An infant with pulmonary interstitial glycogenosis: Clinical improvement is associated with improvement in the pulmonary diffusion capacity

Abstract

Pulmonary interstitial glycogenosis (PIG) is an idiopathic interstitial lung disease of infants. The underlying pulmonary pathophysiology of PIG has not been well characterized. Herein we report a term-gestation infant who presented with persistent tachypnea and hypoxia. A chest CT scan demonstrated a diffuse ground glass appearance and lung biopsy demonstrated increased alveolar septae cellularity with glycogen-containing cells, consistent with a diagnosis of PIG. At 3 months of age, pulmonary function testing included: pre- and post-bronchodilator forced expiratory flows using the raised-volume technique and the ratio of pulmonary diffusing capacity for carbon monoxide to alveolar volume (DLCO /VA ). He was prescribed 5 days of oral prednisolone (2mg/kg/day) and pulmonary function testing (PFT) was repeated at 5, 13, and 20 months of age. Initial PFTs demonstrated reduced forced vital capacity (FVC: Z-score = -2.36) and an increased ratio of forced expiratory volume in 0.5 sec to FVC (FEV0.5/FVC: Z-score = 1.15) with no significant change following an inhaled bronchodilator. There was also a marked reduction in DLCO /VA (Z-score = -4.74) compared to age-matched controls. Follow-up demonstrated progressive clinical improvement as well as an increase in Z-FVC and normalization of DLCO /VA . Our in vivo physiological findings are consistent with previous reports that symptom resolution correlated with histological thinning of the alveolar septae upon repeat lung biopsy. The restrictive lung disease we observed is consistent with expected reduced compliance of an alveolar interstitial lung process like PIG, whereas the absence of a reduction in FEV0.5/FVC confirms the absence of obstructive airway disease.

Persistent Tachypnea of Infancy. Usual and Aberrant

“…Sometimes ground-glass opacities are absent or have a different distribution (3,6,7,21). With regard to biopsy-proven PIG, the few published CT studies have shown mainly ground-glass opacities in a subsegmental, segmental, or diffuse distribution (11,15), very similar to what was found in NEHI (11): interlobar septal thickening or scarring, hyperinflation, air trapping, multifocal atelectasis (7), and multiple air-filled cystic changes of variable size (12).…”

“…Histological examinations show oval, glycogen-rich mesenchymal cells expanding the interstitium. No fibrosis or inflammatory reaction is seen (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Of interest, NECs are also hyperplastic (10).…”

Pulmonary interstitial glycogenosis: Diagnostic evaluation and clinical course

“…6 Outcomes have overall been favorable, but few data on long term follow-up exist, with the longest being 6 years. 2,4,8 …”

Diffuse Lung Disease

“…Pulmonary function testing reveals a restrictive lung disease with marked reduction of pulmonary diffusing capacity. The observations that resolution of PIG on histology and improvement in pulmonary diffusion capacity and forced vital capacity coincide with clinical improvement suggest that PIG impairs respiratory function via alveolar septal thickening (Ehsan et al 2014), although the ultimate clinical outcome primarily depends upon the severity of any underlying lung growth abnormality (King et al 2011), and no mortality is associated with cases of isolated PIG. Corticosteroid therapy may hasten the resolution of PIG, possibly due to acceleration of lung maturation rather than to suppression of inflammation (Deterding 2010;Deutsch and Young 2010;Canakis et al 2002;Onland et al 2005), but should be used judiciously in this self-limited disorder due to the risks of neuro-developmental impairment, immunosuppression, and poor wound healing associated with corticosteroids (Radman et al 2013).…”