eMedicine Specialties > Dermatology > Pediatric Diseases

Acute Hemorrhagic Edema of Infancy

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine

Updated: Sep 25, 2009

Introduction

Background

Snow¹ first described acute hemorrhagic edema of infancy (AHEI) in the United States in 1913. Del Carril, Diaz Sobillo, and Vidal² described the condition in Argentina in 1936. Europeans have recognized Finkelstein's description of this disease since his publication in 1938,³ and, until recently, most reports of this disorder occurred in the European literature under the terms Finkelstein disease, Seidlmayer syndrome,⁴ or purpura en cocarde avec oedema.

AHEI is a distinctive, cutaneous, small vessel leukocytoclastic vasculitis of young children with dramatic characteristic skin findings.^5,6,7,8 The cutaneous findings are dramatic both in appearance and rapidity of onset. The 2 primary features include large cockade (rosette or knot of ribbons), annular, or targetoid purpuric lesions found primarily on the face, ears, and extremities, and edema of the limbs and face (see Media File 1 ).

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.

The typical patient with AHEI is aged 4-24 months with a history of recent upper respiratory tract illness and/or course of antibiotics.⁹ Associated fever is common but tends to be low grade, and despite the impressive clinical presentation, patients usually are nontoxic in appearance. Visceral involvement is uncommon, and spontaneous recovery usually occurs within 1-3 weeks, without sequelae. Recurrent episodes may occur.

Many physicians believe AHEI is a mild variant of Henoch-Schönlein purpura (HSP); others believe it to be a unique disorder.^10,11,12 Gattorno et al¹³ reported a brother and sister aged 3.6 years and 16 months, respectively. Both had pharyngitis treated with amoxicillin for 10 days, which occurred 20 days before admission. The 3.6-year-old girl developed a purpuric rash on her legs and abdominal pain, and HSP was diagnosed.

Subsequently, 3 days later, her brother developed a widespread rash consistent with the diagnosis of AHEI. Neither joint effusions nor abdominal symptoms were present. Cases also exist of children aged 2-4 years who appear to have symptoms with overlap between AHEI and HSP.

Regardless, AHEI may have a clinical presentation distinct from HSP seen in older children. The condition has a much better prognosis in these children.

HSP usually presents with palpable purpura or petechiae associated with 1 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.

Target lesions in AHEI usually are limited to limbs and the face, and progressive extremity edema occurs in AHEI that does not occur in patients with erythema multiforme.

The petechiae and purpura also may resemble lesions of HSP and meningococcemia, although patients often appear much sicker with high fever, malaise, and possible shock in severe cases of meningococcemia. Most patients improve with no residual skin lesions; however, AlSufyani reported a patient with AHEI who resolved with unusual scarring.¹⁴

Angioedema may be found in patients with HSP, but usually not in erythema multiforme or meningococcemia.

The duration of illness varies in patients with meningococcemia, but patients with AHEI usually are back to baseline within 2-3 weeks; patients with HSP and erythema multiforme usually are better by 4-6 weeks.

The treatment for AHEI and erythema multiforme is supportive; prednisone is controversial for HSP, and intravenous penicillin is the drug of choice for meningococcemia.

Pathophysiology

Acute hemorrhagic edema of infancy (AHEI) is a distinct variety of leukocytoclastic vasculitis. Leukocytoclastic vasculitis is probably mediated by immune complexes. Deposition of immunoglobulin A (IgA) is common in patients with Henoch-Schönlein purpura (HSP) but is observed in less than one third of skin biopsy specimens from patients with AHEI.

Frequency

United States

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

International

Until recently, most reports of acute hemorrhagic edema of infancy (AHEI) occurred in the European literature under the terms Finkelstein disease, Seidlmayer syndrome, or purpura en cocarde avec oedema. The disorder is uncommon but has been reported in countries throughout the world.

Mortality/Morbidity

Acute hemorrhagic edema of infancy (AHEI) usually is benign and without sequelae, with spontaneous recovery occurring within 1-3 weeks. Arthritis, nephritis,^15,16 abdominal pain, gastrointestinal tract bleeding, and lethal intestinal complications rarely are reported.¹⁷ Recurrences may occur. AlSufyani reported a patient with AHEI who resolved with unusual scarring.¹⁴

Race

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

Sex

Acute hemorrhagic edema of infancy (AHEI) is slightly more common among male infants than among female infants.¹⁸

Age

Age of onset for acute hemorrhagic edema of infancy (AHEI) usually is 2-60 months (median, 11 mo).^18,19

Clinical

History

Age of onset for acute hemorrhagic edema of infancy (AHEI) usually is 4-24 months.
Clinical findings develop rapidly over 24-48 hours.
Respiratory tract infection, drug intake, or vaccination frequently precedes AHEI.
Fever is common but tends to be low grade.
Patients usually are reported to have been in minimal distress despite the dramatic appearance of skin findings.
Reports of joint or abdominal pain are uncommon.
Recurrent episodes may occur.
Edema develops early in the course of the disorder and frequently involves the dorsum of the hands and feet, extending proximally up the extremities. Edema of the scalp has been reported.

Physical

The clinical picture for acute hemorrhagic edema of infancy (AHEI) is quite typical.

Patients usually are nontoxic in appearance.
Characteristic, large, cockade, annular, or targetoid purpuric lesions are found primarily on the face, ears, and extremities.^20,21
- Purpura may involve the scrotum.^22,23
- Lesions may begin as urticarial plaques and enlarge up to 5 cm in diameter. The borders are sharp.
- Mucosal involvement is rare but has been reported.
Purpura of the umbilicus can be mistaken for Cullen sign (see Media File 4).

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

Acral edema involving the dorsum of the hands and feet frequently extends proximally up the extremities.
Edema is nontender and may be asymmetric.
Associated fever tends to be low grade.
Joint and abdominal examinations are unremarkable.
Involvement of internal organs is uncommon.

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's arm.

Despite the frightening appearance of purpura in these patients, they usually are in no significant distress.

Causes

The cause of acute hemorrhagic edema of infancy (AHEI) is unknown; however, it is most frequently preceded by respiratory tract infections. In addition, numerous other infections, drug intake, and vaccinations have been implicated.^24,25,26,27
AHEI probably is an immune complex disorder; however, immune complexes have been demonstrated in only some cases.^18,28
Most cases of AHEI occur during the winter months.

Differential Diagnoses

Acute Febrile Neutrophilic Dermatosis	Hypersensitivity Vasculitis (Leukocytoclastic Vasculitis)
Dermatologic Manifestations of Hematologic Disease	Meningococcemia
Drug Eruptions	Oral Manifestations of Drug Reactions
Erythema Multiforme	Urticaria, Acute
Henoch-Schönlein Purpura (Anaphylactoid Purpura)

Workup

Laboratory Studies

In acute hemorrhagic edema of infancy (AHEI), routine laboratory tests are nondiagnostic.
Urinalysis results usually are normal.
Hematologic studies (eg, sedimentation rates, clotting studies) most often are normal.
Serum complement levels are normal.
Liver function test results may rarely be elevated.²⁹
Serologic studies are unremarkable.

Imaging Studies

In acute hemorrhagic edema of infancy (AHEI), chest radiographs may demonstrate abnormal findings in cases with tuberculosis (2 reported cases of AHEI occurring with pulmonary tuberculosis).

Histologic Findings

Histologic changes in patients with acute hemorrhagic edema of infancy (AHEI) are those of a leukocytoclastic vasculitis. The characteristics of leukocytoclastic vasculitis are demonstrated as vascular changes with a cellular infiltrate containing many neutrophils. Only small blood vessels in the dermis are involved. Vessels show swelling of their endothelial cells and deposits of fibrin within and around their walls. The result is a smudgy appearance termed fibrinoid degeneration. The cellular infiltrate is predominantly perivascular and consists primarily of neutrophils. A characteristic feature of leukocytoclastic vasculitis is the presence of numerous scattered nuclear fragments, which is termed nuclear dust. Typically, extensive extravasation of erythrocytes is present.

Histopathologic findings in Henoch-Schönlein purpura (HSP) are identical to those seen in AHEI; however, the immunohistologic pattern found in AHEI is different from the pattern of HSP. Patients with HSP usually have IgA deposition. IgA deposition is demonstrable in only approximately one third of patients with AHEI.

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).

Direct immunofluorescence studies in patients with AHEI have revealed depositions of various immunoreactants, including fibrinogen, complement component C3, IgA, immunoglobulin G, immunoglobulin M, and immunoglobulin E (100%, 100%, 33%, 22%, 78%, and 33% of patients, respectively) 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%).

Treatment

Medical Care

No effective therapy exists for acute hemorrhagic edema of infancy (AHEI). Systemic steroids do not appear to alter disease course. Treatment is symptomatic; discontinue antibiotics after obtaining negative culture results.

Consultations

Consult a dermatologist if the diagnosis of acute hemorrhagic edema of infancy (AHEI) is in doubt.
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).

Follow-up

Further Inpatient Care

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.

Further Outpatient Care

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

Deterrence/Prevention

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

Complications

Arthritis, nephritis, abdominal pain, gastrointestinal tract bleeding, and lethal intestinal complications rarely are reported as complications for acute hemorrhagic edema of infancy (AHEI).

Prognosis

Acute hemorrhagic edema of infancy (AHEI) is a self-limited disease of short duration, usually lasting less than 3 weeks.
Long-term sequelae are unlikely.
Recurrences are uncommon.

Patient Education

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

Miscellaneous

Medicolegal Pitfalls

Failure to diagnose child abuse or meningococcemia correctly

Multimedia

Media file 1: 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.

Media file 2: The left leg in this patient with acute hemorrhagic edema of infancy is markedly more edematous than the right leg.

Media file 3: 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).

Media file 4: This toddler with acute hemorrhagic edema of infancy has a discoloration in the area of the umbilicus similar to that described as Cullen sign.

Media file 5: Note the concentric arcs of purpura on the patient's arm.

Media file 6: Despite the frightening appearance of purpura in these patients, they usually are in no significant distress.

References

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Keywords

acute hemorrhagic edema of infancy, AHEI, acute infantile hemorrhagic oedema, Finkelstein's disease, Seidlmayer syndrome, , cockade purpura with edema, postinfectious cockade purpura of early childhood, acute benign cutaneous leukocytoclastic vasculitis of infancy

Contributor Information and Disclosures

Author

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Disclosure: Nothing to disclose.

Medical Editor

Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), NOVA Southeastern University; Investigator, Hill Top Research, Florida Research Center
Daniel J Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, and Canadian Dermatology Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey J Miller, MD, Associate Professor of Dermatology, Penn State University College of Medicine; Staff Dermatologist, Penn State Milton S Hershey Medical Center
Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

Further Reading