Transcript Kawasaki Disease

FEVER AND RASH IN A 5
MONTH OLD INFANT
David H. Rubin, MD
Department of Pediatrics
St Barnabas Hospital
Professor of Clinical Pediatrics
Albert Einstein College of Medicine
CASE HISTORY
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5 month old immunized female
T98.6°F, P 127, RR 32
Diffuse macular eruption on face, arms
and trunk
Decreased intake and urine output
Diarrhea (blood tinged), vomiting,
cough
CASE HISTORY
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Seen 2d prior to ED visit and Rx Amoxicillin
due to otitis media (also did stool culture 
negative)
Developed petechial rash on arms after 2-3
hours in ED
WBC 11.6, 74% lymph, no bands
CSF: glucose 62, protein 38, WBC 4 RBC 170
Rx: ceftriaxone
FEVER AND RASH – DIFFERENTIAL
DIAGNOSIS I
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Rubeola (measles virus)
Rubella (rubella virus)
Erythema infectiosum (5th disease; human
parvovirus B19)
Roseola (human herpesvirus 6)
Lyme disease (borrelia burgdorferi)
Erythema multiforme (idiopathic)
Secondary syphillis (treponema pallidum)
Meningococcemia (neisseria meningitidis)
FEVER AND RASH – DIFFERENTIAL
DIAGNOSIS II
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Rocky Mountain Spotted Fever (rickettsia
rickettsii)
Scarlet Fever (beta-hemolytic streptococcus)
Toxic shock syndrome (staphylococcus aureus)
Kawasaki disease
Varicella (varicella-zoster virus)
Herpes zoster (varicella-zoster virus)
Rickettsialpox (rickettsia akari)
Erythema nodosum (various causes)
Enteroviral infection
INFECTIOUS GASTROENTERITIS ETIOLOGY
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Viruses – rotavirus, Norwalk
Shigella
Salmonella
Campylobacter
Entamoeba histolytica
E coli 0157:H7
Cryptosporidium
C. difficile
Giardia lamblia
Vibrio Cholera
Cyclospora
RECTAL BLEEDING AND DIARRHEA
(Boyle, PIR, 2008)
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Infectious colitis (salmonella, shigella, yersinia,
campylobacter, e coli 0157, aeromonas
hydrophilia, klebsiella, c. difficile, n. gonorrhea,
cmv, e histolytica, trichuris trichura)
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Hemolytic uremic syndrome
Necrotizing enterocolitis
Eosinophilic proctocolitis
IBD – ulcerative colitis, Crohn disease
DEHYDRATION AND SYMPTOMS
RUBEOLA
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Etiology: measles virus – single stranded
RNA paramyxovirus
Affects upper respiratory tract and
regional lymph nodes during brief
viremia
Secondary viremia spreads 5-7 days
later as virus infected monocytes spread
virus to respiratory tract, skin, and other
organs
RUBEOLA
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Rash: macular/papular may become
confluent; begins face, neck spreads out and
inferior, rash secondary to vasculitis
Most common 5-9 year olds
Exposure from large respiratory droplets;
requires close contact
Infected people contagious 1-2 days prior to
symptoms and 4 days after the rash
RUBEOLA
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“Modified measles”
• Cases of mild measles in people with
partial protection
• Usually children vaccinated prior to age
12 months (with or without coadministered immune serum globulin or
• Persons receiving immunoglobulin
RUBEOLA
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Symptoms:
•Stage 1 (invasion): coryza, cough,
conjunctivitis, Koplik spots
•Stage 2 (eruption): fever, high
temperature, maculopapular
(morbilliform) rash (blanches on
pressure), abdominal pain, pneumonia
•Stage 3 (convalescence): rash fades,
low grade temperature
RUBEOLA
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Basis for diagnosis: serology – test for
IgM antibodies
Confirmation of diagnosis
• Multinucleated giant cells in nasal mucosa
smears
• Virus isolation of culture
• Antibody increase between acute and
convalescent serum
RUBEOLA - COMPLICATIONS
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Otitis media (most common); mastoiditis
Abdominal pain – watch for appendicitis due to
swelling of Peyer’s patches, obstruction
Pneumonia from secondary bacterial infection
Myocarditis
Encephalitis (most serious)
Late onset: subacute sclerosing pan
encephalitis (autoimmune phenomenon)
RUBEOLA - TREATMENT
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No specific treatment
Hydration, antipyretics
Avoid intense light (for photophobia)
IV ribavirin ???
High dose vitamin A improves outcome for
• Populations at risk for severe infections – infants 6
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months - 2 years of age
HIV infected infants
Children in endemic areas in developing countries
RUBEOLA - TREATMENT
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Prevention: live virus vaccine at 12-15 months and
4-6 years
• Contraindications: severe HIV disease,
immunocompromised children with congenital
immunodeficiency, cancer chemotherapy,
immunosuppressive dose of steroids
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Susceptible household contacts with a chronic
disease or immunocompromised exposed to measles
need to receive post exposure prophylaxis with
measles vaccine within 72 hours of exposure or
immunoglobulin within 6 days of exposure
MACULOPAPULAR ERUPTION
KOPLIK SPOTS
TYPICAL MEASLES EXANTHEM: ERYTHEMATOUS MACULOPAPULAR RASH
Zenel, J. A. Pediatrics in Review 2000;21:105-107
Copyright ©2000 American Academy of Pediatrics
RUBELLA
(German or 3 days measles)
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Invades respiratory tract and disseminates by
a primary viremia
Low grade temperature
Rash usually starts on face and spreads
outward; maculopapular but not confluent
Most contagious 2 days prior to rash and 5-7
days after rash
Arthralgias, postauricular lymph node swelling
Complications: Encephalitis (rare), ITP from
vaccine
RUBELLA
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20% of patients – Forschheimer spots – rose
spots on soft palate
Mild pharyngitis, conjunctivitis, anorexia,
headache, low grade fever
Polyarthritis of the hands common in older
women
Paresthesias
Tendinitis
Treatment – supportive; maintain hydration
and give antipyretics
RUBELLA
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Infection in utero: congenital rubella
syndrome (crs)
• If infection in 1st trimester – 90% of fetuses
infected
• Cataracts, deafness, PDA
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Infects with CRS may shed virus in
nasopharyngeal secretions and urine for
more than 1 year – can easily transmit
virus
RUBELLA
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MMR at 12-15 months; rubella shed after
vaccination from nasopharynx but not
communicable
Pregnant women should be immunized after
delivery
Avoid pregnancy for 28 days after receiving
vaccine
After vaccination, post pubertal females may
experience arthralgias in 25% of cases
• May occur 1-3 weeks after vaccination
RUBELLA
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Contraindications to vaccination –
similar to rubeola
Susceptible non-pregnant persons
exposed to rubella should receive
rubella vaccination
Immunoglobulin should be
administered when pregnant women
are exposed to rubella and elective
abortion is not an option
RUBELLA
VARICELLA
Chickenpox and zoster - caused by
varicella-zoster virus
 Chickenpox is the primary
infection; zoster is a reactivation
infection
 VZV infects susceptible persons via
conjunctivae or respiratory tract
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VARICELLA
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Disseminates by primary viremia and infects
regional lymph nodes, liver, spleen and other
organs
Secondary viremia follows resulting in a
cutaneous infection/rash
• After resolution of the rash, virus persists in latent
infection in dorsal root ganglia cells
• Zoster (shingles) is a reactivated of latent infection
of endogenous VZV
VARICELLA
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Exposure – respiratory droplets; incubation
9-28 days (mean=13) after contact
Period of communicability is 2 days before
and 7 days after lesions crusted over
Symptoms: low grade fever, lesions of
various sizes/shapes
Treatment: symptomatic, avoid aspirin,
antiviral in selected cases
VARICELLA
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Pre-eruption phase of zoster includes intense pain
and tenderness along dermatome with malaise and
fever
Papules appear which vesiculate ; group of lesions
appear for 1-7 days
Any branch of cranial nerve V may be affected –
which may result in corneal and/or intraoral lesions
If cranial nerve VII involved facial paralysis and
ear canal vesicles (Ramsey Hunt syndrome)
VARICELLA - TREATMENT
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Non aspirin antipyretics
Cool baths
Hygiene
Immunocompromised?
• Early therapy with antivirals (eg acyclovir) may
prevent pneumonia, encephalitis, death
• For nonpregnant persons ≥ 13 yrs and children
≥ 12 months with chronic cutaneous or pulmonary
disease receiving steroids or long term salicylates
VARICELLA - COMPLICATIONS
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Secondary infections (staph/strep) most
common; may be life threatening with toxic
shock syndrome/necrotizing fasciitis
Varicella gangrenosa – thrombocytopenia
with hemorrhagic lesions
Pneumonia
Myocarditis/pericarditis
Hepatitis
VARICELLA - COMPLICATIONS
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Glomerulonephritis
Orchitis
Arthritis
Ulcerative gastritis
Encephalitis (cerebellar ataxia may occur
without encephalitis)
Reyes syndrome
VARICELLA - OTHER ISSUES
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Primary varicella in pregnant woman 
fetal varicella infection
• Low birthweight, cortical atrophy, seizures,
mental retardation, chorioretinitis, cataracts,
intracranial calcifications
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Children exposed in utero to VZV may
develop zoster without varicella
VARICELLA - OTHER ISSUES
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Severe neonatal varicella
• Occurs in newborns of mothers with varicella
(not shingles) 5 days before or 2 days after
delivery
• Child born prior to maternal antibody
response develops
• Treat infants ASAP with varicella zoster
immunoglobulin
VARICELLA
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Children with varicella- no return to
school until all lesions crust over
Live viral vaccine at 12-18 months and
19 months – 13th birthday
Passive immunity with VZIG given within
96 hours of exposure for high risk
persons
• Immunocompromised
• Neonates of mothers with neonatal varicella
VARICELLA
ERYTHEMA INFECTIOSUM – 5TH
DISEASE
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Human parvovirus B19
Slapped cheek syndrome
Spread is respiratory
Initial viremia at 7-10 days; mild flu-like
illness
Rash at 10-17 days represents immune
response; patients are only contagious up
to presence of rash
ERYTHEMA INFECTIOSUM – 5TH DISEASE
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Mild systemic symptoms (fever, malaise, sore
throat) in 50% of children
Complications
• Arthritis: F>M, older>younger
• Aplastic crisis: usually not noticed in patients with
normal erythrocyte half-life BUT results in severe
anemia in those with any chronic hemolytic
anemia (rash follows hemolysis)
• Pregnancy: early miscarriage, late hydrops fetalis
ERYTHEMA INFECTIOSUM – 5TH
DISEASE
ERYTHEMA INFECTIOSUM – 5TH DISEASE
ROSEOLA
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Cause: human herpes virus 6 and 7
Seen in children 6 mo-3 yrs
Clinical findings:
• Sudden onset of fever – common to see >40C
which may last up to 8 days (mean 4 days),
followed by diffuse maculopapular eruption
• Fatigue, irritability, URI symptoms (but no
conjunctivitis or exudative pharyngitis), diarrhea
and vomiting (30% of pts), swollen eyelids may
precede fever
ROSEOLA - COMPLICATIONS
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Febrile seizure (10% of pts)
HHV-6 can cause meningoencephalitis or
aseptic meningitis
Multiorgan disease can occur in
immunocompromised patients
• Pneumonia
• Hepatitis
• Bone marrow suppression
• Encephalitis
ROSEOLA
ROSEOLA
LYME DISEASE
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Subacute or chronic spirochetal infection caused by
Borrelia burgdorferi transmitted by the bite of a deer
tick
Erythema chronicum migrans develops in 6080% of patients (most characteristic feature)
• Occurs between 3-30 days; may reach diameter of 20 cm
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Arthritis – seen in 50% of patients weeks to
months after bite
• Recurrent attacks of migratory, monoarticular or
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pauciarticular involving knees and other large joints
Chronic arthritis develops in 10% of patients
LYME DISEASE
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Neurological symptoms in 20% of patients;
untreated symptoms may become chronic or
permanent
• Bell’s palsy, aseptic meningitis, peripheral neuritis, GuillainBarre syndrome, encephalitis, ataxia, chorea
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Cardiac disease in 5% of patients
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Serologic diagnosis based on
• Heart block or myocardial dysfunction
• ELISA
• Immunoblot to confirm ELISA (if positive or questionable)
• Causative organism difficult to culture
LYME DISEASE - TREATMENT
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Based on ISDA 2006
http://www.journals.uchicago.edu/doi/full/10.1
086/508667
Routine use of antibiotics after tick bite not
supported
Treatment with docycycline (> 8 yrs of age),
amoxicillin, or cefuroxime is recommended for
early or late LD associated with ECM
Neurologic symptoms – ceftriaxone
Cardiac symptoms – ceftriaxone, ?pacemaker
LYME DISEASE
LYME DISEASE
KAWASAKI DISEASE
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Vasculitis of unknown etiology
Multisystem involvement and
inflammation of small and medium sized
arteries with aneurysm formation
More common among children of Asian
decent
Usually children <5 years; peak 2-3
years
KAWASAKI DISEASE
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In children < 3 months of age
• Usually see atypical course leading to rapid and severe
coronary artery damage (CAD)
• ECHO mandatory if considered in this age group;
diagnosis very difficult
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Age is independent risk factor for CAD
CAD develops in 5% of timely treated patients
Incomplete/atypical definition
• Fever, at least 2 of the clinical criteria for KD, and
laboratory data showing systemic inflammation; 2D
echos should be performed
KAWASAKI DISEASE
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Prolonged fever is hallmark of the disease
Lymphadenopathy is least common finding
(seen in 75% of cases compared with 90% for
other signs)
Coronary lesions are usually not present until
10 days; therefore decision to treat made prior
to knowledge of cardiac outcome
Other useful signs
• Extreme irritability
• Inflammation of BCG scar
KAWASAKI DISEASE – CLINICAL
PRESENTATION
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Acute phase (1-2 weeks)
• Sudden onset of high fever followed by
conjunctival erythema, mucosal changes,
cervical adenopathy, swelling of hands and feet
• Irritability
• Abdominal pain, hydrops of gall bladder
• Arthritis
• Carditis – tachycardia, CHF, giant coronary
artery aneurysms
KAWASAKI DISEASE – CLINICAL
PRESENTATION
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Subacute phase
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Convalescent phase
• Lasts up to 4th week
• Resolution of fever and other symptoms
• Desquamation of fingers and toes
• Elevation of platelet count
• Coronary artery aneurysms
• Disappearance of clinical symptoms
• 6-8 weeks after initial symptoms
CLINICAL DIAGNOSIS
KAWASAKI DISEASE
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Still difficult to diagnosis – especially in incomplete
or atypical form
Atypical Kawasaki Disease: 3 clinical criteria
+ identification of coronary aneurysms
Despite timely treatment, 15% of patients have
persistent fever which require steroids, additional
immunoglobulins, and immunosuppressant
medication
Children apparently normal during initial exam may
develop cardiac findings later in life
KAWASAKI DISEASE COMPLICATIONS
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Coronary artery thrombosis and coronary and peripheral
artery aneurysm
Myocardial infarction
Myopericarditis
Congestive heart failure
Hydrops of gall bladder
Aseptic meningitis
Arthritis
Sterile pyuria (urethritis)
Thrombocytosis
Diarrhea
Pancreatitis
Peripheral gangrene
KAWASAKI DISEASE - TREATMENT
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IV Immunoglobulin (mechanism
unknown)
• Single dose of 2 g/kg over 12 hours
• Rapid defervescence and symptom resolution
• Reduces incidence of coronary artery aneurysm
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Aspirin 80-100 mg/kg/day divided q 6
hours for 48 hours then reduce by ½
• Continue for 6-8 weeks until cardiac ECHO
shows no evidence of cardiac pathology
ERYTHEMATOUS MACULAR ERUPTION
- KAWASAKI SYNDROME
DESQUAMATION OF THE SKIN
ANGULAR CHELITIS
STRAWBERRY TONGUE
CONJUNCTIVAL INJECTION
SCARLET FEVER
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Erythrogenic toxin produced by strains of Group A
beta hemolytic streptococci - usually seen 24-48
hrs after pharyngitis
May also be seen following infection of wounds,
burns, streptococcal skin infection, impetigo,
cellulitis
Punctate erythema starts on trunk and spreads to
extremities, becoming confluent; rash fades in 4-5
days; desquamation may occur
Treatment: penicillin or erythromycin
SCARLET FEVER
SCARLET FEVER – STRAWBERRY
TONGUE
MENINGOCOCCEMIA
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Etiology: Neisseria meningitidis; Gram negative organism
with endotoxin in cell walls causing capillary vascular leak
and DIC
May be carried asymptomatically for months in upper
respiratory tract; 1% of carriers develop disease
Classified serologically by groups based on capsular
polysaccharide; systemic disease usually caused by: A, B
(1/3 of cases), C (25%), Y (25%), W-135 (15%)
May produce isolated infection to septic shock and:
meningitis, sepsis, septic arthritis, pericarditis, pneumonia,
chronic meningococcemia, otitis media, conjunctivitis, and
vaginitis
MENINGOCOCCEMIA
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Since 1982, vaccine available
(menomune) against groups A, C, Y, W135; recent release of conjugated
vaccine menactra for superior coverage
• No coverage of Group B – responsible for
cases in infants < 1 year of age and large
number of cases in US and UK
MENINGOCOCCEMIA
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Prodrome of URI followed by rapid onset of high
fever, headache, nausea, toxicity, hypotension
Purpura usually seen on extremities
May be followed by signs/symptoms of meningitis
• Neck stiffness, vomiting, stupor
Complications: permanent CNS damage, deafness,
seizures, paralysis, cognitive deficits
Treatment: vancomycin and cefotaxime to start;
after isolation of N. meningitidis, may use
penicillin
MENINGOCOCCEMIA
MENINGOCOCCEMIA
ROCKY MOUNTAIN SPOTTED FEVER
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Cause is R. rickettsii, gram negative
coccobaccillus, which invades endothelial
walls of blood vessels producing
vasculitis and eventually increased
permeability and organ failure
Most common rickettsial disease in USA
40% of patients unable to recall history
of tick bite
ROCKY MOUNTAIN SPOTTED FEVER
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Nonspecific fever within 5-10 days after tick
bite
Classic presentation rarely seen: fever, rash,
tick bite
• More likely: fever, severe headache, vomiting, muscle
pain, lost appetite
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Early small flat, pink, macules on wrists,
ankles, blanch with pressure
Late rash (petechial), abdominal pain, joint
pain, diarrhea
ROCKY MOUNTAIN SPOTTED FEVER
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Laboratory: hypoNa, increased LFTs,
thrombocytopenia
Multisystem involvement: respiratory, CNS, renal, GI
G6PD deficient patients have high risk for early
death
Indirect immunofluorescence assay (IFA) - reference
standard in Rocky Mountain spotted fever serology
May also use ELISA, latex agglutination, and dot
immunoassays
ROCKY MOUNTAIN SPOTTED FEVER
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Therapy should not be postponed pending
laboratory confirmation
Rx: Docycycline or chloramphenicol
Complications
• Noncardiogenic pulmonary edema (ARDS)
• DIC
• Circulatory collapse
• Multiple organ failure (myocarditis, encephalitis,
hepatitis and renal failure)
ROCKY MOUNTAIN SPOTTED FEVER
ROCKY MOUNTAIN SPOTTED FEVER
TOXIC SHOCK SYNDROME
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Severe prolonged shock caused by a toxin
produced by S. aureus or streptococcal
pyogenes (group A strep)
Approximately 400 cases/year in USA
May be seen in
• Abscesses, animal bite, barrier contraception (cervical
•
cap, diaphragm, sponge), breast augmentation
surgery, burns
Wounds, bursitis, croup, deep and superficial soft
tissue infections
TOXIC SHOCK SYNDROME
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May also be seen in:
• Dermatological surgery, empyema,
endometritis, influenza, insect bite,
lymphadenitis
• Nasal packing, postoperative complication,
postpartum period
• Septic abortion, sinusitis, tampon use
• Tracheitis, varicella zoster
TOXIC SHOCK SYNDROME
TOXIC SHOCK SYNDROME
ENTREROVIRAL INFECTIONS
ENTREROVIRAL INFECTIONS
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Named due to their replication in GI tract
Over 70 different serotypes – originally named
as echovirus, coxsackievirus – now named by
number
Transmission by fecal oral route
Clinical: viral paralysis, acute hemorrhagic
conjunctivitis, herpangina
Watch for myocarditis or pericarditis
ENTEROVIRAL INFECTIONS
•Symptoms variable
-Nonspecific URI symptoms, or
enteric
symptoms
(vomiting and diarrhea), fever,
irritability
•Rash variable (occurring on 2-4th day of fever)
-Usually erythematous maculopapules or
morbilliform; vesicular, urticarial, or petechial
•Transmission is fecal-oral or from upper respiratory
secretions
•Summer - fall outbreaks
•Treatment supportive