A 9-Month-Old With a Purpuric Rash and Peripheral Edema

A 9-month-old, full-term, previously healthy boy presented to the emergency department with acute onset of a purpuric rash and peripheral edema. Two weeks prior to presentation, he had been evaluated by his pediatrician for fever, had received a diagnosis of otitis media, and had been treated with azithromycin. On the day of presentation, the infant had developed papular lesions on his cheeks that had progressed rapidly into purpuric lesions; additionally, he had developed acute-onset swelling of his hands and feet. The parents denied recent medications other than diphenhydramine and the prescribed antibiotic. There was no history of insect bites or stings or other exposures.

The patient appeared very well on physical examination. His vital signs were significant for a temperature of 38.8°C. He had significant edema of the bilateral hands to the level of the wrist and of the bilateral lower extremities to the level of the knees (Figure 1). He demonstrated tenderness of his hands and feet with manipulation. Purpuric macular lesions were visualized on the bilateral cheeks, the pinnae (Figure 2), the arms and legs, the hands and feet (including the palms and soles), the scrotum, and the buttocks. The trunk was spared. Some of the lesions appeared targetoid. He had a 1-cm erythematous area on the hard palate, along with anterior cervical lymphadenopathy of less than 1 cm.

 
What is causing this infant’s widespread rash?

A. Erythema multiforme
B. Acute hemorrhagic edema of infancy
C. Henoch-Schönlein purpura
D. Drug-induced rash

(Answer and discussion on next page)

Answer: B, acute hemorrhagic edema of infancy

Results of laboratory studies were significant for an elevated white blood cell count of 14,300/µL, an elevated platelet count of 858 × 10³/µL, mild hyponatremia (131 mEq/L), and an elevated C-reactive protein (CRP) level (8.45 mg/dL). Liver function test results were within normal limits. Urinalysis results were negative for protein and red blood cells. Respiratory viral and bacterial polymerase chain reaction test results were unrevealing. Urine and blood cultures showed no growth.

The differential diagnosis included erythema multiforme, drug reaction, meningococcemia, and Henoch-Schönlein purpura (HSP). Initially, HSP was considered the most likely etiology, but the lack of gastrointestinal (GI) or renal involvement was inconsistent with this diagnosis. Because the patient was so well appearing, meningococcemia was considered unlikely.

The eventual discharge diagnosis was acute hemorrhagic edema of infancy (AHEI), a rare and benign form of leukocytoclastic vasculitis.^1,2 AHEI typically is seen in infants aged 6 to 24 months with a recent history of a respiratory illness.

Patients are nontoxic and rapidly develop the characteristic purpuric lesions over 24 to 48 hours. The lesions are red to purple plaques that may be targetoid in appearance. The distribution is over the cheeks, ears, and extremities, with sparing of the trunk. Vesicles or bullae may be present in up to 10% of cases,¹ a presentation seen in our patient as his lesions resolved.

AHEI had been considered a variant of HSP but now is recognized as a distinct entity because of the lack of GI involvement.³ Laboratory findings may include mild leukocytosis, thrombocytosis, elevated CRP, elevated erythrocyte sedimentation rate, slightly elevated liver enzymes, and normal urinalysis results. Biopsy findings will be consistent with leukocytoclastic vasculitis of the dermal vessels with fibrinoid necrosis.¹

The etiology of AHEI is unknown but may be related to infection, medications, or immunizations. Typically, lesions resolve completely within 60 days, although they resolve within 21 days in 80% of cases.¹ The illness is self-limiting and is not affected by systemic corticosteroids or antihistamines. 

Jessica Anderson, MD, is at University of North Carolina–Chapel Hill Family Medicine in Chapel Hill, North Carolina.

Peyton Wilson, MD, is at North Carolina Children’s Hospital in Chapel Hill, North Carolina.

Stephen Leinenweber, MD, is executive medical director of Children’s Services for WakeMed Physician Practices at WakeMed Children’s Hospital in Raleigh, North Carolina.

Karen Chilton, MD, is a pediatric hospitalist at WakeMed Children’s Hospital in Raleigh, North Carolina.

Jacob Lohr, MD, is chief pediatrician at North Carolina Children’s Hospital in Chapel Hill, North Carolina.

References

1. Fiore E, Rizzi M, Simonetti GD, Garzoni L, Bianchetti MG, Bettinelli A. Acute hemorrhagic edema of young children: a concise narrative review. Eur J Pediatr. 2011;170(12):1507-1511.
2. Oliveira JA, Lopes L, Fraga A, Soares-de-Almeida L, Águas B, Siborro-Azevedo A. Acute hemorrhagic edema of infancy: a rare cause of purpuric exanthema. J Pediatr. 2015;166(2):498-498.e1.
3. Fotis L, Nikorelou S, Lariou M-S, Delis D, Stamoyannou L. Acute hemorrhagic edema of infancy: a frightening but benign disease. Clin Pediatr (Phila). 2012;51(4):391-393.