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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 4  |  Page : 241-244

Acute Hemorrhagic Edema following COVID-19 Infection

1 Department of Pediatrics, Tokat State Hospital, Tokat, Turkey
2 Department of Pediatric Nephrology, Kirikkale University Faculty of Medicine, Kirikkale, Turkey

Date of Submission08-Sep-2022
Date of Decision28-Oct-2022
Date of Acceptance29-Oct-2022
Date of Web Publication29-Nov-2022

Correspondence Address:
Dr. Cansu Kaymakci
Kirikkale University Faculty of Medicine Research Hospital, Kirikkale University Campus, 71450 Yahsihan, Kirikkale
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_212_22

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Background: Acute hemorrhagic edema of infancy (AHEI) is an immune complex-mediated leukocytoclastic vasculitis. Despite its worrisome appearance, it has a benign disease course with rare systemic involvement. Clinical Description: A 25-month-old male patient was brought to the pediatric outpatient clinic with a pink oval-shaped plaque-like rash all over the body and edema on the lower extremities and left auricle. The child was diagnosed as a case of coronavirus disease 2019 (COVID-19) 5 days before the present complaints. History and physical examination were otherwise unremarkable. Because of the patient's age, the purpuric appearance of lesions, distribution pattern of the rashes, localized edema, and no end-organ involvement, a possibility of AHEI, triggered by COVID-19, was considered and the patient was evaluated for the same. Management and Conclusions: The patient recovered in 15 days with no end-organ involvement. He was advised to continue regular follow-ups to look for long-term complications. AHEI is a benign condition which may occur in children following COVID-19 infection. It is essential to recognize the condition to avoid unnecessary investigations and treatment.

Keywords: Coronavirus disease 2019, immune-complex, leukocytoclastic vasculitis, purpura

How to cite this article:
Kaymakci C, Kandur Y. Acute Hemorrhagic Edema following COVID-19 Infection. Indian Pediatr Case Rep 2022;2:241-4

How to cite this URL:
Kaymakci C, Kandur Y. Acute Hemorrhagic Edema following COVID-19 Infection. Indian Pediatr Case Rep [serial online] 2022 [cited 2023 Jan 30];2:241-4. Available from: http://www.ipcares.org/text.asp?2022/2/4/241/362245

Coronavirus disease 2019 (COVID-19) has become a pandemic during the last 2 years. Many cases have been described in the pediatric age group with various skin manifestations such as erythema multiforme-like lesions, vesicular, maculopapular, urticarial, and papulosquamous lesions.[1] Acute hemorrhagic edema of infancy (AHEI) is an immune complex-associated leukocytoclastic vasculitis known to be a rare disease in children.[2] The age of onset is usually between 4 and 24 months. Clinical manifestations include mild fever, edema of the face and lower extremities, diffuse purpura, and ecchymosis that usually develop rapidly over 24–48 h. An association with upper respiratory tract infections and/or gastroenteritis has been reported. There are also case reports of AHEI following many vaccinations.[3],[4]

In this case report, we aimed to report a pediatric case of AHEI associated with COVID-19 infection, which is rarely described in the literature. Differential diagnosis of purpuric skin lesions in children is wide and consists mostly of infectious and rheumatological diseases that require extensive investigations and treatment. Recognition of AHEI in the early course of clinical presentation can save both the patient and physician from that tiring, unnecessary and expensive process.

  Clinical Description Top

A 25-month-old boy presented to the pediatric outpatient clinic with a pink oval-shaped plaque-like rash all over his body for 2 days. The rash started on the 5th day of COVID-19 diagnosis which was made by antigen test. The patient only had complaints of fever and mild cough before the appearance of the rash. There was no history of diarrhea, change in behavior and level of consciousness, exposure to toxic substances or drug overdose, or recent vaccination. There was no history of similar lesions in the past. On day 1 of the rash, the child was advised antihistaminics considering the possibility of acute urticaria following intake of some over-the-counter medicines but found to have no benefit.

In the present examination, vital signs revealed a body temperature of 37.0°C, respiratory rate of 24/min, mean heart rate of 95/min, and blood pressure of 100/70 mmHg. Peripheral pulses were normal and easily palpable from both the upper and lower extremities. Oxygen saturation was 99% in the right hand. His body weight was 13 kg (lying between the 25th and 50th percentile), length was 87 cm (lying between the 50th and 75th percentile), and head circumference of 48.5 cm (lying at the 50th centile). The patient was a well-nourished infant with no apparent respiratory distress. On general physical examination, there was no pallor, icterus, conjunctival congestion, cyanosis, or lymphadenopathy. There were widespread maculopapular, oval-shaped, plaque-like rashes on the arms, legs, face, and gluteal region, which were also present on the trunk [Figure 1]. The lesions were not blanchable regarding oppression. They were painless and nonpruritic. Edema and mild ecchymotic rashes were observed on the left big toe and on the left auricle [Figure 2]. On systemic examination, respiratory system examination revealed bilateral normal vesicular breath sounds, with no added sounds. On abdominal examination, there was no organomegaly and bowel sounds were well heard. Other systemic examinations including cardiovascular and central nervous system examinations were also normal. Henöch–Schönlein purpura (HSP) and urticarial vasculitis were considered differential diagnosis. Younger age, the nature of lesions, and the absence of other organ involvement were against the diagnosis of HSP in our case. Persistant erythematous papules and plaques and lack of treatment response to antihistamines in our case were typical for urticarial vasculitis, but lack of systemic symptoms and no itching or pain on skin lesions were points against the diagnosis of urticarial vasculitis.
Figure 1: Maculopapular rashes on upper, lower extremities and trunk

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Figure 2: Edema and ecchymosis on left auricle

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Laboratory tests revealed mild leukocytosis (13840/mm3 (differential count: neutrophils: 47.1%, lymphocytes: 44%, and eosinophils: 0.42%). C-reactive protein was 2 mg/L. Coagulation parameters (international normalized ratio: 0.96 and activated partial thromboplastin time: 31.9 s), liver (alanine transaminase: 19 U/L and aspartate transaminase: 47 U/L), and renal function tests (serum creatinine: 0.4 mg/dL and blood urea: 37 mg/dL) were within normal limits for age. There was no electrolyte imbalance (sodium: 139 mmol/L, potassium: 4.2 mmol/L, and calcium: 9.3 mg/dL). On the 2nd day, the rash acquired a typical purpuric appearance, especially on the lower and upper extremities [Figure 3]. Edema and ecchymosis localized on the auricle and foot and also became more prominent. The patient's age, purpuric appearance, the distribution pattern of the rashes, edema involving the auricle and foot, and the absence of end-organ involvement were indicative of a diagnosis of AHEI, triggered by COVID-19. Histopathologic examination of skin lesions was unavailable in our hospital setting, so a clinical diagnosis of AHEI was made with the above findings. Diagnosis of AHEI is majorly based on clinical grounds. In doubtful cases, the skin biopsy may be of great value for diagnosis.[2] The parents were counseled about the expected course of the disease. In outpatient follow-up, rashes and edema disappeared on the 15th day.
Figure 3: Purpuric lesions on the left upper extremity

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  Discussion Top

AHEI is classically characterized by rapidly developing purpuric lesions involving the face, extremities, and bilateral auricles. The appearance of bilateral auricular edema and purpura in a well, nontoxic child should raise clinical suspicion of AHEI.[5] Extracutaneous manifestations may develop in <10% of patients. Glomerulonephritis, abdominal pain, arthralgia, testicular torsion, and invagination are some of these findings.[6] The diagnosis is made mainly on the basis of clinical findings and skin biopsy is generally not required. If a biopsy is performed, IgA deposition can be expected in one-third of the patients by immunofluorescent staining. Histopathologic findings are compatible with leukocytoclastic vasculitis.[7] Laboratory tests do not reveal any disease-specific findings. Leukocytosis, thrombocytosis, increased CRP, and sedimentation rate may be observed.[8]

AHEI has been reported after specific infections including tuberculosis, Coxsackie virus, Campylobacter, rotavirus, hepatitis A virus, cytomegalovirus, and pneumococcal bacteremia.[3],[8] It has also been reported after many vaccinations. In a literature review of 195 AHEI case reports, 18 children developed AHEI in <15 days after immunization, including combined vaccination against diphtheria, pertussis, and tetanus with pr without poliomyelitis, combined vaccination against measles, mumps, and German measles; concurrent vaccination against measles, mumps, German measles, and chickenpox; and isolated vaccination against Haemophilus influenzae type B, measles, tuberculosis, or smallpox.[8] Cases of AHEI have also been reported after the influenza vaccine.[4]

AHEI may be confused with urticarial vasculitis in appearance but can be differentiated based on clinical features. Urticarial vasculitis is often associated with pruritus and the presence of systemic features such as arthralgia, lymphadenopathy, and abdominal pain.[2]

The appearance of AHEI can also resemble HSP.[9] The rash in HSP is in the form of palpable purpura starting as pink macules and developing into petechiae or larger ecchymoses mainly in children between 3 and 10 years. HSP skin lesions are usually symmetric and occur in the gluteal region, lower extremities, and on pressure points. Musculoskeletal, gastrointestinal, renal, and neurologic manifestations are common in HSP. Unlike the rash of HSP, which is usually smaller in size, the rash in AHEI appears as ecchymotic changes, large purpuras, and edema and involves the face, extremities, and scrotum.[10] In our patient, clinical differentiation was made considering these differences.

A large number of skin lesions have been reported in association with COVID-19 infection. In a systematic review that examined the dermatologic manifestations of COVID-19 in children, chilblain-like lesions were the most common cutaneous manifestation in children and adolescents (67.5% of patients). The erythema multiforme-like lesions affected 31.7% of patients and the varicella-like lesions to 0.8% of cases.[11] Chilblain-like lesions, also known as COVID toes, are well-described dermatoses characterized by erythema and swelling localized to acral areas, occurring most commonly on the toes and fingers.[8],[9],[10],[11],[12],[13],[14],[15] The second-most common cutaneous manifestation related to COVID-19 was erythema multiforme-like lesions. Erythema multiforme is an acute, self-limited, manifestation that is considered to be a type IV hypersensitivity reaction. Lesions often start on the extremities and evolve into the pathognomonic target or iris lesions, within a 72-h period.[11],[12] AHEI has also been reported in association with COVID-19.[13],[14],[15] AHEI develops as a result of endothelial damage.[12] To the best of our knowledge, the number of cases of AHEI that have been shown to be triggered by COVID-19 has been very limited in the literature.[13],[14],[15] All cases, as in our case, showed complete recovery without any organ involvement [Table 1]. Acute infantile hemorrhagic edema is a self-limiting disease that usually resolves without the need for treatment. It is also important to be aware that this picture may also occur in children followed up for COVID-19 to avoid unnecessary investigations and treatments in the follow-up of patients.
Table 1: Coronavirus disease 2019-associated acute infantile hemorrhagic edema cases in literature

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Colonna C, Restano L, Monzani N, et al. Rare and common manifestations of COVID 19 in children. JEADV Clin Pract 2022;1:21-30.  Back to cited text no. 1
Alhammadi AH, Adel A, Hendaus MA. Acute hemorrhagic edema of infancy: A worrisome presentation, but benign course. Clin Cosmet Investig Dermatol 2013;6:197-9.  Back to cited text no. 2
Binamer Y. Acute hemorrhagic edema of infancy after MMR vaccine. Ann Saudi Med 2015;35:254-6.  Back to cited text no. 3
Ferreira O, Antunes I, Cruz MJ, et al. Acute hemorrhagic edema of childhood after H1N1 immunization. Cutan Ocul Toxicol 2011;30:167-9.  Back to cited text no. 4
Chesser H, Chambliss JM, Zwemer E. Acute hemorrhagic edema of ınfancy after coronavirus ınfection with recurrent rash. Case Rep Pediatr 2017;2017:5637503.  Back to cited text no. 5
Risikesan J, Koppelhus U, Steiniche T, et al. Methylprednisolone therapy in acute hemorrhagic edema of infancy. Case Rep Dermatol Med 2014;2014:853038.  Back to cited text no. 6
Caksen H, Odabaş D, Kösem M, et al. Report of eight infants with acute infantile hemorrhagic edema and review of the literature. J Dermatol 2002;29:290-5.  Back to cited text no. 7
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;59:684-95.  Back to cited text no. 8
Jindal SR, Kura MM. Acute hemorrhagic edema of infancy-a rare entity. Indian Dermatol Online J 2013;4:106-8.  Back to cited text no. 9
[PUBMED]  [Full text]  
Dongre A, Adhe V, Kothari D, et al. Acute hemorrhagic edema of infancy: A report of two cases. Indian J Dermatol Venereol Leprol 2012;78:121.  Back to cited text no. 10
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Pasquini Neto R, Mazzo FA, Vieira FA, et al. COVID-19 cutaneous manifestations in children and adolescents: A systematic review. Rev Paul Pediatr 2022;40:e2021134.  Back to cited text no. 11
Landa N, Mendieta-Eckert M, Fonda-Pascual P, et al. Chilblain-like lesions on feet and hands during the COVID-19 pandemic. Int J Dermatol 2020;59:739-43.  Back to cited text no. 12
Saraiva BM, Lobato MB, Santos E, et al. Acute haemorrhagic oedema of infancy as a manifestation of COVID-19. BMJ Case Rep 2021;14:e241111.  Back to cited text no. 13
Jari M. Coronavirus disease 2019 and acute hemorrhagic edema of ınfancy. Case Rep Infect Dis 2022;2022:7610402.  Back to cited text no. 14
Atay N, Kara Ulu N, Polat M. Acute haemorrhagic oedema of ınfancy as a manifestation of COVID-19 ınfection. J Paediatr Child Health 2022;58:1282-3.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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