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Egyptian evidence-based consensus on clinical practice recommendations for the management of Kawasaki disease



Kawasaki disease (KD) is an acute, self-limited febrile disease of unidentified cause that mostly affects children less than 5 years of age. This work aimed to provide an appropriate Egyptian evidence-based consensus on clinical practice recommendations for the management of Kawasaki disease. The main objective of this study, which employed the Delphi method, was to reach a consensus among experts on a treat-to-target management approach for KD.


The expert panel was confined to an online survey (n=26), and all the expert completed the three rounds. At the conclusion of round 3, a total of 17 recommendation items were gathered, which were divided into two sections. The range of respondents (ranks 7–9) who agreed with the recommendations was 92.3 to 100%. All 17 clinical standards identified by the scientific committee were written in the same way. There have been algorithms proposed for managing various KD conditions.


The developed evidence-based consensus recommendations for the diagnosis and management of KD represent an up-to-date document that focuses on clinical management questions which are generally posed to health care professionals involved in the management of KD. This guideline was developed considering experience with and availability of treatment and diagnostic options in Egypt.


Kawasaki disease (KD) continues to be an area of evolving understanding in clinical treatment. Since its first description by Dr. Tomisaku Kawasaki, based on the classical clinical symptoms, Kawasaki disease has been recognized as one of the two most common systemic vasculitis in childhood (the other one is IgA vasculitis [Henoch-Schönlein]) [1]. KD is an acute, self-limited febrile disease of unidentified cause that mostly affects children less than 5 years of age. KD is a medium vessel vasculitis which prior to the identification as a distinct illness, children with fulminant forms of the disease used to be identified as “infantile polyarteritis nodosa” [2]. Although inflammation occurs throughout the body, the coronary artery is the commonest vessel to be affected and their involvement can trigger severe coronary artery aneurysms (CAA). This makes those children living with the disease a high-risk cohort of patients.

In the absence of pathognomonic tests, the diagnosis of KD remains a challenge. In addition to the absence of diagnostic tests, the diagnostic clinical criteria may develop sequentially, rather than simultaneously, which may cause further delay in making the diagnosis. Also, a variability in patient presentation has been reported, as many symptoms such as arthritis, gastrointestinal, CNS, or liver manifestations as well as uveitis may accompany the principal criteria. Furthermore, children presenting with incomplete KD never develop all the classic criteria. Several Egyptian healthcare experts have the misconception that KD is not frequent in Egypt [3].

Timely initiation of management for KD has proven its efficacy in securing favorable long-term diagnosis. Untreated KD may lead to the development of coronary artery aneurysms which may cause sudden cardiac death in children. Furthermore, as young persons with post-COVID-19 multisystem inflammatory syndrome in children (MIS-C) may present with Kawasaki-like disease, and because its management is derived from KD therapeutic options thus far, considerable attention has been paid to KD following the COVID era [3]. Given the growing number of available options to treat systemic vasculitis, there have been several reports discussing variable presentations of the disease, whether complete, incomplete, or atypical KD, in Egypt [4,5,6,7]; it was important to set national management recommendations for KD to ensure capturing and treating the disease during the effective window of therapy national guidelines for specific diseases should be based on the most recent research available at the time of release and in the context of the population’s local environment. The Egyptian College of Paediatric Rheumatology has taken this initiative and provide an up to date evidence-based consensus for the management of KD. This is in concordance with the nationwide universal health coverage approach which has been launched in Egypt in 2020. Setting up such guidelines for management of patients is vital to the process. Although intended to help Egyptian children with KD; yet, we hope it will be a beneficial simple guidance for diagnosis and management of KD all over the world.



The development of the evidence-based consensus treatment recommendations for KD using a multistep process strategy. The study’s design was developed in accordance with the CEG guideline development process methodology, which relies on existing scientific data and clinical experience to reach consensus. The publication complied with the criteria for reporting systematic reviews and meta-analyses on preferred reporting items for such studies [8].

Development stages

Core team

Three experts with proven KD management experience made up the team. The core team managed and oversaw the team’s efforts, helped define the project’s parameters and the original Patient/Population, Intervention, Comparison, and Outcomes (PICO) clinical questions, and came to an agreement on the guidelines’ most important inquiries. The core team pre-identified outcomes for each PICO question that were essential for the systematic literature evaluation. The team also proposed the panel of experts and prepared the manuscript.

Key questions used to develop the guideline

The target population, the intervention, the investigation, the comparison(s) employed, and the outcomes used to quantify efficacy, effectiveness, or risk were all defined in this guideline. The stages for collecting the evidence to address the clinical questions were as follows: formulation of the clinical questions, question structuring, search for the evidence, critical evaluation and selection of the evidence, presentation of the findings, and recommendations. These inquiries, which are presented in Table 1, formed the basis for the systematic literature review and, ultimately, the clinical care standards.

Table 1 Key questions used to develop the guideline

Literature review team

The literature evaluation was carried out with the assistance of a methodology expert under the direction of an experienced literature review expert and based on the particular research questions established to concentrate on the management of KD. Using the PubMed/MEDLINE, EMBASE, and Cochrane databases, a systematic literature search was conducted to gather the necessary evidence-based background knowledge for deliberations. The experts in responsible of the literature review revised the data after it had been abstracted, looked over published recommendations, and rated the quality of the evidence [9, 10]. They then provided a thorough list of recommendations for the management of KD based on the research evidence that was currently available and their own clinical expertise. The Oxford Centre for Evidence-based Medicine (CEBM) approach was used to establish the level of evidence for each section (Table 2) [10].

Table 2 Levels of evidence

Data sources and search strategies

The search approach was designed to find all studies involving children living with KD as the study population. The literature search was done using the PICO questions (Table 1). To find randomised clinical trials testing the effectiveness of KD care as well as quality improvement outcomes/approaches, literature search methodologies were used.

The chosen keywords were determined by the various PICO element combinations. PubMed, Cochrane Library, and Embase database searches will take place on January 12, 2022, and January 25, 2022, respectively. Updated on April 4th, 2022, was the search. Electronic duplicate screening of literature search results was done. Reviewing the reference lists of studies found through database search tactics that satisfied the inclusion criteria allowed for the retrieval of additional pertinent studies.

Study selection

Applying inclusion and exclusion criteria to the literature retrieved using the search strategies allowed for the selection of pertinent research.

Inclusion criteria

Systematic reviews, randomized controlled trials (RCTs), uncontrolled trials, observational studies including cohort, case control, and cross-sectional studies, as well as articles where an economic evaluation was done, were all included in the list of articles. Trials were considered eligible if they involved children, regardless of gender, from any medical environment receiving any therapy who had been diagnosed with KD. The classification evidence and suggestions utilised in the included research should be identified. The formal procedure for making recommendations (Delphi exercise, panel conference) is also described.

Exclusion criteria

Editorials, commentary, abstracts from conferences, narrative/personal reviews without supporting data, and articles without an English translation were excluded.

Expert panel

There were 26 members nominated by the core leadership group. A minimum of 8 years of professional experience in the field of rheumatology, management of inflammatory arthritis, specifically KD, and active engagement in rheumatic disease research were requirements for their selection.

The expert panel, which included ophthalmologists, hematologists, pediatric cardiologists, and rheumatologists, provided professional knowledge to help with discussions of the PICO questions and literature review’s conclusions. PICO questions were turned into recommendation statements and forwarded with the evidence report to the expert panel for voting.

Target audience

The aim of the recommendation is to help medical professionals, such as rheumatologists, paediatricians with a focus on pediatric rheumatology, cardiologists, hematologists, dermatologists, and ophthalmologists, who treat and manage patients with KD. The recommendation should serve as a useful tool for patients and those in charge of commissioning treatment for KD patients under the National Health Service.

Developing the clinical care standard framework

To promote consistent identification of guideline components, a structured template was developed based on the responses to the structured key questions and the literature review. The format in which recommendations and information will be supplied and extracted for each guideline component has been determined.

Delphi process

The Delphi method is a structured approach that is frequently used to collect crucial data on a certain subject. It is predicated on the fundamental tenet that group projections are typically more accurate than individual ones. In order to create consensus forecasts from a group of experts in an organised, iterative manner, the Delphi method was developed. Its methodology is based on a number of “rounds” of questions sent to experts. The following phases are typically covered by the Delphi method: (1) A group of experts is put together. (2) The experts are given forecasting assignments and difficulties. (3) The experts provide early predictions and explanations. These are gathered and summarised in order to offer comments. (4) The experts receive input, which they use to review their projections. Up until a suitable degree of agreement is obtained, this phase may be repeated. (5) The expert forecasts are combined to create the final projections. The participants in this method are anonymous, and the feedback is carefully regulated [11,12,13].

Consensus process

To reach consensus on the T2T (treat to target) strategy in KD, three Delphi rounds were conducted. The organized Delphi process makes sure that all participant opinions are taken into account. Online surveys were used to carry out the Delphi process. Seventeen items from the T2T strategy of KD were included in the first round of the electronic questionnaire.

Voting process

Voting took place in three rounds of precisely timed live online delivery. All task force members received invitations to vote and advance notice of the start and end times of each round. Anonymous votes were gathered and processed, and special access links were distributed. During the voting process, comments on rephrasing, potential ambiguity, and unidentified overlaps was obtained in relation to each statement. Voting on the statements was only permitted for task force participants.


Each statement was given a score ranging from 1 to 9, with 1 denoting “total disagreement” and 9 denoting “full agreement.” The numbers 1–3, 4–6, and 7–9, respectively, are used to denote disagreement, doubt, and agreement. Voting was not obliged on any statements, and participants were encouraged to abstain if they believed a statement to be outside of their area of expertise. Voting with “uncertainty” expresses “discomfort about the accuracy of the recommendation.” All statements were open to the entry of comments, which the scientific committee assessed following each vote session. Members were urged to comment throughout every round of voting, especially whenever there was a disagreement. With the use of this, the panel was able to determine a case of misinterpretation of a remark and invalidate the vote on it.

Interpreting the recommendations: definition of consensus

Before data analysis, a definition of consensus was defined. It was determined that agreement (scoring 7–9) or disagreement (scores 1–3), which would then become a recommendation in this guideline, would be attained by at least 80% of participants [11,12,13]. If a statement received a “poor” degree of agreement or a mean vote that was less than 3, it was retired. In view of the comments, statements whose rating fell within the (4–6) range of the uncertainty score were amended. When all votes on a proposal fell into the agreement bracket after the second round of voting, the levels of agreement on each statement of recommendation were considered to be “high” (7-9) [13, 14].

Chronogram of Delphi rounds

The first round was held from June 2 through June 6, 2022 (5 days). In light of the remarks, the elements on which respondents could not agree in this first round were amended and included in the second round. One month after the first round, on July 6, 2022, the second round took place and lasted for 5 days (6th–10th Jul 2022). The third round then began on August 7th, 2022, and lasted for 5 days (7th–11th Aug 2022).

Ethical aspects

In compliance with the Helsinki declaration, this study was carried out. The local ethics commission, Tanta University’s ethical board, and its ethical approval code, 34842/8/21, accepted the Clinical, Evidence-based, Guidelines (CEG) project procedure. Since there were no human participants in this study, Human Studies Committee permission was not necessary. According to national standards, written ethics permission from the experts involved in this work was not deemed essential.


Literature research and evidence selection

By using a search strategy, we identified 2530 possibly relevant studies during the research selection phase. 2375 were dismissed due to duplicates or following title and abstract screening (studies did not examine population or intervention of interest, did not match study design of interest, or did not report outcome measures of interest). One hundred fifty-five studies that were pertinent were therefore included for the entire article review. One hundred thirty-three studies were excluded because the citations did not offer proof that matched a PICO. Twenty-two studies were therefore included in this work.

Expert panel characteristics

The Delphi form was sent to the expert panel (n=26), who participated in the three rounds. The experts were 22 adult and pediatric rheumatologists, 1 pediatric cardiologist, 1 cardiologist, 1 ophthalmologist, and 1 statistician. Respondents came from various governorates and medical centers all around Egypt: Cairo University (26.9%), Ain Shams University (11.5%), Tanta University (15.4%), Benha University (3.8%), Alexandria University (7.7%), Suez Canal University (3.8%), Zagazig University (7.7%), Minia University (3.8%), Mansoura University (3.8%), Fayoum University (3.8%), Assiut University (3.8%), Sohag University (3.8%), and the UK (3.8%).

Delphi round 1

Round 1 had a 100% response rate (26/26). On all of the clinical key questions, an agreement was attained on 100% of the topics, meaning that 75% of respondents strongly agreed or agreed. Concerning the phrasing of some of the recommendations, there were 17 key questions and comments. Key points, disease monitoring, and treatment targets received more comments (excluding small editing suggestions). There was no diversity of opinion in round 1.

Delphi round 2

Round 2’s response rate was 100% (26/26) overall. A high-rank recommendation (rank 7–9) was given to between 88.5 and 100% of applicants. There was consensus (i.e., 75% of respondents strongly agreed or agreed) on all clinical standards. The remarks’ phrasing was agreed upon by all stakeholders (>80% agreement).

Delphi round 3

Round 3’s response rate was 100% (26/26) overall. A high-rank recommendation (rank 7–9) was given to between 92.3 and 100% of applicants. The overarching principles and recommended statements are shown in Table 3.

Table 3 Summary of recommendations

Figures 1, 2, and 3 show different algorithms for KD management.

Fig. 1
figure 1

Algorithm of management of Kawasaki disease

Fig. 2
figure 2

Algorithm of management of incomplete Kawasaki disease

Fig. 3
figure 3

Algorithm of maintenance treatment in the patient with KD after an acute attack

Recommendations for the management of children with KD

At the end of round 3, a total of seventeen recommendation items, categorized into overarching principles and 2 sections (6 recommendations are considered for diagnosis, prognosis, and monitoring of KD and 11 recommendations in the management section), were obtained.


The rationale behind the development of this guideline includes both the prevalence of the disease being the second most common systemic vasculitis in childhood and the fact that there are no Egyptian recommendations published for the treatment of the disease. Furthermore, over the past few years, extra evidence-based outcomes have been published on the management of KD. Therefore, such updated guideline is important as it may lead to prescribing the appropriate medical therapy, which consequently would reduce the risk of poor disease control or the development of cardiac complications.

The developed guideline provided evidence-based consensus recommendations for the diagnosis, treatment, and management of KD in children. Seventeen clinical questions were developed by the Core in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) format. The systematic literature reviews were undertaken by the literature review team. The Expert Panel provided expert knowledge to develop the statements based on an informed discussion of the PICO questions and the literature review findings. In general, the development guidelines agree broadly with the treatment recommendations and guidelines published earlier, though there were some differences. Initially, this guideline provided a specific definition for the typical, atypical, and incomplete KD. Atypical KD was not included in the ACR guideline for the management of KD [15], whereas the American Heart Association guidelines [16] gave the atypical KD the same definition as incomplete KD. Several children may present with some but not all of the KD clinical features, however, may still remain at high risk of developing coronary artery aneurysms. This may cause some confusion in identifying the incomplete or atypical KD, particularly clinical manifestations that may develop sequentially, in that an incomplete or atypical case can progress into a complete case [16,17,18,19,20]. To predict high-risk cases, this guideline endorsed the adoption of a pragmatic strategy to draw an overall picture of disease severity based on clinical manifestations and laboratory measures, parameters that predict high-risk cases include young age (i.e., <12 months), C-reactive protein higher than 200 mg/l, albumin ≤ 2.5 g/dL, Hb at least 2 g/dL below the lower limit of normal for age, liver dysfunction: AST or ALT ≥ 2x upper limit of normal and/or direct bilirubin > 1 mg/dL, overt coronary artery aneurysms, macrophage activation syndrome (MAS) or septic shock, as well as Kobayashi score ≥ 4. This agrees with European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease [21].

The recommendation presented by the American Heart Association (AHA) [16] was targeted mainly for the initial and long-term treatment of KD. Although the ACR recommendations [15] were designed to complement the AHA recommendations and provide extra information for rheumatologists who may be less experienced with KD, they did not mention the systemic complications linked to the acute KD’s active inflammatory process. The developed guideline has taken this extra step and provided specific recommendations for the treatment of ophthalmologic manifestation of KD, arthritis, and MAS as well as prevention and treatment of thrombosis in patients with coronary aneurysms. In agreement with the European recommendations (the SHARE initiative) [21] which included reference to immunization, this guideline provided also recommendations on vaccinations in a child with KD. In contrast neither the ACR [17], nor the Spanish [22] provided recommendations for the immunization for KD patients. This is of importance given the potential lack of effectiveness following IVIG [23, 24].

Kawasaki disease (KD) is a hybrid condition at the junction of infectious diseases, immunology, rheumatology, and cardiology [25]. The disease may be the distinctive manifestation of an immune-mediated vascular inflammation pathway in genetically susceptible children [26]. The clinical experience plays an important role in recognizing and differentiating classic KD patients from other patients who sustained other illnesses and presented with symptoms similar to the KD. In contrast to the European [21] and Spanish [22] recommendations, this guideline includes the similarities between KD and the recently identified multisystem inflammatory syndrome in children (MIS-C) associated with SARS–CoV-2 infection, infectious illnesses, sarcoidosis, and acrodynia. Though the identification of viral or bacterial agents cannot exclude KD diagnosis, it is important to consider such disorders particularly since the world is currently experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2).

All the recommendations published in this guideline aim at facilitating improvement and uniformity of care. All the recommendations for diagnosis and treatment were accepted with a high grade of agreement. Though this guideline can serve as a resource for basic principles of management of KD, caution should be exercised in interpreting the data. As the results of future studies may necessitate amendment of the conclusions or recommendations in this guideline. In the interests of certain patients and unique situations, it might be necessary or even beneficial to depart from the guidelines. Following rules strictly may not serve as a defense against a negligence lawsuit, and following them inconsistently should not necessarily be considered negligent.

In conclusion, Kawasaki disease is the second most common systemic vasculitic disease, after IgA vasculitis, in children. The heterogeneity and complexity of KD presentation, wide-ranging differential diagnosis, and lack of a diagnostic test can be important barriers for making a prompt diagnosis. The developed evidence-based consensus recommendations for the diagnosis and management of KD represent an up-to-date document that focuses on clinical management questions which are generally posed to healthcare professionals involved in the management of KD. This guideline was developed considering experience with and availability of treatment and diagnostic options in Egypt.

Availability of data and materials

The data will be available upon reasonable request.



American Heart Association


Alanine transaminase


Acetylsalicylic acid


Aspartate transaminase


Coronary artery aneurism


Complete blood count


Dual-source CT


Left ventricle




High power field


Intravenous immunoglobulin


Kawasaki disease


Low molecular weight heparin


Macrophage activation syndrome


Multisystem Inflammatory Syndrome in Children


Nonsteroidal anti-inflammatory drug


Patient/Population, Intervention, Comparison, and Outcomes


Randomized controlled trials


Recombinant tissue plasminogen activator


Severe acute respiratory syndrome coronavirus 2 infection


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Authors and Affiliations



Conceptualization and design, YEM and MHA; acquisition of data, YEM and MHA; ST; formal analysis, MEG; investigation, SS and HL; methodology, all authors; writing—original draft, YEM, MHA, and ST; final approval of the version to be submitted, all authors.

Corresponding author

Correspondence to Samar AbdAlhamed Tabra.

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Ethics approval and consent to participate

This study was performed in accordance with the Helsinki Declaration. This was a multistep process which followed the “Clinical, Evidence-based, Guidelines” (CEG) initiative protocol (ethical approval code: 34842/8/21, ethical board Tanta University) aiming at setting up an actionable clinical gold standard for treat-to-target management of rheumatic and bone diseases. All the participants were kept anonymous, in compliance with data protection regulations.

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Not applicable

Competing interests

The authors declare that Mohammed H Abu-Zaid and Salwa Galal are associate editors in the Egyptian Rheumatology and Rehabilitation. Waleed Hassan, Mohammed Mortada, and Yasser El Miedany are from the editorial board of the journal. The other authors declare that they have no competing interests.

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El Miedany, Y., Salah, S., Lotfy, H.M. et al. Egyptian evidence-based consensus on clinical practice recommendations for the management of Kawasaki disease. Egypt Rheumatol Rehabil 50, 21 (2023).

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