Hemophagocytic Syndrome

Classification of Histiocytic Disorders

Benign Disorders with Variable Biologic Behavior

Dendritic Cell-Related Disorders

  • Langerhans Cell Histiocytosis (LCH) (see Langerhans Cell Histiocytosis, [[Langerhans Cell Histiocytosis]])
  • Erdheim-Chester Disease (ECD)
  • Juvenile Xanthogranuloma (JXG)
  • Solitary Histiocytomas with Juvenile Xanthogranuloma Phenotype
  • Secondary Dendritic Cell Disorders

Macrophage-Related Disorders

Other

  • Rosai-Dorfman Disease (RD): sinus histiocytosis with massive lymphadenopathy
  • Solitary Histiocytoma of Macrophage Phenotype

Malignant Disorders

  • Monocyte-Associated
    • Leukemias
      • Acute Monocytic Leukemia (M5A, M5B)
      • Acute Myelomonocytic Leukemia (M4)
      • Chronic Myelomonocytic Leukemia
    • Extramedullary Monocytic Tumor or Sarcoma
  • Dendritic Cell-Related Histiocytic Sarcoma: localized or disseminated
  • Macrophage-Related Histiocytic Sarcoma: localized or disseminated

Epidemiology

  • History: first described in 1939
  • Association with Infection
    • Both sporadic and familial cases of HLH may be precipitated by acute infections
    • HLH may mimic severe sepsis and leptospirosis
    • HLH may obscure the diagnosis of a precipitating, treatable infectious illness (as has been reported for visceral leishmaniasis)

Physiology

  • xxxx

Clinical-Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis (HLH) [MEDLINE]

Diagnostic Requirements

  • Molecular Diagnosis Consistent with HLH or at Least 5 of the Below Criteria

Criteria

  • Fever (see Fever, [[Fever]]): typically persistent and/or daily
  • Splenomegaly (see Splenomegaly, [[Splenomegaly]])
  • Bicytopenia
    • Anemia: Hb <9 g/dL
    • Theombocytopenia: platelets <100k
    • Leukoepenia/Neutropenia
  • Hypertriglyceridemia and/or Hypofibrinogenemia
  • Hemophagocytosis in bone marrow/Spleen/Lymph Node/Cerebrospinal Fluid
  • Low or Absent NK Cell Function: present in approximately 50% of HLH patients
  • Hyperferritenemia (see Hyperferritinemia, [[Hyperferritinemia]]): >500 mg/L
  • Soluble CD25 (IL2Ra) Above Normal Limit for Age

Clinical Manifestations

Clinical Features

  • Fever: 60-100% of cases
  • Splenomegaly: 35-100% of cases
  • Hepatomegaly : 39-97%% of cases
  • Lymphadenopathy: 17-52%% of cases
  • Rash: 3-65% of cases
    • Maculopapular: most common pattern
    • Nodular: occasional pattern
  • Neurologic Symptoms: 7-47% of cases
    • Seizures (see Seizures, [[Seizures]])
    • Encephalopathy/Delirium (see Delirium, [[Delirium]])
    • Meningismus

Laboratory Features

  • Brain MRI Focal Areas of Inflammation
  • Cerebrospinal Fluid (CSF) Pleocytosis
  • Cytopenias
    • Anemia: 89-100% of cases)
    • Neutropenia: 58-87%% of cases
    • Thrombocytopenia: 82-100% of cases
  • Hemophagocytosis: in bone marrow, liver, or lymph nodes
  • Hyperbilirubinemia: 74% of cases
    • Jaundice
  • Hypofibrinogenemia: 19-85% of cases
  • Hypertriglyceridemia: 59-100% of cases
  • Hyperferritinemia (see Hyperferritenemia, [[Hyperferritenemia]])

Treatment

  • xxx

References

  • Mumps virus-associated hemophagocytic syndrome. Emerg Infect Dis. 2005 Feb. Available from http://wwwnc.cdc.gov/eid/article/11/2/04-0993.htm
  • Virus associated hemophagocytic syndrome. Cancer. 1979;44:993-1002
  • Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. 1997 Sep;29(3):157-66 [MEDLINE]
  • Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000;6:601-8
  • Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S82-9. doi: 10.1016/j.bbmt.2009.11.014. Epub 2009 Nov 22 [MEDLINE]