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

  • What is the Buffalo Treadmill Test?

    Patient Presentation
    A 12-year-old male came to clinic after falling off a sled the day prior. He wasn’t sure how he had landed but says there was no loss of consciousness or specific injuries and he continued sledding but soon became tired. He developed a headache on the way home from the sledding hill which continued to be present. The headache was dull to throbbing and described as annoying to hurting. Tylenol and rest improved his symptoms. He and his mother reported that he seemed “slow” today without a lot of energy. Sounds and lights seemed to annoy him. He denied any nausea/emesis, vertigo, difficulty walking or speaking. He stayed home from school and was resting more but wasn’t specifically sleepy. Trying to do homework or using computers made things worse. The past medical history revealed no specific head injuries and was otherwise non-contributory.

    The pertinent physical exam showed a well appearing male with normal vital signs. His physical examination was normal except for some scratches on his forehead.

    The diagnosis of concussion was made. His SCAT (sports concussion assessment tool) had 9 symptoms that were in the mild to moderate range. Cognitive and physical rest was recommended with some reasonable activities of daily living. He was to increase activity once the symptoms went away and followup the next week.

    The patient’s clinical course the following week showed he was worse with increased severity of symptoms and endorsing some dizziness intermittently. He had tried to do some light activity but his symptoms were exacerbated. The following week he started to feel somewhat better again and the family decided to try letting him go to school but his headache and fatigue returned after about 3 hours. The pediatrician who saw him at the point of 3 weeks after the initial injury decided to send him to her partner who was also trained in sports medicine. She said that that boy had remarkably improved over the ensuing week. “By the time I saw him, most of his symptoms were gone and he had increased his activity. Funny thing was that he told me he kept walking his dog because that was when he felt better. He’s going to go back to school this week and I’ll see him again next week,” she told the pediatrician. The pediatrician and her partner briefly started to discuss his activity, but the partner was called away to see a patient. As she walked away she said, “We can talk more later but do you know about the Buffalo Treadmill Test?”

    Head injury and concussion diagnosis and treatment continues to evolve. The current recommendations are evolving from more strict rest and wait to more limited activity and exercise. Interventions have shown data supporting reasonable exercise as not more harmful and potentially beneficial.

    Learning Point
    The Buffalo Concussion Treadmill Test (BCTT) evaluated 13-18 year old athletes (N=103) using a randomized controlled trial of early subthreshold aerobic exercise for sports-related concussion. The control group performed a stretching program for the same amount of time and were given the same general care instructions. The intervention group performed aerobic exercise on a treadmill or stationary bike wearing a heart rate monitor. Baseline heart rate when symptoms were exacerbated was determined at the initial evaluation. Patients were to perform daily exercise that was 80% of this symptom threshold. Exercise was to be for 20 minutes or to stop if symptoms worsened by 2 points on a visual analog scale. Patients in the intervention group recovered (i.e. were asymptomatic) at a mean of 13 days versus 17 days for controls. Other studies with the same participants showed that males reached symptom exacerbation threshold at a slightly lower heart rate than females but “…the BCTT provides comparable information and both sexes reach symptom exacerbation at similar (changes in heart rate).” They have also found similar outcomes for use of a treadmill versus a stationary bicycle. A stationary bicycle may be helpful for patients with limited mobility.

    While heart rate monitoring and supervised aerobic exercise is not practical for the majority of children with concussions, the current recommendation trend seems to be moving toward more focus on having children continue some activity but to slowly increase the intensity and duration of those activities but keeping them below the amount of activity which exacerbates symptoms.

    Questions for Further Discussion
    1. Describe the Glasgow Coma Scale?
    2. What items are on the SCAT or sports concussion assessment tool?

    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: Concussion and Traumatic Brain Injury.

    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.

    Maerlender A, Rieman W, Lichtenstein J, Condiracci C. Programmed Physical Exertion in Recovery From Sports-Related Concussion: A Randomized Pilot Study. Dev Neuropsychol. 2015;40(5):273-278. doi:10.1080/87565641.2015.1067706

    Grool AM, Aglipay M, Momoli F, et al. Association Between Early Participation in Physical Activity Following Acute Concussion and Persistent Postconcussive Symptoms in Children and Adolescents. JAMA. 2016;316(23):2504-2514. doi:10.1001/jama.2016.17396

    Halstead ME, Walter KD, Moffatt K, Council on Sports Medicine and Fitness. Sport-Related Concussion in Children and Adolescents. Pediatrics. 2018;142(6):e20183074. doi:10.1542/peds.2018-3074.

    Leddy JJ, Haider MN, Ellis MJ, et al. Early Subthreshold Aerobic Exercise for Sport-Related Concussion: A Randomized Clinical Trial. JAMA Pediatr. 2019;173(4):319-325. doi:10.1001/jamapediatrics.2018.4397

    Haider MN, Johnson SL, Mannix R, et al. The Buffalo Concussion Bike Test for Concussion Assessment in Adolescents. Sports Health. 2019;11(6):492-497. doi:10.1177/1941738119870189

    Chizuk HM, Willer BS, Horn EC, Haider MN, Leddy JJ. Sex differences in the Buffalo Concussion Treadmill Test in adolescents with acute sport-related concussion. Journal of Science and Medicine in Sport. 2021;24(9):876-880. doi:10.1016/j.jsams.2021.04.005

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

    How Are Port-Wine Stains Treated?

    Patient Presentation
    A 2-week-old female came to clinic for her health supervision visit. She had been noted to have some congenital dermal melanocytosis lesions over her lower back, and also had a different lesion on her right upper extremity. Neither had been bothering the newborn and she had been breastfeeding well.

    The pertinent physical exam showed an interactive female who was only 3% decreased from her birth weight. Her growth parameters were in the 10-50%. Her physical examination was normal except for some slate-grey, blush macules on her lower spine and hips. She also had a flat lesion approximately 3 cm wide and linear down the back of her right arm that skipped the elbow. It was relatively discrete but somewhat streaky in appearance and was a dark red color. She had no other obvious dermal lesions.

    The diagnosis of a healthy female with congenital dermal melanocytosis and a presumed port-wine stain was made. The infant had already been referred to dermatology for lesion confirmation and potential treatment and her parents were happy with that plan.

    Port-wine stains (PWS) or birthmarks are capillary and post-capillary venule malformations which are usually congenital but can be acquired. In newborns they occur in 0.3-0.5% of births. They are pink to dark-red to purple in color, usually flat and solid across the tissue. They are persistent lesions and can develop to have hypertrophy and nodular characteristics. They can occur in any location but tend to involve the head and neck. Isolated PWS are associated with GNAQ, GNA11 and PiK3CA hot spot genetic mutations. PWS are also associated with some syndromes such as Sturge-Weber, Klippel-Trenaunay, other phakomatosis and some overgrowth syndromes. Patients with lesions that are higher risk or have other stigmata for a potential syndrome will need intradisciplinary evaluation and treatment.

    Over time, many lesions in the limb and trunk distribution are stable or lighten and facial lesions may become darker, and can develop to have hypertrophy and nodular characteristics. Long-term patients can experience cosmetic and functional impairments and also intralesional pyogenic granulomas, and squamous or basal cell carcinomas.

    Learning Point
    Selective photothermolysis is the theory that underlies the treatment of vascular lesions using lasers. Light absorbing targets (chromophores) are heated and damaged with surrounding tissues having minimal injuries. The targets are oxyhemoglobin, deoxyhemoglobin and methemoglobin. Laser treatments carefully choose and weigh the wavelength to try to match the target, the pulse duration to the target vessels, and the fluence or energy emitted which is converted to heat to damage the vessels. Other factors that influence treatment planning and outcomes include cooling strategies, skin thickness (infants are 40-50% thinner than adults), melanin, hair follicles, lesion thickness, lesion location and extent, treatment intervals, and patient age.

    Some PWS are monitored over time. Pulsed dye laser (585-595 nm wavelength) is the gold standard for PWS active treatment since the 1980s. It can be safe and effective. Treatment discomfort is often described as “snapping a rubber band against the skin” which may or may not be tolerated by infants and children. Post-treatment often there is swelling which is treated with ice. Other problems can be irritation or even mild blistering or crusting which is usually managed with bland moisturizers. Sunscreen is always recommended. Other problems after treatment include potential scarring, hyperplasia or depressions, and pigmentary changes. Pulsed dye laser penetrates about 1 mm, but PWS may be 3-5 mm which may be why some can be resistant to pulsed dye laser treatment.

    Questions for Further Discussion
    1. What other common vascular stains or abnormalities can you name? A review can be found here
    2. What other types of physical examination signs of Sturge-Weber or Klippel-Trenaunay syndromes?

    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: Birthmarks and Plastic and Cosmetic Surgery.

    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.

    Zallmann M, Leventer RJ, Mackay MT, Ditchfield M, Bekhor PS, Su JC. Screening for Sturge-Weber syndrome: A state-of-the-art review. Pediatric Dermatology. 2018;35(1):30-42. doi:10.1111/pde.13304

    Tran JM, Kelly KM, Drolet BA, Krakowski AC, Arkin LM. Light-based treatment of pediatric port-wine birthmarks. Pediatric Dermatology. 2021;38(2):351-358. doi:10.1111/pde.14503

    Buch J, Karagaiah P, Raviprakash P, et al. Noninvasive diagnostic techniques of port wine stain. Journal of Cosmetic Dermatology. 2021;20(7):2006-2014. doi:10.1111/jocd.14087

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

    What is Prolonged Grief Disorder?

    Patient Presentation
    A 10-year-old female came to clinic for her health supervision visit. She was doing well in school and her dance and swimming classes. She and her mother said she continued to be very sad about her father’s sudden death from a heart attack 9 months previously. She said that she felt happy at school and with her friends and mother and thought they were helping her, but “I just will suddenly cry and feel so sad. I just can’t stop it.” Her mother said that friend’s, family, school and work had been supporting them and she felt grateful for the support, but she too felt like this often. “Her friend’s mother has been really helpful, but she is worried about her too. Her teacher said at conferences that she thinks the patient is doing okay but notices that she still seems sad.” She and her mother denied any self-harm thoughts. Her mother also stated that she personally was also struggling with her own grief.

    The review of systems showed no weight loss, with good appetite. There was improving sleep but still she had at least 2 nights/week where she would have sleep initiation or interruption issues.

    The pertinent physical exam revealed normal growth parameters and vital signs. Her physical examination was normal. During the examination she talked about many things she liked to do by herself or with friends and hopes that she had for the future.

    The diagnosis of a grief reaction were made. The pediatrician said, “It sounds like you are both trying to figure out what his death means for you and your future. You’ve been doing a pretty good job of surviving and I’d say some thriving too. But it sounds like you both could use some more help with processing his death so you can feel a little better. Many people struggle some and need some extra help. I have some counseling resources. Let’s talk about what might work best for you, and her and your mom too.”

    Grief is the process of experiencing different emotions, expressions and action in response to the death of someone the person cares about. This is a personal and private process. Grief can occur for other significant losses such as a divorce, job, or health. People may overlook loss of routine and special activities, presumed safety, and autonomy that can also cause loss and grief. Additional traumas of these loss types have been magnified especially in the past couple of years as the world lives with Covid. Mourning is a public process of showing grief. This often involves religious beliefs and customs, and cultural customs. Bereavement is the time period of grief and mourning.

    The deceased’s relationship with the survivor, the circumstances around the death or loss, previous experiences with death or loss and the supports the person has or can gather are key factors in shaping how the survivor experiences their grief. Often today people use a framework of a 5 stages approach to understanding the grieving process for adults. People may have components of these at any time and some are shorter or longer but generally people experience these stages including:

    • Denial – that the death or loss has occurred or will occur as this can happen even before the death. People may experience fear, shock, numbness, distress, and may avoid reminders of the deceased.
    • Anger – this can last for days to months and people may experience anger, frustration, loneliness, uncertainty, intense pain, agitation, and preoccupation with thoughts.
    • Bargaining – this tends to be shorter and the person is trying to find meaning in the death or loss. People may want to tell their story and as they do it, they make meaning of the death or loss for themselves.
    • Depression – this can be short or long. People feel sadness, may be overwhelmed or feel helpless as the reality of the death or loss sets in. They may withdraw or be aggressive or hostile and extreme emotions may come intermittently like waves.
    • Acceptance – this usually occurs over a few months to a year or more. The person comes to accept the death or loss. This last phase of grief happens when people find ways to come to terms with and accept the loss, adjusting to their new life without the person or other loss.

    Children may not experience death or loss this same way but they do experience the death. Developmentally children will process the death or loss differently. Parents can help their children by allowing children to express their own emotions verbally, behaviorally, or creatively.
    Providing consistency and being there to meet their needs not only helps the child as they are coming to terms with the new reality, but can also help parents with their own grief and loss.
    Consistency of daily routine, meals, activity and sleep supports the physical and emotional healing for all. As children ask questions about what has occurred and what will happen in the future, adults can provide clear, consistent and supportive answers. Children often ask the same questions over and over and questions about death and loss are no different.
    These reminders can be distressing to a grieving parent and they offer an opportunity to support the child, and as well as parents can be reasonably honest about their own feelings. For example, “Mommy is crying because I am sad that grandma has died, but I am crying because I love her so much too just like I love you. It makes me happy when you talk about her but sometimes I cry.”
    Modeling emotional honesty in a way that is supportive of the child and meets the child’s needs, can also help the parent with their own grief.

    “When griefs are too many, last too long, occur too close on the heels of each other, are too grievous and lacerating in nature and call a halt to too many aspects of our lives, we call this morbid or complicated grief.” People usually need additional support and help to process this type of grief. Grief that is complicated can include other mental health issues such as major depression, separation anxiety, post-traumatic stress disorder, and bereavement disorder.

    Learning Point
    Prolonged grief disorder (PGD) was recently added to the Diagnostic and Statistical Manual of Mental Disorders. This occurs when there are more consistent or extreme reactions to the death or loss over a prolonged period of time. It can be diagnosed after 6 months of symptoms in children and 12 months in adults. From the American Psychological Association, PGD symptoms include:

    • “Identity disruption (e.g., feeling as though part of oneself has died).
    • Marked sense of disbelief about the death.
    • Avoidance of reminders that the person is dead.
    • Intense emotional pain (e.g., anger, bitterness, sorrow) related to the death.
    • Difficulty with reintegration (e.g., problems engaging with friends, pursuing interests, planning for the future).
    • Emotional numbness.
    • Feeling that life is meaningless.
    • Intense loneliness (i.e., feeling alone or detached from others).

    In the case of prolonged grief disorder, the duration of the person’s bereavement exceeds expected social, cultural or religious norms and the symptoms are not better explained by another mental disorder.”

    Cognitive behavioral therapy has been shown to be effective for children and adolescents experiencing PGD due to a parental death.

    Questions for Further Discussion
    1. What are some behavioral expressions of grief?
    2. What mental health resources are available for grief in your community?

    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: Bereavement and Child Mental Health.

    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.

    Melhem NM, Porta G, Walker Payne M, Brent DA. Identifying prolonged grief reactions in children: dimensional and diagnostic approaches. J Am Acad Child Adolesc Psychiatry. 2013;52(6):599-607.e7. doi:10.1016/j.jaac.2013.02.015

    Boelen PA, Lenferink LIM, Spuij M. CBT for Prolonged Grief in Children and Adolescents: A Randomized Clinical Trial. Am J Psychiatry. 2021;178(4):294-304. doi:10.1176/appi.ajp.2020.20050548

    APA Offers Tips for Understanding Prolonged Grief Disorder. Accessed April 5, 2022. https://www.psychiatry.org/newsroom/news-releases/apa-offers-tips-for-understanding-prolonged-grief-disorder

    Fitzgerald DA, Nunn K, Isaacs D. What we have learnt about trauma, loss and grief for children in response to COVID-19. Paediatr Respir Rev. 2021;39:16-21. doi:10.1016/j.prrv.2021.05.009

    Grief and Bereavement. Accessed April 5, 2022. https://www.cancer.org/treatment/end-of-life-care/grief-and-loss/grieving-process.html

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