What Causes Hyperammonemia?

Patient Presentation
An 11-year-old male had a recent viral illness. He was improving but during the night he got up to use the restroom, collapsed and died. He was later diagnosed with Reye’s syndrome. His parents, along with other parents and researchers, worked trying to find a cause and advocated for changes in medical practice. Aspirin in the setting of viral illnesses was determined to be a major risk factor, and with continued advocacy, aspirin and aspirin products had warning labels placed on them in 1986. This happy, young boy is still remembered through educational scholarships for local high school students dedicated to his memory.

Discussion
Reye’s syndrome (RS)is named for Dr. Douglas Reye who along with Drs. G. Morgan and J. Baral described encephalopathy and fatty accumulation and degeneration in children in a 1963 Lancet article. RS usually affects children but can occur at all ages. All organs can be affected but the liver and brain are primarily affected causing liver failure and encephalopathy as toxic metabolites (especially ammonia) accumulate, and intracranial hypertension and cerebral edema occurs. As the ammonia levels begin to rise (> 100 mg/dL) patients lose their appetite, have nausea and emesis and mental status changes which includes personality changes, agitation/combativeness, disorientation and insomnia. As the levels continue to rise (150-200 mg/dL) loss of consciousness and seizures can occur. At levels of 200-400 mg/dL coma and respiratory failure can occur.

RS occurs after a previous viral illness, especially varicella or influenza, usually during the recovery phase. Research in the 1970s and 80s determined that salicylates (aspirin) were a major risk factor for RS although the mechanism is still not understood. Warning labels were added to salicylate products in the US starting in 1986. Aspirin is therefore not recommended for use for most acute childhood illnesses and has been replaced by acetaminophen or ibuprofen. Similar products such as bismuth subsalicylate products also should be used with great care at any time particularly around the time of a viral illness. This change in medical practice has caused the number of RS cases to dramatically decrease.

The differential diagnosis of RS includes viral and bacterial meningoencephalitis, sepsis, diabetes, poisons or drug overdose, liver failure, non-accidental trauma, sudden infant death syndrome or psychiatric problems.

Learning Point
The differential diagnosis of hyperammonemia includes:

  • Increased production
    • Protein load
      • Gastrointestinal hemorrhage or bypass
      • Parenteral nutrition
      • Multiple myeloma
      • Stem cell transplant, allogenic
    • Increased catabolism
      • Corticosteroids
      • Exercise, strenuous
      • Starvation
      • Seizures
    • Genitourinary problems
      • Congenital ureteric obstruction with associated infection
      • Urease-producing organisms (e.g. Proteus, Klebsiella) causing infection
    • Infectious
      • Herpes simplex virus infection
      • Severe systemic neonatal illness
      • Neonatal sepsis
      • Reye syndrome
  • Decreased elimination
    • Liver and biliary tract problems
      • Liver failure, acute or chronic
      • Biliary atresia
      • Porto-systemic shunt (vascular bypass) of the liver
    • Inborn errors of metabolism
      • Urea cycle enzyme defects
        • Ornithine transcarbamoylase (OTC) deficiency
        • Arginase deficiency
        • Argininosuccinate synthase (ASS) deficiency – citrullinemia
        • Argininosuccinate lyase (ASL) deficiency – argininosuccinic aciduria
        • Carbamoylphosphate synthase 1 (CPS 1) deficiency
        • N-Acetylglutamate synthase (NAGS) deficiency
      • Transport defects of urea cycle intermediates
        • Aspartate-glutamate shuttle (citrin) deficiency
        • Lysinuric protein intolerance
        • Mitochondrial ornithine transporter (HHH syndrome)
        • Methylmalonic acidemia
        • Organic acidemias
        • Propionic acidemia
      • Fatty acid oxidation disorders
        • Medium-chain acyl-CoA dehydrogenase deficiency
        • Long-chain fatty acid oxidation defects
        • Systemic primary carnitine deficiency
      • Galactosemia
      • Hyperinsulinism-hyperammonemia syndrome
      • Ornithine aminotransferase deficiency
      • Mitochondrial respirator chain defects
      • Pyruvate carboxylase deficiency
      • Tyrosinemia type 1
    • Medications
      • 5-pentanoic acid
      • Acetaminophen
      • Asparaginase
      • Aspirin
      • Carbamazepine
      • Cyclophosphamide
      • Rifampicin
      • Valproic acid
  • Miscellaneous
    • Transient hyperammonemia of the newborn
    • Sampling error – inappropriate sample or sample not analyzed immediately

    Questions for Further Discussion
    1. How to various inborn errors of metabolism present? For a discussion of inborn error of metabolism presentations click here.
    2. How does liver failure present?

    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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Reye Syndrome

    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.

    Reye RD, Morgan G, Baral J (1963). “Encephalopathy and fatty degeneration of the viscera. A Disease entity in childhood”. Lancet. 2 (7311): 749-52.

    Greeley Daily Tribune. Parents Fighting the Puzzle of Reye’s Syndrome. May 26, 1977, Thu, Page 53. Available from the Internet at https://www.newspapers.com/clip/117982/parents_fighting_the_puzzle_of_reyes/(cited 12/16/16).

    New York Times. Aspirin Labels to Warn About Reye Syndrome. March 8, 1986. Available from the Internet at http://www.nytimes.com/1986/03/08/us/aspirin-labels-to-warn-about-reye-syndrome.html (cited 12/16/16).

    National Institute of Neurological Diseases and Stroke. NINDS Reye’s Syndrome Information Page. Available from the Internet at http://www.ninds.nih.gov/disorders/reyes_syndrome/reyes_syndrome.htm (rev. 9/25/2009, cited 12/16/16).

    Singh P, Goraya JS, Gupta K, Saggar K, Ahluwalia A. Magnetic resonance imaging findings in Reye syndrome: case report and review of the literature. J Child Neurol. 2011 Aug;26(8):1009-14.

    Paprocka J, Jamroz E. Hyperammonemia in children: on the crossroad of different disorders. Neurologist. 2012 Sep;18(5):261-5.

    Ahrens-Nicklas RC, Edmondson AC, Ficicioglu C. An 8-year-old girl with abdominal pain and mental status changes. Pediatr Emerg Care. 2015 Jun;31(6):459-62.

    El-Hattab AW. Inborn errors of metabolism. Clin Perinatol. 2015 Jun;42(2):413-39, x.


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

  • At What Radon Level Should Mitigation Be Considered?

    Patient Presentation
    A 2-year-old female came to clinic for her health supervision visit. The family had just moved into an old home. During the interview the mother noted that they had had the home checked for lead and for radon. “The radon test said it was normal,” she said. The pertinent physical exam was normal and the diagnosis of a healthy female was made. When discussing the toddler with the resident, the attending said that he didn’t know what was the normal value range for radon. “We don’t do regular screening for radon like we do for lead, so I just don’t know what normal is,” he stated. Later the attending found the numbers and also found more specific information about radon mitigation in his area to have for future encounters.

    Discussion
    Radon is a naturally occurring, radioactive gas that is colorless, odorless and tasteless. It is produced from the normal radioactive decay of uranium into radium and then into 222R-Radon. Radon gas escapes from soils and rocks into the air and generally concentrates in enclosed spaces such as buildings, mines and caves. The general ionizing radiation dose received by the general public is caused by radon in large part. In homes and other buildings, soil gas is the most important source of residential radon, but other sources which are less important includes building materials and well water sources.

    Indoor radon is the second leading cause of lung cancer after smoking in the US and a major cause of lung cancer deaths worldwide (3-14%). While children could be at higher risk for cancer because of radon exposure, there currently is not conclusive data that supports this. There also is no current strong evidence that radon causes cancers other than lung cancer.

    Radon testing is easy and inexpensive to perform. Depending on the building size, location, construction, materials and radon results, more than 1 testing may be needed to determine the overall risk. Repeated radon testing can also be considered if there is increased exposure such as living in a basement apartment. If more than 5% of current buildings in an have elevated radon, new housing and building construction should have preventive radon measures included as they are considered cost effective. Radon mitigation systems can be built into the new construction. For existing dwellings with elevated radion, specific mitigation techniques vary depending on the building construction and materials. Soil suction techniques gather radon from below or at the foundation and vent it away from the structure. There are numerous ventilation techniques that actively or passively increase the ventilation in particular areas or throughout the building to decrease, and hopefully eliminate, the radon concentration. Sealing cracks in foundations/walls is not considered an adequate mitigation technique by itself but can be used as one part of an overall mitigation plan.

    Learning Point
    Radon concentrates in locations close to the soil and in places with less ventilation. One study of primary schools in Serbia illustrates these points. Radon levels were higher in schools with only one floor, smaller buildings and located geographically in locations known to have higher naturally occurring radon levels. The higher up in the building there was a decrease in the radon levels. The authors point out that an “average” exposure for students really is not possible, as many other factors contribute to the risk including how the school rooms are used, and when are they used (e.g. higher levels on weekends and holidays when building is shut up more, or cold vs. warm seasons)

    The United States Environment Protection Agency provides a map of the general radon risk by county. The average level of radon in a US home is 1.3 pCi/L (picoCuries per liter), and about 0.4 pCi/L of radon is normally found in the outside air. Radon mitigation should be considered if the long term levels are 4.0 pCi/L or more. It would be best if there was no radon risk but that is not generally achieveable considering radon’s ubiquitous nature within the world.

    Questions for Further Discussion
    1. What is the risk of radon in your local area?
    2. What other environmental risks are in your local area?

    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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Radon and Indoor Air Pollution.

    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.

    United States Environmental Protection Agency. Radon. Available from the Internet at https://www.epa.gov/radon (cited 12/13/16).

    United States Environmental Protection Agency. Consumers Guide to Radon Reduction. Available from the Internet at https://www.epa.gov/sites/production/files/2016-02/documents/2013_consumers_guide_to_radon_reduction.pdf (rev. 2013, cited 12/13/16).

    World Health Organization. WHO Handbook on Indoor Radon. Available from the Internet at http://www.who.int/ionizing_radiation/env/9789241547673/en/ (cited 12/13/16).

    World Health Organization. Radon. Available from the Internet at http://www.who.int/ionizing_radiation/env/radon/en/ (rev. 2009, cited 12/13/16).

    Bochicchio F, ZuniC ZS, Carpentieri C, et.al. Radon in indoor air of primary schools: a systematic survey to evaluate factors affecting radon concentration levels and their variability. Indoor Air. 2014 Jun;24(3):315-26.

    Del Risco Kollerud R, Blaasaas KG, Claussen B. Risk of leukaemia or cancer in the central nervous system among children living in an area with high indoor radon concentrations: results from a cohort study in Norway. Br J Cancer. 2014 Sep 23;111(7):1413-20.

    Peckham EC, Scheurer ME, Danysh HE, Lubega J, Langlois PH, Lupo PJ. Residential Radon Exposure and Incidence of Childhood Lymphoma in Texas, 1995-2011. Int J Environ Res Public Health. 2015 Sep 25;12(10):12110-26.

    Madureira J, Paciencia I, Rufo J, Moreira A, de Oliveira Fernandes E, Pereira A. Radon in indoor air of primary schools: determinant factors, their variability and effective dose. Environ Geochem Health. 2016 Apr;38(2):523-33.

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

    What Can Families Do for Fire Safety?

    Patient Presentation
    A 7-year-old male came to clinic for his health maintenance examination. His mother had no concerns and the pertinent physical examination was normal. The diagnosis of a healthy male was made. While discussing some safety anticipatory guidance, the boy became very excited to talk about how his mother had used the fire extinguisher several days before to stop a kitchen grease fire. “You should have seen all the powder all over the place, it was a real mess” he almost shouted. “It got all over my school stuff and they were ruined but they didn’t catch fire,” he added. While retelling the story the mother was quite embarrassed, but the physician noted how she was prepared and used the fire extinguisher. She asked if the smoke detectors also went off. “Oh yeah,” the boys shrieked, “but mom yelled for my brother and I to go outside and we did. Afterwards we got to see the real mess.” The pediatrician praised the boy for following his mother’s instructions. “We didn’t have a real safety plan,” said the mother, “but we do now and we are going to practice it too.”

    Discussion
    Home fire safety is important. Prevention safeguards life and property.

    In 2014, the U.S. Fire Administration reported there were 3,428 deaths caused by fires. The most common pediatric age group is 0-4 years, with decreasing risk with advancing age. In the adult age group, the rates hold steady until the 40-50’s when there starts to be an increasing risk in the older population again. Other groups at risk are those with disabilities, and people living in rural areas. Intentional fires or arson are highest obviously in urban environments.

    The leading cause of fire deaths in the US is because of smoking. Other risk factors include lack of a working smoke alarm, use of a space heater and renting (versus owning) the home. Having a working smoke alarms in the home dramatically decreases fire injuries and property loss. In the US there is a 2-3x lower risk of fire death with a working smoke alarm. Having a smoker as noted also dramatically increases the risk, but this can be mitigated by consistent safety practices including only smoking outside the home.

    Home fires can occur year round, but are more common in the winter months of December, January and February because of associated heating needs. Use of fireplaces and space heaters increases the risk of home fires. Home fires associated with religious and cultural celebrations also peak at these times with home candle fires peaking on Christmas, New Years Eve and New Years Day. Seasonal fire-related injuries are seen globally with the timing based on location and specific practices. Cooking is obviously associated with various methods for heating food and therefore fires. Stoves, ovens, microwave ovens, barbeques and grills, and fryers are just some of the potential fire hazards within the home. Electrical fires from improperly connected home products are also potential fire sources. Appliances washers, fryers, portable generators, portable fireplaces and portable space heaters are all potential fire risks. Gasoline and propane are hazardous fuels that must be stored and handled properly. Use of medical oxygen has increased over time and is another potential fire hazard in homes. Clutter around potential fire sources also increases the risk of fire starting and/or spreading.

    Learning Point
    Basic recommendations to help prevent fires in the home include:

    • Smoke alarms
      • Should be on every level of the home
      • Tested and cleaned monthly
      • Batteries changed yearly and as needed
      • Should be < 10 years old
    • Fire extinguishers
      • Should be easily available throughout the home including each floor and garage
      • Extinguishers types are:
        • A extinguishers are for combustibles such as trash, wood
        • B are for liquids/grease
        • C are for electrical fires
      • Extinguishers should be used by PASS
        • Pull the extinguisher pin
        • Aim the nozzle at the base of the fire
        • Squeeze the handles together
        • Sweep the extinguisher contents at the base of the fire
    • Carbon monoxide alarm
      • Should be one on every level of the home
      • Tested and cleaned monthly
      • Should be < 7 years old
    • Fire safety plan
      • Have a fire safety plan and practice it regularly
      • Have 2 ways to get out of every room
      • Crawl low when escaping to avoid smoke
      • Know where to meet – near front of house is usually best
      • Once out of house, stay out of house
    • Cooking
      • All cooking areas/surfaces should be kept free of flammable materials
      • Hoods are cleaned regularly and vented to the outside
      • Pots are not left unattended on stove
      • Fryers are plugged directly into electrical outlet on a non-flammable surface
      • Food should be removed promptly when cooked.
      • Microwave ovens should only have approved containers used for heating food
    • Smoking in the home
      • Try to help smokers to quit smoking
      • Smoke outside and use fire-safe cigarettes
      • Ashtrays should be large and deep. They should be emptied into fire-proof containers or the containers used directly
    • Heating
      • Furnaces and chimneys should be cleaned regularly and inspected at least yearly
      • All combustible materials are > 3 feet from the heat source
      • Fireplaces should be used under direct supervision and extinguished completely before leaving room or going to bed
      • Do not use extension cords with space heaters – they should be directly plugged into the electrical outlet
      • Any space heater should be laboratory approved and have a tip-over, shut-off mechanism
      • Fireplace and barbeque ashes should be placed into metal containers
    • Electric
      • All appliances are plugged directly into the electrical outlet
      • No frayed or cracked cords
      • No cords under rugs/blankets etc.
      • If needed, multipronged adapters are used for additional electric outlets
      • Dryer lint filters and venting systems are cleaned regularly and as needed
    • Candles, Seasonal, and Recreation
      • Candles or any other open flames should be kept in a fire proof container under direct supervision. They should be extinguished completely before leaving room or going to bed.
      • Electrical lights or decorations should be used as directed by the manufacturer. They should be inspected before use and monitored. They should be turned off before leaving the house or for bed.
      • Use of electric tools, hot glue guns, soldering irons and other home maintenace or recreational products are also potential fire sources. They should be used according to manufacturers instructions, unplugged and stored between uses.

    Questions for Further Discussion
    1. What summer safety tips do you suggest to families? For suggestions click here
    2. What winter safety tips do you suggest to families? For suggestions click 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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Fire Safety

    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.

    Al-Qattan MM, Al-Zahrani K. A review of burns related to traditions, social habits, religious activities, festivals and traditional medical practices. Burns. 2009 Jun;35(4):476-81.

    Lehna C, Fahey E, Janes EG, Rengers S, Williams J, Scrivener D, Myers J. Home fire safety education for parents of newborns. Burns. 2015 Sep;41(6):1199-204.

    Rohrer-Mirtschink S, Forster N, Giovanoli P, Guggenheim M. Major burn injuries associated with Christmas celebrations: a 41-year experience from Switzerland. Ann Burns Fire Disasters. 2015 Mar 31;28(1):71-5.

    Wood RL, Teach SJ, Rucker A, Lall A, Chamberlain JM, Ryan LM. Home Fire Safety Practices and Smoke Detector Program Awareness in an Urban Pediatric Emergency Department Population. Pediatr Emerg Care. 2016 Nov;32(11):763-767.

    National Fire Protection Association. Public Education. Available from the Internet at http://www.nfpa.org/public-education (cited 12/6/16).

    United State Fire Administration. Fire Statistics. Available from the Internet at https://www.usfa.fema.gov/data/statistics/ (cited 12/6/16).

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

    What is Black Spot Poison Ivy?

    Patient Presentation
    A 16-year-old female came to clinic with linear black streaks on her arms that began the day before. She had been in the woods and fields in the morning and in the afternoon noticed the black streaks. During the night she awoke because of intense itching and noticed that she now also had reddened skin with vesicles in the area around the black streaks. She denied direct exposure to any poison ivy, poison oak, etc., and said that after being in the woods she had washed her clothing and showered. She had had poison ivy in the past and thought this looked similar but it had never been black before. The pertinent physical exam showed a healthy female with normal growth parameters and vital signs. Both volar forearms and right dorsal forearm had linear black lines that were 1-3 cm in length and ~2-3 mm wide. There were 2-3 black lines in each location. Surrounding the areas were linear reddened skin with some shiny vesicles and scratch marks. The rest of her examination was negative.

    The diagnosis of of black spot poison ivy was made. “This doesn’t happen very much, but you got a pretty good exposure to some poison ivy and this is why it is black. We treat it the same though. I recommend that you use some antihistamines and I’ll prescribe a steroid cream. I know you said you washed all the clothing but make sure that you wash anything else you might have contacted like garden gloves, backpack etc. because the resin can stay on those too for a long time,” the physician said.

    Discussion
    Poison ivy (PI, Toxicodendron radicans) is a common plant in North America that causes allergic contact dermatitis. Poison oak and sumac also cause similar problems. The rash usually appears as linear erythematous papules or vesicles occurring soon after exposure.

    Patients often do not identify the exposure specifically but will say they were walking/playing in gardens, fields or woods. PI can be a small plant, vine or even a shrub. The coloring changes over the growing season. Fires may also be a source as burning the plants and being in the smoke can cause extensive lesions on the body. The plant has 3 leaves and never more. The leaf stems alternate along the growing plant and are not found directly across from each other. The leaves have smooth edges and are not saw-toothed, serrated or scalloped. There also are no thorns. Several identification guides can be found here.

    PI has an oleoresin called urushiol which causes the main problem but it also contains allergens (pentadecylcatechols). The urushiol does not evaporate well and therefore stays on clothing, sports equipment etc.. for longer time periods. The allergens can contaminate clothing for years. These properties account for exposure at unexpected times of the year (i.e. in the winter children using a contaminated sleeping bag for an overnight party and getting the PI rash), or in unexpected places (e.g. PI rash presenting in the United Kingdom which has no PI after travel to the United States).

    Treatment is by antihistamines and topical or oral steroids, along with appropriate skin hygiene. Oral steroids for extensive lesions usually need to be tapered over a long time to prevent rebound symptoms. Prevention is by avoiding exposure. Use of protective clothing including areas between garments such as socks over pant legs, long-cuffed gloves that cover sleeves, and hoods or handkerchiefs to protect the neck can decrease exposure. As soon as possible, the person and all clothing and equipment should washed thoroughly to prevent the rash and further contamination of other clothing/equipment. Washing with soap and not just plain water increases prevention efficacy. Fresh jewelweed plant mash (Impatiens capensis) has been shown to decrease PI rash after exposure but not its extract or that which is added to soap. Although the author does not have scientific evidence to support the practice, the author personally recommends rubbing soap on potentially exposed areas such as wrists, ankles, neck etc.. before potential exposure and then showering immediately after exposure. In her experience, it is a low-cost, reasonably effective preventative measure.

    PI plant is part of a larger family called Anacardiacaea which is a flowering, sap producing family. Mangos, cashews and pistachios are examples of this family. Other species are used for tanning and lacquers. There is global experience where first exposure to urushiol orally appears to induce tolerance to the resin and people do not react to it when it is encountered dermally; that is, they have an induced oral tolerance for the resin. People who eat mangos from an early age, children who eat chicken off of lacquerware that contains the resin (i.e. “lacquer chicken” in Korea) or Native American orally ingesting the plant are all examples of groups of people who seem to have tolerance after dermal exposure to the resin.

    Learning Point
    Black spot PI is an atypical variation where the initial lesions are spots or linear black streaks that are followed by the more classic presentation several hours later. The black coloring is because of high concentrations of the urushiol which oxidizes in a warm, humid environment. The black lesions cannot be washed off but they will peel away with time and do not scar. It is treated the same as regular PI.

    Questions for Further Discussion
    1. What PI or similar plants are in your location?
    2. What skin hygiene measures do you recommend for PI?

    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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Poison Ivy, Oak and Sumac

    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.

    Poison Ivy. Available from the Internet at http://www.poison-ivy.org. (cited 11/29/16).

    Anacardiacaea. Wikipedia. Available from the Internet at https://en.wikipedia.org/wiki/Anacardiaceae. (cited 11/29/16).

    Abrams Motz V, Bowers CP, Mull Young L, Kinder DH. The effectiveness of jewelweed, Impatiens capensis, the related cultivar I. balsamina and the component, lawsone in preventing post poison ivy exposure contact dermatitis. J Ethnopharmacol. 2012 Aug 30;143(1):314-8.

    Pittman MA, Lane DR. Black spot poison ivy: under the cover of darkness. J Emerg Med. 2013 Apr;44(4):e331-2.

    Colbeck C, Clayton TH, Goenka A. Poison ivy dermatitis. Arch Dis Child. 2013 Dec;98(12):1022.

    Sinha K, Elpern DJ. A baleful weed and the king of fruits: tolerance, immunity, and the microbiome. Int J Dermatol. 2016 Jan;55(1):121-2.

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