www.ArthritisToday.org
A Medical Mystery Solved
Researchers raced to save Jacob Whelan's life and discovered an entirely new arthritis-related autoimmune disease.
By Jennifer Davis
Jacob Whelan is all
smiles, as he poses
with Raphaela
Gold-Mansky, MD,
the rheumatologist
who made the diagnosis.
6/25/09 From the moment he came into the world, Jacob Whelan wasn’t well.
His fingers were strangely swollen, and he had small puss-filled bumps on his hands. He cried out in constant pain.
The worst part was that nobody knew why.
“As a mother, it really tears at you because you feel so helpless,” Joyce Whelan says.
There was no breastfeeding, no hugging and no holding. No first photos, either, because Jacob’s small body was covered in oozing lesions that appeared like clusters of acne that would spread, break open, scab over, and peel off before more would emerge.
“The way we used to describe it was it was like he was dipped in a pot of fat and burned,” Joyce says.
Jacob was a New Year’s baby, one of the first children born January 1, 2007, and 10 months later, through the persistence of his parents and doctors, he would achieve another first – he would become the first baby diagnosed, and saved from, a devastating genetic autoimmune disease that attacks the skin, bone and connective tissues.
“I think what has happened is these children have been thought to have severe infections and because they died early, people thought they died of infection of the bone. But the cultures usually, if you go back, are negative,” says researcher Raphaela Goldbach-Mansky, MD, a rheumatologist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, in Bethesda, Md., who successfully diagnosed Jacob.
Dr. Goldbach-Mansky published a paper about Jacob's case and the cases of 16 other children in the June 4, 2009 issue of the New England Journal of Medicine.
Like Jacob, children with the disorder, called deficiency of the interleukin-1-receptor antagonist, or DIRA, begin to have symptoms from birth to two weeks of age that include swelling of bone tissue, bone pain and deformities, inflammation of a layer of connective tissue around bone and a rash resulting from pustules covering their bodies.
Jacob remained in the hospital for 10 months as his condition worsened. He developed internal bone lesions and such a bad case of reflux that he was put on a feeding tube.
“We thought he would die and there was nothing we could do,” Joyce says.
As his parents hoped for a miracle, his doctors were desperately searching for an answer. They couldn’t identify his condition or explain it, so they were calling doctors all over the world searching for clues.
One of the groups Jacob’s doctor consulted with were specialists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, or NIAMS, part of the National Institutes of Health in Bethesda, Md.
Researchers there suggested finding a drug to make Jacob more comfortable while they tried to figure out what was causing his body to break down.
They suggested anakinra (Kineret), a drug normally used to treat rheumatoid arthritis that also helps with some kinds of juvenile arthritis.
Within 24 hours of the first dose, there was a remarkable response. Some of Jacob’s swelling started to subside, lesions on his skin started to fall off and Joyce could finally pick up her son.
Within 48 hours, Joyce says that Jacob was like a completely new child. He shed a whole layer of skin, like a snake, his pain appeared to lessen and his reflux started to improve.
“He was happier,” Joyce says. He started to do normal things, like he was wanting to play and he was wanting to roll.”
Within a week, Jacob seemed nearly normal and today, at 2-and-a-half years old, you’d never be able to guess he was once so sick. “If you were to see him today, you’d think he’s a normal little child with no medical issues whatsoever,” Joyce says. “It’s so nice to see that because where he came from and where he is now are two different worlds.”
Dr. Goldbach-Mansky says all the children with DIRA have inherited mutations in the gene that encodes for a protein known as interleukin-1 receptor antagonist or (IL-1Ra). Without it, their bodies can’t control systemic inflammation.
“To the physicians who have taken care of him in the ICU, it was like a miracle,” Dr. Goldbach-Mansky says. “They kept telling me how incredibly moving it was to the entire team that had taken care of this child for months and had been very frustrated with him not getting better and being in pain. And then to see the turnaround – he was out of the ICU in two weeks. So it’s pretty amazing.”
So far, scientists have confirmed 17 cases in Newfoundland, the Netherlands, Lebanon and Puerto Rico. Those who survived were treated with anakinra, because it’s a synthetic form of human IL-1Ra. Most have responded like Jacob – quickly and successfully.
“Whenever we discover a gene it’s actually like a big hint to what pathway is involved. It’s almost like opening a dark box and seeing a light at the end of the tunnel because you know what immune pathway is involved so you can develop treatments,” Dr. Goldbach-Mansky says. “What has been so remarkable is the protein these kids are missing is the very protein we are giving them for treatment.”
The gene mutation is rare, but does seem more prevalent in certain populations particularly in northwest Puerto Rico. Dr. Goldbach-Mansky says newborn screening may be needed in these places.
As for Jacob, he’s now taking the medication every day. His blood work has normalized; the bone lesions throughout his body have resolved; he only needs to use the feeding tube occasionally; and he’s walking, talking and starting to run. His Mom says her biggest challenge now is trying to teach him to draw a straight line because he likes to scribble.
“Because Jake is the first one diagnosed with it, it’s hard to know what the future holds for him,” Joyce says. “Everyone is learning as Jake progresses how this illness will unfold.”
But the family is very hopeful – for their own son and any other children who get the condition. “Jake is definitely a miracle, considering he was almost at death’s door and now he’s an angel,” Joyce says. “It’s mind-blowing. It’s incredible. We give so much thanks to Dr. Goldbach-Mansky and her team. They’ve discovered Jake’s problem and now they’re willing to not only help him, but also hopefully to help so many more.”