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Kawasaki disease: Meta Analysis Reveals A Capable Steroid Combination Therapy

Kawasaki disease: Meta Analysis Reveals A Capable Steroid Combination Therapy


Kawasaki disease (KD) poses significant challenges as an acute vasculitis primarily affecting the coronary arteries in children, potentially leading to fatal complications if left untreated. Corticosteroids, notably glucocorticoids, have emerged as crucial therapeutic agents in managing KD and associated cutaneous wounds. However, the efficacy of certain glucocorticoids may be limited, prompting a focused investigation into their impact on cutaneous wounds in KD patients.


Conducting a comprehensive meta-analysis, this study meticulously examined existing literature to elucidate the influence of glucocorticoids on Kawasaki disease and associated skin lesions. Through an extensive search employing various keywords, relevant studies were identified, screened, and data extracted for meta-analysis, employing the metabin function of the R package meta. The meta-analysis encompassed a cohort of 2000 patients across intervention and control groups, aimed at evaluating the efficacy of glucocorticoids in treating Kawasaki disease and cutaneous wounds.


The results of the meta-analysis underscored the significant therapeutic potential of glucocorticoids, particularly when combined with intravenous immunoglobulin (IVIG), in ameliorating KD. The findings, delineated by key statistical parameters (risk ratio [RR]: 1.08, 95% confidence interval [CI]: 0.58–2.00, p < 0.01), highlight the tangible benefits of incorporating glucocorticoids into clinical practice. Importantly, the study advocates for the judicious use of glucocorticoids to mitigate skin lesions and mitigate adverse effects associated with KD.


In conclusion, this study underscores the importance of glucocorticoids as a valuable therapeutic intervention in managing Kawasaki disease and associated cutaneous wounds in children. By synthesizing existing evidence through meta-analysis, it provides robust support for the integration of glucocorticoids, alongside IVIG, into clinical protocols aimed at enhancing patient outcomes and reducing the burden of KD-related complications.


Kawasaki disease (KD) presents a multifaceted challenge in pediatric medicine, characterized by systemic vasculitis that predominantly affects the coronary arteries. First identified by Dr. Tomisaku Kawasaki in 1967, this condition primarily targets children under the age of 5, with a notable preference for boys over girls and a higher incidence among children of Japanese or Korean descent.


The exact etiology of Kawasaki disease remains elusive, although it is hypothesized to involve a complex interplay of genetic predisposition, environmental factors, and dysregulated immune responses. Clinically, the onset of KD is marked by a prolonged and elevated fever lasting at least five days, accompanied by a range of distinctive symptoms such as erythema and edema of the extremities, enlarged lymph nodes, and inflammation of mucous membranes in the oral, throat, and nasal regions.


Cutaneous manifestations play a pivotal role in the clinical landscape of Kawasaki disease. These include an erythematous rash, desquamation, and indurated edema, which contribute to the intricate presentation of the disease. The erythematous rash typically appears diffusely on the trunk, extremities, and perineal region, exhibiting a polymorphous nature ranging from macular to morbilliform in appearance. The underlying pathophysiology involves systemic vasculitis affecting small-to-medium-sized vessels, leading to increased vascular permeability and extravasation of red blood cells into the skin.


During the convalescent phase of Kawasaki disease, desquamation becomes prominent, characterized by the shedding of superficial layers of the skin, particularly noticeable in periungual regions. This process is attributed to inflammatory mechanisms affecting the epidermis and dermis. Additionally, indurated edema, manifesting as palpable firm swelling, occurs in the acute phase of KD due to inflammatory vasculitis affecting subcutaneous tissues.


The integumentary system serves as a crucial interface between the external environment and internal physiological processes, making skin involvement a hallmark feature of KD. The dynamic interplay between the systemic inflammatory response and cutaneous manifestations necessitates a comprehensive evaluation of therapeutic interventions, particularly glucocorticoid therapy.


Glucocorticoids have emerged as pivotal therapeutic agents in managing KD, owing to their potent anti-inflammatory properties. By modulating gene expression, glucocorticoids attenuate the synthesis of pro-inflammatory cytokines, inhibit immune cell activation, and stabilize cell membranes. Consequently, glucocorticoids not only alleviate systemic inflammation but also expedite the resolution of cutaneous manifestations and skin wounds in Kawasaki disease.


This meta-analysis seeks to systematically evaluate the impact of glucocorticoid therapy on skin wounds in Kawasaki disease, drawing from existing randomized controlled trials. By synthesizing data from diverse clinical trials, the study aims to elucidate the specific effects of glucocorticoids on skin lesions, including erythema, edema, and desquamation. Furthermore, it will explore potential variations in treatment outcomes based on different glucocorticoid regimens, dosages, and administration routes.


Understanding the nuanced relationship between glucocorticoid therapy and cutaneous manifestations in KD is imperative for optimizing therapeutic approaches and tailoring interventions to achieve comprehensive disease management. While the efficacy of glucocorticoids in mitigating systemic manifestations of KD has been extensively studied, there remains a paucity of comprehensive analyses focusing specifically on their effect on cutaneous manifestations, highlighting the importance of this meta-analysis in addressing this gap in knowledge.


The study undertook an extensive review of literature spanning two decades, from 2003 to 2023, sourced from reputable databases like Google Scholar and PubMed. Its primary objective was to gather data from randomized controlled trials concerning patients afflicted with Kawasaki Disease (KD) and concurrent skin wounds, aiming to scrutinize the impact of glucocorticoids. Employing a strategic approach, the investigation utilized various combinations of keywords such as ‘glucocorticoids,’ ‘skin wounds,’ and ‘Kawasaki disease,’ alongside free terms, to broaden the scope of inquiry.


The study’s design entailed a systematic literature review and meta-analysis utilizing the R package meta, involving a cohort of 2000 Kawasaki disease patients exhibiting skin wounds. A diverse array of glucocorticoid therapies, often administered alongside intravenous immunoglobulin (IVIG) and other steroids, were examined. Rigorous screening and extraction of data were performed in accordance with predefined inclusion and exclusion criteria, which encompassed patient demographics, publication year, and primary authors. Additionally, the literature review facilitated the identification of specific glucocorticoids employed in the treatment of Kawasaki disease.


In terms of outcomes measured, the study evaluated the efficacy of glucocorticoids in ameliorating both skin wounds and Kawasaki disease. Statistical metrics such as risk ratio (RR), confidence intervals (CIs), p-values, and analyses of adverse effects were employed to gauge the effectiveness of glucocorticoid therapy. This comprehensive analysis aimed to contribute valuable insights into the therapeutic potential of glucocorticoids in the management of Kawasaki Disease and associated skin manifestations.

Inclusion Criteria

To facilitate further meta-analysis, pertinent data was meticulously extracted from the literature review, adhering to specific inclusion criteria. These criteria encompassed several key aspects: 


  1. Patient Characteristics: This included parameters such as the number of patients, age distribution, and gender breakdown (male/female).


  1. Intervention Classification: The interventions were stratified into distinct groups. Intravenous immunoglobulin (IVIG) and glucocorticoids were categorized as the intervention group, while other forms of steroids were designated as the control group.


  1. Outcomes Focus: Emphasis was placed on studies examining gender-specific effectiveness concerning GLP-1 analogues, ensuring a nuanced understanding of outcomes in relation to gender.


  1. Study Design: Both retrospective studies and randomized controlled trials were considered, ensuring a comprehensive analysis encompassing various methodological approaches.


By meticulously selecting and categorizing data according to these criteria, the meta-analysis endeavors to provide a robust synthesis of findings, contributing to the broader understanding of the efficacy and implications of the interventions under investigation.

Exclusion Criteria

Studies lacking sufficient and pertinent data on patient demographics and the effects of glucocorticoids in Kawasaki disease (KD) with skin wounds were excluded from consideration. Additionally, studies lacking full-text accessibility were excluded to ensure the inclusion of relevant information for meta-analysis purposes.

Statistical Analysis

In conducting the meta-analysis, the metabin function within the R package meta version 4.3.2 was utilized. This process involved inputting event numbers and total patient counts for both control and intervention groups in studies focusing on binary outcomes. The aim was to compute effect sizes, confidence intervals, and various statistics such as heterogeneity, weight percentage, and statistical significance (signified by a p-value below 0.05), employing I2 and τ metrics.


The meta-analysis specifically investigated the efficacy of different glucocorticoid therapies for Kawasaki disease patients. Additionally, the analysis included a thorough examination of publication bias through funnel plots and Egger’s test. Furthermore, linear regression was employed to interpret any asymmetry detected in the funnel plots, utilizing Egger’s test results. This comprehensive approach aimed to provide insights into the effectiveness of glucocorticoid therapy while ensuring robust statistical analysis and bias assessment.


The literature screening process comprised four key stages: identification, screening, eligibility assessment, and final inclusion of studies. Thirteen relevant studies were meticulously reviewed, with ten selected for meta-analysis. The primary objective was to identify studies offering detailed patient information and intervention outcomes. Notably, glucocorticoid treatment for Kawasaki Disease (KD) patients with skin wounds demonstrated effectiveness across various glucocorticoid therapies, primarily ‘IVIG + glucocorticoid,’ alongside other analogues such as ‘IVIG-Sensitive,’ ‘IVIG + PSL,’ and ‘DEX.’


The adverse effects of glucocorticoids were analyzed, comparing fever duration between intervention and control groups. Patients receiving glucocorticoids and IVIG exhibited shorter fever duration, with most studies reporting significant values for the intervention group. However, certain studies lacked specific criteria for the control group. Adverse effects were comparatively analyzed across studies, revealing insights into the impact of glucocorticoids.


In the meta-analysis, significant statistical heterogeneity was observed across studies, indicating variability in true effect sizes. A random effects model, considering both within-study variability and between-sampling error, estimated the average effect size. Glucocorticoids, alongside interventions for Kawasaki disease patients, significantly reduced disease impact, with an RR of 1.08 and a 95% CI of 0.58–2.00. Publication bias analysis using Egger’s test yielded insignificantly biased results, ensuring the robustness of findings.


Glucocorticoids have emerged as a promising treatment for Kawasaki Disease (KD) due to their anti-inflammatory and immune-responsive properties. While they have shown significant potential in managing the condition, concerns regarding associated adverse effects necessitate exploration of long-term treatment options. Synthetic glucocorticoids have proven effective against KD and related skin infections, addressing the urgent need posed by the global rise in KD cases.


Despite the effectiveness of glucocorticoids, Kawasaki disease remains challenging to remedy definitively, often leading to complications such as skin rashes and eczema if left untreated. Ongoing research is crucial to understanding the disease better and developing more effective treatment strategies. Of particular concern is the healing of skin wounds in KD patients, which requires focused investigation.


Studies have demonstrated that glucocorticoids, especially when combined with steroids and intravenous immunoglobulin (IVIG), can effectively mitigate the adverse effects of KD. However, significant heterogeneity in research findings underscores the need for further investigation to address potential biases and refine treatment protocols.


Glucocorticoids, particularly when administered alongside IVIG, hold promise for managing adverse effects and infections associated with KD. Future research should prioritize understanding the dynamics of wound healing with glucocorticoid therapy to optimize treatment outcomes.


To enhance our understanding of the impact of glucocorticoids on Kawasaki disease patient outcomes, it is imperative to increase the number of studies and interventions in this area. By doing so, we can improve treatment effectiveness and ultimately contribute to better health outcomes for KD patients.

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