{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:11:49Z","timestamp":1791223909954,"version":"4.1.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072322"],"award-info":[{"award-number":["82072322"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["YDZX20193100002868"],"award-info":[{"award-number":["YDZX20193100002868"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["17DZ2293300"],"award-info":[{"award-number":["17DZ2293300"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["20194Y0294"],"award-info":[{"award-number":["20194Y0294"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Microbiol Infect Dis"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5\u00a0h after treatment initiation, peaked after 8\u00a0h, and subsided after 18\u00a0h. Patients with severe JHR experienced a longer recovery time (26\u00a0h). Patients with general paresis (OR\u2009=\u20096.825), ocular syphilis (OR\u2009=\u20093.974), pleocytosis (OR\u2009=\u20092.426), or a high CSF-VDRL titre (per log<jats:sub>2<\/jats:sub> titre increase, OR\u2009=\u20092.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10096-024-04810-1","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T09:12:10Z","timestamp":1711962730000},"page":"1073-1080","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["An observational prospective study based on a large cohort of HIV-negative neurosyphilis patients with particular reference to the Jarisch-Herxheimer reaction"],"prefix":"10.1007","volume":"43","author":[{"given":"Rui-Rui","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2250-8353","authenticated-orcid":false,"given":"Pingyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"issue":"1","key":"4810_CR1","doi-asserted-by":"publisher","first-page":"46","DOI":"10.4269\/ajtmh.16-0434","volume":"96","author":"T Butler","year":"2017","unstructured":"Butler T (2017) The Jarisch-Herxheimer reaction after antibiotic treatment of Spirochetal infections: a review of recent cases and our understanding of Pathogenesis. Am J Trop Med Hyg 96(1):46\u201352","journal-title":"Am J Trop Med Hyg"},{"key":"4810_CR2","unstructured":"Dhakal A, Sbar E (2022) Jarisch Herxheimer reaction. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright \u00a9 2022. StatPearls Publishing LLC"},{"issue":"8","key":"4810_CR3","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1086\/656419","volume":"51","author":"CJ Yang","year":"2010","unstructured":"Yang CJ, Lee NY, Lin YH et al (2010) Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the hiv infection epidemic: incidence and risk factors. Clin Infect Dis 51(8):976\u2013979","journal-title":"Clin Infect Dis"},{"issue":"10","key":"4810_CR4","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1111\/j.1468-3083.2012.04544.x","volume":"27","author":"J Li","year":"2013","unstructured":"Li J, Wang LN, Zheng HY (2013) Jarisch-Herxheimer reaction among syphilis patients in China. J Eur Acad Dermatol Venereol 27(10):1304\u20131307","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"10","key":"4810_CR5","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1111\/jdv.15078","volume":"32","author":"M Arando","year":"2018","unstructured":"Arando M, Fernandez-Naval C, Mota-Foix M et al (2018) The Jarisch-Herxheimer reaction in syphilis: could molecular typing help to understand it better? J Eur Acad Dermatol Venereol 32(10):1791\u20131795","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"4","key":"4810_CR6","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.tmaid.2013.04.001","volume":"11","author":"GR Belum","year":"2013","unstructured":"Belum GR, Belum VR, Chaitanya Arudra SK, Reddy BS (2013) The Jarisch-Herxheimer reaction: revisited. Travel Med Infect Dis 11(4):231\u2013237","journal-title":"Travel Med Infect Dis"},{"issue":"4","key":"4810_CR7","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s00415-010-5808-9","volume":"258","author":"J Kobayashi","year":"2011","unstructured":"Kobayashi J, Nakagawa Y, Tobisawa S, Isozaki E, Koide R (2011) Deterioration of MRI findings related to Jarisch-Herxheimer reaction in a patient with neurosyphilis. J Neurol 258(4):699\u2013701","journal-title":"J Neurol"},{"key":"4810_CR8","doi-asserted-by":"crossref","unstructured":"Punia V, Rayi A, Sivaraju A (2014) Stroke after Initiating IV Penicillin for Neurosyphilis: A Possible Jarisch-Herxheimer Reaction. Case reports in neurological medicine 2014: 548179","DOI":"10.1155\/2014\/548179"},{"issue":"1","key":"4810_CR9","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1097\/NRL.0000000000000219","volume":"24","author":"JP Rissardo","year":"2019","unstructured":"Rissardo JP, Caprara ALF, Silveira JOF (2019) Generalized convulsive Status Epilepticus secondary to Jarisch-Herxheimer reaction in Neurosyphilis: a Case Report and Literature Review. Neurologist 24(1):29\u201332","journal-title":"Neurologist"},{"issue":"9","key":"4810_CR10","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1056\/NEJMra1901593","volume":"382","author":"KG Ghanem","year":"2020","unstructured":"Ghanem KG, Ram S, Rice PA (2020) The modern epidemic of Syphilis. N Engl J Med 382(9):845\u2013854","journal-title":"N Engl J Med"},{"key":"4810_CR11","doi-asserted-by":"publisher","first-page":"17073","DOI":"10.1038\/nrdp.2017.73","volume":"3","author":"RW Peeling","year":"2017","unstructured":"Peeling RW, Mabey D, Kamb ML, Chen XS, Radolf JD, Benzaken AS (2017) Syphilis. Nat Rev Dis Primers 3:17073","journal-title":"Nat Rev Dis Primers"},{"issue":"9556","key":"4810_CR12","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/S0140-6736(07)60074-9","volume":"369","author":"ZQ Chen","year":"2007","unstructured":"Chen ZQ, Zhang GC, Gong XD et al (2007) Syphilis in China: results of a national surveillance programme. Lancet 369(9556):132\u2013138","journal-title":"Lancet"},{"key":"4810_CR13","unstructured":"Overview of notifiable infectious diseases in China in 2021 (2023) Available at: http:\/\/www.nhc.gov.cn\/jkj\/s3578\/202204\/4fd88a291d914abf8f7a91f6333567e1.shtml Accessed 7 May 2023"},{"issue":"4","key":"4810_CR14","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1111\/jdv.13514","volume":"30","author":"M Shi","year":"2016","unstructured":"Shi M, Peng RR, Gao Z et al (2016) Risk profiles of neurosyphilis in HIV-negative patients with primary, secondary and latent syphilis: implications for clinical intervention. J Eur Acad Dermatol Venereol 30(4):659\u2013666","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"1","key":"4810_CR15","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1128\/CMR.19.1.29-49.2006","volume":"19","author":"RE Lafond","year":"2006","unstructured":"Lafond RE, Lukehart SA (2006) Biological basis for syphilis. Clin Microbiol Rev 19(1):29\u201349","journal-title":"Clin Microbiol Rev"},{"key":"4810_CR16","first-page":"168","volume":"53","author":"National Center for STD Control","year":"2020","unstructured":"National Center for STD Control (2020) Guidelines for diagnosis and treatment of syphilis, gonorrhea and genital Chlamydia trachomatis infection (2020). Chin J Dermatol 53:168\u2013179","journal-title":"Chin J Dermatol"},{"issue":"4","key":"4810_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.rr7004a1","volume":"70","author":"KA Workowski","year":"2021","unstructured":"Workowski KA, Bachmann LH, Chan PA et al (2021) Sexually transmitted infections Treatment guidelines, 2021. MMWR Recomm Rep 70(4):1\u2013187","journal-title":"MMWR Recomm Rep"},{"issue":"3","key":"4810_CR18","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1111\/jdv.16946","volume":"35","author":"M Janier","year":"2021","unstructured":"Janier M, Unemo M, Dupin N, Tiplica GS, Poto\u010dnik M, Patel R (2021) 2020 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol 35(3):574\u2013588","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"6","key":"4810_CR19","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1001\/archinte.1948.00220290095007","volume":"82","author":"MT Hoekenga","year":"1948","unstructured":"Hoekenga MT, Farmer TW (1948) Jarisch-Herxheimer reaction in neurosyphilis treated with penicillin. Arch Intern Med 82(6):611\u2013622","journal-title":"Arch Intern Med"},{"issue":"7","key":"4810_CR20","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1136\/jnnp.57.7.865","volume":"57","author":"U Zifko","year":"1994","unstructured":"Zifko U, Lindner K, Wimberger D, Volc B, Grisold W (1994) Jarisch-Herxheimer reaction in a patient with neurosyphilis. J Neurol Neurosurg Psychiatry 57(7):865\u2013867","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"4810_CR21","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1055\/s-0028-1139096","volume":"28","author":"K Herxheimer","year":"1902","unstructured":"Herxheimer K, Krause D (1902) Ueber Eine Bei Syphilitischen Vorkommende quecksbilberreaktion. Dtsch MedWochenschr 28:895\u2013897","journal-title":"Dtsch MedWochenschr"},{"key":"4810_CR22","first-page":"721","volume":"45","author":"A Jarisch","year":"1895","unstructured":"Jarisch A (1895) Therapeutische Versuche Bei Syphilis. Wien MedWochenschr 45:721\u2013724","journal-title":"Wien MedWochenschr"},{"issue":"4","key":"4810_CR23","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1001\/jama.1949.02900210023006","volume":"139","author":"V Scott","year":"1949","unstructured":"Scott V, Maxwell RW, Skinner JS (1949) The Jarisch-Herxheimer phenomen in late syphilis. JAMA 139(4):217\u2013220","journal-title":"JAMA"},{"issue":"2","key":"4810_CR24","first-page":"50","volume":"28","author":"A Heyman","year":"1952","unstructured":"Heyman A, Sheldon WH, Evans LD (1952) Pathogenesis of the Jarisch-Herxheimer reaction; a review of clinical and experimental observations. Br J Vener Dis 28(2):50\u201360","journal-title":"Br J Vener Dis"},{"issue":"6","key":"4810_CR25","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1054\/jocn.2002.1129","volume":"9","author":"P Silberstein","year":"2002","unstructured":"Silberstein P, Lawrence R, Pryor D, Shnier R (2002) A case of neurosyphilis with a florid Jarisch-Herxheimer reaction. J Clin Neurosci 9(6):689\u2013690","journal-title":"J Clin Neurosci"},{"issue":"8","key":"4810_CR26","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1001\/jamaneurol.2013.2120","volume":"70","author":"LE Davis","year":"2013","unstructured":"Davis LE, Oyer R, Beckham JD, Tyler KL (2013) Elevated CSF cytokines in the Jarisch-Herxheimer reaction of general paresis. JAMA Neurol 70(8):1060\u20131064","journal-title":"JAMA Neurol"},{"key":"4810_CR27","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1007\/s10096-020-04148-4","volume":"40","author":"A Breuer","year":"2021","unstructured":"Breuer A, Megged O, Kashat L, Assous MV (2021) Quantitative real-time PCR in Borrelia persica tick-borne relapsing fever demonstrates correlation with the Jarisch-Herxheimer reaction. Eur J Clin Microbiol Infect Dis 40:1113\u20131116","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"21","key":"4810_CR28","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.2169\/internalmedicine.54.4956","volume":"54","author":"H Hagiya","year":"2015","unstructured":"Hagiya H, Deguchi K, Kawada K, Otsuka F (2015) Neurosyphilis is a long-forgotten disease but still a possible etiology for Dementia. Intern Med (Tokyo Japan) 54(21):2769\u20132773","journal-title":"Intern Med (Tokyo Japan)"},{"issue":"3","key":"4810_CR29","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1177\/155005940003100306","volume":"31","author":"S Kojan","year":"2000","unstructured":"Kojan S, Van Ness PC, Diaz-Arrastia R (2000) Nonconvulsive status epilepticus resulting from Jarisch-Herxheimer reaction in a patient with neurosyphilis. Clin EEG (Electroencephalography) 31(3):138\u2013140","journal-title":"Clin EEG (Electroencephalography)"},{"issue":"1","key":"4810_CR30","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1684\/epd.2007.0058","volume":"9","author":"C Gurses","year":"2007","unstructured":"Gurses C, Kurtuncu M, Jirsch J et al (2007) Neurosyphilis presenting with status epilepticus. Epileptic Disorders: Int Epilepsy J Videotape 9(1):51\u201356","journal-title":"Epileptic Disorders: Int Epilepsy J Videotape"},{"issue":"5","key":"4810_CR31","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1097\/OLQ.0b013e3181ffa5d0","volume":"38","author":"JB Bucher","year":"2011","unstructured":"Bucher JB, Golden MR, Heald AE, Marra CM (2011) Stroke in a patient with human immunodeficiency virus and syphilis treated with penicillin and antiretroviral therapy. Sex Transm Dis 38(5):442\u2013444","journal-title":"Sex Transm Dis"},{"issue":"4","key":"4810_CR32","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1111\/j.1552-6569.2007.00199.x","volume":"18","author":"SQ Zhang","year":"2008","unstructured":"Zhang SQ, Wan B, Ma XL, Zheng HM (2008) Worsened MRI findings during the early period of treatment with penicillin in a patient with general paresis. J Neuroimaging 18(4):360\u2013363","journal-title":"J Neuroimaging"},{"issue":"3","key":"4810_CR33","first-page":"213","volume":"33","author":"WH Sheldon","year":"1949","unstructured":"Sheldon WH, Heyman A (1949) Morphologic changes in syphilitic lesions during the Jarisch-Herxheimer reaction. Am J Syph Gonorrhea Vener Dis 33(3):213\u2013224","journal-title":"Am J Syph Gonorrhea Vener Dis"},{"issue":"1","key":"4810_CR34","first-page":"15","volume":"48","author":"H Gudjonsson","year":"1968","unstructured":"Gudjonsson H, Skog E (1968) The effect of prednisolone on the Jarisch-Herxheimer reaction. Acta Derm Venereol 48(1):15\u201318","journal-title":"Acta Derm Venereol"},{"issue":"2","key":"4810_CR35","first-page":"122","volume":"34","author":"PY Zhou","year":"2001","unstructured":"Zhou PY, Liao KH, Xu M, Wang X (2001) Influence of corticosteroid on peripheral blood lymphocyte in secondary Syphilis and Prognosis of Syphilis. Chin J Dermatol 34(2):122\u2013123","journal-title":"Chin J Dermatol"},{"issue":"5","key":"4810_CR36","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJM199608013350503","volume":"335","author":"D Fekade","year":"1996","unstructured":"Fekade D, Knox K, Hussein K et al (1996) Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha. N Engl J Med 335(5):311\u2013315","journal-title":"N Engl J Med"},{"issue":"14","key":"4810_CR37","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1056\/NEJMra1906228","volume":"381","author":"AH Ropper","year":"2019","unstructured":"Ropper AH (2019) Neurosyphilis. N Engl J Med 381(14):1358\u20131363","journal-title":"N Engl J Med"},{"issue":"7","key":"4810_CR38","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1086\/591535","volume":"47","author":"DM Musher","year":"2008","unstructured":"Musher DM (2008) Neurosyphilis: diagnosis and response to treatment. Clin Infect Dis 47(7):900\u2013902","journal-title":"Clin Infect Dis"}],"container-title":["European Journal of Clinical Microbiology &amp; Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10096-024-04810-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10096-024-04810-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10096-024-04810-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T14:09:45Z","timestamp":1718374185000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10096-024-04810-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["4810"],"URL":"https:\/\/doi.org\/10.1007\/s10096-024-04810-1","relation":{},"ISSN":["0934-9723","1435-4373"],"issn-type":[{"value":"0934-9723","type":"print"},{"value":"1435-4373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,1]]},"assertion":[{"value":"10 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval for this study was obtained from the medical ethics committee of Shanghai Skin Disease Hospital (ethics number: 2016-011).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The written informed consents were obtained from all enrolled cases.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent"}},{"value":"No reported conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}