Associations of Systemic Immune-Inflammation Index and Hematological Markers with Symptom Burden and Radiological...

Background/Objectives: Sarcoidosis is a multisystem inflammatory disease characterized by heterogeneous clinical manifestations and variable disease severity. Hematological inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and systemic immune-inflammation index (SII), have recently attracted attention as accessible indicators of systemic inflammation in sarcoidosis. This study aimed to evaluate radiological stage, symptom burden, pulmonary function parameters, and hematological markers in patients with sarcoidosis. Methods: This retrospective multicenter cohort study included histopathologically confirmed sarcoidosis patients from 10 centers. Demographic characteristics, clinical manifestations, pulmonary function test parameters, serum angiotensin-converting enzyme (ACE) levels, and hematological inflammatory markers (MPV, RDW, NLR, PLR, SII) were evaluated. Patients were categorized according to radiological stage (stage 0-I vs. stage II-IV), symptomatic status, and symptom burden (<3 vs. ≥3 symptoms). Results: Among 458 patients included in the study, stage I (47.8%) and stage II (46.9%) disease were the predominant radiological presentations. Patients with stage II-IV disease were older and demonstrated significantly lower forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and diffusing capacity for carbon monoxide (DLCO) values together with higher serum ACE levels compared with stage 0-I disease. Dyspnea, weight loss, and extrapulmonary involvement were more frequent in stage 2-4 disease. No significant associations were observed between radiological stage and NLR, PLR, or SII values. MPV and RDW values differed significantly between symptomatic and asymptomatic patients. Patients with ≥3 symptoms demonstrated significantly lower pulmonary function parameters together with statistically significant higher NLR, PLR, and SII values. In multivariate analyses, only the SII demonstrated an independent association with a high symptom burden. Conclusions: Serum ACE levels were associated with advanced radiological stage, whereas hemogram-derived inflammatory indices, particularly the NLR, PLR, and SII, were associated with symptom burden rather than radiological stage in sarcoidosis and may reflect symptomatic inflammatory activity.