Kawasaki Disease (MA61)

Epi

-80% of them are <5yo

-boys>girls 1.5:1

-median 2yo in US

-more in Asian/Pacific Islanders, then non-Hispanic blacks, then Hispanics, then whites

-Winter/Spring more then the remainder

-Young infants more likely to have incomplete Sx, and more likely to have cor art aneurysms (!!)

-+genetic role (incr FHx etc in Japan studies)

Etiology/Pathogenesis

-?etiology

-? due to richettsia, proprionibacterium, strep, dust mite Ag, retrovirus?

-none confirmed

-exposure to recently shampooed carpets was linked in case-ctrl studies

-tends to target young kids, w clusters in Winter/Spring, epidemics cycle q3 yrs thus ? infectious

--> activates monos, macros, T4 helpers, B cells; incr IL1,2,6, TNFa--> endothelium susceptible to lysis by Ab's. The endothelium makes ICAM, VEGF, platelet derived growth factors during acute/subacute phases --> inflmn.

-?bc a pathogen entered system via GI/resp--> incr IgA--> xx

Pathology

-in 1st 10 days--> generalized microvasculitis

-in 1st 3-4 wks--> myocarditis w mononuclear ell infiltration & edema in myocardium/conduction syst

-Valvulitis may affect MV or AoVlv

-inflmn continues in medium/large arteries, espec cor arts

-edema, mononuc infiltration, progressive fibrosis, disrupts internal elastic lamina

-worse at proximal segments and branching pts of cor art (areas of HD stress)

Aneurysms: -aneurysms are fusiform, saccular, cylindrical, or segmented (string of beads)

-can affect ther arts- iliac, fem, axillary, renal, rarely ever in cerebral

->1/2 regress in 1-2yrs

-more likely to regress if pt<1yo at onset, F pt, fusiform shape, diam <8mm

-cor thrombi bc incr #/activity of platelets, procoagulant endothelium, stagnant Q in aneurysms, abNl vasc wall shear stresses at aneurysm entrance, --> MI, usually in the 1st 6-8wks

-more likely to dvp in LCA and prox LAD and RCA, w L circ least likely involved

-if diam >8mm (giant aneurysm)--> higher risk for MI

-rarely they rupture--> sudden death

-most episodes occurred with steroid treatment in the acute phase

-Severe stenosis or compete cor art occlusion can --> MI/ischemic CM

-spontaneous revascularization may occur via collaterals and reacnalization

-large aneurysms in RCA may get thrombi after recanalization--> braided small vessels--> "arteriae in arteria" arteries within an artery or dvp focal stenosis. Large aneurysms in L cor art more likely to dvp focal stenosis.

-reduced vasodilatory ability

Sx/Si

-URI/GI prodrome

-Then, abrupt high fever

+ skin rash -variable, starts at diaper area and goes to trunk/limbs, may be evanescent espec in infant

+ conjunct injection

+ red/fissure lips w red buccal mucosa and strawberry tongue

+ nonsuppurative cx LAN

+ erythema/edema of hands/feet +/- swollen IP jts w "constant pain" at hands/feet; some w Raynauds

-rarely--> gangrene at fingers/toes

-most w desquamation at subungal region, then palms/soles during subacute phase (wk2-4)

-some w hepatobiliary Sx- hepatomeg, GB hydrops, jaundice, abNl LFTs

-some get late arthralgia/arthritis, lasting up to 4mo

-some w transient diarrhea/abd pain

-some w urethritis/phimosis, +/- dysuria, proteinuria, sterile pyuria, orchitis

-some w transient isolated periph n xx- facial palsy, phrenic n paralysis, SN hearing loss

-some w aseptic meningitis in acute phase

-fever lasts 1-3 weeks w/o IVIG

-transient anemia, and incr WBC w high PMN and bands; pltlt incr in 2nd-3rd week

-CRP and ESR high, then decr by week 6-8.

-Recurrence in 2-3% of pts who recovered completely after 1st episode

-incr coronary xx if recurrent KD

DDx

-KD must have fever for 5 days minimum, and 4/5 of the main Sx

-mimics: viral or rickettsial exanthems- measles, EBV, RMSF; scarlet fever, leptospirosis, TSS, juvenile RA, SJS, Rx rxn, Sn to Hg.

-see low albumin in acute phase, sterile phyria w WBC on micro but not dipstick (come fr urethra, not fr bladder so don't cath the pt). LP might show aseptic meningitis w monos but Nl gluc and prtn

-15% of cases are Incomplete or Atypical KD

-check echo in any pt <6mo w fever for 7 days bc they might not have other Sx

Cardiac Sx/Si:

-Myocarditis--> sinus tachy, gallop, muffled heart sounds

-rarely causes overt heart failure

-Pericarditis in 1/3 pts, rarely pericardial tamponade

-+syst murmur bc of incr CO and anemia

-sometimes here MR murmur

-echo--> +/- mild diffuse CA dilation and enhanced perivasc brightness in 1/3-1/2 pts during acute ph

-can persisti and become aneurysal in 15-20% pts in 1-3weeks fr onset

-if CA aneurysm >8mm (giant aneurysm)--> more risk for MI, which can --> low BP, arrhythmia, die

-Japan: 3/4 MI are in 1st yr p onset, but some even 6 yrs later

-MI--> shock, CP, vomit, inconsolable crying, abd pain most often; 1/3 ASx at MI;

-22% mortality w first MI, w worse mortality w each subsequent MI

-incr risk if pre-existing tenosis or >1 major CA affected, or LMCA affected

-R/F to dvp CA aneurysms: protracted fever, anemia, incr WBC, low albumin, high CRP, male, <1yo pt

ECG- acute: tachy, long PR and QTc, decr QRS voltage, flat T wave

-ST-T changes if MI

-RCA thrombi can--> silent MI--> deep Q waves in II, III, aVF

CXR- usually Nl, 1/5 w CM in acute phase; if aneurysms x>1yr may have thin eggshell Ca'ions outlining t

Echo-

-check for CA aneurysm, perivasc birghtness, mild cor artery ectasia, lack of CA tapering in acute KD stages = cor arteritis before aneurysm formation

-decr LV contractility, mild valvar regurg (usually MR), and pericardial effusion in acute ph

-at f/u good to assess fx, regional wall motion fx, MR, AR, and prox arteries; can be hard to see distaly

-one study: Cross Sectional echo--> good Sn/Sp for aneurysms

-Nl CA- BSA <0.5 - CA Nl <2.5mm

- BSA 0.5-1 - CA Nl 2.5-3mm

- BSA >1 - CA Nl >3mm

-but published Nl data varies widely

-CA is abNl if -the int diam is >3mm in pt <5yo, or 4mm or more in pt 5yrs or older

-internal diam of a segment is 1.5x the adjacent segment

-CA lumen is irregular

Stress Testing-

-assess for reversible ischemia- check kids w +CA aneurysms,

-can do nuclear stress/exercise stress, exercise echo, stress echo w Rx - dobutamine, adenosine, diphyridamole; MRI, etc.

Cath & Angio-

-help determine Px and Tx strategy in kids w large/multiple CA aneurysms, or ECG/stress test/clinical ischemia Si.

-can assess for CA thrombi

-can check LV EDP if p acute infarct/ch ischemia

MRI/MRA/CT- accurately image prox segments for aneurysms but NOT stenoses

Long Term CV Effects

-good Px if no cor art xx

-small cor art aneurysms- very likely to regress, so generally good Px thru childhood

-large/complex aneurysms- less regression

-even vssls s/p regression still have abNl thick intima and media w less able to vasodilate w nitrate challenge.

-if big aneurysms--> risk for ischemia...

-pts who recovered fr KD may dvp dyslipidemia w mild-mod decr in HDL, but ?implications of this

Tx

Acute Phase

-IVIG - high dose (2gm/kg)

-reduced CA aneurysm incidence to <5% if given within 7-10 days of onset

-IVIG given slowly over 8-12 hours to minimize hyperSn or hyperpyrexic rxn and to prevent solute overloading, bc they may have decr LV contractility

-ideally give it by day 7 of Sx, def by 10 days. If pt at >10 days, then give if fever persists or pt has cor art abNly w persistent clinical or lab evidence of inlfmn

-# of days before pt gets recurrent fever after IVIG correlates to risk of aneurysms

-if pt has fever after 36hrs p first infusion of IVIG, then repeat the dose of IVIG

-if pt doesn't defervesce p 2nd IVIG, you can give a thrid or give 30mg/kg methylpred

-?exact IVIG mech

-IVIG xx

-anaphylaxis, low BP, rigors, HA, hemolytic anemia

-most Tx w benadryl ppx to reduce allergic rxn

-DON'T give measles/VZV vaccine witihin next 11mo p IVIG unless high risk exposure

(bc may not mount serologic response)...

-Aspirin - 80-100mg/kg/DAY DIVIDED QID

-for anti-inflmy and antipyretic effects

-does NOT influence cor art aneurysm incidence

-?if the high dose ASA really helps

-some data to say that NSAIDs may be prothrombotic and inhibit ASA fx on platelet inhibition

-check salicyate and LFTs if pt on high dose ASA for >3 days

-Switch to LOW DOSE of 3-5mg/kg/day daily for antiplatelet effect after pt afebrile

-cont low dose for 6 weeks and stop if pt still doesn't have aneurysms

-if +CA xx, then continue indefinitely

-Reye Syndrome- reported in kids w KD on high dose ASA, not w low dose ASA; still rec getting flu shot for pt on ch aspirin. and withhold it temporarily if pt gets flu Sx (use another Rx if needed- plavex or dipyridamole)

-Other AntiInflmy Tx

-Corticosteroids- used by some for 1y or rescue Tx

-1 Japan study--> it incr risk for CA aneurysms, but later studies show it might shorten fever and inflmy response

-no diff in outcome if you do both IVIG and steroids

-if steroids used w IVIG for recrudescent fever (returned p 1st IVIG dose), then --> smaller CA aneurysms noted later

-Abciximap- chimeric hman-murine monoclonal Ab to pltlt glycoprotein IIb/IIIa R'

--> more regression in aneurysm diamter than historical ctrl

-? mech... may help remodeling

-TNFa also being used as rescue Tx

-Plasma exchange also reportedly used

Chronic Phase

-Coronary Risk Stratification

-tailor Tx to MI risk

-Anticoagulation for Giant Aneurysms

-they are at higher risk for thombotic occlusion - 7.5% per year if treated w ASA alone get thrombi, sev stenosis needing surgery, or death fr MI.

-c/s Lovenox or Warfarin... in addition to ASA...

-Thrombolytic Therapy

-streptokinese/urokinase/tPA...

Surgical and Transcatheter Revascularization

-debatable what the specific indications are for bypass surgery , especially in ASx pt...