Understanding Macrophage Activation Syndrome and Cytokine Storm

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• What is Macrophage Activation Syndrome?
• Terminology and Naming Conventions
• Rheumatologic Origins of MAS
• Pathophysiology and Cell Activation
• Diagnostic Criteria and Clinical Markers
• Full Transcript

What is Macrophage Activation Syndrome?

Macrophage activation syndrome (MAS) is a severe and life-threatening complication of rheumatic diseases. Dr. Randy Cron, MD, describes it as a form of secondary hemophagocytic lymphohistiocytosis (HLH). This condition represents a hyperinflammatory state where the immune system becomes dangerously overactive.

Dr. Anton Titov, MD, initiates the discussion by asking for a clear definition of this complex syndrome. The conversation highlights the clinical urgency of recognizing and treating MAS promptly.

Terminology and Naming Conventions

The medical field uses multiple names for this hyperinflammatory condition, which can cause confusion. Dr. Randy Cron, MD, explains that "cytokine storm syndrome" was chosen as the title for his textbook to create a more accessible term. This phrase is easier for both physicians and the public to understand compared to the jargon-heavy historical names.

HLH, or hemophagocytic lymphohistiocytosis, is a term originating from hematology-oncology. It was first used by cancer doctors treating a genetic form of the disease that presents in infancy. Dr. Randy Cron, MD, notes that while the names are similar, the processes are not entirely identical.

Rheumatologic Origins of MAS

Macrophage activation syndrome is the term adopted by rheumatologists when this condition occurs in their patient population. Dr. Randy Cron, MD, specifies that MAS is most commonly seen in association with Still's disease in adults and systemic juvenile idiopathic arthritis (SJIA) in children.

This classification distinguishes it from the familial or cancer-associated forms of HLH. Dr. Cron positions MAS under the broader "cytokine storm syndrome" umbrella, viewing it as a unifying concept rather than a separate entity.

Pathophysiology and Cell Activation

The core of macrophage activation syndrome involves the extreme activation of immune cells. Dr. Randy Cron, MD, describes how macrophages become activated and transform into cells called histiocytes. These overly active cells can be observed in bone marrow biopsies and other tissues.

A hallmark of this process is hemophagocytosis, where these activated histiocytes engulf other blood cells, including red blood cells and white blood cells. This visible phenomenon under the microscope is a key pathologic feature of the disease.

Diagnostic Criteria and Clinical Markers

Diagnosing macrophage activation syndrome relies on a combination of clinical and laboratory findings. Dr. Randy Cron, MD, explains that the presence of hemophagocytes is a marker used in several classification or diagnostic criteria for cytokine storm syndromes.

However, he cautions that this finding is neither highly sensitive nor highly specific. Diagnosis therefore depends on a broader set of indicators, including ferritin levels, fever, cytopenias, and other signs of systemic inflammation. Dr. Anton Titov, MD, discusses the importance of these criteria for clinicians.

Full Transcript

Dr. Anton Titov, MD: What is macrophage activation syndrome? It's also known as secondary hemophagocytic lymphohistiocytosis. HLH is easier to pronounce?

Dr. Randy Cron, MD: Unfortunately, like a lot of things in medicine, there are multiple names for similar things that are not identical. One of the reasons we titled our textbook that came out right before the pandemic "Cytokine Storm Syndrome" was to use it as a relatively easy thing to roll off the tongue and for people to kind of wrap their heads around, whether it be other physicians who hadn't heard of it or just the lay public.

Storm and syndrome are pretty straightforward. A cytokine is a new term for most people, but it's not all that complicated. So HLH, like you said, it's a mouthful. It's jargon to the general public. Macrophage activation syndrome is not horrific, but it's not great either.

Unfortunately, HLH was termed mostly by hemato-oncologists or the clinicians who are using chemotherapy. These were primarily cancer doctors who were taking care of this familial or genetic form that presents in infancy.

Dr. Anton Titov, MD: When rheumatologists saw this occurring in their conditions, whether it be Still's disease in the adult or systemic juvenile idiopathic arthritis or SJIA for short in children, where it's most commonly seen in kids, it got termed macrophage activation syndrome. And so it's a similar process, not identical.

Dr. Randy Cron, MD: But at least in my mind, MAS is a lumper of these diseases, as opposed to a splitter. I see them under this broader cytokine storm syndrome umbrella, but it's really just the term that the rheumatologists use.

As part of this process, your macrophages do get activated. They become these cells called histiocytes, and you can see them in the bone marrow or in other places you may biopsy. They're activated to a point where they're engulfing other cell types, red cells and white blood cells.

It's a marker. It's not highly sensitive or highly specific, but it is a marker of the disease process. Macrophage activation syndrome is used in a couple of the different classification or diagnostic criteria for cytokine storm syndromes, the presence of these hemophagocytes or these overly activated macrophages.