Assessment of Endothelial Dysfunction in Acute and Convalescent Phases of Kawasaki Disease Using Automated Edge Detection Software A Preliminary Study From North India Santhosh Kumar Routhu, MD,* Manphool Singhal, MD,† Ankur Kumar Jindal, MD, DM,* Vivek Kumar, MD,‡ Ashok Kumar Yadav, MD,§ and Surjit Singh, MD* Objective: The aim of this study was to assess endothelial dysfunction in acute and convalescent phases of Kawasaki disease (KD) using automated edge detection software. Methods: This was a case-control study to assess the flow-mediated dila- tation (FMD) of brachial artery (BA) in patients with KD during acute phase and at least 3 months after diagnosis. A 10-MHz multifrequency lin- ear array probe attached to a high-resolution ultrasound machine (PHILIPS Medical System-IU22) was used to acquire the images. Automated edge detection software was used to assess BA diameter. Results: A total of 16 children with KD and 16 healthy children were en- rolled in the study. Mean ± SD maximum BA diameter was found to be sig- nificantly low during the acute stage of KD (2.56 ± 0.36 mm) as compared with the convalescence phase (2.93 mm ± 0.31) and in healthy controls (2.95 mm ± 0.56). The mean ± SD percentage change in the FMD was found to be significantly low in the acute phase of KD (12.32 ± 6.2) as compared with the convalescence phase of KD (17.99 ± 8.13) and healthy controls (26.88 ± 12.76). The mean ± SD percentage change in the FMD was also found to be significantly low in the convalescence phase of KD as compared with healthy controls. Conclusions: The FMD of the BA is significantly reduced in patients during the acute and convalescence phase of KD as compared with normal healthy children. The endothelial dysfunction was present even in patients who had no obvious coronary artery abnormalities during the acute stage. Key Words: coronary artery abnormalities, endothelial dysfunction, flow-mediated dilatation, Kawasaki disease (J Clin Rheumatol 2019;00: 00–00) K awasaki disease (KD) is a childhood medium vessel vasculitis that may affect coronary arteries. A substantial number of pa- tients with KD have grown into adulthood now and may be at risk of premature atherosclerosis. 1–4 Intravascular ultrasonography has demonstrated that coronary artery aneurysms in KD may be asso- ciated with marked intimal thickening and abnormal functional characteristics even when their size normalizes. 5 Endothelial dys- function may develop prior to the appearance of atherosclerotic plaques and may play an important role in the pathogenesis of hy- pertension and coronary artery disease. 6 Endothelial dysfunction may exist even in children who have no obvious coronary artery abnormalities (CAAs). 7 Assessment of flow-mediated dilatation (FMD) of brachial artery (BA) is a useful tool for evaluating the endothelial function. 8 Although there are several studies on FMD during the late stages of KD 9 including some from India, 7 there is paucity of work on FMD as a marker of endothelial dys- function during the acute stage of KD. Studies in the past have used conventional techniques of manual measurement of BA di- ameter, which may not accurately assess arterial diameters. Hence, this study was planned to assess the FMD of BA both in the acute and convalescent phases of KD using an automated edge detection software approved by the US Food and Drug Administration. PATIENTS AND METHODS This case-control study was conducted in the Pediatric Al- lergy Immunology Unit of a tertiary care referral institute in Northwest India. The study period spanned over 1 year (July 2015 to June 2016). Children were diagnosed to have KD based on standard diagnostic guidelines given by the American Heart Association. 10 All patients received single dose of intravenous im- munoglobulin (IVIg at 2 g/kg) with aspirin (30–50 mg/kg per day) followed by low-dose aspirin (3–5 mg/kg per day) for a minimum of 4 to 6 weeks. Coronary artery abnormalities were classified based on Z-scores. Patients with coronary artery diameters be- tween 2 and <2.5 Z-scores were classified as having coronary ar- tery dilatation; between 2.5 and <5 Z-scores were classified as having small aneurysms; between 5 and <10 Z-scores were classi- fied as having moderate aneurysms, and >10 Z-scores were classi- fied as having giant aneurysms. 10 Patients with associated comorbidities (hypertension, nephritis) and congenital heart dis- eases and patients who had received IVIg before coming to our in- stitute were excluded from the study. Inclusion criteria were complete KD, incomplete KD, or both. We included both incom- plete and complete forms of KD. Healthy, age- and sex-matched controls (either sibling or a healthy child from the outpatient clinic) were also enrolled. Children who had a history suggestive of KD or any other rheumatological illnesses, any chronic disease, and who were on immunosuppressant therapy were not included as control. Clinical details of cases were obtained from their clinic From the *Allergy Immunology Unit, Advanced Pediatrics Centre, †Depart- ment of Radiodiagnosis and Imaging, ‡Department of Nephrology, and §Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interests. Author's contribution: S.K.R. contributed to the conceptualization of study, data collection, writing the manuscript, and patient management; M.S., conceptualization of study, data collection, and editing the manuscript; A.K.J., writing the initial draft of manuscript, revision and editing of manuscript, data collection, and patient management; V.K./A.K.Y., conceptualization of study, data collection, and editing the manuscript; S.S., conceptualization of study, data collection, patient management, editing, critical revision, and final approval of manuscript. Correspondence: Surjit Singh, MD, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160012. E‐mail: surjitsinghpgi@rediffmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-1608 DOI: 10.1097/RHU.0000000000001233 ORIGINAL ARTICLE JCR: Journal of Clinical Rheumatology • Volume 00, Number 00, Month 2019 www.jclinrheum.com 1 Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.