Kawasaki's disease


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Kawasaki's Disease: typical and atypical presentations
May 2013

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Kawasaki's disease

  1. 1. 1Kawasakis DiseaseDr Hugh ReidEmergency Medicine Advanced TraineeNewcastle, AustraliaMay 2013
  2. 2. 2川kawa river崎saki promontory
  3. 3. Kawasakis DiseaseTypical and Atypical PresentationsDr. Tomisaku Kawasaki, Aged 87
  4. 4. 4Kawasakis diseaseOtherwise known as:“ Muco-Cutaneous Lymph Node syndrome”
  5. 5. 5Kawasakis systemic vasculitisMCLN syndrome: Odds RatioConjunctival injection 7.95 muco-Extremity change 6.97cutaneousOropharyngeal changes 5.21muco-Rash 2.43cutaneousCervical LN > 15mm 1.51 [ leastcommon ]
  6. 6. 6Non Standard KD symptomsIn addition there are > 30 clinical findings attributed tothe underlying multi-system vasculitis, includingCNS / Resp / CVS / GIT / GU / Msk /SkinWhy bother with all these symptoms ? – atypicalKawasakis can be diagnosed with 5 days of feverand 2/5 typical signs. You wont remember them all.Just remember to “be suspicious”
  7. 7. 7Non Standard KD symptomsGITDiarrhea, abdominal pain, vomiting, liver dysfunction,pancreatitis, Hydrops gallbladder,parotitis, cholangitis,intussusception, intestinal pseudo- obstruction,ascites, splenic infarction.MSS Polyarthritis and arthralgia.CVS Myocarditis, pericarditis, tachycardia, valvular heartdisease.GU Urethritis, prostatitis, cystitis, priapism, Interstitialnephritis, orchitis, nephrotic syndrome.
  8. 8. 8Non Standard KD symptomsCNS Lethargy, semicoma, asepticmeningitis, and sensorineuraldeafness.Resp Shortness of breath, influenza-likeillness, plural effusion, atelectasis.Skin Erythema and induration at BCGvaccine site, Beaus lines, and fingergangrene.Atypical Kawasakis can be diagnosed with 5 days of fever and 2/5 typical signs
  9. 9. 9Timing of Kawasaki Symptoms
  10. 10. 10Pathophysiology of KDKawasaki disease fits nicely in the spectrumbetween an infectious disease and a trueautoimmune disease, with an infectious triggerleading to a prolonged self-directed immuneresponse.
  11. 11. 11Pathophysiology of KDA normal Ag stimulates one in a million T cells.A Super Antigen [ SAg. ] is a protein which canstimulate a large proportion of T cells - up to10% of the bodys T Cells,In normal people this stimulation peters out fairlyquickly. But in Kawasakis patients, a geneticpredisposition allows this massive TLymphocyte population to persist, rather thansuffering apoptosis [ siblings have a 10 fold riskfor KD ].
  12. 12. 12Pathophysiology of KDCoronary arteries contain large numbers of Tolllike receptors [ no-one knows why yet ]Toll like receptors are part of the innate immunesystem and are designed to recognise parts ofGram Positive bacteria cell walls.Hyperstimulated T cells stimulate these Toll likereceptors on the coronary arteries, via TNF,stimulating matrix metalloproteinases [ MMP ]which dissolve elastin, causing aneurysmformation
  13. 13. 13Pathophysiology of KDSummarySuper antigens affect genetically predisposedpeople and persist in these people. Theystimulate a massive inflammatory response,causing the signs which we can see, and mostimportantly, stimulate Toll like receptors in thecoroanry arteries which switch on MMPs whichdissolve elastin in the arteries, casusinganeurysms.
  14. 14. 14History of Kawasaki DiseaseThe original case was observed in January 1961in a 4year old boy;Diagnosis: “God only knows ... I didnt see another oneuntil February 1962 and then realized that this wasa unique clinical entity not in the textbooks... Iencountered five more patients fromFebruary to July 1962.I presented the seven patients at a meeting of theJapan Medical Society. I belonged to both the Chibaand Tokyo branches of the Society, and I chose Chibabecause I thought I would get a more friendlyreception, but...
  15. 15. 15History of Kawasaki Disease...the Tokyo professors denied the existence of a newentity and thought it a mild form of Stevens-Johnsonsyndrome. They indicated they had also been observingsimilar cases. The professor of pediatrics at TokyoUniversity denied the new syndrome, all respected hisopinion, but then he died and Kawasaki disease becamerecognized as a new diagnosis”.Nothing has changed … !!
  16. 16. 16History of Kawasaki DiseaseClinical presentation recognised early but not thecomplications - c.f. early assertion by Dr Kawasaki that it wasa self limiting disease without sequelae !Coronary artery thrombosis first recognized in 1965 onautopsy of one of his patients previously diagnosed withMCLNS – final resolution in 1970 with 10 autopsy cases ofsudden death after diagnosis of KDFirst Japanese report of 50 cases, 1967By the time of the first English-language publication by Dr.Kawasaki in 1974, the link between KD and coronary arteryvasculitis was well-established.
  17. 17. 17Natural History of untreated KDCoronary arteries: BADNESSAcute: Dilatation / frankly Aneurysmal / Thrombose / InfarctionChronic: Fibrotic / Stenosis / persistent aneurysmCoronary artery aneurysms in 15% to 25% of children*Acute: 2% mortality rate, peak mortality ~ 15-45 days after onset offever[ Mortality highest in < 12 monthers and > 9 year olds - because no-one thinksof it ]Longer Term: 146 aneurysms: 50% regressed, 25% persist,16% stenose, 3% died; of stenoses, 40% infarcted [ of whomhalf died ], and 25% required CABG; aneurysms ? Stent, cant graft[ Source: Dr N.Collins ]* AHA Scientific Staement 2004
  18. 18. 18Natural History of Untreated KDMost common in:Japanese 112 /100,000Asian and Pacific Islanders 32 / 100,000Lowest in whites 9 / 100,000Commonest cause of acquired heart disease in theIndustrialised worldCommonest age 1- 4 yrs – median 22 months
  19. 19. 19Age Distribution< 6 months 6-12 mo 1-4 yrs 5-9 yrs > 9 yrs010203040506070Age Distribution of KDAge at diagnosisPercentage
  20. 20. 20Natural History of Untreated KD*Commonest age 1- 4 yrs – median 22 months butchildren as young as 1 month and as old as 20 yearshave been diagnosed with KD.Children < 6 months and > 9 years were 2.5 times morelikely to be diagnosed after day 12. Young infants aremore likely to have severe disease with a 50%aneurysm rate, whereas older children [ > 9 years ]are more likely to have atypical presentations, so areless likely to be diagnosed, or to be diagnosed toolate, where response to treatment rates are muchlower, aneurysm rates higher, and presumablymortality, as well.* Manlhiot et al, Pediatrics 2009:124:e140
  21. 21. 21TYPICAL KAWASAKIS DISEASE – 2004 AHA CriteriaFever persisting at least 5 days and at least 4 of the following5 features:conjunctival injectionChanges in extremities:Changes in lips and oral cavityPolymorphous exanthemaMarked cervical lymphadenopathy (≥1.5 cm in diameter),In the presence of ≥4 principal criteria, the diagnosis ofKawasaki disease can be made on day 4 of illness.
  22. 22. 22Bilateral, painless conjunctival injection,often with limbic sparing [ diffferent blood supply ],bulbar > palpebral [ ie opposite of conjunctivitis ], withoutexudateVASCULITIS
  23. 23. 23
  24. 24. 24Limbic sparing
  25. 25. 25
  26. 26. 26Changes in extremities: Acute: Erythema and oedemaof hands andfeetVASCULITIS
  27. 27. 27
  29. 29. 29VASCULITIS
  30. 30. 30
  31. 31. 31
  32. 32. 32TYPICAL KAWASAKIS DISEASE – 2004 AHA CriteriaMouth: Changes in lips and oral cavity: Erythema andcracking of lips, strawberry tongue, diffuse injection of oraland pharyngeal mucosaeVASCULITIS
  33. 33. 33
  34. 34. 34VASCULITIS
  35. 35. 35TYPICAL KAWASAKIS DISEASE – 2004 AHA CriteriaRashPolymorphous exanthemaErythematous / MaculopapularUrticarial /ScarlitiniformErythroderma / EMMicropustularNOT bullousNOT vesicular
  36. 36. 36
  37. 37. 37
  38. 38. 38
  39. 39. 39TYPICAL KAWASAKIS DISEASE – 2004 AHA CriteriaMarked LymphadenopathyMarkedcervicallymphadenopathy(≥1.5 cm in diameter),usually unilateral
  40. 40. 40Cervical Lymphadenopathy
  41. 41. 41Cervical Lymphadenopathy
  42. 42. 42Cervical Lymphadenopathy
  43. 43. 43TYPICAL KAWASAKIS DISEASE – 2004 AHA CriteriaFever persisting at least 5 days and at least 4 of the following5 features:Conjunctival injectionChanges in extremities:Changes in lips and oral cavityPolymorphous exanthemaMarked cervical lymphadenopathy (≥1.5 cm in diameter),In the presence of ≥4 principal criteria, the diagnosis ofKawasaki disease can be made on day 4 of illness.
  44. 44. 44Incomplete kawasakis DiseaseTypically, not all of the clinical features arepresent at a single point in time, and watchfulwaiting is sometimes necessary before adiagnosis can be made.Patients with fever for ≥5 days and <4 principalfeatures can be diagnosed as having Kawasakidisease when coronary artery disease isdetected by echocardiography.
  45. 45. 45Incomplete Kawasakis DiseaseKawasaki disease should be considered in thedifferential diagnosis of a young child with unexplainedfever for ≥5 days that is associated with any of theprincipal clinical features of this disease.Incomplete kawasakis – fever 5/7 and 2/5 criteria, noother reasonable explanation for the illness, andlaboratory findings consistent with severe systemicinflammation.We should bear in mind that five of the patients inKawasaki’s original series of 50 would not havesatisifed the current clinical case definition, and that amultitude of other symptoms have since been describedin children who have turned out to have KD.
  46. 46. 46DiagnosticsInflammatory markers – CRP, ESRraised WCCmassive thrombocytosis >750 [esp. late ]low platelet count [ cytokine storm ]Low serum Na, albumin from vascular leakEcho obvious dilation / aneurysm> 3mm lumen diameterincreased vessel wall thickness = oedemaincreased signal intensity
  47. 47. 47Diagnostics - Echo
  48. 48. 48Diagnostics
  49. 49. 49Diagnostics
  50. 50. 50Diagnostics - IVUS
  51. 51. 51Too lateDesquamation commences around week 3, andduration of fever is the most important predictor ofpoor coronary outcome
  52. 52. 52Too late
  53. 53. 53TreatmentIVIG – but treatment failure is not uncommon –up to 10-15% of children dont respond [interms of inflammatory markers ] and are at riskof developing aneuryms. Can repeat IVIG,steroids, TNF blockers, but...5% of children develop aneurysms despite beingtreated:? because of treatment resistance? delay in diagnosis
  54. 54. 54SummaryKawasakis Disease is a bad disease, with asignificant mortality because...delayed or missed diagnosis is associated withincreased aneurysm formation, treatmentfailure and morbidity and mortality.Special attention:Atypical presentations:Unusual age groups:
  55. 55. 55Summary - Special attentionAtypical presentations:2 / 5 signs and fever, multitude of non-standard symptoms“ not all fever with rash is viralUnusual age groups:< 12 months,> 5 years, and up to 20 years !Nick Collins: Chest pain in a young adult? missed KD in childhood – do an ECG !