February Visit to Vanderbilt Medical Center in Nashville

We were honored to once again visit the research lab of Dr. Elizabeth Phillips at Vanderbilt University Medical Center in Nashville.  The research is tedious, complex and encouraging! There are currently 24 sites across the US and Canada focused on the research of drug induced disease. Dr. Phillips’ Laboratory works closely with Murdoch University in Perth, Western Australia as well.

The research team is currently writing a grant to fund universal registries and sample collection.  There is encouraging advances in the study of t-cells and blister fluid however more samples are needed to advance this important research.

Quick Facts:

There are between 1 and 5 cases per million people in the US, however there is no mandatory reporting of SJS at this time.

Only 2-8% of those with the genetic biomarker for SJS will manifest symptoms however it can be devastating for those that do.  Early diagnosis, discontinuing the drug that triggered the attack and specialized treatment of symptoms is essential.

Stevens Johnson Syndrome (SJS) is primarily a drug induced disease which frequently starts with a fever

Awareness is Key and financial funding is helpful so please help us spread the word!  You may donate directly to Vanderbilt University Medical Center using the link from this website.

Update on Progress in SJS/TEN Research 2016/2017– Phillips Lab – Vanderbilt University Medical Center (VUMC)

The mission of the SJS/TEN research program at VUMC is to 1) improve preventive efforts and facilitate translation of genetic screening into the clinical and pre-clinical setting to prevent SJS/TEN through excluding patients at risk from high risk drugs and facilitating the development of safer drugs less likely to cause SJS/TEN. 2) Identify biomarkers associated with SJS/TEN that could lead to earlier diagnosis and specific and sensitive measures for point of care diagnosis in communities without access to specialty care (to expedite transition into specialty care such as Burns centers 3) Identify the mechanisms driving SJS/TEN that will lead to an understanding of the molecular and cellular signals that will lead to discovery of targeted therapies to prevent morbidity and mortality associated with SJS/TEN.

To read the entire update click HERE

Paul’s Speech at the Genomic Medicine Meeting in Silver Spring, Maryland

This is the speech I gave at the Genomic Medicine Meeting in Silver Spring, Maryland on May 2, 2017. I was invited by Duke University’s School of Medicine’s Center for Applied Genomics and Precision Medicine and The National Institute of Health to tell “Angela’s Story” It was not an easy story to tell but it puts a human face on the research these doctors do and shows them that their pie charts and bar graphs and statistics are real people with real names and real families. My goal was and is to inspire them to work harder to conquer Stevens Johnson Syndrome, adverse drug reactions and other genetic diseases.

NIH probes the genome to understand severe drug reaction

By Sheena Faherty, Ph.D.
Science Writer, NHGRI
Angela Anderson, a 22-year-old woman, fell victim to the fatal genetic condition, Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, or SJS/TEN. Photo credit: Paul and Wanpen Anderson.

“Angela was unique. She was a trendsetter … one in a million. The disease that took her was one in a million. Even in death, she stood out from the crowd.” 

These poignant words are from the eulogy for 22-year-old Angela Anderson, a young woman who was taken too soon by a rare genetic condition known as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN).

SJS/TEN is the severest of adverse drug reactions that affect the skin, and one of the most severe of adverse reactions affecting any system in the body. It impacts about 1-3  people per million in the United States each year.

SJS/TEN occurs with an attack from the immune system and starts with a fever and flu-like symptoms. Within a few days, the skin begins to blister and peel, forming very painful areas and looking much like a severe hot-water burn. In up to 80 percent of cases in adults, SJS/TEN develops after someone takes certain medications, such as drugs for seizures, gout or sulfa antibiotics. The reaction likely occurs because a person carries certain changes in their DNA, called genetic variants, that make them more susceptible to developing SJS/TEN.

“We’ve identified some genetic variants that can keep us from using certain drugs in susceptible individuals,” said Teri Manolio, M.D., Ph.D., director of the Division of Genomic Medicine at the National Human Genome Research Institute (NHGRI). “Now, we need to find many more such variants and understand how they cause the syndrome so we can develop effective treatment and prevention strategies.”

At NHGRI, Dr. Manolio’s team supports research to help medical practitioners bring genomic medicine to the clinic; that is, to develop approaches for the use of genome sequencing and other tools to improve diagnosis, treatment and prevention of diseases, such as SJS/TEN, that might have saved Angela Anderson’s life.

“Doctors believe [Angela’s SJS/TEN] was triggered by ibuprofen [she had taken for a fever],” wrote Angela’s father, Paul, in an online article about his family’s ordeal.

What followed the next day was an eye infection, a high fever and rash; then a downward spiral with severe blistering of the skin and mucus membranes; and finally kidney and organ failure. Four days later, on December 28, 2015, she was gone.

“In the three days she was in the hospital, our whole family was put through one of the most heart-wrenching and helpless situations anyone could be put through,” Mr. Anderson wrote.

The search for SJS/TEN research turns up empty

In 2014, Thai researchers reported that they were screening patients in the hospital for risky genetic variants that make them susceptible to developing SJS/TEN. The genetic information was then added to a pharmacogenomics ID card – a purple plastic card that fits easily in a wallet. (See the research talk here).  

Dr. Manolio was intrigued by this approach: could a simple card that alerts doctors and patients to avoid certain medications be a key to saving patients at risk for SJS/TEN?

“We thought that this would be a very effective and important effort to try to adopt as a signature initiative of a global genomic medicine collaborative, using SJS/TEN as a model,” Dr. Manolio said. “We can learn a lot from settings where simple interventions can be implemented system-wide – as in smaller countries with national health systems – and apply their lessons on much broader scales.”

But for this to be successful, more research and more support for research was needed. Dr. Manolio knew that NHGRI could not do this alone, so she and colleagues planned to mobilize other institutes at the National Institutes of Health (NIH) doing work on SJS/TEN. However, this strategy led only to the realization that little work was currently being done on the disorder. So, in March 2015, NHGRI organized a workshop, in collaboration with the Food and Drug Administration (FDA) and other NIH institutes, to identify the research gaps and unmet needs in SJS/TEN research.  

Workshop gives hope to those searching for answers

Dr. Manolio received a call from Paul Anderson in January 2016, less than one month after he had lost his daughter to SJS/TEN, saying that his family had received donations for research on the disorder, and they couldn’t find anyone to give them to. He, too, had come up short in his search for SJS/TEN research.

Dr. Manolio introduced  them to Elizabeth Phillips, M.D., professor of medicine at Vanderbilt University Medical Center, and one of the researchers at the conference on SJS/TEN. Dr. Phillips’ work focuses on identifying the genetic risk factors that predispose patients to severe immune mediated drug reactions like SJS/TEN, as well as studying the immunology of why these dangerous adverse drug reactions occurs in some individuals but not in others.

“We’re looking at the specific molecular and cellular signatures in the skin and blood of those individuals presenting with SJS/TEN, trying to understand if there is a signature that can help us understand and identify which of the small portion of individuals that carry a genetic risk factor will develop the disorder,” she said. “We think if we can get those signatures defined for specific drugs, then those could be used as a screening mechanism before an individual is exposed to a drug.”

SJS/TEN is a disease that affects multiple organs – everything from the skin, to the eye, to the kidneys. To truly understand the disease, the research effort needs collaboration from experts in disparate areas that can put all the pieces together. To that end, on March 2, 2017, Vanderbilt University Medical Center held a multi-disciplinary, one-day meeting, supported by the NIH and the FDA, that focused entirely on SJS/TEN.

“This meeting was successful in bringing researchers together that not only focus on different aspects of SJS/TEN research but who bring together expertise on genetically and ethnically diverse populations that would never be gathered in one room,” said Dr. Phillips. “The intended outcome from this meeting is to build a network of investigators whose research efforts will be synergistic in their contributions to SJS/TEN research.”

The meeting also included representation from the SJS Foundation – including founder Jean Farrell and her daughter, Julie, a two-time SJS sufferer, SJS survivors, and families such as the Andersons, whose recent loss of their daughter was relayed to conference participants.

Discussions from the meeting will be published in the Journal of Allergy and Clinical Immunology: In Practice later this year and will outline how researchers will continue to work on identifying and standardizing the clinical features of SJS/TEN and improve ways to collect data on individual treatment plans.

And moving forward, NHGRI and other NIH institutes are funding research on serious adverse drug reactions, with NHGRI’s focus specifically on a better understanding of genetically-mediated adverse drug reactions – an area in which, people like Dr. Phillips are already making great strides.

“The big advance in this disease has been starting to identify the immunogenetic mechanisms and strong genetic associations that have been seen with drug-induced SJS/TEN,” said Dr. Phillips. “But, the ability to finally put closure on that so other families do not have to go through what they’ve gone through – that would be huge for most families. If they could see, even in the face of losing a loved one with SJS/TEN, that these research accomplishments will lead to better prevention and treatment and lower morbidity and complications in others and other families, I think that would greatly benefit them.”

Making A Difference

Shortly after the article was published in the News Gazette, the reporter, Tom Kacich, received the following email:

Hello Tom,

I’m hoping you can help me. My name is Carrie Victor. On
12/20/2016 I was diagnosed with toxic epidermal necrolysis. Fortunately I
lived to tell. Through this experience I became aware of the tragic story
of Angela Anderson. A google search lead me to your article and as I read
the story with a heavy heart it was all to familiar. I suspect that
Angela’s case raised the awareness necessary among the medical community
for me to get a quick and accurate diagnosis. I was immediately
transferred to Springfield Memorial for 10 days of treatment in ICU in the
burn unit. I believe that it is because of Angela that I am alive today.
It’s important to me that the Anderson family know that I think their
daughter may have saved my life. I want them to know that I join them in
their fight to raise awareness and I hope through our efforts research
with come about. I am working hard to raise awareness among the medical
community as well. Why do so few know what this condition is? Why is it so
commonly misdiagnosed? These are questions that need to be answered. Why
is it not required by physicians to report SJS and/or TEN to the FDA? I
want the Anderson’s to know that I too ask these questions and as I
continue to recover I’m doing my best to spread the word in hopes that no
one else shares in our experience. If there is a way that you can forward
this email or contact the family to let them know that I’d gladly assist
and participate in any way that I can to raise awareness and support them
in our cause I’d really appreciate it.

Thank you Tom.

Grieving family trying to cure disease

CHAMPAIGN — A family is trying to raise money to find a cure for a condition that killed their youngest. It was the Anderson’s first Christmas without their youngest daughter Angela. She contracted a rare disease that killed her almost a year ago. Now, her family is doing what they can to prevent another family from feeling that same pain.

They wrote a check to Vanderbilt University for $22,000. That’s a thousand dollars for each year Angela Anderson was alive, although that wasn’t the intention. That’s just how much they were able to raise.

Anderson contracted Stevens-Johnson Syndrome (SJS) On Christmas Eve last year. It started with an eye infection and she  went to the hospital thinking it was measles or something less mild. It turned out to be SJS, which leads to a rash and blistering on the eyes, mouth and other areas. She only lived four more days.

Paul Anderson says when her daughter died they asked people to send donations for research instead of flowers. The family held a benefit a few weeks later, by that point they had nearly $15,000, but Anderson says they couldn’t find anyone in the u-s working to find a cure. Finally they found a doctor at Vanderbilt who could put the money to good use.

Paul Anderson says, “We felt like we were doing something good to help other people. Something Angela would want us to do to try to keep someone else from going through what she had to go through.” 

The Anderson’s are asking people to keep donating for a cure. If you would like to contribute you can find a link here.

The family is also trying to organize a walk in order to raise more money. That could happen in spring if things go as planned.

Research shows genetics might have something to do with contracting SJS. Doctors says it happens to people with a gene called HLAV. They say that gene reacts poorly to certain types of drugs. Angela Anderson’s doctors say in her case it was Ibuprofen.

By Luke Ray | lray@wcia.com

To view the complete story click here.

My Eulogy at Angela’s Funeral

Angela was unique. She was a trendsetter. Everybody says she was “cool”, but not only that, she made people around her feel cool. She had a way of making everyone feel welcome around her. People that didn’t “fit in” felt like they fit in when they were around her. Friends told me, “She was the life of the party! The party really didn’t get started till she got there and when she left, the party was over”. She was a leader not a follower, a trend setter in fashion and social media. She was one in a million. Her humor was different, which is why she was so funny. Her friends said, “She could make you laugh till you cried”. She could not even die traditionally. The disease that took her was one in a million. Even in death, she stood out from the crowd.

We wanted her to stay here with us. It’s hard to believe that anyone could love her more than we did but God does and He wants her in Heaven now. In John, Chapter 14, Jesus says, “I go to prepare a place for you. And If I go and prepare a place for you, I will come again and receive you unto myself. That where I am you may be also.” Well, that was over 2,000 years ago and he’s still not done preparing heaven. I was comforted this morning as I read this passage that the reason God needed Angela at this time was because He needed her innovative creativity to make Heaven more unique and more fun. But why now, why couldn’t He wait? …Maybe He wanted her now before she “grew up” if you will, before she grew older and more conservative as people do when they get older. He wanted her at the height of her unique, loving and fun spirit. Or, maybe He just needed someone to keep Him laughing. At any rate, Heaven just got a little bit better.

So I say to you remember her spirit and let your memories of her inspire you to step out and share that same unique spirit of hers with the world and make it a brighter place just as she did.

Angela’s Final Days (Updated)

angela-red-eye

On December 23, Angela had plans to go out with her friends but cancelled because she had a fever and didn’t feel good.  She took ibuprofen for the fever and went to bed.

On Christmas Eve Angela texted her mother, Wanpen at 2:38 pm showing a picture of her eye infection and complaining of pain.  She thought she had “pink eye”. Wanpen told her to go to Carle Convenient Care.  She went and saw a doctor at 4pm.  The doctor gave her some erythromycin ointment for her eye and tested her for strep.  The strep test came back negative.  The doctor told her she had a viral infection, to take something for her fever and to get some rest. She went back to her apartment, took some ibuprofen and went to bed.

I called her later asking her if she wanted to go to 7:00 Christmas Eve Mass with us.  She said she didn’t feel up to it.  At about 9:00 pm she called me and asked if she could spend the night with us because she felt so bad.  I picked her up at her apartment and brought her home.  Her eyes were swollen and her throat hurt.  I took her temperature, (103.7) gave her some Tylenol and she went to bed.

At about 2am Angela woke me up saying, “Dad, you have to see this!”  I went into the bathroom where she was and she showed me the inside of her mouth.  The inside of her cheeks and throat were black and blistered.  I gave her some warm salt water to gargle, she went back to bed and I got on the internet to try and find out what I was seeing in her mouth and throat.  Nothing online resembled anything that I had just seen.  She woke up a few hours later and gargled some more salt water.  Her throat hurt and she was in pain.  She went back to bed.

Christmas morning I got up at sunrise to check on her.  Her eyes were swollen and sore and her throat was very sore and her face and neck were swollen.  Wanpen and I decided that she needed to go back to Carle Convenient Care.   Angela and I arrived there and after waiting about 5 minutes she was seen by a nurse practitioner.  She looked at Angela and by this time a rash had formed on her chest and arms.  She said, “You need to go to the Emergency Room ASAP.  I will let them know you’re coming and will get you checked in.”  So we headed for Carle Hospital ER.  On the way there, Angela said, “Why does this have to happen on Christmas?  We’re supposed to be with Fam [Family] today.”

It wasn’t long after we arrived at the ER that she was in a room and a doctor was examining her.  Soon there were 5 doctors examining her and conferring with each other trying to figure out what was happening to her and what the next step should be.  It was like an episode of the TV series “House”.  One doctor told me that she had the symptoms of Stevens Johnson Syndrome.  He also told me that they may have to send her to the burn unit at Memorial Medical Center in Springfield or Barnes Jewish Hospital in St. Louis.  However, someone decided that she should stay at Carle’s ICU. 

Angela arrived at ICU sometime before noon.  By this time, the outer skin on her lips had dried up and peeled off, her eyes were badly swollen (almost shut), her face was swollen, her chest hurt and her throat hurt so bad that swallowing was intolerable.  It wasn’t long before they were giving her morphine for pain.  The morphine took the pain away from her chest and eyes but not from her throat.  They were afraid to give her too much morphine because it might affect her breathing.

Meanwhile back at home, Wanpen was preparing Christmas dinner for 17 guests including her mother.  Wanpen picked up her 95 year old mother at her nursing home that morning.  We thought that this was probably going to be her last Christmas with her family (she died almost a year later on Dec 14, 2016).  Had we known the seriousness of Angela’s condition at this time, we would have cancelled Christmas dinner and Wanpen would have spent the day at the hospital with Angela and me.

She was still in a lot of pain but her cousins, Joe, Adva and Joy came by to visit and it seemed to cheer her up.  Then her brother Tim and his girlfriend Jojo came by and she was joking around with them.  Angela’s mother, Wanpen, her two sisters, Jitra and Suthisa and their friends stopped by to visit after that.  Wanpen told Angela that she would pray for her and asked her to pray for her own healing.  She said that she would.  Wanpen told Angela that she loved her and Angela said, “I love you, too”.  That’s the last words she spoke to her mother.  She still seemed in good spirits at that time even though she was in a lot of pain.

After they left she was hurting more than ever.  She was screaming whenever she had to swallow.  The doctor eventually gave her some more pain medication for her throat and after a while it seemed to help a little bit.  By this time, skin was peeling off of the backs of her ears and the palms of her hands.  But still, she was texting her friends and half joking about what was happening to her body and asking them to come visit her.

I spent the night with her and was awoken by the doctor at about 5am (Dec 26).  The doctor told me that what I saw happening to her outer skin was happening on the inside of her body.  “She’s burning from the inside out”, he said.  He said that they would have to sedate her, put her on a ventilator and drain the fluid out of her lungs because they were full and she wouldn’t be able to breathe without a respirator. 

This is when I first realized that we could lose her.  I completely broke down crying.  When I got my composure I went to see her before they went through with this procedure.  Skin was peeling off of her face now.  I told her I loved her and she said, “I know, I love you too”.  That was the last words she ever spoke.  (Up to this time she continued to text her friends, post status updates on Facebook, tweet her friends on Twitter and send selfie pics of herself right up to the point that they had to put the breathing tube in her).

Her condition seemed to level off after that.  When the doctor that had put her on the respirator that morning came back that night for his next shift he said he was a little encouraged because she hadn’t gotten any worse.  But they still did not know what was causing this.  They were not sure if it was viral or bacterial.  They thought it might be Mono, Mumps or Measles so they put her in an Airborne Isolation room.  They put her on a wide spectrum of antibiotics hoping that one of them would work.

The fact that she wasn’t getting any worse made us feel a little better.  Then the doctor told us that her kidneys were failing.  She would be put on a Continuous Dialysis machine to filter the blood for the kidneys.  Her other organs were weakening also but her heart was still strong. 

It was at some point in this day (Dec 26) that they thought it would be a good idea to send her to Barnes Jewish Hospital in St. Louis.  But there was a problem.  There were severe storms and tornado warnings out and helicopters could not fly.  Also, they thought a 3 hour trip by ambulance was too long and too risky, that she might not survive the trip.

By Sunday, Dec 27, they had ruled out that it was an airborne disease and took her out of isolation.  They narrowed down the antibiotics to treat it as a bacterial infection and gave her Intravenous Immunoglobulin (IVIG) to try to help her own immune system fight it. 

Sometime that day her kidneys failed and she was getting more and more fragile.  In the late afternoon two doctors came to us suggesting that she have lung bypass surgery.  They had tried to drain her lungs again but the fluid had gravitated so far down into her lungs that it was impossible to drain enough fluid to help.  They said that her blood was not getting enough oxygen to sustain her organs.  The lung bypass machine, ECMO (Extracorporeal Membrane Oxygenation) is basically an artificial lung that oxygenizes the blood.  A tube is inserted in the femoral artery (in the groin area) and another tube is placed in the jugular vein (in the neck).  The unoxygenated blood flows from the femoral artery into the ECMO (artificial lung) where the blood is oxygenated and then returns to the body though through the jugular vein and on to the heart with 100% oxygenated blood.

They told us first of all that the surgery was extremely risky and that in her fragile state she may not survive the trip from her room on the 7th floor to the operating room on the first floor.  Also, that if she survived the surgery that she may not survive the trip back up the elevator to ICU.  So our choice was to do nothing with little chance of survival or attempt the risky surgery to give her and the doctors more time to fight the infection.  The surgery was a success.

Wanpen, Tim and I and the many visitors as well as the tremendous following on Facebook were encouraged by this, thinking that if she could survive this, she could survive anything.  However the next day, Dec 28, things got worse.  The doctors were more or less back to square one in fighting this mysterious disease.  Now they weren’t sure once again if it was bacterial or viral. 

At 4am they checked her eyes to see if her pupils responded to light and they did (This is something they did every 4 hours).  It was this morning that they called in a retired Infectious Disease specialist to see if she could come up with something new.  At 8am they checked Angela’s pupils again to see if they reacted to light.  They did not. 

Then they contacted Barnes Hospital again.  The doctors at Barnes said they had a bed for her.  The weather was still not good but they were going to send one of their own “fixed wing” aircraft to pick her up.  It was extremely risky to transport her but by this time it was the last option. 

The doctors at Carle told us that the people at Barnes wanted them to do a CT scan on Angela’s brain.  If blood was in her brain, there was no hope.  If there was not blood in her brain, they would fly her to St Louis.  The CAT scan pictures showed that she had multiple pockets of blood throughout her brain and she was brain dead. 

We were left with the decision of leaving her on life support or turning it off.  Wanpen and I went in and held her hand, hugged her and said our goodbyes.  We told all of Angela’s friends and our friends that were in the waiting room that they all could do the same.  When everyone had said their goodbyes, we asked the doctors to turn off life support and we waited until her heart stopped at 6:01 pm Dec 28.

After multiple diagnoses throughout these 4 days, the doctors now believe that Angela succumbed to Stevens – Johnson syndrome / Toxic Epidermal Necrolysis (TEN), also known as Lyell’s syndrome, a rare, life-threatening skin condition that is usually caused by a reaction to drugs. They now think that it might have been triggered by Ibuprofen.  I might add that Angela has been taking Ibuprofen since she was a baby.  SJS/TEN can be by triggered hundreds of different drugs.

If you would like to donate to SJS research, you may do so at:   https://vanderbilthealth.com/sjsresearchfund