Common Virus May Contribute to Uncommon Bone Disease in Children

PHILADELPHIA -- A common virus may play a major role

in causing a painful disease of immune cells that attacks children's bones,

according to a new study. The research may eventually lead to an easier

diagnosis and to more effective treatments of the disease, Langerhans cell

histiocytosis.

Researchers found evidence of the virus, human herpesvirus 6 (HHV-6) in

the tissues of 25 of 35 children with Langerhans cell histiocytosis (LCH),

compared to virus detected in only five of 19 children without LCH. The

research team, led by John P. Dormans, MD, director of orthopaedic surgery

at The Children's Hospital of Philadelphia, published its findings in the

January/February issue of the Journal of Pediatric Orthopaedics.

Langerhans cells, found in the blood, play an active role in the immune

system. An uncontrolled excess of Langerhans cells leads to LCH, with effects

that range from a limited, spontaneously resolving illness to a chronic,

life-threatening disease involving multiple organ systems. Although rare,

occurring in approximately five children per million, LCH most commonly

strikes bone, causing painful lesions or fractures.

"LCH is called the 'great imitator' because it resembles particular bone

cancers," said Dormans. "Fortunately, most children survive the disease

these days." Most bone lesions resolve on their own without treatment. In

other cases, surgeons successfully treat the disease by removing the abnormal

area of bone.

However, successful treatment may elude physicians when LCH is chronic and

affects multiple systems. Chemotherapy may succeed, at least temporarily, but

only for 50 to 60 percent of patients. The cause of LCH remains unknown, and

the Children's Hospital researchers investigated its origins, with the goal of

advancing treatments.

"It's important to define whether LCH is primarily a tumor-like process or

a reactive process, that is, one in which the immune system reacts to an

infection or other insult," said Michael P. Glotzbecker, of the University of

Pennsylvania School of Medicine, and the first author of the study. "Our

research strengthens the case for a reaction to infection. Understanding the

origin of the disease may help redefine the best treatment."

Previous researchers had proposed a role for HHV-6 infection in LCH, but

the evidence was indirect, or was questioned on grounds of possible

contamination. The current study was the first to identify the virus in the

cytoplasm of immune cells called lymphocytes within LCH tissues. "Our

findings suggest that after the HHV-6 virus infects lymphocytes, the body

mounts an abnormal immune response resulting in the overproduction of

Langerhans cells seen in LCH," said Glotzbecker. The researchers

confirmed the presence of the virus with in situ hybridization, a testing

technique.

The virus, HHV-6, is extremely common in children and adults, but usually

is cleared out of the body or neutralized by a normally functioning immune

system. In fact, the researchers found evidence of the virus in 5 of 18

tissue samples from children without LCH. "Because HHV-6 infection is so

prevalent, but so few children get LCH, our results suggest that the virus

interacts with some underlying predisposition to the disease," said

Dormans.

"We don't know what may cause a predisposition to this disease," continued

Dormans, "but rethinking the cause of LCH may ultimately shift treatment

away from chemotherapy toward antiviral treatments or approaches that modify

the immune system." Much further research is necessary, he added, but in

addition to guiding treatment, future research may lead to a simple blood test

to diagnose the disease. "Such a test would be less invasive and certainly

less painful for children than the tissue biopsy that we now must perform to

diagnose LCH."

The National Institute of Child Health and Human Development provided

support for part of the research. In addition to Dormans and

Glotzbecker, the study's third co-author is David F. Carpentieri, MD,

formerly a pathologist at The Children's Hospital of Philadelphia, and now at

Phoenix Children's Hospital.

Source: The Children's Hospital of Philadelphia

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