Article / Clinical Case Report
Artigo / Relato de Caso Clínico
Acute Hemorrhagic Edema of Infancy: an unusual diagnosis for the
general pediatrician
Diego Fontana Siqueira Cunhaa, Ana Letícia Fornazieri Darcieb,
Gabriel Nuncio Benevidesb, Angela Espósito Ferronatoc, Noely Heinc,
Denise Swei Loc, Cristina Ryoka Miyao Yoshiokac, Maki Hirosec,
Debora Morais Cardosoc, Alfredo Elias Giliob,c
Cunha DFS, Darcie ALF, Benevides GN, et al. Acute Hemorrhagic Edema of Infancy: an unusual diagnosis for the general
pediatrician. Autopsy Case Rep [Internet]. 2015;5(3):37-41. http://dx.doi.org/10.4322/acr.2015.020
ABSTRACT
Acute Hemorrhagic Edema of Infancy (AHEI) is a rare leukocytoclastic vasculitis, clinically characterized by the classical
triad: palpable purpuric skin lesions, edema and fever, and is commonly misdiagnosed as Henoch-Schönlein purpura.
In addition to its sudden onset, AHEI is also characterized by its self-limited course with complete and spontaneous recovery
occurring between 1 and 3 weeks. Because of the scarcity of studies on therapy with corticosteroids, the conservative
approach is usually recommended. The authors report an unusual case of an one-year-old boy who presented with typical
cutaneous rash of AHEI and orchitis, the latter showing complete resolution after less than 24 hours of prednisolone
therapy. The authors call attention to this entity mainly as a differential diagnosis of Henoch-Schönlein purpura and to
the importance of new studies to establish the benefits of corticosteroid therapy for AHEI.
Keywords
Infant; Vasculitis, Leukocytoclastic, Cutaneous; Orchitis; Steroids; Purpura.
INTRODUCTION
Acute Hemorrhagic Edema of Infancy (AHEI) is a
rare leukocytoclastic vasculitis, which typically affects
children between 4 and 24 months.1-3 It is commonly
misdiagnosed as Henoch-Schönlein purpura (HSP) due
to clinical similarities.4-6
AHEI is clinically characterized by the classical
triad of palpable purpuric skin lesions, edema and
fever.7 Visceral involvement is rare, and the scrotum
is involved in less than 10 percent of cases.8 AHEI is
usually considered non-responsive to corticosteroid
a
b
c
therapy, hence a conservative approach is generally
recommended.
CASE REPORT
An one-year-old boy was referred to the hospital
with a four-day history of cough and rhinorrhea and
a two-day history of low-grade fever and hemorrhagic
cutaneous eruption. The skin rash started in both
knees and spread to his upper extremities, feet, face
Department of Pediatrics - Hospital das Clínicas - Faculty of Medicine - Universidade de São Paulo, São Paulo/SP – Brazil.
Faculty of Medicine - Universidade de São Paulo, São Paulo/SP – Brazil.
Division of Pediatrics - Hospital Universitário - Universidade de São Paulo, São Paulo/SP – Brazil.
Autopsy and Case Reports. ISSN 2236-1960. Copyright © 2014. This is an Open Access article distributed
of terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted noncommercial use, distribution, and reproduction in any medium provided article is properly cited.
Acute Hemorrhagic Edema of Infancy: an unusual diagnosis for the general pediatrician
and ears followed by swelling of knees, hands, feet
and scrotum. There was no history of vomiting, urinary
complaints or recent immunizations.
On clinical examination, he was in good overall
clinical condition and afebrile. He had multiple rounded
palpable purpuric patches over the upper and the lower
limbs, face, oral cavity mucosa and both ears, sparing
the trunk. (Figure 1) He also had edema over knees,
hands, feet and hyperemia and edema in his scrotum
(Figure 2). Neither passive restriction of the joints
movements nor signs of joint effusion were present.
There was no evidence of abdominal tenderness.
Scrotal ultrasonography showed marked bilateral
scrotal skin thickening and small bilateral hydroceles,
with normal testicular blood flow. Laboratory studies
revealed normal blood count with elevated erythrocyte
sedimentation rate and C-reactive protein. Urinalysis,
coagulation tests and random protein-to-creatinine
ratio were normal (as shown in Table 1).
Oral prednisolone was prescribed (2mg/kg/day)
and the scrotal inflammatory signs subsided on the
second day after treatment. No new skin lesions were
noticed. The patient was discharged two days after
admission for an outpatient follow-up.
Figure 1. Multiple rounded palpable purpuric patches over upper (left) and lower (middle) limbs, ear and face (right).
Table 1. Laboratory work up
RV
RV
Hemoglobin
11.7
10.5-13.5 g/dL
ESR
47
< 10 mm 1st hour
Leukocytes
11.87
6.0-17.5 × 103/mm3
CRP
100
< 5 mg/dL
Neutrophils
3.917
1.5-8.5 × 103/mm3
Leukocytes (U)
2000
<10.000/mm3
Lymphocytes
6.184
4.0-10.5 ×103/mm3
Erythrocytes (U)
2000
<10.000/mm3
150-450 ×103/mm3
Random protein (U)
23
1-14 mg/dL
Random creatinine (U)
89.5
24-392 mg/dL
Platelets
433
aPTT
1.13
< 1.25
INR
1.09
0.8-1.2
aPTT- activated partial thromboplastin time, CRP= c-Reactive protein, ESR= erythrocyte sedimentation rate,
INR= international normalized ratio, U= urine.
38
Autopsy and Case Reports 2015;5(3):37-41
Cunha DFS, Darcie ALF, Benevides GN, et al.
However, according to some authors6,13 when the
diagnosis of AHEI is suspected, a complete blood
count, urine analysis and clotting tests should be
required to differentiate AHEI from other more severe
diagnosis.
Figure 2. Hyperemia and edema of the scrotum.
DISCUSSION
Acute Hemorrhagic Edema of Infancy (AHEI) is a
leukocytoclastic vasculitis commonly misdiagnosed or
misinterpreted as Henoch-Schonlein Purpura (HSP).
Although the current classification of childhood
vasculitis 9,10 does not include AHEI as a vasculitis
identity, from the first publication by Irving M. Snow11
in 1913, to the year 2004, there were 100 cases of
this disease reported worldwide. 1 AHEI is typically
characterized by the classical triad of palpable purpuric
skin lesions, edema and fever7 and it is more common
in males, between 4 and 24 months, without racial
predominance.2,3
The clinical history usually begins with sudden
appearance of well demarcated, annular, medallion-like,
rosette shaped purpuric plaques, mostly observed on
the face and the extremities, with relative sparing
of the trunk. 3,12 Visceral involvement is rare, but
symptoms like arthritis, gastrointestinal bleeding and
scrotal erythema and edema, as presented in our case,
has been described in literature.13
Although the etiology remains unknown, it is
believed that AHEI is an immune-complex mediated
disease. This hypothesis is based on the observation
that infections (mostly upper respiratory tract infections
and urinary tract infections), drugs or immunizations
preceded almost 75% of AHEI cases.14
Diagnosis of AHEI is majorly based on clinical
grounds. In doubtful cases, the skin biopsy followed by
histopathologic with immunofluorescence examination
may be of great value for diagnosis. 15 Laboratory
tests are usually normal, although leukocytosis,
thrombocytosis and eosinophilia may be observed.6
Autopsy and Case Reports 2015;5(3):37-41
Histologic findings of the skin lesions are
consistent with small-vessel vasculitis, showing typical
leukocytoclastic vasculitis in the dermis with or without
fibrinoid necrosis.3,5,13 Immunofluorescence testing
can reveal C3, fibrinogen and IgM deposits and, less
commonly, IgM, IgE or IgA, the latter a common
finding in HSP.16,17
AHEI is a self-limited disease, running a benign
course, with complete spontaneous recovery in
1 to 3 weeks.3 Although conservative management is
the most frequently adopted approach, few publications
have reported beneficial use of corticosteroids.
These authors18,19 observed a clear improvement of
symptoms after high-dose of corticosteroid therapy
and recommend that, in severe cases of AHEI,
corticotherapy should be considered to shorten the
symptoms and give significant relief. In the case
reported herein, the scrotal inflammation subsided
in less than 24 hours after prednisolone therapy, and
the skin lesions became undetectable after 2 weeks.
Among the differential diagnosis for AHEI,
Henoch Schönlein Purpura (HSP) is probably the most
important. Because of similarities involving both
syndromes, there is a debate in literature if AHEI should
be considered as a separate entity or as a variant of
HSP.13 Currently, most authors5,6,13,20 consider them as
different diseases based on clinical, pathological and
epidemiological differences.
These differences involve the patient’s age; while
AHEI afflicts more often younger children aging from
4 months up to 2 years, HSP occurs in older ones, from
3 to 6 years of age.20 Skin lesions in AHEI are rounded
palpable purpuric plaques, frequently observed on
the face and upper limbs, while in HSP lesions are
uncharacteristic palpable purpura that distribute on
a gravitational pattern, like the buttock and extensor
surface of the legs, usually sparing the face.13,21 Visceral
involvement is very rare in AHEI, in contrast to HSP,
which frequently presents with gastrointestinal and
renal complications. 13,21 Perivascular IgA deposition
is frequently seen in HSP and often absent in AHEI.3
Another important difference is that relapses are
39
Acute Hemorrhagic Edema of Infancy: an unusual diagnosis for the general pediatrician
commonly observed in HSP and rarely reported in
AHEI.5,7
It is likely that the AHEI’s low prevalence may be
due to a number of misdiagnosis as Henoch-Schonlein
Purpura (HSP). Nonetheless as the treatment of
these two entities differs, it becomes important to
accurately differentiate them. While corticosteroid
therapy is indicated for HSP cases, 22 most authors
defend a conservative approach for AHEI. In the case
presented herein, there was marked improvement
of symptoms after corticosteroid therapy, noted by
the rapid regression of scrotal erythema, edema and
discontinuing the appearance of new lesions after
treatment. However, larger series are required to
accurately access the benefit of corticotherapy for AHEI
with extracutaneous complications.
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Conflict of interest: None
Submitted on: July 27, 2015
Accepted on: August 28, 2015
Correspondence
Gabriel Nuncio Benevides
Divisão de Clínica Pediátrica - Hospital Universitário - Universidade de São Paulo (USP)
Avenida Prof. Lineu Prestes, 2565 – São Paulo/SP – Brazil
CEP: 05508-000
Phone: +55 (11) 97484-0708
E-mail: gnbenevides@gmail.com
Autopsy and Case Reports 2015;5(3):37-41
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