Diagnostic value of delayed-phase 99mTc-HSA scintigraphy and treatment outcomes in connective tissue disease-associated protein-losing enteropathy

To characterize the clinical spectrum, diagnostic value of delayed-phase 99mTc-HSA scintigraphy, and therapeutic outcomes in connective tissue disease-associated protein-losing enteropathy (CTD-PLE).

A retrospective study evaluated patients undergoing 99mTc-HSA scintigraphy at the First Affiliated Hospital of Sun Yat-sen University (March 2021-October 2025). The diagnostic protocol included standard early-phase imaging (1 and 3 h), with conditional 6-h delayed imaging for negative or inconclusive initial scans.

Among 77 patients who underwent 99mTc-HSA scintigraphy for suspected PLE, 31 (40.3%) had underlying CTDs, primarily Sjögren's syndrome (n = 12) and systemic lupus erythematosus (n = 11). Severe hypoproteinemia with serous effusions predominated (93.5%), whereas gastrointestinal symptoms were infrequent (35.5%). Conventional endoscopic and cross-sectional imaging findings were largely nonspecific. Scintigraphy most frequently demonstrated tracer leakage in the jejunum and ileum. Delayed 6-h imaging identified additional sites of protein leakage in approximately half of the patients with negative or inconclusive early-phase findings. Following glucocorticoid-based immunosuppression (prednisone in 31, cyclophosphamide in 16, methotrexate in 6), albumin and complement levels improved significantly within 3 months. Complete remission was achieved in 14 patients, and partial remission in 5. Over a median 10-month follow-up (IQR 2-24), no relapses were documented among patients who achieved remission and remained under observation.

In this cohort, delayed 6-h imaging revealed additional protein leakage sites in approximately half of the patients with negative or inconclusive early-phase scintigraphy, suggesting potential diagnostic value. Individualized immunosuppressive therapy targeting the underlying CTD was associated with favorable clinical outcomes. Further prospective studies are warranted to validate these findings. Key Points • A delayed 6-h 99mTc-HSA scintigraphy protocol substantially identified additional protein leakage sites not detected on standard early-phase scintigraphy. • CTD-PLE frequently presents with edema or serous effusions rather than prominent gastrointestinal symptoms, making early recognition challenging. • Accurate localization of gastrointestinal protein loss may facilitate timely glucocorticoid-based treatment and contribute to favorable long-term outcomes.