flare

With autoimmune arthritis (I specify that because osteoarthritis is completely different) symptoms can come and go.  When symptoms are at the worst they are said to be flaring.  It's not something we have really ever experienced until this weekend.

Emily had been off steroids a little over two weeks when we started to notice her rash come back and stay.  It has already been around (I say it is mocking me), but this time it was different because it was more prominent and itchy.

At her last infusion I noticed her lab numbers were not looking good; d-dimer and fertin where on the rise and hemoglobin was taking a dip, all classic symptoms.  So I called the Rheumatologist and asked if the rash and these labs meant that MAS was back.  MAS is macrophage activation syndrome (I wrote about it here) and it is scary because there is a 20% mortality rate associated with it if not treated.  About ten years ago MAS didn’t even have a name; it was a fever that killed because there was no treatment so it’s not something we like.

Sure enough we get a call back, it was MAS.  Hello steroids, it hasn’t been long enough.  We started her again on 2mls per day, not too bad, but enough to invite ‘roid rage back and increase her energy.  It wasn’t enough though, four days later the rash was worse and she was crying it was so itchy…ugh.  So we were told to raise the steroids to 3mls twice a day.  Not that bad, not the 10mls we were on, but it feels like we took one step forward (ending steroids) and two back (6mls a day was months ago).

It seems to be working.  Emily is her old self; she had not been acting right at all this past weekend so I knew something was up. 

Flares are common with this nasty disease and they can happen anytime.  The one thing I find assuring is that for the most part the worst part of the disease is the onset.  So hopefully Emily will never be that sick again.

Rheumatologist

We had our bi-weekly visit with Emily's Rheumatologist and my suspicions were right.  She's been more tired then usual and I had a feeling as we were weaning down on the steroids the disease was becoming more active and labs confirmed this.

There are two different inflammation markers the doctor looks at; one tells if MAS is coming back and one tells us about SOJIA and how active the disease itself is. 

It's now I have to remind myself there is no cure only control through medication.  The medication she is on right now is Prednisone, Cyclosporine, and Kineret.  Kineret is the long term medicine that is supposed to control everything and eventual be the only medicine she takes.  Prednisone is like a band aid medicine, it's what she got in the hospital because she was so very sick.  Prednisone reduced the inflammation quickly and controls it very well, but the side effects are pretty nasty (think best case two hip replacements eventually) and can be life threatening if taken too long so we have to get her off it as quickly as possible. 

We found out yesterday her D-dimer, white blood cell count and platelet counts were all elevated which means SOJIA is still with her and becoming more active as we wean down on the steroids.  Good news was her feritin levels were low, not normal, but not 24,000.  Normal is around 60, Emily's now is a little above 100.  In the hospital with MAS they were 24,000.  So anyways MAS is under control; SOJIA not so much.

I'm worried it's not working as well as we wanted it to, but happy we can try a different medicine.  This one is given via IV in the hospital twice a month.  They can also do labs at the same time so if the IV goes in well that means just two pokes a month...hallelujah!  There is a huge emotional toll that is being paid and if we can reduce that cost just a bit I will take it.  Let's just hope this new medicine works.

Macrophage Activation Syndrome

I failed to mention that one main reason Emily was in the hospital for so long was a diagnosis of Macrophage Activation Syndrome or MAS.  Mainly because it is incredibly difficult to understand let alone explain.  This is from Arthritis Today, Kids Get Arthritis Too Volume 11 Issue 4 By Mary Anne Dunkin.

As I understand it the cells that normally kill damaged cell or viruses get over activated and begin killing normal, healthy cells. 

What Is MAS?

Although not wide­ly recognized, MAS is a relatively common and potentially serious complication of rheumatic diseases in chil­dren, particularly systemic JIA, lupus and vasculitis, says Randy Q. Cron, MD, PhD, who helped diagnose Jacie’s condition and started treatment that may well have saved her life. The condition affects up to half of children with systemic JIA; as many as many as 7 percent to 10 percent of children with systemic JIA will develop a case severe enough to require hospitalization, he says.

The problem occurs when the immune system gets ramped up to fight an infection but then fails to slow back down when infec­tion has been eliminated, says Dr. Cron, director of the UAB Division of Pediatric Rheumatology. Normally, once an infection has been eliminated, white cells called CD8 T cells kill off the cells – typically macro­phages or dendritic cells – that stimulate the immune system to fight invaders. In MAS, a defect in this mechanism sends the immune system into overdrive, producing proteins, called cytokines, including tumor necrosis factor, interferon gamma and interleukin-1.

“When these proteins are in excess, you get what is called a cytokine storm,” says Dr. Cron. “This leads to this pro­longed fever but also leads to cells eating up other cells in the body. Macrophages go around engulfing other cells.”

As a result, blood cell counts fall, lead­ing to a problem known as pancytope­nia. In the worst cases, organs fail, which leads to death if not treated immediately.

New Findings Offer Understanding and Hope

For a doctor not familiar with MAS, it can be mistaken as septicemia, a life-threatening blood infection. But scien­tists have discovered the syndrome shares features with a genetic disorder called familial haemophagocytic lymphohis­tiocytosis (FHLH). Triggered by infec­tion during the first year of life, FHLH is almost always fatal unless the child receives a bone marrow transplant, says Dr. Cron.

To have FHLH, children must receive two mutated copies of one of the critical genes involved in cell lysis (killing), he says. Research in the past few years has revealed that children with MAS often have only one mutant copy of these same genes (e.g., perforin, MUNC 13-4, etc.), suggesting that the syndrome is actu­ally a milder form of FHLH, he says.

While this finding offers understand­ing that could eventually lead to improved therapies for both conditions, another find­ing with more immediate applications is that the biologic agent anakinra (Kiner­et) – which inhibits interleukin-1 (IL-1), a key cytokine produced in both system­ic JIA and MAS – is a rapid and effec­tive component of treatment for it.

“Typically, we use a combination of high-dose corticosteroids, cyclospo­rine and anakinra,” says Dr. Cron. “We are usually able to control it. Anakin­ra, at least for our group, has revolu­tionized the care for these kids.”

What Parents Need to Know – and Do

Although MAS can occur at any time during the course of rheumatic disease, research shows it commonly occurs short­ly after or even before or around the time of diagnosis. Parents should be aware of the condition because it can come on suddenly and become life-threat­ening very quickly, says Dr. Cron.

The main symptom that parents need to watch for is a high fever, he says. “Unlike the typical systemic JIA fever that occurs once (usually in the after­noon) or sometimes twice daily and comes back down, MAS tends to be a more continuous high-grade fever.”

Another sign of danger is the child is not as alert or as arousable, because MAS can affect the central nervous sys­tem, says Dr. Cron. Jaundice (yellow skin) is a sign that comes later, indicat­ing the condition is affecting the liver.

Parents who notice these symptoms should get their child to a doctor as soon as possible. Although there are numer­ous specialized tests for helping to diag­nose MAS, he says one simple and widely available blood test, a serum ferritin lev­el, is a good place to start. The test, which measures the amount of iron-contain­ing protein in the blood, is almost always highly elevated in children with MAS. “Other conditions can also elevate your fer­ritin, but usually not to the degree that it does in patients with MAS,” he says.

If your child is in the emergency room or sees a doctor who is unfamiliar with MAS, he recommends asking for a ferritin test. “There is no downside and it is remark­ably sensitive for picking this up,” he says.

Most of all, he says, be your child’s advocate. Be persistent in pursing the causes of your child’s symptoms.