Pediatr Int. 2022 Jan;64(1):e15191. doi: 10.1111/ped.15191 PDF is behind a $10 paywall
Natsumi Okazaki 1, Hiroyuki Ikeda 1, Takafumi Honda 2, Kazuma Tsuno 1, Fumiya Inoue 1, Satoko Takahashi 1, Ayako Sakurai 1, Hideaki Ueki 1, Yasushi Noguchi 1, Hiromichi Hamada 3, Shunji Igarashi 1
Background: The seasonal epidemic of Kawasaki disease (KD) in winter in Japan suggests that low vitamin D status may affect KD through the immune system. We aimed to evaluate the effect of vitamin D on the onset and clinical course of KD.
Methods: We conducted a case-control study to compare 25-hydroxyvitamin D (25(OH)D) levels in KD patients admitted to our hospital between March 2018 and June 2021, with those in healthy controls from published Japanese data. In patients with KD, we evaluated the association of 25(OH)D levels with intravenous immunoglobulin resistance and coronary artery lesions.
Results: We compared 290 controls and 86 age-group-adjusted patients with KD. The 25(OH)D levels in KD patients were lower than those in the controls (median: 17 vs. 29 ng/mL, P < 0.001). In winter, 25(OH)D levels in KD patients were lower than those in summer (median: 13 vs. 19 ng/mL). The adjusted odds ratios for the onset of KD were 4.9 (95% CI: 2.5-9.6) for vitamin D insufficiency (25(OH)D: 12-20 ng/mL) and 29.4 (95% CI: 12.5-78.2) for vitamin D deficiency (25(OH)D < 12 ng/mL). Among 110 KD patients, 25(OH)D levels at diagnosis of KD were not associated with intravenous immunoglobulin resistance or coronary artery lesions.
Conclusions: The 25(OH)D levels in patients with KD were lower than those in the controls, especially in winter. Lower 25(OH)D levels in winter were associated with an increased risk of KD onset. It remains to be elucidated whether the observed association has a causal relationship.
- Newburger JW, Takahashi M, Burns JC. Kawasaki disease. J. Am. Coll. Cardiol. 2016; 67 (14): 1738-49.
- Makino N, Nakamura Y, Yashiro M et al. Descriptive epidemiology of Kawasaki disease in Japan, 2011-2012: From the results of the 22nd nationwide survey. J. Epidemiol. 2015; 25: 239-45.
- Mailhot G, White JH. Vitamin D and immunity in infants and children. Nutrients 2020; 12 (5): 1233.
- Adams JS, Hewison M. Unexpected actions of vitamin D: New perspectives on the regulation of innate and adaptive immunity. Nat. Clin. Pract. Endocrinol. Metab. 2008; 4: 80-90.
- Yorifuji T, Tsukahara H, Doi H. Breastfeeding and risk of Kawasaki disease: A nationwide longitudinal survey in Japan. Pediatrics 2016; 137: e20153919.
- Meyer K, Volkmann A, Hufnagel M et al. Breastfeeding and vitamin D supplementation reduce the risk of Kawasaki disease in a German population-based case-control study. BMC Pediatr. 2019; 19: 66.
- Wang S, Xiang D, Fang C, Yao B. Association between breastfeeding and Kawasaki disease: A case-control study. Eur. J. Pediatr. 2020; 179: 447-53.
- Nakano S, Suzuki M, Minowa K et al. Current vitamin D status in healthy Japanese infants and young children. J. Nutr. Sci. Vitaminol. (Tokyo) 2018; 64: 99-105.
- Munns CF, Shaw N, Kiely M et al. Global consensus recommendations on prevention and management of nutritional rickets. J. Clin. Endocrinol. Metab. 2016; 101: 394-415.
- Ayusawa M, Sonobe T, Uemura S et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr. Int. 5th rev ed. 2005; 47: 232-4.
- Kobayashi T, Ayusawa M, Suzuki H et al. Revision of diagnostic guidelines for Kawasaki disease (6th revised edition). Pediatr. Int. 6th rev ed. 2020; 62 (10): 1135-8.
- Research Committee of the Japanese Society of Pediatric Cardiology, Cardiac Surgery Committee for Development of Guidelines for Medical Treatment of Acute Kawasaki Disease. 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). Pediatr. Int. 2012; 2014 (56): 135-58.
- Kobayashi T, Inoue Y, Takeuchi K et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation 2006; 113: 2606-12.
- Kobayashi T, Fuse S, Sakamoto N et al. A new Z score curve of the coronary arterial internal diameter using the lambda-mu-sigma method in a pediatric population. J. Am. Soc. Echocardiogr. 2016; 29: 794-801. e29.
- Mccrindle BW, Rowley AH, Newburger JW et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation 2017; 135: e927-99.
- Hara T, Nakashima Y, Sakai Y, Nishio H, Motomura Y, Yamasaki S. Kawasaki disease: A matter of innate immunity. Clin. Exp. Immunol. 2016; 186 (2): 134-43.
- Takahashi K, Oharaseki T, Naoe S, Wakayama M, Yokouchi Y. Neutrophilic involvement in the damage to coronary arteries in acute stage of Kawasaki disease. Pediatr. Int. 2005; 47: 305-10.
- Onouchi Y, Gunji T, Burns JC et al. ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat. Genet. 2008; 40: 35-42.
- Alphonse MP, Duong TT, Shumitzu C et al. Inositol-triphosphate 3-kinase C mediates inflammasome activation and treatment response in Kawasaki disease. J. Immunol. 2016; 197: 3481-9.
- Stagi S, Rigante D, Lepri G, Matucci Cerinic M, Falcini F. Severe vitamin D deficiency in patients with Kawasaki disease: A potential role in the risk to develop heart vascular abnormalities? Clin. Rheumatol. 2016; 35 (7): 1865-72.
- Zhang YD, Li RM, Ji CY et al. Changes in 25-hydroxyvitamin D3 level and its significance in children with Kawasaki disease. Zhongguo Dang Dai Er Ke Za Zhi 2016; 18: 211-4.
- Chen YL, Wang JL, Li WQ. Prediction of the risk of coronary arterial lesions in Kawasaki disease by serum 25-hydroxyvitamin D3. Eur. J. Pediatr. 2014; 173 (11): 1467-71.
- Jun JS, Jung YK, Lee DW. Relationship between vitamin D levels and intravenous immunoglobulin resistance in Kawasaki disease. Korean J. Pediatr. 2017; 60: 216-20.
- Bouillon R, Schuit F, Antonio L, Rastinejad F. Vitamin D binding protein: A historic overview. Front. Endocrinol. 2019; 10: 910.
- Powe CE, Evans MK, Wenger J et al. Vitamin D-binding protein and vitamin D status of black Americans and White Americans. N. Engl. J. Med. 2013; 369 (21): 1991-2000.
- Kitanaka S, Isojima T, Takaki M, Numakura C, Hayasaka K, Igarashi T. Association of vitamin D-related gene polymorphisms with manifestation of vitamin D deficiency in children. Endocr. J. 2012; 59 (11): 1007-14.
- Braegger C, Campoy C, Colomb V et al. Vitamin D in the healthy European paediatric population. J. Pediatr. Gastroenterol. Nutr. 2013; 56: 692-701.
- Zhang W, Stoecklin E, Eggersdorfer M. A glimpse of vitamin D status in Mainland China. Nutrition 2013; 29: 953-7.
- Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004. Am. J. Clin. Nutr. 2008; 88 (6): 1519-27.
- Mithal A, Wahl DA, Bonjour JP et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009; 20 (11): 1807-20.
- Pludowski P, Grant WB, Bhattoa HP et al. Vitamin D status in central Europe. Int. J. Endocrinol. 2014; 2014: 589587.
- Xu WR, Jin HF, Du JB. Vitamin D and cardiovascular risk in children. Chin. Med. J. 2017; 130: 2857-62.
- Smolders J, van den Ouweland J, Geven C, Pickkers P, Kox M. Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence. Metabolism 2021; 115: 154434.
- Yılmaz K, Şen V. Is vitamin D deficiency a risk factor for COVID-19 in children? Pediatr. Pulmonol. 2020; 55: 3595-601.
- Fukazawa R, Kobayashi J, Ayusawa M et al. JCS/JSCS 2020 guideline on diagnosis and management of cardiovascular sequelae in Kawasaki disease. Circ. J. 2020; 84 (8): 1348-407.
- Jolliffe DA, Greenberg L, Hooper RL et al. Vitamin D supplementation to prevent asthma exacerbations: A systematic review and meta-analysis of individual participant data. Lancet Respir. Med. 2017; 5: 881-90.
- Martineau AR, Jolliffe DA, Hooper RL et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583.
- Hattangdi-Haridas SR, Lanham-New SA, Wong WHS, Ho MHK, Darling AL. Vitamin D deficiency and effects of vitamin D supplementation on disease severity in patients with atopic dermatitis: A systematic review and meta-analysis in adults and children. Nutrients 2019; 11 (8): 1854.
- Jolliffe DA, Camargo CA Jr, Sluyter JD et al. Vitamin D supplementation to prevent acute respiratory infections: Systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021; 9: 276-92.
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