A 5-week-old previously healthy male presented with vomiting and diarrhea leading to hypovolemic shock and profound metabolic acidosis. He was subsequently found to have severe methemoglobinemia. The acidosis and shock improved with fluid resuscitation and methemoglobinemia was successfully treated with methylene blue. An extensive workup, including evaluations for infectious and metabolic etiologies, was unremarkable. However, a detailed dietary history revealed a recent change in diet, supporting a diagnosis of food protein-induced enterocolitis syndrome (FPIES). We present this case to highlight the importance of considering FPIES in an infant with vomiting and diarrhea, in the setting of a recent dietary change, leading to profound dehydration, metabolic acidosis, and methemoglobinemia. Diagnosis of FPIES, although difficult to make and one of exclusion, can be potentially life-saving.
Non-IgE-mediated food allergies can have acute or chronic presentations [
A five-week-old previously healthy, full-term male initially presented to an emergency department with a two-day history of profound vomiting and diarrhea. He was well appearing and afebrile at the time of presentation; reassurance was given and he was discharged home with close follow-up. At his follow-up appointment, an upper gastrointestinal series (UGI) was obtained that was reassuring. His symptoms persisted, however, so, roughly 24 hours following his UGI, he was taken to another emergency department for worsening gastrointestinal symptoms and lethargy. His initial blood gas showed severe metabolic acidosis with a pH of 6.7, bicarbonate of 3 mmol/L, and base deficit exceeding −30 mmol/L. Intraosseous access was obtained prior to transport to the tertiary care pediatric facility and the child received 20 ml/kg of normal saline during transport.
Upon arrival to the pediatric intensive care unit, the child was lethargic, cyanotic, and mottled with cool extremities. His exam was notable for decreased muscle tone, labored breathing, a soft but distended abdomen, prolonged capillary refill, and a sunken anterior fontanelle. His initial heart rate was 150 beats per minute, blood pressure was 70/30 mmHg, and oxygen saturation was 85% on 2 liters/minute nasal cannula. Intravenous access was obtained and the patient received aggressive isotonic crystalloid resuscitation. He was intubated due to severe acidosis and altered mental status. A broad workup was initiated after stabilization including evaluation for infectious, metabolic, and cardiac causes. His initial labs were also notable for an elevated white blood cell count of 51 k/cumm (normal 6–18), with 38% bands, 5% myelocytes, and 8% metamyelocytes, an ammonia of 211 mCmol/L (normal 11–35), and a lactate of 1.8 mmol/L (normal 0.5–1.6). Stool hemoccult was positive. He was placed on broad-spectrum antibiotics pending blood, urine, cerebrospinal fluid, and stool cultures. An echocardiogram was obtained that demonstrated normal anatomy and function. The child was persistently hypoxemic after intubation despite receiving 100% fraction of inspired oxygen on the ventilator, so an arterial blood gas was obtained and the blood was noted to be dark chocolate colored in appearance (Figure
This is an arterial blood sample obtained shortly after admission. It was noted to be significantly darker than expected. Cooximetry was obtained and the methemoglobinemia level was reported as greater than 25%.
Multiple subspecialties were consulted to determine the cause of his severe metabolic acidosis and methemoglobinemia, including Metabolism and Gastroenterology. At this point, further history revealed that the infant’s formula had been changed multiple times in the days preceding presentation. Malabsorptive causes were considered unlikely due to normal growth prior to presentation and allergic enteritis/proctitis was considered unlikely due to the severity of presentation. Eosinophilic esophagitis was not considered in the differential from gastroenterology because of the diarrhea and severity of the presentation. Infectious enteritis and colitis were initially presumed to be the most likely cause, but a stool culture, ova and parasite exam, rotavirus antigen, and gastrointestinal pathogen PCR test were all negative. The infant was started on hydrolyzed formula (Elecare) and discharged home with follow-up appointments with a pediatric gastroenterologist and an allergist with a presumed diagnosis of FPIES. At the time of his follow-up, roughly 8 weeks after discharge, he was continuing to do well on Elecare and had not had recurrence of his symptoms, and his weight had returned to the 52nd percentile up from the 6th percentile at his initial presentation (Figure
This is a copy of the infant’s growth chart. The infant was admitted to the PICU and was 3.77 kilograms (kg), which was below his birth weight and at the 6th percentile for age. He was discharged weighing 4.09 kg and at posthospitalization follow-up (6 weeks from discharge) he was 5.95 kg, approximately the 52nd percentile for age.
Pediatric food allergies are common in the first two years of life and have an estimated prevalence between 3 and 8% [
The precise pathogenesis of FPIES has not been clearly defined. T-cells are often considered as a major role player; however, this has come under recent scrutiny [
Decreased catalase activity during acute intestinal inflammation leads to increased intestinal nitrites and can cause increased heme molecule oxidation, which leads to methemoglobinemia [
Given that FPIES can present at a very young age, the differential diagnosis for this clinical presentation is varied and includes sepsis, cardiogenic shock, metabolic disorders, and intestinal etiologies. FPIES is a clinical diagnosis, so obtaining a detailed dietary history as part of the evaluation is crucial. Age of presentation, absence of fever, and recurrent episodes of gastrointestinal symptoms are important keys to the diagnosis [
Treatment of acute FPIES is primarily supportive with fluid resuscitation and close hemodynamic monitoring. Occasionally, vasopressors or inotropes are needed in addition to fluids to treat hypotension. No strong evidence to support the benefit of steroid treatment is available [
In our case report, we discuss the case of an infant presenting with hypovolemic shock, severe metabolic acidosis, and methemoglobinemia due to FPIES. Despite extensive evaluation, no other etiologies were found to explain his symptoms and laboratory findings. Early recognition and aggressive management were key elements for shock reversal. His symptoms and failure to thrive resolved after switching to a hypoallergenic, hydrolyzed formula. FPIES should be suspected in infants who present with diarrhea and methemoglobinemia. As discussed previously, early recognition may prevent excessive diagnostic testing, recurrent hospital admissions, and failure to thrive.
The authors have indicated they have no conflicts of interest relevant to this article to disclose.