Health-Related Quality of Life (HRQoL) in Sarcoidosis: Diagnosis, Management, and Health Outcomes.

Health-related quality of life (HRQoL), though rarely considered as a primary endpoint in clinical trials, may be the single outcome reflective of patient priorities when living with a health condition. HRQoL is a multi-dimensional concept that reflects the degree to which a health condition interferes with participation in and fulfillment of important life areas. HRQoL is intended to capture the composite degree of physical, physiologic, psychological, and social impairment resulting from symptom burden, patient-perceived disease severity, and treatment side effects. Diminished HRQoL expectedly correlates to worsening disability and death; but interventions addressing HRQoL are linked to increased survival. Sarcoidosis, being a multi-organ system disease, is associated with a diffuse array of manifestations resulting in multiple symptoms, complications, and medication-related side effects that are linked to reduced HRQoL. Diminished HRQoL in sarcoidosis is related to decreased physical function, pain, significant loss of income, absence from work, and strain on personal relationships. Symptom distress can result clearly from a sarcoidosis manifestation (e.g., ocular pain, breathlessness, cough) but may also be non-specific, such as pain or fatigue. More complex, a single non-specific symptom, e.g., fatigue may be directly sarcoidosis-derived (e.g., inflammatory state, neurologic, hormonal, cardiopulmonary), medication-related (e.g., anemia, sleeplessness, weight gain, sub-clinical infection), or an indirect complication (e.g., sleep apnea, physical deconditioning, depression). Identifying and distinguishing underlying causes of impaired HRQoL provides opportunity for treatment strategies that can greatly impact a patient's function, well-being, and disease outcomes. Herein, we present a reference manual that describes the current state of knowledge in sarcoidosis-related HRQoL and distinguish between diverse causes of symptom distress and other influences on sarcoidosis-related HRQoL. We provide tools to assess, investigate, and diagnose compromised HRQoL and its influencers. Strategies to address modifiable HRQoL factors through palliation of symptoms and methods to improve the sarcoidosis health profile are outlined; as well as a proposed research agenda in sarcoidosis-related HRQoL.

Benefit of Wearing an Activity Tracker in Sarcoidosis.

Sarcoidosis causes many disabling symptoms, including fatigue and exercise limitations, which have been shown to improve by physical activity programs. The aim of this study was to estimate the effect of continuous activity monitoring using an electronic activity tracker (AT) on exercise performance and fatigue of sarcoidosis patients, compared to controls (cohort study), and the effect of additional personal coaching (randomized trial) over a period of 3 months. Fifty-four sarcoidosis patients received an AT (Group Ia: 27 with coaching and Group Ib: 27 without). A historical group of sarcoidosis patients (Group II; n = 41) who did not follow a physical activity program served as controls. Exercise performance of patients wearing an AT (Group I) improved compared with controls (Group II), including the 6MWD, % predicted (∆4.4 ± 9.1 versus ∆0.7 ± 5.0, respectively), and fatigue levels decreased (∆-3.9 ± 5.7 versus ∆-1.8 ± 5.3). Patients with coaching (Group Ia) showed greater improvement of exercise capacity over time than patients without coaching (Group Ib) as shown by the Steep Ramp Test results (watts: ∆20.2 ± 33.8 versus ∆5.7 ± 26.4; and SRT, VO2max, % predicted: ∆1.6 ± 2.6 versus ∆0.7 ± 2.3). Sarcoidosis patients wearing an AT achieved improvement of exercise performance and reduction of fatigue. We therefore recommend encouraging sarcoidosis patients to wear an AT to stimulate physical activity and reduce fatigue. The additional benefit of coaching needs to be explored in future studies.

Risk and outcome of COVID-19 infection in sarcoidosis patients: results of a self-reporting questionnaire.

BACKGROUND: It has been suggested that sarcoidosis patients, especially those on immunosuppressive medications, are at increased risk for COVID-19 infection and more severe disease. METHODS: A questionnaire was developed in four languages (English, Dutch, Italian, and Spanish). The questionnaire queried whether patients had been infected with COVID-19 and outcome of the infection. Risk factors for COVID-19 infection were collected. RESULTS: A total of 5200 sarcoidosis patients completed the questionnaire with 116 (2.23%) reporting infection and 18 (15.8%) required hospitalization. Increased hazard ratio (HR) for COVID-19 infection were seen for those with a COVID-19 infected roommate (HR=27.44, p<0.0001), health care provider (HR=2.4, p=0.0001), pulmonary sarcoidosis (HR=2.48, p=0.001), neurosarcoidosis (HR=2.02, p<0.01), or rituximab treatment (HR=5.40, p<0.0001). A higher rate of hospitalization was found for those with underlying heart disease (HR=3.19 (1.297-7.855), p<0.02). No other feature including race, other immunosuppressive agent, age, or underlying condition was associated with a significant increased risk for infection or more severe disease. CONCLUSION: The overall rate of COVID-19 was 2.23%, suggesting an increased rate of COVID-19 infection. However, when an analysis of the questionnaires of sarcoidosis and non-sarcoidosis patients was performed in one localized area over this time period, the rate of COVID-19 infection was similar in both groups. Sarcoidosis patients who cohabitated with COVID-19 infected individuals, worked in health care, had pulmonary or neurologic sarcoidosis, or were treated with rituximab had an increased risk for COVID-19 infection. No significant increased risk for hospitalization could be identified based on age, race, gender or any specific immunosuppressive treatment. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (4): e2020009).

Everyday cognitive failure in patients suffering from neurosarcoidosis.

BACKGROUND: Cognitive failure is associated with memory and concentration problems. Previously, a prevalence of one third was found in a general sarcoidosis population. The aim of this study was to assess if neurosarcoidosis patients are at higher risk for developing everyday cognitive failure using the Cognitive Failure Questionnaire (CFQ) and to determine what factors were associated with cognitive failure. METHODS: A cross-sectional web-based survey was conducted from April to May 2017 in a national sample of neurosarcoidosis patients. The survey asked about complaints and included 3 questionnaires (Fatigue Assessment Scale [FAS], Small Fiber Neuropathy Screening List [SFNSL] and CFQ. Data were compared to a general sarcoidosis population. RESULTS: Of the 152 patients who completed the survey, 131 had neurosarcoidosis. The mean CFQ score was significantly higher in the neurosarcoidosis (45.6±20.7) compared to the general sarcoidosis population (36.2±15.9; p< 0.0001). High CFQ scores (≥43) were found in 55.7% and 33.9%, respectively (p<0.0001). The FAS score (OR 21.4) and SFNSL score (OR 4.3) were the strongest positive predictors of a high CFQ score. CONCLUSION: Cognitive failure is a significant problem in neurosarcoidosis. More than half of the patients reported cognitive deficits, compared to one third of a general sarcoidosis population. Fatigue and small fiber neuropathy play a role in cognitive failure.

The Fatigue Assessment Scale: quality and availability in sarcoidosis and other diseases.

PURPOSE OF REVIEW: Fatigue is a problem experienced by many patients suffering from chronic diseases, including sarcoidosis patients. It has a substantial influence on patients' quality of life (QoL). It is, therefore, important to properly assess fatigue with a valid and reliable measure. The Fatigue Assessment Scale (FAS) is the only validated self-reporting instrument classifying fatigue in sarcoidosis. The aim of this review was to examine the psychometric properties of the FAS and the diseases and languages in which it has been used. Studies among sarcoidosis patients were also reviewed in terms of outcomes. RECENT FINDINGS: Studies were identified by searching the electronic bibliographic database Pubmed. Search terms used were: FAS and fatigue. Articles were included in the review if the FAS had been used to assess fatigue. RESULTS: Since its introduction, the FAS was used in 26 different diseases or conditions, including stroke, neurologic disorders, rheumatoid arthritis, idiopathic pulmonary fibrosis and sarcoidosis. Its reliability and validity have proved to be good. Unidimensionality has been established. So far, the FAS is available in 20 languages and widely used in sarcoidosis. Digital versions as well as PDFs of various languages are available online (www.wasog.org). SUMMARY: The FAS has good psychometric qualities for the diseases in which it has been examined, including sarcoidosis, and can be used in clinical practice. Healthcare workers can use the FAS to assess fatigue in the management, follow-up and clinical care programmes for their patients consistently across countries, as well as in clinical research.

Everyday cognitive failure and depressive symptoms predict fatigue in sarcoidosis: A prospective follow-up study.

BACKGROUND: Fatigue is a major and disabling problem in sarcoidosis. Knowledge concerning correlates of the development of fatigue and possible interrelationships is lacking. OBJECTIVE: A conceptual model of fatigue was developed and tested. METHODS: Sarcoidosis outpatients (n = 292) of Maastricht University Medical Center completed questionnaires regarding trait anxiety, depressive symptoms, cognitive failure, dyspnea, social support, and small fiber neuropathy (SFN) at baseline. Fatigue was assessed at 6 and 12 months. Sex, age, and time since diagnosis were taken from medical records. Pathways were estimated by means of path analyses in AMOS. RESULTS: Everyday cognitive failure, depressive symptoms, symptoms suggestive of SFN, and dyspnea were positive predictors of fatigue. Fit indices of the model were good. CONCLUSIONS: The model validly explains variation in fatigue. Everyday cognitive failure and depressive symptoms were the most important predictors of fatigue. In addition to physical functioning, cognitive and psychological aspects should be included in the management of sarcoidosis patients.

Physical activity and training in sarcoidosis: review and experience-based recommendations.

INTRODUCTION: Sarcoidosis is a multisystemic inflammatory disorder with a great variety of symptoms, including fatigue, dyspnea, pain, reduced exercise tolerance and muscle strength. Physical training has the potential to improve exercise capacity and muscle strength, and reduce fatigue. The aim of this review and survey was to present information about the role of physical training in sarcoidosis and offer practical guidelines. AREAS COVERED: A systematic literature review guided an international consensus effort among sarcoidosis experts to establish practice-basic recommendations for the implementation of exercise as treatment for patients with various manifestations of sarcoidosis. International sarcoidosis experts suggested considering physical training in symptomatic patients with sarcoidosis. Expert commentary: There is promising evidence of a positive effect of physical training. Recommendations were based on available data and expert consensus. However, the heterogeneity of these patients will require modification and program adjustment of the standard rehabilitation format for e.g. COPD or interstitial lung diseases. An optimal training program (types of exercise, intensities, frequency, duration) still needs to be defined to optimize training adjustments, especially reduction of fatigue. Further randomized controlled trials are needed to consolidate these findings and optimize the comprehensive care of sarcoidosis patients.

Predictors of fatigue in sarcoidosis: The value of exercise testing.

BACKGROUND: Sarcoidosis patients often are troubled by dyspnea, exercise limitation, and fatigue. Many patients (up to 50-81%) suffer from sarcoidosis-associated fatigue. The etiology of fatigue in sarcoidosis is still unclear. OBJECTIVE: The aim of this study was to assess the relationship between fatigue and both exercise capacity and clinical characteristics in sarcoidosis patients. Additionally, we studied the predictive value of exercise test results and other relevant clinical characteristics for the independent variable of fatigue. METHODS: From November 2012 to September 2014, 201 sarcoidosis outpatients were referred to the Dutch ILD care foundation expertise team, 146 of whom were included in this retrospective cohort study. All patients completed the Fatigue Assessment Scale (FAS). Exercise capacity was assessed by the 6-min walking distance (6MWD) and steep ramp test (SRT) result. Clinical data were gathered from the medical records. RESULTS: Exercise capacity only showed a weak correlation with fatigue (r = 0.25, p = 0.002 for 6MWD % of predicted; r = 0.24, p = 0.003 for SRT). Fatigue was not correlated with the demographic variables of age, body mass index, or time since diagnosis. Inflammatory markers, lung function tests, and hand grip strength showed no significant correlations with fatigue. Backward multiple regression analysis showed that only female sex (t = -2,614, p = 0.01) and 6MWD % of predicted (t = -2.773, p = 0.006) were independent predictors of fatigue. However, the r(2) indicated that these two variables together explained only 11% of the FAS score. CONCLUSIONS: These results show that exercise capacity partly predicts patients' fatigue scores. Fatigue was not explained by lung function test results, inflammatory markers, or other clinical parameters.

Validation of the King's Sarcoidosis Questionnaire (KSQ) in a Dutch sarcoidosis population.

BACKGROUND: The King's Sarcoidosis Questionnaire (KSQ) is a brief questionnaire assessing health status using five modules (General Health Status, Lung, Eyes, Skin, Medication) in patients with sarcoidosis. The KSQ was only validated in one English sarcoidosis cohort. OBJECTIVE: The aim of this study was to validate the KSQ in a Dutch sarcoidosis population. METHODS: The KSQ was translated according to international guidelines and tested in interviews with patients. Consecutive outpatients completed multiple questionnaires twice, two weeks apart. Construct validity, internal consistency and repeatability were determined. RESULTS: Of the 98 patients included 85 had lung, 22 skin and 24 eye disease. There was good construct validity of the KSQ General Health Status module against the World Health Organization Quality of Life-BREF questionnaire. The Medication module correlated weak to moderate with most questionnaires. The correlations with organ-specific questionnaires varied from strong for Eyes (r=0.75), Skin (r=-0.62) to moderate for Lung (r=-0.45 with MRC breathlessness scale). Internal consistency was good for all KSQ modules (Cronbach's α 0.72-0.93). Intraclass correlation coefficients (0.70-0.90) and Bland-Altman plots showed good repeatability of the KSQ. CONCLUSION: The Dutch KSQ is the first translation of the English KSQ, validated in a Dutch sarcoidosis population.

Benefits of Physical Training in Sarcoidosis.

BACKGROUND: Sarcoidosis patients suffer from fatigue and exercise limitation. The aim of this study was to establish whether a physical training program improves these and other outcomes important to sarcoidosis patients. METHODS: From 11/2012 to 9/2014, 201 sarcoidosis patients were referred to the ild care expertise team, Ede, the Netherlands. In our center, all patients are routinely recommended to undergo testing at baseline to determine their physical functioning and encouraged to complete a 12-week, supervised physical training program. Ninety patients underwent baseline testing and returned for repeat testing at 3 months in the interim, 49 completed the training program (Group I) and 41 chose not to participate (Group II). Change over time (from baseline to 3 months) in fatigue, exercise capacity, and skeletal muscle strength were assessed between the two groups. RESULTS: At baseline, there were no between-group differences for fatigue, DLCO%, FVC%, or exercise capacity [assessed by percent predicted six-minute walk distance (6MWD%) and Steep Ramp Test (SRT)]. The 6MWD for Group I improved between baseline and 3 months, while the 6MWD remained the same in Group II (F = 72.2, p < 0.001). Group I showed a significantly larger decrease of fatigue compared with Group II (F = 6.27, p = 0.014). Lung function tests did not change in either group. CONCLUSION: A supervised physical training program improves exercise capacity and fatigue among sarcoidosis patients and should be included in their management regimen.

Benefits of physical training in patients with idiopathic or end-stage sarcoidosis-related pulmonary fibrosis: a pilot study.

BACKGROUND: The natural history of disease in patients with stage IV (fibrotic) sarcoidosis may mirror that of patients with idiopathic pulmonary fibrosis (IPF). Both are bothered by progressive dyspnea, exercise limitation and fatigue. OBJECTIVE: To establish whether patients suffering from pulmonary fibrosis might benefit from a physical training program. STUDY DESIGN: Twenty-four eligible patients referred to the out-patient clinic of the ild care expertise team of Hospital Gelderse Vallei, Ede, The Netherlands between November 2012 and November 2013 were included in this observational pilot study of a 12-week physical training program. Outcomes, including exercise capacity, skeletal muscle strength, lung function and fatigue were assessed at two time points: 1) baseline; and 2) after completion of a 12-week physical training program. RESULTS: At baseline, the percentage predicted DLCO, FVC, FEV1 and exercise capacity (assessed by six-minute walking distance (6MWD) or maximal oxygen uptake) was reduced in both groups. After program completion, exercise capacity improved (>10% improvement 6MWD) in 13 subjects (54.2%): 7 with IPF and 6 with sarcoidosis subjects. Other secondary endpoints, including pulmonary function tests and patient-reported outcome measures improved in some subjects. CONCLUSION: A 12-week physical training program improved or maintained exercise capacity in patients with IPF (despite disease progression) or fibrotic sarcoidosis. The results from this pilot study could be used to design prospective studies aimed at answering lingering questions about exercise training in patients with these progressive, incurable conditions.

Body composition profiling in a Dutch sarcoidosis population.

UNLABELLED: Muscle atrophy is a common problem in many chronic inflammatory diseases. It may occur as part of a generalized wasting process (cachexia) or be hidden due to preservation of fatmass (sarcopenia, sarcopenic obesity). OBJECTIVES: The aim of this study was to assess the prevalence of cachexia and muscle atrophy in sarcoidosis and their association with disease activity and severity. METHODS: A cross-sectional study was performed in 423 sarcoidosis patients. Fat-free mass was assessed as an indirect measure of muscle mass by bioelectrical impedance analysis. Patients were stratified based on body mass index (BMI) and fat-free mass index (FFMI).Muscle atrophy was defined as FFMI <15 kg/m2 for women and <17 kg/m2 for men corresponding to <10th percentile of current reference values; cachexia as BMI <20 combined with muscle atrophy.Multivariate linear regression models were used to adjust for potential confounders. RESULTS: Of the patients examined, 58% were categorized as overweight (37%) or obese (21%), whereas 7% were underweight.Muscle atrophy was present in 25% and cachexia in 5%. Patients with muscle atrophy showed significantly worse lung function (DLCO, FEV1, FVC, all p-values <0.01) and impaired exercise capacity (VO2max, p<0.001). The associations were most pronounced in patients with cachexia. Associations remained significant after adjustment for potential confounders. CONCLUSIONS: Muscle atrophy was present in 25% of sarcoidosis patients and was associated with more severe pulmonary disease. Prospective studies with longitudinal design are needed to assess the association between muscle atrophy and disease severity in sarcoidosis.

Everyday cognitive failure in sarcoidosis: the prevalence and the effect of anti-TNF-alpha treatment.

BACKGROUND: Cognitive symptoms, such as concentration problems, are frequently recorded by sarcoidosis patients. OBJECTIVES: The aim of this study was to assess the prevalence of perceived everyday cognitive failure in sarcoidosis patients and healthy controls. Furthermore, the effect of treatment on cognitive functioning was examined. METHODS: The study included 343 sarcoidosis patients (44.6% females; age 49.3 +/- 11.0 years). They completed the Cognitive Failure Questionnaire (CFQ) and Fatigue Assessment Scale (FAS) at baseline and the 6-month follow-up to evaluate the effect of treatment on cognitive functioning. The control group consisted of 343 age- and sex-matched healthy controls. RESULTS: The mean CFQ score was significantly higher in sarcoidosis patients (37.3 +/- 16.1) compared with the controls (31.3 +/- 10.1; p < 0.0001).A high CFQ sore (> or =43) was found in 35.0% of the patients and only 14.3% of the controls. No relation with disease severity and duration, or disease location was found. The proportion of patients receiving treatment did not differ among the groups with high and normal CFQ score. At the 6-month follow-up, only patients recently treated with anti-TNF-alpha therapy (n = 42) demonstrated a significant improvement in the CFQ score (Delta -7.07 +/- 7.23) compared with the untreated patients (Delta -0.08 +/- 9.35) and patients treated with prednisone with or without methotrexate (Delta 1.67 +/- 9.22; p < 0.0001). After adjustment for the concomitant decrease in fatigue, the effect of anti-TNF-alpha therapy remained high and significant. CONCLUSIONS: Subjective cognitive failure is a substantial problem in sarcoidosis patients regardless of disease severity. Anti-TNF-alpha therapy had a positive effect on cognition, fatigue and other symptoms of sarcoidosis.

Fatigue in sarcoidosis: a systematic review.

PURPOSE OF REVIEW: Several studies have investigated fatigue among sarcoidosis patients. The purpose of this review is to analyze published data on the assessment, prevalence, etiology, and treatment of sarcoidosis-associated fatigue. RECENT FINDINGS: Fatigue was identified as a prominent problem in sarcoidosis, and its presence was frequently associated with impaired quality of life, compared with patients without fatigue. Although the studies with good methodological fatigue assessment found no relationship between clinical parameters and fatigue in sarcoidosis patients, the remaining studies reported associations between fatigue and clinical and psychological parameters. No studies were designed to analyze the etiology of fatigue, but some studies showed that prednisone-treated patients reported more fatigue compared with untreated patients. In addition, only one study focused on a treatment for fatigue, dexmethylphenidate hydrochloride. Several instruments to measure fatigue were used, with the Fatigue Assessment Scale most frequently utilized. SUMMARY: This review illustrates the importance of fatigue as an under-recognized complication of sarcoidosis. It further emphasizes the need for longitudinal prospective studies to better define sarcoidosis fatigue, explore its impact on quality of life, define aggravating or alleviating factors and evaluate new potential treatment strategies.