Amy Tan, writer of "The Joy Luck Club"

The Novelist, Under Treatment for Late-Stage Lyme Disease, Could Never Have Conceived How Hard It Would Be to Get a Diagnosis -- or How Surreal the Symptoms Could Be

By J.J. McCoy
Washington Post Staff Writer
Tuesday, August 5, 2003; Page HE01

It wasn't until she began having hallucinations about a naked man approaching her bed that novelist Amy Tan got really worried.

She first assumed what she was seeing was her husband, who brings her coffee in the morning. "But it was the middle of the night," she recalls, and "he wasn't saying anything or doing anything else. He was just coming toward me [before stopping] next to the bedstand, as though he was turning on the light."

She took his silence to mean the worst.

"I thought someone was dead," she recalls. "I reached for him, and the image started to warp as I realized it wasn't real."

She sprang to in dread and started running through her SoHo loft, calling out for him -- and very soon finding her flesh-and-blood husband, Lou DeMattai, calmly watching TV.

"Oh, thank God, you're alive!" she said.

What Tan didn't realize is that her experience about 18 months ago was perhaps only the strangest manifestation of what has since been diagnosed as late-stage Lyme disease -- an illness she believes she had contracted two years earlier but that continued to cause neurological damage, thanks to several misdiagnoses by doctors unfamiliar with or even hostile to the possibility.

Even now, after several months of treatment with antibiotics, Tan says her symptoms range from fatigue and memory loss to tinnitus (ringing in the ears) and olfactory hallucinations.

"I smelled dead rat briefly, but over a period of hours" and in different locations. "It's definitely weird."

Other symptoms have included hair loss, memory gaps, dropping first letters of words when writing by hand and replacing words with similar-sounding gibberish when speaking. Most recently she's experienced vertigo and expects that she'll continue to feel some joint pain "as a souvenir."

Tan's case dramatizes the growing, increasingly acrimonious division in the medical community over the proper treatment and diagnosis of Lyme disease, an illness caused by a bacterium, Borrelia burgdorferi, that enters the body via the bite of a deer tick.

There are essentially two armies in the Lyme war. The larger is the conventional team, supported by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), the insurance industry, most organized medical groups and the majority of physicians. Members of this camp embrace a standardized set of symptoms, tests and treatment. As described on the CDC Web site (www.cdc.gov), Lyme disease starts with a tick bite and typically involves a "bull's-eye" rash -- a round, red mark surrounded by a paler ring and, often, a larger red ring -- accompanied by symptoms such as fever, fatigue, headache and aching muscles and joints. Early on, diagnosis is usually clinical, with a blood test preempted by symptoms and risk factors for exposure. Standard treatment is oral antibiotics, usually lasting for 10 days to a month depending on severity.

The CDC's Web site adds that some people with Lyme disease left untreated may experience "cognitive disorders, sleep disturbance, fatigue and personality changes," and that the condition may become severe, chronic and disabling, though is "rarely, if ever" fatal. The site says some patients may have recurrent symptoms and require repeated treatments for up to two years.

Then there's the opposing side, where other medical practitioners and patients' groups (and now, Tan) advocate a broader view of the disease that includes less predictable symptoms.

The Bethesda-based International Lyme and Associated Diseases Society (ILADS) contends that fewer than 50 percent of Lyme patients recall either a tick bite or a rash. They also claim the CDC's standard tests often fail to identify the disease.

Furthermore, they maintain that the CDC's standard course of antibiotic treatment is too brief to provide a lasting cure for many and may even leave the bacteria morphing and thriving inside the body, where they can wreak permanent neurological damage.

Gregory Bach, an ILADS board member with a family practice near Philadelphia, says the standard methods miss many people with Lyme, exposing them to harm. Among his clients, "we found that 50 to 90 percent of those tested [by the CDC's initial screening method and not diagnosed with Lyme] subsequently tested positive by other tests."

Paul Mead, an epidemiologist for the CDC, says "certainly this is an area of considerable controversy. There's no question that some in the community have taken exception to the criteria for diagnosis developed by expert panels . . . Testing is a complicated issue that we and others are looking into in further detail. It'd be nice if all the tests were subjected to rigorous validation," he says, but questions remain about the tests and lab analysis of those in the alternative camp.

The reality at this point "is that there is no answer," writes physician and Harvard Medical School assistant professor Jonathan A. Edlow in his new book, "Bull's-Eye: Unraveling the Medical Mystery of Lyme Disease" (Yale University Press, $29.95). "There is something that everyone agrees on: There are these patients who have classic symptoms. The earlier they're treated, the more likely they'll have a good outcome.

"Beyond that," he qualifies, "you have the divergence."

The No Luck Club

Tan's story illustrates how difficult diagnosis and treatment can be for someone whose case does not conform to the standard course. Tan didn't realize how tiny the tick could be -- about the size of the period at the end of this sentence -- and her rash never fit the standard description. As bothersome as her months of joint pain, occasional numbness, headaches and memory lapses had become by 2001, she accepted numerous medical opinions writing them off as signs of getting older. (She was 49.) But she couldn't laugh off the hallucinations and memory lapses.

Both Tan's father and her older brother had died from malignant brain tumors. Her mother had a brain tumor, too, though hers was benign; she died after having been diagnosed with Alzheimer's disease.

"I certainly considered [that I might be suffering from] Alzheimer's," Tan admits, "especially when I started having memory problems, and hiding mistakes that I'd made. I thought that must have been what it was like for my mother."

While her doctors quickly ruled out either those possibilities, they could not tell her what was wrong, even after two CAT scans, an MRI and a 48-hour hospitalized fast.

She broached the possibility of Lyme disease, but her doctor "told me three times he really didn't think I had Lyme, that we didn't have it in California, and that it was rare."

Tan reminded him that she and her husband split their time between the West Coast and New York, but the doctor was unmoved, she said. They left it at that.

A Battle Over Bites

Since Lyme disease was first detected in the United States in 1975, warnings about the risk of deer-tick bites have become routine public safety reminders each summer, along with tips about using sunscreen and avoiding rip tides at the beach. Though it may not be as in vogue as SARS, monkeypox or even White Nile disease, Lyme disease continues to proliferate, in its number of victims, geographic reach and medical controversy.

Cases have been reported in every state except Montana, with the overwhelming majority concentrated in the coastal Northeast and Mid-Atlantic states and in Minnesota, Wisconsin and northern California.

Of the 17,029 cases reported to the CDC in 2001, there were 608 in Maryland, 156 in Virginia and 17 in the District. The national total increased by more than 33 percent between 1991 and 2000.

The CDC adds that while reported cases of the disease have been increasing -- it theorizes that people are being exposed more often to ticks because tick populations are becoming both more dense and widely distributed -- "the disease [remains] greatly under-reported."

As the NIH details on its Web site (www.nih.gov), the particular spirochetes (spiral-shaped bacteria) associated with Lyme are notoriously difficult to diagnose and troublesome to treat in their later phases -- not only because they can change their appearance but because Lyme disease is similar to but separate from other diseases transmitted by different ticks. For diagnosis, the CDC recommends either of two blood tests for mid- or late-presenting cases: an ELISA (enzyme-linked immunosorbent assay) or IFA (indirect fluorescent antibody) test, followed by a Western Blot test.

The CDC's position is that the tests are reliable for late disease; ILADS counters that they miss fully half of late-stage cases.

Unfortunately, Edlow notes, both the ELISA and the Western Blot are imperfect, with frequent false negatives in early testing; in other words, they fail to identify many patients who have the disease. Since the production of antibodies, for uncertain reasons, is a little slower against Lyme than against many other infectious diseases, testing is not recommended within the first month of suspected exposure.

The ELISA, however, also routinely presents false positives -- identifying disease-free people as having Lyme. A random sampling of 100 people might -- due to bacteria as relatively benign as those that cause gingivitis -- suggest that five of them have Lyme, when in fact they have gum disease.

This is why the Western Blot, which produces fewer false positives, is used as confirmation.

Still another problem, though, is that there's disagreement about how to properly interpret a positive Western Blot test. While the test measures which antigens, or proteins, a patient's blood contains antibodies to, there remains technical disagreement over exactly which are significant and to what degree.

The CDC doesn't accept as relevant to a diagnosis of Lyme as many bands -- measures of antigens -- as private labs like IGeneX (a California lab run by Nick Harris, a doctor and ILADS board member) measure.

Shared criteria can also be interpreted differently. Even when the CDC and IGeneX agree on which bands are indicative, Edlow adds, a patient could test positively to the blot, "but have gotten [the disease] three years ago. That doesn't mean you have active infection, even though the antibodies remain positive."

"As with most things Lyme," Edlow says, "it depends on whose opinion you believe and how you define Lyme disease.

"There's legitimate controversy," he continues. "While we all prefer unambiguous results, that's just not possible the way these are used."

Life, Interrupted

Tan says she is "not terribly angry with any of my doctors" for having missed her diagnosis, though the roster included her primary care physician, an endocrinologist, a sleep-disorder specialist, two neurologists, a cardiologist and an orthopedic surgeon. "They were doing the best they could."

"I'm angry at the California Medical Association," she says, "because they have a board policy that recommends that all Lyme disease patients be treated with 10 days' antibiotics. I'm angry that they perpetuate the myth that it's rare, easily tested and easy to treat.

"I'm mad at insurance policies. . . . I'm a typical long-term Lyme patient who's seen a lot of doctors and had a lot of expensive tests done," Tan continues. While she could afford to spend more than $50,000 on diagnostic tests before learning what was ailing her, "I'm luckier than most -- there are many who have it far worse than I do."

"I know people who've lost homes, everything they have. I'm mad at the arbitrary saying that it's two weeks' treatment regardless of what's happening to you."

Nearly half a year before Tan's hallucinations began, she had returned home after a four-month, transoceanic book tour for her novel "The Bonesetter's Daughter." The persistent fatigue plaguing her before she started her itinerary had become life-consuming.

The day-long sleep that she first wrote off to jet lag didn't suffice; in the weeks that followed, she would sleep for 12 to 20 hours a day. Even more disturbing were the trembles that punctuated her sleep, waking her every two or three hours with what she called "Dolby Digital Syndrome" -- a feeling of constant vibration, like reverberation from a bass-heavy stereo.

When she shortly began waking each day with a sore neck, Tan bought a new buckwheat pillow. She tried another type, and still another, adding everything from Tempur-Pedic foam to a U-shaped neck roll.

As the weeks turned into months, the mental toll turned from an extended writer's block to an inability to maintain concentration or short-term memory.

"By page three or four [of her writing], I was unable to recall anything and had to begin anew," she says. At the dinner parties, "I often couldn't keep up with the repartee. . . . I nodded and laughed at the moments when everyone else did."

She decided to consult a psychiatrist for the first time in nearly 20 years; the doctor in turn suggested she also get a complete medical workup.

Finally, after comparing what she knew with what other patients reported on the ILADS Web site (www.ilads.org), Tan discovered Rafael Stricker, a Lyme specialist in San Francisco.

Stricker says Tan's "clinical symptoms and history were very suggestive: striking psychiatric problems and hallucinations, which you can see with Lyme disease."

He tested her with a Western Blot, and had it analyzed by IGeneX.

Stricker says Tan has tested positively on the Western Blot five times in a row. Among the 16 antigen bands that IGeneX identifies, her tests "have been pretty uniform," with positives for seven or eight bands each time. She has consistently tested positive for two of the three bands the CDC considers accurate indicators of Lyme, he says. He considers her diagnosis conclusive.

Stricker points out that as a public health agency, the CDC is interested mainly in surveillance and less in clinical applications of tests. "They're not as concerned in missing something, while I want a test that works for my particular patient's diagnosis."

The CDC's Mead confirms that the agency's analysis of the Western Blot requires a minimum of two of the three bands for a positive diagnosis, and that "this is a surveillance-case definition," which is useful for tracking the disease but may not be sufficient for a specific patient.

"It's a balancing act," he says. "It's true that to a certain extent [we] have different objectives. A clinician can treat, just in case, to help his patient. Nevertheless, there can be problems with over-treatment [with long-term, powerful antibiotics]. Overall it's not helpful to treat someone without a disease."

Stricker recently changed Tan's antibiotic medication to Flagyl (metronidazole) from doxycycline. He says recovery is usually progressive: "Usually when they feel better, they stay better, though there's possibility of relapse. Sometimes it requires months" of treatment for a complete cure, he says. "Sometimes it requires years."

That Tan's answer hadn't been discovered through the CDC's diagnostic protocols doesn't surprise Edlow. After all, he says, the Borrelia burgdorferi spirochetes "are weird bugs. Part of the way that they evade the immune system is to morph, or change themselves to appear like a new bug to the immune system. Or they don't. Or else patients have one or another or more than one at the same time. It gets kind of tricky."

Tan meanwhile argues that Lyme disease patients can't afford to wait for the science to inch its way forward. Her imagination still reels at the thought she was tested for both syphilis (after 29 years of marriage) and Lou Gehrig's disease before her doctors considered her for what the CDC terms "the leading cause of vector-borne infectious illness in the U.S."

"I've never met a single person in my lifetime who had ALS, but they tested me for that before Lyme disease," Tan adds. "It's not the way the medical community should be dealing with these very real problems that people are having."

Imputing her symptoms to age strikes her as no more logical.

"Did most baby boomers lose their hair in clumps? Did [they] read e-mails and respond at length, then have no memory of doing either? Were they amazed to read unfamiliar pages of stories they had evidently composed? . . . Did they become lost in their own neighborhoods, unable to recognize any familiar landmarks, too mortified to ask for help?"

As she concludes in an essay from her upcoming book "The Opposite of Fate" : "I am in this for the long haul, with treatment that will likely last for years. I won't feel safe until the scan of my brain and blood tests on my immune system return to normal, until the Western Blot is negative for Lyme disease, and my myriad symptoms are gone. . . . By having Lyme disease, I have automatically been drawn into the medical schism over both its diagnosis and treatment."

"I now know what is the greatest damage that Borrelia has caused: It is ignorance."•