Additional testing and CXCL9

These tests can help with identifying HLH

Genetic testing takes time, and patients with HLH often require immediate treatment to control their hyperinflammation.¹ There are a range of other tests that can be conducted in the meantime to help identify potential underlying triggers and to help confirm or rule out an HLH diagnosis.

Flow cytometry testing

Screening studies for genetic causes of HLH²

Perforin/granzyme B

SLAM-associated protein (SAP) (for males)

Degranulation (CD107a) or T-cell degranulation

XIAP protein (for males)

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

Flow cytometry for perforin expression and CD107a have high specificity for identifying HLH with a genetic basis.³

Ancillary testing^2,4

Quantitative viral PCRs: EBV, CMV, adenovirus, HSV 1, HSV 2, etc

CT of chest, abdomen, and neck

Testing for tick- or mosquito-borne diseases

PET-CT followed by lymph node biopsy to evaluate for lymphoma

MRI of brain

Lyme disease

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

These tests can help identify an underlying trigger for patients with HLH, or to rule out other conditions.²

Other tests²

Complete blood counts

ALT, bilirubin

CXCL9

Fibrinogen/coagulation tests

Ferritin

IL-18

Triglycerides (fasting)

sCD25

ALT=alanine aminotransferase; CXCL9=chemokine (C-X-C motif) ligand 9; IL=interleukin.

These tests are useful for identifying the typical features of HLH.⁵ There is evidence suggesting that CXCL9 testing can be helpful for measuring the IFNγ levels in patients with HLH.⁶

CXCL9 and IFNγ

CXCL9 is a chemokine (a type of cytokine) released almost exclusively by IFNγ-activated macrophages. The primary function of CXCL9 is to attract T cells into inflamed tissues.⁶

CXCL9 being released from macrophages that have been activated by interferon gamma

Genetic testing

Learn more about genetic testing to help confirm a diagnosis of HLH.

Explore genetic testing

Managing HLH

Learn about the management strategies for HLH.

Explore management

References: 1. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041-4052. doi:10.1182/blood-2011-03-278127 2. Cincinnati Children’s Diagnosing HLH. Accessed October 23, 2023. https://www.cincinnatichildrens.org/service/h/hlh/clinical/test 3. Marsh RA, Haddad E. How I treat primary haemophagocytic lymphohistiocytosis. Br J Haematol. 2018;182(2):185-199. doi:10.1111/bjh.15274 4. Jongbloed EM, Hermans MAW, Wabbijn M, van Kampen JJA, van Laar JAM. HLH caused by an HSV-2 infection: a case report and review of the literature. Neth J Med. 2020;78(5):282-285. 5. Jordan MB, Allen CE, Greenberg J, et al. Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO). Pediatr Blood Cancer. 2019;66(11):e27929. doi:10.1002/pbc.27929 6. Sylvest S. From the Clinical Laboratories of the Cancer & Blood Diseases Institute. Cincinnati Children’s Hospital. Winter 2019;(15):1-4. 7. De Benedetti F, Prencipe G, Bracaglia C, Marasco E, Grom AA. Targeting interferon-γ in hyperinflammation: opportunities and challenges. Nat Rev Rheumatol. 2021;17(11):678-691. doi:10.1038/s41584-021-00694-z