What is the Difference Between HLH and MAS

The key difference between HLH and MAS is that HLH (hemophagocytic lymphohistiocytosis) is a severe, life-threatening hematologic disease, while MAS (macrophage activation syndrome) is a severe, life-threatening rheumatic disease.

Cytokine storm is also known as hypercytokinemia. It is a physiological reaction in humans and other animals in which the innate immune system triggers an uncontrolled and excessive release of cytokines. Cytokines are pro-inflammatory signaling molecules. However, the sudden release of cytokines in large quantities can cause multisystem organ failure. HLH and MAS are two medical conditions that can cause cytokine storms.

CONTENTS

1. Overview and Key Difference
2. What is HLH  
3. What is MAS
4. Similarities – HLH and MAS
5. HLH vs MAS in Tabular Form
6. Summary – HLH vs MAS

What is HLH (Hemophagocytic Lymphohistiocytosis) ?

HLH (hemophagocytic lymphohistiocytosis) is an uncommon hematologic disorder often seen more in children than in adults. It is a life-threatening disease. It causes severe hyper inflammation through the proliferation of activated lymphocytes and macrophages. Normally, HLH is characterized by the proliferation of morphologically benign lymphocytes and macrophages, which secrete excessive amounts of inflammatory cytokines. Therefore, HLH is classified as a cytokine storm syndrome.

There are inherited and non-inherited causes for hemophagocytic lymphohistiocytosis. Moreover, there are two types of HLH: primary and secondary. Primary HLH is caused by inactivating mutations in genes that code for proteins that cytotoxic T cells and NK cells use to kill targeted infected cells. The mutated genes include UNC13D, STX11, RAB27A, LYST, PRF11, SH2DIA, BIRC4, ITK, CD27, and MAGT1. The secondary HLH is associated with malignant and non-malignant diseases that weaken the ability of the immune system to attack EBV-infected cells. The malignant diseases include T cell lymphoma, B cell lymphoma, acute lymphocytic leukemia, etc. Non-malignant diseases, on the other hand, include autoimmune disorders such as juvenile idiopathic arthritis, juvenile Kawasaki disease, systemic lupus erythematosus, etc.

HLH symptoms include fever, enlargement of the liver and spleen, enlarged lymph nodes, yellow discoloration of the skin and eyes, and rash. This medical condition can be diagnosed with physical examination, blood testing, and molecular testing for gene mutations. The treatment regime for this disease includes corticosteroids, immune suppressant drugs (cyclosporine, methotrexate), chemotherapy medications (etoposide, vincristine), intravenous immunoglobulin, cytokine targeted therapy, anti-IFN gamma monoclonal antibody, (emapalumab), and modified recombinant interleukin 1 receptor antagonist (Anakinra).

What is MAS (Macrophage Activation Syndrome)?

Macrophage activation syndrome (MAS) is a severe, life-threatening rheumatic disease. It is a chronic rheumatic disease of childhood. It occurs commonly with systemic-onset juvenile idiopathic arthritis. It is also associated with systematic lupus erythematosus, Kawasaki disease, and adult-onset Still’s diseases. MAS is also thought to be very similar to secondary hemophagocytic lymphohistiocytosis. The cause of this disease is often a viral infection or a medication.

The symptoms of this disease include continuous fever, feeling tired and low energy, headache, confusion, large lymph nodes, large liver and spleen, bleeding and clotting problems, changes in blood pressure, and low blood count. Diagnosis of MAS is through blood testing, bone marrow aspirate, and imaging testing (X-ray, ultrasound, CT-SCAN, MRI). The treatment options usually include steroids (glucocorticoids), intravenous immune globulins, cyclosporine (immune suppressant), biologic therapy (Anakinra), and anticancer drug.

What are the Similarities Between HLH and MAS?

• HLH and MAS are two medical conditions that can cause a cytokine storm.
• Both diseases predominantly affect children.
• Secondary HLH pathophysiologically is similar to MAS.
• Both diseases are associated with juvenile idiopathic arthritis, juvenile Kawasaki disease, and systemic lupus erythematosus,
• They have similar treatment options.

What is the Difference Between HLH and MAS?

HLH is a severe, life-threatening hematologic disease while MAS is a severe, life-threatening rheumatic disease. Thus, this is the key difference between HLH and MAS. Furthermore, there are inherited and non-inherited causes for HLH, but there are only non-inherited causes for MAS.

The below infographic presents the differences between HLH and MAS in tabular form for side by side comparison.

Summary – HLH vs MAS

HLH and MAS are two medical conditions that can cause cytokine storms in the body. Children are predominately affected by both conditions. HLH is a severe, life-threatening hematologic disease, while MAS is a severe, life-threatening rheumatic disease. So, this summarizes the difference between HLH and MAS.

Reference:

1. “Macrophage Activation Syndrome.” An Overview | ScienceDirect Topics.
2. “Hemophagocytic Lymphohistiocystosis.” Johns Hopkins Medicine.

Image Courtesy:

1. “Hemophagocytic syndrome – cropped – very high mag” By Nephron – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “NLRC Mutations Cause Macrophage Activation Syndrome” By National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH (CC BY-NC-SA 2.0) via Flickr