Kawasaki disease (KD) is characterized as an acute systemic vascular disease that affects mostly medium sized and small vessels. It is generally self-limited and the highest incidence occurs in children under five years of age [1]. Main symptoms include fever, conjunctivitis, skin and mucous membrane affection, and cervical lymphadenopahty. The name KD refers to the description of 50 children experiencing this form of vasculitis by Tomakisu Kawasaki in 1967. Generally, inflammatory changes to arteries of all body regions can be present, however, coronary arteries are most commonly affected [2]. In case of incomplete  picture of the disease the statement suggests the use of supportive laboratory testing and echocardiography to help detect patients who are at risk and do not meet the criteria for diagnosis. These were termed “incomplete” KD or “atypical” KD patients [3].

Clinical Outcomes

Possible sequel for KD include

• resolution without cardiac sequelae; 

• the development of coronary artery abnormalities 

• cardiac involvement, including myocarditis, aneurysm thrombosis, cardiac dysrhythmia, or myocardial infarction; and 

• KD recurrence in 3% of patients [4].

The differential diagnosis to rule out KD includes drug hypersensitivity, Stevens-Johnson syndrome, staphylococcal scalded skin syndrome, juvenile idiopathic arthritis, toxic shock syndrome, viral infection, and streptococcal scarlet fever [5].

The epidemic of severe acute respiratory syndrome coronavirus 2, causing COVID-19, has rapidly spread worldwide. In children, the respiratory involvement appears to have a more benign course [6].  Similarly to the Kawasaki disease, COVID-19 is recognized as a systemic vasculitis  affecting not only the lung but all organs, such as the myocardium.

However, a post-infectious process with delayed immune activation leading to a cytokine burst, responsible for fever, skin rash, cardiac failure and a major inflammatory syndrome, seems likely, similar to the presumed pathophysiology of ‘classical’ KD. Onset of the disease appears to occur 2 to 4 weeks after acute infection or exposure. Thus, in the majority of patients, nasal SARS-CoV-2 viral load was low or negative. Where antibodies could be assessed, all patients were IgG positive, suggesting SARS-CoV-2 infection in the previous 2 weeks or more. No concomitant viraemia was observed, Moreover, no other viral pathogens were identified, as assessed by multiplex PCR array. These findings suggest that SARS-COV-2 might act as a trigger of a post-infectious inflammatory disease. Viral elements have been found in endothelial cells infected by SARS-CoV-2, as well as an accumulation of inflammatory cells, apoptosis and pyroptosis. SARS-CoV-2-epithelial damage at an early stage may induce secondary local endothelitis, which may explain a delayed auto-inflammatory vasculitic phenotype with upregulation of IL-1β or IL-6, such as in KD [7].

Acute myocarditis was defined with the following criteria: elevated troponin, ST segment elevation or depression on electrocardiogram, regional wall motion abnormalities with decreased left ventricular function on echocardiography [8] Shock was defined as tachycardia and one of the following signs: arterial systemic hypotension, cold extremity, decrease peripheral pulse, capillary refill time > 3 s, oliguria [9].

Case

Yassin Saad, a previously healthy 3-and-a-half-year male child presented with five days of continuous, high-grade fever, temporarily relieved by antipyretics. Not associated with sweating or rigor. Condition was associated with non- purulent conjunctivitis. 

On the next day patient developed swelling in the small joints of the hands and feet, accompanied by poor feeding and decrease activity.

Two days later, faint erythematous macular rash appears on the trunk and lower limbs. There was history of contact with proved covid-19 positive cases in his family (his uncle and grandfather) before about 4 weeks from his illness.

On Examination

Yassin was irritable, ill looking. Febrile, with cracked lips and white strawberry tongue. Enlarged cervical lymph node.

Vital Signs

Temperature was 39.6 C, blood pressure 90/50 mmHg, RR 50/min, HR 180 beats/ min with gallop rhythm, Chest was clear with soft abdomen and no organomegaly.

Investigations

CBC shows total WBC 8,700 ×10³/L  with (N 77.5%, L 19.4%), HB 10.9 g/dl, platelets 165 ×10³/ML, CRP 200mg/dl, ESR 85mm/hr.

ECHO study shows picture of myocarditis (mild LV systolic dysfunction, LVEF 43%, trace posterior pericardial effusion).

He was admitted to the emergency room of central child teaching hospital, IgG and IgM against SARS-CoV-2 were detected on a blood sample taken on admission by the rapid test (positive IgG and He had been diagnosed as a case of post – covid -19 Kawasaki disease, complicated by myocarditis.

Treatment

IVIG 2 gm./kg over 12 hrs. prednisolone 2 mg/kg, and high dose aspirin

After 2 days of starting treatment Yassin had dramatic response with resolution of fever and improved general condition. New ECHO study revealed normal LVEF.

An increasing number of Kawasaki-like disease in patients with COVID-19 continue to be reported worldwide. This patient fulfilled all the criteria of typical KD, distributive shock and severe myocarditis in the context of a recent SARS-CoV-2 infection suggested by the detection of IgG and IgM against SARS-CoV-2. Myocarditis occurs frequently in KD with a prior study demonstrating up to 20% of patients with left ventricular systolic dysfunction [10].

In the following published paediatric studies [11,12,13,14,15,16] patients with acute myocarditis had either a covid 19 detection or positive serology with IgG present in many patients and we cannot exclude that activation.

Of immune complexes play a role in the development of COVID-19 myocarditis, while no other causes of myocarditis were identified just as our case. In these studies, most children with COVID-19 post-infective acute myocarditis were successfully treated with intravenous immunoglobulins and aspirin, immunoglobulins are well described and known to dampen hyperinflammation, and attenuate the immune complex-mediated response seen in patients with Kawasaki disease.

Further investigation of wide-ranging clinical features of COVID-19 in the pediatric population remains urgent. Possibility  of facing the emergence of COVID-19 post-infective complications is high, urges us to set a systematic clinical, biological and echocardiographic follow-up of all patients who had infected with COVID-19.

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3. Saundankar, J. et al. “The epidemiology and clinical features of Kawasaki disease in Australia.” Pediatrics, vol. 133, no. 4, 2014, pp. e1009–e1014.

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10. Printz, B.F. et al. “Noncoronary cardiac abnormalities are associated with coronary artery dilation and with laboratory inflammatory markers in acute Kawasaki disease.” Journal of the American College of Cardiology, vol. 57, no. 1, 2011, pp. 86–92.

11. Grimaud, M. et al. “Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children.” Annals of Intensive Care, vol. 10, no. 1, 2020, p. 69.

12. Belhadjer, Z. et al. “Acute heart failure in multisystem inflammatory syndrome in children in the context of the global SARS-CoV-2 pandemic.” Circulation, vol. 142, no. 5, 2020, pp. 429–436.

13. Riphagen, S. et al. “Hyperinflammatory shock in children during COVID-19 pandemic.” The Lancet, 2020.

14. Whittaker, E. et al. “Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.” JAMA, vol. 324, no. 3, 2020, pp. 259–269.

15. Ramcharan, T. et al. “Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): cardiac features, management and short-term outcomes.” Pediatric Cardiology, vol. 41, no. 7, 2020, pp. 1391–1401.

16. Belot, A. et al. “SARS-CoV-2-related paediatric inflammatory multisystem syndrome: an epidemiological study.” Eurosurveillance, vol. 25, no. 22, 2020.