Decoding the Enigma of Hemophagocytosis: A Guide to Diagnosis and Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Understanding Hemophagocytosis

Hemophagocytosis, also known as hemophagocytic lymphohistiocytosis (HLH), is a rare and potentially fatal immune disorder characterized by abnormal activation of immune cells, leading to severe inflammation and tissue damage. HLH can be classified into primary (genetic) and secondary (acquired) forms, with the latter often triggered by infections, malignancies, or autoimmune diseases (Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults).

Challenges in Diagnosing Hemophagocytosis

Diagnosing HLH can be challenging due to its rarity and diverse clinical presentations. The current diagnostic criteria for HLH, known as the HLH-2004 criteria, include clinical, laboratory, and histopathological findings. However, these criteria have been criticized for their lack of sensitivity and specificity, which can lead to delayed diagnosis and treatment (Accuracy of the criteria for hemophagocytic lymphohistiocytosis). Thus, a high index of clinical suspicion is crucial for early diagnosis and intervention, as illustrated by a case report of HLH secondary to acute B-cell lymphocytic leukemia (Hemophagocytic Lymphohistiocytosis Syndrome With Hepatic Involvement and Secondary to Acute B-cell Lymphocytic Leukemia: A Case Report).

Distinguishing Primary and Secondary Hemophagocytosis

It is essential to differentiate primary (genetic) HLH from secondary (acquired) HLH, as the treatment approach varies. For instance, a case of HLH due to visceral leishmaniasis highlights the importance of identifying the underlying cause and tailoring treatment accordingly (Hemophagocytic Lymphohistiocytosis as a Manifestation of Underlying Visceral Leishmaniasis). Genetic testing plays a pivotal role in distinguishing primary from secondary HLH and guiding treatment decisions.

Genetic Testing for Primary Hemophagocytosis

Primary HLH is caused by mutations in genes responsible for the normal functioning of immune cells, leading to impaired clearance of pathogens and uncontrolled inflammation. Genetic testing can identify these mutations and confirm the diagnosis of primary HLH. This information is crucial for guiding treatment decisions, such as allogenic hematopoietic stem cell transplantation, which has been shown to improve survival in patients with primary HLH (Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults).

Genetic Testing in Family Members

As primary HLH is a genetic disorder, genetic testing can also be useful for identifying at-risk family members, particularly siblings of affected individuals. Early identification of at-risk individuals allows for closer monitoring and timely intervention if symptoms develop.

Genetic Testing for Treatment Selection

Genetic testing can help guide treatment decisions in patients with HLH. In primary HLH, identifying the specific gene mutation can provide information on the severity of the disease and the likelihood of response to certain treatments, such as immunosuppressive medications or hematopoietic stem cell transplantation. In secondary HLH, genetic testing can help rule out primary HLH and direct clinicians towards identifying and treating the underlying cause of the disorder.

Conclusion

Hemophagocytosis is a rare and potentially fatal immune disorder that requires prompt diagnosis and targeted treatment. Genetic testing plays a critical role in distinguishing primary from secondary HLH, guiding treatment decisions, and identifying at-risk family members. Greater awareness and understanding of this complex disorder, along with advancements in genetic testing, can help improve outcomes for patients with hemophagocytosis.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)