What Are Treatment Options for EOE?

Patient Presentation

A 9-year-old male came to clinic to establish care. His family had recently moved to the area. Overall he was growing and developing well. His mother was concerned as he had a “sensitive stomach” and seemed to gag and have emesis more easily than she expected. It occurred intermittently usually when he had other illness symptoms but her sister had similar problems as a child and was recently diagnosed with eosinophilic esophagitis. When he was well, he denied any bad taste in mouth, heartburn symptoms, chest pain, abdominal pain and no diarrhea or irregular stools. He ate most foods of all textures and had no irregular eating patterns. He said that sometimes when he was upset or would cry he would throw up. His mother endorsed this and said this was what she had meant by “sensitive stomach.” She also said that he seemed to have a strong gag reflex and gave several examples of this, including that his previous dentist had noted it also. His previous doctor had thought that the emesis was more situational along with a strong gag reflex and was not more concerning. Additional evaluation had not been done.

The past medical history was negative. The family history was positive for the maternal aunt with eosinophilic esophagitis, asthma and allergies. A maternal uncle and mother also had seasonal allergies. The father had gastroesophageal reflux as a child. The review of systems was negative.

The pertinent physical exam showed a healthy appearing male with normal vital signs. Growth parameters were tracking along the 50-75%. HEENT had a sensitive gag reflex but did not provoke emesis. He had some mild dry skin. The rest of his examination was normal.

The diagnosis of a healthy male was made.
The child and parent were counseled about potential ways to avoid triggering the gag reflux. As the child did not seem to have dysphagia, abnormal eating patterns or other gastrointestinal problems the pediatrician noted that eosinophilic esophagitis was a very unlikely cause of the problem. “The eosinophilic esophagitis does occur including in people with more allergy problems and asthma, but he doesn’t have those problems so we can just monitor him for now,” she advised.

Discussion
Eosinophilic esophagitis (EOE) is a clinicopathologic condition of the esophagus where a pediatric or adult patient has clinical symptoms of esophageal dysfunction along with 15 or more eosinophils per high powered field in histological samples. The clinical diagnosis is difficult because many presenting symptoms are consistent with gastroesophageal reflux disease (GERD). Clinical features in children include feeding intolerance or refusal, abdominal pain, emesis or reflux symptoms. Other symptoms include chest pain, diarrhea or failure to thrive. Older children and adolescents may have food impaction or dysphagia similar to adults who report these as their most common symptoms. History may also include strategies to improve symptoms such as “washing the food down” with liquids, avoiding hard food such as meats or cutting the food into smaller pieces, and increasing food mastication to make it softer. Not surprisingly these behavioral changes result in longer meal times.

Endoscopic findings are not specific for EOE. They can include linear furrows, circular rings, stricture, loss of vascular patterns and other findings. Multiple biopsies are needed to make the diagnosis as the eosinophilic infiltration is not uniform. And other diseases can also have esophageal eosinophilia also making the diagnosis more difficult. These include “Crohn’s disease, collagen vascular disease, drug-induced esophagitis, hypereosinophilic syndrome, GERD, and eosinophilic gastroenteritis.” A mild peripheral eosinophilia is more common in children than adults and skin testing for some food allergens is sometimes considered as well.

The pathogenesis appears to be multifactorial and not well understood. “EOE has a strong association with atopy….” Many of these patients have aeroallergen sensitivity and fewer have true food allergy. EOE has an estimated prevalence of about 56-58 cases per 100,000 and is similar for children and adults. High rates are described in Europe and the US and fewer in Asia. There is also data supporting that the diagnosis is increasing since it was first described in 1977. It is more common in males than females.

Learning Point
Treatment for EOE can include PPIs (often used as a first-line treatment), swallowed topical corticosteroids (often using inhaled corticosteroids that are swallowed), and/or food elimination diets. Although true food allergy is less common, treating as if it is a food allergy or sensitivity improves many (but not all) patients’ symptoms. “Multiple studies show that milk tends to be the most common identified trigger in EoE, with wheat, egg, and soy/legumes being other frequent culprits.” In a 2006 study of an empiric 6 food elimination diet in children (milk, soy, egg, wheat, nuts, and seafood) with step-wise reintroduction found that esophageal inflammation was caused by 1 food in 72% of the children, 2 foods in another 8% of children, 3 foods in an additional 8% of children, and 11% tolerated reintroduction of all 6 foods. Newer immunomodulator treatments are also being used for some patients. Oral systemic steroids are also sometimes used but have their own potential side effects.

Longer term, some patients appear to “outgrow” the problem, or the problem is managed without long-term interventions. Some patients do require ongoing treatment along with other management such as esophageal dilation for those patients with significant strictures. Additional other disease (e.g. celiac disease, GERD) or anatomical problems (e.g. tracheoesophageal fistula) may require additional treatment considerations.

Questions for Further Discussion
1. How is GERD diagnosed and treated?
2. What causes abdominal pain?
For recurrent abdominal pain a review can be found here, and
for acute abdominal pain can be found here.
3. What causes failure to thrive?
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 this topic: Eosinophilic Esophagitis

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.

Lehman HK, Lam W. Eosinophilic Esophagitis. Pediatr Clin N Am 66 (2019) 955-965. ClinicalKey. Accessed February 19, 2024. https://www-clinicalkey-com.proxy.lib.uiowa.edu/#!/content/journal/1-s2.0-S088985612100062X

Lehman HK, Lam W. Eosinophilic Esophagitis. Immunol Allegy Clin N Am 41 (2021) 587-598. Accessed February 19, 2024. https://www-clinicalkey-com.proxy.lib.uiowa.edu/#!/content/journal/1-s2.0-S0031395519300835

Hirano K, Furuta GT. Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis . Gastroenterology 158 (2020) 840-851. Accessed February 19, 2024. https://www-clinicalkey-com.proxy.lib.uiowa.edu/#!/content/journal/1-s2.0-S001650851941

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

How Do You Diagnose Cerebral Palsy?

Patient Presentation
A 6-month-old corrected age female came to clinic for her health supervision visit. She had been born 6 weeks premature and was born to a mother with a history of multiple miscarriages and thyroid disease. She was small for gestational age, had some respiratory distress at birth that required oxygen for 24 hours, received antibiotics for prolonged rupture of membranes and had early jaundice that required phototherapy. She had been noted at 2 months of age to have general hypotonia and started receiving physical therapy. Her mother said that she had been improving, but now was becoming more “stiff,” in her extremities. She had just seen the neonatologist as part of their followup program and had been diagnosed with cerebral palsy. Developmentally her mother reported that she was on track for her language, and interpersonal and social skills.

The pertinent physical exam showed a smiling infant with normal vital signs who was 5-10% on her growth curves and tracking. Her physical examination had increased tone in all extremities but her trunk was still somewhat hypotonic. Deep tendon reflexes were also increased.

The diagnosis of a healthy former preterm infant with cerebral palsy who was already receiving services was made. The pediatrician asked if the parent had any questions about the cerebral palsy diagnosis and the mother said that she had thought she had a problem, but the neonatologist had confirmed it. “I’m happy that she is continuing to progress and the physical therapist thinks she will do very well. We’ll just have to see with time. I’m grateful that we started her therapy early,” the mother said.

Discussion
Cerebral palsy (CP) is defined as “…a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain.” It is the most common physical disability in childhood. It occurs in 1:500 live births, with a prevalence as high as 2.1 case/ 1000 persons. Most patients are born full term.

There are 4 CP types:

  • Spastic
    • Occurs in 85-91%
    • May occur in one or more limbs
    • Unilateral (hemiplegia, 38%), bilateral (diplegia, 37% with lower limbs affected more than upper extremities), and quadriplegia (24%)
  • Dyskinetic
    • Occurs in 4-7%
    • All limbs affected
  • Ataxic
    • Occurs in 4-6%
    • All limbs affected
  • Hypotonic
    • Occurs in 2%
    • All limbs affected

Common co-morbities include:

  • Chronic pain (75%)
  • Intellectual disability (49%)
  • Epilepsy (35%)
  • Orthopaedic problems – especially hip dislocations (28%)
  • Behavior problems (26%)
  • Incontinence (~24%)
  • Sleep problems (23%)
  • Sialorrhea (~20%)
  • Blindness, functional (11%)
  • Feed problems (~7%)
  • Hearing impairment (4%)

In many CP cases, the cause is not clearly defined but probably is multifactorial with important risk factors. Most patients have prenatal or perinatal risk factors and only 8% have post-natal risk factors. Risk factors can include:

  • Preconception
    • History of stillbirth, miscarriages
    • Multiple birth
    • Low socioeconomic status
    • Assisted reproduction
  • Pregnancy
    • Birth defects
    • Infection
    • Intrauterine growth retardation
    • Fetus is male gender
    • Maternal specific problems
      • Coagulation disorders
      • Thyroid disease
      • Seizures
      • Substance abuse
    • Multiple gestation
    • Preeclampsia
    • Prematurity
  • Perinatal
    • Acute intrapartum hypoxia-ischemia
    • Hypoglycemia
    • Infection
    • Hydramnios – poly- or oligo-
    • Jaundice
    • Labor issues
      • Breech presentation
      • Cesarean delivery
      • Cord problems – prolapse, nuchal
      • Labor length
      • Prolonged rupture of membranes
      • Meconium-stained amniotic fluid
      • Placental abruption
      • Uterine rupture
    • Placental abnormalities
    • Seizures
    • Size – small or large for gestational age
  • Neonatal period
    • Infection
    • Trauma, accidental and non-accidental
    • Respiratory distress
    • Surgical complications
    • Stroke

Learning Point
CP is a clinical diagnosis. Historically it was made after age 12 months, but can be made before 6 months. The sensitivities presented are from a systemic review for CP evaluation before 6 months.

To diagnose CP there MUST be some type of motor dysfunction – this is determined using standardized motor function evaluation tools including the Prechtl Qualitative Assessment of General Movements (GM, 98% sensitivity), and Hammersmith Infant Neurological Examination (HINE, 90% sensitivity).

There MUST ALSO be evidence of abnormal neuroimaging (magnetic resonance imaging is recommended, 86-89% sensitivity, there are various patterns of abnormalities) OR a clinical history with risk factors for cerebral palsy.

Looking at false-positives or false-negatives, the systemic review notes that “[f]alse positives occur less than 5% of the time with standardized tools.” Most parents are aware that something is wrong before the diagnosis is made, and would like to know earlier rather than later so they can help the patient’s development.

Questions for Further Discussion
1. What do you do in your location to diagnose CP?
2. What types of therapies do you have in your location for patients with CP?
3. What is the yield for genetic testing in children with a neurodevelopmental disability? A review can be found here
4. What is the definition of hypoxic-ischemic encephalopathy? 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 this topic: Cerebral Palsy

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.

Novak I, Morgan C, Adde L, et al. Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy Advances in Diagnosis and Treatment. JAMA Pediatr. 2017;171(9):897-907. doi:10.1001/jamapediatrics.2017.1689

Morgan C, Fahey M, Roy B, Novak I. Diagnosing cerebral palsy in full-term infants. J Paediatr Child Health. 2018;54(10):1159-1164. doi:10.1111/jpc.14177

Michael-Asalu A, Taylor G, Campbell H, Lelea LL, Kirby RS. Cerebral Palsy. Adv Pediatr. 2019;66:189-208. doi:10.1016/j.yapd.2019.04.002

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

What Causes Hemoptysis?

Patient Presentation
A 10-year-old male came to the emergency room with a history of 24 hours of fever, chills, muscle aches, headache, rhinorrhea and cough. The cough was described as wet and would come frequently but had not caused spasms of coughing. He was now having chest pain and had coughed up blood twice in the past hour. The parents described it as soaking his pillowcase with a 5 inch circle of blood. They said it was fresh blood and did have some mucous in it. They described it as like a spot for a nosebleed only larger. The patient said that the fluid had come out of his mouth and not his nose. He also said that since this had happened he had been more nauseated.

The past medical history showed no bruising or bleeding problems, no pulmonary problems and he had otherwise been well. He was current with his immunizations but had not yet received his seasonal influenza vaccine.
The family history was negative.

The pertinent physical exam showed an anxious male sitting up. His heart rate was 94/min, respiratory rate of 32/min and mildly dyspneic, blood pressure 102/60, pulse oximeter of 89-91% on room air. His eyes were glassy. His nose had copious clear rhinorrhea that was also seen in oropharynx. His oropharynx was normal. His lungs had diminished breath sounds at the bilateral bases. There was no wheezing, rales or rubs noted. There was no tracheal tugging but there were some mild intercostal retractions. He said that his sternum hurt with coughing and was reproducible on exam. He had no other areas of chest pain. His heart, abdomen and rest of his examination was normal.

The diagnosis of probable hemoptysis in the setting of an acute respiratory illness was made. He was started on oxygen by face mask with improvement of his oxygenation to low 90s. The radiologic evaluation of a chest radiograph showed prominent interstitial markings at the bases but no obvious focal infiltrate. The laboratory evaluation included a complete blood count which had increased lymphocytes, his C-reactive protein and erythrocyte sedimentation rate were mildly elevated. His bleeding profile and urinalysis were normal. A respiratory viral panel was positive for Influenza A. The patient’s clinical course revealed that he was started on anti-viral medication, continued oxygen and monitored closely. Pulmonary medicine was consulted and had no specific additional recommendations. Critical care medicine was made aware of the patient in case he had a decompensation. Over the next 24 hours he had two more episodes of hemoptysis that were smaller in volume each time. He continued to need oxygen for 3 days and was discharged home on the 4th day.

Discussion
True hemoptysis is a very uncommon or rare problem in pediatrics but can be potentially life-threatening. Massive hemoptysis has a high mortality (up to 50%) mainly from asphyxia and inability to ventilate and oxygenate the patient because of blood in the pulmonary airways. Fortunately, most hemoptysis is small in amount that resolves within 24 hours.

Initial evaluation for hemoptysis can include complete blood count, coagulation studies, C-reactive protein, erythrocyte sedimentation rate, urinalysis (possible pulmonary-renal problems), radiographic imaging including chest x-ray and/or computed tomography, and sputum studies. Treatment depends on the underlying cause and severity. Active significant bleeding and any evidence of cardiopulmonary compromise is treated aggressively. This may include bronchoscopy, ventilatory management and possible surgical treatment. Antibiotics are commonly prescribed as this is a common cause.

Learning Point
Data about the epidemiology of hemoptysis is hard to determine as it is uncommon and the causes are quite diverse. Infection is considered the primary cause but other/unknown cases also are common as a broad category. Anatomic abnormalities can be hard to identify but can cause some of the most severe bleeding and/or complications. Bleeding from other sites may cause the parent to believe the child has hemoptysis when in reality they have epistaxis or have bitten their tongue or cheek.

Causes of hemoptysis include:

  • Infection – most common reason thought to be about ~1/3 of the cases
    • Pneumonia – bacterial, viral, fungal
    • Laryngitis
    • Lung abscess
    • Tracheobronchitis
    • Tuberculosis
  • Bleeding from other sites
    • Nasopharyngeal – trauma especially to oronasal structures
    • Esophagitis
    • Gastrointestinal
    • Granulation tissue
    • Swallowed maternal blood
    • Tracheostomy
  • Bronchiectasis
    • Cystic fibrosis
    • Ciliary dyskinesia
  • Cardiac and vascular anomalies
    • Congenital heart disease
    • Hemangioma
    • Hereditary telangectiasia
    • Pulmonary arteriovenous malformations
    • Pulmonary embolism
    • Pulmonary hypertension
  • Drug Toxicity
  • Factitious hemoptysis
  • Foreign body aspiration
  • Idiopathic pulmonary hemosiderosis
  • Tumor
    • Adenoid
    • Carcinoid
  • Vasculitis
    • Goodpasture syndrome
    • Henoch-Schonlein purpura
    • Microscopic polyangiitis
    • Systemic lupus erythematosus
    • Wegner granulomatosis or granulomatosis with polyangiitis

Questions for Further Discussion
1. What are indication for intubation?
2. How is acute pulmonary hemorrhage treated if it is cardiovascular compromising?
3. What are the advantages and disadvantages of different types of bronchoscopy?
4. What is the role of surfactant in the lung?
5. What are the complications of Influenza?

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: Bleeding, Respiratory Failure and Influenza.

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.

Bannister M. Paediatric haemoptysis and the otorhinolaryngologist: Systematic review. Int J Pediatr Otorhinolaryngol. 2017;92:99-102. doi:10.1016/j.ijporl.2016.10.021

Simon DR, Aronoff SC, Del Vecchio MT. Etiologies of hemoptysis in children: A systematic review of 171 patients. Pediatr Pulmonol. 2017;52(2):255-259. doi:10.1002/ppul.23497

Shnayder R, Needleman JP. Hemoptysis. Pediatr Rev. 2018;39(6):319-321. doi:10.1542/pir.2017-0157

Yang J, Liu F, Liang Y, Guo C, Wang J, Chen X. Massive Hemoptysis in Children. Can Respir J. 2020;2020:6414719. doi:10.1155/2020/6414719

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

What is the Dose-Response for Maternal Vitamin D Supplementation in Lactating Mothers?

Patient Presentation
A 5-day-old female came to clinic for their routine health supervision visit after birth. The baby was a term infant born to a 31 year old G1P1 female without problems during the pregnancy or delivery. The baby was breastfed and was doing well. The infant was not jaundiced and was eliminating well.

The pertinent physical exam showed a 3.148 kg infant (25% overall, down 5% from birthweight), length 50 cm (50%), head circumference 35 cm (50%). There was mild facial jaundice without icterus (transcutaneous bilirubin was 6.9 mg/dL) and the rest of the examination was normal.

The diagnosis of a healthy female was made. The pediatrician discussed anticipatory guidance and recommended the family obtain some Vitamin D to supplement the baby. The mother said that she was Vitamin D deficient and was already taking some supplements. She wanted to know that if she kept taking her own supplement and also gave the baby Vitamin D would that give the baby too much Vitamin D. The pediatrician said that he wasn’t sure, but that the easiest thing to do was to just switch the mother to taking her own supplement of 6400 IU of Vitamin D daily and then that would help the mother and would be the recommended dosage for the baby.

Discussion
Vitamin D is an important vitamin for bone formation and mineral homeostasis. Hypocalcemia, hypophosphatemia, osteomalacia, rickets and tetany can all result because of Vitamin D deficiency. Deficiency is caused by inadequate dietary intakes of Vitamin D, inadequate exposure to sunlight or patients with fat malabsorption or renal disease. Even in high sun exposure areas of the world, Vitamin D deficiency can occur because of inadequate exposure due to clothing or cultural practices. Sunscreen blocks sunlight and an SPF (sun protection factor) of 8 blocks 95% of the sun, so there needs to be a careful balance between over- and under- sun exposure also. Adequate sunlight exposure for infants is considered 30 minutes/week clothed in a diaper only, or 2 hours/week fully clothed but without a hat.

25-hydroxy Vitamin D (25(OH)D or calcidiol) is the best indicator of Vitamin D status. More than 15 ng/mL is considered adequate Vitamin D serum levels. For a review of the production of Vitamin D, click here. For a review of how much Vitamin D is in different foods, click here.

Human breast milk is low in Vitamin D. Therefore all infants who are exclusively breastfed need supplementation. Infants with darker pigmentation or living in northern climates with less sunlight are particularly susceptible to Vitamin D deficiency. This supplementation can be stopped if the infant is taking at least 1 liter or quart/day of formula or Vitamin D fortified whole milk. Children taking less than 1 liter/day of Vitamin D fortified milk should also receive supplementation of 400 IU/day. Note that soy milk may or may not be Vitamin D fortified. Breastfeeding women who wish to take their own supplement are recommended to take at least 6400 IU.

Learning Point
A meta-analysis and systematic review of a “…dose-response analysis on the relation[ship] between circulating 24-hydroxy vitamin D … and maternal [v]itamin D supplementation in mother-infant dyads…”” was conducted in 2022. They found that “maternal [v]itamin D supplement dosages were associated with circulating 24(OH)D concentrations in breastfeeding women in a nonlinear fashion.” In contrast, “A linear relation was observed between maternal [v]itamin D supplementation dosage and the infants’ circulating 25(OH)D concentrations. Each additional 1000 IU of maternal [v]itamin D intake was accompanied by a 2.7 ng/mL increase in serum 25(OH)D concentration in their nursing infants.” They also found that “[l]ong-term maternal supplementation with vitamin D at a high dose (>6000IU/d) effectively corrected vitamin D deficiency in both mothers and infants.” As many mothers are Vitamin D deficient, this appears to be a good treatment for both mother and baby.

Questions for Further Discussion
1. What are the recommendation for supplementing iron to infants and young children?
2. How much calcium is recommended for different ages of the pediatric population?
3. What are the recommendations for supplementing late pre-term infants?

Related Cases

    Disease: Vitamin D Supplementation | Vitamins

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: Vitamin D Deficiency and Vitamin D.

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.

Rios-Leyvraz M, Yao Q. Calcium, zinc, and vitamin D in breast milk: a systematic review and meta-analysis. Int Breastfeed J. 2023;18:27. doi:10.1186/s13006-023-00564-2

Niramitmahapanya S, Kaoiean S, Sangtawesin V, Patanaprapan A, Bordeerat NK, Deerochanawong C. Correlation of 25-Hydroxyvitamin D Levels in Serum vs. Breastmilk in Vitamin D-Supplementation Breastfeeding Women during Lactation: Randomized Double Blinded Control Trial. J Med Assoc Thail Chotmaihet Thangphaet. 2017;100 Suppl 1:S165-171.

Kazemain E, Ansari S, Davoodi SH, et al. The Effect of Maternal Vitamin D Supplementation on Vitamin D Status of Exclusively Breastfeeding Mothers and Their Nursing Infants: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Adv Nutr. 2022;13(2):568-585. doi:10.1093/advances/nmab126

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