European Journal of Cardiovascular Medicine

Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 led to serious and life-threatening disease in previously healthy children and adolescents. Kawasaki’s disease (KD) is a vasculitis that normally presents with high fever and acute mucocutaneous inflammation in children less than 5 years of age.^1,2

Although typically a self-limiting condition, some children and adolescents may have severe complications including coronary artery aneurysms, myocardial dysfunction, and thrombotic events.^3,4

Recent reports in many countries suggested that many of the pediatric patients with this hyper-inflammatory syndrome had fever with significant inflammation and mucocutaneous manifestations like those of Kawasaki’s disease (KD), a rare vasculitis of childhood that can cause coronary-artery aneurysms. Some children had features of toxic shock syndrome (TSS) and myocarditis with cardiogenic shock. One of the initial challenges many clinicians faced was differentiating patients of MIS-C versus Kawasaki disease (KD) or toxic shock syndrome (TSS).^4-7

Kawasaki’s disease (KD), can be stratified into classic or incomplete, depending on the number of clinical manifestations of the disease like fever for 5 days with conjunctival injection, rash, erythema& edema of the hands and feet, cervical lymphadenopathy and oral mucosal changes.^7,8

The incomplete Kawasaki disease diagnosis includes fever with 2–3 of the principal features. On the other hand, Toxic shock syndrome (TSS) is a potentially lethal disease resulting from the release of bacterial toxins, it is characterized by fever, rash, shock, vomiting & diarrhea and is treated usually by hemodynamic stabilization and antibiotics.^2,9

Like Kawasaki’s disease, MIS-C is a syndrome with a range of clinical manifestations and an absence of pathognomonic findings or laboratory tests. Although the cause of Kawasaki’s disease remains unknown, a preceding or active infection has always been suspected.^1,10

Unlike Kawasaki’s disease, however, MIS-C has been suggested in initial reports to predominantly affect adolescents and children more than 5 years of age and to be associated with more frequent cardiovascular manifestations.^7,11

There is a paucity of data regarding the Correlation of Kawasaki disease & Multisystem Inflammatory Syndrome in this hilly region. Against this backdrop, the study was conducted to describe the Correlation of Kawasaki disease & Multisystem Inflammatory Syndrome among children admitted as a case of MIS-C in Indira Gandhi Medical College, Shimla.

Aims & objectives

To evaluate the Correlation of Kawasaki disease & Multisystem Inflammatory Syndrome in children admitted as a case of MIS-C.

The study was conducted at the Department of Pediatrics, Indira Gandhi Medical College, Shimla, Himachal Pradesh, from January 2021 to July 2021. This was a cross-sectional, descriptive, retrospective study, all children who fulfilled the WHO definition of MIS-c were included. Operational definition for a case of MIS-C¹¹ , Children and adolescents 0–19 years of age with fever > 3 days, AND two of the following: a) Rash or bilateral non-purulent conjunctivitis or mucocutaneous inflammation signs (oral, hands or feet). b) Hypotension or shock. c) Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP), d) Evidence of coagulopathy (by PT, PTT, elevated d-Dimers). e) Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain). AND Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin. AND No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes. AND Evidence of COVID-19 (RT-PCR, antigen test, or serology positive), or likely contact with patients with COVID-19.

Kawasaki Disease criteria: AHA guidelines for the diagnosis of KD (2004): Fever persisting at least 5 days with, At least four of the five principal clinical features: Changes in extremities Acute: Erythema of palms, soles; edema of hands, feet Subacute: Periungual peeling of fingers and toes in weeks 2 and 3, Polymorphous exanthema (diffuse maculopapular, urticarial, erythroderma, erythema‐multiforme like, not vesicular or bullous), Bilateral bulbar conjunctival injection without exudates, Changes in lips and oral cavity: erythema, lips cracking, strawberry tongue, diffuse injection of oral and pharyngeal mucosae, Cervical lymphadenopathy (> 1.5 cm diameter), usually unilateral. Exclusion of other diseases with similar findings (e.g., scarlet fever, viral infections like measles, adenovirus, Stevens‐Johnson syndrome, toxic shock syndrome)

Permission was obtained from the institutional ethics committee of Indira Gandhi Medical College Shimla in Himachal Pradesh. The data were collected from the record files of admitted children, compiled and entered in MS Excel, and analyzed using appropriate statistical tools in software Epi info V7 by applying the appropriate statistical test in terms of frequencies and percentage.

A total of 31 children were diagnosed and admitted as MIS-C in the pediatric ward of Indira Gandhi Medical College Shimla in Himachal Pradesh between Jan 2021- July 2020.

Mean age of the children diagnosed as MIS-C was 7.12±4.78 years. Maximum 12 (38.7%) were of age group 5-10 years followed by 10 (32.3%) of age group 6-10 years, 8 (25.8%) of 11-15 years and 1 (3.2%) of 15-19 years age group. Of the total 16(51.6%) were males while 15(48.4%) were females.29(93.5%) belonged to the rural area while 2(6.5%) to the urban area. (Table-1)

Table-1: Socio-Demographic variables of MISC-C patients

Out of the 31 cases of MIS-C, 16.13%(n=5) presented as typical Kawasaki disease, with none as incomplete or atypical KD. All of them were males. 3 children were between 0-5 years of age while 2 patients were in the older age group(6-10yrs), fulfilling all the 5 KD criteria, which was unusual. (Figure -1)

Figure-1: Age and gender distribution of MIS-C presenting as Kawasaki Disease

ECG was normal in all these 5 children. Echo was normal in 4 cases and 1 patient had a low ejection fraction on ECHO. All of them received Intravenous Immunoglobulin (IVIG),1 Child received Low molecular weight Heparin (LMWH), Methylprednisolone in low doses was administered to 4 children while 1recieved high dose of Methylprednisolone. 4 children received aspirin, oxygen therapyto 3 children, ventilatory support to 1 child while inotropic support was required by 2. All 5 children were discharged after full recovery. (Table-2)

Table-2: Treatment Modalities in Kawasaki Cases

Thousands of cases of children and adolescents with MIS-C have been diagnosed during this COVID-19 pandemic.Understanding the epidemiology, the clinical course of the multisystem inflammatory syndrome in children (MIS-C), and its association with Kawasaki disease is warranted, given the clinical and public health implications of this syndrome.¹²

Mean age of the children diagnosed as multisystem inflammatory syndrome in children (MIS-C) was 7.12±4.78 years. Maximum 12 (38.7%) were of age group 5-10 years followed by 10 (32.3%) of age group 6-10 years, 8 (25.8%) of 11-15 years and 1 (3.2%) of 15-19 years age group. Among the total 16(51.6%) were males while 15(48.4%) were females.29(93.5%) belonged to rural areas while 2(6.5%) to urban area.

Among these 31 cases of MIS-C, 5 children presented as Kawasaki disease.All these 5 children were males. 3 were between 0-5 years of age while 2were between 6-10 years of age. Similar types of results were observed in the studies done by Levi Hoste et al¹³, Fouriki A et al¹⁴, Leora R et al¹⁵ and M. Ahmed et al.¹⁶

ECG was normal in all these 5 children. Echo was normal in 4 cases, but, 1child had low ejection fraction, but none had any evidence of any coronary involvement. All of them received IVIG, while one child also received LMWH. Methylprednisolone in low doses was given to 4 children, while in 1 received high doses of Methylprednisolone was given. Aspirin was given to 4 children. Oxygen therapywas required in 3 cases, ventilatory support was given to one, while inotropic support was given to 2 patients. All 5 patients made a full recovery and were discharged. Similar types of results were observed in manystudies donein various countries.^11-16

International reports of COVID- 19   associated severe complications in children began in early April 2020 when predominantly healthy children and adolescents were hospitalized with cardiogenic shock or Kawasaki disease-like manifestations temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease.^7,15,17

While different, MIS-C disease has some of the similar symptoms as other rare childhood inflammatory conditions such as Kawasaki disease and toxic shock syndrome. Children with MIS-C may also have thrombosis, poor cardiac function, or kidney injury. The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), or have often an acute abdominal manifestation.^17-19

Cardiovascular complications such as ventricular dysfunction and coronary artery aneurysms triggered recommendations for immune-modulatory treatments, including intravenous immunoglobulin (IVIG), methylprednisolone,Aspirin, LMWH,etcand recommendations for intensive cardiac observation in hospitals .^15-19

Many MIS-C patients showed clinical features similar to KD or TSS, so MIS-C may be within the spectrum of TSS. Clinicians should suspect MIS-C if patients present with fever or KD-like features e.g., skin rash, conjunctivitis, oral mucosa changes, hand or foot edema), or gastrointestinal symptoms e.g., abdominal pain, vomiting, diarrhea and demonstrate evidence of SARS-CoV-2 infection. Given the frequent overlap of clinical manifestations between MIS-C and those of Kawasaki disease (KD), most of the patients with MISC-C have generally been treated with the standard therapeutic protocols used in Kawasaki disease. Despite accompanying shock andcardiac dysfunction, most MIS-C patients responded well to treatments & recovered without sequelae if adequate and timely treatment was given.

The major limitation of our study was the short duration and the small number of casesin the study and we studied only the children who were either referred or admitted to the pediatric ward, some cases may have been missed in the periphery or presented as incomplete or atypical cases which might have bee missed.

Conflict of Interest: None

Funding: None

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