In an 80‑year‑old woman with edema, hypoalbuminemia and low total protein and no evidence of renal or hepatic loss, what is the most likely diagnosis and what is the appropriate work‑up and management for protein‑losing enteropathy?

Protein-Losing Enteropathy in an 80-Year-Old Woman

In an 80-year-old woman presenting with edema, hypoalbuminemia, and low total protein without renal or hepatic loss, the most likely diagnosis is protein-losing enteropathy (PLE), and the immediate priority is to identify the underlying etiology through cardiac screening with echocardiography and gastrointestinal evaluation with endoscopy and biopsies. 1, 2

Diagnostic Work-Up

Initial Laboratory Assessment

• Confirm PLE by measuring fecal alpha-1-antitrypsin clearance or performing nuclear imaging studies with 99mTc-labeled albumin to document excessive gastrointestinal protein loss 3, 4
• Obtain complete blood count, comprehensive metabolic panel, and liver function tests to assess severity and exclude other causes 1, 2
• Check for lymphopenia, which commonly accompanies PLE 3

Cardiac Evaluation (Priority)

• Perform echocardiography immediately to evaluate for constrictive pericarditis, which is a critical reversible cause in elderly patients 1, 2
• Assess for elevated central venous pressure and structural heart disease 1
• While Fontan circulation is the most commonly discussed cardiac cause in guidelines, this is irrelevant in an 80-year-old woman without congenital heart disease history 5

Gastrointestinal Evaluation

• Perform upper endoscopy with duodenal biopsies to identify mucosal abnormalities, intestinal lymphangiectasia, eosinophilic gastroenteritis, or inflammatory conditions 1, 2
• Consider capsule endoscopy or double-balloon enteroscopy if initial endoscopy is unrevealing but suspicion remains high 6
• Obtain stool cultures to exclude infectious etiologies (bacterial, viral, parasitic) 4

Additional Testing Based on Age and Presentation

• Screen for malignancy, as neoplastic processes can cause PLE in elderly patients 3
• Evaluate for autoimmune conditions (ANA, complement levels, anti-SSA/Ro) if clinical features suggest systemic lupus erythematosus, though this typically presents in younger patients 7
• Review medication list for offending agents: olmesartan, mycophenolate mofetil, azathioprine 1, 2
• Consider CT imaging of chest/abdomen/pelvis to assess for lymphadenopathy, masses, or mesenteric abnormalities 4

Immediate Management

Dietary Intervention (Start Immediately)

• Restrict long-chain triglycerides to <5% of total energy intake to reduce intestinal chyle production and lymphatic protein loss 1, 2
• Supplement with medium-chain triglycerides (MCT) to >20% of total energy intake, as MCT bypass intestinal lymphatics and are absorbed directly into the portal circulation 1, 2, 3
• Provide high-protein diet of at least 1.2 g/kg actual body weight/day to compensate for ongoing losses 2
• Ensure adequate energy intake of at least 30 kcal/kg actual body weight/day 2
• Supplement fat-soluble vitamins (A, D, E, K) due to fat malabsorption 4

Critical pitfall: Do not delay dietary modification while awaiting definitive diagnosis—the low long-chain triglyceride/high MCT diet is safe and beneficial across all etiologies 2

Etiology-Specific Treatment

If Constrictive Pericarditis Identified

• Surgical pericardiectomy is the definitive treatment and should be pursued urgently as this is potentially curative 1, 2

If Intestinal Lymphangiectasia (Primary or Secondary)

• Continue strict low-fat/high-MCT diet as primary therapy 1, 2, 3
• Consider octreotide (somatostatin analog) if dietary measures fail, though evidence is limited to case reports 3, 6

If Inflammatory/Erosive Cause Identified

• Initiate immunosuppressive therapy targeting the underlying inflammation (e.g., corticosteroids for inflammatory bowel disease, eosinophilic gastroenteritis) 1, 2
• For medication-induced enteropathy, discontinue the offending agent immediately 1, 2

If No Clear Etiology Despite Work-Up

• Trial of budesonide for patients with persistent hypoalbuminemia poorly responsive to dietary therapy 5, 2
• Monitor closely for hypercortisolism, though budesonide has fewer systemic effects than other corticosteroids 5

Monitoring and Follow-Up

• Measure serum albumin levels regularly (every 2-4 weeks initially) to evaluate treatment efficacy 1, 2
• Perform repeat endoscopy with biopsies at 12 months after initiating treatment to assess histologic response 1, 2
• Monitor for complications of hypoalbuminemia: thromboembolic events (consider prophylactic anticoagulation if albumin <2.0 g/dL), infections due to immunoglobulin loss, and nutritional deficiencies 3, 4

Critical Pitfalls to Avoid

• Do not overlook cardiac causes in elderly patients without obvious gastrointestinal pathology—constrictive pericarditis is a major reversible contributor in this age group 1, 2
• Do not rely solely on dietary management for inflammatory or infectious causes, as these require targeted therapy for the underlying condition 2
• Do not continue potentially offending medications while investigating other causes 1, 2
• Do not assume all PLE is due to intestinal lymphangiectasia—the differential is broad and includes cardiac, inflammatory, infectious, neoplastic, and medication-induced etiologies 1, 8, 3

Prognosis

Prognosis depends entirely on the underlying etiology and its treatability 4. Constrictive pericarditis has excellent outcomes with pericardiectomy, while primary intestinal lymphangiectasia requires lifelong dietary management with variable response 1, 3. Inflammatory causes may respond well to immunosuppression, but malignancy-associated PLE carries a poor prognosis 3.