(Editor’s Note: This article was written by Regina Minerva about her daughter’s journey with SJIA & MAS)
At 13 months old Julianna was diagnosed with SJIA in July of 2017 after 15 days of consecutive quotidian fever and rash. A diagnosis of SJIA was made after ruling out infectious diseases, Kawasaki disease, and malignancy. Joint inflammation & arthritis never presented as one of her symptoms, but doctors warned us that it could take months or years for arthritis to appear.
The First Year and learning the word “Refractory”
On September 1, 2017, after she received her first dose of Anakinra we instantly had our “normal“ little girl back. The fevers stopped and the rash disappeared and we tried to resume our daily lives. Looking back now, after two years of life with SJIA, I realize the course of Julianna’s disease was far from “normal”, she is what doctors describe as having “Subclinical-MAS” and “Refractory SJIA” in that she doesn’t fully respond to biologics.
After she did well on Anakinra, we slowly tapered prednisolone over the next year. Things seemed great to us… but they really weren’t. Julianna’s labs and inflammation markers never normalized. Her inflammation markers; Ferritin, ESR, CRP, LDH, D-Dimer were always elevated, sometimes more, sometimes less, even though she appeared “clinically well”.
I didn’t realize then that nightly breakthrough fevers meant her disease wasn’t fully controlled by her biologic. I just assumed that this is what SJIA life would be- that having SJIA meant that she would have a different quality of life, a lesser quality of life, a “sick-kid” life. I didn’t know then that most SJIA kids can find disease-control with the right biologic nor did I understand how dangerously close Julianna was to having full- blown, life-threatening Macrophage Activation Syndrome.
Meeting Other SJIA Parents
In January 2018, I joined the SJIA Parent Network Facebook group and began to educate myself on SJIA through real-life parent stories, photos and experiences. I learned about SJIA and began to realize how unique each child’s disease course and clinical presentation was. I also learned from parents who had gone through it, how dangerous MAS can be for the children it attacks.
Refractory Life: The New “Normal” of Living with Subclinical MAS
So what does it mean to have “Refractory SJIA” and “Subclinical MAS” and how does it affect her daily life?
Julianna was our first child and we didn’t know what “normal” was. She was diagnosed with this life-altering disease before she began to walk and talk so as new parents, we didn’t realize how much it was affecting her quality of life.
We did not see that our toddler wasn’t as physically active as she should be.
We did not see that she lacked the stamina to keep up with peers.
We did not see how much growth delay she was having.
It wasn’t until spring 2018 when we started to venture out to parks and playdates that we saw how slowly she moved and needed frequent breaks.
We saw that kids half her age towered over her and bulldozed rambunctiously through the playground as our child walked slowly and with trepidation.
We saw that she couldn’t climb stairs or jump.
We didn’t realize that normal toddlers climb furniture, jump off chairs and give their parents near-heart attacks on a daily basis.
We came to accept her being on a “cocktail” of daily oral medications that had various side effects.
We came to accept that a nightly subcutaneous injection was part of our daughter’s bedtime routine.
We came to accept that long-term steroid use had stunted her growth and gave her a cushingoid appearance of a swollen face and belly.
We came to accept that the steroids made her abnormally hairy and that cyclosporine made her even hairier.
We came to accept the unexplainable rashes, dermatitis and mast-cell activation that caused her to scratch herself until she bled.
We came to accept that a fever or simple illness meant a trip to the ER for a full blood workup.
We came to accept that our daughter was immunosuppressed and had to be somewhat isolated, she couldn’t attend daycare or birthday parties in fear of her being exposed to germs.
We came to accept that our daughter’s disease wasn’t being fully controlled by the medication and she would not live a normal life.
Subclinical MAS Strikes Again…
In April 2018 Julianna’s inflammation markers began to climb and her breakthrough symptoms were increasing so she was she was referred to a Hematologist/ Oncologist for further evaluation. Again she was tested for malignancy which came back negative but the doctor said her lymphocyte values were abnormal and quite alarming. When I asked if she had MAS he said “No”, but that she had “parts of MAS” or what is called “Subclinical-MAS”. Her Ferritin was 3,894 in May and climbed to 4,661 by September. Her doctor increased her dose of Anakinra to 45mg (the maximum dose for her weight) and her labs began to trend back downward.
In Fall 2018, 1.5 years post-diagnosis, active arthritis was discovered in her knees. She had hours of morning stiffness and became bedridden for over a month. She couldn’t support her own weight, cried from the pain of moving her limbs during diaper changes and clothing changes. She developed muscle atrophy in her left leg and was given a steroid injection in her knee to help increase mobility and decrease pain. Her once normal gait had changed into an obvious limp. She now needed physical therapy to relearn how to walk.
Despite being on a full regimen of medications including Prednisolone, Cyclosporine, Naproxen and Anakinra, Julianna continued to have breakthrough symptoms and her health and quality of life continued to decline.
Joining the “Clubbed Fingers” Club
In spring 2018 we started to notice her fingertips and toes becoming increasingly red and appeared sore and painful. I scoured the SJIA Facebook group for any mention of finger redness and that’s where I came across the term “clubbing”. Though Julianna’s fingers weren’t yet clubbed several parents had similar stories of redness first, then clubbing. I also learned that clubbing was specific to a subset of patients who developed lung complications- many of them months or years after their initial diagnosis.
It wasn’t until September 2018 that her toes began to physically change. One by one the tips of her toes became swollen and bulbous. Then her fingertips began to become bulbous as well. This physical change got the immediate attention of her Rheumatologist and we were referred to a Cardiologist to rule out Pulmonary Hypertension. All of her tests came back negative and we were told that the swelling in the fingertips was not clubbing as there was no changes to her fingernails. I still was not satisfied and the parents in the SJIA Facebook page suggested I push for a CT scan.
The Official ILD Diagnosis
In January 2019 after asking for additional testing, she was given a referral for a chest X-ray. The X-ray showed opacities in her lungs. In May 2019, a chest CT confirmed what I had suspected for nearly a year and Julianna was officially diagnosed with Interstitial Lung Disease (ILD).
Smoldering MAS Escalates to full-blown MAS
By June 2019 Julianna’s Rheumatologist was concerned about her inflammation markers continuing to rise. They they said she had what they called “smoldering MAS”. At her monthly appointment at the beginning of June, her Ferritin was 1,559, and her team started plans for starting her on pulse steroids but events unfolded too quickly.
On Saturday, 6/22 Julianna woke up with a temperature of 101° which was different than her typical SJIA fevers which usually strike at 7pm. She was the most lethargic I had ever seen. During her nap her breathing was rapid, labored, and her face was flushed. She barely responded when we tried to wake her. The next day, after talking to her doctors, I brought her to the ER for labs as we had done many times before. But this time was different – the ER doctors returned saying that Julianna’s labs had met all of the criteria for full blown MAS; her Ferritin was 30,659, D-dimer 41,755, CRP 76.0, LDH 2,332 and her Fibrinogen dropped to 303. She was immediately admitted with a plan for pulse steroids.
I posted Julianna’s MAS diagnosis on the SJIA FB group and received an outpouring of support from the parents in the group. Little did I know that post would help save my daughter’s life. The post caught the attention of several parents who had experienced MAS with their children. They reached out to me privately to warn me of the dangers of MAS, especially in refractory SJIA kids with lung involvement. They warned about the possibility of organ damage, organ failure and death if MAS was not brought under control quickly.
I received a phone call from Rashmi Sinha, Founder of the Systemic JIA Foundation who informed me about a clinical trial for Emapalumab (Gamifant). Rashmi introduced me to Luke Malinowsky whose daughter Lily had severe MAS and Interstitial Lung Disease Pulmonary Alveolar Proteinosis. She had recently received Emapalumab through compassionate use and had done very well. Rashmi also referred me to the doctors at Cincinnati Children’s Medical Center to see if Julianna was a candidate for the trial. That conversation changed our lives, and it is because of the awareness and advocacy of other SJIA parents that Julianna is still alive today.
And the Ferritin Kept Rising…
While we were learning about Emapalumab, our hope was that Julianna’s MAS would resolve with the med regimen they had started. On Monday, 6/24 after completing her first round of pulse steroids and increasing Anakinra to 50 mg twice per day (every 12 hours). Julianna had regained some energy, and had an appetite, but while she seemed clinically better, her inflammatory markers continued to rise, her Ferritin was now up to 33,175.
On Tuesday, 6/25 she began declining steadily. She slept most of the day, barely spoke and only drank milk from a bottle. Doctors increased her oral cyclosporine dosage and increased Anakinra to 50mg four times per day (every 6 hours). Her labs showed slight improvement and her Ferritin went to 26,185.
The Hardest Day of our Lives
In preparation for her birthday, the following day Child Life had arranged a special visit from Disney Princesses to sing Happy Birthday. When they arrived, Julianna was too sick to even lift her head from her pillow, even though she had been waiting for her birthday for weeks. In that moment, I realized just how critical she was. That night, I actually said out loud that I thought she was going to die, and I would be burying my first child before the birth of my second who was due in just a few weeks. I began asking the doctors about Emapalumab as a treatment option. Most of the doctors I spoke to, had not heard of it. It was then that I knew in order to keep Julianna alive I had to become my child’s biggest advocate.
Wednesday, 6/26 was Julianna’s 3rd birthday and one of the worst days of my life. She was slipping deeper into MAS. She began to have difficulty breathing with labored, belly breathing. Her O2 saturation rates dropped to 88-89 and she was put on supplemental oxygen. A chest x-ray in the afternoon did not show any fluid in the lungs, but they started chest physiotherapy to help her breathe. They also told her she would be transferred to PICU if she didn’t improve. They switched her from oral to IV cyclosporine that afternoon and repeated labs in the evening. Her Ferritin had risen to 40,665. As I sat there singing Happy Birthday to her, while holding an oxygen mask in place, I felt the harsh reality that my baby could die if things didn’t improve quickly.
A Big Decision – to Enroll Julianna in Emapalumab Trial
That evening, her breathing continued to be labored. O2 dropped to 77 so they repeated a chest X-ray. The second x-ray, taken less than 8 hours later showed that she now had fluid in her lungs. In that moment, my husband and I knew it was now or never, and we made the decision to get her to Cincinnati no matter what it would take.
On Thursday, 6/27 she was moved to PICU and was put on Lasiks to help her lungs. She remained on oxygen and was very weak, sleeping for most of the day. I knew we were losing her. That morning we met with the PICU team, the hospital social worker, and the head of Rheumatology and pleaded to be transferred to Cincinnati to participate in the clinical trial for Emapalumab, as she was failing all traditional therapies to combat MAS. They assisted us in coordinating with Cincinnati and agreed to the transfer, however all hinged on a determination meeting with the Clinical Trial team and the pharmaceutical company to see if she met the eligibility criteria. At 4:30 pm we learned she was accepted into the trial. She would be the first child in the United States to participate in the Emapalumab (Gamifant) trial for MAS. We were scared, but had new-found hope.
On Friday, 6/28 at 1:30am Julianna was medevaced from NYC to Cincinnati, Ohio. When she arrived that morning her inflammation markers were still climbing. They prepared her for the Emapalumab infusion scheduled for the next morning with preliminary tests as well as a blood transfusion to stabilize her hemoglobin. Her baseline labs before her first dose of Emapalumab on the morning of June 29th were incredibly high; Ferritin was 75,493, D-Dimer >20.0mcg/ml, LDH 5,505, CRP 1.9mg/dl, Fibrinogen <70. None of the traditional therapies were working for her. How much longer did we really have before she had permanent organ damage, organ failure, or died? The first infusion was scheduled for 10am on Saturday, June 29th. This was our last hope.
The start of an Amazing Turnaround
Within an hour of receiving her first Emapalumab infusion, we saw immediate clinical improvement. After a week of not eating, sleeping most of the day, and barely speaking, she sat up, she said she was hungry and asked for pizza, chips and soda. She came off lasiks, her lungs cleared, and she no longer needed supplemental oxygen. Her O2 sat rates returned to 96-99.
After one infusion her Ferritin had gone down to 50,561 and by the morning of her second infusion it was down to 14,335 (lower than at her original ER admission), by the morning of her third infusion it was down to 7,198 and her fourth it was down to 2,881. All of her other labs followed a similar downward trend. Every day thereafter she continued to rehabilitate and improve in every capacity.
Julianna spent a total of 4.5 weeks in Cincinnati Children’s hospital for the Emapalumab clinical trial, receiving a total of 8 infusions before she met the criteria to be considered in MAS remission. Her labs continue to trend towards normal and many of them are lower now than they ever have been since her SJIA diagnosis in 2017.
Its not just lab that are improved. Julianna went for a repeat Chest CT done recently, 2 months after the course Emapalumab. We were worried that the lung disease would have worsened, but remarkably the CT shows some improvement. The previous CT in May 2019 had shown areas of consolidation which are decreased now, there is lesser interlobular septal thickening and decreased lymph node enlargement. We could not have hoped for better.
Emapalumab gave Julianna a new Lease on Life
Emapalumab didn’t only rehabilitate Julianna from MAS it, changed her life. It has given her a new quality of life, a “normal kid” life. She has more energy and stamina than I have ever seen before. She returned from Cincinnati a new child, a happy child. A child who is fever and rash free. A child who can dance, climb stairs, run and jump. A child who races to the top of the playground and goes down the tallest slide insisting she can do it “all by myself”. My child is able to do things she has NEVER been able to physically do before. It’s exhilarating and exhausting to keep up with her energy level and for so long we didn’t know what we were missing.
But now we know…we know what the right medication can do for a child with Refractory SJIA. The right medication can give them a quality of life they never had before- a real chance at life to be a kid. Every child deserves a chance to live and Emapalumab gave my child that chance. It saved my Julianna’s life and it saved my family.