DOI: 10.12890/2026_007254

Severe secondary hemophagocytic lymphohistiocytosis syndrome due to Crimean-Congo haemorrhagic fever virus: Thinking out of the box

Authors

  • Poulia Asimakopoulou Department of Medicine, Infectious Diseases Unit, and Research Laboratory of Internal Medicine, Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
  • Sara Georgiadou Department of Medicine, Infectious Diseases Unit, and Research Laboratory of Internal Medicine, Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
  • Nikolaos Gatselis Department of Medicine, Infectious Diseases Unit, and Research Laboratory of Internal Medicine, Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
  • George N. Dalekos Department of Medicine, Infectious Diseases Unit, and Research Laboratory of Internal Medicine, Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece

georgedalekos@gmail.com

Keywords

Crimean-Congo haemorrhagic fever virus, haemophagocytic lymphohistiocytosis, haemophagocytic-ferritinemia

Abstract

Introduction: Crimean-Congo haemorrhagic fever is an acute, often severe haemorrhagic disease caused by the homonymous virus. On the other hand, severe life-threatening secondary haemophagocytic lymphohistiocytosis is a rare entity usually associated with underlying haematological malignancies, infectious or autoimmune diseases. Herein, we report a fatal case of severe secondary haemophagocytic lymphohistiocytosis due to the abovementioned virus but also a second case of Crimean-Congo haemorrhagic fever with virus-induced threatening haemophagocytic lymphohistiocytosis in an internist who was responsible for the patient’s management.
Case description: A 72-year-old stockbreeder progressed to fatal secondary haemophagocytic lymphohistiocytosis due to Crimean-Congo haemorrhagic fever virus (fever, hepatosplenomegaly, severe cytopenias, low fibrinogen, hypertriglyceridemia and extremely high ferritin levels), despite aggressive supportive measures and specific treatment with corticosteroids and intravenous gamma-immunoglobulin. The second case was a 54-year-old internist who acquired the Crimean-Congo haemorrhagic fever virus through mucocutaneous exposure to the patient’s blood, recovering fully with prompt double treatment against active viral replication and early stage haemophagocytic lymphohistiocytosis.
Discussion: Crimean-Congo haemorrhagic fever virus is a rare cause of secondary haemophagocytic lymphohistiocytosis with an unfavourable outcome if the patient has a rapidly progressing course as in our first case. Clinicians should maintain a high level of clinical suspicion in the appropriate clinical setting since prompt initiation of treatment for secondary haemophagocytic lymphohistiocytosis as in the second case, can be lifesaving.
Conclusion: These cases emphasize that Crimean-Congo haemorrhagic fever virus can be a cause of severe life-threatening haemophagocytic lymphohistiocytosis even in non-endemic areas, while stringent infection control to prevent secondary healthcare-associated transmission is of the utmost importance.

View the entire article

Downloads

References

  1. Hawman DW, Feldmann H. Crimean-Congo haemorrhagic fever virus. Nat Rev Microbiol 2023;21:463-477. doi: 10.1038/s41579-023-00871-9
  2. Papa A, Maltezou HC, Tsiodras S, Dalla VG, Papadimitriou T, Pierroutsakos I, et al. A case of Crimean-Congo haemorrhagic fever in Greece, June 2008. Euro Surveill 2008;13:18952. doi: 10.2807/ese.13.33.18952-en
  3. Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, et al. The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS). Ann Rheum Dis;82:1271-1285. doi: 10.1136/ard-2023-224123
  4. Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C. Infections associated with haemophagocytic syndrome. Lancet Infect Dis 2007;7:814-22. doi: 10.1016/S1473-3099(07)70290-6
  5. Georgiadou S, Gatselis NK, Stefos A, Zachou K, Makaritsis K, Rigopoulou EI, et al. Efficient management of secondary haemophagocytic lymphohistiocytosis with intravenous steroids and gamma-immunoglobulin infusions. World J Clin Cases 2019;7:3394-3406. doi: 10.12998/wjcc.v7.i21.3394.
  6. Argyraki CK, Gabeta S, Zachou K, Boulbou M, Polyzos A, Dalekos GN. Favourable outcome of life-threatening infectious-related haemophagocytic syndrome after combination treatment with corticosteroids and intravenous immunoglobulin infusions. Eur J Intern Med 2011;22:e155-7. doi: 10.1016/j.ejim.2011.07.010
  7. Dalekos GN, Stefos A, Georgiadou S, Lygoura V, Michail A, Ntaios G, et al. Lessons from pathophysiology: Use of individualized combination treatments with immune interventional agents to tackle severe respiratory failure in patients with COVID-19. Eur J Intern Med 2021;88:52-62. doi: 10.1016/j.ejim.2021.03.026
  8. World Health Organization. Clinical management of patients with viral haemorrhagic fever: A pocket guide for front-line health workers. https://www.who.int/publications/i/item/9789241549608
  9. Pervanidou D, Georgiadou S, Stavropoulou E, Stefos A, Tsioka K, Kefaloudi CN, et al. Two autochthonous cases of Crimean-Congo haemorrhagic fever and the One Health response, Thessaly, Greece, 2025. wo autochthonous cases of Crimean-Congo haemorrhagic fever and the One Health response, Thessaly, Greece, 2025. Euro Surveill 2025;30:2500717. doi: 10.2807/1560-7917.ES.2025.30.50.2500717
  10. Tasdelen Fisgin N, Fisgin T, Tanyel E, Doganci L, Tulek N, Guler N, et al. Crimean-Congo hemorrhagic fever: five patients with hemophagocytic syndrome. Am J Hematol 2008;83:73-6. doi: 10.1002/ajh.20969
  11. Caydasi Ö, Arslan E, Adiyeke E, Kuzan TY, Karadag FY, et al. A case of Crimean-Congo haemorrhagic fever complicated with portal vein thrombosis and hemophagocytosis. Trop Med Int Health 2024;29:536-539. doi: 10.1111/tmi.13995

Published

2026-07-16

Issue

Vol. 13 No. 8 (2026)

Categories

How to Cite

1.
Asimakopoulou P, Georgiadou S, Gatselis N, Dalekos GN. Severe secondary hemophagocytic lymphohistiocytosis syndrome due to Crimean-Congo haemorrhagic fever virus: Thinking out of the box. EJCRIM [Internet]. 2026 Jul. 16 [cited 2026 Nov. 3];13(8). Available from: https://ejcrim.com/index.php/ejcrim/article/view/7254