The Rise and Fall of Gold in Medicine
Gold sodium thiosulfate, also known by names like Sanochrysine and Sodium Aurothiosulphate, is a gold salt historically used as a disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA). This practice, called chrysotherapy or aurotherapy, involves administering gold compounds to reduce inflammation and slow disease progression. The use of gold for medicinal purposes dates back centuries, but its application for RA was pioneered by French physician Jacques Forestier in 1929.
For decades, injectable gold salts like gold sodium thiosulfate and gold sodium thiomalate were a primary treatment for moderate to severe RA, especially in the disease's early, active stages. The therapy showed clinical benefits by reducing the number of swollen joints, pain, and inflammatory markers like Erythrocyte Sedimentation Rate (ESR). However, the treatment was not without significant drawbacks. Its use declined dramatically in the late 1980s and 1990s with the introduction of more effective and less toxic medications, most notably methotrexate.
How Does It Work? Mechanism of Action
The precise mechanism of action for gold salts in treating rheumatoid arthritis is not fully understood, but it's believed they possess immunomodulatory effects. Gold compounds are thought to alter the immune system to reduce inflammation by inhibiting the synthesis of prostaglandins and suppressing the activity of phagocytic cells. They can reduce serum levels of immunoglobulins and rheumatoid factors in patients with arthritis. Additionally, gold salts inhibit various enzymes involved in the inflammatory process, such as acid phosphatase and elastase. The gold in these compounds is in the +1 oxidation state and is thought to form linear structures within the body.
Administration
Gold sodium thiosulfate was administered via intramuscular injection, typically into the gluteal muscle with the patient lying down. Treatment began with a test dose to check for immediate adverse reactions before proceeding to maintenance doses. The therapeutic effects were slow to appear, often taking six to eight weeks for initial improvements like reduced morning stiffness, with full benefits sometimes not seen for months. Due to the potential for severe reactions, patients required close monitoring, including regular urine and blood tests, and had to remain under observation for about 30 minutes post-injection.
Significant Side Effects and Toxicity
The primary reason for the decline of chrysotherapy is its significant toxicity profile. Toxicities are common, occurring in about 30-40% of patients on long-term injectable gold therapy.
Common and Severe Adverse Reactions:
- Mucocutaneous Reactions: These are the most common side effects, accounting for 60-80% of all gold-related toxicities. They include skin rashes (dermatitis), itching (pruritus), and sores in the mouth (stomatitis). A metallic taste often precedes the onset of stomatitis.
- Kidney (Renal) Toxicity: Proteinuria (protein in the urine) is a frequent complication, occurring in 3-19% of patients. In some cases, this can progress to a more serious condition called nephrotic syndrome.
- Blood (Hematologic) Disorders: Potentially life-threatening blood dyscrasias can occur, including thrombocytopenia (low platelet count), leukopenia (low white blood cell count), and aplastic anemia.
- Chrysiasis: Long-term use can lead to a permanent blue-gray discoloration of the skin in sun-exposed areas.
- Nitritoid Reactions: Immediately following an injection, some patients experience a vasomotor reaction with symptoms like flushing, dizziness, and weakness.
Due to these risks, treatment had to be stopped immediately if signs of toxicity appeared.
Comparison of Gold Salts and Methotrexate
The shift away from gold therapy was driven by the availability of drugs like methotrexate, which offered similar or better efficacy with a more manageable safety profile.
| Feature | Gold Sodium Thiosulfate (Injectable) | Auranofin (Oral Gold) | Methotrexate (Oral/Injectable) |
|---|---|---|---|
| Administration | Intramuscular Injection | Oral | Oral or Injection |
| Efficacy | More effective than Auranofin; comparable to low-dose Methotrexate | Less effective than injectable gold | Standard first-line DMARD |
| Toxicity | High incidence of renal, hematologic, and skin reactions | Fewer severe side effects than injectable gold; mainly gastrointestinal | Generally better tolerated than injectable gold, but requires monitoring for liver and lung toxicity |
| Onset of Action | Slow (months) | Slow | Faster than gold salts |
Conclusion: A Relic of Pharmacological History
Gold sodium thiosulfate represents a significant chapter in the history of rheumatoid arthritis treatment. For many decades, it was one of the few available options that could modify the course of the disease, not just treat its symptoms. However, the high rate of serious side effects led to its replacement by newer, safer, and more effective DMARDs like methotrexate. While no longer used clinically for arthritis, gold compounds continue to be found in other areas, such as dental restorations and electronics, and the study of their biological effects has informed modern pharmacology.
For more information on the history and development of different arthritis treatments, a valuable resource is the National Institutes of Health (NIH).
