Advances in management of sarcoidosis-associated fatigue: A narrative review.

Abstract

Sarcoidosis-associated fatigue (SAF) occurs in approximately 30% to 90% of patients. While previous reviews examined select medications, these omitted nonpharmacological and emerging treatments that could significantly improve fatigue for individuals with sarcoidosis. Limited guidance exists for excluding alternative causes of fatigue and selecting between treatment options for these patients. This narrative review synthesized pharmacological and nonpharmacological interventions for SAF and interpreted evidence strength to guide clinical decision-making. PubMed was queried in December 2025 for clinical trials, reviews, and meta-analyses published within the last 10 years. This yielded 41 results which were supplemented by manual review of bibliographies, clinical guidelines, and a search of the Cochrane Library. Evidence was interpreted and analyzed for quality using a modified GRADE-informed approach. Treatment of active disease with prednisone or methotrexate improves systemic inflammation but may paradoxically worsen fatigue with chronic use. Stimulants (e.g., dexmethylphenidate, armodafinil) display low-quality evidence for improving SAF and side effects may be prohibitive for some patients. TNF-α inhibitors (e.g., infliximab) have very low-quality evidence with few studies and negative findings. Pulmonary rehabilitation and exercise training show low-to-moderate quality evidence with few adverse effects but lack specific implementation protocols. Diagnosis of SAF requires exclusion of alternative causes which may be challenging. Active disease should be treated appropriately while monitoring for adverse effects. Despite low-to-moderate quality evidence for most interventions, nonpharmacological approaches (e.g., pulmonary rehabilitation, exercise) are recommended as first-line therapy given favorable risk-benefit profiles. Larger, well-designed RCTs are needed given the substantial disease burden.