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familial hemophagocytic lymphohistiocytoses

FHLs, HPLH, HLH, familial erythrophagocytic lymphohistiocytosis, familial hemophagocytic lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, fatal disorder of early infancy.

- sudden-onset fever
- visceral lymphohistiocytic infiltration
- meningeal lymphohistiocytic infiltration
- hepatic anomalies

  • hepatic failure
  • hepatosplenomegaly
  • hepatorenal failure
  • portal infiltrates of T lymphocytes
  • portal infiltrates of histiocytes
  • periportal infiltrates of T lymphocytes
  • periportal infiltrates of histiocytes
  • activation of the hepatic mononuclear phagocytic system
  • focal hemophagocytosis
  • loss of interlobular bile ducts (biliary ductopenia)
  • paucity of bile ducts (biliary ductopenia)

Loci

- HLH1: at 9q21.3-q22
- HLH2 at 10q21-q22: mutations in the gene encoding perforin (PRF1) (MIM.170280)
- HLH3 at 17q25.1: mutations in the UNC13D gene (MUNC13-4)(MIM.608897)
- HLH4 at 6q24: mutations in syntaxin-11 (STX11) (MIM.605014)

Differential diagnosis

- Omenn syndrome (familial reticuloendotheliosis with eosinophilia) (MIM.603554)

- Faisalabad histiocytosis (hemophagocytic lymphohistiocytosis with sensorineural deafness and joint contractures) (MIM.602782)

- Griscelli disease: GS1 (MIM.214450), GS2 (MIM.607624), GS3 (MIM.609227)

References

- Hong W. Cytotoxic T lymphocyte exocytosis: bring on the SNAREs! Trends Cell Biol. 2005 Dec;15(12):644-50. PMID: 16260137

- Kapelari K, Fruehwirth M, Heitger A, Konigsrainer A, Margreiter R, Simma B, Offner FA. Loss of intrahepatic bile ducts: an important feature of familial hemophagocytic lymphohistiocytosis. Virchows Arch. 2005 Jun;446(6):619-25. PMID: 15906086

- Kakkar N, Vasishta RK, Banerjee AK, Marwaha RK, Thapa BR. Familial hemophagocytic lymphohistiocytosis: an autopsy study. Pediatr Pathol Mol Med. 2003 May-Jun;22(3):229-42. PMID: 12746174

- de Saint Basile G, Fischer A. The role of cytotoxicity in lymphocyte homeostasis. Curr Opin Immunol. 2001 Oct;13(5):549-54. PMID: 11544002

- Ost A, Nilsson-Ardnor S, Henter JI. Autopsy findings in 27 children with haemophagocytic lymphohistiocytosis. Histopathology. 1998 Apr;32(4):310-6. PMID: 9602326

- Favara BE. Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. Semin Diagn Pathol. 1992 Feb;9(1):63-74. PMID: 1561489

- Wieczorek R, Greco MA, McCarthy K, Bonetti F, Knowles DM 2nd. Familial erythrophagocytic lymphohistiocytosis: immunophenotypic, immunohistochemical, and ultrastructural demonstration of the relation to sinus histiocytes. Hum Pathol. 1986 Jan;17(1):55-63. PMID: 3080365

- Akima M, Sumi SM. Neuropathology of familial erythrophagocytic lymphohistiocytosis: six cases and review of the literature. Hum Pathol. 1984 Feb;15(2):161-8. PMID: 6698535