Macrophage Activation Syndrome Session #ACR17

This morning, I was lucky enough to attend a session all about one of my biggest fears – Macrophage Activation Syndrome (MAS).

The first thing I found interesting was that the physician who presented this session – Rayfel Schneider from the University of Toronto – believes that SJIA and AOSD are essentially a spectrum. A person may have juvenile or adult onset and present essentially the same. Newer research over the last few years from leading pediatric rheumatologists – like Dr. Alexei Grom and others – have proven through various pieces of research that SJIA more closely resembles periodic fever syndromes and is autoinflammatory rather than autoimmune.

For those of you who aren’t familiar, MAS is one of the leading causes of death for people with Systemic Juvenile Idiopathic Arthritis (SJIA) or Adult Onset Still’s Disease (AOSD). This can also be a worry for people with SLE lupus or Kawasaki Disease. Otherwise, it’s rare to see MAS in conditions like other JIA subtypes, IBD, etc.

Macrophage Activation Syndrome isn’t well understood. Essentially, though, what MAS is a product of is a “highly stimulated but ineffective immune response.” This can be due to an infection or the underlying disease (SJIA, for example) itself.

Symptoms of MAS include increased fevers, higher ferritin levels, liver issues, cytopenia (low white and/or red blood cells), coagulopathy (difficulty to form blood clots), and hepatosplenomegaly (enlargement of both liver and spleen). Additionally, lymph nodes may swell and a patient’s mental state may change. They may also experience issues in a wide range of bodily systems, including neurological (from seizures to a coma), cardiac, pulmonary, and renal. Schneider explained MAS as a hyperinflammation and cytokine storm, leading to organ damage, multisystem failure, and, potentially, death. In fact, mortality in kids sits at 8-22%. For adults, that’s about 9%.

MAS is related to another condition – Hemophagocytic Lymphohistiocytosis (HLH). I won’t talk much about that for now, but MAS is thought to be one form of secondary HLH brought on as a part of another condition (again, SJIA). There are many types of secondary conditions like SJIA that could cause MAS, such as Epstein-Barr Virus and even some kinds of cancers. The thing I found most interesting about this was that one type of cancer Schneider pointed out was leukemia. In my personal journey, I was misdiagnosed with leukemia and given six weeks to live. It always seemed to me that my physicians had been grasping at straws to find a diagnosis, but this link makes much more sense now – especially when the majority of MAS cases present at SJIA onset. Research shows that 7-17% of SJIA patients will experience MAS.

From a lab standpoint, the following can be considered as potential situations for MAS development:

Decreasing

Increasing

Only recently has there been an effort to revamp the guidelines to diagnose MAS in SJIA patients. Unfortunately, while helpful, these guidelines may not be sensitive enough. Schneider says we should also look to the AOSD diagnostic criteria to make sure we’re paying closer attention to some of these lab values and symptoms.

Schneider played with some lab values, asking providers to think about how we can diagnose MAS earlier and get a head start on treating it. Possible treatments are an IL-1 inhibitor – Anakinra/Kineret has been shown to help a lot in higher doses during MAS episodes. Steroids may need to be given in high doses initially to help get the inflammation under control. A calcineurin inhibitor, such as cyclosporine, is a great tool to add as well.

It’s important to note that some medications – notably Ilaris and Actemra – can alter how MAS presents due to the effects of the drugs on the body. This must be kept in mind by the treating physicians in order to recognize the signs and treat MAS effectively.

New research is showing that interferon gamma (IFNγ) plays a pivotal role in MAS, most specifically CXCL9. Additionally, this can be linked to research that shows higher levels of IL-18 in the bloodstream of SJIA patients dealing with/who have gone through MAS. Understanding the links between CXCL9 and IL-18 – and how we can lower IL-18 – will be pivotal in treating MAS in the future.

The biggest takeaway for me is that MAS doesn’t show up as quickly as I’ve always personally feared. Watching friends and other SJIA patients struggle with MAS is scary, but knowing that we may be able to monitor and predict pre-MAS status is comforting. Furthermore, knowing that my rheumatologist will be open to this information and act upon it if/as needed really helps me feel less anxious. That’s part of why it’s important to snag a HCP that listens as well as mine does.

My secondary takeaway is to start monitoring my own labs more. When I get home, I’ll spend a while and plot my relevant labs into Excel and graph them. While it will help me keep tabs on things – especially concern over heading into MAS territory – maybe it’ll help me find more data around whatever weird neuro-ish thing I’ve been experiencing as well.

The world of rheumatic disease is one that’s ever-changing and improving. I think it will become incredibly important to focus on changing alongside it instead of staying stuck in the old ways like many providers and patients often do.