腺病毒与川崎病临床鉴别研究进展
Advancements in Clinical Differentiation between Adenovirus and Kawasaki Disease
DOI: 10.12677/acm.2025.1551480, PDF,    科研立项经费支持
作者: 龙 玉:贵州医科大学研究生院,贵州 贵阳;崔玉霞*:贵州医科大学研究生院,贵州 贵阳;贵州省人民医院儿童呼吸科,贵州 贵阳
关键词: 川崎病腺病毒感染临床鉴别儿童Kawasaki Disease Adenovirus Infection Clinical Differentiation Children
摘要: 川崎病(Kawasaki Disease, KD)是一种以全身血管炎性、发热出疹性疾病,主要影响5岁以下儿童,病因尚未完全明确。近年来,许多研究表明,感染因素是导致KD的发病的重要因素。其中,腺病毒(Adenovirus, AdV)作为一种常见的病原体,因其感染后临床症状与KD高度重叠,临床误诊风险显著增加。本文通过综述AdV感染与KD的流行病学关联、临床特征、实验室检查及潜在病理机制差别,旨在为临床医生提供鉴别诊断的关键线索,减少误诊率,优化治疗策略。
Abstract: Kawasaki disease (KD) is a systemic vasculitis and febrile exanthematous condition predominantly affecting children under the age of five. The etiology of KD remains incompletely elucidated. Recent studies have increasingly highlighted the significance of infectious agents as potential etiological factors in KD. Notably, adenovirus (AdV), a prevalent pathogen, poses a considerable risk of clinical misdiagnosis due to the substantial overlap in clinical manifestations between AdV infection and KD. This article provides a comprehensive review of the epidemiological associations, clinical characteristics, laboratory diagnostics, and potential pathophysiological distinctions between AdV infection and KD. The objective is to furnish clinicians with critical insights for differential diagnosis, thereby reducing the incidence of misdiagnosis and enhancing treatment strategies.
文章引用:龙玉, 崔玉霞. 腺病毒与川崎病临床鉴别研究进展[J]. 临床医学进展, 2025, 15(5): 1179-1187. https://doi.org/10.12677/acm.2025.1551480

参考文献

[1] Pilania, R.K., Tremoulet, A.H., Prinja, S., Dahdah, N. and Singh, S. (2025) Kawasaki Disease: The Most Common Cause of Acquired Heart Disease among Children Globally. Cardiology in the Young, 35, 441-443. [Google Scholar] [CrossRef] [PubMed]
[2] Conti, G., Giannitto, N., De Luca, F.L., et al. (2020) Kawasaki Disease and Cardiac Involvement: An Update on the State of the Art. Journal of Biological Regulators and Homeostatic Agents, 34, 47-53.
[3] Zhang, D., Liu, L., Huang, X. and Tian, J. (2020) Insights into Coronary Artery Lesions in Kawasaki Disease. Frontiers in Pediatrics, 8, Article 493. [Google Scholar] [CrossRef] [PubMed]
[4] Soni, P.R., Noval Rivas, M. and Arditi, M. (2020) A Comprehensive Update on Kawasaki Disease Vasculitis and Myocarditis. Current Rheumatology Reports, 22, Article No. 6. [Google Scholar] [CrossRef] [PubMed]
[5] McCrindle, B.W., Rowley, A.H., Newburger, J.W., et al. (2017) Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals from the American Heart Association. Circulation, 135, e927-e999.
[6] Barman, P., Pilania, R.K., Cv, G., Thangaraj, A., Arora, M. and Singh, S. (2024) Treatment Intensification in Kawasaki Disease—Current Perspectives. Expert Review of Clinical Immunology, 20, 1179-1191. [Google Scholar] [CrossRef] [PubMed]
[7] Saguil, A., Fargo, M. and Grogan, S. (2015) Diagnosis and Management of Kawasaki Disease. American Family Physician, 91, 365-371.
[8] Stemberger Maric, L., Papic, N., Sestan, M., Knezovic, I. and Tesovic, G. (2018) Challenges in Early Diagnosis of Kawasaki Disease in the Pediatric Emergency Department: Differentiation from Adenoviral and Invasive Pneumococcal Disease. Wiener Klinische Wochenschrift, 130, 264-272. [Google Scholar] [CrossRef] [PubMed]
[9] Chen, Y., Lin, T., Wang, C., Liang, W., Lian, G., Zanin, M., et al. (2022) Human Adenovirus (HAdV) Infection in Children with Acute Respiratory Tract Infections in Guangzhou, China, 2010-2021: A Molecular Epidemiology Study. World Journal of Pediatrics, 18, 545-552. [Google Scholar] [CrossRef] [PubMed]
[10] Zhou, H., Chen, D., Ru, X., Shao, Q., Chen, S., Liu, R., et al. (2024) Epidemiological and Clinical Characteristics of Adenovirus-Associated Respiratory Tract Infection in Children in Hangzhou, China, 2019-2024. Journal of Medical Virology, 96, e29957. [Google Scholar] [CrossRef] [PubMed]
[11] Liu, M., Xu, Q., Li, T., Wang, T., Jiang, B., Lv, C., et al. (2023) Prevalence of Human Infection with Respiratory Adenovirus in China: A Systematic Review and Meta-Analysis. PLOS Neglected Tropical Diseases, 17, e0011151. [Google Scholar] [CrossRef] [PubMed]
[12] Mao, N., Zhu, Z., Zhang, Y. and Xu, W. (2022) Current Status of Human Adenovirus Infection in China. World Journal of Pediatrics, 18, 533-537. [Google Scholar] [CrossRef] [PubMed]
[13] Ho, S., Zhou, Y., Ho, S., Hu, Y., Yen, T., Huang, K.A., et al. (2025) Clinical Characteristics and Severity Predictors of Pediatric Adenovirus Infections. Journal of Medical Virology, 97, e70248. [Google Scholar] [CrossRef] [PubMed]
[14] Liang, Y., Wei, J., Shen, J., Liang, Z., Ma, X., Du, Y., et al. (2025) Immunological Pathogenesis and Treatment Progress of Adenovirus Pneumonia in Children. Italian Journal of Pediatrics, 51, Article No. 4. [Google Scholar] [CrossRef] [PubMed]
[15] Dotan, M., Zion, E., Ben-Zvi, H., et al. (2021) Adenovirus Infection in Children with Down Syndrome. The Israel Medical Association Journal, 23, 416-419.
[16] Huang, S., Chen, C., Weng, K., Chien, K., Hung, Y., Hsieh, K., et al. (2020) Adenovirus Infection and Subsequent Risk of Kawasaki Disease: A Population-Based Cohort Study. Journal of the Chinese Medical Association, 83, 302-306. [Google Scholar] [CrossRef] [PubMed]
[17] 庞晓燕, 冀云鹏, 周雪原, 等. 2020-2021年呼和浩特市儿童呼吸道腺病毒感染的流行病学和实验室检测及临床特征研究[J]. 现代检验医学杂志, 2023, 38(2): 129-135.
[18] Huang, H., Jiang, J., Shi, X., Qin, J., Dong, J., Xu, L., et al. (2022) Nomogram to Predict Risk of Resistance to Intravenous Immunoglobulin in Children Hospitalized with Kawasaki Disease in Eastern China. Annals of Medicine, 54, 442-453. [Google Scholar] [CrossRef] [PubMed]
[19] Kang, J., Jung, J., Kim, Y., Huh, K., Hong, J., Kim, D.W., et al. (2022) Temporal Correlation between Kawasaki Disease and Infectious Diseases in South Korea. JAMA Network Open, 5, e2147363. [Google Scholar] [CrossRef] [PubMed]
[20] Valtuille, Z., Lefevre-Utile, A., Ouldali, N., Beyler, C., Boizeau, P., Dumaine, C., et al. (2023) Calculating the Fraction of Kawasaki Disease Potentially Attributable to Seasonal Pathogens: A Time Series Analysis. E Clinical Medicine, 61, Article 102078. [Google Scholar] [CrossRef] [PubMed]
[21] Kang, J., Kim, Y., Huh, K., Hong, J., Kim, D.W., Kim, M.Y., et al. (2021) Reduction in Kawasaki Disease after Nonpharmaceutical Interventions in the COVID-19 Era: A Nationwide Observational Study in Korea. Circulation, 143, 2508-2510. [Google Scholar] [CrossRef] [PubMed]
[22] Bitsadze, V.O., Grigoreva, K., Khizroeva, J.K., Pervunina, T.M., Tsibizova, V.I., Tretyakova, M.V., et al. (2020) Novel Coronavirus Infection and Kawasaki Disease. The Journal of Maternal-Fetal & Neonatal Medicine, 35, 3044-3048. [Google Scholar] [CrossRef] [PubMed]
[23] 马忠正, 石和丝, 康伟莉, 等. 流感病毒感染与川崎病发病的关系及患儿外周血细胞因子和T淋巴细胞水平变化[J]. 中华医院感染学杂志, 2024, 34(7): 1100-1104.
[24] Sankannaavr, A., Puttalinga, D. and Bagalkot, P.S. (2024) Subsequent Development of Kawasaki Disease Following Acute Human Adenovirus Infection among Siblings. BMJ Case Reports, 17, e257257. [Google Scholar] [CrossRef] [PubMed]
[25] Turnier, J.L., Anderson, M.S., Heizer, H.R., Jone, P., Glodé, M.P. and Dominguez, S.R. (2015) Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics, 136, e609-e614. [Google Scholar] [CrossRef] [PubMed]
[26] Chang, L., Lu, C., Shao, P., Lee, P., Lin, M., Fan, T., et al. (2014) Viral Infections Associated with Kawasaki Disease. Journal of the Formosan Medical Association, 113, 148-154. [Google Scholar] [CrossRef] [PubMed]
[27] Duignan, S., Doyle, S.L. and McMahon, C.J. (2019) Refractory Kawasaki Disease: Diagnostic and Management Challenges. Pediatric Health, Medicine and Therapeutics, 10, 131-139. [Google Scholar] [CrossRef] [PubMed]
[28] Moracas, C., Poeta, M., Grieco, F., et al. (2024) Bacterial-Like Inflammatory Response in Children with Adenovirus Leads to Inappropriate Antibiotic Use: A Multicenter Cohort Study. Infection, 2024, 1-12.
[29] Cai, W. and Ding, S. (2022) Retrospective Analysis of Clinical Characteristics and Related Influencing Factors of Kawasaki Disease. Medicine, 101, e32430. [Google Scholar] [CrossRef] [PubMed]
[30] Hameed, A., Alshara, H. and Schleussinger, T. (2017) Ptosis as a Complication of Kawasaki Disease. BMJ Case Reports, 2017, bcr-2017-219687. [Google Scholar] [CrossRef] [PubMed]
[31] Montenegro-Villalobos, J., Miranda-Jiménez, B., Ávila-Aguero, M.L. and Ulloa-Gutierrez, R. (2020) Subconjunctival Acute Bilateral Hemorrhages Due to Kawasaki Disease in a Costa Rican Girl: An Unusual Clinical Manifestation of the Disease. Cureus, 12, e10212. [Google Scholar] [CrossRef] [PubMed]
[32] Zhu, F. and Ang, J.Y. (2021) 2021 Update on the Clinical Management and Diagnosis of Kawasaki Disease. Current Infectious Disease Reports, 23, 1-11. [Google Scholar] [CrossRef] [PubMed]
[33] Santacruz Valdés, C., Ponce-Rosas, E. and Jimenez-Martinez, M. (2025) Proinflammatory Tear Cytokines in Human Adenoviral Keratoconjunctivitis and Clinical Eye Severity. Clinical Ophthalmology, 19, 439-448. [Google Scholar] [CrossRef] [PubMed]
[34] Bhakta, A., Thosani, P., Surendran, S., Kunchala, A. and Thergaonkar, R.W. (2024) Clinical and Laboratory Findings of Children Affected with Adenovirus Infection. Indian Journal of Pediatrics, 91, 1210-1210. [Google Scholar] [CrossRef] [PubMed]
[35] Imparato, R., Rosa, N. and De Bernardo, M. (2022) Antiviral Drugs in Adenovirus-Induced Keratoconjunctivitis. Microorganisms, 10, Article 2014. [Google Scholar] [CrossRef] [PubMed]
[36] Winters, S., Frazier, W. and Winters, J. (2024) Conjunctivitis: Diagnosis and Management. American Family Physician, 110, 134-144.
[37] Jaggi, P., Kajon, A.E., Mejias, A., Ramilo, O. and Leber, A. (2012) Human Adenovirus Infection in Kawasaki Disease: A Confounding Bystander? Clinical Infectious Diseases, 56, 58-64. [Google Scholar] [CrossRef] [PubMed]
[38] Song, E., Kajon, A.E., Wang, H., Salamon, D., Texter, K., Ramilo, O., et al. (2016) Clinical and Virologic Characteristics May Aid Distinction of Acute Adenovirus Disease from Kawasaki Disease with Incidental Adenovirus Detection. The Journal of Pediatrics, 170, 325-330. [Google Scholar] [CrossRef] [PubMed]
[39] Day-Lewis, M., Son, M.B.F. and Lo, M.S. (2024) Kawasaki Disease: Contemporary Perspectives. The Lancet Child & Adolescent Health, 8, 781-792. [Google Scholar] [CrossRef] [PubMed]
[40] Nakayama, S., Kambe, N., Irie, H., Izawa, K., Nishijima, R., Ueno, H., et al. (2024) Psoriasiform Dermatitis Following Kawasaki Disease: A Case Report and Literature Review. [Google Scholar] [CrossRef] [PubMed]
[41] Isidori, C., Sebastiani, L., Cardellini, M., Di Cara, G., Rigante, D. and Esposito, S. (2017) Early Desquamating Perineal Erythema in a Febrile Infant: A Characteristic Clinical Feature of Kawasaki Disease. International Journal of Environmental Research and Public Health, 14, Article 710. [Google Scholar] [CrossRef] [PubMed]
[42] Loh, A., Kua, P. and Tan, Z. (2019) Erythema and Induration of the Bacillus Calmette-Guérin Site for Diagnosing Kawasaki Disease. Singapore Medical Journal, 60, 89-93. [Google Scholar] [CrossRef] [PubMed]
[43] Tseng, H., Ho, J., Guo, M.M., Lo, M., Hsieh, K., Tsai, W., et al. (2016) Bull’s Eye Dermatoscopy Pattern at Bacillus Calmette-Guérin Inoculation Site Correlates with Systemic Involvements in Patients with Kawasaki Disease. The Journal of Dermatology, 43, 1044-1050. [Google Scholar] [CrossRef] [PubMed]
[44] Zhu, F.H. and Ang, J.Y. (2016) The Clinical Diagnosis and Management of Kawasaki Disease: A Review and Update. Current Infectious Disease Reports, 18, Article No. 32. [Google Scholar] [CrossRef] [PubMed]
[45] Niedermeier, A., Pfützner, W., Ruzicka, T., Thomas, P. and Happle, R. (2014) Superimposed Lateralized Exanthem of Childhood: Report of a Case Related to Adenovirus Infection. Clinical and Experimental Dermatology, 39, 351-353. [Google Scholar] [CrossRef] [PubMed]
[46] Tanaka, A., Inoue, M., Hoshina, T. and Koga, H. (2021) Correlation of Coronary Artery Abnormalities with Fever Pattern in Patients with Kawasaki Disease. The Journal of Pediatrics, 236, 95-100. [Google Scholar] [CrossRef] [PubMed]
[47] Peng, Y., Liu, X., Duan, Z., Cai, S., Duan, J. and Zhou, Y. (2021) Age-Related Differences in Clinical Characteristics of Kawasaki Disease. Brazilian Journal of Medical and Biological Research, 54, e10281. [Google Scholar] [CrossRef] [PubMed]
[48] Muto, T., Masuda, Y., Numoto, S., Kodama, S., Yamakawa, K., Takasu, M., et al. (2019) White Blood Cell and Neutrophil Counts and Response to Intravenous Immunoglobulin in Kawasaki Disease. Global Pediatric Health, 6, Article 2333794X19884826. [Google Scholar] [CrossRef] [PubMed]
[49] Hu, J., Qian, W., Yu, Z., Xu, T., Ju, L., Hua, Q., et al. (2020) Increased Neutrophil Respiratory Burst Predicts the Risk of Coronary Artery Lesion in Kawasaki Disease. Frontiers in Pediatrics, 8, Article 391. [Google Scholar] [CrossRef] [PubMed]
[50] Zhang, R., Wang, H., Tian, S. and Deng, J. (2021) Adenovirus Viremia May Predict Adenovirus Pneumonia Severity in Immunocompetent Children. BMC Infectious Diseases, 21, Article No. 213. [Google Scholar] [CrossRef] [PubMed]
[51] Wu, P., Zeng, S., Yin, G., Huang, J., Xie, Z., Lu, G., et al. (2020) Clinical Manifestations and Risk Factors of Adenovirus Respiratory Infection in Hospitalized Children in Guangzhou, China during the 2011-2014 Period. Medicine, 99, e18584. [Google Scholar] [CrossRef] [PubMed]
[52] Tsai, C., Yu, H., Tang, K., Huang, Y. and Kuo, H. (2020) C-Reactive Protein to Albumin Ratio for Predicting Coronary Artery Lesions and Intravenous Immunoglobulin Resistance in Kawasaki Disease. Frontiers in Pediatrics, 8, Article 607631. [Google Scholar] [CrossRef] [PubMed]
[53] Gómez de Oña, C., Alvarez-Argüelles, M.E., Rojo-Alba, S., Casares, H., Arroyo, M., Rodríguez, J., et al. (2021) Alterations in Biochemical Markers in Adenovirus Infection. Translational Pediatrics, 10, 1248-1258. [Google Scholar] [CrossRef] [PubMed]
[54] Wang, Y., Sun, D. and Hu, H. (2024) Urinary Exosomal MicroRNA-200 Family: Diagnostic Biomarkers for Kawasaki Disease and Their Link to Inflammatory Markers. Cardiology in the Young, 35, 324-331. [Google Scholar] [CrossRef] [PubMed]
[55] Chidambaram, A.C., Ramamoorthy, J.G. and Anantharaj, A. (2023) Neutrophil-Lymphocyte Ratio for Predicting Coronary Artery Lesions in Children with Kawasaki Disease. Indian Pediatrics, 60, 207-211. [Google Scholar] [CrossRef
[56] Sun, J., Xiao, Y., Zhang, M., Ao, T., Lang, S. and Wang, J. (2018) Serum Inflammatory Markers in Patients with Adenovirus Respiratory Infection. Medical Science Monitor, 24, 3848-3855. [Google Scholar] [CrossRef] [PubMed]
[57] Niu, M.M., Jiang, Q., Ruan, J.W., Liu, H.H., Chen, W.X., Qiu, Z., et al. (2021) Clinical Implications of Procalcitonin in Kawasaki Disease: A Useful Candidate for Differentiating from Sepsis and Evaluating IVIG Responsiveness. Clinical and Experimental Medicine, 21, 633-643. [Google Scholar] [CrossRef] [PubMed]
[58] Zeng, L., Wang, C., Song, Z., Liu, Q., Chen, D. and Yu, X. (2023) Prokineticin 2 as a Potential Biomarker for the Diagnosis of Kawasaki Disease. Clinical and Experimental Medicine, 23, 3443-3451. [Google Scholar] [CrossRef] [PubMed]
[59] Kim, S.H., Song, E.S., Yoon, S., Eom, G.H., Kang, G. and Cho, Y.K. (2021) Serum Ferritin as a Diagnostic Biomarker for Kawasaki Disease. Annals of Laboratory Medicine, 41, 318-322. [Google Scholar] [CrossRef] [PubMed]
[60] Popper, S.J., Watson, V.E., Shimizu, C., Kanegaye, J.T., Burns, J.C. and Relman, D.A. (2009) Gene Transcript Abundance Profiles Distinguish Kawasaki Disease from Adenovirus Infection. The Journal of Infectious Diseases, 200, 657-666. [Google Scholar] [CrossRef] [PubMed]
[61] Park, J.H. and Choi, H.J. (2021) Clinical Implications of Thrombocytosis in Acute Phase Kawasaki Disease. European Journal of Pediatrics, 180, 1841-1846. [Google Scholar] [CrossRef] [PubMed]
[62] Arora, K., Guleria, S., Jindal, A.K., Rawat, A. and Singh, S. (2020) Platelets in Kawasaki Disease: Is This Only a Numbers Game or Something beyond? Genes & Diseases, 7, 62-66. [Google Scholar] [CrossRef] [PubMed]
[63] Bratincsak, A., Reddy, V.D., Purohit, P.J., Tremoulet, A.H., Molkara, D.P., Frazer, J.R., et al. (2012) Coronary Artery Dilation in Acute Kawasaki Disease and Acute Illnesses Associated with Fever. Pediatric Infectious Disease Journal, 31, 924-926. [Google Scholar] [CrossRef] [PubMed]
[64] Eichholz, K., Bru, T., Tran, T.T.P., Fernandes, P., Welles, H., Mennechet, F.J.D., et al. (2016) Immune-Complexed Adenovirus Induce Aim2-Mediated Pyroptosis in Human Dendritic Cells. PLOS Pathogens, 12, e1005871. [Google Scholar] [CrossRef] [PubMed]
[65] Lam, J.Y., Shimizu, C., Tremoulet, A.H., et al. (2022) A Machine-Learning Algorithm for Diagnosis of Multisystem Inflammatory Syndrome in Children and Kawasaki Disease in the USA: A Retrospective Model Development and Validation Study. The Lancet Digital Health, 4, e717-e726.
[66] Hicar, M.D. (2020) Antibodies and Immunity During Kawasaki Disease. Frontiers in Cardiovascular Medicine, 7, Article 94. [Google Scholar] [CrossRef] [PubMed]
[67] Chen, Y., Wang, W., Chen, Y., Tang, Q., Zhu, W., Li, D., et al. (2019) MicroRNA-19a-3p Promotes Rheumatoid Arthritis Fibroblast-Like Synoviocytes via Targeting Socs3. Journal of Cellular Biochemistry, 120, 11624-11632. [Google Scholar] [CrossRef] [PubMed]
[68] Zhang, W., Wang, Y., Zeng, Y., Hu, L. and Zou, G. (2017) Serum miR-200c and miR-371-5p as the Useful Diagnostic Biomarkers and Therapeutic Targets in Kawasaki Disease. BioMed Research International, 2017, 1-8. [Google Scholar] [CrossRef] [PubMed]
[69] Ohashi, R., Fukazawa, R., Shimizu, A., Ogawa, S., Ochi, M., Nitta, T., et al. (2019) M1 Macrophage Is the Predominant Phenotype in Coronary Artery Lesions Following Kawasaki Disease. Vascular Medicine, 24, 484-492. [Google Scholar] [CrossRef] [PubMed]
[70] Roe, K. (2020) High COVID-19 Virus Replication Rates, the Creation of Antigen-Antibody Immune Complexes and Indirect Haemagglutination Resulting in Thrombosis. Transboundary and Emerging Diseases, 67, 1418-1421. [Google Scholar] [CrossRef] [PubMed]