Clinical Guidance

Familial hemophagocytic lymphohistiocytosis (fHLH) is an immune deficiency characterized by the overactivation and excessive proliferation of T lymphocytes and macrophages, leading to infiltration and damage of organs including bone marrow, liver, spleen, and brain . Familial HLH usually presents as an acute illness with prolonged and high fever, cytopenias, and hepatosplenomegaly. Rash and lymphadenopathy are less common. Affected individuals may also exhibit liver dysfunction and neurologic abnormalities. Often fHLH-associated inflammation is triggered by infection, especially with herpes viruses, but it can manifest after infection with many other pathogens, or it can occur in the absence of any detectable infection .

Diagnostic Criteria

The diagnosis of familial hemophagocytic lymphohistiocytosis (fHLH) is based on suggestive clinical and laboratory findings and is established by identification of biallelic pathogenic variants in one of four genes: PRF1, STX11, STXBP2, and UNC13D.

Suggestive Findings

Familial HLH (fHLH) should be suspected in young children with the following clinical findings, supportive laboratory findings, and suggestive family history.

Clinical Findings

Common

Management Guidelines

No clinical practice guidelines specifically for familial hemophagocytic lymphohistiocytosis (fHLH) have been published; however, a report by the Steering Committee of the Histiocyte Society provides recommendations on the use of etoposide-containing therapies such as the HLH-94 protocol and hematopoietic stem cell transplantation (HSCT) for individuals with HLH, including those with fHLH . Evaluations Following Initial Diagnosis To establish the extent of disease and treatment needs in an individual diagnosed with fHLH, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Familial Hemophagocytic Lymphohistiocytosis: Recommended Evaluations Following Initial Diagnosis

Surveillance Guidelines

Individuals responding to treatment and HSCT are technically not at risk for other organ system involvement. Surveillance focuses on potential complications of HSCT. Surveillance for changes in neurologic manifestations, respiratory function, GI tract manifestations, renal function, and other systems is per standard of care by primary care health care providers or specialty clinicians.

Source: GeneReviews — "Familial Hemophagocytic Lymphohistiocytosis"