P3C312: Don't Sweat, It's Not CF: A Unique Presentation of Neuroendocrine Hyperplasia of Infancy

Introduction: Chronic respiratory failure in the pediatric patient can be the manifestation of a myriad of pathologies, ranging from upper airway obstruction and neuromuscular disease to interstitial lung disease (ILD). The differential diagnosis for exocrine pancreatic insufficiency is likewise broad, though cystic fibrosis (CF) is decidedly the most common etiology of early-onset disease. Classically, the combined presentation of chronic respiratory failure and failure to thrive lends itself to a sweat chloride test, genetic evaluation, and the subsequent diagnosis of CF. We present a unique case of tachypnea and malabsorption as sentinel signs leading to the diagnosis of neuroendocrine hyperplasia of infancy (NEHI) and pancreatic insufficiency, respectively.

Case Description: A five-month-old female with a history of intrauterine methamphetamine exposure, macrocephaly, and pectus excavatum presented to gastroenterology for moderate malnutrition (weight z = -2.67). On assessment, she was notably tachypneic with grunting and retractions, reportedly her baseline since birth. She was directly admitted and placed on a high-flow nasal cannula for acute-on-chronic respiratory failure. Per history, she had adequate caloric intake, normal stools, and toleration of feeds without aspiration or sweating. An upper GI series and swallow study were unremarkable. Pancreatic enzyme assay revealed total pancreatic insufficiency and the patient was started on pancrelipase, with subsequent weight gain. She was weaned and discharged on 1 L/min of home oxygen. Over the next several months, the patient was admitted several times for respiratory failure secondary to viral illnesses. A sweat chloride test and surfactant mutation panel returned negative. A lung biopsy demonstrated pathology consistent with NEHI.

Discussion: NEHI is a rare childhood ILD that typically manifests with the insidious onset of tachypnea, hypoxemia, rales, and failure to thrive secondary to excessive caloric expenditure. Because of its ubiquitous presentation, it can be mistaken for common respiratory infections. This misdiagnosis can lead to inappropriate use of antimicrobial agents, unnecessary medical interventions, and elevated healthcare costs. Our patient presented uniquely with concurrent pancreatic insufficiency. If misdiagnosed as CF, it would also result in high and futile healthcare utilization and expenditures. Conversely, treatment of NEHI is supportive, and resolution occurs spontaneously, usually by age 4, though the independent resolution of pancreatic insufficiency is unknown.

Conclusion: After an extensive literature review, this is the first case of an infant with NEHI and concurrent pancreatic insufficiency. The case illustrates the importance of a broad differential once common causes of severe disease, like CF, have been excluded. Two symptoms, such as respiratory failure and failure to thrive, may not be tied to the same disease process. This case highlights the importance of collaboration with subspecialists and consideration of NEHI as a rare but important cause of chronic respiratory failure in infancy.