Managing fatigue in sarcoidosis – a systematic review of the evidence

Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients. Eight studies were identified that fulfilled the inclusion criteria. These studies evaluated six different interventions (infliximab, adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)-αtherapies (adalimumab and infliximab) and neurostimulants (methylphenidate and armodafinil), but within five of the studies, the risk of bias was high within most domains and the remaining three studies included only small numbers of participants and were short in duration. Trial evidence for treating fatigue as a manifestation of sarcoidosis is limited and requires further investigation. Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended

Consequences of sarcoidosis

Sarcoidosis is a multisystem disorder of unknown cause(s). Less specific disabling symptoms, including fatigue and physical impairments, may have a major influence on the daily activities and the social and professional lives of the patients, resulting in a reduced quality of life. A multidisciplinary approach focusing on somatic and psychosocial aspects is recommended. Patients self-perceived knowledge about the importance of exercise and lifestyle should be improved. Developing the most appropriate therapeutic approach for sarcoidosis requires careful consideration of the possible impact of fatigue, small fiber neuropathy related symptoms, pain, cognitive functioning, and coping strategies. Personalized medicine and appropriate communication are beneficial

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

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, Medication, Skin, Eyes) 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 a 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

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