The doctors at Children's Hospital Boston were baffled - and worried. In the past, they had treated only a couple of children a year for a rare condition that causes the heart to stop pumping, an illness that can send a previously healthy child plunging toward death.
But a year ago, they began seeing children with myocarditis with alarming frequency. Instead of two children a year, they were sometimes treating two a month.
Since November 2006, 10 children have been diagnosed with the ailment, which can be caused by infectious germs, toxic substances, or an underlying chronic condition. Two died. Two others required heart transplants. And now doctors and public health investigators are trying to crack a medical mystery that they acknowledge they may never solve.
Disease trackers have not been able to find anything that links the children, who ranged in age from 3 months to 17 years and came from Massachusetts, New Hampshire, and Rhode Island.
There is no evidence that any single germ is to blame - or that all the cases were even ignited by an infection. There is nothing to suggest that the youngsters had contact with each other or that they suffered from another illness that predisposed them to the heart irregularity. And there is no reason, disease specialists said, to believe that a broader public health threat exists.
"It's a mystery along several different fronts," said Dr. Anita Barry, director of communicable disease control at the Boston Public Health Commission. "It must be very hard for the families of these children, not knowing what the cause of this severe myocarditis in their children was."
On Monday, Boston's health agency issued a written plea to hospitals and doctors asking them to report any additional pediatric cases they may have seen recently. Children's Hospital alerted city authorities in August that they were concerned about the disease; at least one more case has come to light since then.
There is no state or federal law forcing physicians to report cases of myocarditis, the symptoms of which include fever, fatigue, and rapid heart beat.
"But the fact that we've noticed [the cases at Children's] indicates it warrants some effort to figure out what's going on," said Dr. Bela Matyas, a top disease tracker with the state Department of Public Health, "because nothing obvious jumps out."
Myocarditis, an inflammation of the heart's muscular tissue, can be triggered by a variety of sources, and it is not clear why some patients - children or adults - develop more serious complications than others.
Sometimes, viruses, parasites, or other infectious organisms are to blame, including such garden-variety germs as those that cause the common cold. Other times, myocarditis is a complication stemming from conditions such as lupus, in which the body's disease-fighting system turns on itself.
In still other cases, the heart ailment is a side effect of medications or toxins such as lead or arsenic.
In cases of myocarditis caused by infectious agents, the immune system may successfully kill germs in most of the body, but not the heart, which then sends out a potentially lethal SOS - in effect, the heart gets too much help.
"We turn our attention on ourselves and kill our own heart cells," said Dr. Gerard Boyle, chairman of pediatric cardiology at the Cleveland Clinic.
The heart begins to swell and fluid pools. "It disrupts the mechanical efficiency of the heart," Boyle said, "and the heart squeezes less well." And then, blood that needs to pass through the heart cannot get in, and blood that needs to leave the heart cannot get out. A cascade of complications follows, with the lungs, liver, and other organs sometimes becoming dangerously impaired - in very short order.
National studies estimate that up to 10 of every 100,000 people develop myocarditis annually, and the disease can be found in adults as well as children, sometimes persisting as a chronic condition.
As the number of cases grew at Children's over the last year, doctors watched with increasing curiosity - and concern, especially because the condition struck so forcefully in otherwise healthy children.
"We're not sure if the reason we are seeing more cases is because more cases are being referred to our hospital or if this is a true increase in the incidence of the disease in our community," said Dr. Kathy Jenkins, senior cardiologist and director of the program for patient safety and quality at Children's.
The first child was diagnosed Nov. 17, 2006; the last, a month ago. Half of the children became so sick they were put on a machine that breathes and pumps blood for the patient. The children were also treated with medications that drain excess fluid and slow down the heart.
The two children who died were a 15-year-old girl and a 12-year-old boy. Authorities declined to provide detailed information about the children, citing patient confidentiality laws.
As the children have been treated, specialists have performed a constellation of tests on the children's blood and tissue. Two patients may have had Lyme disease, which has been identified as a cause of myocarditis, although tests were equivocal.
Two other children tested positive for a virus called Coxsackie, but doctors could not tell whether it was a fresh infection or the legacy of an old encounter with the germ.
"What's fair to say at this point is we don't really know for most of the cases what the cause is even though we've looked for most of the common things," said Dr. Thomas Sandora, hospital epidemiologist at Children's. "We don't even know for sure that all of these cases are related to infection."
Investigators reviewing the cases said they feel certain about one thing: There is no reason to believe the region is experiencing a widespread disease outbreak caused by a virulent organism, in part because the cases occurred at different times and in different places.
In addition, the families and friends of the children showed no signs of infectious illnesses.
"I think the likelihood would be fairly high that we're not going to know a lot more than we do right now," Barry said. "I'm hopeful we will know more, but when cases of illness are so dispersed in time and in place and there are so many possible causes, I think it's hard to pin something down."
