Ella was born on a Tuesday in summer of 2011. It was like any warm, late summer day in San Diego, but when she entered the world, it was clear to me it was different. The first time I held her, I was studying her features and it was like looking in the mirror. She had long eyelashes, beautiful complexion, and dimples that would grab attention from admirers and grandparents. Her health was good and everything seemed normal.
At three months old, she seemed susceptible to post nasal drip and was on a nebulizer treatment several times her first year, but it did not seem to slow her down. She was active, growing at the right rate and looking to keep up with her sister. As years went on, it was clear her personality was what drew people to her. Ella’s nature was one that would put a smile on your face and bring joy being in the company of a child. She was loving, active, funny and direct.
THE SJIA DIAGNOSIS
On Sunday, August 30, 2015 Ella turned four. We were out for a walk in the neighborhood and my wife Sandra noticed the inner part of Ella’s thigh had a rash. She did not seem affected by it and we thought it could be a heat rash. We put some topical cream on the spot and thought it would go away.
That is not what happened. The next day, Ella woke up with a fever of 102 degree and by the early afternoon, was complaining of pain in her right knee. We thought she was fighting a bug and hurt her knee playing. On Wednesday, at her 4-year-old wellness check up with the pediatrician, she was limping. As a parent, I do not want my child to be in pain, but I was glad that she had a physical limp so that it would point to a cause with an obvious solution.
We have a wonderful pediatrician who conducted a thorough examination and discussed the possibilities. She mentioned JIA, but only as an outside chance and said that — more than likely — it was a bug. Lab work indicated Ella’s inflammatory markers were up, but not alarming. She was given over-the-counter NSAID to treat the symptoms.
Ella woke up in obvious pain on Friday and the symptoms never went away. I carried her out of bed and examined her knee. It was swollen and warm to the touch. I called her pediatricn, Dr. Giangreco, who got us into her office at 8 a.m. She ordered blood work. At noon, her pediatrician called saying she scheduled an appointment with the Emergency Department at Rady Children’s Hospital as Ella’s labs came back with alarming inflammatory markers.
Our minds were racing. We had no idea what would have caused such a reaction. After more lab work, the hospital determined Ella had a septic joint which required a knee aspiration, irrigation and antibiotics administered. Scary stuff, but looking back 21 months later, it was a walk in the park. The following day, I met with all the doctors treating Ella to discuss the myriad of conditions she might have, one being SJIA. I had never heard of SJIA and immediately began to read up on it as well as all the other conditions mentioned. The symptoms described in what I could find online seemed to align with what we experienced over the last week, but it was so rare in children that other causes seemed more likely.
Ella’s condition did not improve and the cycle of the previous week appeared to continue. Ultimately the infectious disease specialists began to doubt the initial diagnosis and called in rheumatology.
I was anxious to meet with the rheumatologist with the hope that we could find a solution for Ella’s now 7 day-condition. I told the rheumatologist, Dr. Radhakrishnan the whole story and he confirmed my suspicion. I felt a momentary sense of relief and I said to him, “Well, I’m glad we now know what we are dealing with.” The first thing he said to me is, “You don’t want to have this disease.”
My heart sank. I was aware of the complications associated with SJIA and turned that sinking feeling into a math equation. Later, I would constantly searching the internet for information about SJIA, reading available medical literature and read an article that cited research showing that there can be a 90% chance of disease control with early diagnosis. How do you measure early? Hours, days, weeks or months?
The doctor proceeded to tell me Ella was fortunate we were able to diagnosis her early into the course of symptoms and that biologic drugs have been successful in treating patients and some children have even gone into remission.
I was hopeful and took the stance most parents would take: we are going to fit into that 90% category and may even get lucky by going into remission. I was committed to Ella’s health in that it was always going to top of mind and we were going to do everything for her to have a normal life and hope her disease would not get in the way of her childhood experience.
ON ANAKINRA AND HOPING FOR REMISSION
It was a Sunday evening when we went home from the hospital. We were happy to leave but scared for the life ahead of us, post diagnosis. Ella was on prednisolone and seemed to be responding well. We met with Dr Radhakrishnan in clinic who had asked us what we knew about the disease. This was my chance. I had several days to devour any literature I could find to grasp what was going on. I read as many scholarly articles as I could and regurgitated to the doctor all I had memorized. I began with the origin of the disease in England, the naming and classification changes and ended with biologic medication options related to interleukin receptors and the debate whether this is an autoimmune disease or an auto-inflammatory disease. I wanted to convey to the doctor that we as a family were committed to Ella’s health.
We decided on the daily injection of Anakinra option, based on the studies that discussed remission. We began with a half dose injection every other day. For the first six months, Ella seemed to be doing well. She did not have major complications and the injection site reactions were the only thing to cause concern. We even took a family trip to Hawaii and really thought we were sailing smooth. In our minds, we were in the 90% category and had the disease controlled. The doctors were cautiously optimistic and agreed Ella was riding the wave.
WRESTLING WITH INFECTIONS
Our wonderful Rheumatology team had told us, early on, that we needed to be cautious about Ella’s health since we were suppressing her immune system with the biologic medication. I felt we were ready. We were washing hands more regularly, avoiding anyone we knew who was sick. Then it happened. In March 2016, Ella came down with strep throat and her SJIA symptoms came back. Ella was treated for the strep throat and we increased the Anakinra to full doses, daily. She also came down with an unexplainable rash that was unlike her initial SJIA rash. This rash seemed to irritate her and caused her to itch.
In spite of increased Anakinra, Ella could not seem to get back to where she had been the previous months. She would occasionally have fever, rash or both. She continued to itch and had another infection around her belly button from where she scratched herself raw. She was given an antibiotic called cephalexin. After eight days of use, Ella had a skin reaction from head to toe, which I thought was serum sickness, but never confirmed.
MOVING TO ACTEMRA
By the summer of 2016, we decided to try a different biologic and chose Actemra (which is a once every two-week infusion). Our thought was maybe we needed to block a different interleukin receptor. The first time Ella received Actemra, she had an adverse reaction. She turned ghostly white and landed in the hospital for a few days for monitoring. We were confused as what caused the reaction to the medication or even if it was the medication at all.
The following week we decided to try Actemra again but she had another adverse reaction, this time stronger than before. Ella was put on glucocorticoids again and resumed Anakinra injections.
HAPPY DAYS IN KINDERGARTEN
Our next big hurdle was to get Ella ready for kindergarten. Ella’s roller coaster of good days and bad days had affected her pre-school attendance and we were not sure she was ready for kindergarten. Ava was doing well in first grade and Ella wanted nothing more than to be at the same school with her sister. Ella was on a significant amount of steroids and seemed to be improving well. Her cheeks were chubbier which accentuated her beautiful happy smile.
Ella excelled in kindergarten. She loved going to school and being with her friends. Ella was determined to learn to read and wanted to take over the reading duties at bedtime. Ella practiced writing, reading and loved to draw pictures. Most pictures she drew were of herself with a cute ponytail and a bright smile. Halloween came and went and she loved dressing up as a tiger and playing in her costume.
A BOUT WITH PNEUMONIA
Ella’s was still on daily full dose injections of Anakinra but the injections were becoming more difficult to give her. We decided to switch to Ilaris, which is a monthly injection and hoped that we could turn the corner with her symptoms. She got the first shot on Dec 23rd, 2016.
The day after Christmas (Dec. 26, 2016), Ella did not look well. She was tired, quiet and began to shiver as she watched television on the living room floor. I immediately recognized that something was wrong. The following day the doctor diagnosed her with pneumonia. This bout of pneumonia really affected her. She never really seemed to fully recover. Also, the Ilaris did not seem to hold her even till the next dose so two weeks we restarted Anakinra and did not try Ilaris again.
A CASE OF REFRACTORY SJIA?
In January 2017, she had a lump under her armpit and later in the month developed an abscess behind her ear. The SJIA symptoms began to come and go, but Sandra and I were even more concerned because her health picture seemed to be complicated and no one could put a finger on or come up with a treatment that would get her back to where she was a few months after her diagnosis.
In February, Ella’s labs showed high inflammatory markers (Ferritin: 24,000) She also had fever and rashes. I was concerned the Anakinra was losing its effectiveness. By this point, I was constantly searching the internet to find information about SJIA and any emerging treatments. I read ab
out a subset of SJIA patients with refractory cases and how researches were seeking answers as to why and if there was anything that could distinguish them from other SJIA patients. But things were not clear-cut with Ella. There were times she was sick and other times she was fine. Even during the sick times, she was very active. It was only later that I realized her ability to be active in swimming and participating in gymnastics was based on her will to be a kid and keep up with her older sister.
Researches were looking at IL-18 cytokines and there was evidence that children with a higher IL-18 cytokine count had more refractory cases of SJIA. I distinctly remember asking the doctor if there was a way to test this and he said there was no commercial test for it that he was aware of.
Ella again was discharged from the hospital with steroids and now a new oral medication called Tacrolimus (a drugs which is used to suppress the immune system typically post-transplant). Ella complained about the medication because she did not like the taste and it gave her an upset stomach. The doctor gave an over-the-counter acid control drug and attributed the stomach pain to the medication.
Even while up and down with SJIA, Ella forged onward in other ways. As parents we were torn. We were obviously concerned, but we did not want to take away from her quality of life. We kept her active with school, t-ball and her friends.
But by the end of March, Ella started to tire easily and was content with resting in a chair for extended periods, which was out of her character but a symptom of the disease. We hoped we were on the bottom curve of the roller coaster. She obviously was not her normal self, but we were hoping we were getting control of her disease with the new regimen of drugs.
April 3 arrived and Ella complained of pain on her tongue. I looked and it looked like a canker sore. Several days prior, she was eating sunflower seeds at her sister’s softball game, which I thought was the cause of the sore and tried to treat it topically. Throughout that night, Ella was in obvious discomfort. Next day, when Ella woke up her face was obviously swollen, so much so she could not close her mouth and her tongue had thickened.
Luckily, we already had an appointment that day for her anemia. The doctors took a look and were not able to put their finger on what the cause of the sore and swelling, as Ella had a complicated picture. Eventually doctors decided Ella needed to be intubated and given medication for the swelling to her tongue so her airway was not compromised.
It was nothing we were prepared for. I remained optimistic that we could resolve the issue. Days went by without a resolution and the team of doctors were still puzzled as to what was going on with Ella. After being in the hospital for several days, I was told about Dr. Mellins from Stanford who was coming to Rady Children’s Hospital to present research she had been working on regarding SJIA patients with refractory disease.
The rheumatologists were closely talking with Dr. Mellins, who suggested they look for an opportunistic infection. More specifically, for an opportunistic lung infection. Pneumocystis jiroveci pneumonia, or PJP, is very common in our environment and can be treated, but it is eventually deadly if left untreated. Her doctors did a Bronchoscopy and found that indeed Ella did have a PJP infection. We had been giving Ella antibiotics for a wide range of infections so she was already being treated for the PJP, but now doctors could put their finger on it.
After eight days of being intubated Ella was extubated, which was a big relief. We had our daughter back with us, she could talk, and more importantly she could hear us say how much we love her. Ella was weak from being intubated for several days and was not comfortable being in the hospital. We thought we were on the road to recovery. The next several days we focused on building her strength and keeping her symptoms under control with medication. During this time, Ella had spiking fevers, which was of obvious concern because she was heavily medicated to treat the very symptoms that were presenting. Also, she continued to complain of stomach pain.
Easter Sunday came and Ella was downgraded from the PICU to a lower level of care. We thought we had made progress and were gaining momentum. But that night, things took a turn for the worse. Ella continued to have fevers and her face began to swell again. She was transferred back to the PICU and her urine output declined. Ella was retaining fluid and was required to be on dialysis. This was the beginning of MAS, or Macrophage Activation Syndrome. The doctors started a full court press and recognized they needed to address the macrophages in her system that were consuming her platelets. Ella began receiving blood transfusions and undergoing a process called plasmapheresis. The day after the return to the PICU, she also received Etoposide.
Sandra and I were tied to the around the clock hourly lab results. The roller coaster ride continued. One lab test would show positive results and the following lab results would show a backslide. It was agonizing to watch her go through this and to watch very smart people cross their fingers rather than be confident that they knew what would work. As we continued to pray, Ella’s condition worsened and she developed abdominal compartment syndrome. She was oozing blood from her gastrointestinal system. Her stomach had become so distended and tight that blood supply was not reaching her lower GI tract.
We went from hopeful to devastated. Having to decide to let the medicine try to treat her or to allow a surgeon to open her sweet little belly to relieve the pressure. The surgeon was not sure she would survive the procedure and if the disease process would stop altogether. We were crushed, emotionally drained and frightened beyond words. Ella was given little chance to live through Wednesday evening. Ella held on. She fought her way to the following Monday or May 1st 2017, where necrosis had set in and was irreversible. In a matter of 30 days Ella went from being a happy kindergartener to our heavenly angel.
CARRYING ELLA’S SPIRIT FORWARD
After Ella passed, I had several opportunities to speak with the medical staff from Rady Children’s Hospital and it was clear her spirit had touched them all. Her funeral was attended by over 800 people and the outpouring of love and support have been tremendous. Ella lived her life as a fighter, she loved with her whole heart, she was kind and she shone regardless of her disease. Sandra, Ava and I are committed to living our lives to honor her by living the way she did.
We want to help other children with SJIA and complications like lung disease. We want to share our experiences and learnings so that no other family faces the outcome we did. We learned so much, for example, for any child who is failing multiple SJIA meds, there should be a way to dig deeper and test things like IL18, to better understand case and direct treatment. We learned about the PJP infection only in the last two weeks of Ella’s life and that there can be up to 70% mortality with lung complications in SJIA. Doctors and patients should know more about lung issues, and be on constant lookout for it. We think parents should be aware of not just the chances of remission, but also that their child might be refractory. And finally, we need multi-specialty centers dedicated to SJIA so that rheumatologists can work with all the specialists to diagnose and treat these children in time to save their lives.
Sandra and I will be working to bring this message to both doctors and patients, and to raise awareness about SJIA and MAS. Our efforts will not bring Ella back, but our hope is we can help the children and the families struggling with this devastating disease.
Disclaimer: This blog contains general information about Systemic JIA as well as personal insights from the Systemic JIA community. Opinions and experiences shared by members of our community, including but not limited to patients with SJIA / Still’s Disease and their families, belong solely to the blog post author and do not represent the opinion of the Systemic JIA Foundation. In addition, this site is not intended as a substitute for treatment advice from a medical professional. Consult your doctor for all medical questions and before making any changes to your treatment.