Abdominal distension, edema lead to rare diagnosis

An adolescent presenting with abdominal distension, peripheral edema, and severe hypoalbuminemia was ultimately diagnosed with intestinal lymphangiectasia–associated protein-losing enteropathy (PLE) secondary to generalized lymphatic anomaly (GLA)/lymphangiomatosis involving the pancreas and retroperitoneum, highlighting the importance of considering lymphatic malformations in patients with unexplained hypoproteinemia and intestinal edema.

The in-press case study from Gastroenterology was reported by Chia-Hung Tu, of the Division of Gastroenterology at National Taiwan University Hospital in Taipei, and colleagues.

Clinical presentation

The patient was a 12-year-old female with an unremarkable prior medical history who presented with four months of progressive abdominal distension, anorexia, and bilateral lower-extremity edema. Initial treatment with diuretics partially improved abdominal symptoms, but the peripheral edema persisted. On examination, the patient had grade two pitting edema of the lower extremities.

Laboratory testing revealed severe hypoalbuminemia and hypoproteinemia, with a serum albumin level of 1.8 g/dL and total protein of 3 g/dL. Hematologic testing showed a white blood cell count of 3,280/µL, hemoglobin of 15.9 g/dL, and platelets of 215,000/µL. Liver enzymes, bilirubin, renal function, amylase, and lipase levels were normal. Urinalysis showed no evidence of proteinuria, suggesting that the patient’s protein loss was not renal in origin.

Endoscopic and imaging findings

"Abdominal ultrasound and computed tomography revealed a non-cirrhotic liver but identified a 5-cm multicystic mass in the pancreatic head, accompanied by edematous small-bowel walls and mild ascites," noted Tu and colleagues. "Enteroscopy further demonstrated diffuse mucosal swelling and enlarged intestinal villi, enhanced with indigo carmine staining."

Histopathologic analysis of ileal biopsy samples showed dilated submucosal lymphatic channels, findings consistent with intestinal lymphangiectasia. Further evaluation with endoscopic ultrasound (EUS) revealed enlargement of the pancreatic head with numerous 1–5 mm anechoic cystic and tubular structures. EUS-guided fine-needle aspiration produced milky, chylous fluid with a markedly elevated triglyceride level of 934 mg/dL, indicating lymphatic involvement.

Magnetic resonance imaging (MRI) demonstrated extensive multiloculated cystic lesions affecting the pancreatic head and adjacent mesentery, extending into the retroperitoneum with indistinct margins.

Diagnosis

The patient’s presentation suggested PLE, which was confirmed by a markedly elevated 24-hour fecal alpha-1 antitrypsin clearance of 85.5 mL/day (reference ≤27 mL/day). A laparoscopic biopsy of the peripancreatic soft tissue revealed dilated lymphatic channels consistent with lymphatic malformation.

Based on the clinical, histologic, and imaging findings, the patient was diagnosed with intestinal lymphangiectasia–associated PLE secondary to GLA involving the pancreas and retroperitoneum.

GLA, previously termed lymphangiomatosis, is a rare multifocal lymphatic malformation characterized by infiltrative lymphatic overgrowth that can involve soft tissues, viscera, and skeletal structures.

Clinical implications

PLE is a syndrome characterized by excessive gastrointestinal loss of plasma proteins, most commonly measured by fecal alpha-1 antitrypsin clearance. PLE may arise through two main mechanisms: mucosal injury, which increases permeability and protein loss impaired lymphatic drainage, leading to leakage of lymphatic fluid into the intestine

In this case, intestinal lymphangiectasia developed as a consequence of generalized lymphatic anomaly, a rare infiltrative lymphatic disorder.

GLA can involve multiple organs and may present with a wide range of manifestations, from incidental findings to severe complications such as hypoproteinemia, obstruction, hemorrhage, or abdominal symptoms.

Diagnosis typically requires integration of clinical findings, imaging, and histopathology, with MRI considered the preferred modality for assessing disease extent. Biopsy can confirm the diagnosis but carries risks including lymphatic leakage or chylous ascites.

Currently, no standardized treatment exists for GLA, and therapy is typically individualized.

Outcome

Initial treatment focused on stabilizing the patient’s protein loss and symptoms. The patient received long-acting octreotide (30 mg every 6 weeks), which resulted in a rapid but temporary improvement in serum albumin levels.

Because of persistent disease activity, bevacizumab therapy was initiated at 1 mg/kg every three weeks to target the lymphatic malformation. Although early clinical improvement was observed, albumin levels eventually declined, prompting dose escalation to 2 mg/kg and later to 100 mg every three weeks. The intensified regimen produced a sustained reduction in lymphangiomatosis on MRI and gradual normalization of serum albumin levels.

After 12 years of follow-up, the patient remained clinically stable with no recurrence of abdominal distension or edema, and serum albumin levels were maintained between 4-5 g/dL. 

The authors concluded that combined therapy with long-acting octreotide and bevacizumab may represent an effective strategy for symptom control and disease management in patients with intestinal lymphangiectasia–associated PLE secondary to GLA.

 The authors reported no conflicts of interest.