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To the Editor: Trichloroethylene (TCE) is widely used as a metal degreaser, dry cleaning solvent, spot remover, adhesive, lubricant, and anesthetic and analgesic agent.¹ In humans, it can induce acute toxicity, most commonly in the kidney, liver, and central nervous system.² Most TCE toxicity depends on bioactivation by either cytochrome P450–dependent oxidation or glutathione conjugation.² We are not aware of previous reports of human skeletal muscle damage after acute poisoning by TCE.

Case Report
A man in his 40s was admitted to the intensive care unit about 3 hours after oral ingestion of an unknown amount of TCE in a suicide attempt. He was in good physical condition before ingestion but presented with a Glasgow Coma Scale rating of 3, hypotension, sinus tachycardia, and severe diarrhea with normal-colored stool with an odor of TCE. Because of acute respiratory failure, he underwent tracheal intubation and mechanical ventilation. On the fourth day of hospitalization, he developed ventricular bigeminy. Serum electrolytes, urea, creatinine clearance, total bilirubin, alanine aminotransferase, -glutamyltransferase, and alkaline phosphatase levels were within normal ranges. Serum creatine kinase and lactate dehydrogenase levels were persistently elevated (Figure 1); a slight elevation of aspartate aminotransferase occurred 1 week after admission, concomitant with higher creatine kinase levels. Twenty-four days after admission, the patient died of complete heart block.

View larger version (22K): [in this window] [in a new window] Figure 1. Serum Creatine Kinase and Lactate Dehydrogenase Levels During the Patient’s Hospitalization

A muscle biopsy was taken on the 17th day of hospitalization. A mild increase of lipids was observed within many fibers. At the ultrastructural level, large lipid droplets compressed the myofilaments (Figure 2A), and mitochondria were degenerating (Figure 2B). Cytolysosomes containing mitochondrial remnants, sometimes associated with glycogen particles, were present, and a few mitochondria were swollen and had a reduced density of the matrix. Assay of respiratory chain enzyme activity on muscle homogenates showed a severe defect of succinate cytochrome c reductase and reduced nicotinamide adenine dinucleotide cytochrome c reductase (enzyme activity, 17% and 22% of control values, respectively, normalized to citrate synthase) (Table). Trichloroethylene and trichloroacetic acid (TCA), a metabolite of the cytochrome P450–mediated pathway, were measured in the whole muscle. The concentration of TCA in the patient’s muscle specimen was 28.7 µg/g, while it was undetectable in the muscle of 3 tested controls; TCE was absent in patient and control muscle. The concentration of TCA in the patient’s urine, collected on the 17th day after ingestion of TCE, was 15.8 mg/L (normal range, <60 µg/L).

View larger version (75K): [in this window] [in a new window] Figure 2. Muscle Biopsy From Patient With Trichloroethylene Ingestion A, Electromicrograph of skeletal muscle section from the patient shows many large lipid droplets (yellow arrowheads) interspersed among normal myofibrils. Original magnification x 25 200. B, On longitudinal section, 4 degenerating mitochondria (black arrowheads) and 1 large lipid droplet (yellow arrowhead) push on adjacent myofibrils. Original magnification x 33 600.

View this table: [in this window] [in a new window] Table. Mitochondrial Enzyme Activity in Muscle Homogenate From a Patient With Trichloroethylene Poisoning and 30 Healthy Controls*

Comment
Although there are several reports of acute human poisoning by TCE from pulmonary exposure, there are only a few descriptions of toxicity after oral ingestion³ and no previous evidence of skeletal muscle damage from TCE toxicity. Our patient developed signs of acute solvent poisoning, including severe central nervous system depression and signs of cardiotoxicity. No signs of hepatic or renal failure were observed. In our patient, there were muscle abnormalities of lipid storage and mitochondrial degeneration. The absence of evidence for use of drugs or for previous diseases associated with mitochondrial dysfunction and the demonstration of TCE metabolites in the muscle biopsy support that the muscle abnormalities were due to acute intoxication.

In rats and mice, mitochondria are early and sensitive targets of TCE and of its various cytochrome P450– and glutathione-derived metabolites, and a decrease or inhibition of succinate-linked state 3 respiration has been demonstrated.^4-5 In our patient, we observed a severe defect of complex I, II, and III of the respiratory chain, consistent with mitochondrial toxicity in human muscle.

We believe that this is the first report of human skeletal muscle damage from TCE intoxication due to the formation of TCE-derived toxification products. It indicates that serum creatine kinase levels should be monitored in patients with TCE intoxication.

Access to Data: Dr Tomelleri had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosures: None reported.

Funding/Support: This study was funded by Ministero Universita Ricerca Scientifica e Tecnologica (MURST 60%) and Fondazione Cariverona (Bando 2001 Ambiente e Sviluppo Sostenibile).

Role of the Sponsors: The funding agencies had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript.

Gaetano Vattemi, MD, PhD; Paola Tonin, MD; Massimiliano Filosto, MD, PhD; Nicolò Rizzuto, MD; Giuliano Tomelleri, MD
giuliano.tomelleri{at}univr.it
Department of Neurological Sciences and Vision
Section of Clinical Neurology

Luigi Perbellini, MD
Institute of Occupational Medicine
University of Verona
Verona, Italy

Walter Iacovelli, MD; Nicola Petrucci, MD
Department of Anesthesia and Intensive Care
Azienda Ospedaliera Desenzano
Desenzano, Italy

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Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2005;294:554-556.

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