Protein-Losing Enteropathy in the Setting of Iron Deficiency Anemia: A Case Series

**Background:** Iron deficiency (ID) is the most common nutritional deficiency in children, affecting 7%–9% of US toddlers, with about 3% developing iron deficiency anemia (IDA). Protein-losing enteropathy (PLE) involves gastrointestinal protein loss leading to hypoalbuminemia. Historically, case series linked PLE with severe IDA and excessive cow milk intake, but most reports predate widespread iron fortification. This case series highlights the contemporary relevance of this association and the variability in its diagnosis and management.

**Methods:** This retrospective case series reviewed 7 toddlers (median age 20 months, range 14–27 months) presenting with edema between November 2016 and January 2019 at a tertiary care institution. Inclusion criteria were symptoms and laboratory features of PLE (hypoalbuminemia and elevated stool alpha-1 antitrypsin) and IDA (anemia for age with transferrin saturation <16%). Data on presenting symptoms, laboratory values, treatment, and follow-up were abstracted from electronic medical records. Descriptive statistics (medians and ranges) were calculated.

**Key Results:** All patients consumed ≥24 oz/day of cow milk (median 36 oz, range 24–72 oz/day). Common presenting symptoms included periorbital edema, abdominal distension, and pallor; 3 had stooling changes (2 diarrhea, 1 constipation). All initially presented to primary care and were referred to the emergency department; 4 required admission. All had normal growth parameters (average weight-for-length 73rd percentile, range 53rd–99th). Laboratory evaluation confirmed IDA and hypoalbuminemia in all. Management included cow milk elimination and oral iron (median dose 6 mg/kg/day, range 3–6 mg/kg/day). Four patients received parenteral interventions: IV iron (n=1), packed red blood cells (n=3), or IV albumin (n=2); 2 required multiple therapies. Two patients underwent endoscopy and colonoscopy, both with normal gross and histologic findings. Median changes in hemoglobin and albumin pre- to post-treatment were +5.4 g/dL (range 2.9–8.7) and +1.8 g/dL (range 0.2–2.8), respectively. Excluding patients who received parenteral interventions, median changes were +6.25 g/dL (range 2.9–7.1) and +1.6 g/dL (range 0.2–1.8). At follow-up (~3 months post-diagnosis), 6 of 7 had hemoglobin >11 g/dL and normal ferritin; 5 of 7 had transferrin saturation >15%; edema resolved in all patients.

**Clinical Implications:** This series underscores that PLE with IDA should be considered in toddlers presenting with anasarca and a history of excessive cow milk intake. The nonuniform approach to workup and treatment—including decisions on admission, parenteral therapies, and endoscopy—highlights the lack of consensus guidelines. Laboratory evaluation should include complete blood count, albumin, iron studies, and stool alpha-1 antitrypsin. Cow milk restriction (to ≤16–24 oz/day) and high-dose oral iron (6 mg/kg/day) appear effective; parenteral interventions are reserved for selected cases. Follow-up at ~4 weeks is recommended to assess edema resolution and compliance. The normal endoscopic findings in 2 patients suggest mucosal damage may be limited to inaccessible small bowel regions. The incidence of this disorder is likely underrecognized; a prior prospective study found 29% of IDA patients had PLE. Prospective research is needed to identify risk factors and standardize management.