Special issues in diagnosis of Kawasaki disease

1. Alexander K.C. Leung, MD* 2. Consolato Maria Sergi, MD† 3. Kin Fon Leong, MD‡ 4. Paul F. Kantor 5. MD§ 1. *Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada 2. †Departments of Pediatrics, Laboratory Medicine, and Pathology, University of Alberta, Edmonton, Alberta, Canada 3. ‡Pediatric Institute, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia 4. §Division of Cardiology, Department of Pediatrics, University of Southern California, Los Angeles, CA A 3-year-old Chinese boy presents with high spiking fevers of 5 days' duration despite treatment with acetaminophen. He has cracked red lips, a widespread maculopapular rash, and bilateral nonpurulent conjunctival injection. There is no history of joint pain, vomiting, abdominal pain, or diarrhea. The medical history is otherwise normal. On examination the child is irritable. His temperature is 103.6°F (39.8°C), heart rate is 102 beats/min, respiratory rate is 27 breaths/min, and blood pressure is 95/60 mm Hg. He has a generalized blanching polymorphous maculopapular rash (Fig 1). The lips are cracked and erythematous. The bulbar conjunctiva is injected bilaterally with sparing of the limbus and without exudate. The tongue is strawberrylike. Perianal erythema and desquamation are noted (Fig 2). Marked erythema is noted on the lateral aspect of the left upper arm surrounding a previous Bacillus Calmette-Guerin (BCG) inoculation site (Fig 3). The hands and feet are erythematous and edematous (Figs 4 and 5). A sharp demarcation with an abrupt change to normal skin is noted at the wrists and ankles (Figs 4 and 5). A tender, nonfluctuant, freely mobile lymph node measuring 2×3 cm is palpable in the left anterior cervical area. The remaining examination findings are normal. Figure 1. A maculopapular rash over the trunk. Also noted in the picture are cracked red lips. Figure 2. Characteristic perianal desquamation. Figure 3. Erythema is surrounding a Bacillus Calmette-Guerin inoculation site. Figure 4. Erythema and indurated edema of the right foot. Figure 5. Erythema and indurated edema of the left hand. Note the sharp demarcation with an abrupt change to healthy skin. Laboratory findings are as follows: white blood cell count, …

An Unintended Consequence of Pandemic Control Measures: Fewer Cases of Kawasaki Disease

Management of Kawasaki disease in resource-limited settings.

Guidelines for medical treatment of acute Kawasaki disease: report of the Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version).

Kawasaki disease (KD) is an acute systemic inflammatory illness that occurs predominately in children <5 years of age. The reported incidence varies widely depending on the ethnicity of the population and the method of case ascertainment. Recent reports would suggest the annual incidence is ≈20 to 25 per 100 000 children <5 years of age in North America, with the highest reported incidence of 188 being in Japan, where the disease was first described in 1967.1 The illness is self-limited and of unknown cause, but is complicated by a systemic vasculitis with a predilection for small- to medium-sized arteries, particularly the coronary arteries. The majority of patients will have either transient coronary artery dilation or no coronary artery luminal changes as noted on echocardiography. Long-term prognosis for these patients is considered to be excellent. Coronary artery aneurysms occur in 25% of patients, but the prevalence is reduced to ≈4% for patients treated with intravenous immunoglobulin infusion within 10 days of illness onset. Aneurysms are associated with an intense inflammatory cell infiltrate, destruction of the internal elastic lamina, and smooth muscle cell death. Coronary artery involvement is usually maximal within 6 to 8 weeks after the acute episode. Regression of aneurysms can occur primarily through myointimal proliferation, although the arterial structure and function remains abnormal,2 and there is an important ongoing risk of stenoses and occlusions.3 Long-term cardiology assessment and management is required, and some of these patients may require revascularization procedures or, rarely, cardiac transplantation. KD has become the most prevalent acquired cardiac disease in children in developed countries. Article see p 60 Although coronary artery complications are the predominant cause of morbidity and mortality, other cardiovascular abnormalities can occur. Valvulitis is a less prevalent complication, and there have been case reports of important long-term aortic and …

Background: Kawasaki Disease(KD) is a challenging diagnosis at first presentation. Diagnosis relies on the 1993 American Heart Association(AHA) criteria of ≥5 days of fever with ≥4 of the following features: mucositis, cervical lymphadenopathy, non-suppurative conjunctivitis, swollen or desquamating extremities, polymorphous rash. Many present atypically and are not easily identified by the Emergency Department(ED) physician. This leads to delays in diagnosis and treatment of KD. Aim: To reduce miss rates and overdiagnosis in the ED through identifying early clinical predictors for KD, within and out of the AHA criteria. Methods: Retrospective case-controlled study on patients discharged with a diagnosis of KD at KK Women’s and Children’s Hospital (KKH) from April 2007 - December 2010. Patients admitted from the ED over the same period with initial diagnoses of KD, but with discharge diagnoses that stated otherwise formed the control group. We analysed the presentation patterns in both groups. Using multivariate logistic regression, we identified significant clinical predictors of KD. Results: The diagnostic guidelines in the ED were neither specific nor sensitive, resulting in high overdiagnosis and miss rates, respectively. Of the patients admitted with the initial diagnosis of KD, 59.2% did not have KD. 44.3% and 29.1% of KD diagnoses were missed at first visit and during reattendences respectively. Miss rates were higher in infants than in older children(≥1 year old). In older children, lymphadenopathy (OR1.79, p=0.013), non-suppurative conjunctivitis (OR2.22; p=0.001), irritability (OR2.24, p=0.005) and age (OR0.75, p&lt;0.0001) were early predictors for true KD. With reattendances, lymphadenopathy (OR2.23, p=0.002), conjunctivitis (OR3.02, p&lt;0.0001), irritability (OR1.86, p=0.040) and age (OR0.75, p&lt;0.0001) remained significant, while changes in extremities (OR1.93, p=0.008) emerges as a useful predictor. No significant predictors were found for infants. Conclusion: ED physicians should be aware of early predictors of KD. We advocate incorporating irritability into diagnostic guidelines for older children. These measures would reduce overdiagnosis and miss rates, permitting appropriate institution of early treatment.

IntroductionThe main focus of concern in Kawasaki disease (KD) hitherto has been on children who develop coronary artery abnormalities (CAA). There is emerging evidence to suggest that several long term...

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: Two Different Illnesses with Overlapping Clinical Features

BackgroundWe sought to systematically standardize the documentation of clinical and laboratory features in Kawasaki disease (KD) on the day of initial treatment and correlate the presentation with clinical outcomes.MethodsKawasaki disease features and classification were documented by the attending physician using a standardized documentation tool on the day of treatment for KD, including confidence in the KD diagnosis on a 4-point scale. Incomplete KD was further classified using American Heart Association (AHA) criteria (sufficient or insufficient) and baseline echocardiogram data. We prospectively recorded intravenous immunoglobulin (IVIG) resistance, coronary artery abnormalities (CAAs), periungual peeling, and retrospectively identified subsequent diagnoses of autoimmune/inflammatory disease.ResultsFrom November 2012 to October, 2015, 162 patients were treated for KD: 105 with complete KD (Group 1), 7 with incomplete KD based on CAAs on day of KD diagnosis (Group 2), 23 with incomplete KD meeting AHA criteria (Group 3), and 27 with incomplete KD and insufficient AHA criteria (Group 4). Group 4 patients had lower baseline median C-reactive protein levels (Group 4 median 4.65 mg/dL [interquartile range {IQR}, 2.3–13.6] vs Group 1 median 8.0 mg/dL [IQR, 4.5–17], Group 2 median 13.9 mg/dL [IQR, 1.4–18.2], Group 3 median 13.3 mg/dL [IQR, 4.9–20.2]), and no coronary abnormalities developed, although 11% had IVIG resistance. Group 4 had higher rates of subsequent autoimmune/inflammatory conditions diagnosed (11.1% in Group 4 vs <5% for all others, P = .02).ConclusionsStandardized documentation and classification of KD features may be useful to correlate with clinical outcomes, including subsequent diagnosis of autoimmune/autoinflammatory disease. Among patients with incomplete KD who did not meet AHA criteria and had a normal baseline echocardiogram, the IVIG resistance rate may have been related to a lower likelihood of an accurate diagnosis of KD.

Point-of-Care Differentiation of Kawasaki Disease from Other Febrile Illnesses

Initial intravenous immunoglobulin (IVIG)-refractory status and prolonged fever are established risk factors for the development of coronary artery abnormalities (CAAs) among patients with acute-phase Kawasaki disease (KD). However, whether different risk factors exist for initial unresponsiveness to IVIG and CAA development remains unclear. To evaluate whether different risk factors exist for initial unresponsiveness to IVIG and CAA development among patients with KD (stratified by age at disease onset). This retrospective cohort study included a consecutive sample of 2414 patients from a database of patients with KD from October 1, 1999, to September 30, 2019. The data were based on annual surveys (response rate, 100%) using hospital medical records across Wakayama Prefecture, Japan. Data were analyzed from March 6 to March 26, 2022. The patient's age and diagnosis of KD by board-certified pediatricians using the criteria established by the Japan KD Research Committee. Initial unresponsiveness to IVIG, defined as treatment with optional or advanced therapies, and development of CAAs. Echocardiograms performed 1 month after KD onset using the Japanese Ministry of Health criteria evaluated the presence or absence of CAAs. Odds ratios (ORs) with 95% CIs of patient age at KD onset for unresponsiveness to IVIG and developing CAAs were calculated using multivariable logistic regression models. A total of 2414 patients (1403 male patients [58.1%]; median age at onset of KD, 25 months [range, 1-212 months]) were included in the study: 550 younger than 12 months, 1342 aged 12 to 47 months, and 522 older than 47 months. A total of 535 patients (22.2%) received optional or advanced treatment and 68 patients (2.8%) developed CAAs 1 month after disease onset. The sex-adjusted OR among patients younger than 12 months for unresponsiveness to IVIG was 0.77 (95% CI, 0.59-0.99) and for development of CAAs was 1.94 (95% CI, 1.07-3.52); among those older than 47 months, the OR for unresponsiveness to IVIG was 1.32 (95% CI, 1.05-1.67) and for development of CAAs was 2.47 (95% CI, 1.39-4.39). After adjusting for IVIG administration, ORs among boys older than 47 months for unresponsiveness to IVIG was 1.14 (95% CI, 0.84-1.56) and for development of CAAs was 2.15 (95% CI, 1.08-4.30); among girls younger than 12 months, the OR for unresponsiveness to IVIG was 1.02 (95% CI, 0.65-1.60) and for development of CAAs was 3.79 (95% CI, 1.21-11.90). The results of this study suggest that risks of unresponsiveness to IVIG and the development of CAAs differ between infants with KD and older patients with KD. Residual risk factors for KD-related CAAs other than initial unresponsiveness to IVIG should be addressed, particularly in infants.

BackgroundIn 2017, the American Heart Association published new Kawasaki disease (KD) guidelines including echocardiographic (echo) criteria for diagnosis of incomplete KD (iKD). Echo is positive if 1 or more coronary arteries (CA) show aneurysmal dilation (Z score of ≥ 2.5), or if a CA has milder dilation (Z score of 2–2.49) plus ≥2 of the following: decreased left ventricular function, mitral regurgitation, and pericardial effusion. While CA dilation is seen commonly in KD and iKD, specificity of this finding is unclear because patients with systemic febrile illnesses may have CA dilation. To assess specificity of the American Heart Association criteria, blinded readers measured CA dimension in patients with KD and iKD and in febrile and healthy patient controls.MethodsThis is a single-center retrospective study. De-identified echo clips of CA from patients age 0–10 years were interpreted blindly and independently by six pediatric cardiologists. KD and iKD diagnoses were based on clinical data and IVIG treatment. Control groups were healthy patients evaluated for a benign murmur and febrile patients with fever ≥72 hours without a KD diagnosis or IVIG treatment. Detection of left ventricular dysfunction, mitral regurgitation and effusion was recorded. An echo was considered positive if the reading from at least one reader met AHA criteria for iKD.ResultsEchos from 29 KD, 30 iKD, 28 febrile, and 27 healthy patients were reviewed. The initial echo of 41% of KD and 43% of iKD groups met echo criteria for diagnosis of iKD and 55% and 57%, respectively, had CA dilation or aneurysm. Among febrile patients, 7 (25%) had an abnormal CA size of which 4 (14%) met echo criteria for iKD. In the healthy patients, four (15%) had abnormal CA of which two (7.4%) met echo criteria for iKD. Among patients with a positive echo read, the median number of readers who read a CA as dilated was similar for each group. Furthermore, of all patients meeting echo criteria for iKD, 90% had aneurysmal CA dilatation.ConclusionAlthough CA abnormalities diagnostic of KD were commonly present at time of diagnosis in patients with KD or iKD, these findings were also present in some healthy and some febrile patients. Diagnosis of iKD in febrile children using echo criteria may result in an over-diagnosis of KD.DisclosuresAll authors: No reported disclosures.

Background: Kawasaki disease (KD) is predominantly seen in young children (<5 years). Diagnosis of KD is often delayed in older children and adolescents, leading to a higher risk of coronary artery abnormalities (CAAs). There is a paucity of literature on KD in older children.Methods: Data were collated from a review of records of patients diagnosed with KD who were aged ≥10 years at the time of diagnosis, during the period from January 1994 to June 2019.Results: Eight hundred and sixty five patients were diagnosed with KD during this period. Of these, 46 (5.3%; 26 boys and 20 girls) were aged 10 years or older at the time of diagnosis. The median age at diagnosis was 11 years (range of 10–30 years). The median interval between the of fever and the diagnosis of KD was 12 days (range of 4–30 days). Eight patients (17.4%) presented with hypotensive shock. Coronary artery abnormalities (CAAs) were seen in six patients (13.04%), and three patients had myocarditis. Patients with CAAs were found to have significantly higher median platelet counts and higher median C-reactive protein levels. First-line treatment included intravenous immunoglobulin. Adjunctive therapy was given in five patients (infliximab in four patients and steroids in one patient). The median time between the onset of fever and the administration of IVIg was 13.5 days (range of 6–2). The total duration of follow up is 2,014.5 patient-months.Conclusion: Diagnosis of KD in children older than 10 years is usually delayed, and these patients are thus at a higher risk of CAAs.

To formulate practice guidelines on diagnosis and management of Kawasaki disease (KD) for Indian children. KD is a systemic vasculitis that predominantly affects infants and children less than 5 years of age. Coronary artery abnormalities (CAA) develop in around 15-25% of untreated children with KD. Coronary artery involvement can lead to long-term cardiovascular implications such as development of premature coronary artery disease. Diagnosis of KD is essentially clinical based on recognition of a constellation of characteristic symptoms and signs. Timely diagnosis and initiation of intravenous immunoglobulin (IVIG) therapy is known to produce five-fold reduction in the incidence of CAA. As there is no confirmatory laboratory test for KD, the diagnosis may be missed if one is not familiar with the nuances of clinical diagnosis. A committee was formed under the auspices of Indian Academy of Pediatrics in early 2018 for preparing guidelines on KD in Indian children. A meeting of the consultative committee was held in Mumbai, and a draft protocol was devised. All members scrutinized the recent publications on the subject and an attempt was made to arrive at a broad consensus. Published guidelines on the subject were also reviewed. The diagnosis is clinical and is aided by laboratory and 2D echocardiography. First line of therapy is IVIG, and should be started expeditiously once the diagnosis is made.

Dear Editor: Kawasaki disease (KD) is an acute inflammatory syndrome of middle-sized arteries such as the coronary artery, and its pathogenesis and etiology remain unclear1. The diagnosis of classic KD is based on the presence of fever lasting longer than 5 days and four of five specific clinical criteria, including bilateral nonpurulent conjunctival injection, oral mucosal changes, redness and swelling of the hands and feet, skin rash, and cervical lymphadenopathy1. Among the cutaneous features of KD, typical nail changes have previously been described, such as transverse leukonychia, onychomadesis, and pincer nails2,3. In addition, Pal and Giri4 reported that patients with KD may show transverse orange-brown chromonychia and suggested to incorporate it as add-on clinical finding of KD. A 5-year-old Korean girl presented with transverse orange-brown discoloration of the finger and toe nails with periungual desquamation. There was no evidence of any other disease or use of drugs that could lead to chromonychia. Ten days previously, she was found to have KD, and was then treated with aspirin at a local hospital. On her visit, she showed orange-brown discoloration at the distal portion of the nail (Fig. 1). Conjunctival hyperemia, cracking of the lips, and strawberry tongue were also observed (Fig. 2). On the basis of the clinical findings, we diagnosed her nail discoloration as orange-brown chromonychia that occurred with KD on the basis of the clinical findings. Two weeks later, the almost transverse orange-brown discoloration disappeared with other symptoms. Fig. 1 (A) Orange-brown discoloration at the distal portion of the nail. (B) Closer view. Fig. 2 (A) Conjunctival hyperemia. (B) Cracking of the lips. (C) Strawberry tongue. A variety of nail abnormalities have been reported in KD. Ciastko2 reported onychomadesis in a boy with KD, that started 6 weeks after a fever. Pincer nail deformity and Beau's lines in KD were also reported2,3. These nail abnormalities commonly develop in the chronic phase and spontaneously resolve. Otherwise, Lindsley5 was the first to describe red transverse nail-bed lines in four KD patients during the acute phase. He considered that chromonychia may be related to localized vasculitis or nail-bed hyperemia, because the lines occurred during active inflammation. Thereafter, Pal amd Giri4 studied about the typical transverse orange-brown discoloration of the nails observed in KD patients, and reported that it was present in almost 75% of the patients (29 of 40). Also, they recognized that this orange-brown chromonychia started appearing between the fifth and eight day of the onset of fever and slowly faded away with time. Therefore, they suggested to include orange-brown chromonychia as an additional clinical feature in the diagnosis of KD, differently to other nail changes. Chromonychia is described after the use of antineoplastic drugs, including adriamycin, cyclophosphamide, and vincristine. In addition, thermal injury, contact exposure to elemental iron, angiotensin-receptor blockage therapy, use of a nail hardener, systemic lupus erythematosus, and hyperbilirubinemia may cause these changes. In summary, we report a case of orange-brown chromonychia in a KD patient, and suggest that it should be considered as a reference of in the diagnosis of KD, based on the basis of its appearance in the acute phase.