Kawasaki Disease
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Transcript 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