"You know, it's really not normal": a chance encounter leads to a rare diagnosis of the girl

The pediatrician was direct but not mean. Despite everything, his unequivocal message made Jan Wiese bristle

"You know, it's really not normal," the doctor said to Wiese after seeing Lucy Wiese, 2, for the first time. Struck by the girl's medical history, especially her repeated skin infections, the Washington suburban doctor recommended Lucy to see a pediatric immunologist in Baltimore.

"I was a little offended," remembers Wiese. Her husband's doctor did not realize that their daughter's infections could signal something more serious than the normal susceptibility – so acute – of unfamiliar germs.

Years later, Wiese indignantly recalled his indignation. "Of course, she was right," conceded Wiese.

In the months following this routine meeting in 2010, it became clear how extraordinary Lucy's medical situation was. The timing and the luck were crucial: a chance meeting with a specialist allowed to establish a diagnosis that can take decades. And proximity has facilitated Lucy's access to one of the world's most important treatment centers

Over the past eight years, Lucy's odyssey has exhausted her family, which was amazed by his repeated treatments. His precarious health, which had been spiraling downward, seems to have rebounded in recent months.

"She's just a really brave kid," her mother said. "It's really a miracle that she's here."

Lucy's birth in June 2008 at a hospital in Richmond, Virginia, had an uneventful pregnancy. The doctors noted what they characterized as a mild rash of the newborn who covered his body. For Wiese, the rash looked like small freckles, which contracted and fell. Lucy also had a slight case of jaundice – common in newborns – which required a week of treatment by exposure to light at home.

At nine months, she developed an infection near her fingernail. The area was swollen and filled with pus, but it was not painful. The pediatrician drained it and the toe healed.

Three months later, something similar happened to two of Lucy's fingers, which she usually sucked.

"It looks like she's been burned," said a doctor in Wiese. "Fortunately, they believed me," remembers Wiese. Lucy received antibiotics, and the doctor advised her not to suck her fingers – easier said than done, her mother remarked.

Lucy had also developed periodic rashes on her face and torso that looked like a rash. Wiese and her husband, Scott, then a fourth-year medical student, thought Lucy could simply be vulnerable to the germs that he brought back from the hospital.

Around the time of her first birthday, the family moved to Charlottesville, Virginia, where a new pediatrician noted the large size and unusual shape of her head, which was a bit long and narrow. "We have a big head in our family," Wiese told the new pediatrician. After a scan revealed a sagittal craniosynostosis, a congenital abnormality that results in the premature closure of bones in a baby's head, Lucy was referred to a pediatric neurosurgeon at the University of Virginia. He thought his case mild and recommended not to have surgery, which can be risky.

Five months later, Lucy developed an abscess behind her left ear. More serious than previous infections, it had to be drained surgically and required that she be hospitalized for IV antibiotics. This infection, unlike the previous ones, healed more slowly and required a series of oral antibiotics as well as corticosteroids.

At the time of Lucy's second birthday, the family moved again, temporarily settling in the suburb of Reston, Virginia. A few months later, she saw the pediatrician who recommended a job of immunology in Baltimore

Lucy's parents agreed, and she was placed on a waiting list at Johns Hopkins.

But a few weeks before his third birthday, the little girl has developed a severe case of oral thrush, a fungal infection that causes white spots in the mouth and esophagus.

"It was so painful that she could not swallow her own saliva," remembers Wiese. Lucy was admitted to the MedStar University Hospital in Georgetown, Washington, where her father was a resident in anesthesiology.

An infectious disease specialist noted that thrush, one of the opportunistic infections that can affect HIV-infected patients, was extremely unusual.

Less than a month later, Lucy was back in Georgetown with a second serious case of lily of the valley. This time she saw Charlotte Barbey-Morel, then head of the Pediatric Infectious Diseases Hospital. (Barbey-Morel has since retired and returned to his native Switzerland.)

Wiese recalled that the specialist had told her that she was confident enough that she knew what was wrong. did not go. A colleague of Barbey-Morel, who divided her time between Georgetown and the National Institutes of Health, had treated patients with a rare diagnosis whose symptoms closely resembled those of Lucy

"Charlotte called me and m & # 39; Said: "You're not going I think I've got a patient with this disease," recalls Alexandra Freeman, a colleague of Barbey-Morel, today's director of the clinic's ### Primary immunodeficiency of the National Institute of Allergy and Infectious Diseases

. There was a lot of congratulations for Lucy to come in there and I was working there, but it is really Charlotte who understood that. "

Lucy's symptoms were consistent with a rare disorder called Job's Syndrome, also known as Hyper IgE syndrome.The immunodeficiency, estimated at about one in a million, is caused by a mutation in the STAT gene 3.

This deficiency stimulates and under-stimulates the immune system, causing severe bacterial and fungal skin infections that result in lesions and boils. (hence the biblical name.) Other features include infections pulmonary, fractures, skeletal problems, including a curved spine or craniosynostosis, hyperflexible joints and dental problems

Some employment cases are inherited – a parent up to 50% of having a child with it – while others occur as a result of a spontaneous mutation.

There is no cure.Antibiotics and antifungal drugs are commonly prescribed to prevent and treat related infections.

A definitive diagnosis requires sophisticated genetic testing. And the best place to get that, Barbey-Morel told Wiese, was NIH, home to one of the world's largest treatment programs. In 2007, two teams of scientists, one from the NIH, identified the gene responsible for the disorder, which was first reported in 1966.

In early 2012, tests revealed that Lucy had the mutation. Because her parents and younger brother do not, Lucy's case is not considered hereditary, but rather as an accident due to chance.

For Wiese, Lucy's diagnosis was difficult but not unexpected. "I was getting a bit desperate," she said. "I think we finally felt like we could get some answers." She enrolled her daughter in a long-term study of the disorder that Freeman is driving.

Freeman, who saw about 130 patients of Job, said that unlike many in her study, Lucy was diagnosed at a young age. Some of his other patients, who include several generations of the same family, have not been diagnosed until the age of 40, although they have been sick most of their lives .

"This disease is particularly delicate because it's multi-system," Freeman said.

When she was 4, Lucy landed in the Georgetown Pediatric Intensive Care Unit with a lung infection that almost killed her and led to a cascade of recurrent severe infections.

Three years later, in the spring of 2015, Freeman proposed an experimental treatment to Lucy's parents: a bone marrow transplant Even if it did not heal, a transplant could reduce the severity and frequency of Lucy's lung disease, which posed a permanent threat to her life, says Freeman

The Wieses, who had returned to Richmond, were of the opinion that a transplant was necessary.It is worthwhile to try, and Lucy became the first of three patients at work at the NIH to undergo the grueling procedure. "Her parents are unbelievable" Freeman said, "They are so optimistic."

"I knew it was not a cure, but it was an experimental procedure that could help it," Jan said. Wiese.

Lucy and her mother spent months in the Washington suburb of Bethesda, Maryland, shuttle between the NIH Clinic Center and the Children's Inn, a free residence open to critically ill children undergoing treatment at the clinic. # 39; research hospital

In March 2016, about three months after the transplant. her right lungs collapsed due to pneumonia and she was operated on at the National Children's Medical Center

"I remember melting in tears when [the surgeon] came out and told us that she had been so successful, "said Wiese. In the past year, Lucy's health has improved considerably.

"She's doing a lot, a lot better," said Freeman, who saw her in June. "Her lungs look really good" and she has had no skin infections since transplantation. "We hope that transplant and lung surgery have helped her to pass the milestone," said her mother. Although Lucy is home-schooled for health reasons, "she has friends" and, in many ways, her life is no different from that of other 10-year-olds

"We expect that She'll go to college one day, "Wiese said. "I think and hope that she will lead a normal life."