Advertisement

Forensic Science, Medicine and Pathology

, Volume 14, Issue 3, pp 372–376 | Cite as

Fatal unexpected death due to familial hemophagocytic lymphohistiocytosis type 3

  • Jiao Mu
  • Chunting Jin
  • Zhenglian Chen
  • Jianfeng Li
  • Bin Lv
  • Hongmei Dong
Case Report

Abstract

Familial hemophagocytic lymphohistiocytosis is a rare autosomal recessive disorder of immune dysregulation associated with uncontrolled activation of cytotoxic T cells and macrophages. Herein, we report a case of a 14-month-old Chinese boy who presented with fever, abdominal distension and thrombopenia, and died within 3 days of admission to the hospital. Postmortem examination revealed pleuroperitoneal fluid, enlarged mesenteric lymph nodes and hepatosplenomegaly. Histopathological examination showed interstitial pneumonia, hepatonecrosis and hemophagocytosis. Immunohistochemical staining of the spleen, lymph node and liver specimens revealed numerous cytotoxic T cells (CD8+) and histiocytes (CD68+). EBER1-positive cells were observed in lymphocytes of the spleen, lymph node, liver and lungs by in situ hybridization. UNC13D mutation was identified, although the boy had no family history. The following medico-legal autopsy case is being reported for its rarity in the forensic setting. We addresses the need for genetic testing in addition to a thorough clinical history, appropriate laboratory tests, histological examination and immunohistochemical analysis for the rapid and accurate diagnosis of familial hemophagocytic lymphohistiocytosis.

Keywords

Familial hemophagocytic lymphohistiocytosis Thrombopenia Histopathology UNC13D 

Notes

Acknowledgements

This study was supported by Hebei Natural Science Foundation (Grant No. H2017405021) and National Natural Science Foundation of China (Grant No. 81471821).

Author contributions

Jiao Mu, Chunting Jin and Jianfeng Li carried out the autopsy and histological study. Jiao Mu and Chunting Jin participated in the design and drafted the manuscript. Jiao Mu and Bin Lv carried out the gene detection. Jiao Mu and Zhenglian Chen carried out the immunohistochemical study. Hongmei Dong conceived the case report and revised the manuscript.

Funding

This study was supported by Hebei Natural Science Foundation (Grant No. H2017405021) and National Natural Science Foundation of China (Grant No. 81471821).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Ethics approval and informed consent

This article does not contain any studies involving human participants or animals performed by the author. Informed consent was obtained from the patient’s father in the study.

References

  1. 1.
    Serrão T, Dias A, Nunes P, Figueiredo A. An uncommon presentation of EBV-driven HLH. Primary or secondary? An ongoing dilemma. BMJ Case Rep 2015;2015.Google Scholar
  2. 2.
    Liapis K, Apostolidis J, Delimpasis S. EBV-associated hemophagocytic syndrome. Am J Hematol. 2011;86:422.CrossRefPubMedGoogle Scholar
  3. 3.
    Antonodimitrakis P, Wassberg C, Gerovasileiou S, Back J, Hällgren R, Olsen B. Fulminant hemophagocytic lymphohistiocytosis secondary to a reactivated EBV infection: a case report. Ups J Med Sci. 2013;118:42–5.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Farquhar JW, Claireaux AE. Familial haemophagocytic reticulosis. Arch Dis Child. 1952;27:519–25.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Elstak E, Jong AD, Sluijs PVD. A platform for complementation and characterization of familial haemophagocytic lymphohistiocytosis 3 mutations. J Immunol Methods. 2011;365:58–66.CrossRefPubMedGoogle Scholar
  6. 6.
    Gholam C, Grigoriadou S, Gilmour KC, Gaspar HB. Familial haemophagocytic lymphohistiocytosis: advances in the genetic basis, diagnosis and management. Clin Exp Immunol. 2011;163:271–83.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bell MD, Wright RK. Fatal virus-associated hemophagocytic syndrome in a young adult producing nontraumatic splenic rupture. J Forensic Sci. 1992;37:1407–17.PubMedGoogle Scholar
  8. 8.
    Chute DJ, Rawley J, Cox J, Bready RJ. Sudden unexpected death due to hemophagocytic lymphohistiocytosis syndrome. J Forensic Sci. 2013;58(4):1080.CrossRefPubMedGoogle Scholar
  9. 9.
    Ondruschka B, Habeck JO, Hädrich C, Dreßler J, Bayer R. Rare cause of natural death in forensic setting: hemophagocytic syndrome. Int J Legal Med. 2016;130:777–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang JR, Liang XL, Jin R, Lu G. HLH-2004 protocol: diagnostic and therapeutic guidelines for childhood hemophagocytic lymphohistiocytosis. Chin J Contemp Pediatr. 2013;15:686.Google Scholar
  11. 11.
    Ishii E, Ueda I, Shirakawa R, Yamamoto K, Horiuchi H, Ohga S, et al. Genetic subtypes of familial hemophagocytic lymphohistiocytosis: correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions. Blood. 2005;105:3442.CrossRefPubMedGoogle Scholar
  12. 12.
    Feldmann J, Callebaut I, Raposo G, Certain S, Bacq D, Dumont C, et al. Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell. 2003;115:461.CrossRefPubMedGoogle Scholar
  13. 13.
    Santoro A, Cannella S, Bossi G, Gallo F, Trizzino A, Pende D, et al. Novel Munc13–4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. J Med Genet. 2006;43:953–60.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lewkowicz E, Darnige L, Auffret N, Damotte D, Andrieu JM, Jenabian A. Atypical skin lesions revealing an EBV-associated hemophagocytic syndrome after a large B cell lymphoma in complete remission. Leuk Lymphoma. 2007;48:421.CrossRefPubMedGoogle Scholar
  15. 15.
    Janka G, Stadt UZ. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2007;166:233–46.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyHebei North UniversityZhangjiakouPeople’s Republic of China
  2. 2.Department of Pathology, Liyuan Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  3. 3.Department of Forensic MedicineHebei North UniversityZhangjiakouPeople’s Republic of China
  4. 4.Department of Forensic MedicineTongji Medical College of Huazhong University of Science and TechnologyWuhanPeople’s Republic of China

Personalised recommendations