There are a lot of new and exciting/terrifying updates in this post. I really wanted to write this blog post myself but as you know, It is the end of the fall semester (AKA hell on earth) and after being completely useless for 7 days, I am way behind on school work. So, I have asked my dad – Dr. Eric Schwam, to step in and help write another guest post for me. I have also added in some blurbs of my own which will be labeled, and italicized teal font in order to avoid confusion.
We met with Dr. Lawrence and Riley yesterday and there are some new developments. After a week of fever, shaking chills, and night sweats, Elana is swamped with schoolwork, so she asked me to write this post for her.
Blogpost #13 left off on Saturday when she visited the MGH ER. On Saturday night and Sunday morning she again had a fever of over 103 ºF. She took her first dose of prednisone on Sunday morning. The good news is that she did not spike another fever since then. The bad news is that on Monday, her liver enzymes came back abnormal. They were elevated during the interferon treatment, but had returned to normal afterwards. Specifically (for you science nerds and medical people), her alkaline phosphatase is 203 (normally 30-100), her AST is 154 (normally 9-32), her ALT is 114 (normally 7-33), and her LDH is 452 (normally 110-210), but her bilirubin, albumin and total protein are normal. To put these results in perspective, these are significant elevations, but they are not terribly abnormal, as these numbers can go into the thousands if there is serious liver injury.
Elana: Also important to note is that when my liver enzymes were elevated during interferon treatment, it was because my liver was just “overwhelmed” with the astronomical amount of interferon we forced it to process, but was not actually causing any real damage to the liver. It is different with Ipi, where it’s more possible that the liver enzymes could be elevated due to damage done to the liver, but we hope otherwise and my dad explains more about that below.
Another test result that came back abnormal that my dad has not mentioned (because these results became available after my appointment was over and the discussion was between only Riley and myself) is that my thyroid gland is probably toast AKA no longer functioning. Riley believes that the interferon may have exhausted my thyroid and this is just a delayed response. My TSH (thyroid stimulating hormone) was 5.52 (norm is 0.40-5.00) and my free T4 was 0.8 (norm range is 0.9-1.8). When your TSH is high and your Free T4 is low, this means clinical hypothyroidism. As you can see I am very borderline but this has been going on for some time and we were hoping it would bounce back. Riley plans to retest these labs again on Thursday but she told me she anticipates having to start me on synthetic thyroid hormone (called levothyroxine), in the next week or so pending my labs. Levothyroxine essentially replaces the thyroid hormone in the form of one pill that I will take for the rest of my life. Hypothyroidism is no fun. It makes you excessively tired/fatigued, cold, irritable, depressed and you easily gain weight. I will be happy not to have this happen.
Dr. Schwam: In regard to the fever, there is no evidence of an infection, and the fact that the fever resolved so quickly following the start of prednisone suggests that the fever had an immune rather than infectious cause.
As for the abnormal liver enzyme tests, there are two possible explanations for this. The first (and the one we and Dr. Lawrence are hoping for) is that these elevations are nonspecific and have been caused by the fever. These liver enzymes are actually contained in a variety of tissues, including liver, muscle, kidney, heart, brain, etc. When these tissues are injured, the enzymes are released into the bloodstream. Elana’s entire body certainly took a beating from that week of fever and maybe these elevated blood levels merely reflect that fact. If this is the case, Dr. Lawrence feels that the prednisone can be tapered rapidly over a week. The other possibility is that the ipilimumab (ipi) is now causing autoimmune hepatitis. (There are many causes of hepatitis. This hepatitis has NOTHING to do with alcohol or IV drug use. Elana does NOT have a viral or infectious cause of hepatitis. It is NOT contagious.) In this version of autoimmune hepatitis, the T lymphocytes that are stimulated by the ipi go looking for melanoma cells to kill but mistake the liver cells for their intended targets. They attack the liver cells and liver enzymes are released into the bloodstream, causing the test results to be elevated. The liver is an innocent bystander in this process, which needs to be stopped before it gets serious. Again, the mainstay of treatment for this is prednisone, but the treatment course usually lasts weeks, if not months. Long term treatment with prednisone is usually accompanied by many significant side effects which Elana would like to avoid.
Elana: It’s me again. I really can’t not throw in my 2 cents about prednisone. I have a like/hate relationship with it, but mostly hate. I like it because it made my fevers go away and it should theoretically calm any other inflammation that Ipi has fired up by accident. But the side effect profile is just the fucking worst. The longer you are on prednisone, the more the side effects occur and It makes me real angry that I have to put my body/mind through more bullshit.
Here’s a list (not-exhaustive) of side effects should I be on it long term. The top 3 side effects can occur with only short-term treatment as well. For the next week I am on the highest dose possible of prednisone at 60mg/day.
- Mood changes (euphoria, depression, excitability, psychosis, irritability, anxiety, aggression, etc)
- weight gain and excessive hunger/increased appetite
- thinning skin
- slow healing wounds
- increased risk for infection
- fat deposition in face (moon face), back of neck (buffalo hump), and abdomen
- thinning/muscle loss of extremities (arms and legs)
- acne & red face
- osteoporosis – increased risk of fractures
- GI upset and stomach ulcers
- thinning hair
- And much more –> Prednisone side effects
And if you’re more of a visual learner, here’s an image. Prednisone side effects are also grouped into what can be called a “Cushing-like syndrome. “
Dr. Lawrence has suggested (and Elana has agreed) that she undergo a liver biopsy to see if there is evidence of autoimmune hepatitis. Barring a dramatic improvement in her lab tests on Thursday, this will likely happen at the end of this week or early next week. The procedure will be done on an outpatient basis. Medications are given to reduce pain and anxiety. A needle is inserted through the skin into her liver and a small amount of tissue is removed. The actual biopsy takes seconds and the whole procedure should take no more than 5 minutes. Significant complications are very rare. In medicine in general, and in Elana’s case as well, decisions have to be made in the face of so many unknowns. Hopefully the results of this test will provide information that Dr. Lawrence can use to guide her treatment.
Elana: If the biopsy comes back negative for autoimmune hepatitis, then I may get to taper down the prednisone much more quickly (please oh please oh please oh please). If it comes back positive than I will likely need to be on prednisone for a few months and will probably walk around wearing a ski mask and I may be seen barking at small children. Also if it comes back positive, my liver will have earned itself a name. When I think about my liver, It reminds me of the character Louise Belcher from the show “Bob’s Burgers.” Louise could not be a more perfect fit for the name of my Liver. Here’s a description of her character:
“Louise is the youngest in the family, and an anti-heroine of the series. Her off-balance sense of humor and hunger for conflict makes her somewhat of a liability in the kitchen…She has a Machiavellian and controlling personality. Thriving on drama and adventure, she will go to great lengths to create them, even if it means endangering herself and her family… In most episodes, she will manipulate people into thinking or acting a certain way…She understands how to control a situation and get people to do whatever she wants. Even if she is blamed, she is usually able to charm herself out of the situation. She seems to enjoy causing pain and misfortune to others”
Dr. Schwam: In all likelihood, Elana will not go back on Ipi. The two doses she received have done the job of stimulating the immune system. If it were to be restarted, the same complications would likely happen again. There is some data from the scientific trials that suggests that patients who have immune complications from the ipi are more likely to have anti-melanoma activity as well, so maybe there is somewhat of a silver lining to these events.
Elana: I sort of anticipated that this was going to happen during fever hell week and was mildly upset at first but you know what? I have had enough of Ipi and all of it’s side effects so I am okay with being done with it. I am especially okay if what they say is true about immune complications being a good prognostic factor and that the efficacy of the drug is not related to how many infusions you get through. So here’s to hoping 2 is enough and I’m pretty sure my immune system was activated when I was having 103 degree fevers and floating toward a teal light in the distance.
Dr. Schwam: I’m honored that Elana has asked me to do this blog post for her. I hope it conveys the important information without being too technical and boring. Maybe once the prednisone taper is completed, she will be done with Melanie, and (except for follow up scans and blood tests for the next 10 years), my brave, intelligent, quirky, loving, and beautiful daughter can go back to living a normal life. I will continue to do blog posts for her whenever she asks.
Elana: Dad, you did a great job as always and saved me at least 2 days of editing. I love you. To everyone else, we will continue to update when we know more, likely after Thursday. Please know I am trying my best to stay positive and keep my head up, but I do apologize in advance for any potential future prednisone related outbursts. I love you all and am so grateful for support that continues to pour in. I’m Keeping my head up and throwing away all the leftover pie.
And for no reasons other than I’m emotional and grateful for having such an intelligent, loving, and adventurous father, here is a small collection of pictures I could find of us/my fam from my computer over the years. They are in rough chronological order. Enjoy.
Also I finally updated the timeline again.