MEDICINE / RESEARCH : Physicians Struggle to Find Cure for Tryptophan Illness

Identifying impurities in L-tryptophan nutritional supplements associated with the eosinophilia-myalgia syndrome has been far easier than learning how to treat those afflicted with the painful and potentially fatal disease.

Although new cases of the syndrome have declined precipitously after a nationwide recall of tryptophan products last November, many of those afflicted are still severely ill.

Treatment “is still a big black box,” said Dr. Joseph Duffy of the Mayo Clinic in Rochester, Minn., where 67 patients with the syndrome have been treated. “We don’t know enough about what is reversible or irreversible in this disease. We are still groping.”

As a two-day medical meeting on the blood and muscle ailment concluded Wednesday, physicians from across the country presented inconclusive data on the value of high-dose steroids and other treatments. Specific symptoms, such as muscle pains, do seem to improve in the short term with steroid therapy, but the long term benefit of this treatment remains unclear.

Other therapies, ranging from drugs that suppress the immune system to experimental techniques to remove tryptophan from the blood, have been tried on very few patients. They have yet to be tested in rigorous clinical trials or compared to placebo treatments.

Discontinuing tryptophan is a necessary part of treating the syndrome but is no guarantee that improvement will occur. Indeed, physicians reported that some of their patients first became ill months after stopping the supplements.

So far, 1,517 eosinophilia-myalgia cases, including 27 deaths, have been reported to the U.S. Centers for Disease Control. A disproportionate number--270 cases and six deaths--have been reported from California, presumably reflecting the relatively high consumption of nutritional supplements such as tryptophan in the state.

The reported cases, as with many other diseases, significantly underestimate the actual number of illnesses that have developed. In addition, some patients with the illness do not meet the “official” federal definition of the syndrome, which was established when far less was known about the ailment. “I wouldn’t be surprised if we really had 5,000 to 10,000 cases” in the United States, said Dr. Henry Falk of the Centers for Disease Control.

Before the recall, tryptophan supplements were widely used for a variety of problems, primarily difficulty sleeping, anxiety, depression and premenstrual syndrome.

Eosinophilia-myalgia syndrome is characterized by high concentrations of eosinophils, a type of white blood cell that is usually uncommon, as well as severe muscle pains. Severe problems seen in some cases include life-threatening nerve injuries, heart and lung disease, swelling of the body and skin inflammation and thickening.

The epidemic of eosinophilia-myalgia in the fall of 1989 appears to be linked to product manufactured by Showa Denko, a large Japanese chemical company. In separate studies, researchers at the CDC and the Mayo Clinic and the Minnesota Health Department have identified specific impurities in the Showa Denko product made in late 1988 and early 1989 that are strongly associated with the disease.

The impurities appear to be “indoles,” a class of organic chemicals that are structurally related to tryptophan, the researchers said. Of potential significance is that a disease of cows, known as “fog fever,” has similarities to eosinophilia-myalgia and is caused by an indoles compound.

In one dramatic study involving a single psychiatric practice in South Carolina, state and federal researchers found that 45 of 157 patients taking a brand of tryptophan containing the Showa Denko product became ill. Of the patients taking four grams a day--a very large dose--about 60% became ill.

The 60% statistic “really blew the socks off of everyone,” said Dr. Gerald Gleich, an immunologist at the Mayo Clinic. “It suggests that everyone would become ill if they took enough.”

Researchers are less certain how to explain 85 reported cases of the syndrome where patients first became ill between January, 1987, and March, 1989. Investigation of these cases is more difficult because far fewer tryptophan samples are available for analysis.

A large proportion of these patients continue to be disabled, according to Dr. Steven Auerbach of the Centers for Disease Control. This finding is a sobering reminder that while the incidence of new cases has returned to pre-epidemic levels, the clinical problems of those already afflicted, as well as the death toll, may increase.

Of 33 such individuals studied in detail, “roughly two-thirds have continued to have illness that impairs daily living, primarily skin inflammation and weakness,” Auerbach said. “I don’t think we know to what degree these people will get better.”