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Dermatology > PEDIATRIC DISEASES
Acute Hemorrhagic Edema of Infancy
Article Last Updated: Nov 20, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Editors: Daniel Hogan, MD, Chief of Dermatology, Professor, Departments of Internal Medicine and Pediatrics, Louisiana State University Medical Center; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center; 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; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Author and Editor Disclosure
Synonyms and related keywords:
acute infantile hemorrhagic oedema, Finkelstein's disease, Seidlmayer syndrome, purpura en cocarde avec oedema, cockade purpura with edema, postinfectious cockade purpura of early childhood, acute benign cutaneous leukocytoclastic vasculitis of infancy, AHEI
Background
Snow first described acute hemorrhagic edema of infancy (AHEI) in the US in 1913. Europeans have recognized Finkelstein's description of this disease since his publication in 1938 and, until recently, most reports of this disorder occurred in the European literature under the terms Finkelstein's disease, Seidlmayer syndrome, or purpura en cocarde avec oedema. AHEI is a distinctive, cutaneous, small vessel leukocytoclastic vasculitis of young children with dramatic characteristic skin findings. 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). The typical patient with AHEI is aged 4-24 months with a history of recent upper respiratory illness and/or course of antibiotics. 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. Gattorno et al 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 (EM). The petechiae and purpura also may resemble lesions of HSP and meningococcemia (MC), although patients often appear much sicker with high fever, malaise, and possible shock in severe cases of MC. Angioedema may be found in patients with HSP, but usually not in EM or MC. The duration of illness varies in patients with MC, but patients with AHEI usually are back to baseline within 2-3 weeks; patients with HSP and EM usually are better by 4-6 weeks. The treatment for AHEI and EM is supportive; prednisone is controversial for HSP, and intravenous penicillin is the drug of choice for MC.
Pathophysiology
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 HSP but is observed in less than one third of skin biopsy specimens from patients with AHEI.
Frequency
United States
AHEI is uncommon in the United States. Specific frequency data have not been reported.
International
Until recently, most reports of AHEI occurred in the European literature under the terms Finkelstein's disease, Seidlmayer syndrome, or purpura en cocarde avec oedema. The disorder is uncommon but has been reported in countries throughout the world.
Mortality/Morbidity
AHEI usually is benign and without sequelae, with spontaneous recovery occurring within 1-3 weeks. Arthritis, nephritis, abdominal pain, gastrointestinal tract bleeding, and lethal intestinal complications rarely are reported. Recurrences may occur.
Race
No racial predilection has been described.
Sex
AHEI may be slightly more common among male infants than among female infants.
Age
Age of onset usually is 4-24 months.
History
- Age of onset 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 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.
- Purpura may involve the scrotum.
- 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).
- 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.
Causes
- The cause of this disorder is unknown; however, it frequently is preceded by respiratory tract infections, drug intake, or vaccination.
- AHEI probably is an immune complex disorder; however, immune complexes have been demonstrated in only some cases.
- Most cases of AHEI occur during the winter months.
Acute Febrile Neutrophilic Dermatosis
Dermatologic Manifestations of Hematologic Disease
Drug Eruptions
Erythema Multiforme
Henoch-Schönlein Purpura (Anaphylactoid Purpura)
Hypersensitivity Vasculitis (Leukocytoclastic Vasculitis)
Meningococcemia
Oral Manifestations of Drug Reactions
Urticaria, Acute
Other Problems to be Considered
Child abuse
Lab Studies
- Routine laboratory tests are nondiagnostic.
- Urinalysis usually is normal.
- Hematologic studies (eg, sedimentation rates, clotting studies) most often are normal.
- Serum complement levels are normal.
- Serologic studies are unremarkable.
Imaging Studies
- 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 AHEI are those of a leukocytoclastic vasculitis (LCV). The characteristics of LCV 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 LCV is the presence of numerous scattered nuclear fragments, which is termed nuclear dust. Typically, extensive extravasation of erythrocytes is present.
Histopathologic findings in 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.
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%).
Medical Care
No effective therapy exists. 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 is in doubt.
- Consult a gastroenterologist or nephrologist if significant abdominal symptoms or renal involvement is noted.
Diet
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.
Further Inpatient Care
- Inpatient care is not usually required unless the diagnosis is in doubt. If MC or another significant condition remains in the differential diagnosis, patients may require monitoring or therapy as appropriate for those disorders.
Further Outpatient Care
- Treatment 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 this condition or recurrences.
Complications
- AHEI usually is benign and without sequelae, with spontaneous recovery within 1-3 weeks.
- Arthritis, nephritis, abdominal pain, gastrointestinal tract bleeding, and lethal intestinal complications rarely are reported.
- Recurrences are uncommon.
Prognosis
- 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 the disorder and the fact that recurrences can occur.
Medical/Legal Pitfalls
- Failure to diagnose child abuse or MC correctly
| 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. |
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| Media file 2:
The left leg in this patient with acute hemorrhagic edema of infancy is markedly more edematous than the right leg. |
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| 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). |
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| 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. |
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| Media file 5:
Note the concentric arcs of purpura on the patient's arm. |
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| Media file 6:
Despite the frightening appearance of purpura in these patients, they usually are in no significant distress. |
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Acute Hemorrhagic Edema of Infancy excerpt Article Last Updated: Nov 20, 2006
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