Acute Hemorrhagic Edema of Infancy 

Updated: May 18, 2018
Author: Donald Shenenberger, MD, FAAD, FAAFP; Chief Editor: William D James, MD 

Overview

Background

First described in 1913 by Snow,[1] acute hemorrhagic edema of infancy (AHEI) was originally thought to be a purely cutaneous variant of Henoch-Schönlein purpura (HSP). Over the years, many others have described AHEI, including Del Carril, Diaz Sobillo, and Vidal[2] in Argentina in 1936 and Finkelstein in Europe 1938.[3] AHEI has also continued to be known by other names, including Seidlmayer cockade purpura,[4] purpura en cocarde avec oedema, urticarial vasculitis of infancy, and acute benign cutaneous leukocytoclastic vasculitis of infancy.[5]

To date, approximately 300 cases of AHEI have been published in medical literature worldwide.[6] AHEI is now considered a separate entity from HSP because of the infrequency of both visceral involvement and immunoglobulin A (IgA) skin depositions,[7, 5, 8, 9] as well a better prognosis. AHEI is characterized by the triad of fever; edema; and rosette-, annular-, or targetoid-shaped purpura primarily over the face, ears, and extremities in a nontoxic infant or young child (see the image below).[10, 11, 12, 13] The cutaneous findings are dramatic both in appearance and rapidity of onset.

Large cockade (rosette or knot of ribbons), annula Large cockade (rosette or knot of ribbons), annular, or targetoid purpuric lesions found primarily on the face, ears, and extremities are characteristic of acute hemorrhagic edema of infancy.

HSP, in comparison, usually presents with palpable purpura or petechiae associated with one or more symptoms, including abdominal pain, arthritis/arthralgias, and nephritis; however, any of these symptoms may be absent, which often leads to confusion in diagnosing the condition. The diagnosis may be particularly difficult to make when a patient presents with isolated symptoms, such as abdominal pain, without the typical rash. Scalp edema and/or scrotal swelling also may be seen in patients with HSP.

Pathophysiology

The specific etiology of acute hemorrhagic edema of infancy (AHEI) is unknown, although some consider the disease to be an immune complex–mediated vasculitis.[14] Eighty-four percent of reported cases were preceded by viral infections (acute upper respiratory tract infection, gastroenteritis), medication use (ie, antibiotics), and immunizations.[15, 16] In one review of a large referral center in Israel, various infectious conditions were identified in patients with AHEI, including Escherichia coli urinary tract infection, rota virus gastroenteritis, adenovirus upper respiratory tract infection, Streptococcus pyogenes tonsillitis, and herpes simplex gingivostomatitis.[17] In addition, reports have also described an association with Coxsackie virus infection.[18, 19]

Etiology

The cause of acute hemorrhagic edema of infancy (AHEI) is unknown. AHEI is considered to be an immune complex disorder; however, immune complexes have been demonstrated in only some cases.[6, 20]

Epidemiology

Frequency

United States

Acute hemorrhagic edema of infancy (AHEI) is uncommon in the United States. Specific frequency data have not been reported.

International

Acute hemorrhagic edema of infancy (AHEI) has been reported in countries throughout the world, although incidence is unknown.

Race

No racial predilection has been described for acute hemorrhagic edema of infancy (AHEI).

Sex

Acute hemorrhagic edema of infancy (AHEI) is more common among male infants than among female infants[6] ; the male-to-female ratio is approximately 4.6:1.

Age

The age range of onset for acute hemorrhagic edema of infancy (AHEI) is 2-60 months (median, 11 mo; mean, 13.75 mo).[6, 21] However, a congenital case of AHEI has been reported.[22]

Prognosis

Acute hemorrhagic edema of infancy (AHEI) is usually benign, self-limited, and without sequelae, with spontaneous recovery occurring within 1-3 weeks. Rare reports have described complications such as arthritis, nephritis,[23, 24] abdominal pain, gastrointestinal tract bleeding, intussusception,[25] scrotal pain, and testicular torsion.[26] AHEI may recur, but this is uncommon. One case report describes an AHEI patient whose eruption resolved with unusual scarring.[16]   

Patient Education

Educate parents about the benign self-limited nature of acute hemorrhagic edema of infancy (AHEI) and the fact that recurrences, although uncommon, can occur.

 

Presentation

History

Age of onset for acute hemorrhagic edema of infancy (AHEI) usually is 4-24 months but ranges from birth to 60 months. Clinical findings develop rapidly over 24-48 hours. Associated fever is common but tends to be low grade. Upper respiratory tract infection, gastroenteritis, medications (ie, antibiotics), or vaccination have been frequently reported to precede AHEI.[27, 28, 29, 30] Most cases occur in winter months.

Visceral and systemic involvement are uncommon but may include the following:

  • Joint pain

  • Abdominal pain, gastrointestinal tract bleeding, lethal intestinal complications (eg, intussusception)[25]

  • Scrotal pain and testicular torsion[26]

  • Periorbital edema[31]

A report of compartment syndrome has been described.[32]

Spontaneous recovery usually occurs within 1-3 weeks,[18] with a reported duration of up to 35 days. Episodes of AHEI may recur.[9]

Physical Examination

Patients usually are nontoxic in appearance. Characteristic, rosette-, annular-, or targetoid-shaped purpuric lesions are symmetrically distributed primarily on the face, ears, and extremities.[33, 34]

Purpura may involve the scrotum.[26, 35] Lesions may begin as urticarial plaques and enlarge up to 5 cm in diameter. The borders are sharp. Purpura of the umbilicus can be mistaken for the Cullen sign (a sign of possible intraperitoneal hemorrhage).

This toddler with acute hemorrhagic edema of infan This toddler with acute hemorrhagic edema of infancy has a discoloration in the area of the umbilicus similar to that described as Cullen sign.

Mucosal involvement is rare but has been reported.[36]

Acral edema involving the dorsum of the hands and feet frequently extends proximally up the extremities. Edema is usually nontender and may be asymmetric. The scalp may be involved. Joint and abdominal examinations are usually unremarkable.

The left leg in this patient with acute hemorrhagi The left leg in this patient with acute hemorrhagic edema of infancy is markedly more edematous than the right leg.
Note the concentric arcs of purpura on the patient Note the concentric arcs of purpura on the patient's arm.
Despite the frightening appearance of purpura in t Despite the frightening appearance of purpura in these patients, they usually are in no significant distress.

Complications

Rare reports have described complications such as arthritis, nephritis,[23, 24] abdominal pain, gastrointestinal tract bleeding, intussusception,[25] scrotal pain, compartment syndrome,[32] and testicular torsion.[26]

 

DDx

 

Workup

Laboratory Studies

In acute hemorrhagic edema of infancy (AHEI), routine laboratory tests are nondiagnostic, although the following may be performed to exclude other conditions:

  • Urinalysis results usually are normal.

  • Hematologic studies (eg, blood cell counts, clotting studies) are often normal, although leukocytosis and thrombocytosis may be found.[37]

  • Erythrocyte sedimentation rates may be normal or elevated.[16, 37, 38]

  • Serum complement levels are normal.

  • Liver function test results may rarely be elevated.[39]

  • Serologic studies are unremarkable.

Imaging Studies

No imaging studies are necessary in the workup for acute hemorrhagic edema of infancy (AHEI).

Histologic Findings

Acute hemorrhagic edema of infancy (AHEI) is an immune complex-mediated leukocytoclastic vasculitis, usually limited to the small blood vessels of the dermis.[18] The characteristics of leukocytoclastic vasculitis are demonstrated as vascular changes with a perivascular infiltrate consisting primarily of neutrophils; nuclear dust is commonly seen. Vessels show swelling of their endothelial cells and deposits of fibrin within and around their walls, resulting in a “smudgy” appearance termed fibrinoid degeneration. Typically, extensive extravasation of erythrocytes is present.

Direct immunofluorescence studies in patients with AHEI reveal depositions of various immunoreactants, including fibrinogen, immunoglobulin A (IgA), immunoglobulin G, immunoglobulin M, immunoglobulin E, and complement C3 deposition[5] in the wall and around small vessels. Similar deposition of C1q complement also was present in 3 infants in whom C1q complement could be studied (100%). Of the immunoglobulins, IgA deposition is the most common, although this finding occurs in only 10-35% of AHEI cases,[37] thus helping to differentiate AHEI from Henoch-Schönlein purpura.

Note the image below.

Leukocytoclastic vasculitis and fibrinoid necrosis Leukocytoclastic vasculitis and fibrinoid necrosis is seen in patients with acute hemorrhagic edema of infancy. This histologic pattern also is seen in Henoch-Schönlein purpura, although patients with Henoch-Schönlein purpura usually have immunoglobulin A deposition, and immunoglobulin A deposition is demonstrable in only approximately one third of patients with acute hemorrhagic edema of infancy (hematoxylin and eosin, magnification X40).
 

Treatment

Medical Care

No effective therapy exists for acute hemorrhagic edema of infancy (AHEI). The use of steroids and antihistamines has been controversial, and they do not appear to alter the disease course. However, systemic corticosteroids may be used to ameliorate the acute manifestations of the disease.[31] Treatment is symptomatic; discontinue antibiotics after obtaining negative culture results.

Inpatient care is not usually required unless the diagnosis of acute hemorrhagic edema of infancy (AHEI) is in doubt. If meningococcemia or another significant condition remains in the differential diagnosis, patients may require monitoring or therapy as appropriate for those disorders.

Consultations

Consult a dermatologist if the diagnosis of acute hemorrhagic edema of infancy (AHEI) is in doubt. Additionally, consult a gastroenterologist or nephrologist if significant abdominal symptoms or renal involvement is noted.

Diet

Acute hemorrhagic edema of infancy (AHEI) patients usually are nontoxic in appearance. Although visceral involvement is rare, maintain a relatively bland diet with plenty of fluids to maintain hydration.

Activity

No particular restrictions in activity are required for acute hemorrhagic edema of infancy (AHEI).

Prevention

No known method exists for preventing acute hemorrhagic edema of infancy (AHEI) or recurrences of the condition.

Long-Term Monitoring

Treatment for acute hemorrhagic edema of infancy (AHEI) is symptomatic. Monitor patients for abdominal or renal involvement, which, although rare, has been reported.