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Hemophagocytic Lymphohistiocytosis (HLH)

Life-threatening hyperinflammatory syndrome driven by uncontrolled immune activation

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Hematoloji department. Book Appointment →

What is Hemophagocytic Lymphohistiocytosis (HLH)?

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome resulting from uncontrolled activation of innate immunity. It exists in primary (genetic) and secondary (acquired) forms, with secondary HLH triggered by infections, malignancies, or autoimmune disease.

Diagnosis follows the HLH-2004 criteria: fever, splenomegaly, bicytopenia or pancytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis on biopsy, low NK-cell activity, elevated ferritin (>500 ng/mL), and elevated soluble IL-2 receptor (sCD25). Ferritin above 10,000 ng/mL has high predictive value for HLH.

The HLH-94/2004 backbone (dexamethasone, etoposide, and cyclosporine A) remains the cornerstone of treatment. Emapalumab (anti-interferon-gamma antibody) is FDA-approved for primary HLH, and ruxolitinib has emerging evidence in refractory disease. Concurrent treatment of the underlying trigger (infection control, malignancy therapy) is essential.

Symptoms

Persistent high fever
Hepatosplenomegaly
Pancytopenia involving multiple cell lines
Markedly elevated ferritin levels
Coagulopathy with bleeding manifestations
Jaundice and progressive liver failure

Risk Factors

Primary immunodeficiency (e.g., perforin deficiency)
Epstein-Barr virus and other viral infections
Hematologic malignancies, especially T- and NK-cell lymphomas
Autoimmune disease such as systemic JIA or SLE
Use of immunosuppressive therapy

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Unexplained high fever combined with pancytopenia
  • Rapid and marked rise in ferritin levels
  • Signs of multi-organ failure

Treatment Methods

01
HLH-2004 protocol (dexamethasone, etoposide, cyclosporine A)
02
Emapalumab (anti-IFN-gamma) for primary HLH
03
Ruxolitinib (JAK1/2 inhibitor) in refractory cases
04
Targeted therapy for the underlying trigger
05
Allogeneic hematopoietic stem cell transplant (curative in primary HLH)
06
Intensive care support

Which Department to Visit?

You can visit our Hematoloji department for these complaints. Our specialist physicians will create the most suitable treatment plan for you.

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Health Disclaimer: The information on this page is prepared for general informational purposes only. It does not replace medical diagnosis and treatment. Please consult your physician for your complaints. Saygı Hospital does not accept responsibility for actions taken based on the information on this page.