The Rise and Fall of Gold Therapy
For many decades, injectable gold salts were a mainstay in the treatment of active, progressive rheumatoid arthritis (RA), a class of medications known as Disease-Modifying Anti-Rheumatic Drugs (DMARDs). Gold sodium thiomalate, sold under the brand name Myochrysine, was one of the most commonly used forms. While the precise mechanism of action remains unknown, it was thought to alter the immune system to reduce inflammation, potentially by inhibiting prostaglandin synthesis or interfering with macrophage function. However, the therapeutic benefits came with a significant and often severe risk of toxicity, which ultimately led to its decline and discontinuation in favor of newer, safer medications like methotrexate.
Significant and Systemic Toxicity Risks
As a heavy metal compound, gold sodium thiomalate is toxic and can cause widespread adverse effects throughout the body, with severe side effects leading to discontinuation in up to one-third of patients. The risk of toxicity is dose-dependent and can manifest at any time during treatment. Physicians were required to be familiar with the potential toxicities and benefits to manage the risks adequately.
Dermatologic and Mucocutaneous Reactions
Skin and mucous membrane issues are among the most frequent adverse effects of gold therapy, with skin rash occurring in as many as 30% of patients. Pruritus (itching) is a crucial early warning sign. A variety of reactions can occur:
- Rashes: Can be macular, papular, or nonspecific, sometimes aggravated by sunlight.
- Exfoliative Dermatitis: A serious, generalized skin peeling condition.
- Stomatitis: Inflammation and sores on the mucous membranes of the mouth, which may be preceded by a metallic taste.
- Chrysiasis: Permanent gray-blue pigmentation of the skin in sun-exposed areas, though uncommon.
Renal (Kidney) Toxicity
Gold can be toxic to the kidneys, and renal adverse reactions are a well-documented risk. Issues range from mild to severe and include:
- Proteinuria: The presence of protein in the urine, a common sign of kidney damage.
- Nephrotic Syndrome: A condition causing the body to excrete too much protein in the urine.
- Glomerulitis and Nephritis: Inflammation of the kidney's filtering units. Fortunately, if renal toxicity is recognized early and the medication is stopped, the effects are often reversible.
Hematologic (Blood) Disorders
Serious blood dyscrasias, though rare, represent a life-threatening form of gold toxicity. These can occur separately or in combination and include:
- Thrombocytopenia: A low platelet count, which can lead to easy bruising or bleeding.
- Leukopenia and Agranulocytosis: Low white blood cell counts, increasing the risk of infection.
- Aplastic Anemia: Failure of the bone marrow to produce new blood cells.
- Eosinophilia: An elevated number of eosinophils, a type of white blood cell.
Other Systemic Adverse Effects
Beyond the more common reactions, gold sodium thiomalate can cause other systemic problems:
- Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramps, and rarely, fatal ulcerative enterocolitis.
- Cardiovascular: Vasomotor (or nitritoid) reactions can cause flushing, fainting, and weakness immediately after injection.
- Respiratory: Interstitial pneumonitis, alveolitis, and pulmonary fibrosis have been reported.
- Neurological: Rare but serious effects such as peripheral neuropathy (nerve damage) and encephalopathy (brain dysfunction).
Critical Monitoring and Risk Management
Due to the significant risk profile, physicians must closely monitor patients receiving gold sodium thiomalate. Monitoring includes regular clinical evaluation and laboratory tests.
Monitoring Protocol:
- Before each injection: Perform a urinalysis to check for proteinuria or hematuria.
- Before every other injection: Conduct a complete blood count (CBC) to check for hematologic changes.
- Patient observation: Observe the patient for 15-30 minutes after injection for immediate reactions like anaphylaxis.
- Discontinuation signals: Immediate discontinuation of therapy is warranted if significant signs of toxicity are observed, such as persistent diarrhea, a rash, stomatitis, or changes in blood counts.
Gold Sodium Thiomalate vs. Modern DMARDS
Today, older injectable gold compounds have been largely replaced by newer, often safer, and more effective DMARDs. The table below compares injectable gold with modern alternatives.
| Feature | Gold Sodium Thiomalate (Injectable) | Modern DMARDs (e.g., Methotrexate) | Biologics (e.g., TNF blockers) |
|---|---|---|---|
| Toxicity Risk | High; systemic effects are common and can be severe. | Lower overall risk, though side effects can still occur. | Varies, but often more targeted; risk of serious infections. |
| Administration | Intramuscular injection, typically weekly initially, then tapered. | Usually oral, with a weekly dose; some are injectables. | Subcutaneous injection or intravenous infusion. |
| Efficacy | Effective for some patients, leading to remission in about one-fifth of those who tolerate it. | Considered highly effective and a cornerstone of RA treatment. | Highly effective for many patients who fail to respond to other treatments. |
| Monitoring | Frequent and mandatory lab work (CBC, urinalysis). | Regular blood tests to monitor for liver and blood toxicity. | Regular monitoring for potential infections and lab abnormalities. |
| Side Effects | Diverse and often severe, affecting skin, kidneys, and blood. | Gastrointestinal issues, liver enzyme elevation, blood count changes. | Injection site reactions, increased infection risk, potential for allergic reactions. |
Conclusion: A Legacy of Risk
In conclusion, the answer to the question, Is gold sodium thiomalate toxic?, is unequivocally yes. The medication carries a substantial risk of dose-dependent, severe, and systemic adverse reactions that affect multiple organ systems. Its use required a high degree of medical supervision and frequent laboratory monitoring to mitigate the risk of potentially life-threatening complications. The advent of less toxic and often more effective alternatives means that gold therapy is now rarely used in modern clinical practice for rheumatoid arthritis. The history of this treatment serves as an important reminder of the balance between therapeutic efficacy and safety in pharmacology.
For more information on the side effects of this and other medications, consult the drugs database at Drugs.com.
