Peripheral Levels of Selected Biomarkers in Patients with Post-Sarcoidosis Chronic Fatigue Syndrome.

INTRODUCTION

Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and multiple symptoms such as cognitive impairment and muscle pain, often linked to immune-inflammatory dysfunction. Sarcoidosis, a granulomatous disease with systemic inflammation, commonly causes fatigue, even during remission. This study examined whether fatigue and depressive symptoms in sarcoidosis remission relate to residual inflammation or oxidative stress. Recent studies highlight parallels between post-infectious fatigue syndromes, including Long COVID, and sarcoidosis-related fatigue, emphasizing IL-6 mediated pathways. Theoretical frameworks of immune-metabolic interactions further support the hypothesis that residual inflammation drives persistent fatigue in remission.

MATERIALS AND

METHODS

Seventy-one sarcoidosis patients were divided into three groups: remission with fatigue (RS/CFS, n=22), remission without fatigue (R/S, n=23), and active sarcoidosis (A/S, n=26). Fatigue was assessed with the Fatigue Assessment Scale (FAS), depressive symptoms with the Beck Depression Inventory (BDI), and quality of life with PHQ-9. Pulmonary function tests measured FEV1 and FVC. Serum biomarkers (hsCRP, IL-6, TNF-α, total antioxidant status, and 8-isoprostanes) were measured by ELISA.

RESULTS

RS/CFS and A/S groups showed significantly higher fatigue, and depressive scores compared to R/S (P <0.05). HsCRP and IL-6 levels were elevated in fatigued patients (RS/CFS and A/S) versus non-fatigued (R/S) (P <0.05). IL-6 correlated moderately with fatigue and depression scores (r =0.33). No significant differences were found in TNF-α or oxidative stress markers. Pulmonary function was slightly reduced in fatigued patients and weakly correlated with mental fatigue (r = -0.26).

CONCLUSION

Our data support a role for low-grade systemic inflammation, especially elevated hsCRP and IL-6, in fatigue and depressive symptoms during sarcoidosis remission. Further research integrating inflammatory, oxidative, metabolic, and neuroendocrine pathways is needed to elucidate fatigue pathogenesis and develop targeted interventions. IL-6 may represent a potential biomarker of fatigue in sarcoidosis. These findings highlight the importance of persistent low-grade inflammation and may guide the development of future therapeutic strategies.