P1896 - Cow’s Milk Protein Allergy-Induced Methemoglobinemia in an Infant

Abigail Schneller, MD¹, Melissa Castro, MD¹, Kacie H. Denton, MD, MPH¹, Matthew A. Buendia, MD²
1Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN; 2Vanderbilt University Medical Center, Nashville, TN

Introduction: Cow’s milk protein allergy (CMPA) can be an IgE or non-IgE mediated allergy, typically diagnosed by the presence of fecal blood or mucus, frequent spit-ups, and/or food refusal in an otherwise healthy infant. This case describes a rare complication of CMPA: methemoglobinemia.

Case Description/

Methods: A 45-day-old term, previously healthy male presented with profuse, watery diarrhea, fever, and poor weight gain. A neonatal sepsis workup revealed leukocytosis, mild normocytic anemia, and high anion gap metabolic acidosis. Blood, urine, and cerebrospinal fluid studies including cultures were non-infectious. Patient was discharged after improvement with supportive care.

Four days later he returned with irritability, poor feeding, fever, and gray discoloration. Workup revealed a venous blood gas pH <7, methemoglobin >30%, hyperammonemia, worsened leukocytosis, and profound metabolic acidosis. In the intensive care unit, he was given methylene blue with rapid improvement of methemoglobin level to 3.1%. Feeds were restarted with cow’s milk-based formula, but subsequent methemoglobin levels began to rise. Fecal studies were notable for markedly elevated calprotectin. CMPA was suspected so he was switched to hydrolyzed formula. He then had improvement of symptoms and labs. Remaining workup included a normal hemoglobin electrophoresis and low cytochrome b5 reductase activity.

Discussion: Methemoglobinemia results in decreased oxygen delivery to the tissues. Patients can present with cyanosis, dyspnea, lethargy, vomiting, diarrhea, and seizures. Etiology includes acquired exposures (topical anesthetics, nitrates, dapsone, or sulfonamides) or, less commonly, congenital methemoglobinemia. This can be due to defective cytochrome b5 reductase or globin gene mutations leading to Hemoglobin M disease. Although not defective, our patient had low cytochrome b5 reductase activity, which may have contributed to his severe presentation.

The mechanism for methemoglobinemia in CMPA is thought to be due to an altered gut microbiome, bacterial overgrowth, and increased production of nitrites that indirectly oxidize ferrous iron, inducing methemoglobinemia. Treatment involves removal of the offending agent (switching to hydrolyzed formula), and, in severe cases, methylene blue. Our patient exhibited rapid improvement of methemoglobin levels within hours of administration. While it remains incredibly rare, CMPA-induced methemoglobinemia should be considered in infants with diarrhea, acidosis, and hypoxia.

Disclosures:
Abigail Schneller indicated no relevant financial relationships.
Melissa Castro indicated no relevant financial relationships.
Kacie Denton indicated no relevant financial relationships.
Matthew Buendia indicated no relevant financial relationships.

Abigail Schneller, MD¹, Melissa Castro, MD¹, Kacie H. Denton, MD, MPH¹, Matthew A. Buendia, MD². P1896 - Cow’s Milk Protein Allergy-Induced Methemoglobinemia in an Infant, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.