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Introduction Rubinstein‐Taybi syndrome (RSTS) is a rare genetic syndrome caused primarily by a mutation in the CREBBP gene found on chromosome 16. Patients with RSTS are at greater risk for a variety of medical problems, including upper airway obstruction and aspiration. Childhood interstitial lung disease (ILD) thus far has not been definitively linked to RSTS. Here we present three patients with RSTS who developed ILD and discuss possible mechanisms by which a mutation in CREBBP may be involved in the development of ILD. Methods Routine hematoxylin and eosin staining was performed on lung biopsy tissue for histological analysis. Immunofluorescent staining was performed on lung biopsy tissue for markers of fibrosis, surfactant deficiency and histone acetylation. Cases 1 and 2 had standard clinical microarray analysis. Case 3 had whole exome sequencing. Bioinformatics analyses were performed to identify possible causative genes using ToppGene. Results Computed tomography images in all cases showed consolidated densities overlying ground glass opacities. Lung histopathology revealed accumulation of proteinaceous material within alveolar spaces, evidence of fibrosis, and increased alveolar macrophages. Immunofluorescent staining showed increase in surfactant protein C staining, patchy areas of increased anti‐smooth muscle antibody staining, and increased staining for acetylated histone 2 and histone 3 lysine 9. Discussion Clinical characteristics, radiographic imaging, lung histopathology, and immunofluorescent staining results shared by all cases demonstrated findings consistent with ILD. Immunofluorescent staining suggests two possible mechanisms for the development of ILD: abnormal surfactant metabolism and/or persistent activation of myofibroblasts. These two pathways could be related to dysfunctional CREBBP protein.

Electronic cigarette or vaping product use–associated lung injury (EVALI) is a disease process that has become prevalent in the United States.1 The Centers for Disease Control and Prevention reported there have been almost 2700 cases of this condition in the United States as of January 14, 2020, with >50% of these patients aged ≤24.2 We present a 13-year-old boy with a history of functional abdominal pain who presented with recurrent episodes of nausea, emesis, periodic fevers, and severe episodic abdominal pain after a 12-month history of significant electronic cigarette use. On admission, he had severe abdominal pain and appeared anxious. A computed tomography scan of the abdomen was unremarkable, but a computed tomography scan of the chest demonstrated both multifocal ground-glass and crazy-paving pulmonary opacities bilaterally, with scattered septal thickening and dependent bibasilar opacities associated with volume loss. Inflammatory markers were significantly elevated, and cell counts were remarkable for leukocytosis and neutrophilia. The patient was ultimately diagnosed with EVALI and treated with intravenous methylprednisolone, resulting in improvement. This is an example of a case of EVALI in an adolescent, in which the presenting symptoms are largely gastrointestinal. It is important to keep EVALI in the differential diagnosis of patients who exhibit gastrointestinal symptoms, have markers of increased systemic inflammation, and endorse a history of vaping or are in the age range of electronic cigarette users. Although obtaining an accurate history of vaping can be challenging in the pediatric population, it is especially critical to do so.

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