When 10-year-old Andrea began having vision problems, there was no way her family could have predicted the complex diagnostic odyssey they were about to embark upon, or that it would take four years, four hospitals and advanced genetic testing to finally determine the genetic disorder she suffered from, and which treatment would lead to her recovery.

Andrea's medical journey began in September 2016, just as she was beginning 5th grade. In school one day, Andrea "couldn't see part of the paper in front of her," says her mom, Beth.

Concerned, Beth called the family's optometrist who recommended they bring her to the local hospital to be checked out. Emergency Room doctors diagnosed Andrea with a migraine, suggested over-the-counter medication and discharged her with instructions to return if she vomited.

"We didn't even make it out of the hospital before she threw up," Beth says. ER doctors ordered an MRI of Andrea's head and discovered substantial swelling. Then, she lost her peripheral vision. Unsure what was causing her symptoms, doctors transferred Andrea to a nearby pediatric hospital for more tests.

Pediatric specialists were also puzzled. After ruling out several possible causes, they believed she had acute disseminate encephalomyelitis (ADEM), a rare inflammation of the brain and spinal cord. She was prescribed steroids to shrink the inflammation and released home.

Treating seizures

Over the next two months, Andrea suffered seizures, which doctors treated with steroids and then switched to anti-seizure medication, recommending more testing.

A follow-up MRI revealed widespread inflammation in Andrea's brain – so much that the doctors "wondered how she was even walking," Beth says.

That's when a more urgent search began to find the cause of the inflammation and determine the best way to stop it.

"They tested her for everything – multiple sclerosis, neuromyelitis optica and a whole slew of other things," Beth says. "Finally, they told us she had a demyelinating disease of the central nervous system that was attacking her brain. It wasn't an exact diagnosis, but at least they could begin treating her."

Andrea was prescribed Rituxan® to suppress her immune system and fight the inflammation in her brain. The medication alleviated some of Andrea's symptoms, but not all. She continued to have vision problems, balance issues and recurring brain inflammation.

Searching for answers

While the medication was helping, Andrea's family continued to worry and searched for more complete answers. While at a meeting of the Siegal Rare Neuroimmune Association (formerly the Transverse Myelitis Association), they learned about a doctor who was making great strides with demyelinating diseases: Brenda L. Banwell, MD, Chief of Neurology at Children's Hospital of Philadelphia (CHOP) and a specialist in diagnosing and treating neuroimmune disorders.

"She was the go-to expert for demyelinating disease," Beth says. "So, we made an appointment, loaded up the car and traveled to Philadelphia for a few days of doctors' appointments and visiting historic sites."

The family met with Dr. Banwell in June 2018. After an examination and review of  previous test results, the doctor offered the family advice about changing some of her medications – specifically weaning off steroids before puberty to avoid stunting her growth. Dr. Banwell recommended intravenous immunoglobulin (IVIG), a relatively new therapy designed to help children with weakened immune systems fight infections. Dr. Banwell worked with Andrea's medical team in Cleveland to ensure ongoing monitoring during the medication changes.

Andrea responded to the new treatment regimen, grew a few more inches, and experienced fewer noticeable symptoms. However, ongoing tests revealed she continued to have significant areas of brain inflammation.

“We were all stumped: What does Andrea have? How can we help her?" her mom says. "Dr. Banwell said 'we have to get to the bottom of this.'"”

She asked the family if she could present Andrea's case to the Immune Dysregulation Program at CHOP. The unique program includes a multidisciplinary team of experts, state-of-the-art diagnostic and genetic testing, as well as comprehensive research to offer personalized treatment to children with autoimmune and autoinflammatory disorders, especially complex and rare cases. The family agreed.

More testing and Immune Dysregulation at CHOP

In December 2019, the family returned to CHOP for a series of visits with specialists from the Immune Dysregulation Program. Afterwards, the clinical team discussed and ordered a brain biopsy and genetic testing. The biopsy was performed in January and showed the inflamed cells in Andrea's brain were not being affected by her current medication. The team recommended switching to an intravenous (IV) chemotherapy medication that would suppress the T-cells that were mistakenly attacking her brain.

Andrea started the new IV medication in February 2020. Because she lived so far away from CHOP and would need regular infusions, Dr. Banwell partnered with clinicians near the family's home to provide care, while she oversaw Andrea's treatment and advised if changes were needed.

In March, Andrea and her parents sent mouth swabs to CHOP for genetic testing. Then, the COVID-19 pandemic hit the United States, affecting schools, businesses and families.

A rare diagnosis

Two months later, Dr. Banwell called Beth with news: Andrea's genetic test results were in. Dr. Banwell and several members of the Immune Dysregulation Program team – including Rheumatologist Edward M. Behrens, MD, Oncologist and Researcher David T. Teachey, MD, and Genetic Counselor Christopher Gray, MS, LCGC – met with Andrea's parents, Beth and Brian, via videoconference to explain the results and possible next steps.

Andrea tested positive for primary hemophagocytic lymphohistiocytosis (HLH), a group of rare disorders of the immune system that cause the body to attack healthy blood cells. Because Andrea's inflammation primarily affected her brain, she was diagnosed with central nervous system HLH. HLH leads to inflammation, a weakened immune system and a variety of symptoms. Without treatment, HLH can lead to severe organ damage and death.

More About HLH

"Dr. Banwell told us they now knew what it was and how to treat it," Beth says. During a series of virtual meetings, Dr. Banwell introduced the family to members of the Immune Dysregulation Program who would oversee her care: Immunologist Neil D. Romberg, MD, Dr. Behrens and Gray.

The Immune Dysregulation team had assessed Andrea months before, and now – armed with complete diagnostic and genetic results – they collaborated to develop a customized treatment plan including chemotherapy and a bone marrow transplant.

Bone marrow transplant

When neither of Andrea's parents matched as possible bone marrow donors, doctors contacted the National Bone Marrow Transplant Registry. Two months later, a 10/10 match was found and the question of where the surgery should be performed – in Philadelphia or Cleveland – was addressed.

Because of the continued risk of COVID-19 and the need to stay within an hour's drive of the hospital for three months post-transplant, the family decided Andrea should receive her bone marrow transplant in Cleveland, close to their home – but they asked the CHOP team to consult throughout the procedure and through recovery.

At the end of July, 14-year-old Andrea was admitted to the hospital for a week of intense chemotherapy to destroy her existing bone marrow. Then on Aug. 7, she received the donated bone marrow that would serve as a base for her new, healthy immune system. After about a month in the hospital, Andrea was able to go home.

Getting stronger

Nearly two months after her bone marrow transplant – and four years after her initial visit to the ER – Andrea is doing well and working hard to regain her strength and mobility. She hopes to be well enough to join her high school cross-country team next year.

Andrea's immediate goals include getting as healthy as possible 100 days post-transplant, and making her life as normal as possible given COVID-19 restrictions. The pandemic has been a leveling factor in her life – she must attend virtual schooling to reduce her risk of infection after transplant; her peers are also learning virtually due to the pandemic.

"We'll always be eternally grateful to Dr. Banwell and the Immune Dysregulation team at CHOP," Beth says. "They guided the ship to help us get the answers we needed and find the right treatment for our daughter."