous QoL studies showed that the QoL of patients with sarcoidosis is predicted by fatigue, depressive symptoms, reduced exercise capacity, dyspnea, and arthralgia [1, 4, 8, 12-16]. Recently, Moor et al. [17] demonstrated that sarcoidosis leads to anxiety, psychological distress, and impaired well-being not only in the patients but also in their partners. Studies on the influence of other nonspecific symptoms and studies examining the impact of living with a partner with sarcoidosis are scarce.

Therefore, the aim of our study was to evaluate whether living with a partner suffering from sarcoidosis influences the QoL of that partner, as well as to evaluate the QoL of the patients themselves. Moreover, we aimed to assess whether nonspecific symptoms, including fatigue, cognitive failure, SFN-related symptoms, and psychological factors including depressive symptoms and anxiety in sarcoidosis patients predict the QoL of partners and patients.

We conducted a cross-sectional, prospective cohort study evaluating fatigue and QoL in sarcoidosis patients and their partners between 2007 and 2009. Data regarding fatigue in sarcoidosis patients were previously used in De Kleijn [18]. Data from the current study regarding the QoL of sarcoidosis patients and their partners were analyzed in 2018 and not reported previously. Patients (n = 588) evaluated and/or treated at the ILD Center of the Department of Pulmonology of Maastricht University Medical Center, a tertiary referral center in The Netherlands, were asked to participate between September 2007 and July 2008. After inclusion of the patients, their partners (if they had a partner) were also asked to participate. Patients were all diagnosed with sarcoidosis based on the guidelines of the world association of sarcoidosis and other granulomatous disorders [2]. The Medical Ethics Committee of MUMC+ (07-4-015) approved the study protocol, and written informed consent was obtained from all patients.

Information about the study was sent by E-Mail (which every patient and/or partner asked to participate had access to), and patients as well as their partners were asked to complete and return an informed consent form if they were willing to participate. After having agreed to participate, they received the set of questionnaires and were asked to return the completed set to the hospital in an enclosed envelope.

The following characteristics were collected: gender and age (patients and partners) and time since diagnosis of sarcoidosis and sarcoidosis treatment (patients). Patients completed several questionnaires: World Health Organization QoL-BREF (WHOQoL-BREF), Fatigue Assessment Scale (FAS), SFN Screening List (SFNSL), cognitive failure questionnaire (CFQ), state and trait anxiety inventory (STAI), Center for Epidemiological Studies Depression Scale (CES-D), and Perceived Social Support Scale (PSSS). The partners were asked to complete the WHOQoL-BREF, FAS, and CFQ.

Questionnaire scores of patients and partners in the present study were compared with corresponding questionnaire scores of a healthy control sample (n = 62) recruited for a study by Marcellis et al. [19]. These healthy controls were recruited in the same geographical area/institution and timeframe as our study sample. We used the raw data of this healthy control population.

Detailed descriptions of the questionnaires (WHOQoL-BREF, FAS, SFNSL, CFQ, STAI, CES-D, PSSS) can be found in the online supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000501657) [20-26].

All statistical analyses were performed using SPSS version 24 for Mac. The chi-square test, the independent-samples t test (partners vs. controls and patients vs. controls), and paired t tests (patients vs. partners) were used to test for statistically significant differences between patients, their partners, and controls. Hierarchical linear regression analyses were used to assess the associations between the scores for the various domains of the sarcoidosis patients’ and partners’ WHOQoL-BREF and the sarcoidosis patients’ fatigue (FAS), SFNSL, CFQ, CES-D, STAI, and PSSS. Adjustments were made for age, sex, treatment, and time since diagnosis in the analysis regarding patients and for age and sex in the analysis regarding partners. Since each WHOQoL-BREF domain was analyzed by means of a separate regression model, a Bonferroni correction was used to reduce the risk of false-positive findings, by adjusting the significance level in these 5 regression analyses from 0.05 to 0.01. Hence, within each of the 10 WHOQoL-BREF regression models (5 for patients and 5 for partners), p values of <0.01 were considered to indicate statistical significance. In view of this correction, we also reported 99% CIs (instead of the conventional 95% CIs) around the estimated regression coefficients.

In a post hoc analysis, we have performed a mediation analysis using the Baron and Kenny method [27]. A moderation analysis was performed by including the product of 2 mean-centered predictors in a regression analysis, on top of the main effects of these 2 predictors.

Three quarters of the approached sarcoidosis patient sample (443/588) agreed to participate, of whom 10 were excluded from further analyses because they did not complete the main outcome measure QoL. Two-hundred and eight partners decided to participate and completed the questionnaires. The sarcoidosis patients whose partners participated in the study (n = 208) did not differ from those without a partner or whose partners did not participate (n = 225), except for age (Table 1).

Table 1 summarizes the demographic and clinical data, and the questionnaire scores of the 433 included patients are summarized. The prevalence of the various nonspecific symptoms among the sarcoidosis patients and their partners is shown in Figure 1.

Table 2 summarizes the characteristics and outcomes of the partners of the sarcoidosis patients and the sarcoidosis patients themselves as well as the comparison with healthy control subjects.

The overall QoL scores of the partners were lower than those of the healthy controls (p < 0.001). The QoL domain scores (Physical, Psychological, Social, Environment) were also lower for partners than for healthy controls.

The QoL of the sarcoidosis patients was significantly more impaired than that of their partners, overall as well as in the different domains (all p values <0.001, except social relationships p = 0.002).

Hierarchical multiple linear regression analyses demonstrated that, after adjustment for the covariates age and gender of the partner, none of the nonspecific symptoms (fatigue, SFN-associated symptoms, cognitive failure, state/trait anxiety, depressive symptoms, and perceived social support) of the patients, including their QoL, were associated with the overall QoL score and those for the 4 QoL domains of their partners.

Hierarchical multiple linear regression analyses demonstrated that, after adjustment for the covariates age, gender, and time since diagnosis and treatment, all nonspecific symptoms we studied, except momentary anxiety, were associated with the overall QoL score and those for the 4 QoL domains of the sarcoidosis patients, predicting 32–63% of the variance (Table 3).

Depressive symptoms were negatively associated with the overall QoL score and those for all domains, except social relationships. Perceived social support was positively associated with all QoL domains, except physical health. Fatigue was negatively associated with the overall QoL score and those for the physical and psychological QoL domains. SFN-associated symptoms were negatively associated with the physical and environmental QoL domains. Trait anxiety was negatively associated with the psychological and social QoL domains. Finally, cognitive problems were only negatively associated with the QoL domain of physical health, but this association was subject to a mediation effect (see below).

To simplify, overall QoL is predicted by fatigue and depressive symptoms. The QoL domain physical health is predicted by fatigue, SFN-associated symptoms, depressive symptoms, and cognitive failure. The QoL domain psychological health is predicted by fatigue, trait anxiety, depressive symptoms, and perceived social support. The QoL domain social relationships is predicted by trait anxiety and perceived social support. And last, the QoL domain environment is predicted by SFN-associated symptoms, depressive symptoms, and perceived social support (Fig. 2).

The QoL predictors for partners were not significant and are therefore not described any further here.

As regards the patients, the predictors explained 62.9% of the variance in the physical health domain scores. This domain was best predicted by fatigue, followed by SFN-associated symptoms, depressive symptoms, and cognitive failure.

The predictors explained 61.9% of the variance in the psychological health domain. This domain was best predicted by trait anxiety, depressive symptoms, fatigue, and perceived social support. Perceived social support had a positive effect on the psychological QoL, while the other variables had negative effects.

The predictors explained 41.7% of the variance in the social relationships domain. This domain was best predicted by trait anxiety and perceived social support. Perceived social support had a positive effect on QoL, while trait anxiety had a negative effect.

The predictors explained 31.8% of the variance in the environment domain. This domain was best predicted by the depressive symptoms, SFN-associated symptoms, and perceived social support. Again, perceived social support had a positive effect on QoL, while depressive symptoms and SFN-associated symptoms had a negative effect.

The predictors explained 50.7% of the variance in the overall QoL score, and this was best predicted by fatigue and depressive symptoms.

The results in Table 3 suggest that cognitive failure had a positive effect on QoL (unstandardized B 0.024), indicating that patients with more cognitive failure had a higher physical QoL. Since cognitive failure has a great impact on the lives of sarcoidosis patients, and given that the present sample included mostly young patients with a busy social and working life, this finding was against our expectations. In regression models, a significant association between a predictor and an outcome may in fact be explained by a third variable, such as a confounder, mediator, or moderator. Therefore, we inspected the partial and zero-order correlations between the physical domain of QoL and the predictors. The zero-order correlations showed that there was, as expected, a negative association between CFQ and physical QoL. However, after adjusting for the influence of other predictors (primarily fatigue and depressive symptoms), this negative association disappeared through collinearity. Figure 3 shows 2 mediation models where fatigue and depressive symptoms, respectively, mediate the association between cognitive failure and physical QoL. Indeed, the significant zero-order correlation between these 2 measures disappeared when the mediating effects of fatigue and depressive symptoms were included in the model (Fig. 3a, b). Furthermore, a moderation analysis showed a significant interaction effect between the CFQ and FAS as well as CESD on physical QoL (CFQ-FAS: β = 0.078, SE = 0.001, t = 2.182, p = 0.03, respectively, CFQ-CESD: β = 0.176, SE = 0.001, t = 3.795, p < 0.001). These results suggest that there may be multiple mechanisms underlying the relations between these variables.

This is the first study to show that the QoL of couples where one of the partners suffers from sarcoidosis is reduced compared to that of healthy controls. Neither the QoL nor nonspecific symptoms of the sarcoidosis patients predicted the QoL of the partners of the sarcoidosis patients we studied. Predictors of the QoL of the sarcoidosis patients themselves were fatigue, depressive symptoms, SFN-associated symptoms, cognitive failure, anxiety, and perceived social support. All of these non-specific symptoms, except perceived social support, had a negative impact on various aspects of the QoL of the sarcoidosis patients. This underlines the importance of determining all these non-specific symptoms in sarcoidosis patients.

The importance of patient-centeredness in healthcare has grown over the years. So far, family involvement and perspectives have infrequently been studied in sarcoidosis. A novel finding from our study is that partners of sarcoidosis patients also had a lower QoL than healthy persons, but to a lesser extent than that of the sarcoidosis patients we studied. The QoL of the partners living with a sarcoidosis patient was mainly lower in the psychological and social domains. We did not study the perceived social support for partners, but one could speculate that partners have less perceived social support and often feel misunderstood by people in their environment because of the lack of awareness of sarcoidosis as a disease. Previous studies have shown a relationship between social support and the QoL of partners of patients [28, 29]. This needs to be examined in future studies. They may also experience psychological distress, leading to anxiety [17], as sarcoidosis can be unpredictable and they worry about the consequences regarding the future of the patient as well as their own future. There is a need for further studies into dyadic coping in sarcoidosis.

In line with other studies, we found a lower QoL for our sarcoidosis patient sample than for healthy controls, especially in the physical health domain, meaning that they feel less physically healthy than the healthy population [13, 14, 16, 30]. Apart from major organ involvement, sarcoidosis patients can be bothered with reduced muscle strength, loss of physical condition, pain, extreme fatigue, and SFN-associated symptoms [1, 31]. Psychological factors are pervasive and include anxiety, depressive symptoms, and mental fatigue, including memory problems, lack of mental clarity, poor concentration, and inability to focus. These factors may not correspond with inflammatory disease activity nor respond to sarcoidosis treatment [1, 5]. The symptoms are disabling, persist after other signs of sarcoidosis activity have resolved, and adversely impact on major life areas, including QoL and work ability [32, 33]. Tan et al. [34] did find that the more symptoms affecting the patient, the more it affected the partner’s QoL.

Depressive symptoms, anxiety, and cognitive failure have increasingly been reported in clinical practice as well as in studies [4, 6, 7, 35-38]. Depressive symptoms are a known predictor of QoL in sarcoidosis [4, 38]. A novel finding is that not only depressive symptoms but also trait anxiety and subjective cognitive failure predicted QoL in our sarcoidosis sample. The association between cognitive failure and QoL disappeared when we included fatigue and depressive symptoms as mediators (Fig. 3a, b). This may imply multiple competing interpretations. First, cognitive failure presumably results in more depressive symptoms or fatigue, which in turn results in a lower physical QoL. This is in line with a previous study by Hendriks et al. [5] who found that cognitive failure predicted fatigue. Alternatively, it could indicate that depressive symptoms or fatigue causally affect both cognitive failure and physical QoL. Since we also found significant moderating effects between cognitive failure and depressive symptoms as well as fatigue on physical QoL, there may also be a moderating mechanism underlying the associations between these variables. This hypothesis was also supported by a previous study by our group in neurosarcoidosis patients, showing fatigue to be a strong predictor of cognitive impairment [39]. Studies in dialysis patients also found that depressive symptoms predicted cognitive impairment [40, 41]. As follow-up data were lacking in our study and cross-sectional studies generally have limitations with regard to establishing causality, the results have to be interpreted with some caution, and future follow-up studies are warranted to distinguish between these 2 interpretations for sarcoidosis patients.

To date, studies have shown a high prevalence of fatigue [8, 12, 42-45] and SFN-associated symptoms [46, 47] in sarcoidosis patients. In line with previous studies [13-15], our study found that sarcoidosis-associated fatigue was negatively associated with overall QoL, as well as the physical and psychological QoL domains, indicating that these QoL domains tend to decrease as patient fatigue increases. Of the partners, only 15% experienced fatigue (mainly moderate; 30/31 partners) in comparison with 78% of the sarcoidosis patients. Whether the moderate fatigue in a small proportion of partners might be caused by their own disabilities and/or health problems needs to be explored in future studies. In agreement with earlier studies, a substantial number of our sarcoidosis sample were suffering from SFN-associated symptoms [31, 46, 47]. SFN is a very difficult disease to diagnose and to treat [48]. This causes a lot of uncertainty and frustration for those having to deal with these problems. The presence of SFN-associated symptoms was found to be negatively associated with the physical and environmental QoL domains, indicating that physical and environmental QoL tends to decrease when patients experience more SFN-associated complaints. This could, at least partly, be explained by the fact that patients feel they are not being taken seriously by relatives and friends and experience misunderstanding because of lack of awareness of sarcoidosis and SFN.

The clinical course of sarcoidosis is highly variable, ranging from spontaneous resolution to disabling chronic disease with various manifestations [49]. In our cohort, no relation was found between the various manifestations and QoL (data not shown), stressing the importance of assessing not only the organs affected by sarcoidosis but also the nonspecific symptoms [5, 31].

All of the above-mentioned nonspecific symptoms are not visible in sarcoidosis patients, making it difficult for them to get acknowledged, leading to feelings of misunderstanding in many patients and even their partners [17]. Sarcoidosis patients have reported that QoL is the most important outcome of their treatment and of care, more important than radiographs, pulmonary function tests, and blood tests [32]. Most patients would like to see more attention and support for their psychological problems [17, 50]. We also found that patients with better support show a better QoL in all domains, except for physical health. Moreover, although it was beyond the scope of this study, it would be interesting to evaluate how not living with a partner might influence the QoL of sarcoidosis patients.

Sarcoidosis clinicians usually work in a multidisciplinary team. Our results underline the importance of a multidisciplinary approach assessing not only organ involvement but also any symptoms (organ-related or non-organ-related) and of using a holistic approach with attention to psychological support, for both patients and their partners. One of the possible interventions could be mindfulness-based exercise interventions, which have been found to reduce psychological symptoms and fatigue [51].

A limitation of the present study was that all patients were recruited in a tertiary referral center. This could have led to selection bias, since it is the more complex patients (in terms of affected organs and symptoms) who are often referred to tertiary referral centers. Hence, our results may not be generalizable to all sarcoidosis patients. However, our results are comparable with those of other QoL studies in sarcoidosis patient samples. Another limitation is that not all partners of the patients with sarcoidosis seen at the outpatient clinic participated in this study, and some patients did not have a partner. However, the sample of sarcoidosis patients whose partners participated did not differ from those without a partner or with a partner who did not participate in our study (except for age). Unfortunately, information on the medical health status of the partners was not collected in this study. It is tempting to speculate that this explains for the lower QoL of the partners compared to healthy controls. Though, the QoL of partners was higher than the QoL of the sarcoidosis patients. Strikingly, however, no relation was found between the QoL of the partners and the burden of the sarcoidosis experienced by the patients themselves indicating that this does not have an impact on the QoL of their partners. One final limitation was the fact that we did not have a matched control group and that the sample of healthy controls used in our study was rather small, which might increase the influence of sampling error on the estimated statistics in the control sample. Our control group did consist of persons living in the same geographical area/institution and timeframe and was previously used by our group for similar comparisons in previous studies [13, 19, 44].

Couples living with sarcoidosis have a lower QoL than healthy controls. Sarcoidosis patients often struggle with fatigue, SFN-associated symptoms, anxiety, depressive symptoms, and memory and concentration problems. All these symptoms have a negative impact on the QoL of patients, but not on that of their partners. Although these factors pose challenges for objective assessment, they are recognized illness-related symptoms meriting formal consideration with validated instruments. Perceived social support positively impacts on the QoL. Further studies are needed to investigate whether offering psychosocial support at the outpatient clinic for sarcoidosis patients as well as their partners would lead to better coping strategies and improve QoL for both of them.

We would like to thank the sarcoidosis patients and their partners for participating in this study.

The authors who took part in this study declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. All authors read and approved the final manuscript.

This study was supported by a research grant of the ild care foundation: www.ildcare.nl. The study sponsor had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.