Management of Kawasaki Disease and its Cardiac Sequelae

- Executive Summary

- Recommendations

- Acknowledgments

▪️The GDG/ GAG acknowledges EPG for its help in completing this project.

▪️   We acknowledge The European Single Hub and Access point for pediatric Rheumatology in Europe, the Italian Society of Pediatrics, The Japanese Circulation Society\ the Japanese Society of Cardiovascular Surgery, and the American College of Rheumatology/Vasculitis Foundation guidelines (the source original guidelines) for their cooperation in providing the permission for adapting our guidelines.

▪️   We thank Mrs. Safa Rashad for drawing the Kawasaki boy caricature.

▪️  Finally, we wish the best for all our patients and their families who inspired us. It is for them this work is being finalized.

Funding

▪️This work is not related to any pharmaceutical or industrial company. The members of the GDG/ GAG and their institutes and universities volunteered their participation and contributions

- Abbreviations

- Introduction

➡️Background:

The Egyptian experience in the diagnosis and management of Kawasaki disease (KD) has evolved and intensified over the past years, especially with the emergence of atypical, incomplete cases and with the appearance of Multisystem Inflammatory Syndrome in Children (MISC). Meanwhile, a survey conducted by Kawasaki Disease Arab Initiative (Kawarabi) in 13 Arab countries, showed that the quality of medical services received by children with KD in large cities was rated as excellent in 6/13 or good in 7/13 countries compared to fair in 4/13 or poor in 4/13 countries in rural areas and they concluded that KD patients in mid-size cities and rural areas have limited access to standard healthcare in the Arab world ⁽⁹⁾. Accordingly, the establishment of Egyptian evidence-based guidelines for the management of KD in children is a necessity with consideration of the available facilities and the local limitations.

➡️What is Kawasaki Disease?

KD is an acute, self-limited febrile illness that predominantly affects young children, especially those under 5 years of age, with a median age of onset of 9 to 11 months. Approximately 25% of cases occur in older children, and it rarely affects adults ^(10). It is more common in males than females by a ratio of 1.5 to 1 ⁽¹⁰⁾. Age and gender play an important role as risk factors for complications, as age less than one year or above 9 years, and male gender have universally been identified to be significant risk factors for developing coronary artery aneurysms ^(11).

➡️Seasonal peaks: -

Evidence of seasonal variations has been demonstrated with a peak incidence in January through March in the Northern hemisphere, compared to a peak in May through June in the Southern hemisphere ⁽¹²⁾. This seasonality is suggestive of an environmental agent that may play a role in disease causation in different regions and ethnicities. Because the incidence of Kawasaki disease peaks during winter and spring, an infectious agent as a primary trigger may be suggested ⁽¹³⁾.

➡️Etiology and pathogenesis:

Despite more than 50 years of study, the exact etiology of Kawasaki disease remains unknown. Immunologic response to an exposure in the respiratory system or gastrointestinal (GI) tract or both in a genetically susceptible child is the most accepted theory. The immunologic cascade leads to systemic inflammation in medium-sized arteries and multiple organs in the acute phase ⁽¹⁴⁾.

➡️Diagnostic criteria: -

Recommendations for the diagnosis of KD are shown in table A

KD is categorized into two types: Classic KD(CKD) and Incomplete KD (IKD) ⁽¹¹⁾. Typical KD or CKD have clear diagnostic criteria which are shown in figure (1) a and (1) b. Not all features of KD appear at the same time and watchful waiting might be needed to reach a diagnosis.

Figure (1a): Features of classic Kawasaki disease (KD).

Figure (1b): Features of classic Kawasaki disease (KD).

Additional symptoms can be evident in KD patients but are not encompassed by the principal criteria (fig 1c and fig 1 d), they include arthritis, gastrointestinal involvement, irritability, lethargy, neurological manifestations, cough, and rhinorrhea. Arthritis, primarily affecting the large joints of the lower extremities (such as the knees, hips, and ankles), can be identified in 7.5% to 25% of patients and is typically temporary and non-deforming ^(15,16).  In exceptional instances, abdominal imaging techniques such as radiographs or computed tomography (CT) scans might reveal indications of pseudo-obstruction, a condition that can sometimes manifest before the appearance of cardinal symptoms ⁽¹⁷⁾.

In incomplete KD (IKD), children have some symptoms appearing late or not at all, making it somewhat invisible and overlapping with the clinical symptoms of various pediatric infectious or connective tissue diseases. This increases the likelihood of misdiagnosis and underdiagnosis, leading to residual cardiac complications, and even death ⁽¹⁸⁾.

The estimated ratio of male to female patients in children with IKD is 1.5: 1.

The main clinical features of children with IKD, are the high incidence of periungual desquamation around the finger (toe) and redness at the site of BCG inoculation during the fever and recovery period, low incidence of erythema and cracking of the lips, conjunctival congestion, oedema of the hands and feet, strawberry tongue, enlarged cervical lymph nodes, and high serum levels of C-reactive protein (CRP) ⁽¹⁹⁾ .

Among the mucocutaneous manifestations, nail abnormalities can be observed. Orange-brown transverse chromonychia has also been occasionally described. During the convalescent phase, transverse leukonychia and Beau’s lines are the most common ⁽²⁰⁾.

On the other hand, Atypical KD occurs in patients who, along with the usual clinical features of KD, also have a few unusual clinical manifestations, such as pulmonary involvement and renal impairment ⁽²¹⁾.

Figure (1)c: Additional clinical features of KD.

CNS: Central Nervous System: Bacillus Calmette Guerin; GIT: Gastrointestinal tract; GU: Genitourinary

Figure (1)d: Induration of BCG scar in atypical KD patient.

Recommendations for diagnosis of classic, incomplete and atypical Kawasaki disease are shown in Recommendation table A.

➡️Disease Course:

Kawasaki Disease natural clinical course can be divided into three phases:

Acute (1st-2nd Week), Extreme irritability exists, by the end of which CAA can occur

Subacute (3rd-4th week), characterized by defervescence, periungual skin desquamation, thrombocytosis and progress of or appearance of new CAA,

Convalescence phase (5th–8th week), in which all KD signs disappear, inflammatory markers normalize, and transversal nail indentations (Beau’s lines) may appear ⁽²²⁾.

➡️Cardiovascular Involvement in Kawasaki Disease:

Coronary artery involvement is the most serious complication in children with KD. Coronary artery abnormalities occur in 25% of untreated patients and 5% of patients treated with intravenous immunoglobulin (IVIG) ^(7). A study from Egypt reviewed a series of 580 patients ≤ 40 years of age presenting with symptoms of coronary artery ischemia and reported lesions consistent with antecedent KD in 6.7 % of cases ⁽²⁴⁾. Data on exact prevalence of CAA in Egyptian children is not yet determined.

The proximal left anterior descending artery and the proximal right CA are the most frequent locations of CAA, and the posterior descending artery is the least common. ⁽²⁵⁾

Table 2 Highlights Cardiac affection in KD according to the American Heart ➡️Association (AHA) Guidelines 2017 ⁽⁷⁾:

Several non-coronary complications have now been identified in this condition, but these are often overlooked. Myocarditis is an integral component of KD and may be more common than coronary artery abnormalities. Myocarditis is universal in almost all patients with KD during the acute phase of disease. Transient left ventricular dysfunction can occur in more than 50% of patients. Pericardial involvement and valvular abnormalities have also been observed in patients with KD ⁽²⁵⁾. Cardiac affection in KD is shown in figure (2).

Figure (2): Cardiovascular affection in KD.

CHF: Congestive heart failure, RCA: Right coronary artery, LAD: Left anterior descending, LMCA: Left main coronary artery.

 On the other hand, KD shock syndrome (KDSS) is now being recognized and may be difficult to differentiate clinically from toxic shock syndrome ⁽²⁶⁾. In KDSS, KD manifestations are accompanied by multiorgan involvement and reduced organ perfusion due to systolic hypotension. KDSS is a serious condition that can present to the emergency department as an initial feature when typical clinical symptoms of KD have not been detected ⁽²⁷⁾. Patients may have more prominent inflammatory markers and result in shock and hypotension, which requires critical care support at an early stage. Features that enable distinguishing KDSS from the usual KD case presentation include: (1) patients with KDSS are older than the usual patient with KD and have a higher prevalence and severity of GI symptoms; (2) patients with KDSS present with worse biological and inflammatory markers, (3) exhibit a higher resistance rate to IVIG, (4) have a higher rate of CAA, and (5) have greater number of reported cases of ventricular systolic dysfunction and atrioventricular valve regurgitation.

This is different from Toxic Shock syndrome, which should be diagnosed according to the CDC criteria ⁽²⁹⁾

Kawasaki disease and Multisystem inflammatory syndrome in children: -

Recommendations for differentiation of KD and MISC are shown in Recommendation table A.

MIS-C and KD are considered 2 distinctive diseases triggered by different infectious agents. They may belong to the same umbrella of inflammatory disorders but differ in many aspects of etiology, demography, epidemiology, clinical and laboratory findings, and pathology. Both diseases share many clinical features such as fever, rash, and mucocutaneous involvement, and can affect multiple organ systems. The intensity of the inflammatory response and long-term cardiovascular sequelae diverge between KD and MIS-C. Whereas MIS-C presents a more intense inflammatory syndrome, myocardial dysfunction, and cardiogenic shock. KD vasculitis is associated with pathologic changes in the coronary arteries and long-term cardiovascular sequelae ^(30,31).

Differential Diagnosis of KD is displayed in Annex Table 4^(32-37).

 ➡️Investigations:

A.   Laboratory Investigations

Recommendations on investigations required in KD are provided in Recommendation table B.

Investigations in suspected KD patients are shown in Table2

Table 2: Investigations in suspected KD patients ⁽²⁾

^{*Diagnostic positive level used in Egyptian laboratories is > 5mg/L}

^{•    CRP: C -reactive protein, ESR: Erythrocyte sedimentation rate, WBCs: White blood cells, HPF: High power field.}

N-terminal prohormones of brain natriuretic peptide (NT-proBNP) The utility of NT-proBNP as a biological marker in KD is based on the universal myocardial inflammatory component early in the course of the disease. Patients with KD have higher NT-proBNP at the time of diagnosis than other febrile patients, with a pooled sensitivity of 89%, and a specificity of 72%. Moreover, patients with resistance to intravenous immunoglobulin treatment and CAA were found to have higher levels of NT-proBNP, suggesting a prognostic role. Nevertheless, the non-specificity of NT-proBNP to KD limits its use as a stand-alone test. It is worth mentioning that NT-proBNP proved superior to BNP in the evaluation of KD at the onset of the disease, thanks to the longer half-life of the former providing greater sensitivity and specificity ⁽²³⁾

Evaluation of Suspected incomplete KD shown in the following figure

     Fig 3: Evaluation of Suspected incomplete Kawasaki Disease ^(1,36)

B.   Echocardiography :

It should be performed in all patients suspected or confirmed to have KD. Recommendations on the protocol of echocardiographic examination in KD are shown in Recommendation table B.

Routine use of CA Z scores has brought a level of standardization to quantification of CA size. It is important for centers to use the same Z score equation for comparisons over time in patients with KD.

Recommended frequency of echocardiographic examination in KD patients is shown in Fig 4.

Fig (4): Recommended frequency of echocardiographic examination in KD patients.

Coronary artery measurements should be taken from the inner edge to inner edge of the vessel wall, avoiding the orifices and points of branching which may have normal focal dilatation ⁽²³⁾

The presence of marked perivascular brightness, the absence of the physiological gradual reduction of coronary artery caliber, and mild ectasia, if isolated, are not indicative of KD. These findings could be considered a positive echocardiographic KD sign when are all three simultaneously present ^(1).

Follow up of KD and CAA: TTE is the primary imaging tool for follow up CAA. Owing to its limited acoustic windows in distal CA, TEE and CT angiography are recommended. Advanced CA imaging using MRI or CTA may be needed for better designations in patients with KD. CTA will delignate aneurysm and stenosis. MRI for Myocardial function analysis and inducible ischemia. Stress echo can be used to follow pts with CCA and ischemia symptoms ⁽³⁶⁾.

 ➡️KD Treatment: -

At presentation, the low-risk KD should be differentiated from high-risk cases (baseline CAA Z score ≥2.5, infants < 12 months or in high-risk category using the Son risk score, in addition to patients presenting with KD shock syndrome) ⁽⁸⁾ (Fig 5). Patients with standard risk can be treated with IVIg and aspirin. The general approach for treating low risk KD cases is administering a single high dose (2 g/kg) of IVIG intravenously over 10–24 hours within 10 days of disease onset. This should be accompanied by the oral administration of aspirin (30–50 mg/kg), until the patient is afebrile for 48 to 72 hours. In a classic KD, treatment should be initiated without waiting for echocardiography. ^(23,5) This can quickly and effectively relieve symptoms and decrease the incidence of CALs and CAAs ^(37).

To reduce the risk of hemolytic anemia in obese patients, IVIG dosing should be based on lean body mass. ⁽³⁸⁾

Patients with high-risk KD may benefit from intensification of initial therapy with IVIg plus adjunctive anti-inflammatory therapy to reduce the risk of CAA. These therapies include corticosteroids, tumor necrosis factor α inhibitors (eg, Infliximab & Etanercept), interleukin-1 inhibitors (eg, Anakinra), and cyclosporine ⁽⁸⁾. Proposed treatment regimen for KD is shown in figure 5.

KD: Kawaski Disease, MAS: Macrophage activating Syndrome, DIC: Disseminated Intravascular Coagulation SD: Standard Deviation, ALT: Alanine Transaminase, IVIG: Intravenous Immunoglobulins, ASA: Acetyl Salicylic Acid, CST: Corticosteroid Therapy, CA: Coronary Artery. 1Most practitioners start with standard dose of steroids (2 mg / kg / day IV methylprednisolone) but some practitioners prefer high dose steroids (10-30g / kg / day methylprednisolone  for 3-5 days then decrease to standard IV dose ) especially in low income countries in which IVIG treatment could be delayed to 12-24 hours after diagnosis  of KD ( or more )  due to shortage of that  expensive drug.2 Infliximab is given IV , 10 mg/kg over 2 hours single dose .3 Anakinra ,10 mg/kg/day ,is given IV/SC (preferred IV divided /12 hours).   

Figure 5: Proposed algorithm for management of KD^(38,39,40).

For corticosteroids therapy as an intensification therapy, the RAISE study suggested the use of IV prednisolone, 2 mg/kg per day divided every 8 h for 5 d (maximum 60 mg/d) while hospitalized; then PO prednisolone 2 mg/kg per d divided every 8 h; slow tapering over 15 d (maximum 30 mg/dose) once CRP normalized. On the other hand, North American studies suggested using Methylprednisolone with the same doses given every 12 hours and to be tapered over 2–4 weeks with the dose cut in half every 5 days. ^(42,43) Another protocol for non-responders with KD should be managed with a second IVIG cycle and - in case of failure - with 3 pulses of methylprednisolone (30 mg/kg/day), followed by oral prednisone (2 mg/kg/day, then gradually tapered up to the resolution of symptoms and normalization of CRP)⁽¹⁾

If the child has been ill for more than 14 days and inflammatory symptoms and laboratory changes are no longer present, only low-dose anti- aggregation dose of aspirin (3–5 mg/kg/d) should be administered to prevent thrombosis.  Echocardiography should be performed in these patients at the time of presentation and at regular intervals within the next 2 months to follow up on coronary arteries to decide on the duration of aspirin therapy ⁽⁴⁴⁾. There is increasing evidence that medium- or high-dose aspirin in the acute phase is likely not associated with improved CA outcomes ^(45,46).

Patients with no coronary dilation should be maintained on LDA (low dose aspirin) for 6-8 weeks with no further interventions. For patients with Z score 5 - <10 and absolute dimension < 8 mm they should be maintained on double antiplatelet ill regression of the aneurysm ⁽²³⁾

Medium-high dose ASA should be replaced in case of concurrent varicella or influenza to avoid the potential development of Reye’s syndrome though low-dose aspirin has not been associated with any documented cases of Reye syndrome and therefore is safe to continue in the event of intercurrent infection. Children may receive dipyridamole (1–5 mg/kg/day divided into 3 doses), ticlopidine (2–7 mg/kg/day divided into 2 doses), or clopidogrel (1 mg/kg/day in a single dose up to a maximum of 75 mg/day in children > 2 years or 0.2 mg/kg of body weight in children < 24 months) in replacement of ASA ⁽⁴⁷⁾.  It is recommended to avoid non-steroidal anti-inflammatory drugs such as ibuprofen in children receiving low-dose aspirin as they can antagonize platelet inhibition sought for with by aspirin ^(48,49).

Management recommendations for children with KD are shown in Recommendation table C.

 Commonly used medications in treatment are shown in table (3).

IVIG resistance: -

Recommendations for the identification of risk factors of IVIG resistance as well as management are shown in Recommendation table C.

Patients with persistent or recurrent fever ≥36 hours after the completion of the initial IVIg infusion are defined as IVIg resistant ⁽⁵⁰⁾. Fifteen to 20% of individuals with KD seem to be IVIG resistant and are at greater risk of developing CAA formation (15%) than those who respond to IVIG (5%). Various IVIG resistance (refractory) prediction scores, such as the Kobayashi score (table 4) have been devised for predicting IVIG resistance if total score exceeds 4. Son risk score also can be used to determine risk score. It comprises age <6 months, Asian race, CA Z score >2 on initial echocardiogram, and C-reactive protein >13 mg/dL (each with 1 point assigned, except for 2 points assigned to CA). A risk score ≥3 points is strongly predictive of CAA by 8 weeks after acute illness ⁽²³⁾. These scoring systems are thought to contribute to the continuous reduction of CAL occurrence ⁽⁵⁰⁾. Current evidence supports the use of infliximab as rescue therapy in IVIG- and methylprednisolone-refractory patients with KD. IL-1 blockade with anakinra is highly promising in treating the most dramatically severe multi-refractory patients with KD, with potential benefits also on the cardiovascular complications ⁽⁵¹⁾. ^{Table 5 shows the additional anti-inflammatory therapies in high-risk KD patients or those resistant to initial IVIG treatment}

Table (4)   Kobayashi Scoring System for prediction of IVIG resistance ⁽⁵⁰⁾

^{AST: Aspartate aminotransferase, CRP: C reactive protein. Kobayashi score ≥5 points has a sensitivity of 76% and a specificity of 80% in Japanese population}

 ^{Table (5): Additional anti-inflammatory therapies in high-risk KD patients or those resistant to initial IVIG treatment *(51,52,53)}

*Plasma exchange and biologic disease modifying anti-rheumatic drugs (DMARDs) like infliximab, anakinra cannot be recommended, except on an individual basis after consultation with a specialist unit.

*Non-biologic DMARDs such as cyclosporin, cyclophosphamide and methotrexate might be used in refractory-KD. They should only be considered in severe refractory cases because of potential adverse reactions, after consultation with a specialist unit.

IgG: immunoglobulin G, TNF: Tumor necrosis factor, SC: Subcutaneous, AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, BUN: Blood urea nitrogen, MAS: Macrophage activation syndrome.

KD and Macrophage activation syndrome (MAS):

The recommendation of the identification and management of MAS in patients with KD is shown in Recommendation table C. Formal diagnostic criteria for MAS in the setting of KD have not been developed. However, drawing on experience with other secondary Hemophagocytic syndrome presentations, MAS may be suspected in KD patients with persistent fever, splenomegaly, elevated ferritin levels, and thrombocytopenia. Inadequate treatment of either KD or MAS could result in severe consequences. These include large coronary aneurysms or coronary artery stenosis, leading to death via cardiac infarct or coronary rupture in KD, or death due to multiorgan dysfunction in MAS. Thus, to ensure appropriate therapy, each disease entity should be considered separately with appropriate targeted therapy. KD should be treated with IVIG as the first-line therapy, and MAS should also be treated with appropriate agents for targeting cytokine storms or underlying triggers. Anakinra and glucocorticoids are preferred for treatment in these patients over a primary HLH-directed treatment protocol with cytotoxic agents. ⁽⁵¹⁾

^{Thromboprophylaxis}

KD patients with small or medium-size aneurysms receive antiplatelet therapy, following the belief that thrombus development is initiated by platelet activation and adhesion. In large aneurysms, however, humoral clotting factors are involved secondary to flow stasis; therefore, anticoagulant therapy is deemed necessary. Both Warfarin and LMWH have been shown to have similar efficiency in preventing thrombosis in KD patients with large aneurysms. They both have similar safety profiles with no substantial differences in the cumulative incidence of major bleeding complications ⁽⁵²⁾.

Frequent blood work is required for routine monitoring of warfarin to ensure maintenance within a therapeutic window, and dosing can be challenging due to warfarin’s possible interactions with food. Certain foods that are rich in vitamin K may affect the therapeutic effects of warfarin, while other foods, such as grapefruit juice, interact with the metabolism of warfarin via the cytochrome P450 pathway ⁽⁵³⁾. Furthermore, warfarin has many known drug interactions. Antimicrobials such as trimethoprim-sulfamethoxazole and erythromycin have been known to enhance the effects of warfarin, whereas rifampicin has been reported to reduce its effects. In addition, genetic polymorphisms have been found to be associated with warfarin metabolism, which further complicates the issues with dosing ⁽⁵⁴⁾.

LMWH has added advantages over warfarin because of its somewhat less intensive monitoring requirements and faster achievement of monitoring levels within the therapeutic window, although potential negative effects on bone health associated with long-term treatment and discomfort associated with the injections make it less than ideal as a solution. It is a particularly useful option for younger patients in whom frequent blood work is less feasible ⁽⁵⁵⁾

 Warfarin is advantageous compared with LMWH because of its ability to counter the anticoagulation effect promptly by means of vitamin K administration. The anti–factor Xa activity of LMWH is only partially reversible with protamine.

 In the last decade, direct-acting oral anticoagulants, namely, direct thrombin inhibitors and anti–factor Xa agents, and novel antiplatelet agents have been introduced in adults. ⁽²⁹⁾ These agents have been known to have certain advantages over classic anticoagulants, such as minor or absent food and drug interactions. In addition, they require limited or no monitoring and are delivered via the oral route, which may be a better option for patients who are averse to daily injections. Although their nonreversible nature has long been a limitation of direct oral anticoagulants from a safety point of view, antidote therapies for those agents are emerging which will allow reversal in case of severe bleeding events. However, these agents have not been adequately studied in children. Once there is more safety and efficacy data, regulatory approval, and availability of pediatric preparations, direct-acting oral anticoagulants will likely replace warfarin, not only for KD patients, but also for many other pediatric patients ⁽⁵⁶⁾.

Recommendations table D shows the Management of coronary involvement in children with KD.

Coronary thrombosis and Myocardial Infarction in relation to KD:

KD patients with CAA are at highest risk of myocardial infarction in the first 2-3 months after illness. The presentation of these patients is different than adults. Patients with giant CAA have a lifelong risk of ischemia ^(58,59,3). The algorithm for management is shown in figure 6 .

Figure (6): Management of possible coronary thrombosis in children with KD

Long-term management (after convalescence) of KD patients with coronary lesions

Recommendations table E shows the long-term management of KD

Medical therapy for myocardial protection such as beta- blockers (carvedilol, metoprolol, or bisoprolol) decrease the risk of myocardial infarction and death by reducing myocardial oxygen demand. Angiotensin converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs) also protect against myocardial infarction and death. Statins in addition to their cholesterol-lowering action have other pleiotropic effects in inflammation, endothelial dysfunction, oxidative stress, platelet aggregation, coagulation, and fibrinolysis, which make them useful in the management of KD. Huang, et al. reported a beneficial effect of short-term (3 months) statin treatment (simvastatin, 10 mg/day as a single dose at bedtime) in KD patients complicated with CAL. Chronic vascular inflammation is also significantly improved, as well as endothelial dysfunction, with no adverse effects. ⁽⁶¹⁾ However, long-term and randomized control trials are needed before further conclusions can be made.

The use of an ACE inhibitor in combination with a beta-blocker during the acute phase of Kawasaki disease (KD) in normotensive infants has been proposed in some observational studies; however, this approach has not been formally recommended by current guidelines. While there is a theoretical rationale based on the role of angiotensin II in promoting endothelial proliferation and vascular remodeling, which may contribute to coronary artery aneurysm (CAA) progression, the clinical evidence supporting such an intervention in the acute phase of KD is limited and of low certainty. Therefore, the panel judged this strategy to be speculative and not supported by sufficient high-quality data to inform a clinical recommendation. Further research is needed to assess the potential benefits and risks of this approach.

Following up of patients depends largely on the degree of coronary affection:

Patients with no coronary dilation should be maintained on LDA (low dose aspirin) for 6 weeks with no further interventions. If dilatation only was present at the acute stage, it should be reassessed at regular intervals till 1 year post convalescence.

For patients with small coronary artery aneurysms (Z score 2.5–4.9), regular follow-up with echocardiography is recommended. Aspirin may continue until normalization of coronary dimensions. The routine use of stress testing or coronary CT angiography (CTA) in this group is not currently supported by strong evidence and may be reserved for selected cases based on clinical risk factors or symptoms. Further studies are needed to determine the optimal imaging interval in this subgroup.

 Patients with Medium and Large Coronary Aneurysms (Z score ≥5):

For medium aneurysms (Z 5–<10, diameter <8 mm): Dual antiplatelet therapy (e.g., aspirin + clopidogrel) should be considered until aneurysm regression with baseline ischemia assessment (stress echo or coronary CTA) at ~1-year post-illness to be repeated every 2–5 years, based on symptoms or clinical risk. Beta-blockers and stains may be considered for possible endothelial protection and ischemia risk reduction ⁽⁶²⁾.

For Large aneurysms (Z ≥10 or diameter ≥8 mm): should consider combined antiplatelet and anticoagulation therapy in addition to beta blockers.  Contact or high-impact sports should be restricted due to bleeding and ischemic risk. In addition to regular advanced imaging and close specialist follow-up ⁽⁶³⁾.

Transition to adult care:

Patients with KD and coronary artery lesions, either persistent or those that have been remodeled and have decreased to a normal internal luminal dimension, should have long‐term follow‐up, with their care transitioned to an adult cardiologist once they reach adulthood, generally between the ages of 18 and 21 years.

The transition from pediatric to adult care for these patients needs to be a process involving a deliberate and coordinated series to ensure uninterrupted care. Transition should involve 6 cores:

1.The policy: preparing an office transition guide for families, including discussion of the practice's approach to an adult model of care around privacy and consent.

2. Tracking: ensuring that patient is offered a transition readiness/self‐care skill assessment conducted periodically.

3. Transition readiness. The pediatric clinician should have a standardized way of assessing the youth's self‐care skills.

4. Planning should include creating a transition plan jointly developed with youth and families that includes preparing decision-making support, assembling a medical summary and emergency care plan shared with youth and families, identifying an adult cardiologist and primary care clinician, and preparing transfer information for and communication with the new clinician.

5. Transfer of care, which requires engagement during this vulnerable transition time of both the adult clinician and the pediatric subspecialist to help the young adult schedule a follow‐up appointment with the adult health care clinician within 3 to 6 months of leaving the pediatric clinician.

6. The sixth core element is transition completion, during which the pediatric clinician confirms that the young adult has been seen by the adult clinician and facilitates obtaining patient feedback about the HCT process.

The 6 core elements is a process that evolves over several years and includes working with the adolescent's developmental stages to achieve maturity, education, and self‐management. More details on transition can be checked on the scientific statement from AHA 2021 ⁽⁶⁴⁾.

- Methods of search

A comprehensive search for guidelines was undertaken to identify the most relevant guidelines to consider for adaptation. Keywords used for the search are Kawasaki disease, Cardiovascular sequelae of Kawasaki disease, Coronary affection in Kawasaki disease in children, Coronary artery aneurysms, coronary artery lesions.

Inclusion/exclusion criteria followed in the search and retrieval of guidelines were adapted:

• Selecting only evidence-based guidelines (guideline must include a report on the methodology of development including the systematic literature searches and explicit links between individual recommendations and their supporting evidence)

• Selecting national and/or international guidelines

• Specific range of dates for publication (using Guidelines published within the last 5 years)

• Selecting peer-reviewed publications only

• Selecting guidelines written in the English language

• Excluding guidelines written by a single author

➡️The following three categories of databases and websites were searched:

1.    CPG databases and libraries (e.g., GIN, ECRI, SIGN, DynaMed, BIGG-REC PAHO)

2.    Bibliographic databases (e.g., PubMed, Google Scholar)

3.    Specialized professional societies (related to the pediatric subspecialty)

All retrieved Guidelines were screened and appraised using AGREE II instrument (www.agreetrust.org) by at least two members. The panel decided on a cut-off point or ranked the guidelines (any guideline scoring above 60% on the rigor dimension was retained)

After reviewing all the previous criteria, the GDG/ GAG recommended using 5 guidelines:

1.    Revised recommendations of the Italian Society of Pediatrics about the general management of Kawasaki disease (2021) based on the Guidelines of the Italian Society of Pediatrics on Management of Kawasaki disease 2018.

2.    American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease. (2021).

3.    European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease - the SHARE initiative (2019)

4.    JCS/JSCS 2020 Guideline on Diagnosis and Management of Cardiovascular Sequelae in Kawasaki Disease (2020)

5.    American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 2(2022)

We did Adolopment for these guidelines: (Adoption, Adaptation, and Development)

         -    Adoption for most of the guideline recommendations.

         -    Development of Good Practice Statement

➡️Contributors to the guideline development process:

Guideline Development Group (GDG)/ Guideline Adaptation Group (GAG):

The GDG/ GAG included two subgroups: the clinicians/ healthcare providers subgroup and the guideline methodologists’ subgroup.

➡️Clinicians Subgroups

The clinicians’ subgroup or clinical panel for this guideline included experts with a range of knowledge, technical skills, and diverse perspectives in the field of Pediatric Cardiology, as well as rheumatology and immunology. and clinical pharmacy.

The main functions of the clinical panel were adolopment of Kawasaki disease Guidelines, determining the scope of the guideline and guidelines, reviewing the evidence, and formulating evidence-informed recommendations in case of changing the strength of recommendations.

➡️Guideline Methodologists Subgroup

Guidelines methodologists with expertise in guidelines development, adaptation, GRADE, and translation of evidence into recommendations participated in the adaptation process. They provided orientation and overview of evidence-informed guideline development processes using the GRADE approach, guideline adaptation using the Adapted ADAPTE, provided AGREE II assessment of the source guidelines in collaboration with the clinician's subgroup, generation of the EtD frameworks whenever applicable.

➡️External Review Group:

The External Review Group for this guideline comprised 3 clinical international and national  experts who have interest and expertise in Kawasaki disease. They were identified by the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG) as people who can provide valuable insights during the guideline development process.

The External Review Group was asked to comment on (peer review) the final guideline to identify any criticism on the content and to comment on clarity and applicability as well as issues relating to implementation, dissemination, ethics, regulations, or monitoring, but not to change the recommendations formulated by the GDG/ GAG. The members of the External Review Group were required to submit declarations of interest before the peer review process.

➡️Guideline Development/ Adaptation Group meetings:

GDG/ GAG meetings were organized virtually (weekly/bimonthly). Due to the extensive scope of the guideline, EPG was responsible for overseeing the adolopment process. the timetable and the objectives of each meeting. GDG/ GAG meetings were also attended by members of the methodologists. Working rules for each contributor type were outlined by the chair at the start of each meeting, covering aspects such as vocal rights, voting, and evidence to decision and recommendation formulating processes.

➡️Declarations of interests:

Prospective members of the GDG/ GAG were asked to fill in and sign the standard WHO declaration of interest and confidentiality undertaking forms. All guideline members and methodologists were also asked to fill in and sign the standard WHO declaration-of-interests.

Members of the external review group will be asked to fill in and sign the standard WHO declaration-of-interest form before the peer review process.

 Evidence for the guideline:

We used the GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) for assigning the quality of evidence and strength of recommendations that includes the following definitions ^[61]. Description of the interpretation of the GRADE four levels of certainty of evidence:

Table 5. Classification of the Quality of Evidence

GRADE EtD’s contextual factors, criteria and considerations that link to the strength of recommendations:

Criteria and Considerations:

1.    Benefits and harms: When a new recommendation is developed, desirable effects (benefits) need to be weighed against undesirable effects (risks/harms), considering any previous recommendation or another alternative. The larger the gap or gradient in favor of the desirable effects over the undesirable effects, the more likely that a strong recommendation will be made.

2.    Certainty of the evidence about the effects: The higher the certainty of the scientific evidence base, the more likely that a strong will be made.

3.    Values and preferences: If there is no important uncertainty or variability in how much people value the main outcomes, it is likely that a strong recommendation will be made. Uncertainty or variability around these values that could likely lead to different decisions, is more likely to lead to a conditional recommendation.

4.    Economic implications: Lower costs (monetary, infrastructure, equipment or human resources) or greater cost-effectiveness are more likely to support a strong recommendation.

5.    Equity and human rights: If an intervention will reduce inequities, improve equity or contribute to the realization of human rights, the greater the likelihood of a strong recommendation.

6.    Feasibility: The greater the feasibility of an intervention to all stakeholders, the greater the likelihood of a strong recommendation.

7.    Acceptability: If a recommendation is widely supported by health workers and program managers and there is widespread acceptance for implementation within the health service, the likelihood of a strong recommendation is greater.

Table 6. Classification of the Strengths of Recommendations

➡️Developing good practice statements:

The GDG/ GAG also developed good practice statements for this guideline, which are actionable messages relevant to the guideline questions. The justification for each good practice statement was carefully considered by the GDG/ GAG with an emphasis that they are needed. Good practice statements were developed, guided by the following GRADE criteria:

1- Message is necessary about actual healthcare practice

2- Have large net positive consequences (relevant outcomes and downstream consequences) (GRADE EtD domains)

3- Collecting and summarizing the evidence is a poor use of time and resources

4- Include a well-documented, clear rationale connecting indirect evidence

5- Are clear and actionable statements.

The GDG/ GAG collectively drafted and finalized good practice statements with relevant justifications and remarks to help with their interpretation, with close support and input from the consultant and guideline methodologists.

We have used the Reporting Items for Practice Guidelines in Healthcare (RIGHT) extension for adapted guidelines (RIGHT-Ad@pt Tool) as a reporting checklist for this guideline adaptation process as recommended by the EQUATOR network.

- Implementation Tools and Considerations

To improve healthcare provision, quality, safety, and patient outcome, evidence-based recommendations must not only be developed, but also disseminated and implemented at national and local levels and integrated into clinical practice.

Dissemination involves educating related healthcare providers to improve their awareness, knowledge and understanding of the guideline’s recommendations. It is one part of implementation, which involved translation of evidence-based guidelines into real life practice with improvement of health outcomes for the patients.

Implementation requires an evidence-based strategy involving professional groups and stakeholders and should consider the local cultural and socioeconomic conditions. The cost-effectiveness of implementation programs should be assessed.

Specific steps need to be followed before clinical practice recommendations can be integrated into local clinical practice, particularly in low-resource settings.

➡️Steps of implementing Kawasaki disease diagnosis, treatment, and prevention strategies into the Egyptian health system:

1.  Develop a multidisciplinary working group.

2.  Assess the status of nutritional care delivery, care gaps, and current needs.

3.   Select the material to be implemented, agree on the main goals, identify the key recommendations for diagnosis, treatment, and prevention, and adapt them to the local context or environment.

4.  Identify barriers to and facilitators of implementation.

5. Select an implementation framework and its component strategies.

6.  Develop a step-by-step implementation plan:

·  Select the target populations and evaluate the outcome.

·  Identify the local resources to support the implementation.

·  Set timelines.

·   Distribute the tasks to the members.

·   Evaluate the outcomes.

7.  Continuously review the progress and results to determine if the strategy requires modification.

➡️Guideline implementation strategies will focus on the following: -

1.  For Practitioners

·  Educational meetings: conferences, lectures, workshops, grand rounds, seminars, and symposia.

·   Educational materials: printed or electronic information (software).

·   Web-based education: computer-based educational activities.

·   A trained person meets with providers in their practice setting to provide information with the intention of changing the provider’s practice. The information may include feedback on the performance of the provider(s).

·   Reminders: the provision of information verbally, on papers or on a computer screen to prompt a health professional to recall information or to perform or avoid a particular action related to patient care.

·   Optimize professional-patient interactions, through mass media campaigns, reminders, and education materials.

·   Practice tools: tools designed to facilitate behavioral/practice changes, e.g., flow charts.

2.  For Patients and care givers

·  Patient education materials (Arabic booklet): Printed/electronic information aimed at the patient/consumer, family, caregivers, etc.

·   Reminders: the provision of information verbally, on papers or electronically to remind a patient/consumer to perform a particular health-related behaviors.

·   Mass media campaigns.

3.   For Nurses

·   Educational meetings: lectures, workshops or traineeships, seminars, and symposia.

·  Educational materials: printed.

·   A trained person meets with nurses in their practice setting to provide information with the intention of changing the provider’s practice.

·  Reminders: the provision of information verbally, on paper or on a computer screen to prompt them to recall information or to perform or avoid a particular action related to patient care.

· Practice tools: tools designed to facilitate behavioral/practice changes.

4.  For Stakeholders

Plans have been made to contact with all the health sectors in Egypt including all sectors of the Ministry of Health and Population, National Nutrition Institute, University Hospitals, Ministry of Interior, Ministry of Defense, Non-Governmental Organizations, Private sector, and all Health Care Facilities.

·  Information and communication technology: Electronic decision support, order sets, care maps, electronic health records, office-based personal digital assistants, etc.

·  Any summary of clinical provision of health care over a specified period may include recommendations for clinical action. The information is obtained from medical records, databases, or observations by patients. Summary may be targeted at the individual practitioner or the organization.

·  Administrative policies and procedures.

·  Formularies: Drug safety programs, electronic medication administration records.

5.  Other activities to assist the implementation of the adapted guideline’s recommendations include:

·  International initiative: Dissemination of the presented adapted CPG internationally via sending the final adapted CPG to the Guidelines International Network (GIN) Adaptation Working Group and contacting the CPG developers.

·  Gantt chart has been designed to manage the dissemination and implementation stages for the adapted CPG over an accurate time frame (Appendix).

➡️Guideline Implementation Tools

Educational materials based on this Adapted CPG for treatment of CAP in children have been made available in several forms including:

1. Manual for physician for diagnosis and algorithm for atypical kawaski , and differentiation of KD from other diseases.

3. Arabic Educational materials for nurses and mothers

- Limitations and suggestions for further research needs

➡️Future research recommendations for the management of KD and its cardiac sequalae in children in the Egyptian context could include:

·  Large RCTs on the use of low dose IVIG versus high dose or IVIG replacement by steroids.

· Study of the long term microvascular coronary affection in children with history of Kawasaki disease.

·   The benefits of cardio-protective medications post KD treatment.

These recommendations aim to address specific challenges and characteristics of the Egyptian context, potentially leading to more effective prevention and management strategies for KD in children.

➡️Challenges

· Difficulty of reaching diagnosis of KD especially in incomplete or atypical forms.

·  Lack of sufficient data on cardiac sequalae in children with KD.

Strengthen the evidence base of the next update of this guideline by generating GRADE summary of finding tables, evidence profiles, and EtD frameworks.

- Monitoring and evaluating the impact of the guideline

The following are three performance measures or indicators for implementing this adapted CPG for

 KD management in children:

1.   Adherence to KD Guidelines

· Numerator: Number of children with KD who received treatment as per guideline recommendations.

·  Denominator: Total number of children diagnosed with KD

· Data Source: Hospital or clinic patient records.

2. Duration of Hospital Stay

·  Numerator: Total number of hospitals stay days for children with KD.

·   Denominator: Total number of children admitted.

·   Data Source: Hospital admission and discharge records.

3. Rate of Readmission

·   Numerator: Number of children readmitted with symptoms of KD within a certain period (e.g., 30 days) after discharge.

·  Denominator: Total number of children initially admitted with KD

·   Data Source: Hospital readmission records.

These key performance indicators are designed to measure the effectiveness and adherence to the guidelines, the efficiency of the treatment in terms of resource utilization (hospital stay), and the success of the treatment in preventing further complications (readmissions).

- Updating of the guideline

The EPG KD GAG has decided to conduct the next review of this adapted CPG for updates after five years. This should be carried out in 2029 after checking for updates in the source CPGs, consultation of expert opinion on the changes needed for updating according to the newest evidence and recommendations published in this area and the clinical audit and feedback from implementation efforts in the local healthcare settings except if any breakthrough evidence- based recommendations are published before that date. The process will be guided by the Checklist for the Reporting of Updated Guidelines (Checkups) Tool that is freely provided by the AGREE Enterprise and by the Reporting Items for Practice Guidelines in Healthcare (RIGHT) extension for adapted guidelines RIGHT-Ad@pt Checklist.

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- Annexes

Annex Table 1.

Declaration of Conflict of Interests

The members of the guideline development/ adaptation group and the external review group have no academic, financial, or competing interests to declare and none of them were involved in the development of the original source guideline(s).

Any identified potential COI has been reported below.

Annex Table 2. Results of the AGREE II assessment of the Five source guidelines

Annex 3. Nurses and Parents Educational Guide in Arabic

الملخص التعليمى الخاص بالتمريض و أهالى الأطفال المصابين بداء كاوازاكى

أهداف و ارشادات التمريض:-

قد تشمل الأهداف والنتائج المتوقعة ما يلي:

Ø   أن يحافظ الطفل على درجة حرارته الطبيعية.

Ø   أن يكون الغشاء المخاطي لفم الطفل خاليًا من الجفاف والتهيج.

Ø   أن يشعر الأهل بقلق أقل.

Ø   أن يشعر الطفل بألم أقل.

Ø   أن يبدأ شفاء الطفل من الطفح الجلدى.

Ø   أن يقوم الطفل بالاعتماد على نفسه فى الأنشطة الحياتية أو أقصى ما يكون في حدود المرض.

كيفية الوصول الى تنفيذ الأهداف:-

١. إلمساعدة على التحكم فى الالتهابات وارتفاع الحرارة

المرضى الذين يعانون من مرض كاواساكي، وهي حالة تسبب التهاب الأوعية الدموية في جميع أنحاء الجسم، قد يعانون من ارتفاع درجة الحرارة كجزء من أعراضهم. يجب خفض حمى المريض ومراقبة علاماته الحيوية لمنع المضاعفات المرتبطة بارتفاع الحرارة. علاوة على ذلك، يمكن أن يسبب مرض كاواساكي التهابًا في الفم والحلق والشفتين، مما يؤدي إلى احمرار وتورم وألم في الغشاء المخاطي للفم. يمكن أن يؤدي ذلك إلى صعوبة في البلع والتحدث وتناول الطعام، الأمر الذي يتطلب رعاية تمريضية دقيقة لمنع المزيد من المضاعفات وتعزيز الشفاء.

v  مراقبة درجة الحرارة كل ٤ ساعات؛ كل ساعتين إذا كانت مرتفعة.

v  يبدأ مرض كاواساكي في البداية بحمى شديدة (٣٩ درجة إلى ٤٠ درجة) لمدة 5 أيام أو أكثر.

v  تقييم التغيرات في الشفاه وتجويف الفم.

v  تشمل التغيرات النموذجية في الغشاء المخاطي احمرار الفم واللسان الذى بشبه الفراولة والشفاه الحمراء الجافة والمتشققة.

v  توفير حمامات الاسفنج  الفاترة لدرجات الحرارة التى تزيد عن ٣٨ درجة وذلك يساعد على فقدان الحرارة من خلال التوصيل والتبخر.

v  توفير فترات راحة كافية. فالراحة في الفراش تقلل من متطلبات التمثيل الغذائي واستهلاك الأكسجين.

v  تشجيع تناول كمية كافية من السوائل لأن الجفاف أو التعرق يزيد من الحمى.

v  إعطا ء الطفل المريض الدواء كما هو محدد.

v  •أسبرين. وهو دواء مضاد للالتهابات يعطى لتقليل الالتهاب.

•      الغلوبولين المناعي الوريدى يتم إعطاؤه بجرعة واحدة لعلاج الالتهاب وتقليله وبالتالي تقليل مدة الحمى.

v  تقديم الأطعمة الناعمة وغير المهيجة .

v  يتطلب الطعام اللين مضغًا أقل ويقلل التهيجً أ للغشاء المخاطي للفم.

v  توفير السوائل الباردة للمحافظة على ترطيب الفم وتقليل الام الفم بوضع المراهم المهدئة على الشفاه.

v  الحفاظ على الشفاه رطبة باستخدام زبدة كاكاو مرطبة لتجنب الألم.

v  استخدام فرشاة ذات شعيرات ناعمة  أثناء العناية بالفم حيث ان الفرشاة ذات الشعيرا ت الناعمة تحد من تهيج الغشاء المخاطي.

v  توفير رعاية منتظمة للفم باستخدام غسول الفم الخالي من الكحول الذى يحد من تراكم البكتيريا التي يمكن أن تسبب العدوى.

٢- كيفية المساعدة على التحكم فى الألم وتخفيفه:-

v  مرض كاواساكي يسبب التهابًا في جدران الأوعية الدموية في جميع أنحاء الجسم. يمكن أن يؤدي هذا الالتهاب إلى آلام في أجزاء مختلفة من الجسم، بما في ذلك المفاصل والبطن والصدر. ويعد تخفيف الألم عنصرًا مهمًا في خطط الرعاية التمريضية للمرضى الذين يعانون من مرض كاواساكي للمساعدة في تخفيف انزعاجهم وتحسين نوعية حياتهم.

v  تقييم مستوى الألم من خلال الملاحظة (التعبيرات اللفظية عن الألم، تكشيرة الوجه)، وذلك باستخدام تقييم مقياس الألم، ومن خلال الحصول على معلومات الألم ذات الصلة من الوالدين.

v  الحفاظ على غرفة الطفل هادئة وإبقاء الاضاءة خافتة للاقلال من انزعاج العين الناجم عن التهاب الملتحمة.

v  الشرح للوالدين سبب انزعاج/تهيج الطفل يعزز التفاهم والتعاون.

v  الشرح للوالدين أن التهيج قد يستمر لمدة تصل إلى شهرين؛و أن تقشر الجلد في اليدين والقدمين أمر طبيعي وغير مؤلم.

v  الشرح للوالدين أن آلام المفاصل قد تستمر لعدة أسابيع 

v   تعليم الوالدين  تمارين المدى الحركى لمفصل الركبة والتمارين السلبية في حمام دافئ تساعد على زيادة المرونة

v  ضع قطعة قماش باردة على الجلد، وغسولًا، وملابس ناعمة وفضفاضة على الطفل يخفف من حكة الجلد، وبالتالي يعزز الراحة.

v  التعامل مع الطفل بلطف وتجنب الحركات غير الضروريةل ان الحركة تسبب عدم الراحة.

٣. الحفاظ على سلامة الجلد و الاهتمام بالأغشية المخاطية:-

قد يصاب المرضى المصابون بمرض كاواساكي بطفح جلدي وتقشير ومظاهر جلدية أخرى بسبب الالتهاب الناجم عن المرض. وهذا يمكن أن يؤدي إلى ضعف سلامة الجلد، مما يجعل المرضى أكثر عرضة للإصابة بالتهابات الجلد والمضاعفات الأخرى. تعد العناية بالبشرة والمراقبة المناسبة من المكونات الأساسية لخطط الرعاية التمريضية للمرضى الذين يعانون من مرض كاواساكي لتعزيز الشفاء ومنع المزيد من تلف الجلد.

v  تقييم الجلد من حيث الملمس والتورم واللون والرطوبة وأى شكل غير صحى.

v  تشتمل السمات الجلدية الكلاسيكية لمرض كاواساكي على احمرار وتورم وطفح جلدي متعدد الأشكال وتقشير يؤثر على جلد الأطراف .

v  ألبسي الطفل ملابس خفيفة. الملابس الثقيلة قد تؤدي إلى تهيج الطفح الجلدي

v  عدم التشجيع على استخدام الصابون  لانه يجعل الجلد جافًا .

v  قم بإزالة أغطية السرير الرطبة والمتجعدة.

v  ضع كمادة باردة ورطبة على مناطق الحكة الجلدية لتوفير الراحة وتقليل الحكة.

v  تشجيع تناول كمية كافية من السوائل للحفاظ على الترطيب وتقليل ألم الفم.

v  التشجيع على تناول الأطعمة الغنية بالبروتين مثل البيض والفاصوليا والدجاج.

لان البروتين ضروري لصحة وصيانة الجلد

٤. تعزيز القدرة على الحركة البدنية:-

مرض كاواساكي يمكن أن يؤدي إلى تمدد يالأوعية الدموية في الشرايين التاجية. وقد يسبب مرض كاواساكي فى ضعف العضلات وآلام المفاصل والتورم، مما قد يؤدي إلى محدودية الحركة، ويتطلب ذلك رعاية تمريضية دقيقة لمنع المضاعفات وتعزيز التعافي.

v  تقييم مستوى طاقة الطفل وقدرته على أداء أنشطة الحياة اليومية.

v  تؤثر الحركة المقيدة الناتجة عن آلام المفاصل على القدرة على أداء أنشطة الحياة اليومية بشكل فعال.

v  توفير الدعم المشترك باستخدام الوسائد.

v  يمكن استخدام الوسائد لتثبيت المفصل وتقليل خطر الإصابة بقرح الضغط.

v  تزويد الطفل بالوقت الكافي لإنجاز الأنشطة المتعلقة بالتنقل وتشجيعه على الراحة بينهما.

v  تعظيم التزام الطفل ومشاركته في النشاط؛ يعزز الحفاظ على الطاقة وتقليل التعب.

v  المساعدة في تمارين المدى الحركى لمفصل الركبة السلبية كما هو مسموح به.

v  يحافظ على وظيفة المفاصل وقوة العضلات والقدرة على التحمل بشكل عام ويحسنها.

v  تقديم تعليمات حول استخدام الأجهزة المساعدة المناسبة أثناء التمشي.

v  التشجيع على تناول الأطعمة مثل السلمون والتونة والحبوب الكاملة والجزر.

v  تساعد هذه المواد الغذائية على تقوية الحركة وتعظيم إنتاج الطاقة

٥-التحكم فى القلق :-

-قد يعاني المرضى المصابون بمرض كاواساكي من القلق بسبب عدم اليقين المحيط بالمرض، واحتمال حدوث مضاعفات طويلة الأمد، والحاجة إلى تدخلات طبية متكررة. بالإضافة إلى ذلك، قد يكون الأطفال المصابون بمرض كاواساكي عرضة بشكل خاص للقلق وذلك لطبيعة المرض نفسه.

v  تثقيف الوالدين حول المعلومات المتعلقة بالمرض وعلاماته وأعراضه وتشخيصه وطرق التعامل معه.

v  الشرح  بأن سبب المرض غيرمعروف يساعد في تخفيف أي شعور بالذنب لدى الوالدين فيما يتعلق باكتساب المرض.

v  إبلاغ الوالدين بالتعامل بلطف مع الطفل حسب الحاجة.

v  -توفير المعلومات التي يحتاجها الآباء لتوفير الراحة 

v  تجنب اللمس غير الضروري للمريض.

v  تشجيع الوالدين على التعبير عن مشاعرهم بحرية. طمأنة الوالدين بأن بعض القلق طبيعى عندما يكون طفلهما مريضاً.

v  يساعد التشجيع والطمأنينة الوالدين على التعرف على عواطفهم واستعادة السيطرة عليها.

v  الشرح للوالدين أن الطفل قد يعاني من حمى متكررة في المنزل ونعلمهم كيفية قياس درجة حرارة الطفل ومتى يجب إخطار الطبيب .

v  التأكد من حصول الطفل على رعاية فعالة في المنزل يقلل من القلق المرتبط بعدم اليقين.

v  الشرح للوالدين أن التهيج هو أحد أعراض مرض كاواساكي وأنه ليس خطاهم ؛ وتشجيعهم على أخذ قسط من الراحة بينما تعتني الممرضة بالطفل. 

v  تقديم الدعم والإغاثة للآباء والأمهات في أوقات الأحداث العصيبة. 

٦-مراقبة العلامات الحيوية للطفل عن كثب أثناء إعطاء الجلوبيولين المناعي الوريدى :- 

v  غاما جلوبيولين هو أحد منتجات الدم ويتطلب المراقبة الدقيقة وهذا يطمئن الوالدين بأن طفلهم يتلقى الرعاية المناسبة 

v  قم بإنهاء التسريب فى حالة حدوثه  والإبلاغ فورًا عن ردود الفعل غير المرغوب فيها مثل الحمى والقشعريرة وضيق الصدر وضيق التنفس والغثيان / القيء. 

v  تعليم الوالدين كيفية التعامل مع الأسبرين و الإبلاغ عن أي علامات سمية (طنين الأذن، والصداع، والدوخة، والارتباك). اشرح أن الأسبرين قد يسبب كدمات

v  يجب إيقاف الأسبرين وإخطار الطبيب إذا تعرض الطفل للجديرى المائى أو الأنفلونزا (خطر الإصابة بمتلازمة راي). 

٧- مساعدة أولياء الأمور في تحديد مواعيد الإحالة والمتابعة للطفل.

المساعدة تساعد على تقليل القلق. 

ارشادات الآباء:

ما هو مرض كاواساكي؟ 

   مرض كاواساكي هو التهاب فى الاوردة يؤدى لارتفاع حاد فى درجات الحرارة  وغالبًا ما يصيب  الأطفال الذين تقل أعمارهم عن ٥ سنوات ولكنه وارد الحدوث فى الأطفال الاكبر سنا

    و هو نتيجة التهاب جهاز الأوعية الدموية مجهول السبب، وعادة ما ينتهى المرض من تلقاء نفسه وعلى الرغم من أن التنبؤ بتمام الشفاء جيد مع العلاج، إلا ان  حوالى٢٥% من  الذين لا يعالجون يصابوا بمضاعفات قلبية مثل التهاب الشرايين التاجية و تمدد الأوعية الدموية . 

الاسباب:-

حتى الان لم يتم اكتشاف السبب المؤدى لمرض كواساكى ولكن يعتقد انه التهاب فيروسى أو بكتبرى سابق مصحوب بتفاعل مناعى يؤدى الى التهابات بالأوعية الدموية 

اعراض المرض:- 

ينقسم المرض الى ثلاث مراحل:-

المرحلة الحاده (الأسبوع الأول و الثانى):-

Ø   تبدا بحمى شديدة قد تصل درجة حرارة جسم طفلك إلى 40 درجة مئوية.

و الحرارة لا تستجيب للمضادات الحيوية أو مخفضات الجرارة مثل الإيبوبروفين أو الباراسيتامول.

Ø   عادة ما تستمر درجة الحرارة المرتفعة لمدة ٥ أيام على الأقل، ولكنها يمكن أن تستمر لمدة اسابيع اذا لم يعطى العلاج المناسب لمرض كاواساكي.

§      وارتفاع الحرارة يكون مصحوبا باربعة من الاعراض التالية:

v  طفح جلدى على الجسم والوجه والاذرع والسيقان وله أشكال مختلفة

v  التهاب بالحلق واللسان والشفايف

v  التهاب العينبن واحمرارهما

v  وتورم اليدين و القدمين

v  تضخم العقد الليمفاوية بالرقبة 

·  الشفاه والفم والحلق واللسان:-

Ø   قد تكون شفاه طفلك حمراء أو جافة أو متشققة. وقد تنتفخ أيضًا وتتقشر أو تنزف.

Ø   قد يكون أيضًا الجزء الداخلي من فم طفلك وحلقه ملتهبًا.

Ø   قد يكون السان أحمر اللون، منتفخًا ويُعرف هذا باسم "لسان الفراولة".

·      اليدين والقدمين

Ø   قد تتورم يدي طفلك وأقدامه، وقد يصبح الجلد على يديه وأقدامه أحمر أو جامدا

Ø   قد يشعر طفلك بأن يديه وأقدامه مؤلمة عند لمسها أو ، ,وقد يجد صعوبة في المشي أو الزحف أثناء استمرار

·      تورم الغدد الليمفاوية وهى كتل منتفخة فى رقبة طفلك عادة على جانب واحد

ويعتبر التهيج هو أحد أعراض مرض كاواساكي وقد تكون هناك اعراض اخرى مثل مشاكل في القلب ,آلام البطن ,القيء,إسهال,بول يحتوي على صديد,الشعور بالنعاس ونقص الطاقة ,صداع ,آلام المفاصل وتورم المفاصل واصفرار الجلد وبياض العينين (اليرقان)

قد لا يعاني الأطفال الذين تقل أعمارهم عن سنة واحدة من العديد من الأعراض الرئيسية مقارنة بالأطفال الأكبر سنًا. والتشخيص قد يكون صعبا فى ذلك السن. 

المرحلة تحت الحادة(الأسبوع الثالث والرابع):-

تصبح أعراض طفلك أقل حدة.

من المفترض أن تهدأ درجة الحرارة المرتفعة، لكن قد يظل طفلك عصبيًا.

قد تشمل الأعراض تقشر جلد اليدين ثم القدمين، وأحيانًا أيضًا على راحتي اليدين أو باطن القدمين ويبدا التقشير فى اليدين ثم القدمين و يكون الطفل أكثر عرضة للاصابة بتمدد الأوعية الدموية التاجية وتزيد الصفائح الدموية. 

مرحلة النقاهة  (من خمسة الى ثمانى اسابيع)

حيث تختفى  الأعراض بالتدريح وتبدا نتائج التحاليل فى التحسن.

لكن قد يظل طفلك يعاني من نقص الطاقة ويتعب بسهولة خلال هذا الوقت. 

التشخيص:- 

لايوجد اختبار محدد لتشخيص مرض كاواساكي، ولكن هناك بعض العلامات الاكلينيكية الرئيسية التي تشير إلى احتمال إصابة الطفل بهذه الحالة و بعض التحاليل التى يجب اجرائها  . 

الرجاء اخبار طبيبك المعالج بأى عرض يظهر ويستمر أو يختفى 

التشخيص المعملى: 

يمكن إجراء العديد من الاختبارات للمساعدة في دعم تشخيص مرض كاواساكى. قد لا تكون الاختبارات حاسمة بشكل فردي ، ولكن عند دمجها مع بعض الأعراض الرئيسية لمرض كاواساكي، فإنها يمكن أن تساعد في تأكيد التشخيص وقد يحتاج الطفل إلى إجراء اختبارات لاستبعاد الامراض الأخرى التي قد تسبب أعراض مشايهة  

فحوصات القلب:-

عادةً ما تؤثر مضاعفات مرض كاواساكي على القلب. وهذا يعني أن طفلك قد يحتاج إلى بعض الاختبارات للتأكد من أن قلبه يعمل بشكل طبيعي مثل:

  ١- مخطط كهربية القلب (ECG)

  ٢-  مخطط صدى القلب  والتي يمكن أن تؤكد ما إذا كانت هناك أي مشاكل في بنية القلب أو وظيفته 

العلاج: 

يتم علاج مرض كاواساكي في المستشفى لأنه يمكن أن يسبب مضاعفات خطيرة. يجب أن يبدأ العلاج في أقرب وقت ممكن.

قد يستغرق طفلك وقتًا أطول للتعافي و يزيد خطر الإصابة بتمدد الشراين التاجية إذا لم يتم العلاج على الفور.

العلاجان الرئيسيان لمرض كاواساكي هما:

v  الجلوبيولين المناعي الوريديIVIG.

o     أظهرت الأبحاث أن IVIG يمكن أن يقلل من الحمى وخطر الإصابة بمشاكل في القلب.

o     بعد إعطاء طفلك IVIG، يجب أن تتحسن أعراضه خلال ٣٦ ساعة.

إذا لم تتحسن درجة حرارتهم المرتفعة بعد ٣٦ ساعة، فقد يتم إعطاؤهم جرعة ثانية من IVIG و علاجات اخرى.

v  الأسبرين

o     يتم استخدامه لعلاج مرض كاواساكي لأنه يمكن تخفيف الألم والانزعاج.    يمكن أن يساعد في تقليل درجة الحرارة المرتفعة

  عند تناول جرعات عالية، يعتبر الأسبرين مضادًا للالتهابات (يخفف التورم). عند تناول جرعات منخفضة، يعتبر الأسبرين مضادًا للصفيحات (يمنع تكون جلطات الدم)

جرعة الأسبرين الموصوفة لطفلك والمدة التي يحتاجها لتناولها تعتمد على الأعراض التي يعاني منها.

o     يتم إعطاء جرعة عالية من الأسبرين حتى تنخفض درجة الحرارة.

o     ويمكن بعد ذلك وصف جرعة منخفضة من الأسبرين لهم لمدة 6 أسابيع.وذلك لتقليل جلطات الدم .

الكورتيكوستيرويدات

يوصى بها إذا لم تكن IVIG فعالة، أو إذا وجد أن طفلك معرض لخطر كبير للإصابة بمشاكل في القلب.

بعد العلاج

عندما يخرج طفلك من المستشفى، يجب أن تحصل على النصائح حول كيفية العناية به في المنزل.

قد يشمل ذلك التأكد من أنهم مرتاحون قدر الإمكان وأنهم يشربون الكثير من السوائل.

تأكد من أن طفلك يستمر في تناول أي دواء موصوف له وابحث عن أي آثار جانبية.

سيتم تحديد موعد متابعة لطفلك وستستمر مراقبة قلبه.

بمجرد التأكد من فحص القلب بالموجات فوق الصوتية (مخطط صدى القلب) أن طفلك لا يعاني من أي مشاكل في القلب، يمكنه عادةً التوقف عن تناول الأسبرين.

قد يستغرق التعافي الكامل حوالي ٦ أسابيع، ولكنه قد يستغرق وقتًا أطول عند بعض الأطفال.

قد تكون هناك حاجة إلى متابعة العلاج إذا أصيب طفلك بمزيد من المضاعفات.

الآثار الجانبية للأسبرين

عادةً لا يُعطى الأسبرين للأطفال دون سن ١٦ عامًا لأنه يمكن أن يسبب آثارًا جانبية، بما في ذلك متلازمة راي. متلازمة راي نادرة وتشمل أعراضها القيء المستمر ونقص الطاقة.

احصل على المساعدة الطبية فورًا إذا كان طفلك يعاني من أي من هذه الأعراض.

المضاعفات: اصابة الشرايين التاجية للقلب

مع العلاج الفوري، يتعافي معظم الأطفال

وترتبط مضاعفات مرض كاواساكي بشكل أساسي بالقلب.

تحدث نتيجة لالتهاب وتمدد الأوعية الدموية يالقلب وقد يؤثر هذا أحيانًا على الأوعية الدموية خارج القلب

.وقد يسبب هذا فى نوبة قلبية - حيث يموت جزء من عضلة القلب بسبب حرمانها من الأكسجين

ومن الممكن أيضًا أن تتأثر الشرايين الأخرى المتوسطة الحجم.

وقدتشفى بعض هذه المضاعفات من تلقاء نفسها مع مرور الوقت. لكن قد يتعرض بعض الأطفال لمزيد من المضاعفات التي تتطلب متابعة وعلاج يمنع التجلط فى تمددات الأوعية الدموية.

تعد المضاعفات المرتبطة بالقلب المرتبطة بمرض كاواساكي خطيرة وقد تكون قاتلة في 2 إلى 3٪ من الحالات التي لا يتم علاجها.

من المعروف أن الأطفال الذين تقل أعمارهم عن سنة واحدة أكثر عرضة لخطر الإصابة بمضاعفات خطيرة بالقلب.

علاج المضاعفات

تشمل العلاجات الممكنة ما يلي:

   استخدام الأدوية المضادة للتخثر والأدوية المضادة للصفيحات

– الأدوية التي توقف تخثر الدم، والتي قد تمنع إصابة طفلك بنوبة قلبية إذا كان يعانى من تمدد شرايين القلب.

    وقد يحتاج الطفل  لرأب الأوعية التاجية – إجراء لتوسيع الشرايين التاجية المسدودة أو الضيقة لتحسين تدفق الدم إلى القلب؛ وفي بعض الأحيان يتم إدخال دعامة في الشريان المسدود لإبقائه مفتوحًا

نادرا ما يحتاج الطفل لعملية جراحية لتحويل الدم بالشرايين الضيقة أو المسدودة، لتحسين تدفق الدم وإمداد الأكسجين إلى القلب

قد يعاني الأطفال الذين يعانون من مضاعفات خطيرة من تلف دائم في عضلات القلب أو الصمامات.

هؤلاء الاطفال سيكون لديهم مواعيد متابعة منتظمة مع أستشارى قلب الاطفال حتى يمكن مراقبة حالتهم عن كثب.

وبعد سن ثمانى عشر سنة يتم تحويل المريض الى رعاية طبيب قلب الكبار متخصص فى مرض كواساكى .

                                        Annex  Table 4: Differential diagnosis:

Table (4)a DD of Kawasaki disease, scarlet fever and Measles.

Table (4)b DD Kawasaki Disease with autoimmune: Systemic onset juvenile idiopathic arthritis, Rheumatic Fever  and Steven Johnson Syndrome.

Table (4)c Critical cases commonly mistaken for Kawasaki disease