Classic Kawasaki Disease Research Articles

6 Evaluation of a Standardized Kawasaki Disease Protocol for Management and Follow-Up

Abstract Background In 2017, it was recognized that there was significant variation in the management and follow-up of Kawasaki disease (KD) at our institution, resulting in inefficient use of hospital resources and patient confusion. A multidisciplinary team from cardiology, rheumatology, emergency medicine, infectious diseases (ID), and general paediatrics created a standardized protocol distributed on October 10th, 2019. With the evolution of multisystem inflammatory syndrome in children associated with SARS-COVID 19 (MISC), we expanded our protocol in December 2021 to include a 1-week follow-up echocardiogram (echo). Objectives It has been 3 years since the KD standardized protocol was implemented. As a result, we seek to evaluate its effectiveness in improving patient care, specifically in the patients with normal coronary arteries. Design/Methods We reviewed the cardiology echo database to define patients who had an echo performed for KD (January 1, 2020-August 17, 2022). These patients were reviewed in the electronic hospital record to define those with a discharge diagnosis of KD. Results Of the 138 patients defined, 47 patients were discharged with KD; normal coronary arteries (N=38) were seen in 81% (38/47). Classic KD: 47% (18/38); incomplete KD: 53% (20/38); 13% (5/38) were diagnosed with both MISC and KD. Average age: 3.4 years (3 months to 9.5 years). We observed that rheumatology was consulted in 89% (34/38), cardiology in 100%, and ID in 50% (19/38). All patients were treated with low-dose acetylsalicylic acid (38/38), and the majority were treated with intravenous immunoglobulin, 92% (35/38). Some patients were treated with steroids, 26% (10/38). Average length of stay: 4.8 days (1-18 days). Twenty-one patients were seen from when we initiated performing a 1-week echo. In addition to the existing protocol, 24% (5/21) of cases missed having a 1-week follow-up echo because the cardiologist was not aware of the practice. Eighty-nine% (34/38) had their 6-week follow-up echo and follow-up in the post-hospitalization clinic (PHC) at the appropriate time. Patients were incorrectly scheduled to see the cardiologist in 13% (5/38) and the PHC in 3% (1/38) cases. Conclusion With the implementation of a standardized management and follow-up protocol for KD, our patients are now guaranteed follow-up with access to effective patient-centred care in a streamlined manner that targets appropriate use of resources. A satisfaction survey should be performed to inquire if families are pleased with this process.

Novel Score to Predict Immunoglobulin Resistance in Kawasaki Disease.

To evaluate existing scoring systems and develop a new model to predict intravenous immunoglobulin (IVIG) resistance in patients with Kawasaki disease (KD). A retrospective cohort study performed between 2004 and 2017 identified 115 patients treated with IVIG for classic or incomplete KD. In our practice, IVIG resistance was defined as fever for > 24h and patients were divided into responders and non-responders. A univariate analysis was performed to identify independent predictors of IVIG resistance. The predictors were combined into a new scoring system and compared with existing scoring systems. Sixty-five patients had classic KD and 50 had incomplete KD. Among the 115 patients, 80 (69.6%) responded and the remaining 35 were resistant (30.4%) to IVIG. Of the 35 resistant patients, 16 patients had incomplete KD. Hispanic children comprised 43% of our sample population. Coronary artery abnormalities developed in 14 of the 35 IVIG-resistant patients (39%). Univariate analysis showed that IVIG-resistant patients were older and present with lower platelets, potassium, and creatinine (P < 0.05). Multivariate logistic regression analysis used platelets, potassium, body surface area (BSA), and creatinine to devise the Las Vegas Scoring System (LVSS), which demonstrated a sensitivity of 76.2% and a specificity of 68.6%. Compared to published data, we observed a higher rate of IVIG resistance and coronary artery abnormalities in our patient population. The LVSS (using platelets, potassium, BSA, and creatinine) showed higher specificity and comparable sensitivity to other scoring systems devised to predict IVIG resistance.

Epidemiological Profile and Management of Kawasaki Syndrome at Rabat Children’s Hospital: A retrospective study from Morocco

Kawasaki disease (KD) is a common pediatric vasculitis with a risk of coronary artery aneurysm. In this report, we review some particularities of KD disease, especially coronary involvement, and highlight its aspects during the COVID-19 epidemic which saw the emergence of a syndrome named multisystem inflammatory syndrome in children (MIS-C). Because of its many similarities with KD, MIS-C is often referred to as Kawasaki-like disease (KLD) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).We report on a retrospective study on the different epidemiological, clinical, and evolutionary aspects of KD and the coronary involvement resulting from this disease before and after the pandemic. The study is based on the echocardiography records of the P4 Department at Rabat Children’s Hospital, from January 2002 to December 2021. A total of 379 patients were diagnosed with KD during that period. This includes 47 cases that were reported during the first year of the COVID-19 epidemic in Morocco (March 2020). Echocardiography results for our series show that cardiac complications wererelatively more frequent among KD patients during the COVID-19 period, perhaps because they were relatively older (67 months on average) than classic KD patients (37 months on average). However, all patients had a favorable outcome after treatment with a combination of intravenous immunoglobulin (IVIG) and aspirin. The few patients who did not respond to standard treatment received corticosteroids, and no mortality occurred. We conclude that as far as cardiac complications,KD, KLD, and MIS-C are the same core disease that is triggered under different conditions for different age groups.The emergence of the Sars-Cov-2 virus changed the epidemiologic profile of KD but not its treatment. Insights from this study would help in the decision to initiate targeted immunotherapy quickly and reduce the risk factors associated with KD.

COVID-19 and Kawasaki Disease in a 4-year-old Child: A Case Report

Background and Aim: Although Kawasaki disease syndromes have previously been linked to other viral infections, patients with higher levels of pro-inflammatory markers than different cohorts reflect a particularly strong immunological reaction to SARS-CoV-2. This article examines a comorbidity between Kawasaki and COVID-19 in a 4-year-old child who complained of fever. Case Report: We describe the case of a 4-year-old child admitted and diagnosed with classic Kawasaki disease, who also screened positive for COVID-19 in the setting of fever and minimal respiratory symptoms. The patient has been treated per treatment guidelines with intravenous immunoglobulin and high-dose aspirin and subsequently effervesced with a resolution of her clinical symptoms, with instruction to quarantine at home for 14 days from the date of her positive test results for COVID-19. Conclusion: Considering that the results of this case report are essential for other pediatric care professionals with COVID-19, the understanding of clinical demonstration patterns continues to evolve. More information on the clinical course of children with COVID-19, especially in cases where the disease coincides with the Kawasaki disease, is necessary.

Coronavirus disease 2019-related Kawasaki syndrome: a case report

BackgroundCoronavirus disease 2019 has changed the pattern of some diseases in the world, especially in pediatrics. Despite data suggesting that the pediatric population is less affected by coronavirus disease-19 infection, new concerns have been raised owing to reported cases with hyperinflammatory conditions such as Kawasaki disease.Case presentationWe report herein the case of a pediatric patient diagnosed and treated for classic Kawasaki disease in the setting of confirmed coronavirus disease 2019 infection. She was an 8-year-old, previously healthy, and fully immunized Iranian girl who initially presented to the pediatric emergency department with 5 days of intermittent fever, followed by abdominal pain, nausea, and vomiting. She was admitted for fever and abdominal pain to the surgery service of Akbar Hospital with suspected appendicitis.ConclusionsThis case report may serve as a useful reference to other clinicians caring for pediatric patients affected by coronavirus disease 2019 infection. Standard therapeutic interventions for Kawasaki disease must be performed to prevent critical coronary aneurysm-related complications in the coronavirus disease 2019 era.

A machine-learning algorithm for diagnosis of multisystem inflammatory syndrome in children and Kawasaki disease in the USA: a retrospective model development and validation study

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a novel disease that was identified during the COVID-19 pandemic and is characterised by systemic inflammation following SARS-CoV-2 infection. Early detection of MIS-C is a challenge given its clinical similarities to Kawasaki disease and other acute febrile childhood illnesses. We aimed to develop and validate an artificial intelligence algorithm that can distinguish among MIS-C, Kawasaki disease, and other similar febrile illnesses and aid in the diagnosis of patients in the emergency department and acute care setting.MethodsIn this retrospective model development and validation study, we developed a deep-learning algorithm called KIDMATCH (Kawasaki Disease vs Multisystem Inflammatory Syndrome in Children) using patient age, the five classic clinical Kawasaki disease signs, and 17 laboratory measurements. All features were prospectively collected at the time of initial evaluation from patients diagnosed with Kawasaki disease or other febrile illness between Jan 1, 2009, and Dec 31, 2019, at Rady Children's Hospital in San Diego (CA, USA). For patients with MIS-C, the same data were collected from patients between May 7, 2020, and July 20, 2021, at Rady Children's Hospital, Connecticut Children's Medical Center in Hartford (CT, USA), and Children's Hospital Los Angeles (CA, USA). We trained a two-stage model consisting of feedforward neural networks to distinguish between patients with MIS-C and those without and then those with Kawasaki disease and other febrile illnesses. After internally validating the algorithm using stratified tenfold cross-validation, we incorporated a conformal prediction framework to tag patients with erroneous data or distribution shifts. We finally externally validated KIDMATCH on patients with MIS-C enrolled between April 22, 2020, and July 21, 2021, from Boston Children's Hospital (MA, USA), Children's National Hospital (Washington, DC, USA), and the CHARMS Study Group consortium of 14 US hospitals.Findings1517 patients diagnosed at Rady Children's Hospital between Jan 1, 2009, and June 7, 2021, with MIS-C (n=69), Kawasaki disease (n=775), or other febrile illnesses (n=673) were identified for internal validation, with an additional 16 patients with MIS-C included from Connecticut Children's Medical Center and 50 from Children's Hospital Los Angeles between May 7, 2020, and July 20, 2021. KIDMATCH achieved a median area under the receiver operating characteristic curve during internal validation of 98·8% (IQR 98·0–99·3) in the first stage and 96·0% (95·6–97·2) in the second stage. We externally validated KIDMATCH on 175 patients with MIS-C from Boston Children's Hospital (n=50), Children's National Hospital (n=42), and the CHARMS Study Group consortium of 14 US hospitals (n=83). External validation of KIDMATCH on patients with MIS-C correctly classified 76 of 81 patients (94% accuracy, two rejected by conformal prediction) from 14 hospitals in the CHARMS Study Group consortium, 47 of 49 patients (96% accuracy, one rejected by conformal prediction) from Boston Children's Hospital, and 36 of 40 patients (90% accuracy, two rejected by conformal prediction) from Children's National Hospital.InterpretationKIDMATCH has the potential to aid front-line clinicians to distinguish between MIS-C, Kawasaki disease, and other similar febrile illnesses to allow prompt treatment and prevent severe complications.FundingUS Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Heart, Lung, and Blood Institute, US Patient-Centered Outcomes Research Institute, US National Library of Medicine, the McCance Foundation, and the Gordon and Marilyn Macklin Foundation.

Explainable deep learning algorithm for distinguishing incomplete Kawasaki disease by coronary artery lesions on echocardiographic imaging

Background and Objective: Incomplete Kawasaki disease (KD) has often been misdiagnosed due to a lack of the clinical manifestations of classic KD. However, it is associated with a markedly higher prevalence of coronary artery lesions. Identifying coronary artery lesions by echocardiography is important for the timely diagnosis of and favorable outcomes in KD. Moreover, similar to KD, coronavirus disease 2019, currently causing a worldwide pandemic, also manifests with fever; therefore, it is crucial at this moment that KD should be distinguished clearly among the febrile diseases in children. In this study, we aimed to validate a deep learning algorithm for classification of KD and other acute febrile diseases. Methods: We obtained coronary artery images by echocardiography of children (n = 138 for KD; n = 65 for pneumonia). We trained six deep learning networks (VGG19, Xception, ResNet50, ResNext50, SE-ResNet50, and SE-ResNext50) using the collected data. Results: SE-ResNext50 showed the best performance in terms of accuracy, specificity, and precision in the classification. SE-ResNext50 offered a precision of 81.12%, a sensitivity of 84.06%, and a specificity of 58.46%. Conclusions: The results of our study suggested that deep learning algorithms have similar performance to an experienced cardiologist in detecting coronary artery lesions to facilitate the diagnosis of KD.

Tricky Presentation of Multisystem Inflammatory Syndrome in Children (MIS-C) with in Pediatric

Introduction: In emergence a COVID patient with multisystem inflammatory syndrome in children (MIS-C), associated with SARS-CoV-2, has shown increasing number among pediatric. Even the same presentation of Kawasaki disease we have to keep in mind MIS-C, in order to reach a consensus on this new disease in the future. Three variations of the disease patterns were reported: a group of children with increase in inflammatory activity and persistent fever, without criteria for Kawasaki disease, a second group with Kawasaki disease criteria, and a third group with shock, coronary aneurysms, severe cardiac dysfunction, and gastrointestinal symptoms. Classic Kawasaki disease is self-limited vasculitis which affects medium-sized vessels, almost occurred in children under five years old. Here, we bring a Saudi case, present to emergency department in Prince Sultan Military Medical City. Case report: 10 years old female, medically free, presented with abdominal pain, fever and skin rashes. Patient had history of COVID-19 infection 1 month before presentation. Initial investigations showed acute kidney injury with elevated inflammatory markers. Conclusion: Further evidence of the increase in the incidence of pediatric MIS-C, temporarily is associated with SARS-CoV-2. Physician should give more attentions to this new diagnosis with more fatal outcomes than Kawasaki cases.

Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): Distinct from Kawasaki disease or part of the same spectrum?

One of the most challenging and intriguing phenomena observed during the COVID‐19 pandemic has been the multisystem inflammatory syndrome in children (MIS‐C). Patients with this condition present with some clinical features similar to those of Kawasaki disease (KD) and display signs and symptoms that are uncommon or rarely occur in this disorder, such as gastrointestinal complaints and myocarditis, often leading to myocardial failure and shock. In addition, patients’ age is older than that of children with classic KD. Management is based on administering intravenous immunoglobulin, glucocorticoids, and anakinra in the most severe instances. It is still debated whether MIS‐C and KD are different illnesses or represent a disease continuum.

Impact of the COVID-19 pandemic on the frequency of the pediatric rheumatic diseases.

The impact of the COVID-19 pandemic, and implemented restrictions on the frequency of pediatric rheumatic diseases remain unknown, while they have probably prevented common infections in children. We present the effects of the COVID-19 on our pediatric rheumatology practice in a main referral center. We retrospectively reviewed the medical records of patients presenting to pediatric rheumatology department in 4 years before March 2020 and compared it to the pandemic year (March 2020–March 2021). Since there was an overall decrease in patient numbers, we calculated the percentage according to the total number of that year. A total of 32,333 patients were evaluated. The mean annual number of patients decreased by 42% during the COVID-19 pandemic. When follow-up visits (25,156) were excluded, there were 2818 new diagnoses of rheumatic diseases. In the pre-pandemic period, familial Mediterranean fever (FMF) (n = 695, 28.1%) was the most frequent, whereas in the pandemic period multisystem inflammatory syndrome in children (MIS-C) (n = 68, 19.2%) was the most common diagnosis. There were no significant differences in the percentages of juvenile idiopathic arthritis, autoimmune diseases, rare autoinflammatory diseases, and other vasculitides. However, there was a significant decrease in patients diagnosed with FMF, IgA vasculitis (IgAV), acute rheumatic fever (ARF), classic Kawasaki disease (KD), and macrophage activation syndrome (MAS) (all p < 0.05). During the pandemic year, the percentage of most common diseases did not differ. On the other hand, we suggest that the decreases in IgAV, KD (classic), and MAS, which parallels the decrease in ARF, confirm the role of infections in the pathogenesis for these diseases.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00296-021-05027-7.

A Study on the Cardiac Manifestations and their Short-Term Outcome in Patients with Kawasaki Disease in an Indian Population

Objectives: This study aimed to assess the prevalence of cardiac manifestations and their short-term outcome in patients with Kawasaki disease (KD) in an Indian population. Methods: This single-center prospective study enrolled a total of 56 consecutive patients with classic and incomplete KD. Six months and 1-year clinical outcomes were analyzed. Results: Fifty-six consecutive patients were enrolled in the study and followed up for 1 year. About 87% completed 6 months follow-up. A diagnosis of complete KD was made in 41 (73%) patients and incomplete KD in 15 (27%). Cardiac manifestations were present in 25% of patients with KD. Coronary involvement was observed in 11 (20%) patients by either Japanese Ministry of Health Criteria or a z score of ≥2.5. Nonpurulent conjunctivitis was significantly higher among children with cardiac involvement (79% vs. 43% P= 0.04). The mean value of erythrocyte sedimentation rate (ESR) was significantly higher among patients with cardiac involvement (101.92 ± 22 vs. 74.26 ± 28.6; P= 0.002). An ESR value of &gt;100 mm/hr was predictive of cardiac involvement (P = 0.03). The mean serum glutamic-pyruvic transaminase value was higher among those with cardiac involvement (P = 0.008). Coronary dilatation got resolved in 3 months in 73% of patients. Valvular regurgitations, aortic root involvement, and depressed left ventricular myocardial function were not observed in the population studied. Conclusions: Cardiac manifestations were present in 25% of patients with KD, 20% of children had coronary involvement in the form of an aneurysm, or ectasia. About 73% of patients with coronary dilatation got resolved in 3 months. Significant valvular heart diseases, aortic root involvement, and myocardial contractile dysfunction were not seen in the studied population with KD.

Hydrocele in a case of atypical Kawasaki disease: case report and review of diagnostic criteria

BackgroundKawasaki Disease (KD) is a self-limiting vasculitis of unknown etiology. Although there are well-recognized clinical features associated with classic KD, there have been increasing numbers of atypical clinical presentations with increased dependence on the American Heart Association diagnostic algorithm for incomplete KD.Case presentationWe report on a child who was initially treated for Escherichia coli left pyelonephritis and Influenza A and Rhinovirus / Enterovirus upper respiratory tract infection. The child developed an acute hydrocele and a maculopapular rash during the illness course, which prompted further evaluation for concomitant atypical KD, although there were no other physical signs suggestive of classic KD at the time. Subsequent diagnosis of atypical KD was made with confirmation on echocardiography, with timely administration of intravenous immunoglobulin.ConclusionsAlthough there are well recognized clinical features associated with classic Kawasaki Disease, there have been increasing numbers of atypical clinical presentations with increased dependence on the American Heart Association diagnostic algorithm for incomplete Kawasaki Disease. This case report highlights the importance of considering a diagnosis of KD in a child with prolonged fever and unexplainable symptoms suggestive of inflammation, in this case, the rare presentation of an acute hydrocele. We recommend that for any child with prolonged unexplained fever, Kawasaki Disease should be considered.Trial registrationNot applicable.

Atypical Kawasaki Disease in a Two-Year-Old Girl with Initial Presentation of Acute Diarrhea

Kawasaki Disease is a spectrum of idiopathic, self-limited fever disease affecting childrenunder 5 years old. This disorder can be challenging to be diagnosed by a pediatrician since thereis no specific diagnostic laboratory test. One atypical Kawasaki Disease case presented withgastrointestinal symptoms, a two-year-old girl was hospitalized with fever, accompanied by non-hemorrhagic diarrhea three days before admission. Physical examination revealed unilateralcervical lymph enlargement and mild-moderate dehydration. Initial laboratory examinationresult showed thrombocytosis, leukocytosis (shift to the left), and normal routine fecal analysis.The patient was initially diagnosed with acute diarrhea with mild-moderate dehydration. She wastreated with a rehydration regimen and antibiotic, but her fever persisted. On the third day ofhospitalization, she fulfilled 3 of the classic Kawasaki Disease criteria (conjunctivitis, crackedlips with strawberry tongue, and lymphadenopathy). Further blood work resulted in increased C-reactive protein 43.35 mg/L and ESR 72 mm/hour, while chest X-ray and electrocardiographwere within normal limit. This patient was proceed to Hasan Sadikin General Hospital for furtherexamination and therapy. Atypical Kawasaki Disease can be a puzzling diagnosis due to itsuncommon presentations. Clinicians should importantly keep it in mind as a differential diagnosisin patients with prolonged fever.&#x0D; Keywords: atypical Kawasaki disease; diarrhea; prolonged fever

Refractory Kawasaki Disease-a Challenge for the Pediatrician.

Kawasaki disease (KD) is an acute, self-limiting febrile illness of childhood associated with vasculitis, mainly of the medium-sized arteries. The clinical significance and impact of this condition arise from its predilection for the coronary arteries. The criteria for classic Kawasaki disease are clearly defined, but many children present with atypical forms, and clinicians need to consider this possibility. Although most diagnosed cases respond to intravenous immunoglobulin (IVIG) and aspirin, some have proven resistant to the standard treatment. This article aims to provide a brief overview of Kawasaki disease, focusing on the resistant/refractory cases, and the treatment options available for such cases.

Epidemiological Features and Clinical Study of Kawasaki Disease in Iran

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology and the major cause of pediatric acquired cardiac disease worldwide, particularly in developed countries. This study characterizes the epidemiologic and clinical features of KD in the Pediatric Rheumatology Department service in a general hospital. 120 patients with the diagnosis of KD between 1990 and 2009 were enrolled. We investigated the epidemiologic and clinical features of coronary artery involvement of the patients. Frequency of many parameters including age, sex, season, clinical and laboratory findings, response to treatment, and complications of the patients determined. During the 20-year study period, 120 patients &lt;15 years of age were admitted for KD. Among them, 39.2% were at the extremes of the age spectrum, with 2.5% &lt;6 months and 36.7% &gt;5 years of age, male to female ratio of 1.3:1 and the classic KD to incomplete KD ratio of 3.1:1. KD recurred in 5% of all cases. It occurred most frequently in the winter and least frequently in the summer. The occurrence of coronary artery abnormalities (CAA) was 4.2%. Kawasaki disease should be considered in any pediatric patients with a prolonged refractory febrile illness in order to prevent CAA formation.

Distinctive Features of Kawasaki Disease Following SARS-CoV-2 Infection: a Controlled Study in Paris, France.

BackgroundAn outbreak of multisystem inflammatory syndrome in children, including Kawasaki disease (KD), emerged during COVID-19 pandemic. We explored whether Kawasaki-like disease (KD), when associated with confirmed SARS-CoV-2 infection, has specific characteristics.MethodsWe included children and adolescents with KD criteria admitted in the department of general pediatrics of a university hospital in Paris, France, between January 1, 2018, and May 26, 2020. The incidence of KD was compared between the outbreak and a pre-outbreak control period (January 1, 2018, to April 25). Characteristics of patients with positive SARS-CoV-2 testing (KD-SARS-CoV-2) were compared to those of the pre-outbreak period (classic KD).ResultsA total of 30 and 59 children with KD were admitted during the outbreak and pre-outbreak periods, respectively (incidence ratio 13.2 [8.3–21.0]). During the outbreak, 23/30 (77%) children were diagnosed as KD-SARS-CoV-2. When compared with patients with classic KD, those with KD-SARS-CoV-2 were more frequently of sub-Saharan African ancestry (OR 4.4 [1.6–12.6]) and older (median 8.2 vs. 4.0 years, p < 0.001), had more often initial gastrointestinal (OR 84 [4.9–1456]) and neurological (OR 7.3 [1.9–27.7] manifestations, and shock syndrome (OR 13.7 [4.2–45.1]). They had significantly higher CRP and ferritin levels. Noticeably, they had more frequently myocarditis (OR 387 [38–3933]).ConclusionsChildren and adolescents with KD-SARS-CoV-2 have specific features when compared with those with classic KD. These findings should raise awareness and facilitate the study of their pathogenesis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-020-00941-0.

Dalla Kawasaki Disease alla MIS-C: l’esperienza di Bergamo

Kawasaki disease (KD), although rare (affects about 15 children out of 100,000/year) and self-limiting, it is the second most frequent cause of pediatric acquired heart disease in Western countries. The classic KD is diagnosed by fever and at least 4 clinical signs between conjunctivitis, mucositis, polymorphic rash, erythema and edema of hands and feet or lymphadenopathy; if clinical signs are less than 4 the incomplete KD can be diagnosed together with specific laboratory criteria. Since March 2020, at the time of the greatest spread of the SARS-CoV-2 epidemic in our province, we found over 20 children, admitted to the Pediatrics of our hospital, with clinical pictures very similar to Kawasaki disease. In addition to signs of mucocutaneous inflammation, some children had a significant systemic inflammation with severe heart involvement, up to shock in some cases. In the next months, similar cases were reported in areas of the world with a high spread of the virus, and the scientific community coined the name of Multisystem Inflammatory Syndrome in Children (MIS-C) for this form linked to SARS-CoV-2. KD conventional therapy based on intravenous immunoglobulin, acetylsalicylic acid and systemic steroids resolved the inflammation in all children. This article critically discusses the common characteristics of the two diseases and hypothesizes that they belong to the same pathological condition with a wide spectrum of clinical manifestations; it proposes the diagnostic framework for this new inflammatory condition based on clinical and laboratory characteristics and, finally, outlines the principles of treatment.

БОЛЕЗНЬ КАВАСАКИ И МУЛЬТИСИСТЕМНЫЙ ВОСПАЛИТЕЛЬНЫЙ СИНДРОМ ПРИ ИНФЕКЦИИ COVID-19 У ДЕТЕЙ

During the COVD-19 pandemic, some pediatric patients in many countries around the world experienced a syndrome resembling a severe Kawasaki disease (KD), often accompanied by shock. Due to the incomplete signs of the classic KD in the era before the present pandemic, in many publications from European countries and the United States, this condition was called «multisystem inflammatory syndrome in children – MIS-C» or «hyperinflammatory shock» or «Kawasaki-like syndrome». This syndrome with a new coronavirus infection is characterized by refractory fever, frequent gastrointestinal symptoms, heart damage (including coronary dilation in some patients, and acute left ventricular failure in the majority), increased ESR and CRP levels, neutrophilia, extremely high troponin levels, increased ferritin, AST, ALT, lactate dehydrogenase, creatine phosphate kinase, interleukin-6 and interleukin-10, coagulopathy with an increase in D-dimer and fibrinogen, thrombocytopenia, sometimes procalcitonin increase. The manifestations of a cytokine storm may meet the criteria for secondary hemophagocytic syndrome. The mechanism of myocardial damage remains unclear. Treatment with high-dose intravenous immunoglobulin is effective, and in the presence of signs of hemophagocytic syndrome, dexamethasone or methylprednisolone. Further research is needed to understand the pathogenesis, resemblance and differences of this syndrome with classic KD, understanding of heart injuiry and early recognition for the need of urgent care.

Insights on Kawasaki disease and multisystem inflammatory syndrome: relationship with COVID-19 infection

At the beginning of coronavirus disease 2019 (COVID-19) children seemed to be less affected and with milder symptoms than adults. Afterward, however, a warning was released regarding the possible association between COVID-19 and Kawasaki disease (KD) or Kawasaki-like disease. Thereafter, labels of Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) in Europe and Multisystem Inflammatory Syndrome in Children (MIS-C) in the USA were coined to refer to this new disease entity. The reality is that PIMS-TS/MIS-C resembles certain KD complications such as toxic shock syndrome and macrophage activation syndrome than to classic KD. PIMS-TS/MIS-C and KD share the viral origin (however just supposed for KD) and consequent dysregulated innate immune system inflammatory reaction. PIMS-TS/MISC symptoms occur about 2-4 weeks after the onset of COVID-19 or having been exposed to somebody positive for COVID-19, rather than in the acute phase of the infection. Clinically PIMS-TS/MIS-C affects older children than KD and presents more often with gastrointestinal symptoms, shock, and multi-organ dysfunction. myocarditis is more common in PIMS-TS/MIS-C than coronary artery aneurysms formation seen in KD. There are also differences in laboratory tests and immunology responses in KD and PIMS-TS/MIS-C. Thus PIMS-TS/MIS-C seems to be a new and multifaceted entity, distinct from KD, notwithstanding some common features in both. The dysregulated innate immune system reaction is responsible for PIMS-TS/MIS-C onset and outcome. A multidisciplinary approach, involving paediatric intensivists, paediatric cardiologists, infectious disease specialists, immunologists, and rheumatologists, is needed for the treatment of these children.

Cutaneous and histopathological features of coronavirus disease 2019 in pediatrics: A review article.

Prevalence of dermatological manifestations of coronavirus disease 2019 (COVID‐19) is estimated between 0.25% and 3% in children and adolescents. In this review article, we decided to describe the cutaneous and histopathological manifestations of COVID‐19 infection in pediatrics. We searched published articles in PubMed database for key words of “children” or “pediatric” and “cutaneous” or “dermatology” or “skin” and “COVID‐19” or “SARS‐CoV‐2” or “Coronavirus disease 2019” in abstract or title from December of 2019 until September 2020. Finally, 38 articles were selected. The majority of patients were between 11 and 17 years old with predominantly male gender. Most of the patients were either asymptomatic or had a few general symptoms. The latency time from appearance of general symptoms to cutaneous ones was between 1 day and weeks. Skin lesions faded between 3 and 88 days without any sequelae, spontaneously or with either topical or systemic corticosteroids. Skin manifestations were chilblain‐like (pseudochilblain), erythema multiforme‐like, dactylitis, acral erythema, acute urticaria, livedo reticularis, mottling, acro‐ischemia, generalized maculopapular lesions, eyelid dermatitis, miliaria‐like, varicelliform lesions, and petechiae and/or purpura. Kawa‐COVID‐19 patients were presented more frequently with cardiogenic shock, neurological symptoms, lymphocytopenia, and thrombocytopenia as compared to classic Kawasaki's disease. Furthermore, more number of cases were resistant to the first‐line treatments.