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IVIG resitant kawasaki

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IVIG resitant kawasaki

  1. 1. IVIG Resistant Kawasaki Disease: Xenia Katrina Lucero
  2. 2. • 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)
  3. 3. Chief Complaint
  4. 4. History of Present Illness Day of Illness Paracetamol
  5. 5. History of Present Illness Day of Illness Val Gen: UTI Cefuroxime Ibuprofen
  6. 6. History of Present Illness Day of Illness Red lips Dysuria vomiting
  7. 7. History of Present Illness Day of Illness Red lips Dysuria vomiting VGHVGH
  8. 8. History of Present Illness Day of Illness vomiting Swelling on LE
  9. 9. History of Present Illness Day of Illness vomiting Swelling on LE
  10. 10. History of Present Illness Day of Illness vomiting
  11. 11. History of Present Illness Day of Illness A KD
  12. 12. History of Present Illness
  13. 13. History of Present Illness SE Post correction Na+ 135.7 K+ 4.76
  14. 14. History of Present Illness Acute phase reactants Result ESR 62 CRP 108 Urinalysis 4/17 Color yellow Characteristics clear pH 8.5 SG 1.010 Sugar/Protein (-) RBC - WBC -
  15. 15. History of Present Illness Day of Illness A ASA (30)
  16. 16. History of Present Illness A 2D-Echo 4/17 Trivial MR Left Atrial Enlargement Normal coronary artery size Proximal Distal RCA 0.18/0.2 0.17cm/0.2 LCA 0.16 0.16 Normal PAP by PAT Good LV systolic function with EF of 72% Left sided aortic arch Minimal pericardial Effusion
  17. 17. History of Present Illness Day of Illness A ASA
  18. 18. History of Present Illness Blood GS/CS 4/21/2012 Heavy Growth S. coagulase negative organism Sensitive Resistance Chloramphenicol Clindamycin Erythromycin Oxacillin Tetracycline Penicillin Vancomycin
  19. 19. History of Present Illness Day of Illness A
  20. 20. History of Present Illness Day of Illness A ASA
  21. 21. History of Present Illness Day of Illness A ASA
  22. 22. History of Present Illness Day of Illness A ASA MGH ASA (5)
  23. 23. History of Present Illness Day of Illness A ASA MGH ASA (5)
  24. 24. History of Present Illness Day of Illness A ASA MGH ASA (5) Swelling of LE, painful extremities Red Lips Perianal desquamation
  25. 25. History of Present Illness Day of Illness A ASA MGH ASA (5) Swelling of LE, Painful extremities Red lips Perianal desquamation
  26. 26.  (-) AGE  (-) Pneumonia  (-) Measles  (-) PTB  (-) Bronchial Asthma
  27. 27. o (+) Hypertension: Maternal o (-) Diabetes o (-) Bronchial Asthma o (-) Heart Disease o (-) Cancer
  28. 28. • 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.
  29. 29. • Born to a 21 year old G1P1 (1001) • Live • Fullterm • via NSD • Chinese General Hospital • (-) fetomaternal complications
  30. 30. • (+) 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
  31. 31. • fullterm, • cephalic, • NSD • Chinese General Hospital. • BW : 2900g • (+) good suck • (+) good cry • (+) spontaneous activity • (-) jaundice • (-) cyanosis
  32. 32. • 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
  33. 33. Growth and Development • 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
  34. 34. Immunization History 1 BCG 3 DPT OPV Hepa B measles
  35. 35. 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
  36. 36. 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
  37. 37. • 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
  38. 38. • 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
  39. 39. Neurologic exam: awake, active, GCS 15 CN I – able to smell CN II - pupils 1-2mm equally reactive to light, (+) ROR CN III, IV, VI – intact extraocular muscle movements CN V – no facial asymmetry CN VII – no facial asymmetry with facial expressions CN VIII – able to hear CN IX, X – good gag CN XI – good shoulder shrug CN XII – no tongue deviation Motor Sensory DTR
  40. 40. 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
  41. 41. Differential Diagnosis TB Typhoid fever HRCI (Sepsis) IVIG Resistant KD Recurrent KD
  42. 42. Differential Diagnosis Rule IN Rule OUT Prolonged fever No hepatosplenomegaly (+) CLAD No weight loss Swelling and joint pains No bleeding tendencies Malignancy
  43. 43. Differential Diagnosis TB Typhoid fever HRCI (Sepsis) IVIG Resistant KD Recurrent KD
  44. 44. Differential Diagnosis Infectious TB Rule IN Rule OUT Fever No cough Loss of appetite Weight loss CLAD No exposure (-) CXR
  45. 45. Differential Diagnosis Infectious Typhoid fever Rule IN Rule OUT Fever (-) diarrhea/ constipation Loss of appetite (-)Abdominal pain vomiting (-) Blood culture
  46. 46. Differential Diagnosis Infectious Health Care Related Infection (Sepsis) Rule IN Rule OUT Admitted for 14 days (+) recurrence of fever 3 days post discharge
  47. 47. Differential Diagnosis Connective 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
  48. 48. Differential Diagnosis Connective 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
  49. 49. Course in the Ward Course in the Ward
  50. 50. CBC 5/2/1 2 ABO A­­+ Hgb 85 Hct 0.28 RBC 3.62 WBC 15.72 Neutro 65.8 Lympho 27.2 Platelet 665 Urinalysis 5/2/212 Color L. yellow Characteristics S. turbid pH 6.5 SG 1.020 Sugar/Protein (-) RBC 0-2 WBC 10-25 Antibiotics ASA (30) 1HD Swelling of LE Perianal desquamation Red lips
  51. 51. Acute phase reactants 5/6/2012 Result NV ESR 142 0-9 CRP >384 <6 mg/l 5HD Swelling of LE Perianal desquamation Red lips D1 AntibioticsD1 Antibiotics D2 Antibiotics D2 Antibiotics
  52. 52. Culture and sensitivity Final result Urine (5/7) No growth 6HD Swelling of LE Perianal desquamation Red lips
  53. 53. 5/8/2012 Trivial MR Left Atrial Enlargement Normal coronary artery size Proximal Distal RCA 0.21/0.4/.37 0.17/0.24/0.29 LCA 0.2/0.3 0.2/0.31 cm Normal PAP by PAT Fair LV systolic function with EF of 55% Left sided aortic arch Minimal pericardial Effusion 7HD Swelling of LE Perianal desquamation Red lips D3 AntibioticsD3 Antibiotics
  54. 54. Culture and sensitivity Final result Blood (5/9) No growth 8HD Swelling of LE Perianal desquamation Red lips IVIG ordered IVIG ordered
  55. 55. 11HD Swelling of LE Perianal desquamation Red lips
  56. 56. IVIG
  57. 57. DISCUSSION
  58. 58. • “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
  59. 59. • 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.
  60. 60. 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
  61. 61. 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
  62. 62. • US: ˜3,000 annually Japan: 200,000 cases since the 1960s
  63. 63. – 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.
  64. 64. • 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.
  65. 65. 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
  66. 66. Pathology Severe: involves all layers, with destruction of internal elastic lamina Vessel wall weakens dilatation
  67. 67. • high (≥101F) • Unremitting • unresponsive to antibiotics without treatment is generally 1-2 weeks but may persist for 3-4 weeks. Clinical presentation
  68. 68. Five principal clinical criteria of KD
  69. 69. Clinical Manifestations
  70. 70. Initial Phase - lasts 2 weeks • 101° temperature for 5 days • Red eyes • Sore throat • Swollen lymph nodes
  71. 71. Skin Reactions
  72. 72. Skin Reactions Rashes on the body
  73. 73. 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
  74. 74. Phase 2 – Lasts 2 Weeks • Thrombocytosis • Desquamation • Swollen and joint pains • Devt of coronary aneurysms • Highest risk of sudden death
  75. 75. Phase 3 – convalescent • All clinical signs disappeared • ESR returns to normal (6-8 weeks)
  76. 76. Associated Signs and Symptoms Respiratory Rhinorrhea, cough, pulmonary infiltrate GI Diarrhea, vomiting, abdominal pain, hydrops of the gallbladder, jaundice Neurologic Irritability, aseptic meningitis, facial palsy, hearing loss Musculoskeletal Myositis, arthralgia, arthritis
  77. 77. Diagnostic Test
  78. 78. 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
  79. 79. • 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
  80. 80. • 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.
  81. 81. 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
  82. 82. • 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.
  83. 83. Complications Coronary Artery Aneurysm commonest Most life threatening 25% untreated KD 6-8 wks from onset of illness
  84. 84. Complications Coronary Artery Aneurysm Coronary thrombosis death M I
  85. 85. Complications Coronary Artery Aneurysm Size Small = <5 mm diameter Medium = 5-8 mm Giant = ≥ 8 mm Highest risk for sequelae Shape Size Small = <5 mm diameter Medium = 5-8 mm Giant = ≥ 8 mm Highest risk for sequelae Shape
  86. 86. Echocardiography Onset of DX 2–3 wks of illness N 6-8 wks of illness (-) CAA/ ESR: Normal 2D- echo: optional
  87. 87. 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
  88. 88. Echocardiographic Findings •Myocarditis with dysfunction •Pericarditis with an effusion •Valvar insufficiency •Coronary arterial changes
  89. 89. 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
  90. 90. 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
  91. 91. treatment 1. 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
  92. 92. • 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
  93. 93. 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.
  94. 94. 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
  95. 95. KT H A N YOU!!!

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