Case Presentation: A previously healthy 12 month old presented to the emergency department with three weeks of progressively worsening generalized edema and one week of fatigue and pallor. Patient was born at term, and growth and development had been appropriate. Mother had stopped breastfeeding several weeks prior to presentation, just before patient’s first birthday. Patient’s diet was appropriate for age and consisted of table foods and approximately 16 oz of whole milk per day. She had had no fevers, vomiting, or diarrhea.
On presentation, patient was tachycardic with HR 167. She was afebrile and normotensive. Exam revealed a well-developed toddler with significant pallor and generalized edema. Edema was most pronounced in hands, feet, and periorbital area. Cardiac exam revealed tachycardia and S4 gallop. Lungs were clear to auscultation. Hepatic border was palpable 2cm below costal margin.
Initial labs were notable for hemoglobin 5.6, WBC count 24.8, platelets 902, total protein 3.1 (reference range 5.7 – 8.0g/dL), albumin 0.9, and normal creatinine, liver enzymes, and coagulation tests. Urinalysis (UA) was normal, ruling out urinary protein losses as the etiology for patient’s hypoproteinemia. Iron studies were consistent with iron deficiency anemia, and fecal occult blood test was positive. Patient received one dose of albumin and furosemide with significant improvement in edema. Further workup revealed positive alpha 1-antitrypsin, indicating gastrointestinal protein loss. She was started on a strict milk protein-free diet and oral iron supplementation. Symptoms were ultimately attributed to a protein-losing enteropathy and iron deficiency anemia secondary to cow’s milk protein allergy.
Discussion: Cow’s milk protein allergy is relatively common in the pediatric population, affecting approximately 2.8% of children at one year of age. This case describes an uncommon presentation of a common condition, highlighting the importance of considering milk protein allergy in a variety of clinical presentations.
This patient presented with generalized edema. The differential diagnosis of edema in the pediatric population is broad and includes renal, hepatic, cardiac, and gastrointestinal etiologies. This patient’s profound hypoalbuminemia initially raised suspicion for nephrotic syndrome. After UA was negative for protein, GI loss of protein became the most likely diagnosis. Positive stool alpha 1-antitrypsin confirmed the diagnosis of protein-losing enteropathy.
While protein-losing enteropathy can be caused by a variety of disorders, this patient’s age, recent introduction of cow’s milk, and positive fecal occult blood suggested cow’s milk protein allergy as the etiology for her protein-losing enteropathy. Cow’s milk protein is one of the most common inciting allergens in non-IgE-mediated gastrointestinal food-induced allergic disorders (non-IgE-GI-FAs), a term that encompasses food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). While FPIES has been increasingly recognized in recent years, FPE remains rarely diagnosed. Patients with FPE often present with significant iron deficiency anemia, as seen in this patient.
Conclusions: Protein-losing enteropathy secondary to cow’s milk protein allergy is an uncommon cause of edema, hypoalbuminemia, and iron deficiency anemia in pediatric patients. This diagnosis must be considered when the clinical presentation is appropriate.