My Experience At Mayo Clinic
It's Saturday, January 14th, 2023, and Liz, Chloe, and I are headed to the airport to fly out to Rochester, Minnesota.
I decided that our next stop would be Mayo Clinic to consult with hematology and rheumatology to get their take on what's happening with our daughter. We flew in a couple of days before our appointment date in the event our flight got canceled or delayed due to the weather.
Although this wasn't meant to be a vacation, it would be the first time Liz and Chloe both spent time in the snow. So, the original plan was to have our appointments in the morning and then do some activities in the afternoon.
The idea was excellent in theory but wasn't realistic. The appointments took hours, we were sleep deprived, and we had to deal with the time change. So, we had nothing left in the tank to keep going after our morning appointments.
We had hematology Monday and rheumatology Tuesday. Both physicians spent a lot of time with us, answering every question we had. They knew we had flown in, so they spent the time ensuring this appointment was worth our trip. I can't say enough good things about the experience.
We saw Dr. Ahmad H Al-Huniti in hematology. He was honest and told us they usually see about 2-3 new cases of ITP per month, but only about 2-3 new cases per year that are Chloe's age.
He thought it would be a good idea to rule out ALPS (autoimmune lymphoproliferative syndrome) to complete the workup. Interestingly enough, I brought up ALPS to our original rheumatology appointment and was instead "pawned" off to immunology. Can you tell I haven't had a good experience with our first rheumatologist? Lol.
In any event, I was happy that was being done, although this was also being checked with the primary immunodeficiency panel we ordered through Invitae. ALPS is a disorder that leads to lymphocyte proliferation. Approximately 75% of ALPS patients have a genetic defect, usually in the FAS gene. Patients typically present with autoimmunity (typically cytopenias), lymphadenopathy, and splenomegaly.
Primary immune deficiency is also known as an inborn error of immunity. This is the name given to a group of disorders that arise from a genetic mutation. There are 500 known disorders, and the presentation varies. But, usually, you'll see frequent infections, severe infections, autoimmunity, and/or malignancy.
The main question we had was what medication would be best to treat Chloe's thrombocytopenia. She is becoming increasingly active and is starting to assert her independence. For example, Sunday night, we went for a Target run. Chloe decided she didn't want to be held; she wanted to hold my hand and walk.
Because of the weather, Chloe had multiple layers of clothing, which made it difficult for her to move, especially for someone with her level of coordination or lack thereof. After only a few steps, she attempted to run, tripped over herself, and fell.
She busted open her lip and continued to bleed throughout our target trip. Over the next few hours, her lip became engorged with blood, and the following day it looked like she went 12 rounds in the ring.
Because she's already failed four medications, we're looking to be more intentional when picking our next medication. We don't want to continue down the cookie-cutter algorithm, as this isn't a simple case of primary ITP.
Dr. Al Huniti's take was very similar to what we've been hearing thus far, but because of the abnormal rheumatology labs, we knew that more of our answers would be coming Tuesday. Seeing as how rituximab is one of the potential options, I asked if he had any experience giving the medication to someone of Chloe's age for this indication; he said he didn't. Interestingly, many hematologists advocate for rituximab as the next step, but none have prescribed the medication for someone who fits Chloe's profile.
He finished the visit by saying we should get all the results before moving forward. In the meantime, he sent a prescription for tranexamic acid for us to have on hand. He likes to prescribe this to patients with bleeding disorders if there is a hard-to-manage bleed. This could save us a trip to the emergency department. Grateful for this.
Tuesday rolled around, and our rheumatology visit provided a lot more clarity. We met with Dr. Matthew Basiaga. When he turned on his computer, I saw his notes ready to go with the pertinent positives. He did his homework regarding Chloe's history based on the questions he was asking. He did a comprehensive physical exam as well.
Believe it or not, this was the first time I'd experienced this; it was a breath of fresh air.
Many of the questions I had, which our current rheumatologist initially dismissed, were validated. He spent a lot of time giving thorough answers and citing specific studies. At the end of the visit, he laid out the entire game plan moving forward; this is what I wanted from this visit.
Here is our current differential diagnosis:
Primary immunodeficiency.
We are waiting for the genetic results from Invitae to rule this in or out.
Hematology is also screening for ALPS.
Dr. Basiaga is rechecking C3, C4, AH50, and CH50 to rule out a complement deficiency. Her original labs (November) showed a decreased C3 with a normal C4, AH50. and CH50.
Drug-induced lupus.
Chloe has been on nplate and promacta (TPO agonists) from July 25th, 2022 - December 18th, 2022.
This was my latest theory, seeing as how she improved clinically after we stopped the promacta. Our original rheumatologist checked for histone antibodies when I asked if this could be possible. They were positive, but histone antibodies are also present in SLE (so it doesn't help differentiate between the two).
Although she doesn't have the classic presentation per his experience (he believes that the rash and joint pain would be more prominent), it's important to remember that specific medications have specific presentations that differ from this classic appearance. Because the TPO agonists aren't on the list of medications known to cause drug-induced lupus, they may have their unique presentation.
Viral infection leading to a transient elevation in antibodies.
It's known that viral infections can lead to transient elevations in antibodies. Chloe tested positive for COVID on August 6th, 2022, and the first rheumatology labs were drawn on November 7th, 2022.
IVIG leading to a transient elevation in antibodies.
IVIG is a collection of antibodies collected from many donors. Because of this, it's possible that the elevated IgG antibody levels were caused by the donor plasma.
Elevations typically last 1-3 months, and Chloe received IVIG 8 months before antibody testing. This makes it unlikely, but he still included this as a possibility.
SOC-1 gene mutation.
He's seen a few cases of young children with this genetic mutation who presented with a lupus-like picture following COVID infection. He knows six total reported cases and has been involved in the care of one.
This is a new finding for apparent reasons (COVID has only been around for three years), but they all had one thing in common: refractory thrombocytopenia at a very young age.
Here's the game plan:
Repeat Chloe's labs to see if there's any resolution or improvement. This will help address the following possibilities:
Drug-induced lupus
Viral infection and/or IVIG leading to a transient elevation in antibodies
Wait for the pending lab results (ALPS and the primary immunodeficiency panel).
Dr. Basiaga will contact genetics at Mayo to see if the gene can be tested there or if it would need to be sent out.
If one of the three options above yields answers, we move forward in that direction. If her labs are still abnormal and the genetic testing doesn't yield results, he would diagnose Chloe with SLE; this would be very rare in someone her age, so he wants to ensure we've ruled everything else out. At this point, we would discuss possible treatment options.
Before we came home, we repeated Chloe's rheumatology labs. We are five months post-COVID, and it's been one month since we stopped the TPO agonists.
Interestingly enough, on the flight home, we were sitting in front of a NICU nurse, and I overheard her conversation with a flight attendant. She said she noticed an increase in children with an autoimmune disease presenting with severe manifestations. About six months back, our pediatrician told me he noticed the same.
Could all this be related to COVID? Either from the vaccine or the infection?
Liz received two doses of Moderna when she was about 3-4 weeks pregnant. The vaccines didn’t undergo the same level of scrutiny as other vaccinations; there wasn’t a way to determine all the possible fetal outcomes if given during pregnancy.
Unfortunately, it may be 5-10 years before we learn anything substantial about what’s happened these last few years. Even then, it’s no guarantee as the COVID virus we know today is not the same virus we knew in 2020.
In any event, this is where we are in our journey to uncover our daughter’s diagnosis.
Now, we wait.
Sounds like a thorough visit. Fingers crossed this yields some answers. The unknown liminal period is so difficult to navigate. Thinking good thoughts for you all.