Clinical characteristics and risk factors of protein-losing enteropathy: a retrospective study

Protein-losing enteropathy (PLE) is characterized by excessive gastrointestinal protein loss, yet systematic comparative studies across etiologies remain limited. This study aimed to characterize the confirmed PLE cohort in our center, with a focused comparison between connective tissue disease-associated PLE (CTD-PLE) and lymphatic drainage disorder-associated PLE (LDD-PLE), describe follow-up observations, and explore routine clinical indicators that may assist etiologic differentiation.

This retrospective study included 146 patients admitted to Beijing Shijitan Hospital between January 2014 and December 2024 with PLE confirmed by 99mTc-HSA scintigraphy. Patients were classified as CTD-PLE or LDD-PLE according to the final clinical diagnosis. Clinical features, laboratory findings, and available follow-up data were analyzed, and logistic regression together with receiver operating characteristic (ROC) analyses were used to explore factors associated with CTD-PLE.

The cohort included 146 patients (median onset age 26 years; 30 CTD-PLE and 116 LDD-PLE). Edema (84.2%) and serous cavity effusions (76.7%) were the most frequent manifestations. Comparative analysis showed that CTD-PLE patients were older, predominantly female, and had more frequent thrombosis and higher D-dimer levels than LDD-PLE patients. CTD-PLE also showed distinct laboratory features, including higher total cholesterol, triglycerides, and globulin levels, whereas LDD-PLE was associated with lower lymphocyte counts and more frequent diarrhea. Multivariate analysis identified age at onset, Hb, and total cholesterol as independent predictors of CTD-PLE. The three-variable model showed good apparent discrimination in this single-center cohort (AUC = 0.890), while C3 showed the best single-variable discrimination. Among patients with available follow-up, 19/20 CTD-PLE patients receiving glucocorticoids plus immunosuppressants achieved symptom remission with a median ALB improvement of 9.5 (3.8, 19.6) g/L, whereas 23/43 surgically treated LDD-PLE patients achieved symptom remission with a median ALB improvement of 2.0 (-0.5, 5.8) g/L.

PLE with different etiologies shows distinct clinical and laboratory patterns. Age at onset, Hb, and total cholesterol may assist preliminary etiologic differentiation, although the proposed model requires validation in independent cohorts. The observed lipid, coagulation, and correlation patterns, together with the follow-up findings, provide exploratory clues to distinct mechanisms and treatment trajectories.