Is there a difference between Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS)?

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From the Guidelines

Difference between Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS)

Yes, there is a difference between Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS). While both conditions involve excessive immune system activation, they have distinct clinical and pathological features. HLH is a rare, life-threatening disorder characterized by uncontrolled proliferation of lymphocytes and histiocytes, leading to tissue damage and organ dysfunction. MAS, on the other hand, is a subtype of HLH that is often associated with autoimmune or inflammatory conditions, such as systemic juvenile idiopathic arthritis 1.

Clinical Features and Treatment

The clinical features of HLH and MAS can overlap, making diagnosis challenging. HLH is typically characterized by fever, cytopenia, liver dysfunction, and a sepsis-like syndrome, while MAS is often associated with symptoms such as fever, multiorgan dysfunction, and CNS issues 1. In terms of treatment, HLH is typically managed with a combination of immunosuppressive medications, including etoposide, dexamethasone, and cyclosporine 1. In contrast, MAS is often treated with high-dose corticosteroids, such as methylprednisolone, and may also require additional immunosuppressive agents, such as anakinra or tocilizumab 1.

Key Differences in Treatment Approach

  • HLH: Typically managed with etoposide (150-200 mg/m² on days 1,3, and 5), dexamethasone (10 mg/m² on days 1-5), and cyclosporine (6 mg/kg/day) 1.
  • MAS: Often treated with high-dose corticosteroids, such as methylprednisolone (1 g/d for 3-5 consecutive days), and may also require additional immunosuppressive agents, such as anakinra (2-6 mg/kg up to 10 mg/kg per day) or tocilizumab 1.

Importance of Early Recognition and Diagnosis

Early recognition and diagnosis of HLH and MAS are essential for efficacious management. A personalized and graded treatment approach is advised, taking into account the individual patient's response and underlying condition 1.

From the Research

Difference between Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS)

  • HLH is a life-threatening clinical syndrome that occurs in many underlying conditions and in all age groups, characterized by a severe, uncontrolled hyperinflammatory reaction 2.
  • MAS is also known as secondary HLH (sHLH) and is a distinct entity that complicates hematologic malignancies, autoimmune disorders, and infections mainly of viral origin 3.
  • Both HLH and MAS are characterized by the uncontrolled activation of cytotoxic T lymphocytes, NK cells, and macrophages, resulting in an overproduction of pro-inflammatory cytokines 4, 5.
  • The main features of MAS include fever, hepatosplenomegaly, hepatobiliary dysfunction, coagulopathy, cytopenia of two to three cell lineages, increased triglycerides, and hemophagocytosis in the bone marrow 3.
  • HLH can be primary (familial) or secondary, while MAS is a type of secondary HLH 3, 5.
  • The treatment of HLH and MAS differs, with familial HLH requiring hematopoietic stem cell transplantation, while MAS is treated with glucocorticoids, IL-1 blockade, or cyclosporine A 2, 6.
  • The prognosis of HLH and MAS is generally poor, especially in adults, with high mortality rates 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hemophagocytic lymphohistiocytosis: pathogenesis and treatment.

Hematology. American Society of Hematology. Education Program, 2013

Research

Hemophagocytic Lymphohistiocytosis.

Annual review of pathology, 2018

Research

Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy.

Best practice & research. Clinical rheumatology, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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