Chronic fatigue - a pattern in medicine?

From today's Wall Street Journal

By AMY DOCKSER MARCUS

Researchers have linked an infectious virus known to cause cancer in animals to chronic-fatigue syndrome, a major discovery for sufferers of the condition and one that concerned scientists for its potential public-health implications.

An estimated 17 million people world-wide suffer from chronic-fatigue syndrome, and the Centers for Disease Control and Prevention puts the U.S. figure at between one million and four million. CFS is characterized by debilitating fatigue and chronic pain, but there are no specific treatments, and the diagnosis is often made by ruling out other diseases. Thus there is disagreement in the medical community as to whether CFS is a distinct disease. A study showing a strong viral association with CFS could change that equation.
[Researchers] Michael Hillerby, Whittemore Peterson Institute.

Researchers Judy Mikovits and Vincent Lombardi work in the lab at Whittemore Peterson Institute.

But the significance of the finding, published Thursday in Science, extends far beyond the community of people living with CFS. Researchers are just as concerned about the finding that nearly 4% of healthy people used as controls in the study were also infected with the virus, called XMRV. If larger studies confirm these numbers, it could mean that as many as 10 million people in the U.S. and hundreds of millions of people around the world are infected with a virus that is already strongly associated with at least two diseases.

The study was done by researchers at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nev., the National Cancer Institute and the Cleveland Clinic.

In September, researchers at the University of Utah and Columbia University Medical Center found XMRV in 27% of the prostate-cancer samples they examined. That study also showed that 6% of the benign prostate samples had XMRV. The chronic-fatigue study is the first to find live XMRV virus in humans.

Neither study conclusively shows that XMRV causes chronic-fatigue syndrome or prostate cancer. But the National Cancer Institute was sufficiently concerned to convene a closed-door workshop in July to discuss the public-health implications of XMRV infection. "NCI is responding like it did in the early days of HIV," says Stuart Le Grice, head of the Center of Excellence in HIV/AIDS and cancer virology at NCI and one of the organizers of the July workshop.

Like HIV, XMRV is a retrovirus, meaning once someone is infected, the virus permanently remains in the body; either a person's immune system keeps it under control or drugs are needed to treat it. The virus creates an underlying immune deficiency, which might make people vulnerable to a range of diseases, said Judy Mikovits of the Whittemore Peterson Institute and one of the lead authors on the paper.

So far, XMRV, known fully as xenotropic murine leukemia virus-related virus, doesn't appear to replicate as quickly as HIV does. Scientists also don't know how XMRV is transmitted, but the infection was found in patients' blood samples, raising the possibility that it could be transmitted through blood or bodily fluids.

Dr. Le Grice of the NCI said the highest priority now was to quickly develop a validated blood test or other assay that could be used in doctors' offices to determine who has XMRV. At the workshop, participants also raised the issue of protecting the nation's blood supply. Dr. Le Grice said there isn't enough evidence yet to suggest that people with XMRV shouldn't be blood donors but that determining how XMRV is transmitted was a critical issue. "A large effort is under way to answer all these questions," he said. "I do not want this to be cause for panic."

Although Thursday's scientific paper doesn't demonstrate conclusively that XMRV is a cause of CFS, additional unpublished data make it a very strong possibility. Dr. Mikovits said that using additional tests, the scientists determined that more than 95% of the patients in the study are either infected with live virus or are making antibodies that show their immune systems mounted an attack against XMRV and now had the virus under control. "Just like you cannot have AIDS without HIV, I believe you won't be able to find a case of chronic-fatigue syndrome without XMRV," Dr. Mikovits said.

At the July workshop, Dr. Mikovits also presented preliminary data showing that 20 patients of the 101 in the study have lymphoma, a rare form of cancer. The link between XMRV and lymphoma is still being investigated, but it raised the possibility that XMRV may be associated with other cancers in addition to prostate cancer. NCI's Dr. Le Grice said studies will be launched to determine whether XMRV is associated with other diseases. At the Whittemore Peterson Institute, Dr. Mikovits said they also found XMRV in people with autism, atypical multiple sclerosis and fibromyalgia.

The Science study was based on blood samples from a national repository at the Whittemore Peterson Institute collected from doctors in cities where outbreaks of chronic-fatigue syndrome occurred during the 1980s and '90s. One of the key questions that the NCI's Dr. Le Grice says must now be answered is whether XMRV shows up in large numbers of CFS patients all over the country.

Robert Silverman, a professor at the Cleveland Clinic Lerner Research Institute who is one of the co-authors of the study and one of the discoverers of the XMRV virus, said he believes the virus began in mice and then spread to humans, and that "in most cases, people's immune systems are probably able to control the virus." Researchers are already starting to test antiretroviral therapies developed for AIDS to see if they are effective against XMRV.

The work on XMRV in chronic-fatigue patients initially was funded by Annette and Harvey Whittemore and the University of Nevada, Reno. The Whittemores set up the institute in 2006 after watching their daughter Andrea suffer from chronic-fatigue syndrome for most of her life. They spent millions of their own money to pay for administrative services, office space, lab equipment and research operations. They were frustrated by the lack of government funding for scientific research into the disease.

At their home in Reno, Andrea Whittemore-Goad, 31 years old, used oxygen before speaking about the devastating toll CFS has taken on her.

Ms. Whittemore-Goad says she was a regular school girl, playing sports and involved in school activities, until the age of 10, when she became ill with a monolike virus that she couldn't shake. She said doctors first told her parents that the illness was psychological, that she had school phobia and was under stress from her parents. "We kept searching for an answer," says Ms. Whittemore-Goad, who says lymph nodes in her groin were so painful that her brothers and sisters used to have to carry her upstairs. She was diagnosed at age 12 with chronic-fatigue syndrome.

Over the years, doctors have treated her symptoms, like intense headaches and severe pain, but the illness persists. She has had her gallbladder, spleen, and appendix removed because they became infected. She tried an experimental drug that she says gave her relief for years, but she then started experiencing side effects and had to stop taking it. Recently the illness has become worse; she began suffering seizures and can no longer drive.

Sitting on the couch next to her husband, whom she married six months ago, Ms. Whittemore-Goad says the news that she is infected with XMRV "made everything that has happened to me make sense." Brian Goad, her husband, said he felt relieved knowing "now we can find a way to treat and hopefully cure it." For both of them, the discovery of the virus is life-changing. There are more than 10 families in the group where family members also tested positive for XMRV. Members of the Whittemore family are now being tested.

Write to Amy Dockser Marcus at amy.marcus@wsj.com

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I think I have detected a pattern in my profession. For far too many physicians, when they encounter something they don't know about they tend to:

1. deny its existence

2. blame it on a psychiatric disorder

3. demonize the patient

There is nothing dumber than a really dumb, really smart, person.

JSH