We present a child whose symptoms began as an apparent life threatening episode (ALTE), initially thought to be secondary to gastroesophageal reflux but over time, she developed persistent tachypnea and hypoxemia and she was ultimately found to have neuroendocrine hyperplasia of infancy (NEHI).
A 9 week old girl was admitted for evaluation of an ALTE. Her birth history, review of systems, family and environmental histories were non-contributory to her present illness. During her evaluation, her lung fields were hyperinflated and she had radiographic evidence of increased bronchovascular marking and a barium esophogram demonstrated gastroesophageal reflux. She was discharged home on oral ranitidine. Over the next three months, she developed persistent wheezing and tachypnea which worsened despite aggressive outpatient supportive management. She was readmitted and since an extensive work up was negative the decision was made to obtain an open lung biopsy. Routine histopathology and microbiology were non-conclusive but immunohistochemical staining with bombesin showed the presence of increased neuroendocrine cells in the bronchial epithelium, confirming the diagnosis of NEHI (figure 1). She was treated with intravenous methylprednisone 30 mg/kg once daily for three days every month for six months and hydroxychloroquine (10mg/kg/day) orally daily for six months with good response. She is now 30 months old, growing and developing normally, she takes inhaled budesonide twice daily and she has needed two courses of oral corticosteroids in the last year.
This case describes the presentation of an ALTE that evolved into an interstitial lung disease (ILD) that was ultimately diagnosed as NEHI. Although her initial symptoms were characteristic of an ALTE, her initial chest radiograph had some subtle signs suggestive of an interstitial process. When she developed tachypnea and hypoxemia that was only corrected by supplemental oxygen therapy, a computerized tomographic (CT) scan of the chest (Figure 2) showed bilateral ground glass opacities, confirming our suspicions of ILD. In pediatrics, acute interstitial lung diseases are usually due to viral pneumonias and less commonly, pulmonary hemorrhage and edema. This child had repeated negative cultures for viruses and other microorganisms and her echocardiographic evaluation was normal. Since her symptoms persisted and the interstitial changes on her chest radiograph did not improve, a lung biopsy was necessary for diagnosis and determination of the best therapy.Neuroendocrine (NE) cells are granulated epithelial cells that produce bioactive products such as bombesin, serotonin and calcitonin that are capable of causing bronchoconstriction, vasoactivity, epithelial differentiation and smooth muscle alteration. NE cells appear in developing conducting airways of fetuses by 10 weeks’ gestation and increase in number primarily in bronchioles as gestation progressed. They are felt to play a role in lung development and gradually disappear by 12 months of age. NE cells and bodies hyperplasia in the lungs have been reported in patients with SIDS, BPD, cystic fibrosis, prolonged ventilation, congenital diaphragmatic hernia, and congenital central hypoventilation syndrome. There are recent reports of patients with persistent tachypnea whose lung biopsies showed NE cell hyperplasia. Our patient had a negative sweat test, normal alveolar ventilation studies and abnormal chest radiograph. She has no identifiable cause for NE cells and bodies hyperplasia. The mainstay of treatment for ILD of unknown origin is glucocorticosteroids and/ or hydroxychloroquine. She responded well to these treatments and now she is asymptomatic.
In an infant with ALTE and lower respiratory tract symptoms of undefined etiology with progressive deterioration, NEHI and other interstitial lung diseases should be included in the differential diagnosis since there are potential therapies available and NEHI has a good prognosis.
Rasik Shah, None.