Upload
xenia-katrina-lucero
View
241
Download
1
Tags:
Embed Size (px)
Citation preview
IVIG Resistant Kawasaki Disease:
Xenia Katrina Lucero
• Patient A• 2 years old • Male• Filipino• R. Catholic• born on April 7, 2009 • from 17 Little Tagaytay, Marulas Valenzuela• admitted for the 2nd time in JRRMMC (May 2,
2012)
Chief Complaint
History of Present Illness
Day of Illness
Paracetamol
History of Present Illness
Day of Illness
Val Gen: UTICefuroximeIbuprofen
History of Present Illness
Day of Illness
Red lips
Dysuriavomiting
History of Present Illness
Day of Illness
Red lips
Dysuriavomiting
VGHVGH
History of Present Illness
Day of Illness
vomiting
Swelling on LE
History of Present Illness
Day of Illness
vomiting
Swelling on LE
History of Present Illness
Day of Illness
vomiting
History of Present Illness
Day of Illness
A
KD
History of Present Illness
History of Present Illness
SE Post correction
Na+ 135.7K+ 4.76
History of Present Illness
Acute phase
reactants
Result
ESR 62CRP 108
Urinalysis 4/17Color yellowCharacteristics clearpH 8.5SG 1.010Sugar/Protein (-)RBC -WBC -
History of Present Illness
Day of Illness
A ASA (30)
History of Present Illness
A
2D-Echo4/17
Trivial MRLeft Atrial EnlargementNormal coronary artery size Proximal DistalRCA 0.18/0.2 0.17cm/0.2LCA 0.16 0.16Normal PAP by PATGood LV systolic function with EF of 72%Left sided aortic archMinimal pericardial Effusion
History of Present Illness
Day of Illness
AASA
History of Present Illness
Blood GS/CS 4/21/2012Heavy Growth S. coagulase negative organismSensitive ResistanceChloramphenicol ClindamycinErythromycin OxacillinTetracycline PenicillinVancomycin
History of Present Illness
Day of Illness
A
History of Present Illness
Day of Illness
AASA
History of Present Illness
Day of Illness
AASA
History of Present Illness
Day of Illness
AASA
MGHASA (5)
History of Present Illness
Day of Illness
AASA
MGHASA (5)
History of Present Illness
Day of Illness
AASA
MGHASA (5)
Swelling of LE, painful extremities
Red Lips
Perianal desquamation
History of Present Illness
Day of Illness
AASA
MGHASA (5)
Swelling of LE, Painful extremities
Red lipsPerianal desquamation
(-) AGE (-) Pneumonia (-) Measles (-) PTB (-) Bronchial Asthma
o (+) Hypertension: Maternalo (-) Diabeteso (-) Bronchial Asthmao (-) Heart Diseaseo (-) Cancer
• only child of the couple
• Father: 25 year-old, HS graduate, factory worker
• Mother: 23 year-old HS graduate, housewife
• lives in two-storey semi-concrete house
• no rooms, portions are divided only by cabinets
• 1 pour-flush toilet
• Water supply: NAWASA
• garbage is collected 2x a week.
• Born to a 21 year old G1P1 (1001)• Live• Fullterm• via NSD• Chinese General Hospital• (-) fetomaternal complications
• (+) regular PNCU c/o CGH starting 2 mos AOG
• (+) regular intake of MVS and FESO4, FA
• (+) maternal URTI: 9mos AOG: Amoxicillin
• (-) exposure to radiation/ intake of teratogenic drugs
• fullterm,
• cephalic,
• NSD
• Chinese General Hospital.
• BW : 2900g
• (+) good suck• (+) good cry• (+) spontaneous
activity• (-) jaundice• (-) cyanosis
• Breastfed: up to 1 week, per demand
• bottle-fed with Promil at 1:1 dilution
• Complementary feeding: 6mos with cereals
• Currently: milk, rice, meat and vegetables
Growth andDevelopment
• 1month: social smile
• 3 months: controls head
• 5 months: rolls over
• 7 months: crawls
• 10 months: sit and stands with support
• 11 months: walks with support
• 1 yr 4 months: walks alone
Immunization History
1 BCG
3 DPT
OPV
Hepa B
measles
General: no weight loss, decreased in appetite
Respiratory: no difficulty of breathing, no cough, no
colds
Cardiovascular: no easy fatigability, no orthopnea
Gastrointestinal: no diarrhea, no constipation
Genitourinary: no hematuria, no frequency, no
oliguria
Neurological: no seizures, no loss of consciousness,
Review of Systems
Physical Examination:
• Vital signs:
• HR- 136bpm • RR- 38/min • Temp- 38.8 C • BP- 100/70mmHg• Weight: 9.5kg• Height: 85 cm
•Z scores:
•Height-for-age:
below -1 – -2 (Normal)•Weight- for-age:
below -3 (severely underweight)•BMI-for-age:
below -3 (severely wasted)
awake, comfortable, not in cardio-respiratory distress
• Skin: warm to touch, good skin turgor
• HEENT:anicteric sclerae, pink palpebral conjunctiva, no nasoaural discharge, no cervical lympadenopathy, no tonsillo-pharyngeal congestion, with red dry lips
• Lungs: symmetric lung expansion, no retractions, clear breath sounds
• Heart: adynamic precordium, normal rate, regular rhythm, PMI at 4th ICS L MCL, no murmur
• Abdomen: slightly globular, normoactive bowel sounds, soft, nontender, with perianal desquamation
• Extremities: grossly normal, no cyanosis, with edema on lower extremities, grade I, CRT <3s
Neurologic exam: awake, active, GCS 15CN I – able to smellCN II - pupils 1-2mm equally reactive to light, (+)
RORCN III, IV, VI – intact extraocular muscle movementsCN V – no facial asymmetryCN VII – no facial asymmetry with facial expressionsCN VIII – able to hearCN IX, X – good gag CN XI – good shoulder shrugCN XII – no tongue deviation
Motor Sensory DTR
Salient features
• 2 yo male
• Previously admitted with a diagnosis of KD– given IVIG on 11 day of illness
– Afebrile phase noted 5 days post IVIG
• 3 days post discharge/ 13 days post IVIG– Recurrence of fever
– Recurrence of swelling on LE, perianal desquamation
and red lips
Differential Diagnosis
TB
Typhoid fever
HRCI (Sepsis)
IVIG Resistant KD
Recurrent KD
Differential Diagnosis
Rule IN Rule OUT
Prolonged fever No hepatosplenomegaly
(+) CLAD No weight loss
Swelling and joint pains No bleeding tendencies
Malignancy
Differential Diagnosis
TB
Typhoid fever
HRCI (Sepsis)
IVIG Resistant KD
Recurrent KD
Differential Diagnosis
Infectious
TB
Rule IN Rule OUT
Fever No cough
Loss of appetite Weight loss
CLAD No exposure
(-) CXR
Differential Diagnosis
Infectious
Typhoid fever
Rule IN Rule OUT
Fever (-) diarrhea/ constipation
Loss of appetite (-)Abdominal pain
vomiting (-) Blood culture
Differential Diagnosis
Infectious
Health Care Related Infection (Sepsis)
Rule IN Rule OUT
Admitted for 14 days
(+) recurrence of fever 3 days post
discharge
Differential DiagnosisConnective Tissue Disease
Recurrent Kawasaki Disease
Rule IN Rule OUT
13 days post IVIG, Recurrence of:
Recurrence of fever 13 days post IVIG transfusion
fever no available criteria which defines recurrent KD
Perianal desquamation
Majority of cases recurs at 2 years post IVIG
Red lips
Edema of LE
Differential DiagnosisConnective Tissue Disease
IVIG-Resistant Kawasaki Disease
Rule IN Rule OUT
(+) IVIG transfusion
Afebrile phase noted 5 days post IVIG
13 days post IVIG:
(+) fever
(+) red lips
(+) edema of LE
(+) perianal desquamation
Course in
the Ward
Course in
the Ward
CBC 5/2/12
ABO A +Hgb 85Hct 0.28RBC 3.62WBC 15.7
2Neutro 65.8Lympho 27.2Platelet 665
Urinalysis 5/2/212
Color L. yellowCharacteristics S. turbid
pH 6.5SG 1.020
Sugar/Protein (-)RBC 0-2WBC 10-25
Antibiotics
ASA (30)
1HD
Swelling of LEPerianal desquamationRed lips
Acute phase reactants5/6/2012 Result NV
ESR 142 0-9CRP >384 <6 mg/l
5HD
Swelling of LEPerianal desquamationRed lips
D1 AntibioticsD1 Antibiotics
D2 AntibioticsD2 Antibiotics
Culture and sensitivity
Final result
Urine (5/7) No growth
6HD
Swelling of LEPerianal desquamationRed lips
5/8/2012Trivial MRLeft Atrial EnlargementNormal coronary artery size Proximal DistalRCA 0.21/0.4/.37 0.17/0.24/0.29LCA 0.2/0.3 0.2/0.31 cmNormal PAP by PATFair LV systolic function with EF of 55%Left sided aortic archMinimal pericardial Effusion
7HD
Swelling of LEPerianal desquamationRed lips
D3 AntibioticsD3 Antibiotics
Culture and sensitivity
Final result
Blood (5/9) No growth
8HD
Swelling of LEPerianal desquamationRed lips
IVIG ordered IVIG ordered
11HD
Swelling of LEPerianal desquamationRed lips
IVIG
DISCUSSION
• “A self-limited vasculitis of unknown etiology that predominantly affects children younger than 5 years. It is now the most common cause of acquired heart disease in children in the United States and Japan.”
• *Burns, J. Adv. Pediatr. 48:157. 2001.
Kawasaki Disease:Mucocutaneous Lymph Node
Syndrome
• 1967: Dr Tomisaku Kawasaki– 50 cases of a distinctive illness in children at
Tokyo Red Cross Medical Center in Japan.1
• 1976: Melish et al – United States, in a group of 12 children from
Honolulu examined from 1971-1973.2
1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi. Mar 1967;16(3):pp 178-222.
2. Melish ME, Hicks RM, Larson EJ. Mucocutaneous lymph node syndrome in the United States. Am J Dis Child. Jun 1976;130(6):599-607.
Leading cause of acquired heart disease in children in the developed world
In the US, KD has surpassed acute rheumatic fever as the leading cause of acquired heart
disease in children younger than 5 years
Newburger JW, et al. Summary and abstracts of the Seventh International Kawasaki Disease Symposium: December 4-7, 2001, Hakone, Japan. Pediatr Res. Jan 2003;53(1):pp 153-7
Kawasaki Disease
• Leading cause of acquired heart disease
• disease of childhood • 80%: < 5 years of age• Boys: girls 1.5:1• Highest incidence in Japan
• US: ˜3,000 annually
Japan: 200,000 cases since the 1960s
– One case report in the literature documents a 35-day-old infant who developed Kawasaki disease after his second hepatitis B vaccination. 6
6. Miron D, Fink D, Hashkes PJ. Kawasaki disease in an infant following immunization with hepatitis B vaccine. Clin Rheumatol. Dec 2003;22(6):pp 461-3.
• 2007: FDA
– required the makers of RotaTeq rotavirus vaccine to report in the package insert that 9 cases of Kawasaki disease had occurred in children who had received the vaccine.
• However, most believe that there is no connection between the vaccine and the disease. 5
5. Hua W, Izurieta HS, Slade B, Belay ED, Haber P, Tiernan R, et al. Kawasaki disease after vaccination: Pediatr Infect Dis J. Nov 2009;28(11):pp 943-7.
Pathology
vasculitis Med-sized arteries
Med-sized arteries
Coronary Arteries
Acute/subacute: Edema of endothelial smooth muscle cells with intense inflammatory infiltration of the vascular wall
Severe: involves all layers, with
destruction of internal elastic lamina
Pathology
Severe: involves all layers, with destruction of internal elastic lamina
Vessel wall
weakensdilatation
• high (≥101F)• Unremitting• unresponsive to antibiotics
without treatment is generally 1-2 weeks but may persist for 3-4 weeks.
Clinical presentation
Five principal clinical criteria of KD
Clinical Manifestations
Initial Phase - lasts 2 weeks
• 101° temperature for 5 days
• Red eyes
• Sore throat
• Swollen lymph nodes
Skin Reactions
Skin ReactionsRashes on the
body
Skin Reactions
• Palms of hands swell• Soles of feet swell• Red - purple in color
• Palms of hands swell• Soles of feet swell• Red - purple in color
Phase 2 – Lasts 2 Weeks• Thrombocyto
sis• Desquamatio
n• Swollen and
joint pains• Devt of
coronary aneurysms• Highest
risk of sudden death
Phase 3 – convalescent
• All clinical signs disappeared
• ESR returns to normal (6-8 weeks)
Associated Signs and Symptoms
RespiratoryRhinorrhea, cough, pulmonary infiltrate
GIDiarrhea, vomiting, abdominal pain,
hydrops of the gallbladder, jaundiceNeurologic
Irritability, aseptic meningitis, facial palsy, hearing lossMusculoskeletal
Myositis, arthralgia, arthritis
Diagnostic Test
Laboratory findings
• WBC: normal to elevated with neutrophilic predominance
• Elevated ESR, CRP, may persist for 4–6 wk• Normocytic, normochromic anemia• platelet count: normal- 1st week, rapidly increases
by the 2nd–3rd week (1,000,000/mm3)• ANA/rheumatoid factor: Negative• Sterile pyuria• mild elevations of the hepatic transaminase
• The incidence of KD refractory to initial IVIG therapy increased to 38 percent in 2006 from a range of 10 to 20 percent between 1998 and 2005.
– This increase did not appear to be related to any changes in the formulations of IVIG used.
Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 2008; 153:117
• Risk factors associated with the need for retreatment included:
• Initial treatment at or before the fifth day of illness
• Recurrent episodes of KD
• Male sex
Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 2008; 153:117.
Risk Factors for unresponsiveness to IVIG
• Young patient age, < 1 yo
• Early diagnosis, with initial treatment < 4DOL
• Elevated C-reactive protein (≥10 mg/dL )
• Elevated liver enzymes (AST/ALT)
• Platelet count ≤300,000/mm2
• Elevated band count
• Serum sodium ≤133 mmol/L
• Low serum albumin
Sundel, Robert, Treatment of refractory Kawasaki disease, UpToDate, June 17, 2011
• In a study done by Young-Sun Do, et.al, they found out that IVIG resistant group has significantly longer febrile period and hospital days than those IVIG-responsive groups.
• Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group.
• Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group.
• Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients.
Complications
Coronary Artery Aneurysm
commonest
Most life threatening
25% untreated KD
6-8 wks from onset of illness
Complications
Coronary Artery Aneurysm
Coronary thrombosis
death
M I
Complications
Coronary Artery Aneurysm
SizeSmall = <5 mm diameter Medium = 5-8 mmGiant = ≥ 8 mm
Highest risk for sequelaeShape
SizeSmall = <5 mm diameter Medium = 5-8 mmGiant = ≥ 8 mm
Highest risk for sequelaeShape
Echocardiography
Onset of DX
2–3 wks of illness
N6-8 wks of
illness
(-) CAA/ ESR: Normal
2D- echo:optional
Coronary Artery Changes
• 15% to 25 % of untreated patients develop coronary artery changes
• 3-7% if treated in first 10 days of fever with IVIG
• Most commonly proximal, can be distal
• Left main > LAD > Right
Echocardiographic Findings
•Myocarditis with dysfunction
•Pericarditis with an effusion
•Valvar insufficiency
•Coronary arterial changes
The HARADA score
• 1) WBC count: >12 ×103/μl, • 2) Platelet count: < 35×104/μl, • 3) CRP: > 4 mg/dl, • 4) Hematocrit: <35%, • 5) Serum albumin: < 3.5 g/dl, • 6) Gender: male, • 7) Age: equal to or less than 12 months.
> 4 :high risk of developing coronary artery lesions
treatment
1. IVIG 2g/kg as a single infusion over 12H
2. Aspirin 30-50 mg/kg/day in four doses (in USA 80-100mg/kg/day in 4 doses) until afebrile for 2-3 days
3. Aspirin 3-5 mg/kg/day once daily for 6-8 weeks minimum
treatment1. Second dose of IVIG 2 g/kg
2. Third dose of IVIG or
3. Methylprednisolone 30mg/kg for 3 days or prednisolone 2 mg/kg/day orally and tailored based on clinical/ inflammatory marker improvement
Fever persists after 48H or recrudescent fever within 2 weeks
4. Cyclophosphamide, cyclosporin, plasmapheresis and monoclonal antibodies to TNFalpha have been reported
Tizard E.J., Complications of Kawasaki disease, Current Pediatrics, 2005 Volume 15, pp 62-88
• Patients receiving long-term aspirin therapy– annual influenza vaccination– Varicella vaccination
• Patients treated with 2 g/kg IVIG
delay measles-mumps-rubella and varicella vaccinations delayed for 11 mo
prognosis
Recovery is complete and without apparent long-term effects for patients who do not develop coronary disease
In Japan, fatality rates are very low, about 0.01%. Overall, 50% of coronary artery aneurysms resolve as assessed by echocardiogram 1–2 yr after the illness.
prognosis
Recurrence of the disease has been previously noted with reported rates varying between 0.8% in the United States to 3% in Japan.
The proportion of patients suffering a recurrence increases with age, while the majority of recurrences occur within 2 years of the initial attack.
9. Pemberton1, I M Doughty2, R J Middlehurst3 & M H Thornhill4, British Dental Journal 186, 270 - 271 (1999), Case study: Recurrent Kawasaki disease
KT H A N
YOU!!!