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Secondary HLH includes infection\u2010 (eg viral\/bacterial\/fungal\/parasitic) and non\u2013infection\u2010 (eg collagen disease or malignancy) related diseases. Viral HLH is the major type among all age groups. Secondary viral HLH and primary HLH must be differentiated carefully because primary HLH can be associated with viral infection(s), and the outcome is dismal without a timely diagnosis and hematopoietic stem cell transplantation (HSCT). Epstein\u2010Barr virus (EBV)\u2010related HLH (EBV\u2010HLH) is the most common type of viral HLH in childhood. For non\u2013EBV\u2010HLH, appropriate treatment of viral infection, followed by immunomodulatory agent(s) such as corticosteroids, intravenous immunoglobulin or cyclosporine A, is usually successful; however, recent SARS\u2010CoV\u20102\u2010related HLH may become life\u2010threatening. EBV\u2010HLH may occur heterogeneously associated with the primary infection, with chronic active EBV infection or with underlying primary HLH. Although immunomodulatory agent(s) are effective in the majority of EBV\u2010HLH cases, management differs from that of non\u2013EBV\u2010HLH because severe and refractory cases may require etoposide\u2010containing HLH\u20101994\/2004 regimens or other experimental agents. The novel agent, emapalumab (an anti\u2013IFN\u2010\u03b3 monoclonal antibody) can be used to treat EBV\u2010HLH cases to avoid the risk of secondary malignancy due to etoposide. Finally, HSCT is required for refractory EBV\u2010HLH cases and can also be curative in some other cases.<\/jats:p>","DOI":"10.1111\/apa.15973","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T05:10:38Z","timestamp":1623042638000},"page":"2729-2736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Virus\u2010triggered secondary hemophagocytic lymphohistiocytosis"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-0819","authenticated-orcid":false,"given":"Shinsaku","family":"Imashuku","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Uji\u2010Tokushukai Medical Center  Uji Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jichi Medical University School of Medicine  Shimotsuke, Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Ishii","sequence":"additional","affiliation":[{"name":"Director Imabari City Hospital  Imabari, Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-041610-134208"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.06.053"},{"key":"e_1_2_8_4_1","first-page":"291","article-title":"Inflammatory cytokines in virus\u2010associated hemophagocytic syndrome. 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