Saving Vanessa, part 1: A mystery rash, a stroke and an epic rescue

DADA2-Vanessa

Vanessa’s rash first appeared on her arms and legs when she was 3 or 4 months old. It was red and bumpy and went away when she was sick with a virus, which happened often. Then it would come back. The dermatology team she saw at Boston Children’s Hospital was puzzled.

“I was expecting they were going to think it was nothing, but they took it very seriously,” says Katherine Bell, one of Vanessa’s mothers. “They took a biopsy and very quickly realized they had no idea what it was.”

Vanessa’s case was even featured at a regional dermatology conference where doctors take up mystery patients. “A hundred to 150 dermatologists looked at her,” says Katherine. But no one could pinpoint a diagnosis.

Vanessa was then hit with a series of viral infections, and the rash went away for good. But other problems surfaced: she became anemic and increasingly fatigued. A hematologist prescribed iron supplements, which didn’t work.

“It got to the point where she was barely eating, was throwing up, wasn’t playing,” Katherine says. “She was clearly in pain. She was fading away, losing weight, wasn’t walking.”

Finally, a vomiting episode worried Katherine and her wife, Nancy Mendoza, enough to bring Vanessa, who had just turned 2, to Boston Children’s Emergency Department (ED). She was admitted for testing, received a feeding tube and had a brain MRI, which was normal. The Rheumatology Program team was consulted, and she saw Dr. Pui Lee, a fellow in the Division of Allergy and Immunology.

Living with uncertainty

Based on her blood work, Lee and Rheumatology Program director Dr. Robert Sundel, diagnosed Vanessa with periodic fever syndrome, a catch-all term for various disorders in which the immune system is activated despite no apparent infection. Not knowing the exact cause, Lee prescribed an anti-inflammatory medication to calm the immune response.

Katherine has pushed for scientific study of Vanessa’s disease, spearheading an academic conference and a patient registry. More on our science blog, Vector.

That helped a little, but over the next three months, Vanessa had fevers every day. She was switched to a different anti-inflammatory medication, but she remained lethargic, vomited frequently, had joint pain and no appetite. Genetic testing, a spinal tap and a colonoscopy all came back negative.

Since Vanessa had high blood levels of IL-6, an inflammatory protein, her rheumatologists decided to try an IL-6 inhibitor that had recently become available for systemic juvenile arthritis. It seemed to work almost immediately: Vanessa began eating, playing and gaining weight — even went on vacation in Maine.

But soon after, Vanessa woke up one night crying, saying, “I don’t feel good,” and began throwing up. She’d had similar episodes, but Katherine and Nancy followed their instincts and brought her to the ED.

“Something just seemed different,” Katherine says.

An assault on the brain

The charge nurse in the ED agreed. Vanessa’s heart rate was falling, her blood pressure spiking. The Code Team and Dr. Todd Lyons, the attending emergency physician, worked to get her heart rate up and her blood pressure down. “Dr. Lyons was listing priorities, keeping everyone focused,” Katherine says. “He told me, ‘Stand next to me and I will explain everything.’”

Around 4:30 a.m., Vanessa had a CT brain scan, which showed massive bleeding. Emergency treatments were started to try to lower the dangerously high pressure inside her head. Around 6 a.m., neurosurgeon Dr. Scellig Stone, did emergency surgery, pausing briefly on the way to the operating room to get more imaging. He was looking for abnormal arteries that might have caused the bleed.

Vanessa in the hospital after a craniotomy.

“She had bleeding both inside the brain and on the surface of the brain,” says Stone. “Together, these bleeds were causing critical pressure on the brain. With those sorts of findings, every minute counts.”

In the OR, Stone and colleagues removed the blood clot and the blood around and inside Vanessa’s swelling brain tissue. Then he went to speak with her parents.

“He looked pretty devastated,” recalls Katherine. “She was having a massive stroke on the operating table. They weren’t sure she would make it.”

The surgeons left a portion of Vanessa’s skull bone off after surgery to accommodate the brain swelling. “It’s a desperate move, something we do in only the most severe situations,” says Stone. “I was concerned she would not survive the injury and that if she did, she would have significant brain damage.”

A reprieve, a setback and a question

But the quick action — launched by her mothers’ instincts — saved Vanessa’s life. “If it had been a week earlier, we’d have been in Maine,” says Katherine. “She would not have survived.”

After several days in the ICU, Vanessa started moving her hands, fighting her breathing tube. “Dr. Stone saw hope in that,” says Katherine.

Amazingly, when Vanessa woke up, she was herself again. Except for one thing: she talked to her doctors for the first time. The loss of part of her brain’s frontal lobes to the stroke had made her less inhibited.

Vanessa is feeling better, but her condition DADA2 is still a mystery.

But nine days later, Vanessa had another stroke — on the other side of her brain —causing a prolonged, intractable seizure. This required another brain operation to place a temporary drain, which was later removed without incident. She remained in the hospital another month.

Last November, Stone and plastic surgeon Dr. Carolyn Rogers-Vizena, grafted in bone from the opposite side of Vanessa’s skull to replace what had been removed, as well as bone around the surgical site that the toddler’s body had absorbed (a common occurrence in children this age). They replaced that bone with bits of bone from various skull locations. “We created a kind of paste that grows over time and solidifies into a firm skull bone,” Stone explains.

A healthy child, a lingering mystery

Today, to all eyes, Vanessa has had a remarkable turnaround. Now age 4, she’s back to being a playful, creative, articulate, imaginative child who loves music and dancing. Her cognition seems intact. Because she lost part of her frontal lobes, she may have issues with attention and impulsiveness — but it’s something that can be lived with.

Vanessa now has a genetic diagnosis: deficiency of the enzyme ADA2, or DADA2. She receives a weekly injection of Enbrel, another drug originally approved for arthritis. For now, her immune condition seems to be under control, but the diagnosis is so rare that there is almost no data on what to expect in the long term.

Vanessa with her big sister Margot.

What happened to Vanessa’s immune system to cause her stroke? Is there a long-term “fix”? Those lingering questions have launched an ongoing inquiry.

Part two of Vanessa’s story continues on our science blog.