Diagnostic Accuracy of the Kveim Test and Clinical Features in Stage 0 Sarcoidosis: A 52-Year Retrospective Cohort Study

Background and aim: Stage 0 sarcoidosis is characterized by granulomatous inflammation without radiologic evidence of pulmo- nary involvement often poses a significant diagnostic challenge due to diverse heterogenous clinical manifestations and lack of specific clinical, laboratory, and radiologic features. We aimed to evaluate the symptoms, laboratory, nuclear imaging manifestations, bronchoscopy findings, and the Kveim test results in patients with stage 0 sarcoidosis to identify this precursor stage. Second objective is to define the exclusive and collaborative diagnostic accuracy of these procedures. Third goal was to to shed light on the pathogenesis of sarcoidosis through the Kveim test. Materials and Methods: We conducted a retrospective analysis of 132 patients with stage 0 sarcoidosis admitted between 1972 and 2024 at our center. Diagnostic yield was assessed for constitutional, clinical, and organ-specific symptoms, serum ACE, calcium, 24h uri- nary Ca, nuclear imaging (67Ga scintigraphy, 18FDG-PET/CT), and the Kveim test findings. Distinctive sensitivity was calculated for each modality individually and through a collaborative assessment. Results: The cohort had a mean age of 46.2 years with a female predominance. The prevalant symptoms were fatigue (25.8% ), dry cough (21.2%), and dyspnea on exertion (13.6%), while extrapulmonary involvement was more common, with cutaneous manifestations in 25.7% and ocular involvement in 18.2% of the patients. Serum ACE was elevated at 56.1% and tuberculin anergy was detected at 62.1%, whereas other laboratory markers showed limited diagnostic significance. The Kveim test achieved the highest yield at 82.4% on its own. Nuclear imaging acuity for detecting extrapulmonary organ involvement due to granulomatous inflammation were 58.9% for 18FDG-PET/ CT and 51.3% for 67Ga scintigraphy. Sensitivity of individual bronchoscopy interventions remained low but their integrated analysis was clinically significant but statistically reached marginal values individually. A collaborative analysis integrating clinical, laboratory, nuclear imaging, and the Kveim test findings achieved the highest overall diagnostic accuracy with 94.7% sensitivity. Conclusions: Kveim test was the hallmark diagnostic tool for the early identification of stage 0 sarcoidosis, likely reflecting its abil- ity to boost low-intensity granulomatous inflammation emerging at this initial phase of the disease. Constitutional, clinical symptoms, and the standard laboratory tests lacked sufficient sensitivity other than serum ACE and tuberculin anergy. Nuclear imaging modalities revealed moderate sensitivity for identifying organ involvement in this stage revealing cellular tracer uptake. A collaborative approach integrating symptoms, nuclear imaging, bronchoscopy, and the Kveim test findings achieved an almost absolute certainty in this early stage of sar- coidosis for a robust framework for early diagnosis. Our findings revealed that the low intensity potential of granulomatous inflammation with the associated borderline granuloma load augmented by the Kveim test in stage 0 shed light into sarcoidosis pathogenesis.