Calling out rheumatology.
It's December 18th at about 9:00 pm. I'm doing a bit of writing when I hear screams coming from my daughter's room. My wife and I quickly got up and ran to see what was happening.
I open her door, turn the lights on, and see my daughter. She's hunched over, crying, with vomit all over her hair.
Liz picks up Chloe and starts to clean her hair while I tackle the mattress and sheet. As Liz took her shirt off, I noticed how visible her ribs were.
Chloe was jaundiced, lethargic, and looked sick. I put her on the scale, and she weighed 17.5 pounds.
I began to review her length and weight after her last physical a few days back. Starting in June, she dropped from the 55th percentile to the 8th percentile in length and from the 24th percentile to the 14th percentile in weight.
She was now in the 5th percentile.
Starting December 8th, we noticed she would have waves of nausea and loose stools. It was an insidious process.
In the last couple of months, we also began to see an increased difficulty swallowing solids (I'm not sure if this is dysphagia or painful swallowing, as I can't ask her). She also began to have color changes (blue, purple, red) in both hands. I initially thought Raynaud's due to the abnormal rheumatological workup. But, she never seemed to be in pain, and the color changes weren't isolated to the fingers (the entire hand was affected).
With all this in mind, we're looking at our little girl curled up in mom's arms. Liz expresses concern that she may need to go to the emergency department to get fluids for dehydration.
I hate the emergency room (no offense to any ER people) and didn't want to go unless necessary. So, I did what I could at home: generalized physical exam, heart rate, and skin turgor. Everything seemed to check out. When I put the stethoscope on her chest, her eyes lit up. She smiled and held it in place for me as I listened.
So, we opted not to go to the emergency department. But, we did decide to stop the promacta. The medication had been our concern from the moment we first noticed slightly jaundiced skin (although her direct bilirubin, ALT, and AST had all been normal).
I messaged heme/onc and let them know the situation. The following morning I received two messages:
Heme/onc advised us not to stop the medication until we can evaluate her LFTs.
Rheumatology asked if we could push back her follow-up visit even further. If you saw my previous post, you'll know I already had a problem with their lack of communication; I still hadn't received a call from Dr. "x."
My wife and I decided to ignore heme/onc and skipped her dose of promacta. But, first thing in the morning, we went in for bloodwork.
After returning home from the lab, I decided to reply to rheumatology with a few facts and statistics. I wasn't very nice about it either. They magically had a cancellation in the next hour for a telehealth visit.
I filled Dr. "x" in on everything that's been happening and voiced the concerns I had outlined in the previous post. I didn't get any great answers from her either. I got the impression that she didn't know what to do and was trying to buy some time.
Before we ended the call, she placed orders for stool testing. A genetic kit was also to be sent to our house to test for monogenic lupus/primary immune deficiency.
Side note: monogenic lupus is when lupus develops in a young child (<5 years of age) from a gene defect. This can become a bit convoluted as that same gene defect may lead to a primary immune deficiency, blurring the lines between rheumatology and immunology. It typically presents with severe manifestations, which Chloe doesn't have. However, we must remember she is only 1, and a lot can happen in four years. Which is why I'm so adamant about figuring out what is happening sooner rather than later.
This was the one thing I wanted to rule out on November 7th during our first rheumatology appointment. I asked Dr. "x" if this could be done. She replied that hematology had already screened for this when they ordered immunoglobulins; anything more was beyond her scope. This was when she referred us to immunology (which was also a horrible experience).
Dr. "x" either lied to us about what she could do or just now consulted with other clinicians who advised her to do this. As I said in a previous post, the trust is gone.
The next day we got a call from rheumatology letting us know Chloe's stool tested positive for Shiga toxin-producing E. coli (STEC) and C-Diff. C-Diff in children under two years of age is tricky. Many are asymptomatic carriers, and the data is limited on why that is. So, odds are, this was the case for Chloe.
STEC, on the other hand, is the cause of her diarrhea and episodic vomiting. A few pearls with this infection:
There are two variants:
Gene encoding Shiga toxin 1 and toxin 2. Shiga toxin 2 is more virulent, which leads to abdominal pain, bloody diarrhea, and hemolytic uremic syndrome.
Do not give antibiotics, as this can worsen hemolytic uremic syndrome.
So, we went for more blood work for a CBC and creatinine to ensure we didn't have HUS. We didn't.
A few hours later, we got this message from heme/onc:
"Chloe's labs show her ALT increased now to 288. This is greater than 3x the upper limit of normal, so I agree we should stop the promacta now. We will continue to work on getting IVIG set up as a backup option since I would expect that her platelets will fall once she is off the promacta. Infection (usually viral) can also sometimes cause liver enzyme elevation, so I'm not sure if her intestinal infection may be contributing to the rise in liver enzymes. It's probably still better to be on the safe side and discontinue promacta. Her bilirubin is now increased to 2.8, but the direct bilirubin is still 0.1. Her AST is now also elevated. I will release the labs results to you now. I will ask the clinic team to set Chloe up to get repeat liver enzymes and CBC next week."
We had a feeling this was the case, which is why we stopped the promacta.
Our next step was to get an IVIG infusion on December 29th. This would buy us time to finish the evaluation, so we don't just throw another random medication her way.
But, come December 27th, I had a few observations. I typed them up and sent them to heme/onc and rheumatology:
"We started romiplostim in July 2022; at this time, Chloe was tracking at the 24th percentile in weight. Then on December 18th, she dropped to the 4th percentile in weight. Her last dose of eltrombopag was on December 18th.
Since then, her appetite and energy levels have increased significantly. She stopped being fussy & is sleeping through the night (something she hadn't done in months). She went from 17.5 lbs - 20 lbs since stopping the medication. She is now back at the 27th percentile.
It has now been 8 days without a dose, and the medication should have cleared her system. Interestingly enough, we haven't seen any signs of bleeding or petechiae.
Is it prudent to check a platelet count before the IVIG? I know it's doubtful that she has a normal platelet count, but is it possible for her counts to have increased enough to allow us to hold off on the IVIG?
I also found that eltrombopag and romiplostim are known to cause drug-induced antiphospholipid syndrome. These medications aren't on the list for drug-induced lupus, but are also newer medications. Because of Chloe's rheumatology labs, coupled with the improvement in symptoms, could it be possible that these TPO agonists caused drug-induced lupus?"
Side note: most medications clear your body after about five half-lives (rough estimate). Promacta (eltrombopag) has a half-life of 35 hours, which means any clinically significant levels should clear by December 25th (175 hours or seven days).
Hematology agreed to draw a CBC and wait for the results (about 45 minutes) before giving IVIG. The rheumatologist agreed that drug-induced lupus could be possible and ordered a histone antibody to be drawn on the same day.
December 29th is here, and off we go to the infusion center. The nurse who will attempt to put in the IV suggests we swaddle Chloe with a blanket so we can strap her arms by her side.
I told them it was unnecessary as she does just fine with needles. So, she sits on my lap, and we play her favorite youtube channel (song for littles, lol). Unfortunately, the nurse dug around in her arm for a few minutes but couldn't get her vein. Chloe kept watching her show without yelling or crying. She was seemingly annoyed (rightly so), but that was the extent of it. My wife, on the other hand, had to look away. The site of seeing them move the needle in and out and all around made her nauseous.
The nurse asked if she could try again, and they would call for an ultrasound if she couldn't get it. I wasn't sure what would change the second time, and I want to keep this experience the least traumatic as possible as we don't know how long we'll be doing blood draws and infusions. So, I opted to get an ultrasound.
After one hour, they were finally able to use a vein in her right hand. My poor girl is tough beyond measure.
As we awaited the CBC results, I hopped on a telemedicine visit with a hematologist from another hospital to get another opinion on Chloe's case. While I was reviewing everything with the physician, the nurse walked in and said, "Chloe's platelet count is 18,000."
This was the highest we had ever seen her platelets (aside from shortly after the initial IVIG infusion)!
My wife and I looked at each other, and tears came down. These were happy tears. It was a glimmer of hope that she may be on her way out, and we were elated beyond imagination.
I finished the visit with the hematologist and opted not to move forward with the IVIG. Instead, we would see how her platelets behaved in one week.
Sadly, one week later, on January 4th, 2023, her platelets returned to 4,000. What an emotional rollercoaster, to say the least. At this same visit, our hematologist asked why we had a histone antibody done. I explained and asked if the result was back. She said yes, and said this was positive.
Once again, a bit of anger set in. Not because of the result. But because I have to hear about the rheumatology lab result from our hematologist. Their team's level of communication is abysmal; as you can see below, I'm actively looking for alternatives.
Still, I reach out to rheumatology to see what they have to say. This is what I got:
"Since Chloe is no longer taking the eltrombopag or romiplostim, time will tell if that was causing her issues as it clears out of her system. But, what gives pause is that the positive histone doesn't explain why she got ITP at such a young age. Dr. "x" has a message out to UCSF Benioff immunology for their thoughts and will let us know what they say."
Although I won't say who the physician is out of respect as she works at two different institutions, I will say that the rheumatology care has taken place at MemorialCare Miller Children's & Women's Hospital in Long Beach, California. I only say this because if anyone is listening and thinking about rheumatology at this institution, please go elsewhere.
With that said, the heme/onc department has been excellent. In fact, we have no other complaints besides rheumatology; everyone from the receptionists to the phlebotomists has been great.
At this point, we've looked to get consults from:
MemorialCare Miller Children's & Women's Hospital Long Beach
CHOC (Children's Health of Orange County)
UCLA
Mayo Clinic
UCSF Benioff immunology
Here's what January looks like for us:
January 4th: hematologist follow-up visit
January 6th: first genetic appointment
January 14th - 18th: first rheumatology and hematology appointments at Mayo Clinic (had a telehealth consult with hematology prior)
January 19th: first rheumatology appointment at UCLA
January 23rd: first immunogenetics appointment at UCLA
Our genetic results for monogenic lupus/primary immunodeficiency are still pending but should be ready any day. But I'm especially interested in our January 23rd appointment. This office is run by two physicians who are board certified in immunology, assistant professors in rheumatology, and explore the world of genetics. They have a lab specifically focusing on infections, autoimmunity, and cancer.
The second major focus of the lab is on improving the diagnosis and treatment of patients with rare genetic immune diseases (primary immunodeficiency or inborn errors of immunity). One of the physicians is a co-Investigator in the NIH-funded Undiagnosed Diseases Network and one of the founding co-directors of the California Center for Rare Diseases.
I'm cautiously optimistic that we'll finally get answers before the month ends.
We just finished our genetics appointment. This was a two-hour visit which is unheard of in any other specialty. But, it left my wife and me with a lot to consider.
I'll share the details regarding this visit in the next post.
Until next time.