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DESCRIPTION
Gold compounds are anti-inflammatory medications used orally and parenterally in the treatment of rheumatoid arthritis.
FORMS AND USES
Therapeutic forms of gold include auranofin (Ridaura), gold thiopolypeptide (GTPP), gold sodium thioglucose (Solganal), gold sodium thiomalate (Myochrysine), gold thiosulfate (Sanocrysin), and gold thioglycanide.
TOXIC DOSE
For unknown reasons, there is little correlation between the cumulative dose of a gold compound and clinical toxicity.
PATHOPHYSIOLOGY
- Gold compounds inhibit the activity of enzymes in lysosomes, but the full mechanism of action is unknown.
- Toxicity results from bone marrow suppression and may form immune complexes.
EPIDEMIOLOGY
Poisoning is uncommon.
CAUSES
- Toxicity is usually an adverse drug reaction during therapeutic use.
- Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.
PREGNANCY AND LACTATION
US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in animals or women.
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DIFFERENTIAL DIAGNOSIS
Other causes of mucous membrane inflammation include colchicine and several antineoplastic drugs.
SIGNS AND SYMPTOMS
HEENT
- Stomatitis is the second most commonly observed reaction.
- Glossitis, gingivitis, keratitis, and corneal deposits have been noted.
Dermatologic
- Nonspecific dermatitis is the most common toxic effect.
- Alopecia also occurs.
Cardiovascular
- Peripheral vasodilation may produce syncope and hypotension.
- In one case, ventricular tachycardia occurred after acute ingestion.
Pulmonary
Interstitial pneumonitis and fibrosis have occurred during chronic use.
Gastrointestinal
Diarrhea, enteritis, and colitis are common effects.
Hepatic
Hepatitis and cholestasis develop rarely.
Renal
- Nephrotic proteinuria is not an uncommon effect.
- Nephritis occurs less commonly.
Hematologic
- Eosinophilia is the most common abnormality.
- Thrombocytopenia is also common and may occur months after the last dose.
- Granulocytopenia may develop.
- Aplastic anemia occurs rarely.
Neurologic
Toxicity occurs rarely and includes Guillain-Barré syndrome, encephalopathy, and stroke.
PROCEDURES AND LABORATORY TESTS
Essential Tests
Complete blood count and urinalysis should be obtained throughout therapy to evaluate hematopoietic effects of exposure.
Recommended Tests
- Creatinine and BUN should be obtained to evaluate renal injury.
- Liver function tests are used to monitor for possible hepatic and cholestatic effects.
Not Recommended Tests
Serum levels of gold are highly variable and do not correlate well with toxic reactions.
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- Treatment should focus on termination of drug exposure followed by general symptomatic care.
- Discontinuation of the drug is usually sufficient to reverse mild toxicity.
DIRECTING PATIENT COURSE
The health-care professional should call the poison control center when:
- Severe or persistent effects develop.
- Toxic effects are not consistent with gold toxicity.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
The patient should be referred to a health-care facility when:
- Suicide or homicide attempt is possible.
- Toxic effects develop.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
Admission Considerations
Patients with acute toxicity, or those with chronic toxicity causing clinically significant bone marrow depression, should be admitted.
DECONTAMINATION
Out of Hospital
Emesis should be induced with ipecac within 1 hour of ingestion for either pediatric or adult patients, if health-care evaluation will be delayed.
In Hospital
- Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
- Administration of activated charcoal also may be useful, especially if a coingestant may be involved.
- One dose (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
- Metallic gold is poorly absorbed by charcoal, and its effectiveness is unknown.
ANTIDOTES
Chelation can be achieved with the following substances, which all require 10 to 14 days of therapy. See individual chapters for further details of chelator administration.
- Dimercaprol (British anti-Lewisite) is the most commonly used chelation agent but may produce hypertension, fever, and urticaria.
- D-penicillamine increases urinary excretion but cannot be used in penicillin-allergic or pregnant patients and may produce multiple side-effects.
- N-acetylcysteine also enhances excretion.
ADJUNCTIVE TREATMENT
- Hemodialysis is not effective.
- Immunosuppressive therapy using cyclophosphamide and prednisone has been used for bone marrow toxicity.
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PATIENT MONITORING
Serial laboratory studies should be obtained to confirm reversal of toxicity.
EXPECTED COURSE AND PROGNOSIS
- The slow absorption and elimination of gold compounds requires patients to be treated beyond their acute presentation.
- Chelation agents require 1 to 2 weeks of therapy to eliminate gold effectively.
- Immunosuppressive therapy may require weeks to reverse hematopoietic effects.
DISCHARGE CRITERIA/INSTRUCTIONS
Patients may be discharged from the emergency department or hospital when toxic effects resolve or stabilize and after psychiatric evaluation, if needed.
Section Outline:
ICD-9-CM 961.2Poisoning by antiinfectives: heavy metal antiinfectives.
See Also: SECTION III, British Antilewisite and penicillamine chapters.
RECOMMENDED READING
Felson DT, et al. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis; results of two metaanalyses. Arthritis Rheum 1990;33:1449-1461.
Schumacher HR, ed. Primer on the rheumatic diseases, 9th ed. Atlanta: The Arthritis Foundation, 1995.
Author: John P. Marshall
Reviewer: Richard C. Dart