Which histiocytosis disorders are classified as H Group (hemophagocytic lymphohistiocytosis)?

Updated: Sep 16, 2020
  • Author: Cameron K Tebbi, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP  more...
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The H group includes the following:

  • Primary hemophagocytic lymphohistiocytosis (HLH) - Mendelian-inherited condition
  • Secondary HLH - HLH that is apparently non-Mendelian

Primary HLH

This includes the following:

  • HLH associated with lymphocyte cytotoxic defects - Familial hemophagocytic lymphohistiocytosis type 2 (FHL2 [ PRF1]), FHL3 ( UNC13D), FHL4 ( STX11), FHL5 ( STXBP2), X-linked lymphoproliferative disease type 1 (XLP1 [ SH2D1A]),  Griscelli syndrome type 2 ( RAB27A),  Chediak-Higashi syndrome ( LYST)​
  • HLH associated with abnormalities of inflammasome activation - XLP2 ( BIRC4), NLRC4
  • HLH associated with defined Mendelian disorders affecting inflammation - Lysinuric protein intolerance ( SLC7A7), HMOX1, other defined Mendelian disorders affecting inflammation
  • Familial (apparently Mendelian) hemophagocytic lymphohistiocytosis of unknown origin

Secondary HLH - infection associated

Infection-associated secondary HLH includes the following:

  • Viral - Epstein-Barr virus, cytomegalovirus, herpes, human immunodeficiency virus, influenza
  • Bacterial
  • Fungal
  • Parasitic agents

Secondary HLH - malignancy associated

Malignancy-triggered HLH occurring at the onset of malignancy is associated with the following:

  • Hematologic malignancies - T-cell lymphoblastic leukemia/lymphoma, T-cell non-lymphoblastic lymphomas, B-cell leukemias, B-cell lymphomas (non-Hodgkin), Hodgkin lymphomas, NK-cell lymphomas/leukemias, myeloid neoplasia, other hematologic malignancies
  • Solid tumors 
  • Unclassified malignancies

Other malignancy-associated forms of HLH include the following:

  • HLH occurring during chemotherapy - Unassociated with the initial malignancy diagnosis
  • HLH associated with a malignancy but not further defined

Secondary HLH associated with rheumatologic conditions

This includes HLH associated with the following:

  • Systemic onset juvenile idiopathic arthritis
  • Adult-onset Still disease
  • Systemic lupus erythematosus
  • Vasculitis
  • Additional defined or undefined autoimmune conditions

Secondary HLH - other types

  • Transplant-related HLH
  • HLH associated with iatrogenic immune activation 
  • HLH associated with iatrogenic immune suppression
  • HLH associated with other apparently non-Mendelian conditions
  • HLH of unknown/uncertain origin

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