Synonyms

HLH 

Brief Description

A rare disorder which has many genetic causes.  It  is characterized by multi-system inflammation and is   potentially fatal disease of normal but overactive histiocytes and lymphocytes that commonly appears in infancy,  although it has been seen in all age groups.

Defect

Blood cell and immune cell   (Gene defect includes, chromosome 9; mutation on perforin gene 10q22;mutation in UNC13D gene; mutation STX11; mutation in STXBP-2)

Manifestation

  • Fever, hepatosplenomegaly, pancytopenia, lymphadenopathy, and rash often comprise the initial presentation.
  • Clinical findings, including evidence of infection due to decreased immunity and white cell killing defects, easy bruisability, and pallor.
  • Jaundice is often present due to hyperbilirubinemia.

Incidence

1 case per every 50,000 births.

Inheritance

heterogeneous autosomal recessive disorder found to be more prevalent with parental consanguinity

Diagnosis

Diagnosis was based on five criteria

  • fever
  • splenomegaly
  • bicytopenia
  • hypofibrinogenemia and
  • hemophagocytosis

In HLH-2004 three additional criteria are introduced

  • low/absent NK-cell-activity
  • hyperferritinemia
  • high-soluble interleukin-2-receptor levels

Altogether five of these eight criteria must be fulfilled, unless family history or molecular diagnosis is consistent with HLH.

Prognosis

Familial hemophagocytic lymphohistiocytosis is uniformly fatal if not treated; the median survival time reported in various studies is 2-6 months after diagnosis.

Treatment/Management

  • Patients who  are classified to be high risk should receive or undergo etoposide therapy treatment.
  • Subsequent  hematopoietic stem cell transplantation (HSCT) is recommended for patients with familial disease or molecular diagnosis, and patients with severe and persistent, or reactivated, disease
  • Low risk can be treated with cyclosporine, corticosteroid or IVIG   intravenous immunoglobulin (IVIG) was effective in suppressing symptoms when administered within hours of disease onset.
  • Bone Marrow Transplantation

References