What Are Causes of Childhood Interstital Lung Disease?

Patient Presentation
An 8-year-old male came to clinic for a rash on his arms. He had been playing outside the day before in a field and this morning had red, papular lesions on his forearms and lower legs that were pruritic. His mother had used some hydrocortisone but was concerned. “You know he has dermatomyositis but this rash is different than his other ones,” his mother noted.

The past medical history showed he was diagnosed at age 6, with muscle weakness and rash and he was monitored by the rheumatology service. There had also been a concern for possible interstitial lung disease and he was being monitored by the pulmonary service. The review of systems was negative for any other exposures, except he had been wearing sunscreen and insect repellent that he had previously used without a problem. He had no fevers or other signs of infections.

The pertinent physical exam revealed a happy child who was itching. Vital signs were normal but he had a slightly elevated respiratory rate at 32/minute but was not in any respiratory distress. His forearms and legs in exposed areas had a non-specific macular-papular rash that had discrete and confluent areas. HEENT was negative and so was his lung examination.

The diagnosis of a non-specific rash was made. The pediatrician recommended to monitor the patient and use a low-potency hydrocortisone cream and an antihistamine to help with the pruritis. As the family was very compliant with specialty treatment and followup, the pediatrician just briefly reviewed his overall health plan.

Interstitial lung disease in children (chILD) is less understood than adult interstitial lung disease (ILD) and is rare. Prevalence is ~ 0.13 to 16.2 per 100,000 children under age 17 years. chILD is an general term for respiratory disorders that are heterogeneous, chronic and impair lung function. While some define diffuse parenchymal lung disease (DPLD) separately, the term ILD usually encompases DPLD. chILD has variable definitions and is “usually diagnosed if three of the following features are present:

    1) respiratory symptoms (cough, rapid and/or difficult breathing, and exercise intolerance),
    2) respiratory signs (tachypnea, adventitious sounds, retractions, digital clubbing, and failure to thrive or respiratory failure),
    3) hyposemia, and
    4) diffuse abnormalities on chest radiograph or computer tomography (CT) scan.”

Different diagnostic tests can be used including pulmonary function testing, bronchoalveolar lavage, genetic testing and lung biopsy. For radiologic imaging the same is true including plain radiography, ultrasound, and magnetic resonance imaging but CT is considered the standard.

The natural history varies depending on the etiology and some some etiologies hasten mortality. The main concerns are diseases leading to pulmonary fibrosis. The causes are listed below but it appears that progression is likely due to repetitive injuries in vulnerable lung cells. Genetic and epigenetic factors are known to play a part, but also injuries from infection and inflammation can also contribute.

As the etiologies are broad, the treatments may or may not be specific. Generally providing oxygen therapy, nutritional support, prevention of infectious diseases (primarily influenza and COVID), treatment of infectious illnesses, and avoiding particulates and irritants such as tobacco smoke and air pollution are first-line treatments. Steroid medications can decrease inflammation as can macrolide antibiotics. Lung transplantation is also an options for some patients.

Learning Point
Excluded are other more common diseases such as bronchopulmonary dysfunction, cystic fibrosis, recurrent aspiration and infection, before considering these causes of chILD below.

  • Infancy-specific ILD
    • Neuroendocrine cell hyperplasia of infancy
    • Pulmonary interstital glycogenosis
    • Diffuse developmental disorders
    • Acinar dysplasia
    • Congenital alveolar dysplasia
    • Filamin A disorder
  • Environmental exposure
    • Hypersensitivity pneumonitis
      • Bronchiolitis obliterans, post-infectious
      • Bird fancier’s disease
      • Chemical lung disease – paints, fumes
      • Humidifier lung disease – due to aerosolization of various infectious diseases
    • Medication including chemotherapy
    • Radiation
  • Idiopathic
  • Primary lung dysfunction
    • Altered lung development
      • Plmonary dyplasia or hypoplasia
    • Diffuse alveolar hemorrhage
    • Eosinophilic lung disease
    • Lymphatic disorders
    • Surfactant disorders
    • Viral infections
  • Systemic problems
    • Autoinflammatory disease
    • Connective tissue disease
      • Ankylosing spondylitis
      • Dermatomyositis
      • Juvenile idiopathic arthritis
      • Mixed connective tissue disease
      • Systemic lupus erythematosus
      • Sjorgren syndrome
    • Granuloma
      • Sarcoidosis
    • Metabolic
      • Gaucher’s disease
      • Hermansky-Pudlak disease
      • Niemann-Pick disease
  • Neurocutaneous disorders
  • Organ transplantation
  • Vasculitis
    • ANCA-associated vasculitis
    • Anti-glomerular basement membrane diseases
    • Diffuse alveolar hemorrhage
    • Cryoglobulinimia
    • Henoch-Schonlein purpura

    Questions for Further Discussion
    1. How do cystic fibrosis and bronchopulmonary dysplasia present?
    2. How does dermatomyositis present?
    3. What causes respiratory distress? A review can be found here

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Interstitial Lung Disease and Myositis.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Cunningham S, Jaffe A, Young LR. Children’s interstitial and diffuse lung disease. Lancet Child Adolesc Health. 2019;3(8):568-577. doi:10.1016/S2352-4642(19)30117-8

    Deterding RR, DeBoer EM, Cidon MJ, et al. Approaching Clinical Trials in Childhood Interstitial Lung Disease and Pediatric Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019;200(10):1219-1227. doi:10.1164/rccm.201903-0544CI

    Griese M. Chronic interstitial lung disease in children. European Respiratory Review. 2018;27(147). doi:10.1183/16000617.0100-2017

    Nathan N, Berdah L, Delestrain C, Sileo C, Clement A. Interstitial lung diseases in children. La Presse Medicale. 2020;49(2):103909. doi:10.1016/j.lpm.2019.06.007

    Semple TR, Ashworth MT, Owens CM. Interstitial Lung Disease in Children Made Easier…Well, Almost. Radiographics. 2017;37(6):1679-1703. doi:10.1148/rg.2017170006

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa