Late diagnosis of Kawasaki disease is associated with haptoglobin phenotype

Lee, WC; Kp, Hwang; Yt, King; Hc, Chen; Ss, Chiou; Rc, Yang; Ty, Huang

doi:10.1046/j.1365-2362.2000.00646.x

Cited by 12 publications

(8 citation statements)

References 22 publications

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“…Several previous studies reported increased levels of certain cytokines or cytokine regulators in association with KD, 13,[18][19][20][21] and a haptoglobin phenotype that may help in diagnosis at a late stage has been identified. 25 Although we confirmed the elevation of IL-6 levels compared with healthy controls, this marker was not as specific or sensitive of a predictor of KD when compared with IP-10 because of lack of discrimination in the suspected cases with fevers ( Figure 1). Although IL-1β was critical in the development of coronary lesions in a mouse model of KD 26 , the plasma levels of IL-1β were not significantly elevated in the patients with acute KD in the present study (Figure 1).…”

Section: Discussionmentioning

confidence: 56%

CXCL10/IP-10 Is a Biomarker and Mediator for Kawasaki Disease

Kuo

Chang

et al. 2015

Circulation Research

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Rationale: Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. Objective: To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. Methods and Results: We enrolled 214 children with fever and clinical features suggestive of KD. Of those, only 100 were diagnosed with KD. Their plasma samples were globally analyzed for cytokines, chemokines, and cell adhesion molecules using an unbiased, large-scale, quantitative protein array. This study was conducted in 3 stages: discovery, replication, and blinded validation. During the discovery phase (n [KD]=37; n [control]=20), the expression of interleukin-17F, sCD40L, E-selectin, CCL23 (myeloid progenitor inhibitory factor 1), and CXCL10 (IFN-γ-inducible protein 10 [IP-10]) were upregulated during the acute phase in patients with KD when compared with that in the controls. A notable increase was observed in the IP-10 levels (KD, 3037±226.7 pg/mL; control, 672±130.4 pg/mL; P =4.1×10 –11 ). Receiver-operating characteristic analysis of the combined discovery and replication data (n [KD]=77; n [control]=77) showed that the IP-10 level had high area under the curve values (0.94 [95% confidence interval, 0.9055–0.9778]; sensitivity, 100%; and specificity, 77%). With 1318 pg/mL as the optimal cutoff, the blinded validation study confirmed that the IP-10 levels were a good predictor of KD. With intravenous immunoglobulin treatment, the IP-10 levels returned to normal. The downstream receptor of IP-10, CXCR3, was activated in the T cells of patients with acute KD. Conclusions: IP-10 may be used as a biomarker to facilitate KD diagnosis, and it may provide clues about the pathogenesis of KD.

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Section: Discussionmentioning

confidence: 56%

CXCL10/IP-10 Is a Biomarker and Mediator for Kawasaki Disease

Kuo

Chang

et al. 2015

Circulation Research

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“…Haptoglobin, an acute-phase protein synthesized by the liver in response to inflammatory cytokines, has been seen in association with vascular disease [2, 3]. The haptoglobin 2–1 phenotype has been reported in association with incomplete KD [9]. …”

Section: Discussionmentioning

confidence: 99%

Acute-Phase Reactants and a Supplemental Diagnostic Aid for Kawasaki Disease

et al. 2010

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The diagnosis of acute Kawasaki disease (KD) is based on characteristic clinical signs and not on a specific diagnostic test. The authors performed a comprehensive evaluation of acute-phase reactants in KD to determine which of the acute-phase reactants would most accurately distinguish KD from other febrile illnesses. Blood was collected from 218 cases of febrile children with KD (64 cases); bacterial pneumonia (74 cases); hand, foot, and mouth disease (31 cases); and upper respiratory tract infection (49 cases) in acute-stage illness before any therapy. The demographics, body temperature, and laboratory markers including white blood cell count, red blood cell count, and levels of hemoglobin, platelets, C-reactive protein, haptoglobin, apolipoprotein A-I, and apolipoprotein B were evaluated. Using post hoc analysis, the platelet count (103/μl) and haptoglobin/apolipoprotein A-I ratio were significantly higher for the KD patients (404.64 ± 161.68, P = 0.004; 4.74 ± 2.73, P < 0.001) than for the other groups including patients with pneumonia (272.76 ± 115.07, 2.03 ± 1.88); hand, foot, and mouth disease (274 ± 105.9, 2.24 ± 1.19); and upper respiratory tract infection (b282.06 ± 107.72, 1.4 ± 0.98). The best cutoff value of the haptoglobin/apolipoprotein A-I ratio obtained from receiver operating characteristics (ROC) curves for KD was 2 (area under the ROC curve, 0.88; 95% confidence interval, 0.801–0.955), with a sensitivity of 89.7% and a specificity of 85.6% for detecting KD. Our data indicate that the serum haptoglobin/apolipoprotein A-I ratio could be a useful supplemental laboratory marker for the acute phase of KD.

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“…IVIG resistance with persistent or recrudescent fever occurs in approximately 18 % of KD patients. Retreatment involved more individual adjustment, consisting of intravenous steroid pulse therapy, infliximab, cyclophosphamide, anakinra, etanercept, methotrexate, or plasmapheresis [ 1 , 4 – 6 ]. Additionally, antioxidants, as vitamin C, and drugs affecting cholesterol levels, can reduce endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Kawasaki disease and hepatobiliary involvement: report of two cases

2016

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BackgroundKawasaki disease (KD) without affection of the coronary artery system is rare. Optic nerve pathology together with KD has not been described earlier.Case presentationWe present one case of KD in a 12-year-old girl predominantly with prolonged cholestasis, and a second case of multiple recurrent KD in a 9-year-old boy with hepatomegaly and ischemic optic nerve neuropathy. The coronary artery system was not involved in either case.ConclusionsKD warrants rapid diagnosis and immediate specific treatment in order to prevent the high risk of coronary artery aneurysm and stenosis.

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Late diagnosis of Kawasaki disease is associated with haptoglobin phenotype

Abstract: Patients with Hp 2-1 have patterns of delayed or incomplete presentation of clinical symptoms. Therefore, the late diagnosis of KD is associated with haptoglobin phenotype.

Cited by 12 publications

References 22 publications

CXCL10/IP-10 Is a Biomarker and Mediator for Kawasaki Disease

CXCL10/IP-10 Is a Biomarker and Mediator for Kawasaki Disease

Acute-Phase Reactants and a Supplemental Diagnostic Aid for Kawasaki Disease

Kawasaki disease and hepatobiliary involvement: report of two cases

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