Article Data

  • Views 240
  • Dowloads 123

Original Research

Open Access

Severe pneumonia complicated by hemophagocytic lymphohistiocytosis in adults: a retrospective and exploratory clinical analysis

  • Ling Zhang1,*,†,
  • Qi-Gang Yang1,†
  • Min Shao1,*,

1Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, China

DOI: 10.22514/sv.2025.034 Vol.21,Issue 3,March 2025 pp.36-45

Submitted: 20 August 2024 Accepted: 05 December 2024

Published: 08 March 2025

*Corresponding Author(s): Ling Zhang E-mail: zhangling1702@126.com
*Corresponding Author(s): Min Shao E-mail: shaomin@ahmu.edu.cn

† These authors contributed equally.

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening com-plication that can arise in adults with severe pneumonia (SP). This retrospective study analyzed the clinical characteristics, diagnostic approaches and treatment outcomes of adult patients diagnosed with SP complicated by HLH. Methods: The clinical data of 9 related adult patients were collected from the Department of Critical Care Medicine and analyzed. Results: The mean age of the patients was 41.11 ± 13.02 years, with 88.9% (8/9) being male. Comorbidities included post-renal transplantation, lymphoma, pregnancy, hepatitis E, syphilis and hypertension. The observed 28-day mortality rate was 22.2% (2/9), while the 60-day to 1-year mortality rates were both 77.8% (7/9). The etiological agents responsible for SP included bacteria (16%), viruses (52%), fungi (28%) and chlamydia (4%). Chest computed tomography revealed bilateral multiple exudative lesions. All patients met the 2004 HLH diagnostic criteria and had a mean HScore of 246.78 ± 44.11 and median ferritin level of 2828 µg/L (Inter Quartile Range (IQR) 2284–5152). Bone marrow cytology revealed mononuclear-phagocytic histiocytes in 8 of 9 patients. Lymphocyte subpopulations, including total lymphocyte count, cluster of differentiation (CD)4+ and CD8+ cells, were found to be significantly reduced (p < 0.01), while serum levels of interleukin (IL)-6 and IL-8 were markedly elevated (p < 0.001). Therapeutic interventions included targeted anti-infective treatment, with glucocorticoids administered to 5 patients, low-dose etoposide to 4 patients, intravenous immunoglobulin to 7 patients, and plasma exchange in 6 patients. Despite these interventions, mortality remained high. Conclusions: Routine monitoring of HLH diagnostic indicators in patients with SP is crucial, and anti-infective and supportive therapies, as well as immunosuppressive and cytotoxic agents, may offer potential benefits for critically ill patients.


Keywords

Severe pneumonia; Hemophagocytic lymphohistiocytosis; Adults; Clinical characteristics


Cite and Share

Ling Zhang,Qi-Gang Yang,Min Shao. Severe pneumonia complicated by hemophagocytic lymphohistiocytosis in adults: a retrospective and exploratory clinical analysis. Signa Vitae. 2025. 21(3);36-45.

References

[1] Seguin A, Galicier L, Boutboul D, Lemiale V, Azoulay EJC. Pulmonary involvement in patients with hemophagocytic lymphohistiocytosis. Chest. 2016; 149: 1294–1301.

[2] Song R, Zhang Q, Wu T, Pan Y, Wei A, Shi Y, et al. SARS-CoV-2 reactivates fungal-associated hemophagocytic lymphohistiocytosis: case report and review of the literature. International Immunopharmacology. 2024; 142: 113141.

[3] Martin-Loeches I, Torres A, Nagavci B, Aliberti S, Antonelli M, Bassetti M, et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. The European Respiratory Journal. 2023; 61: 2200735.

[4] Cillóniz C, Torres A, Niederman MJB. Management of pneumonia in critically ill patients. British Medical Journal. 2021; 375: e065871.

[5] Bhatraju P, Ghassemieh B, Nichols M, Kim R, Jerome K, Nalla A, et al. Covid-19 in critically ill patients in the Seattle region—case series. The New England Journal of Medicine. 2020; 382: 2012–2022.

[6] Lafarge A, Chean D, Whiting L, Clere-Jehl R. Management of hematological patients requiring emergency chemotherapy in the intensive care unit. Intensive Care Medicine. 2024; 50: 849–860.

[7] Henter J, Horne A, Aricó M, Egeler R, Filipovich A, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric Blood & Cancer. 2007; 48: 124–131.

[8] Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis & Rheumatology. 2014; 66: 2613–2620.

[9] Mandell L, Wunderink R, Anzueto A, Bartlett J, Campbell G, Dean N, et al. Infectious diseases society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clinical Infectious Diseases. 2007; 44: S27–S72.

[10] Meng M, Chen L, Zhang S, Dong X, Li W, Li R, et al. Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients. BMC Infectious Diseases. 2021; 21: 398.

[11] Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta M, Bosch XJL. Adult haemophagocytic syndrome. The Lancet. 2014; 383: 1503–1516.

[12] Prilutskiy A, Kritselis M, Shevtsov A, Yambayev I, Vadlamudi C, Zhao Q, et al. SARS-CoV-2 infection-associated hemophagocytic lymphohistiocytosis. American Journal of Clinical Pathology. 2020; 154: 466–474.

[13] Lachmann G, Spies C, Schenk T, Brunkhorst FM, Balzer F, La Rosée P. Hemophagocytic lymphohistiocytosis: potentially underdiagnosed in intensive care units. Shock. 2018; 50: 149–155.

[14] Nyvlt P, Schuster FS, Ihlow J, Heeren P, Spies C, Hiesgen J, et al. Value of hemophagocytosis in the diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients. European Journal of Haematology. 2024; 112: 917–926.

[15] West J, Stilwell P, Liu H, Ban L, Bythell M, Card T, et al. 1-year survival in haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003–2018. Journal of Hematology & Oncology. 2023; 16: 56.

[16] Shi Y, Yu X, Zhao H, Wang H, Zhao R, Sheng JJCc. Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan. Critical Care. 2020; 24: 108.

[17] Rafeq R, Igneri LA. Infectious pulmonary diseases. Infectious Disease Clinics of North America. 2024; 38: 1–17.

[18] Di Pasquale M, Sotgiu G, Gramegna A, Radovanovic D, Terraneo S, Reyes L, et al. Prevalence and etiology of community-acquired pneumonia in immunocompromised patients. Clinical Infectious Diseases. 2019; 68: 1482–1493.

[19] Ren K, Yong C, Wang Y, Wei H, Zhao K, He B, et al. Cytomegalovirus pneumonia in inflammatory bowel disease: literature review and clinical recommendations. Infection and Drug Resistance. 2023; 16: 6195–6208.

[20] Bichon A, Bourenne J, Allardet-Servent J, Papazian L, Hraiech S, Guervilly C, et al. High mortality of HLH in ICU regardless etiology or treatment. Frontiers in Medicine. 2021; 8: 735796.

[21] Yunis J, Short KR, Yu D. Severe respiratory viral infections: T-cell functions diverging from immunity to inflammation. Trends in Microbiology. 2023; 31: 644–656.

[22] Azoulay E, Russell L, Van de Louw A, Metaxa V, Bauer P, Povoa P, et al. Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Medicine. 2020; 46: 298–314.

[23] Griffin G, Shenoi S, Hughes GC. Hemophagocytic lymphohistiocytosis: an update on pathogenesis, diagnosis, and therapy. Best Practice & Research Clinical Rheumatology. 2020; 34: 101515.

[24] Steffen CJ, Koch N, Eckardt KU, Amann K, Seelow E, Schreiber A. Hemophagocytic lymphohistiocytosis and thrombotic microangiopathy after parvovirus B19 infection and renal transplantation: a case report. BMC Nephrology. 2021; 22: 337.

[25] Choi E, Lee S, Oh C, Kim Y, Bang JB. Cytomegalovirus-associated hemophagocytic syndrome diagnosed by liver biopsy in a kidney transplant recipient. Yonsei Medical Journal. 2021; 62: 274–277.

[26] Wu Y, Sun X, Kang K, Yang Y, Li H, Zhao A, et al. Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms. Journal of Hematology & Oncology. 2024; 17: 106.

[27] Sun L, Su Y, Jiao A, Wang X, Zhang B. T cells in health and disease. Signal Transduction and Targeted Therapy. 2023; 8: 235.

[28] Boechat JL, Chora I, Morais A, Delgado L. The immune response to SARS-CoV-2 and COVID-19 immunopathology—current perspectives. Pulmonology. 2021; 27: 423–437.

[29] Knaak C, Nyvlt P, Schuster F, Spies C, Heeren P, Schenk T, et al. Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore. Critical Care. 2020; 24: 244.

[30] Khare N, Jinkala SR, Kanungo S. Performance of HScore in reactive hemophagocytic lymphohistiocytosis. Indian Journal of Hematology & Blood Transfusion. 2021; 37: 256–263.

[31] Hansen S, Alduaij W, Biggs CM, Belga S, Luecke K, Merkeley H, et al. Ruxolitinib as adjunctive therapy for secondary hemophagocytic lymphohistiocytosis: a case series. European Journal of Haematology. 2021; 106: 654–661.

[32] Shi YF, Shi XH, Zhang Y, Chen JX, Lai WX, Luo JM, et al. Disseminated tuberculosis associated hemophagocytic lymphohistiocytosis in a pregnant woman with Evans syndrome: a case report and literature review. Frontiers in Immunology. 2021; 12: 676132.

[33] Cheng S, Yan Z, Ma H, Liu Y. Lymphoma-associated hemophagocytic syndrome: a retrospective, single-center study of 86 patients. Annals of Hematology. 2024; 103: 3649–3656.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus: CiteScore 1.3 (2023) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time

Conferences

Top