==== Front Ann Saudi MedAnn Saudi MedAnnals of Saudi Medicine0256-49470975-4466King Faisal Specialist Hospital and Research Centre 2640980110.5144/0256-4947.2015.254asm-3-254Case ReportAcute hemorrhagic edema of infancy after MMR vaccine Binamer Yousef Department of Dermatology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaCorrespondence: Yousef Binamer, MD, FRCPC, DABD, Department of Dermatology, MBC 104 King Faisal Specialist Hospital & Research Centre PO Box 3354, Riyadh 11211 Saudi Arabia, ybinamer@kfshrc.edu.saMay-Jun 2015 35 3 254 256 Copyright © 2015, Annals of Saudi Medicine2015This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Acute hemorrhagic edema of infancy (AHEI) is a rare type of leuckocytoclastic vasculitis. It affects mainly children less than two years of age. Many precipitating factors have been reported, including infectious etiology and vaccination. We are reporting a two-year-old boy with AHEI after measles, mumps, and rubella (MMR) vaccine. To our knowledge this is the second reported case after an MMR vaccine. ==== Body Acute hemorrhagic edema of infancy (AHEI) is a rare type of cutaneous vasculitis. Despite its impressive clinical presentation, it has a very benign course limited to skin and resolves in three weeks. Trigger factors have been reported including drugs, infections and vaccination. Measles, mumps, and rubella (MMR) vaccine has been implicated once before as a precipitating factor by Blasini et al.1 CASE A two-year-old male presented to our clinic with a 5-day history of progressive dusky red indurated plaques with a targetoid appearance over the extremities and face. The ears and cheeks were swollen and edematous (Figure 1). There was no history of preceding infection or medication intake. However, he was vaccinated for MMR two weeks before presentation. He had no systemic symptoms. A skin biopsy showed leuckocytoclastic vasculitis, with fibrinoid necrosis of the blood vessels, extravasation of RBCs, karyorrhexis and neutrophilic infiltrates (Figure 2). However, direct immunofluorescence was not done. Blood tests were normal including CBC, kidney and liver function test and ESR, but CRP was 17.5 mg/L. Mycoplasma and herpes simplex virus type 1 and 2 serology tests were all negative. He was labeled as AHEI based on clinical presentation and the skin biopsy. He was given a short course of prednisolone 1 mg/kg (12 mg) over three weeks. On follow up one month later, the lesions cleared completely. DISCUSSION AHEI is a rare small-vessel leuckocytoclastic vasculitis. Snow et al2 described the first case in the United States in 1913, but the description of the disease in Europe only appeared in 1938 by Finkelstein3 and later by Seidlmayer as “Seidlmayer cockade purpura”.4 More than 80% of cases have been reported in children less than two years of age, but it has been reported in children at five years of age and the male to female ratio is 2:1.1,5 In addition, a congenital case was reported after maternal gastroenteritis six weeks before delivery.6 It occurs more during winter, which supports infectious agents as a triggering factor.7 Children with AHEI usually have fever, nonpitting edema and indurated dusky red plaques with a targetoid or annular purpuric configuration. It affects the face and ears, sparing the trunk in most cases. However, severe truncal involvement has been reported as well.5,8,9 The edema occurs mainly over the face and ears,5,10,11 and is associated typically with a low grade fever in 50% of cases. Despite the dramatic presentation the child looks well and nontoxic. A rare bullous variant was reported in a 9-month-old child.12 Other uncommon presentations are pruritus, urticaria, conjunctival injection and oral petechiae.10 Despite the dramatic presentation, most of blood tests are normal. The erythrocyte sedimentation rate and C-reactive protein can be elevated. Skin biopsy shows fibrinoid necrosis, extravasation of red blood cells, leukocytoclasia. 10% of these patients will have perivascular IgA deposition detected by direct immunofluorescence. AHEI generally has a benign course with aduration of illness lasting 1 to 3 weeks.5,10,11 However, very rare complications have been reported including intussusception, 7 hematuria, proteinuria, hypocomplementemia13 and scarring.14 Other systemic symptoms such as abdominal pain, gastrointestinal bleeding, arthritis and nephritis have been rarely reported as well.15 Severe articular involvement has been described in one case16 as well as testicular torsion.10 Mucosal involvement is rare.17,18 The differential diagnosis of AHEI includes Henoch-Schönlein purpura (HSP), meningococcemia, erythema multiforme, Kawasaki disease, and drug eruption. The distinction between AHEI and HSP is among the most challenging. HSP usually affects children between 2–10 years with predominant lower limb involvement and minimal edema. HSP commonly has systemic involvement with a 50% chance of recurrence. On direct immunofluorescence, IgA deposition is noted in most cases with HSP. 5,10–12,19,20 Many triggers have been reported. However, no strong evidence suggest one more than the other. Among them are infections, drugs and vaccination. The average interval between the onset of AHEI and the possible causative agent ranges from two days to one month.5,10,11 AHEI was reported after vaccination with Bacillus Calmette–Guérin (BCG) 11, H1N1,19,21 Hemophilus influenza type B, diphtheria, tetanus, acellular pertussis, hepatitis B, polio, and conjugate pneumococcal vaccines. 22 Blasini et al1 reported a 12-month-old male who presented with a two-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 three weeks prior to admission, he received vaccines for varicella and MMR.5 Therefore, MMR vaccine is a probable triggering factor in their case. We are reporting the second case of AHEI apparently triggered by MMR. AHEI was reported as well after specific infections, including adenovirus,23 streptococci,24 staphylococci,25 tuberculosis, Coxsackie virus,11 Campylobacter,11 rotavirus,26 hepatitis A virus, cytomegalovirus28 and pneumococcal bacteremia.29 Figure 1 Dusky red targetoid edematous plaques over face and arm. Figure 2 Skin biopsy showing leuckocytoclastic vasculitis. ==== Refs REFERENCES 1 Blasini W Saini R Vincek V Acute hemorrhagic edema of infancy: a case report Dermatol Online J 2007 7 13 13 3 27 2 Snow IM Purpura, urticaria and angioneurotic edema of the hands and feet in a nursing baby JAMA 1913 61 18 29 3 Finkelstein H Lehrbuch der Sauglingskrankheiten 4th ed Amsterdam 1938 814 30 4 Seidlmayer H Die Fruhinfantile postinfektiose Kokarde-Purpura Z Kinderheilk 1939 61 217 55 5 Fiore E Rizzi M Simonetti GD Acute hemorrhagic edema of young children: a concise narrative review Eur J Pediatr 2011 12 170 12 1507 11 21674141 6 Cunningham BB Caro WA Eramo LR Neonatal acute hemorrhagic edema of childhood: case report and review of the English-language literature Pediatr Dermatol 1996 Jan-Feb 13 1 39 44 8919524 7 Yu JE Mancini AJ Miller ML Intussusception in an infant with acute hemorrhagic edema of infancy Pediatr Dermatol 2007 Jan-Feb 24 1 61 4 17300653 8 Morrison RR Saulsbury FT Acute hemorrhagic edema of infancy associated with pneumococcal bacteremia Pediatr Infect Dis J 1999 9 18 9 832 3 10493349 9 Carder KR Hypersensitivity reactions in neonates and infants Dermatol Ther 2005 Mar-Apr 18 2 160 75 15953145 10 Fiore E Rizzi M Ragazzi M Acute hemorrhagic edema of young children (cockade purpura and edema): a case series and systematic review J Am Acad Dermatol 2008 10 59 4 684 95 18656284 11 Legrain V Lejean S Taieb A Infantile acute hemorrhagic edema of the skin: study of ten cases J Am Dermatol 1991 24 17 22 12 Lai-Cheong JE Banerjee P Hill V Bullous acute haemorrhagic oedema of skin in infancy Clin Exp Dermatol 2007 7 32 4 467 8 17376214 13 Watanabe T Sato Y Renal involvement and hypocomplementemia in a patient with acute hemorrhagic edema of infancy Pediatr Nephrol 2007 11 22 11 1979 81 17704952 14 AlSufyani MA Acute hemorrhagic edema of infancy: unusual scarring and review of the English language literature Int J Dermatol 2009 6 48 6 617 22 19538372 15 McDougall CM Ismail SK Osmerod A Acute hemorrhagic oedema of infancy Arch Dis Child 2005 3 90 3 316 15723928 16 Gattorno M Picco P Gambini C Erythema multiforme-like manifestations and arthritis in a 3-year-old child with leukocytoclastic vasculitis Clin Exp Rheumatol 1997 May-Jun 15 3 329 32 9177932 17 Poyrazoglu HM Per H Gunduz Z Acute hemorrhagic edema of infancy Pediatr Int 2003 12 45 6 697 700 14651544 18 Dubin BA Bronson DM Eng AM Acute hemorrhagic edema of childhood: An unusual variant of leukocytoclastic vasculitis J Am Acad Dermatol 1990 23 347 50 2394853 19 Garty BZ Pollak U Scheuerman O Acute hemorrhagic edema of infancy associated with herpes simplex type 1 stomatitis Pediatr Dermatol 2006 Jul-Aug 23 4 361 4 16918634 20 Millard T Harris A MacDonald D Acute infantile hemorrhagic edema J Am Acad Dermatol 1999 41 837 839 10534663 21 Ferreira O Antunes I Cruz MJ Acute hemorrhagic edema of childhood after H1N1 immunization Cutan Ocul Toxicol 2011 6 30 2 167 9 21121877 22 Obeid M Haley J Crews J Acute hemorrhagic edema of infancy with abdominal pain and elevated transaminases Pediatr Dermatol 2008 Nov-Dec 25 6 640 1 19067875 23 Jeannoel P Fabre M Payen C Oedeme aigu hemorragique du nourrisson: role de l’adenovirus. A propos d’une observation Pediatrie 1985 40 557 560 3831903 24 Snoussi N Strobel M Heid E Oedeme aigu hemorragique du nourrison: demonstration d’une vascularite allergique dermique Arch Belg Dermatol Syphiligr 1973 29 259 260 4789509 25 Laugier P Oedema aigu hemorragique (purpura en cocarde avec oedema) Bull Soc Fr Dermatol Syphiligr 1969 76 462 463 5405351 26 Lo Scocco G Di Lernia V Lombardi M Infantile acute hemorrhagic edema and rotavirus infection Pediatr Dermatol 2004 Sep-Oct 21 5 548 50 15461759 27 Bozaykut A Atay E Atay Z Acute infantile haemorrhagic oedema associated with hepatitis A Ann Trop Paediatr 2002 3 22 1 59 61 11926052 28 Savino F Lupica MM Tarasco V Acute Hemorrhagic Edema of Infancy: A Troubling Cutaneous Presentation with a Self-Limiting Course Pediatr Dermatol 2012 11 21 10.1111/pde.12004 29 Saraclar Y Tinaztepe K Adalioglu G Tuncor A Acute hemorrhagic edema of infancy (AHEI)-a variant of Henoch-Schönlein purpura or a distinct clinical entity? J Allergy Clin Immunol 1990 86 473 83 2229809