Musculoskeletal research
Nervous nine-year-old Nathan Byrd sits on the exam table, listening intently
as his parents exchange information with Lauren Pachman, MD. Then, with an
ice-melting smile, Pachman looks at young Nathan, who has traveled to Children's
Memorial Hospital from Comanche, Texas, for treatment of juvenile
dermatomyositis (JDM). "You're not alone," she says sympathetically. "I take
care of 185 children like you and there are more than 300 across the
country."
Pachman, an internationally recognized pioneer in immunology/rheumatology,
has a special place in her heart for children with JDM, a rare, often rapidly
progressive, disease characterized by acute muscle weakness. It's accompanied by
a purple-red rash—typically on the face and hands—swelling and vasculitis, which
is an inflammation of the blood vessels. The vasculitis can cause devastating
lesions in the skin, eyes, gastrointestinal tract and myocardium (a layer of
heart muscle), which in rare cases can lead to heart block—a rhythm disorder
that can cause dizziness, fainting or stroke. A later sign of disease is
calcinosis, an abnormal amount of calcium salts in the tissues.
JDM once was fatal in about 33 percent of cases. Today, thanks to the
research and devotion of Pachman and others, that number has dwindled to two
percent. The primary treatment is prednisone, a steroid.
Facilitating research on a national scale
Pachman established a diagnosis-based national registry of JDM patients
in 1994. Maintained at Children's Memorial Hospital and funded by the National
Institute of Arthritis and Musculoskeletal Diseases, the registry is
facilitating JDM research across the nation. Based on interviews with parents of
the 323 patients enrolled, Pachman and her fellow researchers have learned
several important factors.
First, the incidence of JDM in the United States is 3.1 cases per million
children each year. That rate is about the same whether the child is Caucasian,
African-American or Hispanic. Research also revealed that more than 50 percent
of the children had an upper respiratory illness in the months prior to
diagnosis.
On the surface, the link between the kidney and bone is not
immediately apparent. However, the kidney is where Vitamin D is activated before
the body puts it to use.
Interestingly enough, while the rate of JDM doesn't vary with demographics,
some symptoms do. For example, African-American children might lose more weight.
Children younger than seven have more upper respiratory complaints, which older
kids are more likely to complain about muscle pain and weakness.
Pachman is taking advantage of the newly mapped human genome, looking for
genetic markers that indicate a predisposition to JDM. "We already have
identified several genetic markers that appear to be associated not only with
disease susceptibility, but also the course of the disease and whether the child
is at risk for calcifications," Pachman explains.
While steroids like prednisone are helpful, they have drawbacks. One of them
is an adverse effect on bones, including a reduction in bone density.
One way to combat this, says Pachman's colleague Craig Langman, MD, head of kidney diseases at Children's
Memorial, is with Vitamin D and calcium. Langman's clinical practice is closely
aligned with his research into bone mineral metabolism in children. On the
surface, the link between the kidney and bone is not immediately apparent.
However, the kidney is where Vitamin D is activated before the body puts it to
use. And Vitamin D helps calcium be absorbed into the bones and regulates
hormones that work on calcium. Without Vitamin D, the calcium is very hard to
absorb. One of his team's discoveries is the use of the compound alendronate to
treat children with insufficient bone mass development.
"Bone is living tissue that's constantly being built up and broken down,"
Langman explains. "Most bone disease in children is a disturbance between the
breakdown and the buildup, with the breakdown becoming greater. Alendronate
halts the breakdown and accelerates the buildup." Alendronate also has helped in
the battle against Jansen's disease, which results in disfigurement and
dwarfing.
Children with cancer who must undergo chemotherapy also face the possibility
of diminishing bone mass. "Some of the disease and most of the therapies
accelerate bone breakdown," Langman says. "Some cancers produce more of the
cells that slows buildup of the bones. Survivors of childhood cancer often
develop bone disease within a decade. A lot of chemotherapy agents act as
poisons hindering how the kidneys develop Vitamin D."
As with Lauren Pachman, Langman gets great joy out of seeing his patients
improve. "I had a patient with brittle-bone disease come to us all the way from
England," he says. "He suffered about 18 fractures a year and was in a wheel
chair. Now he has less than a fracture a year is out of the chair. That kind of
progress is very gratifying."