Download Kawasaki Disease

A Pain in the Neck
PRESENTED BY:
DR. MUNSIF BHIMANI
DR. MARIA TAMBAKIS
Outline of Presentation
 Case Presentation
 Case Discussion
 Approach to Neck Mass
 Differential Diagnosis
 Investigations
 Course in Hospital
 Case Complications
 Treatment
 Topic Review
 Topic Summary
Case: J.H., a 13-y old boy with neck pain
J.H., a 13-year-old boy, presents to the UH Emergency
Department in May
 Chief Complaint: Left neck swelling, tenderness and pain
worsening over 1 week
Other Symptoms
 Fatigue/Myalgias
 Sore throat
 Spiking Fevers
 Mild dysphagia/odynophagia

2nd to swelling/neck mass
 Review of systems
 Otherwise negative
Case: J.H., a 13-year old boy with neck pain
 Other Historical Questions?
Case: Relevant Medical History
PMHx:
 Overall, he has been a well child.
Previous Reactive Airway Disease
FHx:
 Mom and dad are both healthy. Maternal hypothyroidism.
 Sister has celiac disease.
 Maternal grandfather had RA and dad’s uncle
died of cardiac arrhythmia age of 39.
Meds: None
Allergies: NKDA
Immunizations: UTD
Case: Physical examination
 Vitals: Weight- 72 kg, NAD, Afebrile, AVSS
 Mildly tender, firm left neck mass.
 No airway concerns.
 Oral cavity examination and oropharyngeal
examination normal
 Remaining head and neck examination
was normal.
 CVS/RESP/GI N physical exam
Neck Mass in a Teenager
 Differential Diagnosis??
 Management??
DDx of Neck Mass
Inflammatory
Congenital/ Developmental
 Adenitis
 Brachial cleft cyst
 Bacterial (Streptococcus,
 Thyroglossal duct cyst










Staphylococcus)
Viral (HIV, EBV, HSV)
Fungal (coccidioidomycosis)
Parasitic (toxoplasmosis)
Cat-scratch disease
Tularemia
Local cutaneous infections
Sialoadenitis (parotid and
submaxillary glands)
Thyroiditis
Mycobacterium avium-intracellulare
Mycobacterium tuberculosis
 Dermoid cyst
 Cystic hydromas
 Torticollis
 Thymic masses
 Teratomas
 Ranula
 Lymphangioma
 Laryngocele
Rosen’s Emergency Medicine
DDx of Neck Mass
Neoplastic
Benign
Malignant
 Mesenchymal tumors (lipoma,
Primary tumors
 Sarcoma
 Salivary gland tumor
 Thyroid or parathyroid tumors
 Lymphoma
Metastasis
 From primary head and neck
tumors
 From infraclavicular primary
tumors (e.g., lung or esophageal
cancer)
fibroma, neural tumor)
 Salivary gland masses
 Vascular abnormalities
(hemangiomas, AVM,
lymphangiomas, aneurysm)
Rosen’s Emergency Medicine
J.H. Case
 Management Plan???
J.H. Case
 Management Plan???
 How would you manage this differently if you were
in a Community Hospital ED???
Case: Investigations
LABS
Day 1
WBC
13.3 H
HGB
136
MCV
86.7
Plt
290
PMN
10.9 H
Lymph
0.7 L
Mono
1.6 H
Eosino
0.2
What additional
investigations
would you order?
Case: Investigations
 Blood C + S Sent
 Throat C+S Sent
 Monospot Negative
 Next Step???
Case: Course in Hospital
 Referred to Peds ER
 Peds ENT consulted
 Admitted to hospital for further management of neck
mass
 IV antibiotics started

Metronidazole and Cefotaxime
Case: Investigations
 CT Neck
 Left palatine tonsillitis with reactive lymphadenopathy in the
left neck.
 No definite drainable collections.
Throat C+S
Group A Streptococcus (Strep pyogenes) NOT isolated.
Blood C+S
No growth at Day 1 and Day 5
Heterophile Ab
(Monospot)
Negative
Case: Course in Hospital
 Despite antibiotic therapy:
 Ongoing neck swelling and pain
 Ongoing associated spiking fevers
 J.H. also developed new symptoms:
 Conjunctivitis
 Nausea, diarrhea
 Maculopapular rash on his torso
Additional Differential Dx?
Investigations?
Case: Additional Investigations
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
WBC
13.3 H
11.6 H
12.8 H
15.9 H
18.6 H
22.1 H
18.4 H
HGB
136
135
147
134
137
135
136
MCV
86.7
85.3
85.4
84.9
85.9
86.1
85.7
Plt
290
297
392
382
387
412 H
403 H
PMN
10.9 H
16.4
ESR
67
CRP
149.8 H
SMA-7
U/A
N
N
H
16.3 H
H
75 H
151.4 H
N
Neg
ALT/AST
25/30
Albumin
31 L
Case: Course in Hospital
• Neck swelling /fatigue improved over 1 week
• Remained afebrile over a 48 hour period
• J.H. was discharged home on oral Keflex x 2 weeks with
•
follow-up with ENT in 2 wks.
Discharge Diagnosis:
 Left neck lymphadenitis
 Associated viral URI
 Rash secondary to reaction to antibiotic use
Return to ER
Day 4 Post Discharge
 Parents concerned about:
 Weight loss of 20 lbs since start of illness
 Bilateral conjunctivitis/rash not resolved fully
 Continued Cervical LAD
 Additional
Questions??? Management
Return to ED
• Before patient is discharged home, he shows you
a new rash on his hands
• Diagnostic considerations? Next step?
Return to ED
• Before patient is discharged home, he shows you
a new rash on his hands
• Diagnostic considerations? Next step?
• Patient is wondering why fingers are now peeling
Two Week Follow-Up Visit- ENT
 ENT noted new desquamation to palms and fingertips
 Referred back to ID for ??Incomplete Kawasaki disease
 ID diagnosed J.H with Incomplete KD Started on ASA daily
What are the important sequelae of iKD?
Sequelae of KD
 Cardiac
 Myocarditis and pericarditis
 Aneurysm Formation with associated SCD, MI, rupture
 Erythema and edema on the hands and feet
 Strawberry tongue and lip fissures
 Hepatic, renal, and GI dysfunction
 Lymphadenopathy
 Arthritis
Pediatric Cardiology Assessment
 Physical Exam- N
 ECG- N
 Echo
 Grossly dilated R/L coronary arteries ( >2 cm
diameter) with multiple distal coronary aneurysms
 LVEF= >65% with no regional wall abN to suggest
myocardial involvement
 No valvular AbN
 Small Pericardial effusion
 CXR- N
Pediatric Cardiology Assessment
 Diagnosis
 Incomplete Kawasaki Disease with multiple giant coronary
artery aneurysms
 Treatment suggestions
 EC ASA 81 mg po OD
Case: Additional Complications
 Referral to Peds Cardiology at SickKids
Repeat Echo= LAD clot Admitted for anticoagulation and
antiplatelet therapy
 Discharged on Enoxaparin and ECASA 81 mg po OD

 CABG (SickKids- Toronto)
 Ongoing follow-up demonstrating ischemia CABG
performed
GOALS OF TOPIC REVIEW
1.
Clinical suspicion to diagnose KD must be high
2. Features of disease not all present at the same
time
3. Incomplete KD exists
4. Treat them early
Kawasaki Disease (KD)
 Mucocutaneous lymph node syndrome is a
generalized systemic vasculitis
Unknown etiology
 Complete (or classic) and incomplete disease

 Peaks at 18 to 24 months
 Rare below the age of 4 months or after 5 years of age.
 Younger infants have increased risk for long-term
sequelae and sudden death
Kawasaki Disease (KD)
 Incomplete KD (iKD) clinical manifestations are
more common in children <1 yr or >5 yr
 Leading cause of acquired heart disease in children
in N.A.
 High index of clinical suspicion is key for diagnosis
Epidemiology of KD
 Age of Onset
 Peak incidence at 1 year, mean 2.6 years, uncommon after 8
years.
 Incidence

U.S.A.: 9/100,000 (Caucasian) 32/100, 000 (Asian)
 Sex
 Male predominance, 1.5:1.
 Race
 In United States: Japanese > blacks > whites.
 Affects all races worldwide.
Epidemiology of KD
 Etiology
 Community outbreaks every 2-3 yrs suggest potential
transmissible cause.
 Season
 Winter and spring in N.A.
 Geography
 First reported in Japan, 1961; United States, 1971.
 Morbidity/Mortality
 Reported mortality rate of KD is low (0.1 to 0.3 percent)
 Often secondary to cardiac sequelae.
 Peak Mortality=15-45 days after onset of fever
Classic Kawasaki Disease
Fever for 5 days or more
plus FOUR of the following symptoms:
1. Bilateral Conjunctival injection (Nonexudative)
2. Changes to the Lips and Oral cavity

Erythema, peeling, cracking of lips, "strawberry tongue," or diffuse oropharyngeal mucosa
injection
3. Changes of the Extremities


Acute: Erythema of palms/soles, edema of hands/feet
Subacute: Peeling of finger tips/toes (Weeks 2-3)
4. Rash

Polymorphous, diffuse, maculopapular exanthem
5. Cervical adenopathy

Greater than or equal to 1.5 cm in diameter, usually unilateral, minimal erythema to skin,
non tender LAD
Clinical Features of KD
NOTE!!
 Typically all of the clinical features are not present at a single
point in time
 History is key
Kawasaki disease is divided into three phases:
 Acute febrile phase during first 2 weeks of illness
 Subacute phase from 2 to 4 weeks
 Convalescent phase from 4 to 6 weeks
 In most cases, all external clinical manifestations have resolved
by 6 weeks.

Coronary artery aneurysm development is most prevalent as the fever
begins to lessen
Manifestations of KD
Classic KD Clinical Criteria: Pearls
 Fever
 High- Spiking, Remittent with peak temp >39 C
 Not responsive to antibiotics or antipyretics
 Lips and Oral Cavity (90% cases)
 Typically no oral ulcerations or pharyngeal exudates
 Rash (70 to 90 %)
 Within 5 days of fever onset
 Diffuse non-specific maculopapular rash
Classic KD Clinical Criteria: Pearls
 Extremities (50-85%)
 Acute Erythema/Edema of Palms/Soles Desquamation
 Conjunctival Injection (>75%)
 Bilateral Non-Exudative
 Painless
 No associated corneal edema/ulcers
 Cervical LAD (25 to 70 %)
 Least common feature
 Occasionally mistaken for Bacterial adenitis
Incomplete Kawasaki Disease
Fever for 5 days and two to three clinical criteria of
classic Kawasaki disease
plus
 C-reactive protein 3.0 milligrams/L and/or
erythrocyte sedimentation rate 40 mm/h
plus
 Three or more of the following supplemental labs
or positive echo






1. Albumin <3 grams/dL
2. Anemia for age
3. Elevated alanine aminotransferase
3
4. Platelets >450,000/mm after 7 d of fever onset
3
5. White blood cell count >12,000/mm
6. Presence of pyuria (> 10 WBC/HPF)
Nondiagnostic Supplemental
Lab Criteria
1. Albumin <3 grams/dL
2. Anemia for age
3. Elevated ALT
3
4. Platelets >450,000/mm after
7 d of fever onset
5. White blood cell count
3
>12,000/mm
6. Presence of pyuria (> 10 WBC/
HPF)
Incomplete KD: Pearls
 More common in the extremes of the age spectrum
 ≤1 y/o or ≥5 to 9 y/o
 Labs help to increase or reduce the suspicion of KD
 ESR/ CRP are consistently elevated after day 7 of illness in KD
and should prompt echocardiogram
 iKD diagnosis often based on positive Echo findings
suggestive of early coronary arteritis
Cardiac Complications
• Coronary artery aneurysms or ectasia occur in 15% to 25% of
untreated children
• May lead to further myocardial infarction, sudden death,
or ischemic heart disease
• Treatment within 10 days reduces severe aneurysms to <1%
Phase of Illness
Cardiac Complications
Acute (0–2 wk)
Myocarditis, pericarditis, coronary arteritis,
arrhythmias, valvular regurgitation, LV
dysfunction, pericardial effusion
Subacute (2–4 wk)
Coronary artery aneurysms
Convalescent (4–6 wk)
Coronary artery aneurysms
Risk Factors for Coronary Artery Aneurysm
Development
Clinical Course
Patient
Characteristics
Laboratory Values
Age <1 year old
Prolonged fever (>16 d)
Hematocrit <35%
Male
Recurrent fever after 48 h White blood cell count
afebrile
>12,000/mm3
Cardiomegaly on
presentation
Platelets >350,000/mm3
C-reactive protein >3
milligrams/dL
Albumin <3.5 grams/dL
Investigations for KD: Echocardiogram
 Echo assessment is ideal as it is a non-invasive test
 Echo is used to assess coronary artery morphology, LV
and left valvular function, and the evolution of
pericardial effusions
Coronary artery aneurysms rarely form before 10 days of
illness but may see signs of coronary arteritis in acute KD
 Aneurysms most commonly involve the proximal LAD/RCA

Echocardiogram
 Echocardiogram is Positive if any conditions are met:
Aneursyms are
classified by size based
on Internal vessel
diameter
• Small= <5 mm
• Medium= 5-8 mm
• Large= >8 mm
Echocardiogram- Follow-Up
 Uncomplicated Cases
 Echo at time of diagnosis 2 weeks 6-8 weeks after onset
 Follow-up Echocardiograms
 Progression/Regression of Coronary AbN, evaluate
ventricular and valve function, and assess for pericardial
effusions
 Complicated Cases
 Persistently Febrile, Coronary abN, ventricular dysfunction,
pericardial effusion, or valvular regurgitation
 May need more frequent Echo or additional invasive testing
such as angiogram, CT, MRI, and cardiac stress testing
Angiogram- Giant Coronary Aneurysms
Newburger J W et al. Pediatrics 2004;114:1708-1733
Noncardiac Manifestations of KD
System
Associated Signs and Symptoms
Gastrointestinal
Vomiting, diarrhea, abdominal pain, gallbladder hydrops, elevated
transaminases, paralytic ileus, mild jaundice
Blood
Elevated ESR or CRP, leukocytosis with left shift, hypoalbuminemia,
mild anemia in acute phase and thrombocytosis in subacute phase
(usually second to third week of illness)
Renal
Sterile pyuria (urethral origin) , proteinuria
Respiratory
Cough, rhinorrhea, hoarseness, infiltrate on chest radiograph
Joint
Arthralgia and arthritis
Neurologic
Mononuclear pleocytosis of cerebrospinal fluid, irritability, facial palsy
Skin
Perineal rash and desquamation in subacute phase, transverse furrows
of fingernails (Beau’s lines) during convalescence
Differential Diagnosis of KD















Viral infections ( Measles, Adenovirus, Enterovirus, EBV)
Scarlet Fever
Toxic shock syndrome
Staphylococcal scalded-skin syndrome
Bacterial Cervical Lymphadenitis
Adverse cutaneous drug eruption/hypersensitivity
Stevens- Johnson Syndrome
Juvenile rheumatoid arthritis
Leptospirosis
Rocky Mountain spotted fever
Erythema multiforme
Serum sickness
SLE
Reactive arthritis syndrome
Mercury Hypersensitivity Reaction
Treatment of KD
 Directed at reducing inflammation and preventing
cardiac complications.
Acute phase
 Combination of IVIG and high dose ASA

Aspirin works synergistically with IVIG to combat acute
inflammation, provides symptomatic relief of fever, and may
prevent thrombosis of inflamed or dilated coronary arteries

Steroids are not routinely indicated but may be useful in refractory
cases that do not improve with IVIG.
Treatment of KD
 Patients who develop aneurysms or coronary sequelae
are referred to a pediatric cardiologist and/or
cardiothoracic surgeon for further management
 Long-term therapy in individuals who develop
coronary aneurysms is aimed at preventing
myocardial ischemia or infarction

Dependent on severity of disease and aneurysm location/size
Treatment of Kawasaki disease
ASA
 Anti-inflammatory (high dose) and antiplatelet (low
dose) effects
 Must use in combination with IVIG to reduce coronary
abnormalities
 Treat with high-dose aspirin (20 to 25
milligrams/kg/dose every 6 hours)
 Dose is later reduced to 3 to 5 milligrams/kg once daily
for 6 to 8 weeks

Varied Protocols for when to reduce dose:
Afebrile x 48-72 hrs OR
 Continue until day 14 of illness and > 3-5 days afebrile

Treatment of Kawasaki disease
IVIG
 Unknown MOA but likely anti-inflammatory effects
 Single dose IV immunoglobulin (IVIG) (2 grams/kg
over 12 hours)

Rapid, symptomatic improvement in 90% of patients and
prevents aneurysm formation in 95%.
 Despite timely therapy, 5% will develop transient CA
dilation and 1% develop giant aneurysms
 IVIG may be readministered for persistent symptoms
Treatment of Acute Complications
Coronary Thrombosis/AMI
 Promoted by sluggish flow within dilated aneurysm
and occurrence of stenotic lesions at proximal and
distal ends

Differs from typical adult acute thrombosis related to
plaque rupture
 Treatment often aimed at targeting multiple steps in
coagulation cascade
 May benefit from interventional and surgical
techniques in acute and progressive CAD
Cardiology: Long Term Follow-Up
 Children without cardiovascular abnormalities treated
fully in the acute and subacute phase appear to be
clinically asymptomatic 10 to 21 years later
 CA dilatation <8 mm generally regresses over time
 Most smaller aneurysms fully resolve by echo
 Patients with giant aneurysms are at the greatest risk
for myocardial infarction resulting from CA occlusion
Long-Term Management in Kawasaki Disease
Risk
Level
Definition
Management Guidelines
I
No coronary artery changes at No ASA is needed beyond the subacute phase (6–
8 wk). No P.A. restrictions > 6–8 wks. No followany stage of the illness
up beyond the first year.
II
Transient ectasia of coronary Same as above, or clinical follow-up ± ECG every
arteries during acute phase
3–5 y. No P.A. restrictions >6–8 wks.
III
Single small to medium
coronary aneurysm
IV
Giant aneurysm or multiple
small to medium aneurysms
without obstruction
V
Coronary artery obstruction
ASA until abnormality resolves. Annual follow-up
with ECG and echo if < 10 y and every other-year
stress testing if > 10 y. P.A. restrictions guided by
stress testing.
Long-term ASA ± warfarin. Annual follow-up with
ECG, echo, and stress testing. P.A. restrictions
guided by stress testing. No contact sports. Angio.
Long-term ASA ± warfarin ± calcium
channel/beta blocker to reduce myocardial oxygen
consumption. Echo and ECG every 6 mo. Stress
testing and Holter examination annually. P.A.
restrictions as above. Angiogram.
Incomplete KD Algorithm- Does it work??
KD with isolated cervical lymphadenopathy
 Case series

Initial presentation of only fever and cervical LAD at the
time of admission.
 These patients tended to be older and to have a more
severe course, with increased risk of coronary artery
disease and lack of response to IVIG

Thus, certain presentations may be associated with a worse
prognosis
Incomplete KD- Delayed Diagnosis
 Incomplete KD should not be equated with mild KD
(Sonobe et al., 2007)

Literature suggests that patients with Incomplete KD are more
likely to develop coronary artery abnormalities, probably
because they are less likely to be diagnosed expeditiously
 14.2
% in Complete KD vs. 18.4 % in Incomplete KD
 Repeated histories and physical examinations are
important for:
 Diagnosis of KD
 Consideration of alternative diagnoses
Kawasaki Disease: Summary
 KD is a systemic illness characterized by fever,
conjunctivitis, mucositis, rash, extremity changes, and
cervical lymphadenopathy.
 Patients who lack a sufficient number of findings to
fulfill the classic criteria may have incomplete KD
 No laboratory or cardiac studies are included among
the classic diagnostic criteria for KD, but certain
findings characteristic of KD may support the
diagnosis in ambiguous cases
Kawasaki Disease: Pearls
 Must consider KD in the DDx of a child with unexplained
fever for 4-5 days that is associated with any clinical
features of KD
 History is Key Features often do not occur at the same
time so must ask if clinical criteria have been present
 When entertaining the diagnosis of possible iKD, using the
algorithmic approach and consulting a specialist is advised
 Early treatment of KD with IVIG and high dose ASA can
drastically reduce the likelihood of development of cardiac
complications
References
1.
.
Anderson MS, Todd JK, Glode MP. Delayed diagnosis of Kawasaki syndrome: An
analysis of the problem. Pediatrics. 2005; 115 (4): e428
2. Barone SR, Pontrelli LR, Krilov LR. The differentiation of classic Kawasaki
disease, atypical Kawasaki disease, and acute adenoviral infection: use of clinical
features and a rapid direct fluorescent antigen test. Arch Pediatr Adolesc Med.
2000;154:453–456.
3. Council on Cardiovascular Disease in the Young; Committee on Rheumatic Fever,
Endocarditis, and Kawasaki Disease; American Heart Association. Diagnostic
guidelines for Kawasaki disease. Circulation. 2001;103:335–336
4. Minich LL, Sleeper LA, Atz AM, et al. Delayed diagnosis of Kawasaki disease:
what are the risk factors? Pediatrics. 2007;120(6):e1434.
References
5. Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-
term management of Kawasaki disease: A statement for health professionals from
the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council
on Cardiovascular Disease in the Young, American Heart Association. Circulation
2004 Oct 26;110(17):2747–2771.
6. Sundel, R. Kawasaki disease: Clinical features and diagnosis. In: UpToDate,
Tepas, E (Ed), UpToDate, Waltham, MA, 2013.
7. Sundel, R. Kawasaki disease: Epidemiology and etiology. In: UpToDate, Tepas, E
(Ed), UpToDate, Waltham, MA, 2013.
8. Sundel, R. Incomplete (atypical) Kawasaki disease. In: UpToDate, Tepas, E (Ed),
UpToDate, Waltham, MA, 2013
References
9. Sundel, R. Kawasaki disease: Initial treatment and prognosis. In: UpToDate,
Tepas, E (Ed), UpToDate, Waltham, MA, 2013
10. Tintinalli, JE (Eds). Pediatric Heart Disease: Acquired Heart Disease. In:
Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e. McGrawHill Education, 2011.
11. Yellen ES, Gauvreau K, Takahashi M et al. Performance of 2004 American
Heart Association recommendations for treatment of Kawasaki disease.
Pediatrics. 2010;125:e234–e241
12. Yu, JJ. Diagnosis of incomplete Kawasaki disease. Korean J Pediatr. 2012
March; 55(3): 83–87.
2D Echocardiogram
Newburger J W et al. Pediatrics 2004;114:1708-1733