KAWASAKI DISEASE

- also known as mucocutaneous lymph node syndrome (refers to mucous membranes

which are wet surfaces such as the mouth & eyes and cutaneous referring to skin like skin
of the palms and soles as well as body surfaces while the nodes refer to the cervical
lymph nodes); these parts of the body are the ones that are affected in the classic
symptoms of the disease which we will be discussing later
- described in Japan in 1967 by Dr. Tomisaku Kawasaki (1925-2020, June); there were 50
cases back then in Japan and then after some years, nagkaroon din ng case sa Hawaii and
then other parts of the world. Although first reported in Japanese children, the disease
affects children of many races, occurs worldwide, and is increasing in frequency
- is a systemic vasculitis (i.e., inflammation of the blood vessels) and can develop multiple
organ injuries (e.g. kidney injuries, hepatitis, gastrointestinal abnormalities) in most
cases, it affects medium-sized arteries such as the coronaries. Although the vascular
inflammation is most pronounced in the coronary vessels, vasculitis can also occur in
veins, capillaries, small arterioles, and larger arteries
- the disease affects the skin, brain, eyes, joints, liver, lymph nodes, and heart
- most common cause of acquired heart disease in young children (more than 3000
children with Kawasaki’s disease are diagnosed annually in the United states, and 0.5%
to 1.0% of those die of complications of coronary artery involvement
- No one knows what causes Kawasaki disease, but scientists don't believe the disease is
contagious from person to person. A number of theories link the disease to bacteria,
viruses or other environmental factors, but none has been proved. Certain genes may
make your child more likely to get Kawasaki disease but it is thought to be of
immunologic origin.

o It is believed to be caused by the immune system. However, the reason why the
immune system decides to damage the blood vessels in this disease is
UNKNOWN.

- usually a self-limited condition (meaning, it will resolve on its own; in the case of
Kawasaki disease, it resolves after 6-8 weeks with or without treatment)

However, when left untreated, there is a 20-25% risk of developing heart complication
(which we will be discussing on the next slides)
Treated patients can also have 4% risk of developing heart complication and .1% to 2%
chance of mortality from cardiac complications

- The disease can produce aneurysmal disease of the coronary arteries

We can rarely see cardiac symptoms in the first few weeks (unless the patient already has
an underlying cardiac condition. And so cardiac symptoms typically evolve later.
HOW DOES THIS HAPPEN?

PATHOPHYSIOLOGY
With KD the immune system attacks the arteries. Ultimately, it’s not quite known why
this happens though. Some theories suggest that it has an infectious cause however, autoimmune
reactions and genetic predisposition probably plays a role as well
When the endothelial cells in the blood vessels are attacked, they become damaged which
exposes the underlying collagen & tissue factor found in the middle layer of the blood vessel
(tunica media) which leads to a few serious problems
First these exposed materials increase the chance of blood coagulation (which also
increases the risks for clots) and then blocks the blood flow leading to ischemia of the heart
muscle.
Secondly, damaged endothelial cells in the coronary arteries (means weak artery walls)
which can lead to coronary aneurysms. These aneurysms form because fibrin deposited in the
blood vessel wall as part of the healing process. Fibrin makes the vessels stiffer, less elastic and
unable to gently stretch with high arterial pressures. Instead, the arteries develop permanent
bulges which we call aneurysms. Aneurysms 8mm or larger are the most risk for rupturing
which reduces blood flow to the heart causing ischemia in heart and potentially myocardial
infarction (heart attack).
Ischemic means that an organ (e.g. heart) is not getting enough blood and oxygen.
Thirdly, in some cases of fibrosis doesn’t lead to aneurysms. Instead, the fibrosis of the
blood vessel walls makes the blood vessel thicker which reduces the lumen diameter (normal: 30
micrometers) and restricts blood flow. If blood flow is restricted or reduced, the heart AGAIN
may become ischemic leading to heart attack.

Let’s now proceed to the phases wherein we will talk about the classic symptoms

Manifestations
The course of the disease is triphasic (having or occurring in three phases) and includes:

1. acute febrile phase — lasts about 7 to 14 days

2. subacute phase — follows the acute phase and lasts until days 10 through 24
3. convalescent phase — follows the subacute phase inflammatory response have subsided
and the signs of the illness have disappeared

ACUTE FEBRILE PHASE (lasts for about 7-14 days)

 begins with an abrupt onset of fever— (typically high, reaching 40C (104F) or higher;
has an erratic spiking pattern; unresponsive to antibiotics, paracetamol and ibuprofen;
persists for 5 or more days

 followed by conjunctivitis— bilateral, non-exudative; sparing limbus (border of cornea

and sclera); begins shortly after onset of fever, persists throughout the febrile course of
the disease; may last as long as 3-5 weeks (differentiating it from many other types of
 conjunctivitis, there is no exudate, discharge, or conjunctival ulceration); leads to
photophobia, discomfort or pain dues to light exposure

 rash— (usually) a urticarial (AKA hives: causes itchiness) rash; begins during the first
few days due to sensitivity to sunlight (polymorphous: a rash caused by sun exposure in
people who have developed sensitivity to sunlight); maculopapular rash is made of both
flat and raised skin lesions. (the name is a blend of the words “macule,” which are flat
discolored skin lesions, and “papule,” which are small raised bumps)

- some children develop e perianal rash with a diaper-like distribution

 involvement of the oral mucosa (oropharyngeal manifestations)

- including fissuring of the lips (cracking of lips)
- diffuse erythema of the oropharynx (middle compartment of pharynx)
- hypertrophic papillae of the tongue creating a strawberry appearance;
“strawberry tongue”
o may be related to inflammatory process, dehydration, and mouth
breathing.
 extremity changes
- redness of palms and soles
- edema/ swelling of the hands and feet—palms and soles becomes reddened,
painful and swollen
Note: The rash, oropharyngeal manifestations and changes in hands and feet appear within 1
to 3 days of fever onset and usually disappear as the fever subsides

 adenopathy/ enlarged cervical lymph nodes— least constant feature of the disease;
which tends to primarily involve the anterior cervical nodes overlying the
sternocleidomastoid muscles
- it is cervical and unilateral, single, firm, enlarged lymph node (usually larger
than 1.5 cm in diameter)
note: normal lymph node is 1cm in diameter

SUBACUTE PHASE (follows the acute phase and lasts until days 10 through 24)
 begins with the defervescence of fever (the stage of breaking of fever; patient’s body
temperature returning to normal)
- characterized by sweating
 lasts until all signs of the disease have disappeared
 (During subacute phase), desquamation (i.e. peeling) of the skin of the fingers and toe
tips begins and progresses to involve the entire surface of the palms and soles
- Patchy peeling of skin areas (other than the hands and feet may occur in some
children)
- May be related to inflammatory process, altered circulation, and edema formation.

CONVALESCENT STAGE (usually takes about 8 weeks)

 It is also known as the recovering stage
  Persists from the complete resolution of symptoms until all signs of inflammation have
disappeared
 NOTE: Cardiac abnormalities may still be apparent. Smaller CAAs tend to resolve on
their own (60% of cases), but larger aneurysms may expand, and MI may occur.

(In addition to the major manifestations that occur during the acute stage of the illness, there are)
associated, less specific characteristics:
 Arthritis- occurs in 30% of children with the disease
- Characterized by symmetric joint swelling (that involves large and small joints)
 Urethritis- inflammation of urethra
 Pyuria- condition of urine containing WBC or pus
 Gastrointestinal manifestations (e.g. diarrhoea, abdominal pain)
 Hepatitis- inflammation of the liver
 Hydrops of the gallbladder- term denoting an overdistended gallbladder filled with
mucoid or clear and watery content
 CNS involvement- occurs in almost all children
- Characterized by pronounced irritability and lability (exaggerated changes in
mood) of mood
 Rhinorrhea- refers to thin, mostly clear nasal discharge; inflammation of nasal tissues;
“runny nose”
 Cough
 Vomiting

CHRONIC STAGE (persistence of any cardiac complications into adulthood)

MOST IMPORTANT MANIFESTATION—Cardiac Involvement

 rarest but most serious effect
 10%- 40% of children develop coronary vasculitis (within the first 2 weeks of the
illness); manifested aneurysm formation in the coronary arteries (as seen on two-
dimensional echocardiography)
 Manifestations of coronary artery involvement includes signs and symptoms of:
- Arrythmias- abnormal heart rhythms
- Heart failure
- Myocardial ischemia- when blood flow to your heart is reduced, preventing the
heart muscle from receiving enough oxygen
- Rupture of the aneurysm- 8mm aneurysms (bulges)
- Overt myocardial infarction (rarely) --- “heart attack”
Typically an ECG or Echocardiogram are done in individuals with KD to look for cardiovascular
involvement.

Note: pericarditis, myocarditis, endocarditis, heart failure and dysrhythmias may also
develop

TREATMENT:
 Chest radiographs- to look for calcifications
  ECG tests
 two-dimensional echocardiography
These are used to detect coronary artery involvement and follow its progress
. In rare occasions, if echocardiography is not available,
 Computed tomographic angiography
 Magnetic resonance angiography
can be used instead

Differential Diagnosis – done by doctors

--- wherein they differentiate between two or more conditions that could be behind a
person's symptoms
Examples:

Measles KD
Exudate conjunctivitis Nonexudative conjunctivitis
Koplik spots (little spots in mouth Strawberry tongue
which looks like tiny grains of white
sand)
Rash—head then migrates to trunk Measle-like rashes

Infections (because infections are associated to the development of Kawasaki)

Streptoccocus pharyngitis can lead to Scarlet Fever, Rheumatic fever, and may also
lead to KD.

Viral Rash
Stevens Johnson Syndrome

DIAGNOSIS
There is no specific test to diagnose KD. However, there are a number of lab tests that
can serve as clues.

At the beginning of the disease, many patients are anemic and have an increase in WBC with a
shift to the left which means that are more immature WBC than normal (moderate to high ito
wherein 50% of patients ay may WBC greater than 15,000/uL; normal: 4,500 to 11,000/uL).
They also have an increase C-reactive protein and erythrocyte sedimentation rate as well
as increase liver enzymes which are all good clues that tells us that a sort on inflammation is
happening.
Microscopic urinalysis shows mononuclear WBCs in urine without evidence of bacteria
After a few weeks, the platelets count generally rises as well (which as we all know
increases risk for coagulation therefore, increasing risks for blood clots
The last test would be an echocardiogram which is used to look at coronary arteries and
heart muscle to see if any of the complications that we talked about earlier have something to do
with what’s happening to the heart.
  Full/Complete Blood Count- to look for signs of infection
 Electrolytes (sodium, potassium and chloride), urea, creatinine (EUC)- aside from
looking at the basic chemical balance of the blood, it is also used for kidney
involvement
 Liver Function Test (LFT)- look at how well the liver is functioning and can indicate
whether there is any damage or inflammation inside the liver; for viral causes affecting
the liver
 C-Reactive Protein Test- inflammatory marker (high in KD as well as in infections)
 Erythrocyte Sedimentation Rate (ESR)- inflammatory marker (high in KD as well as in
infections)

 Urinalysis- is good for evidence of increase in WBC

 2D Echo should be performed once the diagnose of KD is made as well as 6-10 weeks
after to check for myocardial information and coronary artery aneurysm formation
(enlargement of an artery caused by weakness in the arterial wall)
o Aside from 2D Echo; Magnetic resonance imaging (MRI), magnetic resonance
angiography (MRA), and ultrafast computed tomography (CT) scanning are other
noninvasive tests that can be used to evaluate coronary artery abnormalities.

In order for Kawasaki disease to be diagnosed the patient must have a persisting fever for 5 or
more days without reasonable explanation AND at least 4 of the following symptoms:
conjunctivitis, rashes, erythema/ edema of the extremities, adenopathy or enlargement of cervical
lymph nodes and/ or mucous membrane changes such as the red tongue, dry, cracked lips and
“strawberry tongue”

KD is diagnose base on the patient’s symptoms and lab tests.

Vasculitis in the coronary artery is the definitive sign that the disease is Kawasaki Disease. But
of course hindi na natin aantayin pang umabot sa ganun.

Patients that don’t meet all the diagnostic criteria of KD are sometimes classified as incomplete
KD. There are guidelines in place that help healthcare providers figure out if they should treat
these atypical cases as Kawasaki disease or not. But know that there are cases wherein it is
possible that they don’t meet all of the diagnostic requirements.

Tests:
For coronary artery involvement and in following its progress
 Chest radiographs (Chest X-rays)—not routinely performed in evaluating KD
- If coronary aneurysm and calcification of the coronary artery aneurysm wall are
present, they may be detected as cystic calcification in the region of the coronary
vessels, overlying the heart shadow
 ECG tests—records the electrical activity of the heart at rest
 Two-dimensional echocardiography (2-D Echo)—especially useful in the approach to
patients who fall short of full clinical criteria (incomplete KD), as the presence of the
following is diagnostic
 o Coronary artery dilation
 Dilation which exceeds the mean coronary artery diameters by 2.5
standard deviations is classified as aneurysmal (normal:
o Left ventricular dysfunction
 inflammation of the myocardium may produce systolic or diastolic
dysfunction
o Mitral regurgitation
 manifestation of endocardial inflammation
o Pericardial Effusion

May also be used (when echocardiography is unavailable):

 Computed tomographic angiography (CT angiography)
 Magnetic resonance angiography (MR angiography)

TREATMENT
Now treating Kawasaki disease also is helpful diagnostically because if a therapy works,
then that also reassures you that the right diagnosis was made. The principal goal of treatment for
Kawasaki disease is to prevent coronary artery disease and to relieve symptoms.

The main treatment is to give a single dose of IVIG or Intravenous gamma globulin
which is an antibody taken from other individuals. 2g/kg for 8-12 hrs. Administered within the
first 10 days of illness (before aneurysms typically develop). It should be administered even
beyond the 10 day window (in individuals with persistent vasculitis or systemic inflammation so
just persistent fever, laboratory markers like elevated ESR & CRP). It is thought that this helps
calm down the immune system and reduce inflammation.
In addition, ASA or Aspirin is also given for it inhibits cyclooxygenase which prevents
platelets from aggregating together. Giving a total daily aspirin dose of 30-50mg/kg in 4 doses
while fever lasts and then it is continued for 48 hours after the resolution of fever at a low dose
of 3-5mg/kg per day until laboratory markers return to normal which typically takes about 2
months UNLESS merong coronary artery involvement in which low dose of aspirin is continued.
Unless from Kawasaki Disease and few other indications, aspirin is otherwise normally
NOT recommended for children d/t its association with Reye syndrome which is the rapidly
progressive encephalopathy (a disease that affects the brain). Because children with KD will be
at aspirin for a long time, vaccination against varicella and influenza is required (because these
infections are the ones that cause Reye Syndrome). Importantly, varicella vaccine should be
postponed for at least 11 months after the IVIG has been given because it can interfere with
vaccine IVIG.

Individuals that have coronary aneurysm have to undergo stress testing to evaluate for
myocardial perfusion & inducible ischemia which measures the heart ability to respond to
increase stress or demand in a controlled setting. The stress is induced by exercise (which is
preferred) or with a medication dobutamine (which used in certain types of cardiac stress tests;
directly stimulates beta-1 receptors of the heart to increase myocardial contractility and stroke
volume, resulting in increased cardiac output)

Nursing interventions for the patient with Kawasaki disease are:

  Monitor pain. Monitor pain level and child’s response to analgesia.
 Cardiac monitoring and assessment. Take vital signs as directed by conditions; assess for
signs of myocarditis (tachycardia, gallop rhythm, chest pain); and monitor for heart
failure.
 Monitor I&O. Closely monitor intake and output, and monitor hydration status by
checking skin turgor, weight, urinary output, specific gravity, and presence of tears. Plan
periods of rest and activities.
 Allow the child periods of uninterrupted rest; encourage the child to move about freely
under supervision; provide soft toys and quiet play and encourage use of hands and
fingers; and provide quiet, peaceful environment with diversional activities.
 Provide oral care. Offer cool liquids (ice chips and ice pops); progress to soft, bland
foods; and give mouth care every 1 to 4 hours with special mouth swabs; use soft
toothbrush only after healing has occurred.

Once diagnosis of KD is made, it is essential that a pediatrician is involved. Admit the child and
commence immunoglobulin IV as well as aspirin
 Intravenous gamma globulin and aspirin are considered as the best therapy for prevention
of coronary artery abnormalities in children with Kawasaki’s disease
 Commence IV immunoglobulin within 10 days of fever onset has shown to reduce
cardiac complications
Aspirin—larger doses in acute phase; for its anti-inflammatory and antipyretic effect
*after the fever is controlled, aspirin dose is lowered and the drug is given for its anti-
platelet-aggregating effects
Reye’s Syndrome

For cardiac follow up evaluation (are based on the level of coronary artery changes)
Stress testing—
Coronary angiography— provides required excellent imaging findings
For children with multiple or large coronary aneurysm
Anticoagulant therapy (may be recommended)
Restrictions in activities (i.e. competitive sports) may be advised for children with
significant coronary artery abnormalities

TERM DEFINITION
mucocutaneous lymph node syndrome refers to mucous membranes which are wet
surfaces such as the mouth & eyes and
cutaneous referring to skin like skin of the
 palms and soles as well as body surfaces
while the nodes refer to the cervical lymph
nodes
Acute febrile disease
Aneurysmal disease
Convalescent
Coronary Vasculitis
Defervescence This stage is characterized by sweating. The
fever breaks, and the patient's body
temperature returns to normal.
Erythema Large patches of red skin
Immunologic origin

Triphasic Having or occurring in three phases

Reference:

https://radiopaedia.org/articles/kawasaki-disease
https://emedicine.medscape.com/article/965367-overview#a1