Clinical Correlates of Fatigue in Adults With Sickle Cell Disease

Abstract Background Fatigue is a prevalent and functionally limiting symptom in adults with sickle cell disease (SCD), yet its clinical correlates remain incompletely characterized. We examined neuropathic pain features, global pain intensity, and perceived stress as independent correlates of fatigue in this population. Methods This cross-sectional study included 136 adults with SCD who were predominantly Black (97%), largely female (63.2%) and aged 36.6 years on average (SD = 11.7). Their Fatigue (PROMIS) ranged from 29.4 to 83.2, neuropathic pain status (S-LANSS) ranged from 0 to 24, average pain intensity (0-10) ranged from 0 to 9.3), and stress (Perceived Stress Scale) ranged from 0.06-0.96). Multivariable linear regression assessed whether neuropathic pain independently predicted fatigue after adjusting for pain intensity and stress. Results The mean scores were: fatigue 56.5 (SD = 9.0), pain intensity 4.5 (SD = 2.4), and stress was 0.39 (SD = 0.18). Neuropathic pain status was common, 39% had S-LANSS > =12. Fatigue correlated with neuropathic pain (r=.26, p=.002), pain intensity (r=.42, p < .001), and stress (r=.57, p< .001). In the adjusted regression model, pain intensity (β = 1.00, p=.0001) and stress (β = 24.95, p< .0001) were significant positive predictors of fatigue, however, neuropathic pain status was not significantly associated with fatigue (β = 0.18, p=.072). Together, neuropathic pain status, pain intensity, and stress explained approximately 43% of the variance in fatigue. Conclusions Fatigue in SCD is strongly associated with psychological stress and overall pain burden, with neuropathic pain features contributing modestly in this sample. These findings support a multidimensional model of fatigue in which both sensory and psychosocial factors play clinically meaningful roles. Comprehensive assessment strategies that extend beyond pain intensity alone, including evaluation of neuropathic pain characteristics and stress, may enhance symptom management and improve functional outcomes and quality of life for adults living with SCD.