What is Acute Hemorrhagic Edema of Infancy?

Patient Presentation
A 5-month-old male came to the emergency room with a 2 day history of a fever to 102.1° and a new onset of rash. He was a full-term infant who had been otherwise well with no medication or drug exposure or recent travel. He was not drinking well because of the fever. The family history was negative for any dermatological problems. The pertinent physical exam showed a tired male with normal vital signs. His examination was negative except for 1-3 cm purpura on the legs, buttocks, and cheeks. They were not palpable. His feet, eyes and ears were edematous. He had no mucosal involvement and only some shoddy anterior cervical and groin nodes.

The diagnosis of mild dehydration and possible Henoch-Schonlein purpura was made and the patient was admitted for further evaluation. The work-up was negative with a normal complete blood count, liver function tests, BUN, creatinine, erythrocyte sedimentation rate, C-reactive protein, complement, anti-nuclear antibodies, antistreptolysin O and numerous serologies including herpes virus, adenovirus, Mycoplasma and Rickettsia rickettsii. The patient’s clinical course showed the child developing new lesions over the next day and mildly painful edema. A dermatologist was consulted and made the diagnosis of acute hemorrhagic edema of infancy. The dermatologist didn’t recommend any specific treatment and the patient was sent home with followup after he was afebrile and drinking well. The resident who initially saw the patient also saw his brother in the emergency room later in the month and the mother said that he was well and the lesions were almost faded away.

Discussion
The differential diagnosis for acute hemorrhagic edema of infancy (AHEI) is similar to purpura and includes:

  • Vascultitis
    • Henoch-Schonlein purpura (HSP)
    • Drug induced
    • Kawasaki disease
    • Rocky Mountain Spotted Fever
    • Trauma induced
  • Infectious Disease
    • Meningococcemia
    • Sepsis
  • Dermatologic
    • Erythema multiforme
    • Gianotti Crosti
    • Hemorrhagic urticaria
    • Sweet’s syndrome
  • Child maltreatment
  • Neonatal lupus

Learning Point
Acute hemorrhagic edema of infancy (AHEI, also called Seidlmayer or postinfectious cockade purpura, medallion-like purpura, or Finkelstein’s disease) is an uncommon, self-limited cutaneous leukocytoclastic vasculitis that usually affects children 4-24 months. Despite their appearance, the children generally feel well. It usually presents with fever, and 1-5 cm rosette- or cockade-shaped hemorrhagic purpuric lesions especially of the lower extremities, buttocks, ear, eye and face. Edema, often painful, of these same areas occurs. The skin changes have rapid onset and the coloring may evolve from red/purple to brown/yellow as the blood in the lesions is degraded. The lesions may spread to other body areas such as the upper trunk but this occurs later in the disease course. Mucous membranes are spared and visceral involvement is rare. Laboratory evaluation is basically negative including erythrocyte sedimentation rate, C-reactive protein, urine, stool, ASO titre, antinuclear antibodies, rheumatoid factor and infectious disease’s serologies. Mild leukocytosis with increased neutrophils, lymphocytes or eosinophils has been noted. Generally complements are normal but a few cases have noted transient low complement levels. Skin biopsy shows small dermal vessel vasculitis with all immunoglobulin classes being deposited. Recovery occurs in a few days or weeks, and recurrence is almost unheard of.

AHEI is felt to be an autoimmune phenomena but the actual cause is unknown. It has been associated with prodromes of mild or systemic infectious diseases (i.e. upper respiratory tract infection, otitis media, urinary tract infections, and pneumonia) medications and vaccines. Recently one case report showed positive cytomegalovirus titres.

Steroids and antihistamines have been used with patients but are not effective. AHEI was felt at one time to be a variation of HSP, but they are now considered to be distinct from each other. HSP is the major entity that is confused with AHEI. HSP usually is seen in older children (> 2 years), they usually appear unwell, visceral involvement is common, and the disease course can wax/wane for weeks and recurs 50% of the time. HSP also usually has palpable purpura of the buttocks and lower extremities and usually spares the face. IgA is the predominant immunoglobulin deposited in a skin biopsy. For more information about HSP, see Is it Really Henoch-Schonlein Purpura?

Questions for Further Discussion
1. List the most important history and physical examination findings for distinguishing a purpural rash needing immediate treatment from one that does not.
2. List other hypersensitivity reactions in infants and neonates.

Related Cases

    Disease: Acute Hemorrhagic Edema of Infancy | Vasculitis

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: Vasculitis

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

To view images related to this topic check Google Images.

Carder KR. Hypersensitivity reactions in neonates and infants. Dermatol Ther. 2005 Mar-Apr;18(2):160-75.

Savino F, Lupica MM, Tarasco V, Locatelli E, Viola S, Cordero di Montezemolo L, Coppo P. Acute Hemorrhagic Edema of Infancy: A Troubling Cutaneous Presentation with a Self-Limiting Course. Pediatr Dermatol. 2012 Nov 21. epub ahead of publication.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author

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

  • What is the Physiology of Vomiting?

    Patient Presentation
    A 15-year-old male came to clinic with vomiting and diarrhea for 24 hours. The diarrhea was watery without mucous or blood and was already decreasing. The vomiting had occurred early in the illness and he had not had any for more than 12 hours. He was drinking and urinating well. The pertinent physical exam had normal vital signs and growth percentages were 10-25%. His examination showed moist mucus membranes and brisk capillary refill. His abdominal examination was negative.

    The diagnosis of gastroenteritis was made. The patient and family were educated about signs of dehydration or increasing abdominal pain and fever. Afterwards, the medical student who had seen the patient had remarked about the very vivid description the boy had of his vomiting episodes and asked the attending to explain the physiology of vomiting. The attending said he remembered some general concepts that it was the abdominal musculature that was one of the real propulsive forces, plus the glottis closed off to protect the lungs. The medical student said he would look it up and talk with the attending again the next day.

    Discussion
    Regurgitation is a passive expulsion of ingested material out of the mouth. It is a normal part of digestion for ruminants such as cows and camels. Nausea is an unpleasant abdominal perception that the person may describe as feeling ill to the stomach, or feeling like he/she is going to vomit. Anorexia is frequently observed. Nausea is usually associated with decreased stomach activity and motility in the small intestine. Parasympathetic activity may be increased causing pale skin, sweating, hypersalivation and possible vasovagal syndrome (hypotension and bradycardia). Retching or dry heaves is when there are spasmodic respiratory movements against a closed glottis. This often occurs just before emesis.

    Differential diagnoses of different types of emesis can be found here.

    Learning Point
    Emesis, vomiting or vomition is when stomach (sometimes small intestine also) contents are propelled up the esophagus and out the mouth.
    It is composed of three basic parts:

    • A deep breath is taken, the glottis closed to prevent aspiration into the lungs, while the larynx is raised which helps to open the upper esophageal sphincter. There is a decrease in respiration.
      The soft palate also closes to try to protect the posterior nares. The pylorus also contracts.

    • The diaphragm contracts downward sharply which creates negative thoracic pressures. This also assists the opening of the lower esophageal sphincter and the esophagus itself.
    • As the diaphragm contracts, the abdominal wall muscles vigorously contract which increases the intragastric pressure. As the pylorus is closed, the path of least resistance is through the relatively open esophagus.

    Note the stomach’s fairly passive role in the process.

    The area postrema lying inferior to the 4th ventricle in the medulla is the brain’s vomiting center. Neural structures in this area integrate information from the gastrointestinal tract and other organs (i.e. heart, bile ducts, peritoneum, etc.), other brain areas (i.e. vestibula) and direct chemoreception. This information is integrated and the decision to trigger or not trigger the process of emesis is made. Many antiemetic medications target the chemoreceptive area to help supress triggering the emesis process.

    Questions for Further Discussion
    1. List the complications of emesis?
    2. What elements of the history and physical make the symptom of emesis more concerning for a higher risk etiology?

    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: Nausea and Vomiting.

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

    To view images related to this topic check Google Images.

    Isselbacher KJ. Anorexia, Nausea and Vomiting in Harrison’s Principles of Internal Medicine. McGraw-Hill Book Company. New York, New York. 1987;174-175.

    R. Bowen. Physiology of Vomiting.
    Available from the Internet at http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/vomiting.html (rev. 4/10/96, cited 11/26/12).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    16. Learning of students and other health care professionals is facilitated.

    Author

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

  • Could Renal Abscess Be a Complication of Pyelonephritis in this Patient?

    Patient Presentation
    A 3-year-old female came to clinic with a 2 day history of malodorous urine and increased urinary frequency. She did not complain of pain or itching of her genitalia but her parents noted that she would “hold herself.” She began to have a high fever the night before, but was drinking well. Her parents described her as more tired but she would play more when her fever came down. There was no emesis, diarrhea, abdominal pain or rashes. The past medical history was negative. The family history was negative for kidney disease and hearing problems. The review of systems was otherwise negative. The pertinent physical exam showed a tired appearing female with a temperature of 104.1°, pulse of 120, and respiratory rate of 38, and a blood pressure of 109/69. Mucous membranes were moist and she had 2 second capillary refill. Abdominal examination was negative. Genitourinary examination showed mild erythema of the vulva. The rest of her examination was negative.

    The laboratory evaluation showed a white blood cell count of 16.2 x 1000/mm2 with 50% neutrophils and 7% polymorphonuclear lymphocytes. Her C-reactive protein was 14.3 mg/dl. Her urinalysis showed a specific gravity of 1.010, positive blood, leukocyte esterase and nitrites, 50-100 white blood cells, and 5-10 red blood cells. A urine culture and blood culture were sent. The diagnosis of acute pyelonephritis (i.e. febrile urinary tract infection) was made and as the patient’s temperature had returned to normal after antipyretics, she was taking fluids easily and was playing, she was sent home on oral trimethoprim-sulfa antibiotics with instructions to follow-up the next day in clinic. Parents were also instructed to monitor her closely and if she was not able to drink, take her antibiotics, seemed more listless or the fever could not be controlled then the patient needed to be evaluated right away.

    The patient’s clinical course at 18 hours showed that the blood culture grew Escherichia coli. Her urine culture also eventually grew E. coli. The family was called and the patient brought to the hospital for admission with IV antibiotics. Interval history showed that her fever was controllable, she was drinking and had taken two doses of antibiotics. The patient received 3 days of intravenous ceftriaxone and was discharged after she had been afebrile for 18 hours. After going home her parents called the hospital again because she continued to be febrile at intervals although her temperature maximum was decreasing. During her hospitalization she was noted to have mild hypertension. On day 7 she was seen again the clinic. She had been afebrile since the night prior and continued to act well. Her blood pressure had decreased but was still above the 95% for age. Because of the slow resolution of the fever and continued mild hypertension, the physician decided to recheck her laboratory tests and to order her screening renal ultrasound while still on antibiotics to determine anatomical abnormalities, vesicoureteral reflux and the possibility of renal abscess. The radiologic evaluation of a renal ultrasound was normal. Her C-reactive protein and white blood cell counts were almost normal but her urinalysis still showed 10 white blood cells and 1-2 red blood cells. Over the next month her urinalysis and blood pressure normalized.

    Discussion
    Urinary tract infections (UTI) are common. By the age of 7 years up to 8% of girls and 2% of boys have had a UTI. The current American Academy of Pediatrics criteria for a UTI diagnosis includes presence of pyruria (determined by microscopy) or leucocyte esterase (on dipstick) AND a culture-positive urine of 100,000 colony-forming units on a voided specimen. Because of possible contamination, bagged specimens are not acceptable. Clinical pyelonephritis (ie febrile UTI) is a fairly common problem in the pediatric population.

    Learning Point
    Renal abscesses are uncommon with the exact incidence unknown and are defined as collections of purulent material within or adjacent to the kidney itself. The two most common bacteria are Escherichia coli (assumed to be due to ascending UTI) and Staphylococcus aureus (associated with hematogeneous spread). Patients with renal abscesses may present with clinical pyelonephritis symptoms such as fever, nausea, weight loss, dysuria, malodorous urine, abdominal or flank pain. Renal abscess should be considered when there is prolonged fever without a source and when response to treatment of clinical pyelonephritis is prolonged. Renal ultrasound is a good imaging modality for renal abscess but computed tomography may be needed to differentiate abscess from renal changes associated with pyelonephritis itself.

    Overall 20-90% of children with acute pyelonephritis have some acute renal parenchymal damage with about 40% of these having renal scarring. Renal scarring may lead to hypertension, renal insufficiency and potential failure.

    Complications of acute pyelonephritis includes:

    • Bacteremia and sepsis
    • Vesicoureteral reflux (VUR) – which overall usually resolves
      • Reflux related injury in females is more likely to be acquired and have less severe grades of VUR (i.e. Grades I, II, III)
      • Reflux related injury in males is more likely to be congenital (ie associated with anatomical defects) and have more severe grades of VUR (i.e. Grades III, IV, V)
    • Renal scarring
    • Hypertension – transient or permanent
    • Renal insufficiency or failure
    • Renal abscess
    • Electrolyte abnormalities or secondary pseudohypoaldosteronism

    Questions for Further Discussion
    1. What is the current standard in your country for evaluation of urinary tract infections in children?
    2. What are the advantages and disadvantages of renal ultrasound, voiding cystourethrogram and dimercaptosuccinic acid (DMSA) renal scans in the evaluation of children with urinary tract infections?

    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: Urinary Tract Infections.

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

    To view images related to this topic check Google Images.

    Smith EA. Pyelonephritis, renal scarring, and reflux nephropathy: a pediatric urologist’s perspective. Pediatr Radiol. 2008 Jan;38 Suppl 1:S76-82.

    Koyle MA, Elder JS, Skoog SJ, Mattoo TK, Pohl HG, Reddy PP, Abidari JM, Snodgrass WT. Febrile urinary tract infection, vesicoureteral reflux, and renal scarring: current controversies in approach to evaluation. Pediatr Surg Int. 2011 Apr;27(4):337-46.

    Srinivasan K, Seguias L. Fever and renal mass in a young child. Renal abscess. Pediatr Ann. 2011 Sep;40(9):421-3.

    Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011 Sep;128(3):595-610.

    Tolan RW. Pediatric Pyelonephritis. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/968028-overview (rev. 2/9/2012, cited 11/20/2012).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author

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

  • What Do You Do About Barotrauma to the Ear?

    Patient Presentation
    An 18-year-old male came to clinic 24 hours after sustaining direct barotrauma to his left ear. He had been playing football with friends and was hit by the wide part of the ball right after the ball had been kicked. He was knocked to the ground but could describe in detail that he had no loss of consciousness but had some decrease in acuity, tinnitus and mild imbalance right after impact. At presentation he described no imbalance but still had his “ears plugged up a bit like a cold.” He watched his friends play the rest of the game and drove himself home. He described some pain right after the event that gave way to a headache later that evening. The headache resolved after sleeping and he denied ear pain currently. He did not describe any head injury symptoms at presentation. The review of systems had no otorrhea, rhinorrhea, dental or neck pain. The pertinent physical exam showed normal vital signs. HEENT revealed mild hemorrhage around the long process of the left malleus (ie umbo) but had otherwise normal landmarks, mobility and no fluid or perforation visible. Neurological examination showed normal gross auditory acuity, and normal cerebral and cerebellar function. Skin had no bruising or edema of the ear or head was noted.

    The diagnosis of direct barotrauma to the left ear was made. Otolaryngology was contacted and because there was no obvious physical damage to the outer or middle ear and his symptoms were slowly improving, they recommended to followup with an audiogram in 2 weeks. They also recommended giving the patient head injury instructions and to call immediately if he had any worsening of the acuity problems or a reoccurrence of the vestibular problems. The patient’s clinical course at two weeks showed a normal audiogram.

    Discussion
    Most ear barotrauma discussions are directed toward diving barotrauma where patients may have sudden nausea, headache, ear pain, tinnitus, deafness and vertigo. The tympanic membrane itself is evaluated on the Teed scale:

    • 0 – Normal ear
    • 1 – Congestion around the umbo, (happens with pressure differential of 2 pounds per square inch)
    • 2 – Congestion of entire tympanic membrane (happens with a pressure differential of 2-3 pounds per square inch)
    • 3 – Middle ear hemorrhage
    • 4 – Extensive middle ear hemorrhage with visible blood bubbles behind the tympanic membrane, and tympanic membrane may rupture.
    • 5 – Entire middle ear filled with deoxygenated (dark) blood

    The patient above would be a Teed 1 who had congestion around the umbo and not the entire ear or middle ear hemorrhage. Another type of barotrauma is blast injury which the above patient’s injury was more consistent with.

    Primary blast injury is due to the high-pressure blast wave acting on the body. This has the most effect on air containing organs such as the ear, lung and bowel. Secondary blast injury is due to flying debris from the blast itself. Tertiary blast injury is due to impact with another object such as being thrown by the blast wind. Obviously all 3 types of injuries can occur in a patient and severity depends on many factors especially distance from the blast.

    With blast injuries the most common symptoms are hearing loss, tinnitus (most improve but may be permanent) and otalgia (temporary but may last for weeks) and fortunately most of these improve with time. Vertigo is uncommon. Rupture of the tympanic membrane is the most common middle ear injury and can vary from a mild tear to gross defects. Depending on the blast type, 2-94% of blast patients will have a tympanic membrane rupture. For example, 8% of British service personnel evacuated for blast injuries had tympanic membrane rupture and 48% of the July 2005 London bombing survivors had rupture. Tympanic membrane rupture does not appear to correlate with the most severe lung blast injury.

    Learning Point
    Ear barotrauma treatment depends on the mechanism of injury, severity of the ear injury, and concomitant injuries (particularly head injury). In general, less severe injuries generally resolve with time and/or anti-histamines/inflammatory medication to decrease swelling/congestion in the middle. If tympanic rupture is evident then antibiotic drops and/or steroid drops are indicated, along with monitoring for additional complications such as cholesteatoma. With diving injuries in the Teed 3-5 range, myringotomy may be indicated. Obviously whenever acute trauma occurs such as direct barotrauma, blast injury, etc. then searching for concomitant injuries and treating them is extremely important. Consultation by an otolaryngologist is often needed for more severe injuries. Followup audiograms should also be considered for most patients.

    Questions for Further Discussion
    1. At what noise level (decibels) can there be temporary or permanent hearing loss?
    2. What patient education should wearers of head phones/ ear buds be given?

    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: Ear Disorders

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

    To view images related to this topic check Google Images.

    Kaplan J. Barotrauma in Emergency Medicine. Medscape.
    Available from the Internet at http://emedicine.medscape.com/article/768618-overview (rev. 3/9/11, cited 11/13/12).

    Okpala N. Management of blast ear injuries in mass casualty environments. Mil Med. 2011 Nov;176(11):1306-10.

    Akin FW, Murnane OD. Head injury and blast exposure: vestibular consequences. Otolaryngol Clin North Am. 2011 Apr;44(2):323-34, viii.

    Breeze J, Cooper H, Pearson CR, Henney S, Reid A. Ear injuries sustained by British service personnel subjected to blast trauma. J Laryngol Otol. 2011 Jan;125(1):13-7.

    Radford P, Patel HD, Hamilton N, Collins M, Dryden S. Tympanic membrane rupture in the survivors of the July 7, 2005, London bombings. Otolaryngol Head Neck Surg. 2011 Nov;145(5):806-12.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Systems Based Practice
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Author

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