Testing for primary HLH

Additional testing and CXCL9 in primary HLH

When it comes to treating primary hemophagocytic lymphohistiocytosis (HLH), there’s no time to wait. Prior to receiving genetic testing results, other assessments can help you determine the likelihood of primary HLH so that you can initiate treatment as soon as possible.1

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Flow cytometry testing

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Decreased levels of the following can help identify a genetic cause1,2

Perforin/granzyme B

  • A reduction or absence of perforin is suggestive of a biallelic PRF1 mutation2

Degranulation (CD107a) or T-cell degranulation

  • Decreased CD107a expression is suggestive of mutations in genes involved in the cytotoxic degranulation pathway, which includes UNC13D, STXBP2, STX11, RAB27A, LYST, and AP3B12

SLAM-associated protein (SAP) (for males)

  • A reduction or absence of SLAM-associated protein is suggestive of an SH2D1A mutation2

XIAP protein (for males)

  • A reduction or absence of XIAP protein is suggestive of a XIAP/BIRC4 mutation2

CD=cluster of differentiation; SLAM=signaling lymphocytic activation molecule; XIAP=X-linked inhibitor of apoptosis protein.

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Flow cytometry for perforin expression and CD107a have high specificity for identifying primary HLH1

Ancillary testing1,3

Specialized labs:

Coagulation tests:

Infectious workups:

Imaging:

Procedures:

  • CXCL9
  • Prothrombin time/partial thromboplastin time
  • D-dimers
  • Viral PCRs
    • EBV
    • CMV
    • Adenovirus
  • Test for tick- or mosquito-borne diseases in areas at risk
  • Lyme disease
  • PET-CT to rule out lymphoma
  • CT of chest/abdomen/neck
  • MRI of brain
  • Spinal fluid analysis
  • Bone marrow aspiration and biopsy
Specialized labs:
  • CXCL9
Coagulation tests:
  • Prothrombin time/partial thromboplastin time
  • D-dimers
Infectious workups:
  • Viral PCRs
    • EBV
    • CMV
    • Adenovirus
  • Test for tick- or mosquito-borne diseases in areas at risk
  • Lyme disease
Imaging:
  • PET-CT to rule out lymphoma
  • CT of chest/abdomen/neck
  • MRI of brain
Procedures:
  • Spinal fluid analysis
  • Bone marrow aspiration and biopsy

CMV=cytomegalovirus; CT=computed tomography; EBV=Epstein-Barr virus; MRI=magnetic resonance imaging; PCR=polymerase chain reaction; PET=positron emission tomography.

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It is important to rule out other conditions such as malignancy, viral infection, and underlying rheumatic disease in all suspected cases of primary HLH.4,5