Kawasaki disease is an acute vasculitis of childhood. Its clinical presentation is well known, and coronary artery aneurysms are classical complications. Shock and pleural or pericardiac effusion are rare presentations of the disease. In intensive care units, the disease may be mistaken for septic shock or toxic shock syndrome. Owing to the fact that immunoglobulin therapy improves the course of the disease, especially if given early, and thus the diagnosis should not be delayed

Amano

Julia Natterer

Marie-Hélène Perez

Stefano Di Bernardo

Wiesenthal

AbstractKawasaki disease is an acute vasculitis of childhood. Its clinical presentation is well known, and coronary artery aneurysms are classical complications. Shock and pleural or pericardiac effusion are rare presentations of the disease. In intensive care units, the disease may be mistaken for septic shock or toxic shock syndrome. Owing to the fact that immunoglobulin therapy improves the course of the disease, especially if given early, and thus the diagnosis should not be delayed.</jats:p

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Cardiology in the Young

Capillary leak leading to shock in Kawasaki disease without myocardial dysfunction

Natterer, J.

Perez, M.H.

Di Bernardo, S.

Serveur académique lausannois

Cardiology in the Young (2012), 22, 349–352doi:10.1017/S1047951111001314r Cambridge University Press, 2011Brief ReportCapillary leak leading to shock in Kawasaki disease withoutmyocardial dysfunctionJulia Natterer,1 Marie-He´le`ne Perez,1 Stefano Di Bernardo21Pediatric Intensive Care Unit; 2Pediatric Cardiology Unit, Department of Pediatrics, University Hospital andUniversity of Lausanne, CHUV, SwitzerlandAbstract Kawasaki disease is an acute vasculitis of childhood. Its clinical presentation is well known, andcoronary artery aneurysms are classical complications. Shock and pleural or pericardiac effusion are rarepresentations of the disease. In intensive care units, the disease may be mistaken for septic shock or toxic shocksyndrome. Owing to the fact that immunoglobulin therapy improves the course of the disease, especially ifgiven early, and thus the diagnosis should not be delayed.Key words: Shock; intensive care; vasculitisReceived: 13 December 2010; Accepted: 7 August 2011; First published online: 21 September 2011KAWASAKI DISEASE IS AN ACUTE, SYSTEMICvasculitis of unknown aetiology, whichmostly occurs in young children. In theabsence of specific tests, the diagnosis is based onthe presence of fever and at least four of the fivewell-known clinical features. Incomplete Kawasakidisease is defined by fever, two or three clinicalfeatures, and coronary disease on echocardiography.Approximately 15% to 25% of untreated childrendevelop coronary aneurysm. Owing to the fact thatintravenous immunoglobulin treatment reduces theprevalence of coronary artery aneurysms to less than5%,1 patients should rapidly be treated. Aspirin isalso part of the common treatment. Some patientsremain febrile despite the treatment and should betreated again with intravenous immunoglobulin.2Even though unusual, severe Kawasaki disease withpleural and pericardial effusion or patients mimickingtoxic shock syndromes are possible but rare.3–5Therefore, we report the cases of three childrenadmitted to our paediatric intensive care unit forhaemodynamic instability, respiratory failure, andneurological impairment due to Kawasaki disease.Case reportsOur institution is a tertiary centre in a region ofabout one million inhabitants. In our paediatriccardiology department, 15 to 20 cases of Kawasakidisease are diagnosed per year. Of these, five to eightare treated in our institution – small children,severe disease, or particular risk factors.The first child was a 5.5-year-old girl, presentingfirst a classical Kawasaki disease. Cardiac echocar-diography showed coronary hyperechogenicity anddilatation, with significant z-scores for the commontruncus and the right coronary artery (Table 1).Systolic function was normal, with an ejectionfraction of 63%, and the echocardiography did notshow any diastolic dysfunction. The girl was treatedwith intravenous immunoglobulin and aspirin onthe fourth day of fever. Initially she improved for3 days, but then she suddenly complained ofabdominal pain. Her general and neurologicalstate worsened. She was referred to the paediatricintensive care unit. Initial work-up showed increasedC-reactive protein (241 milligrams per deciliter) andwhite blood cell count of 12.83 109 per litre – 29%of immature granulocytes – and decreased haemo-globin of 90 grams per litre and serum albumin of19 grams per litre. There was no sign of otherorgan dysfunction, and troponin levels were slightlyCorrespondence to: M.-H. Perez, Pediatric Intensive Care, Department ofPediatrics, University Hospital and University of Lausanne, CHUV, Rue duBugnon 46, 1011 Lausanne, Switzerland. Tel: 0041 79 556 40 82; Fax: 0041 21314 37 59; E-mail: marie-helene.perez@chuv.chhttps:/www.cambridge.org/core/terms. https://doi.org/10.1017/S1047951111001314Downloaded from https:/www.cambridge.org/core. University of Basel Library, on 30 May 2017 at 21:29:33, subject to the Cambridge Core terms of use, available atelevated (Table 2). Chest X-ray and abdominalsonography revealed a large amount of ascites andpleural effusion. Mechanical ventilation was initiatedfor respiratory failure. After volume replacement withcolloid and albumin, we had to start catecholaminesbecause of persistent haemodynamic instability. Asecond dose of intravenous immunoglobulin wasadministered on the ninth day of fever – that is,48 hours after admission to intensive care – andaspirin was continued. Owing to this unusualevolution mimicking septic shock, we also intro-duced antibiotics after complete septic work-up.Bacterial cultures were all negative. She graduallyimproved over 5 days after the second intravenousimmunoglobulin dose. Catecholamines were stoppedafter 7 days. She was discharged from the paediatricintensive care unit after 8 days and from the hospitalafter another 7 days. Control echocardiography2 months later showed no coronary aneurysm.The second child was a 6-year-old boy, presentingwith a cervical mass and fever, treated withamoxicillin and clavulanic acid without any improve-ment. He developed a rash after 4 days. After 7 days,his clinical state worsened, with the apparitionof respiratory distress and rapidly progressive haemo-dynamic instability. Initial work-up showed haemo-globin (109 grams per litre), white blood cell countof 33 109 per litre (57% of immature granulocytes),C-reactive protein (220 grams per deciliter), and lowserum albumin (18 grams per litre). There was onlya slight elevation of liver enzymes and no sign oforgan failure (Table 2). He was admitted to theintensive care with suspicion of either septic shock ortoxic shock syndrome. Chest X-ray and abdominalsonography showed pleural and peritoneal effusion.Mechanical ventilation was initiated because ofrespiratory failure, and cardiovascular support withvolume replacement and cathecholamines because ofrefractory hypotension. Antibiotic treatment waschanged to vancomycin, imipenem, and amikacin;corticoid therapy was initiated because of capillaryleak and shock. Owing to the fact that the clinicalsigns were indicative of Kawasaki disease – that is,fever, cervical mass, and rash – an echocardiographywas performed the next day, showing coronaryaneurisms with a positive z-score (Table 1). Systolicand diastolic functions were normal. The diagnosisof incomplete Kawasaki disease was made, as othercauses were excluded and infectious work-up wasnormal. Intravenous immunoglobulin and aspirintreatment were started. The boy rapidly improvedwithin 24 hours. Catecholamines were stopped after2 days, he could be extubated after 3 days, wasdischarged from intensive care after 4 days and fromhospital after 3 weeks. The last available controlechocardiography, a few days after hospital stay,showed no sign of coronary aneurysm.The third child was a 3-year-old boy with aprenatal history of Galien vein aneurism treated bytwo successful embolisations in the first year of life.He presented with a 1-week history of fever, sorethroat, and conjunctival injection. Oral amoxicillinand clavulanic acid treatment was started; however,the boy’s clinical state worsened, and thereforehe was admitted to the hospital for intravenousantibiotic treatment. Laboratory studies showed signsof important systemic inflammation, with an elevatedC-reactive protein (480 milligrams per deciliter),Table 1. Echocardiographic values.Anterior interventricularcoronary artery z-scoreCommun coronarytruncus z-scoreRight coronaryartery z-scoreEjection fraction(%)Patient 1 11.6 13.26 14.4 63Patient 2 12.75 14.02 16.86 62Patient 3 13.6 14.97 12.32 73Table 2. Laboratory values at admission.GOT(IU/l)GPT(IU/l)Creatinin(mmol/l)BUN(mmol/l)CRP(mg/dl)WBC(g/l)Immaturegranulocytes(%)Hb(g/l)CK(IU/l)CK-MB(IU/l)Troponin(mg/l)Serumalbumin(g/l)Patient 1 54 44 78 8.3 468 12.8 29 90 231 47 0.09 19Patient 2 46 44 57 8.7 164 3.5 57 83 140 12 0.74 18Patient 3 31 79 32 14.1 372 21.4 39 75 21 30 0.03 26BUN5 blood urea nitrogen; CK5 creatine kinase; CK-MB5 creatine kinase-muscle and brain types; CRP5 carbon-reactive protein;GOT5 glutamic-oxaloacetic transaminase; GPT5 glutamic-pyruvic transaminase; Hb5 haemoglobin; WBC5white blood cell350 Cardiology in the Young June 2012https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S1047951111001314Downloaded from https:/www.cambridge.org/core. University of Basel Library, on 30 May 2017 at 21:29:33, subject to the Cambridge Core terms of use, available atelevated white blood cell count (21.43 109 perdeciliter) with 39% of immature granulocytes. Hisserum albumin was low (26 grams per litre). Therewas no sign of organ dysfunction and troponin wasnormal during the entire stay in the intensive careunit (Table 2). The chest X-ray showed an enlargedheart and the echocardiography showed pericardialeffusion. The boy was referred to the paediatricintensive care unit. He progressively showed signs oftamponade, thus making drainage necessary. Approxi-mately 50 to 60 millilitres of exudate was removed,and a drain was left in the pericardia. A biopsy wasalso conducted, showing pericarditis. In spite of thedrainage, haemodynamic instability persisted and heneeded catecholamine. On echocardiography, coronaryaneurysms were described with positive z-scores(Table 1), and systolic function was normal – withan ejection fraction of 73% after drainage and 58%before drainage – as was diastolic function. Coronaryaneurysms, in association with fever, sore throat,and conjunctival injection, made the diagnosis ofKawasaki disease very likely. Intravenous immuno-globulin and aspirin treatment were introduced.The course was complicated by a thrombus of thesuperior caval vein, on the third day of the stay. Hewas treated with alteplase (1 milligram per kilogramover 3 hours), and subsequently he developed cerebralhaemorrhage with signs of intracranial hypertension.Despite surgical and medical treatment, the childdied on day 7 after admission to intensive care.DiscussionThese three children presented haemodynamicinstability and respiratory failure due to Kawasakidisease. They had severe vascular leakage andhypoalbuminaemia, with pleural and pericardialeffusions and ascites. The shock was probably dueto an important inflammatory state and vascularleakage, as none of them showed signs of cardiacdysfunction on echocardiography.Kawasaki disease is a systemic vasculitis; how-ever, inflammatory lesions have been described inother organs, including the heart, the lungs, thehaematopoietic and the nervous systems. Thisinflammation leads to an exudative oedema andincreased vascular permeability.6 Terai et al workedon the impact and physiopathology of inflammationand vascular leakage in Kawasaki disease.7,8 Theincreased vascular permeability in the acute phaseof Kawasaki disease is in relation with the elevationof vascular endothelial growth factor expression.Low serum albumin may be due to the increasedproduction of vascular endothelial growth factorand consecutive increased vascular permeability.Furthermore, they found a direct relation between theseverity of oedema and the development of coronaryaneurysms. They concluded that vascular leakage maybe a key feature of the physiopathology of Kawasakidisease. Consequently, the vascular leakage andinflammatory state could explain a great part of theseverity of the disease in our three children.Owing to the fact that the diagnosis of this diseaseis infrequent in the paediatric intensive care unit, andthat the way of presentation with shock may mimictoxic shock syndrome or sepsis, there is a risk ofdelayed diagnosis, and therefore delayed treatment. Inthe report of eight patients admitted for toxic shocksyndrome, Wiesenthal and Todd9 described onepossible case of Kawasaki disease, revealed by coronaryaneurysms on control echocardiography. Dominguezet al10 published the first English-written case-controlstudy of patients with Kawasaki disease presentingwith shock. They reviewed 14 paediatric intensivecare unit children with discharge diagnosis ofKawasaki disease. The most common diagnosis atadmission was toxic shock syndrome or septic shock.These children were mainly admitted to the paediatricintensive care unit because of fluid-refractory hypo-tension and the need for inotropic support, as did ourthree patients. Interestingly, they found a significantelevation in immature granulocytes and C-reactiveprotein. Albumin was also significantly lower in thechildren admitted to the paediatric intensive care unitcompared with their control population. We alsonoticed these laboratory perturbation in our children,which is a sign of important inflammatory state.However, in contrast to their results, our children didnot present with renal failure, low platelet count, orcoagulopathy. High blood urea nitrogen values of ourchildren at admission were rapidly corrected withfluid replacement; however, creatinine stayed withinthe normal range and our children did not show anyother organ dysfunction.Cardiac echocardiography of all three childrenshowed coronary artery dilatations. Troponin valueswere normal to slightly elevated, showing somemyocardial inflammation; however, all three childrenhad good systolic and diastolic function, and there-fore the shock was not due to myocardial dysfunction.ConclusionAlthough the diagnosis of Kawasaki disease is rarein the paediatric intensive care unit, the disease canmimic septic shock or toxic shock syndrome.Therefore, clinicians should carefully look for clinicalsigns of the disease and conduct an echocardio-graphy whenever there is a doubt. Shock inKawasaki disease can be present even with normalmyocardial function, because of severe inflammationand vascular leakage.Vol. 22, No. 3 Natterer et al: Life-threatening Kawasaki disease 351https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S1047951111001314Downloaded from https:/www.cambridge.org/core. University of Basel Library, on 30 May 2017 at 21:29:33, subject to the Cambridge Core terms of use, available atReferences1. Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis,treatment, and long-term management of Kawasaki disease: astatement for health professionals from the Committee onRheumatic Fever, Endocarditis and Kawasaki Disease, Councilon Cardiovascular Disease in the Young, American HeartAssociation. Circulation 2004; 110: 2747–2771.2. Cha S, Yoon M, Ahn Y, Han M, Yoon KL. Risk factors for failureof initial intravenous immunoglobulin treatment in Kawasakidisease. J Korean Med Sci 2008; 23: 718–722.3. Gamillscheg A, Zobel G, Karpf EF, et al. Atypical presentationof Kawasaki disease in an infant. Pediatr Cardiol 1993; 14:223–226.4. Hamada H, Terai M, Honda T, Kohno Y. Marked pleural andpericardial effusion with elevated Vascular Endothelial GrowthFactor production: an uncommon complication of Kawasakidisease. Pediatr Int 2005; 47: 112–114.5. Sittiwangkul R, Pongprot Y. Large pleural effusion: an unusualmanifestation of Kawasaki disease. Clin Pediatr (Phila) 2004; 43:389–391.6. Amano S, Hazama F, Kubagawa H, Tasaka K, Haebara H,Hamashima Y. General pathology of Kawasaki disease. On themorphological alterations corresponding to the clinical manifes-tations. Acta Pathol Jpn 1980; 30: 681–694.7. Terai M, Honda T, Yasukawa K, Higashi K, Hamada H, Kohno Y.Prognostic impact of vascular leakage in acute Kawasaki disease.Circulation 2003; 108: 325–330.8. Yasukawa K, Terai M, Shulman ST, et al. Systemic production ofvascular endothelial growth factor and fms-like tyrosine kinase-1receptor in acute Kawasaki disease. Circulation 2002; 105: 766–769.9. Wiesenthal AM, Todd JK. Toxic shock syndrome in children aged10 years or less. Pediatrics 1984; 74: 112–117.10. Dominguez SR, Friedman K, Seewald R, Anderson MS, Willis L,Glode MP. Kawasaki disease in a pediatric intensive care unit: acase–control study. Pediatrics 2008; 122: e786–e790.352 Cardiology in the Young June 2012https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S1047951111001314Downloaded from https:/www.cambridge.org/core. University of Basel Library, on 30 May 2017 at 21:29:33, subject to the Cambridge Core terms of use, available at

Capillary leak leading to shock in Kawasaki disease without myocardial dysfunction.

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Capillary leak leading to shock in Kawasaki disease without myocardial dysfunction.

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