Acute hemorrhagic edema of infancy: A case report
Published Web Locationhttps://doi.org/10.5070/D38vg89839
Acute hemorrhagic edema of infancy: A case report1. Department of Pathology, University of Miami School of Medicine. email@example.com. Department of Dermatology, University
of Miami School of Medicine
Wilfredo Blasini MD1, Ritu Saini MD2, Vladimir Vincek MD PhD1
Dermatology Online Journal 13 (3): 27
A 12-month-old male presented with edematous purpuric plaques on the extremities (including the palms and soles), and violaceous targetoid macules on the hard palate and earlobes. The patient had an upper respiratory infection and conjunctivitis 10 days prior to the development of the skin lesions, and was vaccinated 3 weeks before this presentation. He was found to have increased IgA levels and increased ESR. Skin biopsies demonstrated leukocytoclastic vasculitis and IgA granular deposition on superficial dermal vessels. These findings are characteristic of acute hemorrhagic edema of infancy, an entity that must be distinguished from other leukocytoclastic vasculitis, especially Henoch-Schönlein purpura.
Acute hemorrhagic edema of infancy (AHEI) is a rare benign acute cutaneous vasculitis that occurs in children between 4 and 24 months of age. The disease is characterized by the acute appearance of skin lesions, edema, and fever; however, it is self-limiting. The differential diagnosis for the disease includes important clinical entities such as Henoch-Schönlein purpura (HSP), erythema multiforme, septic vasculitis, Kawasaki disease, drug induced vasculitis, meningococcemia, trauma-induced purpura, and child abuse. The recognition of AHEI allows making the diagnosis of this benign entity rather than a more serious disease.
A 12-month-old male presented with a 2-day history of a purple rash and swelling on the legs, palms, soles, and earlobes. He had a 10-day history of upper respiratory infection, fever, conjunctivitis, and vomiting treated with tobramycin, amoxicillin, and ibuprofen. Approximately 3 weeks prior to admission, he received vaccines for varicella and MMR. His birth and developmental history were uncomplicated. The past medical history was unremarkable and the family history was only significant for asthma.
Physical examination revealed a temperature of 39.3° C, and multiple diffuse and edematous purpuric plaques on the extremities, including the palms and soles. He also presented several violaceous targetoid macules on the hard palate and earlobes. Urinalysis, liver and renal function test, serum complement, and complete blood count were within normal limits. Stool was negative for occult blood. Echocardiogram and electrocardiogram were normal. Immunoglobulin levels revealed increased IgA and IgG levels. Erythrocyte sedimentation rate was elevated.
The initial differential diagnosis included erythema multiforme, HSV, and vasculitis. The patient was started on vancomycin and cefotaxime, but showed no response.
|Figure 1||Figure 2|
|Figure 1. Violaceous targetoid macules on the earlobes|
Figure 2. Perivascular neutrophilic infiltrate, nuclear dust, and fibrinoid necrosis of the vessels walls
|Figure 3||Figure 4|
|Figure 3. Direct immunofluorescence showing granular IgA deposits in and around the superficial dermal blood vessels|
Figure 4. Diffuse and edematous purpuric plaques on the upper extremities
Two skin biopsies were taken from the center of a plaque on the left arm. Routine H&E stain and direct immunofluorescence were performed. Histology revealed a perivascular neutrophilic infiltration with nuclear dust, fibrinoid necrosis of the vessels walls, and extravasations of red blood cells. Direct immunofluorescence disclosed granular IgA deposits in and around the superficial dermal blood vessels. IgG, IgM, C3, C5b-9, and fibrinogen were not seen in the specimen. Viral cultures for HSV were negative.
The patient was started on prednisone 1 mg/kg daily, to slowly taper over 3-4 weeks. Supportive care was given and complete resolution was acquired without sequelae.
Acute hemorrhagic edema of infancy (AHEI), also known as postinfectious cockade purpura, Seildlmayer's disease and Finkelstein's disease, is an acute cutaneous leukocytoclastic vasculitis first described in the United States in 1913 by Snow [1, 2]. It is a disease that affects children between 4 and 24 months of age and is characterized by a triad of fever, large palpable purpuric skin lesions, and edema [3, 4]. Its presentation is dramatic in appearance and rapid in onset . It starts with the sudden appearance of well demarcated, annular, medallion-like purpuric plaques, almost entirely limited to extremities and face, with relative sparring of trunk [3, 6, 7]. Fever and painful edema of the distal extremities, ears, and eyelids are associated features of AHEI .
Approximately 100 cases have been reported in the English and European literature since the disease was first described. The low number of reported cases may represent low incidence, disease underdiagnosis, or confusion with other similar entities . There is a slight male predominance and the majority of the cases have been seen to occur in winter [9, 10].
The pathogenesis and etiology is unknown, but a various infections have been documented in children with AHEI, such as upper respiratory infection, pharyngitis, conjunctivitis, otitis media, bronchitis, urinary tract infection, and pneumonia . Serious infections are occasionally associated with the disease. A case in association with pneumococcal bacteremia has been reported as well as cases associated with tuberculosis and cervical nodes abscesses [2, 6, 11]. Its association with serious infection and the similarities between AHEI and anaphylactoid purpura have suggested a role for complement deficiency in the pathogenesis of the disease . However, the disease is frequently seen preceded by a prodromal period, which is characterized by a bacterial or viral infection, drugs side effects, or immunization side effects [9, 13, 14] AHEI has been categorized as an immune complex hypersensitivity reaction in response to the previously mention factors. Antigen-antibody complexes are deposited within blood vessels and lead to the activation of the complement cascade, which results in endothelial damage, typically of the postcapillary venules .
The head and distal portion of the extremities are preferred sites in AHEI, and the disease is limited to the skin . Visceral involvement is rare but it has been reported involving the kidneys and intestines, causing symptoms such as hematuria, mild proteinuria, and bloody diarrhea . Other systemic symptoms such as abdominal pain, gastrointestinal bleeding, arthritis, and nephritis, have been rarely reported . Severe articular involvement has been described in one case . The disease had been reported as not involving the mucosa, but rare cases have demonstrated mucosal involvement [9, 17, 18]. Also, one case of severe genital and trunk involvement has been described .
Light microscopy examination of skin biopsies typically show normal epidermis, leukocytoclastic vasculitis of the dermal vessels with extravasated red blood cells in the dermis, and fibrinoid necrosis in the blood vessels [2, 14]. Direct immunofluorescence on skin biopsies specimens have revealed vessel wall deposition of fibrinogen (100 %), C3 (100 %), IgG (22 %), IgM (78 %), IgA (33 %), and IgE (33 %) . Deposition of Ciq has also been reported .
Laboratory tests typically show normal results. Elevated erythrocyte sedimentation rate, leukocytosis, thrombocytosis, and eosinophilia have been seen in AHEI . The disease runs a benign course with complete spontaneous recovery occurring in 1-3 weeks, although relapses have been reported rarely [2, 3, 13, 15, 19, 20]. The treatment is supportive and antibiotics are recommended when there is evidence of infection [7, 13]. Systemic corticosteroids and antihistamines have not demonstrated to alter the course of disease; although antihistamines may prompt more rapid healing [2, 5, 10, 13, 14]. There is no therapy indicated, but ibuprofen and acetaminophen may be used to relieve fever, systemic symptoms, and discomfort .
The differential diagnosis of AHEI includes other dermatoses such as Henoch-Schönlein purpura (HSP), Sweet's syndrome, acute febrile neutrophilic dermatosis, erythema multiforme, or septic vasculitis [14, 15]. In addition, other entities such as Kawasaki disease, drug induced vasculitis, meningococcemia, trauma-induced purpura, and child abuse have to be considered in the differential diagnosis [9, 10]. All these disorders are differentiated by the clinical presentation, history, physical examination, laboratory tests, and histopathology of the skin lesions .
The main entity in the differential diagnosis of acute hemorrhagic edema of infancy is Henoch-Schönlein purpura. AHEI was initially considered as a HSP variant, but evidence demonstrates that they are separate entities . However patients with overlapping features of both have also been reported . Both disorders have histologic features of leukocytoclastic vasculitis. AHEI does not commonly contain the perivascular IgA deposition that is seen in 100 percent of HSP cases, although IgA deposition has been seen in a percent of AHEI cases [9, 21]. Both AHEI and HSP may present IgM, fibrinogen, and C3 perivascular deposits, but only AHEI depicts Ciq deposition . Moreover, AHEI patients are 4 to 24 months-old with male predominance, while HSP patients range between 3 to 10 years-old . AHEI is almost always confined to the skin, whereas HSP usually shows renal, joints, and gastrointestinal tract involvement [7, 8, 21]. HSP is characterized by polymorphic skin lesions in the form of palpable purpura on the extensor surfaces of the lower extremities with a tendency to spare the face . In AHEI, larger purpura and ecchymoses are found on the face, head, ankle, wrists, auricles, with more extensive edema and fever [2, 21]. In addition, there is more extensive vasculitis with fibrin deposits and IgA deposits are seen only in a third of cases .
The classic features of AHEI are the contrast between the acuteness of the skin lesions and the good clinical condition of the patient, the absence of visceral involvement, and its self-limiting behavior . Recognizing this as a distinct clinical entity allows an appropriate prognosis to be made for this rare benign disease in children.
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