Virus-associated hemophagocytic syndrome caused by influ B and varicella-zoster virus co-infection

Virus-associated hemophagocytic syndrome caused by influ B and varicella-zoster virus co-infection | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Virus-associated hemophagocytic syndrome caused by influ B and varicella-zoster virus co-infection Xiaojun Chen, Yuyu Wang, Dongning Yan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3928011/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Varicella (chicken pox), which caused by the varicella-zoster virus(VZV), is usually self-limiting and benign. However, VZV can lead to significant and serious complications, especially in immunocompromised patients or accompanied by other pathogens infection. HPS caused by varicella-zoster and influ B virus co-infection is rare. Case presentation: A 15-years-old boy was admitted to our hospital because of general rash, severe back and low back pain. CT scan revealed pneumonia in left upper lobe. Initial blood tests showed normal blood WBC and PLT, mild liver dysfunction, enhanced D-dimer and myocardial enzyme. However, after 4-days treatment of acyclovir, antibiotics, and analgesic therapy, his pain did not relieved and fever developed. At the same time, hyperferritinemia, abrupt reduction on blood WBC and PLT count were observed. Virus-associated hemophagocytic syndrome (VHAS)was confirmed.Then, intravenous drip dexamethasone(10mg/day) and gamma globulin(10mg/day) were administrated. He recovered completely at last. Conclusions: Disseminated Varicella which was accompanied by influenza B virus and bacteria infection is infrequent. Disseminated varicella may cause significant morbidity and even mortality in immunocompromised patients. Hemophilic syndrome induced by duel-virus and bacteria infection is limited and usually fetal.Anti-bacterial therapy, early identification of haemophilus syndrome and timely administration of glucocorticoids and gamma globulin are the key links of treatments. Coinfection Varicella-zoster virus Varicella pneumonia Varicella hepatitis Varicella myocarditis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Varicella, which caused by the varicella-zoster virus(VZV), is usually self-limiting and benign. However, VZV can lead to significant and serious complications, especially in immunocompromised patients or in those who is accompanied by other pathogens infection. HPS caused by varicella-zoster and influ B virus co-infection is rare.In this study, we report a HPS case which is correlated with influ B and varicella-zoster virus co-infection in a boy who is immunocompromised because of oral prednisolone. Case presentation A 15-year-old boy went to the hospital complaining of 2 days of rash(Fig. 1 Appearance of rash on admission ), back pain and headache, 1 day of aggravation.Two days ago, he felt headache along with fixed, unbearable and continuous pain in his back. At the same time, distributed red papules were discovered in his chest, back, and both upper limbs.Then he was transferred to hospital and admitted to Department of Pain Treatment of our hospital. The patient suffered Mycoplasma pneumonia two weeks ago.He was treated with 10 days anti-Mycoplasma antibiotics and had a complete recovery on both symptoms and imageological examination. Oral 20mg prednisolone per day was administrated as discharge medications. At admission, the patient’s temperature was 36.7°C, heart rate was 61 bpm, respiratory rate was 13 per minute, blood pressure was 119/66 mmHg, and oxygen saturation in room air was 97%. Further laboratory examination showed blood WBC of 9.9×10^9, lymphocyte of 2.27×10^9, PLT of 247×10^9, PCT of 0.358ng/ml, IL-6 of 9.04pg/ml, SAA of 31.65mg/L,D-dimer of 1.65ug/ml and FDP 5.8ug/ml.Liver function revealed TP of 60.4g/L, ALB of 39.7g/L, globulin of 20.7g/L, AST of 52U/L and ALT of 49U/L. Myocardial enzymes showed AST of 318U/L, CK of 578U/L, CK-MB of 52U/L and LDH 1405 of U/L. ECG displayed .Cerebrospinal fluid tests showed no abnormalities. Triglyceride and FDP were normal. IgM antibody of Mycoplasma pneumoniae was positive. PCR of oropharyngeal swab was positive on Influ B. Both oropharyngeal and rash swab results on VZV were positive. T cell subsets revealed CD3 + of 1069 /ul, CD4 + of 133 /ul and CD8 + of 934 /ul.Serum soluble IL-2 receptor was 1197U/mL and ferritin is greater than 2000ng/mL. CT-scanning displayed infiltration in multi-lobes(Fig. 2 Pulmonary exudation changes on admission). The young man was diagnosed as varicella, varicella pneumonia, varicella hepatitis, varicella myocarditis and influ B infection.However, after 4-days treatment of acyclovir, antibiotics, and analgesic therapy, his pain did not relieved and fever developed. At the same time, hyperferritinemia, abrupt reduction on blood WBC and PLT count were observed. Virus-associated hemophagocytic syndrome (VHAS)was confirmed.Then, intravenous drip dexamethasone(10mg/day) and gamma globulin(10g/day) were administrated. Other adjuvant therapy, including liver protection and down-enzyme measurements, were also used. His temperature dropped to normal rapidly. The papules gradually dried up, crusted(Fig. 3 Rash changes after treatment). The pain eased until it disappeared. Reduced blood PLT slowly rising to normal. Rising serum PCT, ferritinemia, myocardial and liver enzyme lowered to normal gradually. Exudative lesion in left superior lobe was absorbed completely(Fig. 4 Pulmonary exudation changes after treatment). He recovered completely. After 4 weeks of follow-up, the rash basically subsided(Fig. 5 Rash changes after four weeks later). Discussion and conclusions Varicella zoster virus infection can occur in any population, but is common in immunocompromised individuals. The boy oraled prednisone treatment for other reason before admission, which suppressed his immune system and result in his lowed CD4 + count of 133 /ul. Abnormal immunity increased risk of opportunistic VCV infection. VZV infection causes varicella(chickenpox) or herpes zoster(shingles). Mild varicella is a self-limiting disease. Disseminated varicella involve varicella pneumonia, varicella hepatitis, varicella myocarditis, varicella encephalitis and other complications. Varicella-zoster virus (VZV) may cause significant morbidity and even mortality in immunocompromised patients. Varicella has more serious consequences than herpes zoster, although zoster is more common[ 1 ]. In central nervous system, progressive encephalomyelitis with rigidity and myoclonuss, progressive lower cranial and upper cervical polyneuropathy or Encephalitis can be triggered by VZV infection or other virus coinfection[ 2 ][ 3 ][ 4 ][ 5 ][ 6 ]. Rare myelitis cases were presented in the literature. [ 7 ]. A case of multifocal intracranial stenosis which was ultimately discovered to be led by vasculitis due to VZV infection was reported[ 8 ]. A Korea retrospective analysis showed meningitis incidence of 17.8% and meningoencephalitis incidence of 1.5% in adult patients with clinical manifestations of CNS disease[ 9 ]. In digestive system, VZV infection may lead to gastritis[ 10 ], acute pancreatitis[ 11 ], or acute liver failure (ALF)[ 12 ]. VZV infection also play a role in severe autoimmune hepatitis because of immune cross reaction and autoimmune disorder[ 13 ][ 14 ]. In blood system, autoimmune haemolytic anaemia (AIHA) associated with varicella infection was reported[ 15 ]. A M Yeager et al hypothesize the existence of at least infectious and post-infectious pathogenetic mechanisms in varicella-associated thrombocytopenia[ 16 ]. In cardiovascular system, acute myopericarditis can be sequelae of varicella[ 17 ][ 18 ]. VZV infection have a causal role in triggering autoimmunity which can induce polymyositis[ 19 ]. Varicella zoster also have a rare association with erythema multiforme[ 20 ]. Few cases of acute calvarial osteomyelitis or rhabdomyolysis associated with VZV infection or reactivation were reported[ 21 ][ 22 ]. VZV is also considered to be a common causative virus in younger acute retinal necrosis patients[ 23 ]. According to literature, incidence of Varicella-zoster pneumonia (VZP) is less than 5% in healthy individuals and 5–10% in immunocompromised hosts respectively. Patients with VZP have the rash for a few weeks. A neonatal case of bronchopneumonia and hemorrhagic pulmonary edema caused by VZV infection was reported in literature[ 24 ]. Disseminated Varicella which was accompanied by influenza B virus and bacteria infection is infrequent. Clinicians need to recognize this infection which caused by three pathogens. Hemophilic syndrome induced by duel-virus and bacteria infection is limited and usually fetal. Anti-bacterial therapy, early identification of haemophilus syndrome and timely administration of glucocorticoids and gamma globulin are the key links of treatments. Declarations Acknowledgements Not applicable. Authors’ contributions Wang Yuyu and Yan Dongning took care of the patient, wrote the draft. Wang Yuyu prepared figures 1-5. Chen Xiaojun took care of the patient and critically revised the manuscript. All authors read and approved the final manuscript. Funding Natural Science Foundation of Gansu Province, 20JR10RA392 Availability of data and materials All data generated or analysed during this study are included in this published article. Ethics approval and consent to participate Ethics approval or consent to participate was not applicable. Consent for publication Verbal and written consent for publication was obtained from patient and his parents. Competing interests The authors declare that they have no competing interests. References H H Balfour Jr. Varicella-zoster virus infections in the immunocompromised host. Natural history and treatment. Scand J Infect Dis Suppl. 1991:80:69-74. Jing Yuan1, Aihua Wang , Yunfeng Hou, Xuxu Xu. Case report: Varicella-zoster virus infection triggering progressive encephalomyelitis with rigidity and myoclonus. Front Neurol. 2022 Nov 29:13:1042988 Nathan VanderVeen, Nikki Nguyen, Kenny Hoang, Jason Parviz, Tahuriah Khan, Andrew Zhen, Brett W Jagger. Encephalitis with coinfection by Jamestown canyon virus (JCV) and varicella zoster virus (VZV). IDCases. 2020 Oct 8:22 N Wagner, D Staab, R Rosskamp.Cerebral complications in varicella: case report and review.Klin Padiatr. 1987 Sep-Oct;199(5):321-4. Fangzhi Jia, Eugene R Ting, Joo Hyen Ahn, Andrew Duggins.Varicella zoster-associated progressive lower cranial and upper cervical polyneuropathy: a case report.J Med Case Rep. 2022 Aug 17;16(1):313. Boby Varkey Maramattom. Indolent varicella encephalitis with vasculopathy in an immunocompromised patient. J R Coll Physicians Edinb. 2020 Mar;50(1):39-41. Yagmur Basak Polat, Asli Yaman Kula, Serdar Balsak, Zeynep Oran, Alpay Alkan. MR Features of Varicella-zoster Myelitis in an Immunocompetent Patient Curr Med Imaging. 2023;19(4):394-397. Philippe-Antoine Bilodeau, Yasmin Aghajan, Saef Izzy. Rash, Facial Droop, and Multifocal Intracranial Stenosis Due to Varicella Zoster Virus Vasculitis. Neurohospitalist. 2023 Apr;13(2):178-182. Rihwa Choi, Gyeong-Moon Kim, Ik Joon Jo, Min Seob Sim, Keun Jeong Song, Byoung Joon Kim, Duk L Na, Hee Jae Huh, Jong-Won Kim, Chang-Seok Ki, Nam Yong Lee.Incidence and clinical features of herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult Korean population with aseptic meningitis or encephalitis. J Med Virol. 2014 Jun;86(6):957-62. Erik W Nohr, Doha M Itani, Christopher N Andrews, Margaret M Kelly. Varicella-Zoster Virus Gastritis: Case Report and Review of the Literature.Int J Surg Pathol. 2017 Aug;25(5):449-452. Sasmit Roy, Subhasish Bose, Ramesh K Pandey, Srikanth Naramala, Muhammad Rajib Hossain. Acute Pancreatitis Due to Disseminated Varicella Zoster Infection in an Individual with Newly Diagnosed Human Immunodeficiency Virus. Cureus. 2020 Feb 18;12(2):e7027. Li-Na Zhang, Wei Guo, Ji-Hong Zhu, Yang Guo.Successful rescue of acute liver failure and hemophagocytic lymphohistiocytosis following varicella infection: A case report and review of literature. World J Clin Cases. 2018 Nov 6;6(13):659-665. Deepak Jain, Harpreet Singh, Gaganpreet Singh, Promil Jain. Autoimmune Hepatitis with Autoimmune Haemolytic Anemia Triggered by Varicella - a Rare Presentation. Maedica (Bucur). 2016 Dec;11(4):349-351. Waleed K Al-Hamoudi.Severe autoimmune hepatitis triggered by varicella zoster infection. World J Gastroenterol. 2009 Feb 28;15(8):1004-6. Deepak Jain, Harpreet Singh, Gaganpreet Singh, Promil Jain.Autoimmune Hepatitis with Autoimmune Haemolytic Anemia Triggered by Varicella - a Rare Presentation. Maedica (Bucur). 2016 Dec;11(4):349-351. A M Yeager, W H Zinkham.Varicella-associated thrombocytopenia: clues to the etiology of childhood idiopathic thrombocytopenic purpura. Johns Hopkins Med J. 1980 Jun;146(6):270-4. Kai-Liang Kao, Shu-Jen Yeh, Chia-Chun Chen.Myopericarditis associated with varicella zoster virus infection. Pediatr Cardiol. 2010 Jul;31(5):703-6. Aliva De, Dorothy Myridakis, Margot Kerrigan, Fuad Kiblawi. Varicella myopericarditis mimicking myocardial infarction in a 17-year-old boy. Tex Heart Inst J. 2011;38(3):288-90. F Masini, K Gjeloshi, E Pinotti, R Ferrara, C Romano, G Cuomo.Polymyositis following varicella and mumps infection in adults: report of two cases. Reumatismo. 2023 Dec 19;75(4). B Nanda Kishore, Nandini S Ankadavar, Ganesh H Kamath, Jacintha Martis.Varicella zoster with erythema multiforme in a young girl: a rare association. Indian J Dermatol. 2014 May;59(3):299-301. Taylor Sommer, Michael Karsy, Meghan J Driscoll, Randy L Jensen. Varicella-Zoster Virus Infection and Osteomyelitis of the Skull. World Neurosurg. 2018 Jul:115:297-300. L Rodríguez Ferrán, A Vernet Bori, P Poo Argüelles, E Fernández Alvarez, J García Calatayud.Varicella induced rhabdomyolysis. An Esp Pediatr. 2001 Oct;55(4):374-7. Hai-Yan Xu, Meng-Da Li, Jun-Jie Ye, Chan Zhao, Yun-Tao Hu , Yu Di.Varicella-zoster virus as a causative agent of acute retinal necrosis in younger patients.Chin Med J (Engl). 2019 Mar 20;132(6):659-663. I Martín Ibáñez, E P Díaz González, J M Rodríguez Miguélez, J Figueras Aloy. [Neonatal varicella: report of a case of bronchopneumonia and hemorrhagic pulmonary edema. An Esp Pediatr. 2001 Jul;55(1):58-60. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3928011","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":289919788,"identity":"cff3c4d4-c6cf-4b56-93b4-afbca78c7ddb","order_by":0,"name":"Xiaojun Chen","email":"","orcid":"","institution":"Gansu Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaojun","middleName":"","lastName":"Chen","suffix":""},{"id":289919789,"identity":"cf47fe92-a3b5-4792-aa12-58504ba155f6","order_by":1,"name":"Yuyu Wang","email":"","orcid":"","institution":"Gansu Provincial 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13:25:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2549292,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3928011/v1/b4bcd81a-6ce5-4fee-9582-0bb7cc48433e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Virus-associated hemophagocytic syndrome caused by influ B and varicella-zoster virus co-infection","fulltext":[{"header":"Background","content":"\u003cp\u003eVaricella, which caused by the varicella-zoster virus(VZV), is usually self-limiting and benign. However, VZV can lead to significant and serious complications, especially in immunocompromised patients or in those who is accompanied by other pathogens infection. HPS caused by varicella-zoster and influ B virus co-infection is rare.In this study, we report a HPS case which is correlated with influ B and varicella-zoster virus co-infection in a boy who is immunocompromised because of oral prednisolone.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 15-year-old boy went to the hospital complaining of 2 days of rash(Fig.\u0026nbsp;1 Appearance of rash on admission ), back pain and headache, 1 day of aggravation.Two days ago, he felt headache along with fixed, unbearable and continuous pain in his back. At the same time, distributed red papules were discovered in his chest, back, and both upper limbs.Then he was transferred to hospital and admitted to Department of Pain Treatment of our hospital.\u003c/p\u003e \u003cp\u003eThe patient suffered Mycoplasma pneumonia two weeks ago.He was treated with 10 days anti-Mycoplasma antibiotics and had a complete recovery on both symptoms and imageological examination. Oral 20mg prednisolone per day was administrated as discharge medications.\u003c/p\u003e \u003cp\u003eAt admission, the patient\u0026rsquo;s temperature was 36.7\u0026deg;C, heart rate was 61 bpm, respiratory rate was 13 per minute, blood pressure was 119/66 mmHg, and oxygen saturation in room air was 97%.\u003c/p\u003e \u003cp\u003eFurther laboratory examination showed blood WBC of 9.9\u0026times;10^9, lymphocyte of 2.27\u0026times;10^9, PLT of 247\u0026times;10^9, PCT of 0.358ng/ml, IL-6 of 9.04pg/ml, SAA of 31.65mg/L,D-dimer of 1.65ug/ml and FDP 5.8ug/ml.Liver function revealed TP of 60.4g/L, ALB of 39.7g/L, globulin of 20.7g/L, AST of 52U/L and ALT of 49U/L. Myocardial enzymes showed AST of 318U/L, CK of 578U/L, CK-MB of 52U/L and LDH 1405 of U/L. ECG displayed .Cerebrospinal fluid tests showed no abnormalities. Triglyceride and FDP were normal. IgM antibody of Mycoplasma pneumoniae was positive. PCR of oropharyngeal swab was positive on Influ B. Both oropharyngeal and rash swab results on VZV were positive. T cell subsets revealed CD3\u0026thinsp;+\u0026thinsp;of 1069 /ul, CD4\u0026thinsp;+\u0026thinsp;of 133 /ul and CD8\u0026thinsp;+\u0026thinsp;of 934 /ul.Serum soluble IL-2 receptor was 1197U/mL and ferritin is greater than 2000ng/mL. CT-scanning displayed infiltration in multi-lobes(Fig.\u0026nbsp;2 Pulmonary exudation changes on admission).\u003c/p\u003e \u003cp\u003eThe young man was diagnosed as varicella, varicella pneumonia, varicella hepatitis, varicella myocarditis and influ B infection.However, after 4-days treatment of acyclovir, antibiotics, and analgesic therapy, his pain did not relieved and fever developed. At the same time, hyperferritinemia, abrupt reduction on blood WBC and PLT count were observed. Virus-associated hemophagocytic syndrome (VHAS)was confirmed.Then, intravenous drip dexamethasone(10mg/day) and gamma globulin(10g/day) were administrated. Other adjuvant therapy, including liver protection and down-enzyme measurements, were also used.\u003c/p\u003e \u003cp\u003eHis temperature dropped to normal rapidly. The papules gradually dried up, crusted(Fig.\u0026nbsp;3 Rash changes after treatment). The pain eased until it disappeared. Reduced blood PLT slowly rising to normal. Rising serum PCT, ferritinemia, myocardial and liver enzyme lowered to normal gradually. Exudative lesion in left superior lobe was absorbed completely(Fig.\u0026nbsp;4 Pulmonary exudation changes after treatment). He recovered completely. After 4 weeks of follow-up, the rash basically subsided(Fig.\u0026nbsp;5 Rash changes after four weeks later).\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eVaricella zoster virus infection can occur in any population, but is common in immunocompromised individuals. The boy oraled prednisone treatment for other reason before admission, which suppressed his immune system and result in his lowed CD4\u0026thinsp;+\u0026thinsp;count of 133 /ul. Abnormal immunity increased risk of opportunistic VCV infection.\u003c/p\u003e \u003cp\u003eVZV infection causes varicella(chickenpox) or herpes zoster(shingles). Mild varicella is a self-limiting disease. Disseminated varicella involve varicella pneumonia, varicella hepatitis, varicella myocarditis, varicella encephalitis and other complications. Varicella-zoster virus (VZV) may cause significant morbidity and even mortality in immunocompromised patients. Varicella has more serious consequences than herpes zoster, although zoster is more common[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn central nervous system, progressive encephalomyelitis with rigidity and myoclonuss, progressive lower cranial and upper cervical polyneuropathy or Encephalitis can be triggered by VZV infection or other virus coinfection[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e][\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Rare myelitis cases were presented in the literature. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A case of multifocal intracranial stenosis which was ultimately discovered to be led by vasculitis due to VZV infection was reported[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA Korea retrospective analysis showed meningitis incidence of 17.8% and meningoencephalitis incidence of 1.5% in adult patients with clinical manifestations of CNS disease[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn digestive system, VZV infection may lead to gastritis[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], acute pancreatitis[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], or acute liver failure (ALF)[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. VZV infection also play a role in severe autoimmune hepatitis because of immune cross reaction and autoimmune disorder[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn blood system, autoimmune haemolytic anaemia (AIHA) associated with varicella infection was reported[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A M Yeager et al hypothesize the existence of at least infectious and post-infectious pathogenetic mechanisms in varicella-associated thrombocytopenia[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn cardiovascular system, acute myopericarditis can be sequelae of varicella[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e][\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVZV infection have a causal role in triggering autoimmunity which can induce polymyositis[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Varicella zoster also have a rare association with erythema multiforme[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Few cases of acute calvarial osteomyelitis or rhabdomyolysis associated with VZV infection or reactivation were reported[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e][\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVZV is also considered to be a common causative virus in younger acute retinal necrosis patients[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to literature, incidence of Varicella-zoster pneumonia (VZP) is less than 5% in healthy individuals and 5\u0026ndash;10% in immunocompromised hosts respectively. Patients with VZP have the rash for a few weeks.\u003c/p\u003e \u003cp\u003eA neonatal case of bronchopneumonia and hemorrhagic pulmonary edema caused by VZV infection was reported in literature[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDisseminated Varicella which was accompanied by influenza B virus and bacteria infection is infrequent. Clinicians need to recognize this infection which caused by three pathogens. Hemophilic syndrome induced by duel-virus and bacteria infection is limited and usually fetal. Anti-bacterial therapy, early identification of haemophilus syndrome and timely administration of glucocorticoids and gamma globulin are the key links of treatments.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWang Yuyu and Yan Dongning took care of the patient, wrote the draft. Wang Yuyu prepared figures 1-5. Chen Xiaojun took care of the patient and critically revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNatural Science Foundation of Gansu Province, 20JR10RA392\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval or consent to participate was not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVerbal and written consent for publication was obtained from patient and his parents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eH H Balfour Jr. Varicella-zoster virus infections in the immunocompromised host. Natural history and treatment. Scand J Infect Dis Suppl. 1991:80:69-74.\u003c/li\u003e\n\u003cli\u003eJing Yuan1, Aihua Wang , Yunfeng Hou, Xuxu Xu. Case report: Varicella-zoster virus infection triggering progressive encephalomyelitis with rigidity and myoclonus. Front Neurol. 2022 Nov 29:13:1042988\u003c/li\u003e\n\u003cli\u003eNathan VanderVeen, Nikki Nguyen, Kenny Hoang, Jason Parviz, Tahuriah Khan, Andrew Zhen, Brett W Jagger. Encephalitis with coinfection by Jamestown canyon virus (JCV) and varicella zoster virus (VZV). IDCases. 2020 Oct 8:22\u003c/li\u003e\n\u003cli\u003eN Wagner, D Staab, R Rosskamp.Cerebral complications in varicella: case report and review.Klin Padiatr. 1987 Sep-Oct;199(5):321-4.\u003c/li\u003e\n\u003cli\u003eFangzhi Jia, Eugene R Ting, Joo Hyen Ahn, Andrew Duggins.Varicella zoster-associated progressive lower cranial and upper cervical polyneuropathy: a case report.J Med Case Rep. 2022 Aug 17;16(1):313.\u003c/li\u003e\n\u003cli\u003eBoby Varkey Maramattom. Indolent varicella encephalitis with vasculopathy in an immunocompromised patient. J R Coll Physicians Edinb. 2020 Mar;50(1):39-41. \u003c/li\u003e\n\u003cli\u003eYagmur Basak Polat, Asli Yaman Kula, Serdar Balsak, Zeynep Oran, Alpay Alkan. MR Features of Varicella-zoster Myelitis in an Immunocompetent Patient Curr Med Imaging. 2023;19(4):394-397.\u003c/li\u003e\n\u003cli\u003ePhilippe-Antoine Bilodeau, Yasmin Aghajan, Saef Izzy. Rash, Facial Droop, and Multifocal Intracranial Stenosis Due to Varicella Zoster Virus Vasculitis. Neurohospitalist. 2023 Apr;13(2):178-182.\u003c/li\u003e\n\u003cli\u003eRihwa Choi, Gyeong-Moon Kim, Ik Joon Jo, Min Seob Sim, Keun Jeong Song, Byoung Joon Kim, Duk L Na, Hee Jae Huh, Jong-Won Kim, Chang-Seok Ki, Nam Yong Lee.Incidence and clinical features of herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult Korean population with aseptic meningitis or encephalitis. J Med Virol. 2014 Jun;86(6):957-62. \u003c/li\u003e\n\u003cli\u003eErik W Nohr, Doha M Itani, Christopher N Andrews, Margaret M Kelly. Varicella-Zoster Virus Gastritis: Case Report and Review of the Literature.Int J Surg Pathol. 2017 Aug;25(5):449-452.\u003c/li\u003e\n\u003cli\u003eSasmit Roy, Subhasish Bose, Ramesh K Pandey, Srikanth Naramala, Muhammad Rajib Hossain. Acute Pancreatitis Due to Disseminated Varicella Zoster Infection in an Individual with Newly Diagnosed Human Immunodeficiency Virus. Cureus. 2020 Feb 18;12(2):e7027.\u003c/li\u003e\n\u003cli\u003eLi-Na Zhang, Wei Guo, Ji-Hong Zhu, Yang Guo.Successful rescue of acute liver failure and hemophagocytic lymphohistiocytosis following varicella infection: A case report and review of literature. World J Clin Cases. 2018 Nov 6;6(13):659-665. \u003c/li\u003e\n\u003cli\u003eDeepak Jain, Harpreet Singh, Gaganpreet Singh, Promil Jain. Autoimmune Hepatitis with Autoimmune Haemolytic Anemia Triggered by Varicella - a Rare Presentation. Maedica (Bucur). 2016 Dec;11(4):349-351.\u003c/li\u003e\n\u003cli\u003eWaleed K Al-Hamoudi.Severe autoimmune hepatitis triggered by varicella zoster infection. World J Gastroenterol. 2009 Feb 28;15(8):1004-6.\u003c/li\u003e\n\u003cli\u003eDeepak Jain, Harpreet Singh, Gaganpreet Singh, Promil Jain.Autoimmune Hepatitis with Autoimmune Haemolytic Anemia Triggered by Varicella - a Rare Presentation. Maedica (Bucur). 2016 Dec;11(4):349-351.\u003c/li\u003e\n\u003cli\u003eA M Yeager, W H Zinkham.Varicella-associated thrombocytopenia: clues to the etiology of childhood idiopathic thrombocytopenic purpura. Johns Hopkins Med J. 1980 Jun;146(6):270-4.\u003c/li\u003e\n\u003cli\u003eKai-Liang Kao, Shu-Jen Yeh, Chia-Chun Chen.Myopericarditis associated with varicella zoster virus infection. Pediatr Cardiol. 2010 Jul;31(5):703-6. \u003c/li\u003e\n\u003cli\u003eAliva De, Dorothy Myridakis, Margot Kerrigan, Fuad Kiblawi. Varicella myopericarditis mimicking myocardial infarction in a 17-year-old boy. Tex Heart Inst J. 2011;38(3):288-90.\u003c/li\u003e\n\u003cli\u003eF Masini, K Gjeloshi, E Pinotti, R Ferrara, C Romano, G Cuomo.Polymyositis following varicella and mumps infection in adults: report of two cases. Reumatismo. 2023 Dec 19;75(4). \u003c/li\u003e\n\u003cli\u003eB Nanda Kishore, Nandini S Ankadavar, Ganesh H Kamath, Jacintha Martis.Varicella zoster with erythema multiforme in a young girl: a rare association. Indian J Dermatol. 2014 May;59(3):299-301.\u003c/li\u003e\n\u003cli\u003eTaylor Sommer, Michael Karsy, Meghan J Driscoll, Randy L Jensen. Varicella-Zoster Virus Infection and Osteomyelitis of the Skull. World Neurosurg. 2018 Jul:115:297-300. \u003c/li\u003e\n\u003cli\u003eL Rodr\u0026iacute;guez Ferr\u0026aacute;n, A Vernet Bori, P Poo Arg\u0026uuml;elles, E Fern\u0026aacute;ndez Alvarez, J Garc\u0026iacute;a Calatayud.Varicella induced rhabdomyolysis. An Esp Pediatr. 2001 Oct;55(4):374-7.\u003c/li\u003e\n\u003cli\u003eHai-Yan Xu, Meng-Da Li, Jun-Jie Ye, Chan Zhao, Yun-Tao Hu , Yu Di.Varicella-zoster virus as a causative agent of acute retinal necrosis in younger patients.Chin Med J (Engl). 2019 Mar 20;132(6):659-663. \u003c/li\u003e\n\u003cli\u003eI Mart\u0026iacute;n Ib\u0026aacute;\u0026ntilde;ez, E P D\u0026iacute;az Gonz\u0026aacute;lez, J M Rodr\u0026iacute;guez Migu\u0026eacute;lez, J Figueras Aloy. [Neonatal varicella: report of a case of bronchopneumonia and hemorrhagic pulmonary edema. An Esp Pediatr. 2001 Jul;55(1):58-60. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Coinfection, Varicella-zoster virus, Varicella pneumonia, Varicella hepatitis, Varicella myocarditis","lastPublishedDoi":"10.21203/rs.3.rs-3928011/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3928011/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eVaricella (chicken pox), which caused by the varicella-zoster virus(VZV), is usually self-limiting and benign. However, VZV can lead to significant and serious complications, especially in immunocompromised patients or accompanied by other pathogens infection. HPS caused by varicella-zoster and influ B virus co-infection is rare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003eA 15-years-old boy was admitted to our hospital because of general rash, severe back and low back pain. CT scan revealed pneumonia in left upper lobe. Initial blood tests showed normal blood WBC and PLT, mild liver dysfunction, enhanced D-dimer and myocardial enzyme. However, after 4-days treatment of acyclovir, antibiotics, and analgesic therapy, his pain did not relieved and fever developed. At the same time, hyperferritinemia, abrupt reduction on blood WBC and PLT count were observed. Virus-associated hemophagocytic syndrome (VHAS)was confirmed.Then, intravenous drip dexamethasone(10mg/day) and gamma globulin(10mg/day) were administrated. He recovered completely at last.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eDisseminated Varicella which was accompanied by influenza B virus and bacteria infection is infrequent. Disseminated varicella may cause significant morbidity and even mortality in immunocompromised patients. Hemophilic syndrome induced by duel-virus and bacteria infection is limited and usually fetal.Anti-bacterial therapy, early identification of haemophilus syndrome and timely administration of glucocorticoids and gamma globulin are the key links of treatments.\u003c/p\u003e","manuscriptTitle":"Virus-associated hemophagocytic syndrome caused by influ B and varicella-zoster virus co-infection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 17:53:01","doi":"10.21203/rs.3.rs-3928011/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ed92e927-af2d-4c4f-827c-bb1daf2fe914","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-05T13:16:53+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-19 17:53:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3928011","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3928011","identity":"rs-3928011","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}