Epidemiologic Notes and Reports Eosinophilia-Myalgia Syndrome -- New Mexico

On October 30, 1989, the New Mexico Department of Health and Environment (NMDHE) was notified of three patients with eosinophilia and severe myalgia who had been taking oral preparations of the amino acid L-tryptophan (LT). Even though the patients had undergone extensive clinical evaluation and testing, their illnesses were not consistent with any known diagnostic entity. Public announcement of the cluster led rapidly to reports of similar cases. Using a provisional case definition of eosinophil count of greater than or equal to 2000 cells per mm3 and absence of documentation in the clinical record of any known cause of eosinophilia (e.g., parasitic or fungal infection, end-stage renal disease, leukemia, allergic disorder, and drug reactions), NMDHE initiated an active search for additional cases through review of laboratory records of eosinophil counts.

As of November 13, 1989, 30 potential cases had been identified. Most cases were reported in Albuquerque and Santa Fe, but cases were also reported in other parts of the state. The 17 female patients ranged in age from 20 to 80 years (mean: 42 years), and the 13 males, from 4 to 78 years (mean: 48 years). Reported eosinophil counts ranged from 2064 to 12,100 cells per mm3 (mean: 2300 cells per mm3) (normal: 50-350 cells per mm3 (1)).

Fifteen of the 30 patients were hospitalized. Detailed clinical histories were available for 14 patients, each of whom reported myalgia; for 11 (79%) the myalgias were incapacitating. Other clinical findings included subjective weakness (11 (79%) of patients), fever 99.7-105 F (11 (79%)), arthralgia (11 (79%)), shortness of breath (nine (64%)), rash (eight (57%)), edema in the extremities (eight (57%)), and clinical pneumonia (five (36%)).

Eleven of these 14 patients are known to have been users of LT. Multiple brands and dosages were involved. To further assess a possible association between use of LT and this syndrome, a case-control study is under way. Reported by: WL Blevins, MD, Taos; P Hertzman, MD, Los Alamos; M Ting, MD, K Keith, MD, J Mayer, MD, BM Greenfield, MD, Santa Fe; M Eidson, DVM, R Voorhees, MD, M Tanuz, CM Sewell, DrPH, State Epidemiologist, New Mexico Dept of Health and Environment. GJ Gleich, MD, Rochester, Minnesota. Health Studies Br and Surveillance and Programs Br, Div of Environmental Hazards and Health Effects, Center for Environmental Health and Injury Control, CDC.

Editorial Note

Editorial Note: Although the syndrome described in patients from New Mexico shares some features with previous case reports (2-4), it has not been described in epidemic form. In addition, the illness in New Mexico closely parallels the intermediate and chronic phases of toxic-oil syndrome (TOS), which occurred in epidemic form in Spain in 1981. In that epidemic, patients also had severe myalgia and intense eosinophilia, as well as other manifestations (5,6). However, the full range of clinical findings and the severity of illness described for TOS are not apparent in this outbreak.

By November 15, following media publicity and contact by NMDHE with other state health departments concerning the New Mexico cases, CDC had received reports of a total of 154 potential cases of a similar illness from public health agencies, physicians, and the general public in 17 states and the District of Columbia. The extent of this epidemic is unknown. Most of the patients in New Mexico had onset after July 1989. However, reports from other states suggest that illness in some patients occurred before that time.

LT is an essential amino acid that is normally ingested as a constituent of dietary protein. LT supplements are used by some persons for disorders such as insomnia, depression, and premenstrual syndrome (7). On November 11, the Food and Drug Administration (FDA) advised consumers to discontinue use of LT-containing tablets, capsules, and caplets pending further evaluation of their potential adverse effects. FDA is investigating the composition and sources of these products. To date, at least four states (California, Minnesota, New Mexico, and Oregon) have made recommendations or taken action to suspend the sale of LT products within their states.

Because this syndrome represents an apparently new clinical entity, diagnostic criteria have not yet been established. Many of the potential cases reported to CDC had initially been diagnosed as other illnesses, such as eosinophilic myositis, eosinophilic fasciitis, polyarteritis nodosa, and suspected trichinosis. For surveillance purposes, CDC recommends defining a case of eosinophilia-myalgia syndrome (EMS) as an illness characterized by all of the following: 1) eosinophil count greater than or equal to 1000 cells per mm3; 2) generalized myalgia (at some point during the course of illness) of severity sufficient to affect a patient's ability to pursue his or her usual daily activities; 3) one or both of the following: a) exclusion of trichinosis by serologic tests performed at an appropriate interval after onset of symptoms and/or b) muscle biopsy that does not show trichinella larvae but does show an inflammatory infiltrate including eosinophils; and 4) absence of any infection or neoplasm that could account for 1 or 2 above. However, the physician's clinical judgment will continue to be important in diagnosing the syndrome in specific patients, and a variety of different case definitions may be appropriate for specific epidemiologic investigations and research studies.

The surveillance case definition should be considered provisional and subject to change as knowledge of EMS evolves. Since the potentially causal relationship between LT use and EMS remains the subject of active investigation, a patient's use or nonuse of LT should not influence case reporting.

CDC is working with state health departments to develop state-based surveillance of EMS using a uniform case report form with standardized instructions. CDC requests, therefore, that possible cases be reported to state health departments.

References

1. Elin RJ. Reference intervals and laboratory values of clinical importance. In: Wyngaarden JB, Smith LH Jr, eds. Cecil textbook of medicine. 18th ed. Philadelphia: WB Saunders, 1988:2394-404.

2. Yonker RA, Panush RS. Idiopathic eosinophilic myositis with preexisting fibromyalgia. J Rheumatol 1985;12:165-7.

3. Symmans WA, Beresford CH, Bruton D, et al. Cyclic eosinophilic myositis and hyper immunoglobulin-E. Ann Intern Med 1986;104:26-32.

4. Lakhanpal S, Duffy J, Engel AG. Eosinophilia associated with perimyositis and pneumonitis. Mayo Clin Proc 1988;63:37-41.

5. Kilbourne EM, Rigau-Perez JG, Heath CW Jr, et al. Clinical epidemiology of toxic-oil syndrome: manifestations of a new illness. N Engl J Med 1983;309:1408-14.

6. Toxic Epidemic Syndrome Study Group. Toxic epidemic syndrome, Spain, 1981. Lancet 1982;2:697-702.

7. Boman B. L-tryptophan: a rational anti-depressant and a natural hypnotic? Aust NZ J Psychiatry 1988;22:83-97.

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