Acute Hemorrhagic Edema of Infancy

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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.

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.

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]

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]

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.

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

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.

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]

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]   

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

Snow IM. Purpura, urticaria and angioneurotic edema of the hands and feet in a nursing baby. JAMA. 1913. 61:18-19.

Del Carril MJ, Diaz Sobillo I, Vidal J. Edema agudo hemorra´gico en un lactante. Prensa Med Argent. 1936. 23:1719-22.

Finkelstein H. Lehrbuch der Sauglingskrankheiten. 4th ed. Amsterdam: 1938. 814-30.

Seidlmayer H. Die Fruhinfantile postinfektiose Kokarde-Purpura. Z Kinderheilk. 1939. 61:217-55.

Saraclar Y, Tinaztepe K, Adalioglu G, Tuncer A. Acute hemorrhagic edema of infancy (AHEI)–a variant of Henoch-Schönlein purpura or a distinct clinical entity?. J Allergy Clin Immunol. 1990 Oct. 86(4 Pt 1):473-83. [Medline].

Fiore E, Rizzi M, Ragazzi M, et al. Acute hemorrhagic edema of young children (cockade purpura and edema): a case series and systematic review. J Am Acad Dermatol. 2008 Oct. 59(4):684-95. [Medline].

Al-Sheyyab M, El-Shanti H, Ajlouni S, Sawalha D, Daoud A. The clinical spectrum of Henoch-Schönlein purpura in infants and young children. Eur J Pediatr. 1995 Dec. 154(12):969-72. [Medline].

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Legrain V, Lejean S, Taieb A, Guillard JM, Battin J, Maleville J. Infantile acute hemorrhagic edema of the skin: study of ten cases. J Am Acad Dermatol. 1991 Jan. 24(1):17-22. [Medline].

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Sites LY, Woodmansee CS, Wilkin NK, Hanson JW, Skinner RB Jr, Shimek CM. Acute hemorrhagic edema of infancy: case reports and a review of the literature. Cutis. 2008 Nov. 82(5):320-4. [Medline].

Roh MR, Chung HJ, Lee JH. A case of acute hemorrhagic edema of infancy. Yonsei Med J. 2004 Jun 30. 45(3):523-6. [Medline].

Cox NH. Seidlmayer’s syndrome: postinfectious cockade purpura of early childhood. J Am Acad Dermatol. 1992 Feb. 26(2 Pt 1):275. [Medline].

AlSufyani MA. Acute hemorrhagic edema of infancy: unusual scarring and review of the English language literature. Int J Dermatol. 2009 Jun. 48(6):617-22. [Medline].

Limor Parker, Keren Shahar-Nissan, Liat Ashkenazi-Hoffnung, Liora Harel, Jacob Amir, Omer Trivizki, et al. Acute hemorrhagic edema of infancy: the experience of a large tertiary pediatric center in Israel. World J Pediatr. 2017. 13(4):341-45. [Medline].

Krause I, Lazarov A, Rachmel A, et al. Acute haemorrhagic oedema of infancy, a benign variant of leucocytoclastic vasculitis. Acta Paediatr. 1996 Jan. 85(1):114-7. [Medline].

A. Ferrarinia, G.P. Milanib, M.G. Bianchettia, S.A.G. Lava. Acute hemorrhagic edema of infancy associated with Coxsackie virus infection. Arch Pediatr. Apr 2018. 25(3):244. [Medline].

Goraya JS, Kaur S. Acute infantile hemorrhagic edema and Henoch-Schonlein purpura: is IgA the missing link?. J Am Acad Dermatol. 2002 Nov. 47(5):801; author reply 801-2. [Medline].

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Donald Shenenberger, MD, FAAD, FAAFP Board Certified Dermatologist

Donald Shenenberger, MD, FAAD, FAAFP is a member of the following medical societies: American Academy of Dermatology, American Academy of Family Physicians, Association of Military Dermatologists, Medical Society of Virginia, Uniformed Services Academy of Family Physicians

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster 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, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania 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, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Daniel J Hogan, MD Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; 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, Canadian Dermatology Association

Disclosure: Nothing to disclose.

Tina S Chen Twu, MD Pediatric Dermatologist/Dermatologist, Sharp Rees-Stealy Medical Group, San Diego, CA

Tina S Chen Twu, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

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.

Brandie J Metz, MD Assistant Clinical Professor of Dermatology and Pediatrics, Chief of Pediatric Dermatology, University of California, Irvine, School of Medicine

Brandie J Metz, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology, and Women’s Dermatologic Society

Disclosure: Nothing to disclose.

Acute Hemorrhagic Edema of Infancy

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