{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T06:18:14Z","timestamp":1783491494165,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adult hemophagocytic lymphohistiocytosis (HLH) may be triggered by infection, malignancy, or systemic inflammatory disease. Attribution is challenging when recent SARS-CoV-2 infection, quiescent adult-onset Still\u2019s disease (AOSD), and an occult B-cell clonal disorder coexist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>A 71-year-old man with AOSD controlled for 14 years on low-dose methotrexate developed persistent fever and fatigue after mild SARS-CoV-2 infection. He subsequently developed cytopenias, hyperferritinemia, markedly elevated lactate dehydrogenase, diffuse FDG-avid lymphadenopathy, hepatosplenomegaly, elevated soluble interleukin-2 receptor, reduced natural killer-cell activity, and bone marrow hemophagocytosis, fulfilling HLH criteria. Broad pathogen evaluation, including blood and bone marrow metagenomic next-generation sequencing, did not identify an alternative infectious trigger. Bone marrow histopathology did not show definite tumor cells; however, flow cytometry identified monoclonal mature B cells, and peripheral-blood smear high-throughput sequencing detected lymphoma-associated mutations including MYD88, CD79B, IGLL5, PRDM1, DTX1, DUSP2, and BTG1. Multidisciplinary consultation favored probable lymphoma-associated HLH with clinically diagnosed stage IVB diffuse large B-cell lymphoma. HLH-directed therapy followed by rituximab-based lymphoma-directed chemotherapy led to transient clinical improvement, but the patient later died from infectious complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Mild SARS-CoV-2 infection may act as a co-trigger or unmasking event rather than the sole cause of HLH. Persistent high lactate dehydrogenase and soluble interleukin-2 receptor, diffuse lymphadenopathy, clonal mature B cells, lymphoma-associated mutations, and negative broad pathogen testing should prompt evaluation for occult lymphoma-associated HLH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1879628","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:54:25Z","timestamp":1783490065000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Hemophagocytic lymphohistiocytosis after SARS-CoV-2 infection revealing clinically diagnosed stage IVB diffuse large B-cell lymphoma in quiescent adult-onset Still\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Ting","family":"Long","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University International Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Peking University International Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Guang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University International Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2024.286477","article-title":"Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy","volume":"110","author":"Meyer","year":"2025","journal-title":"Haematologica"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018894618","article-title":"Recommendations for the management of hemophagocytic lymphohistiocytosis in adults","volume":"133","author":"La Rosee","year":"2019","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr Blood Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/art.38690","article-title":"Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome","volume":"66","author":"Fardet","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017012310","article-title":"Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH","volume":"1","author":"Hayden","year":"2017","journal-title":"Blood Adv"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30826","article-title":"A consensus review on Malignancy-associated hemophagocytic lymphohistiocytosis in adults","volume":"123","author":"Daver","year":"2017","journal-title":"Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012764","article-title":"An improved index for diagnosis and mortality prediction in Malignancy-associated hemophagocytic lymphohistiocytosis","volume":"139","author":"Zoref-Lorenz","year":"2022","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014005","article-title":"The OHI index predicts early mortality from organ dysfunction and survival benefit from etoposide in patients with lymphoma","volume":"9","author":"Zoref-Lorenz","year":"2025","journal-title":"Blood Adv"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02135-8","article-title":"Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH): a scoping review unveils clinical and diagnostic patterns of a lymphoma subgroup with poor prognosis","volume":"38","author":"Knauft","year":"2024","journal-title":"Leukemia"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.htct.2025.106087","article-title":"Lymphoma-associated hemophagocytic lymphohistiocytosis","volume":"48","author":"Marcondes","year":"2026","journal-title":"Hematol Transfus Cell Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.3455","article-title":"Cytokine storms in COVID-19, hemophagocytic lymphohistiocytosis, and CAR-T therapy","volume":"8","author":"Long","year":"2025","journal-title":"JAMA Netw Open"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6137","DOI":"10.1038\/s41598-025-90766-x","article-title":"Secondary Hemophagocytic Lymphohistiocytosis in severe COVID-19 - 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