Introduction: Peripheral lymphopenia in sarcoidosis results from lymphocyte migration to sites of inflammation.
Objectives: To determine whether peripheral lymphopenia could serve as a laboratory marker useful in assessing the severity and extent of sarcoidosis.
Materials and Methods: Eighty-four patients participating in a diagnostic accuracy study of [18F] FDG PET/CT for evaluating disease activity and multi-organ involvement in sarcoidosis underwent routine laboratory tests, including complete blood count and routine pulmonary function tests. Carb-free [18F]FDG PET/CT whole-body scans were performed in 84 steroid naïve patients. PET/CT images were qualitatively analyzed to assess the presence of active organ lesions.
Results: Lymphopenia was identified in 55 patients. Compared to patients with normal white blood cell counts, those with lymphopenia were younger at sarcoidosis diagnosis (<40 years; p=0.04), had significantly lower BMI (p=0.02), significantly worse spirometry results (both FEV1 and FVC as percent predicted and z-scores), and showed a trend toward restriction on plethysmography (p=0.08). Patients with lymphopenia had significantly higher serum gamma-globulin levels (p=0.05). Patients were stratified by metabolic activity patterns on [18F] FDG PET/CT into groups:
• With vs. without metabolically active pulmonary changes
• With metabolically active extrapulmonary changes vs. isolated pulmonary activity
• With vs. without metabolic activity, regardless of organ location
Lymphopenia was significantly more frequent in patients with [18F] FDG-avid metabolically active pulmonary sarcoidosis compared to those without active pulmonary changes in PET/CT scans (p=0,03), in those with [18F] FDG-avid metabolically active-multiorgan sarcoidosis vs. isolated pulmonary sarcoidosis (p=0,0006) and showed a trend toward [18F] FDG-avid metabolically active sarcoidosis, regardless of lesion location(p=0,06)
Conclusions: In young patients (<40 years) with sarcoidosis and peripheral lymphopenia, [18F] FDG PET/CT imaging is warranted to assess for multi-organ involvement. This approach is supported by associations with younger age at diagnosis, impaired lung function, elevated serum gamma-globulins, and higher prevalence of metabolically active disease on PET/CT—findings that may guide escalation to systemic therapy.