Navigating the diagnostic process

For patients with HLH, prompt diagnosis is crucial

Hemophagocytic lymphohistiocytosis (HLH) is heterogeneous, rapidly progressive, and can be fatal if untreated. It’s critical to ensure that patients are diagnosed as soon as possible.¹

It’s also essential to identify any underlying triggers that can be associated with the development of HLH in patients.¹

These potential triggers can include¹:

Genetic abnormalities

Infections

Malignancies

Rheumatologic diseases

The presence or absence of certain triggers will influence the management strategies you will pursue.²

Diagnosing primary HLH

There are 3 recognized options for making a possible diagnosis of primary HLH. These options include³:

The fulfillment of 5 of the 8 HLH-2004 criteria in the absence of an underlying cause, such as malignancy.

or

A positive genetic test for mutations associated with primary HLH.

or

Family history consistent with primary HLH.

It can be challenging to navigate the diagnostic process while also trying to manage a patient’s condition. Explore the sections below for some guidance that you may find helpful.

Things to consider when seeking a diagnosis

The HLH-2004 diagnostic criteria

The HLH-2004 diagnostic criteria provides a list of physical assessments and labs to consider when suspecting a diagnosis of HLH. See how you can apply the HLH-2004 diagnostic criteria to your patients here.

See the diagnostic criteria

Genetic testing for HLH

A variety of genetic abnormalities are identified as being associated with the development of HLH. Learn more about the genetic testing for HLH here.

Explore genetic testing

Flow cytometry, ancillary testing, and CXCL9

Additional testing can be performed to help you confirm or rule out a diagnosis of HLH. Find out more about helpful testing strategies here.

Additional testing guidance

View this flash card for information about differential diagnosis between HLH and another condition that can mimic its presentation: sepsis.

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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. George MR. Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med. 2014;5:69-86. doi:10.2147/JBM.S46255 3. Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039

Diagnosing HLH