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Eosinophilia-myalgia syndrome

Eosinophilia-myalgia syndrome is an incurable and sometimes fatal flu-like neurological condition that was caused by contaminated L-tryptophan supplements. Similar to regular eosinophilia, it causes an increase in eosinophil granulocytes in the patient's blood. more...

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In 1989 an outbreak of eosinophilia-myalgia syndrome was traced to an improperly prepared batch of tryptophan. The bacterial culture used to synthesise tryptophan had recently been genetically engineered to increase tryptophan production: unfortunately, with the higher tryptophan concentration in the culture medium, the purification process had also been modified to reduce costs, and a purification step that used charcoal absorption to remove impurities had been modified so that reduced amounts of charcoal were used. It is possible that one or more of these modifications allowed new or greater impurities through the purification. The specific impurity (or impurities) responsible for the toxic effects is still equivocal, although several impurities have been associated with the disease, and their chemical structures determined. Regardless of the origin of the toxicity, tryptophan was banned from sale in the US, and other countries followed suit. In February 2001, the FDA loosened the restrictions on the marketing of tryptophan (though not on importation).

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Eosinophilia-myalgia syndrome: follow-up survey of patients - New York, 1990-1991
From Morbidity and Mortality Weekly Report, 6/21/91

As of December 1, 1990, 151 cases of eosinophilia-myalgia syndrome (EMS)* had been reported to the New York State Department of Health (NYSDOH); 10 of these patients died. Of the 151 case-patients, 149 were known to have used supplemental L-tryptophan (LT) before onset of illness. Because anecdotal reports indicated that some patients in New York had changes in mental status and other symptoms not previously described in association with EMS, the NYSDOH conducted a survey from December 1990 through March 1991 to determine the prevalence of self-reported symptoms in patients with EMS.

A detailed questionnaire was sent by the NYSDOH to all living patients, asking them to report on the presence of 47 specific symptoms at any time during their illness and at the time of the survey. For each symptom, severity was reported as minimal, moderate, or extreme.

Of the 139 living case-patients who had used LT before onset of EMS, 91 (65%) completed the questionnaire a median of 16 months after onset of illness (range: 11-40 months). The median age of respondents was 51 years (range: 32-84 years); 78% were women. Thirty-seven (41%) had been hospitalized at least once following onset of symptoms. Patients who completed and who did not complete the questionnaire were similar in age, sex, and peak eosinophil count.

Patients reported symptoms involving multiple organ systems during their illness (Table 1). At least 75% of patients reported musculoskeletal, neurologic, and dermatologic symptoms. Specific cognitive problems at any time during illness included difficulty concentrating (63%), difficulty remembering words or names of persons (52%), difficulty thinking logically (52%), difficulty conversing (43%), and impairment of short-term memory (42%). Of the 74 patients who reported depression and/or anxiety as an EMS symptom, pre-EMS medical and psychiatric history was available for 54. Of these patients, 32 (59%) denied psychiatric problems before developing EMS.

At follow-up, 64% of patients reported having moderately or extremely severe EMS symptoms. The most commonly reported persistent symptoms included fatigue (64%), muscle weakness (60%), muscle cramping (57%), myalgia (55%), arthralgia (48%), anxiety (46%), depression (41%), tight skin (40%), and difficulty concentrating (40%) (Table 1). Seventy-five (82%) patients reported that symptoms had become less severe since peak illness; nine (10%) patients reported that they were symptom-free.

One case-patient who did not participate in the survey had undergone a neuropsychologic evaluation in November 1985 before onset of EMS and again in September 1990 while still ill. This evaluation indicated a 29% decrease in intelligence may be a primary manifestation of inflammatory central nervous system effects, similar to those observed in peripheral nerves and other organ systems (6-8). Third, because many of these manifestations are subtle, they may be obscured by the severe pain and disability that characterize EMS, thereby resulting in delayed clinical recognition.

The high prevalence of cognitive and other symptoms reported by patients with EMS in New York requires further clinical and epidemiologic evaluation. The prevalence of symptoms described here is based on self-reports and not on objective evaluations; subsequent evaluations of patients with EMS might include neuropsychologic tests.

References

1. Swygert LA, Maes EF, Sewell LE, Miller L, Falk H, Kilbourne EM. Eosinophilia-myalgia syndrome: results of national surveillance. JAMA 1990;264:1698-703.

2. CDC. Clinical spectrum of eosinophilia-myalgia syndrome-California. MMWR 1990;39: 89-91.

3. Kaufman LD, Seidman RJ, Gruber BL. L-tryptophan-associated eosinophilic perimyositis, neuritis, and fascitis: a clinicopathologic and laboratory study of 25 patients. Medicine 1990;69:187-99.

4. Martin RM, Duffy J, Engel AG, et al. The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion: clinical features in 20 patients and aspects of pathophysiology. Ann Intern Med 1990; 1 13:124-34.

5. Philen RM, Eidson M, Kilbourne EM, Sewell CM, Voorhees R. Eosinophilia-myalgia syndrome: a clinical case series of 21 patients. Arch intern Med 1991;151:533-7.

6. Heiman-Patterson TD, Bird SJ, Parry GJ, et al. Peripheral neuropathy associated with eosinophilia-myalgia syndrome. Ann Neurol 1990;28:522-7.

7. Seidman RJ, Kaufman LD, Sokoloff L, Miller F, lliya A, Peress NS. The neuromuscular pathology of the eosinophilia-myalgia syndrome. J Neuropathol Exp Neurol 1991;50:49-62.

8. Smith BE, Dyck PJ. Peripheral neuropathy in the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Neurology 1990;40:1035-40.

* Cases met a modified surveillance case definition of eosinophil count [greater than or equal to] 1000 cells/mm[sup.3], generalized myalgia (but not necessarily severe enough to affect the patient's ability to pursue usual daily activities, as used in national surveillance conducted by CDC [1]), and absence of contributing infection or neoplasm.

COPYRIGHT 1991 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group

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