© 2002 American Thoracic Society
Pediatric Interstitial Lung DiseaseChildren Are Not Small AdultsInterstitial or diffuse lung diseases in children comprise a large and heterogeneous group of rare, mostly idiopathic disorders characterized by diffuse infiltrates, restrictive functional defect, and disordered gas exchange. The relative frequencies of these disorders are quite different in children compared with adults and, more importantly, there are unique forms seen mainly in infants and very young children that have not been reported in adults (1). It is unfortunate that for many years pediatric lung specialists have tried to fit their childhood cases of interstitial lung disease (ILD) into categories originally described in adults. For example, there are over 100 cases of idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis, the clinical and radiologic terms, and usual interstitial pneumonitis (UIP), the pathologic term, reported in infants and children. Yet, to our knowledge the defining pathologic feature of UIP, heterogeneous fibrosis with the coexistence of fibroblastic foci and dense scarring, has not been described in any pediatric case. This has led some authorities to conclude that UIP probably never occurs in children (2). The tendency to place a number of undefined or poorly defined interstitial processes in children into the category of UIP probably accounts for the better outcome of children given this diagnosis, but it has confused rather than clarified the nature of these disorders. Progress has been made in addressing this problem with the recent descriptions of several specific diffuse lung disorders that appear to be unique to infants and young children. These include infantile cellular interstitial pneumonitis (3), chronic pneumonitis of infancy (4, 5), and persistent tachypnea of infancy associated with neuroendocrine cell hyperplasia (6). In addition, the genetic basis of some forms of ILD, including surfactant protein B and C deficiencies (7, 8), has been identified mainly from the study of infants and children. In this issue of the AJRCCM (pp. 1557–1565), Canakis and colleagues describe a form of neonatal ILD that they term pulmonary interstitial glycogenosis (9). The case histories presented and the pathology illustrated suggest that this is the same entity as infantile cellular interstitial pneumonitis, originally described by Schroeder and colleagues (3). The pathologic examination of these particular cases has been exceedingly thorough. The light microscopic findings and immunostaining characteristics are identical with those seen in infantile cellular interstitial pneumonitis. Indeed, our cases of infantile cellular interstitial pneumonitis (10) are quite similar to those presented here with the characteristic widening of the interstitium by primitive mesenchymal cells containing a paucity of organelles and a generally empty cytoplasm. As the presence of cytoplasmic glycogen in interstitial cells is described as patchy by light microscopy and not well preserved in routine electron microscopic studies, without electron microscopic examination of the quality seen here, it is quite likely to be overlooked. Thus, pulmonary interstitial glycogenosis is probably not a new entity but rather a more complete description of infantile cellular interstitial pneumonitis. The demonstration of glycogen-laden, immature interstitial cells, in the absence of significant inflammation or abnormalities of epithelial or endothelial cells, is consistent with the authors' suggestion that this may be a selective developmental defect of interstitial cells, although there are alternate possibilities. Fortunately, pulmonary interstitial glycogenosis carries a favorable prognosis. Thus, it is critical to distinguish it from other pediatric conditions that are associated with higher morbidity and mortality. Infantile cellular interstitial pneumonitis has sometimes been confused with a more severe and potentially lethal form of ILD, known as chronic pneumonitis of infancy (11). Pathologically, chronic pneumonitis of infancy resembles some of the variant defects of surfactant proteins with prominent alveolar epithelial hyperplasia and interstitial widening with generally only a minor inflammatory component, but with increased numbers of macrophages, small amounts of PAS-positive material present as globules, and occasionally cholesterol clefts within airspaces. We have found that some cases with the histologic picture of chronic pneumonitis of infancy are associated with abnormalities of surfactant protein C, thus making it likely that other cases of chronic pneumonitis of infancy are manifestations of surfactant protein defects that have yet to be identified. Although it remains to be determined if corticosteroids or any therapy is truly effective in any of these conditions, patients with pulmonary interstitial glycogenosis/infantile cellular interstitial pneumonitis can avoid the need for prolonged and potentially toxic treatment reserved for other children with more severe types of ILD. The classification of adult ILD has been refined recently to separate true UIP from other entities, such as nonspecific interstitial pneumonia, cryptogenic organizing pneumonia or idiopathic bronchiolitis obliterans with organizing pneumonia, and desquamative interstitial pneumonia, all of which carry a better prognosis. Likewise in infants and children, the classification of ILD is undergoing changes, which ultimately will more accurately define unique pediatric processes. Only with precise pathologic and clinical descriptions and long-term follow up, such as reported with pulmonary interstitial glycogenosis, can progress be made to uncover the etiologies and mechanisms involved in the wide variety of pediatric ILD. LELAND L. FAN, M.D. CLAIRE LANGSTON, M.D. Texas Children's Hospital and Baylor College of Medicine Houston, Texas REFERENCES
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