Kawasaki Disease: What you need to know from the 2017 Guidelines
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1 Kawasaki Disease: What you need to know from the 2017 Guidelines S. Kristen Sexson Tejtel, MD, PhD, MPH Pediatric Preventive Cardiology TCHAPP Conference April 4, 2019 No disclosures to report
2 Outline History of KD/Epidemiology 2017 Guidelines - Diagnosis Classic cases The challenges of diagnosis Echocardiography in KD Need for additional imaging - Treatment The future of initial KD therapy IVIG resistance - Knowing when to retreat Complex cases KDSS KD with severe coronary artery aneurysms Persistent features without fever Thromboprophylaxis in KD - Follow-up When to follow-up Immunizations after IVIG for KD Page 1 xxx00.#####.ppt 4/10/19 10:37:31 AM
3 What is Kawasaki Disease (KD)? Ka wa sa ki dis ease - noun a disease of unknown cause, occurring primarily in young children and giving rise to a rash, glandular swelling, and sometimes damage to the heart. Page 2 xxx00.#####.ppt 4/10/19 10:37:32 AM
4 Who Owns KD? Etiology: Infection? à Infectious Disease? Diagnosis/Treatmentà Pediatrics/Hospitalists? Pathophysiology: Vasculitis à Rheumatology? Consequence: Coronary Aneurysms à Cardiology? Page 3 xxx00.#####.ppt 4/10/19 10:37:33 AM
5 Kawasaki Disease (KD) History Page 4 xxx00.#####.ppt 4/10/19 10:37:33 AM
6 Epidemiology Annual US incidence ~25 per 100,000 children <5yrs old 80-90% of cases occur in children <5yrs old Peak mo Rare beyond late childhood Older children may experience delays in diagnosis Boys > Girls (1.5:1) Page 5 xxx00.#####.ppt 4/10/19 10:37:34 AM
7 Epidemiology Japan: 10x increased risk with an affected sibling 2x increased risk with a previously affected parent Page 6 xxx00.#####.ppt 4/10/19 10:37:35 AM
8 Pathophysiology Page 7 xxx00.#####.ppt 4/10/19 10:37:36 AM
9 Complete KD Page 8 xxx00.#####.ppt 4/10/19 10:37:37 AM
10 Page 9 xxx00.#####.ppt 4/10/19 10:37:37 AM
11 Page 10 xxx00.#####.ppt 4/10/19 10:37:38 AM
12 Page 11 xxx00.#####.ppt 4/10/19 10:37:39 AM
13 Page 12 xxx00.#####.ppt 4/10/19 10:37:39 AM
14 Page 13 xxx00.#####.ppt 4/10/19 10:37:40 AM
15 IRRITABILITY Page 14 xxx00.#####.ppt 4/10/19 10:37:41 AM
16 KD Characteristics Systemic inflammation of medium-sized arteries and multiple organs Associated clinical findings: -liver (hepatitis), -lung (interstitial pneumonitis), -gastrointestinal tract (abdominal pain, vomiting, diarrhea, gallbladder hydrops), -meninges (aseptic meningitis, irritability), -heart (myocarditis, pericarditis, valvulitis), -urinary tract (pyuria), -pancreas (pancreatitis), -lymph nodes (lymphadenopathy). Page 15 xxx00.#####.ppt 4/10/19 10:37:42 AM
17 The Challenges of Diagnosis The signs are common There is no gold standard lab test The stakes are high A missed diagnosis may manifest years (or decades) later However, are we over-diagnosing? Page 16 xxx00.#####.ppt 4/10/19 10:37:42 AM
18 The Challenges of Diagnosis How about incomplete KD? Page 17 xxx00.#####.ppt 4/10/19 10:37:43 AM
19 2017 Guideline Page 18 xxx00.#####.ppt 4/10/19 10:37:44 AM
20 Echo in KD Page 19 xxx00.#####.ppt 4/10/19 10:37:45 AM
21 2017 Guidelines What Defines a Positive Echocardiogram? Any of 3 conditions are met: -Z score of LAD or RCA 2.5 -Coronary artery aneurysm - 3 other suggestive features: decreased left ventricular function mitral regurgitation pericardial effusion Z scores in the LAD or RCA of 2 to 2.5 Page 20 xxx00.#####.ppt 4/10/19 10:37:46 AM
22 TCH KD Echo Read Summary: 1. Echobrightness 2. Ectasia 3. Lack of distal tapering 4. Dilation 5. Aneurysm formation 6. Valve regurgitation 7. Aortic root involvement 8. Function 9. Pericardial Effusion Page 21 xxx00.#####.ppt 4/10/19 10:37:47 AM
23 Coronary Artery Involvement Z-Score Classification Risk Level 1. No involvement: Always <2 2. Dilation only: 2 to <2.5; or if initially <2, a decrease in Z score during follow-up 1 3. Small aneurysm: 2.5 to <5 4. Medium aneurysm: 5 to <10, and absolute 5. dimension <8 mm 6. Large or giant aneurysm: 10, or absolute dimension 8 mm Page 22 xxx00.#####.ppt 4/10/19 10:37:47 AM
24 Assessing Aneurysms Page 23 xxx00.#####.ppt 4/10/19 10:37:48 AM
25 Giant Aneurysms and Prognosis Patients with giant aneurysms have worst prognosis 30 year survival- 90% Only 36% cardiac event free (Tsuda et al AM Heart J 2014; 167: ) (Manlhoit/PHN Pediatr Cardiol 2010) Page 24 xxx00.#####.ppt 4/10/19 10:37:49 AM
26 Kawasaki Echo Read Summary: 1. Echobrightness 2. Ectasia 3. Lack of distal tapering 4. Dilation 5. Aneurysm formation 6. Valve regurgitation 7. Aortic root involvement 8. Function 9. Pericardial Effusion Page 25 xxx00.#####.ppt 4/10/19 10:37:50 AM
27 2017 Guidelines Advanced Imaging in KD It is reasonable to obtain advanced imaging studies -computed tomographic angiography (CTA) -cardiac magnetic resonance imaging (CMRI) -invasive angiography Recommended on patients with: -severe proximal coronary artery abnormalities -when management decisions depend on visualization of distal segments -difficult to be seen by echocardiography Other vasculature can be imaged simultaneously Page 26 xxx00.#####.ppt 4/10/19 10:37:51 AM
28 MR in KD - Demonstrates distal aneurysms - Viability/delayed enhancement - Myocardial perfusion - See extracardiac dilation - Frequently need anesthesia CT in KD - Better than MR for thrombus evaluation - Smaller slices than MRI - Down side: Radiation Page 27 xxx00.#####.ppt 4/10/19 10:37:51 AM
29 Catheterization in KD Page 28 xxx00.#####.ppt 4/10/19 10:37:52 AM
30 Goal of Therapy Decrease systemic inflammation Prevent coronary aneurysms Minimize peak dimensions of coronary aneursysm(s) Prevent coronary thrombosis Page 29 xxx00.#####.ppt 4/10/19 10:37:53 AM
31 The Future of Initial KD Treatment 2017 Guideline states -IVIG Patients with complete and incomplete KD should be treated with high-dose IVIG (2 g/kg) -Aspirin: Administration of moderate (30 50 mg/kg/day) to high dose ( mg/kg/day) ASA is reasonable until the patient is afebrile, although there is no evidence that it reduces coronary artery aneurysms Page 30 xxx00.#####.ppt 4/10/19 10:37:54 AM
32 The Future of Initial KD Treatment What about steroids? -Traditionally has been a controversial topic -But should we consider steroids as part of initial therapy? Page 31 xxx00.#####.ppt 4/10/19 10:37:54 AM
33 The Future of Initial KD Treatment 2017 Guideline states - Single-dose pulse methylprednisolone should not be administered with IVIG as routine primary therapy - A longer course of corticosteroids (tapering over 2 3 weeks), together with IVIG and ASA may be considered for treatment of high-risk patients when such high risk can be identified in patients before initiation of treatment Page 32 xxx00.#####.ppt 4/10/19 10:37:55 AM
34 When to Retreat? 2017 Guideline states - Approximately 10 20% of patients with KD develop recrudescent or persistent fever at least 36 hours after the end of their IVIG infusion and are termed IVIG resistant. Page 33 xxx00.#####.ppt 4/10/19 10:37:56 AM
35 IVIG resistance - Pathophysiology Page 34 xxx00.#####.ppt 4/10/19 10:37:56 AM
36 2017 Guidelines - IVIG Resistance 1. Second dose of IVIG (2 g/kg) after 36 hours OR 2. Methylprednisolone mg/kg IV x 3 days, +/- taper of oral steroids OR Second dose of IVIG (2 g/kg), IV steroids x 3 days, +/- taper of oral steroids OR 3. Second dose of IVIG (2 g/kg) with prolonged oral taper of prednisolone/prednisone OR 4. Infliximab (5 mg/kg) instead of 2 nd IVIG or corticosteroids Brian W. McCrindle et al. Circulation. 2017;135:e927-e999 Page 35 xxx00.#####.ppt 4/10/19 10:37:57 AM
37 2017 Guidelines - IVIG Resistance 5. Cyclosporine in those who have failed above 6. Highly refractory patients - Anakinra - Cyclophosphamide - Plasma exchange Brian W. McCrindle et al. Circulation. 2017;135:e927-e999 Page 36 xxx00.#####.ppt 4/10/19 10:37:58 AM
38 Problems with 2017 Guidelines No robust data from clinical trials for IVIG resistance No guidelines for sickest patients: children < 1 year of age, KD shock syndrome, severe CA abnormalities or macrophage activation syndrome Persistent disease (worsening labs, persistent to worsening symptoms) in the absence of fever Page 37 xxx00.#####.ppt 4/10/19 10:37:58 AM
39 Children <1 Year of Age These children are at greater risk of treatment failure and CA abnormalities -Hispanics with worse outcomes -61% male, 39% female Unpublished PHIS data (14,325 pts from ): -<6 months 5.9% (852) months 11.1% (1,595) Delayed diagnosis due to paucity of signs - Incomplete KD - May present in shock Page 38 xxx00.#####.ppt 4/10/19 10:37:59 AM
40 Kawasaki Disease Shock Syndrome (KDSS) Kawashocki -Hypotension plus KD symptoms -Incidence of 7% Compared to typical KD patients -Higher CRP, hyponatremia, hypoalbuminemia and thrombocytopenia - IVIG resistance - rates of CA abnormalities -Increased risk of MR and prolonged myocardial dysfunction Kanegaye JT, et al. Pediatrics. 2009;123:e783 e789. Page 39 xxx00.#####.ppt 4/10/19 10:38:00 AM
41 KDSS 2017 Guidelines Initial IVIG and ASA Guidelines hint that KDSS are IVIG resistant TCH Initial IVIG and ASA w/ IV methylprednisolone 30 mg/kg x (3 pulses) w/ oral steroid taper 2 nd dose of IVIG if IVIG resistant [2] If IVIG resistant proceed with options 1,2, 3 or 4, etc Additional therapy driven by clinical course Page 40 xxx00.#####.ppt 4/10/19 10:38:01 AM
42 KD with Severe CA Abnormalities 2017 Guidelines TCH No guidelines Only case reports with limited outcomes Worrisome since these patients are at greatest risk of morbidity and mortality Initial IVIG and ASA +/- 2 nd dose of IVIG [1] if IVIG resistant IV methylprednisolone 30 mg/kg x (3 pulses) w/ oral steroid taper and infliximab vs other anakinra Page 41 xxx00.#####.ppt 4/10/19 10:38:02 AM
43 Persistent Features w/o Fever 2017 Guidelines No guidelines outside of initial therapy TCH Initial IVIG and ASA IV methylprednisolone 30 mg/kg x (~3 pulses) w/ oral corticosteroid taper [2] Additional therapy driven by clinical course Page 42 xxx00.#####.ppt 4/10/19 10:38:03 AM
44 Thromboprophylaxis in KD Most common in first 45 days Contributing factors: -thrombocytosis -increased platelet adhesion -inflammation -endothelial dysfunction -abnormal flow conditions Page 43 xxx00.#####.ppt 4/10/19 10:38:04 AM
45 Thromboprophylaxis in KD Aspirin low dose until coronary artery normalization Clopidogrel - increased risk of thrombosis or aspirin nonresponder Lovenox - the antiinflammatory actions and anticoagulant effects Page 44 xxx00.#####.ppt 4/10/19 10:38:05 AM
46 2017 guidelines KD Risk Evaluation Page 45 xxx00.#####.ppt 4/10/19 10:38:06 AM
47 2017 Guidelines - Echo Surveillance Twice weekly while rapidly expanding First 45 days: weekly First 3 months: monthly Every 3 months for first year Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease: A Scientific Statement from the AHA. 2013; Circulation Page 46 xxx00.#####.ppt 4/10/19 10:38:07 AM
48 Kawasaki Disease Follow Up Page 47 xxx00.#####.ppt 4/10/19 10:38:07 AM
49 Kawasaki Disease Follow Up Page 48 xxx00.#####.ppt 4/10/19 10:38:09 AM
50 Kawasaki Disease Follow Up Page 49 xxx00.#####.ppt 4/10/19 10:38:10 AM
51 Kawasaki Disease Follow Up Page 50 xxx00.#####.ppt 4/10/19 10:38:11 AM
52 Kawasaki Disease Follow Up Page 51 xxx00.#####.ppt 4/10/19 10:38:13 AM
53 Kawasaki Disease Follow Up At TCH -Infrequent follow-up throughout childhood Echocardiogram Electrocardiogram Clinic visit If sports perfusion imaging (cmri) Page 52 xxx00.#####.ppt 4/10/19 10:38:15 AM
54 Rheumatology Follow Up Children < 1 year or any child with a complicated KD course Follow up labs (i.e., CBC, LFTs, inflammatory markers, albumin, sodium) and clinical course Tapering of corticosteroids and other therapies if necessary, are based on improvement of labs and collaboration with cardiology Page 53 xxx00.#####.ppt 4/10/19 10:38:16 AM
55 2017 Guidelines Immunizations After IVIG in KD Defer live virus vaccines for 11 months -MMR -Varicella -Flumist -Rotavirus -Zoster -Smallpox -Yellow fever Page 54 xxx00.#####.ppt 4/10/19 10:38:17 AM
56 Thank you Page 55 xxx00.#####.ppt 4/10/19 10:38:17 AM
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