Superhuman: An Update on Yzzy

Long time readers will remember the saga of Yssabelle, one of the little humans on my caseload. Two years ago today, Yzzy’s parents made the heart wrenching decision to move forward with the only remaining option: a bone marrow transplant.

For the uninitiated, Yzzy had true systemic mastocytosis, which is rare in a child. She also had a primary immunodeficiency, adrenal insufficiency, seizures and a half dozen other things. She reacted to everything. She couldn’t eat. She couldn’t go to school. She couldn’t run around. She had a central line and received continuous infusion 24 hours a day. She shocked multiple times a month. Just awful.

In 2016, after months of decompensating, Yzzy was diagnosed with hemophagocytic lymphohistiocytosis, a rare blood disorder that causes her body to eat up its own red blood cells. Mast cell patients around the world prayed for her, sent cards and presents, and bought the Girl Scout cookie she was shilling like a pro. We tried several therapies to manage the HLH. None of them worked.

There were a lot of things that we didn’t disclose at the time. People knew Yzzy was sick. Most have no idea how sick she was. Yzzy was dying. She was going downhill at a breakneck speed. She had failed other treatments for HLH. She had significant organ damage. The pain was awful. Without the transplant, Yzzy would die of HLH. But there was a less than 50% chance of surviving the brutal induction chemo and transplant. Truly the stuff of nightmares.

Because Yzzy was already assuming all the risk of a transplant, our goal became curing not just HLH but her systemic mastocytosis. While having no experience with mastocytosis, her transplant team was excellent. They were open to learning about mast cell disease and taking advice from experts. Ultimately, her induction chemo protocol was altered to increase our chances of success in killing two birds with one stone.

I don’t know a word strong enough to convey the terror I felt everyday for this little girl. Afraid to the point of paralysis. The stakes were so, so high. There was no margin for error.

I really thought she was going to die. I said to a close friend, “When Yzzy Eddlemon dies, I’m out.” Done with working patient cases. This wasn’t a moment of hysteria. I meant it. I didn’t think my heart could take watching another child suffer through everything that Yzzy had experienced.

But then something miraculous happened: she didn’t die. Against incredible odds (literally almost dying two days before the transplant), she survived. We anxiously waited for months to see if the transplant had cured her HLH and mast cell disease.

It did. It worked. Her mastocytosis and HLH were both cured. Her immunodeficiency and adrenal insufficiency and seizures all resolved. She could eat food. She wasn’t reacting constantly. There was no anaphylaxis.

She will be monitored for the rest of her life and some damage to her body was permanent. But compared to her life two years ago, a few appointments every six months is barely a blip on the radar.

Two years later, Yzzy is in third grade. She eats whatever she wants. She exercises as much as she wants. Laughing doesn’t cause reactions. She no longer has tubes running out of her body. She’s no longer on masto meds at all. She doesn’t have anaphylaxis.

Many mast cell patients have to cope with the fact that despite the seriousness of their disease, they often don’t look sick. Not so for Yzzy. Her illness was never invisible. She was covered in mast cell lesions and hives. She always wore a mask. Her alert dog was constantly by her side. Her lost her hair. She was sometimes so skinny she looked frail and at others was swollen to the point that she no longer looked like herself.

She has reached an important milestone in her life: she finally looks healthy. Her outside matches her inside. And because of this, I imagine that she looks ordinary. She’s not. She is the match that lit every candle extended toward her. A tiny vessel that held the hopes and dreams of thousands of people worldwide.

Healthy. Superhuman.

Wonder Woman.

Stability of compounded IV Benadryl

Hey,

I’ve been working on the IV Benadryl shortage from a different angle and I’m starting to see results. Currently, compounded IV Benadryl is considered a high risk sterile compound because it’s prepared from a non sterile solution (edit: I initially wrote non sterile solution here by mistake). Board of Pharmacy/FDA guidelines state that in the absence of other evidence on day supply, compounded IV Benadryl is good for three days in the refrigerator. They also state that freezing breaks the molecule, rendering it much less effective. I found data that demonstrates that both of these things are false. Compounded IV Benadryl CAN be frozen without affecting molecular stability. There’s also data demonstrating that compounded IV Benadryl is stable much longer than three days both at room temperature and refrigerated. This is without preservative. Just diphenhydramine and water.

Pharmacists can use this data to inform day supply at their discretion. If they decide to do this, patients can pick up large supplies with much less labor and cost to pharmacies.

I would urge patients who are unstable without this medication to contact a local sterile compounding pharmacy. In some places, large hospitals will sterile compound for established outpatients, but this is very location specific.

I know this is a scary and stressful time for many of us. I want to be clear that patients who require this medication are not at fault for its shortage. There are all kinds of process controls to prevent critical shortage of ubiquitous, life saving medications. Manufacturers, distributors, and pharmacies are ALL required to track usage to allow for increased production runs if needed. Hundreds of meds are used off label and production is increased when usage is properly reported. So if you’re barking up this tree, stop barking.

There are multiple factors contributing to the shortage, including shortage of FDA approved sterile diluents like saline; the fact that some manufacturers buy their IV Benadryl premade from another manufacturer and just relabel it; manufacturing sites closing for reasons including natural disaster and acquisition by other pharma groups; and communication issues from literally every agency and organization involved in the shortage and public notification. It is so, so complex. I would love to work with an investigative journalist to tell this story once the emergency is resolved. I do not release information I cannot prove and that is not the best use of my time right now. There will be a reckoning once people are safe.

Fresenius released a small lot of IV Benadryl on Monday. Most of this lot will be used to replenish institutions and emergency services providers before there is enough to distribute to patients. The fact that even a small amount is available is a good sign.

There is a rumor flying around that IV Benadryl is not going to be made anymore. I have worked in this industry for fifteen years, have contacts at the FDA and the CDC, and spent a lot of time talking to Global Program Management for this med for US licensed distributors. I have no reason to believe IV Benadryl won’t be made again. I believe that when the shortage resolves, patients will have ready access to this medication. If I learn anything that contradicts that, I will let people know.

This will end. We are getting through this. Okay? Okay. Courage.

xoxo,

Lisa

Link to data on stability of IV Benadryl

For patients affected by the IV Benadryl shortage

From the Mastocytosis Society:

URGENT Announcement about Diphenhydramine (benadryl) IV solution:

If you had been on IV diphenhydramine solution continuous infusion prior to the backorder, and are now seriously unstable because of it, please send an email to nurses@tmsforacure.org with the following information:

1. your name

2. the name of the physician who prescribes the

diphenhydramine and actually writes the order

3.your email address

4.your phone number

5.the name of your pharmacy and phone number or

infusion company if you would like it delivered there.

Please include a statement saying,”On November 6, 2018, I agree to let the TMS nurses share this information with pharmaceutical companies who make IV diphenhydramine.”

Please do not send in your name “just in case”. We have patients who are critically ill right now and need this medication.

Thank you.

Valerie M. Slee, RN, BSN, TMS Chair