December 2019 marked the start of the coronavirus disease 2019 (COVID-19) outbreak, becoming a global pandemic only months later, with numbers growing in an exponential manner. To date, there are approximately 37 million cases worldwide,1 with children accounting for 1%–5% of these cases.2 Pediatric cases are mostly characterized by asymptomatic or mild disease, with 5.2% and 0.6% having severe and critical disease, respectively.2 These numbers may even be underestimates due to under diagnosis of mild and asymptomatic infected children. While the adult population primarily display an acute febrile respiratory illness, children have developed multisystem inflammatory manifestations including vasculitis syndromes, namely Kawasaki-like disease.3,4 We present a novel case of a 3-year-old male who developed Henoch–Schonlein Purpura (HSP) in the setting of COVID-19 infection.
The patient is a 3-year-old male with a history of surgically corrected Hirschsprung disease, for which he receives daily metronidazole and as-needed enemas. He is immunized according to national standards and has no known allergies.
He presented to the emergency department with acute onset purpuric rash involving his lower limbs, generalized abdominal pain and nonbilious emesis. He had no history of fever and denied intercurrent or preceding illness. The patient’s father and brother were diagnosed with COVID-19 2 days before presentation.
On presentation to the emergency department, he was afebrile, heart rate 87 beats/min, normotensive (106/87 mm Hg), with oxygen saturations 100% on room air. He was lethargic, pale and mildly dehydrated. There were no signs of respiratory distress, neck rigidity or other signs of meningeal irritation. A palpable purpuric rash extended from the dorsum of his feet to the buttocks and elbows (Fig. 1). Apart from mild generalized tenderness on palpation, the abdomen was soft without signs of peritoneal irritation. Cardiac, pulmonary, neurologic, musculoskeletal and lymph node examinations were unremarkable.
Complete blood count showed normal white cell count (9.8 × 109/L), microcytic anemia (hemoglobin 11.8 g/dL) and mild thrombocytosis (4.9 × 109/L). He had normal liver and renal function. Venous blood gases demonstrated mild metabolic acidosis. He had no proteinuria or hematuria on urinalysis. Blood cultures were drawn and a nasopharyngeal swab for SARS-CoV-2 was taken. He received empirical antibiotic therapy and a fluid bolus.
He was diagnosed with HSP, fulfilling 2 clinical criteria (palpable purpura and abdominal pain), without renal or musculoskeletal involvement. He was admitted to the general pediatric department for further medical evaluation.
During his admission, he was treated conservatively with nonsteroidal anti-inflammatory drugs and parenteral fluid hydration. Reverse transcriptase-polymerase chain reaction (RT-PCR) of a nasopharyngeal swab was positive for SARS-CoV-2. Blood cultures were negative after 48 hours. An abdominal ultrasound demonstrated increased bowel wall thickness localized to the left abdomen, consistent with the provisional diagnosis of HSP. Plain abdominal radiography similarly showed a thickened bowel wall. Over the course of his admission, his vomiting ceased and abdominal pain gradually improved. He was discharged home on day 4 and advised to continue analgesia and to self-isolate in accordance with the national COVID-19 protocol.
The subsequent day he returned to the emergency department due to worsening abdominal pain. Vital signs were within the normal range. Physical examination showed worsening of the purpuric rash on his upper limbs. His abdomen was tender without signs of peritoneal inflammation. Repeat blood panels were drawn with no significant changes. He was started on methyl prednisone 2mg/kg and was readmitted to the general pediatric ward. The patient’s abdominal pain responded well to glucocorticoid therapy and he was discharged home after 3 days of steroids treatment.
This case of classic HSP as the clinical presentation of COVID-19 is the first such report to the best of our knowledge. HSP is an immune-mediated vasculitis involving IgA deposition in the blood vessel walls, which primarily affects children 3–15 years of age.5 The pathophysiology is influenced by immunologic, genetic and environmental mechanisms with most cases occurring in the context of an intercurrent upper respiratory tract infection.
The association between vasculitis and COVID-19 has already been described. The current literature reports cases of Kawasaki disease occurring with SARS-CoV-2 infection. Jones et al3 presented a case of a 6-month-old female with classic Kawasaki disease and a concurrent positive RT-PCR test for COVID-19. Cases have also been reported after seroconversion with negative nasopharyngeal swabs, representing a later phase association.4 Moreover, the incidence of Kawasaki disease during the pandemic increased by 30-fold compared with the preceding year.6
One of the proposed mechanisms of this association is an ACE2-driven inflammatory response with a subsequent cytokine storm. ACE2 transmembrane protein receptors are located in embryonic endothelial structures including the vascular endothelium. The single-stranded RNA SARS-CoV-2 virus enters the human cell by binding to these receptors, subsequently inducing a systemic inflammatory response.7 This widespread endothelial dysfunction underlies the pathophysiology of Kawasaki disease.
IgA vasculitis associated with COVID-19 infection has been documented in 2 adult patients. Suso et al8 describe a 78-year-old male that developed cutaneous vasculitis, arthritis and nephritic syndrome 3 weeks following respiratory disease due to PCR-confirmed COVID-19 infection. At the time of readmission, PCR for SARS-CoV-2 was negative; however, serology was positive. Renal biopsy was consistent with IgA vasculitis.8 The second case described a 24-year old male with cutaneous, musculoskeletal, and gastrointestinal manifestations of HSP; however, he was afebrile and without respiratory disease.9 Skin biopsy showed IgA vasculitis. Dissimilar to the previous case, PCR was positive for SARS-CoV-2. Serology for COVID-19 was positive for IgA and negative for IgG. Both cases were successfully treated with systemic corticosteroids.
Given the proposed hypothesis that Kawasaki disease is a form of IgA vasculitis,10 it is understandable that the vasculitic manifestations of COVID-19 lie on the spectrum between these 2 diseases.
Moreover, SARS-CoV-2 IgA is the first immunoglobulin to rise following infection, strengthening the possible association between IgA vasculitis and COVID-19 infection.9
Of note, there is no diagnostic test to prove the association between HSP and COVID-19 infection. However, it can be postulated that in this otherwise healthy child, without any intercurrent febrile or respiratory illnesses during the preceding month, that COVID-19 was a likely trigger for the systemic vasculitis described.
We report a novel case of HSP during an active COVID-19 infection. With the increasing spread of the infection worldwide and the paralleled increase in vasculitis cases in the pediatric population, we suspect to see further cases of COVID-19-associated HSP.
1. Johns Hopkins University. Coronavirus Resource Center. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins University and Medicine. 2020. Available at: https://coronavirus.jhu.edu/map.html
. Accessed October 13, 2020.
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3. Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020; 10:537–540
4. Licciardi F, Pruccoli G, Denina M, et al. SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome: a novel COVID phenotype in children Pediatrics. 2020; 146:e20201711
5. Dyga K, Szczepańska M. IgA vasculitis with nephritis in children. Adv Clin Exp Med. 2020; 29:513–519
6. Viner RM, Whittaker E. Kawasaki-like disease: emerging complication during the COVID-19 pandemic Lancet. 2020; 395:1741–1743
7. AbdelMassih AF, Kamel A, Mishriky F, et al. Is it infection or rather vascular inflammation? Game-changer insights and recommendations from patterns of multi-organ involvement and affected subgroups in COVID-19 Cardiovasc Endocrinol Metab. 2020; 9:110–120
8. Suso AS, Mon C, Alonso IO, et al. IgA vasculitis with nephritis (Henoch-Schönlein purpura) in a COVID-19 patient Kidney Int Rep. 2020; 5:2074–2078
9. Allez M, Denis B, Bouaziz JD, et al. Covid-19 related IgA vasculitis Arthritis Rheumatol. 2020; 72:1952–1953
10. Noval Rivas M, Wakita D, Franklin MK, et al. Intestinal permeability and IgA provoke immune vasculitis linked to cardiovascular inflammation. Immunity. 2019; 51:508–521.e6