The History of Gold-Based Therapy (Chrysotherapy)
The therapeutic use of gold compounds, historically referred to as chrysotherapy or aurotherapy, dates back centuries but gained notable traction in the treatment of rheumatoid arthritis (RA) in the 20th century. A pivotal moment occurred in 1929 when French internist Jacques Forestier observed that gold compounds could alleviate joint pain in people with RA. His findings led to a new era of treatment for this debilitating autoimmune disease. Before this, gold was even explored for its potential against other infectious diseases like tuberculosis, though these applications were largely unsuccessful.
During its peak use, gold therapy was a mainstay for managing progressive rheumatoid disease that failed to respond to less aggressive treatments like nonsteroidal anti-inflammatory drugs (NSAIDs). The treatment was valued for its disease-modifying properties, meaning it could slow the progression of RA and reduce long-term joint damage, rather than simply masking symptoms. However, the slow onset of action—often taking three to six months to see a noticeable improvement—and the frequent, sometimes severe, side effects meant it was not a perfect solution.
Gold Compounds Used for Treatment
For rheumatoid arthritis, gold compounds are not administered as pure gold metal but as chemically reactive gold salts. These are classified as Disease-Modifying Antirheumatic Drugs (DMARDs). The two primary routes of administration were intramuscular injection and oral capsules, each with a different safety and efficacy profile.
Injectable Gold Compounds
Injectable gold was considered more effective than the oral form, but it came with a higher incidence of side effects. Prominent injectable compounds included:
- Gold Sodium Thiomalate (Myochrysine): This injectable form was administered intramuscularly, typically in weekly doses. Its use has been largely discontinued in many countries, including the United States, due to the availability of safer, more effective treatments and a shortage of active ingredients.
- Aurothioglucose (Solganal): Another injectable gold salt, aurothioglucose, was also widely used for RA. Similar to gold sodium thiomalate, it was a slow-acting treatment requiring careful and consistent monitoring.
Oral Gold Compounds
For patients unable to tolerate the injections, or with less severe disease, an oral option was available:
- Auranofin (Ridaura): Administered as capsules, auranofin was an oral gold compound for rheumatoid arthritis. While it generally caused fewer and milder side effects than injectable gold, its efficacy was also more limited. Auranofin is a lipophilic compound, allowing it to be absorbed through the gastrointestinal tract, though its oral administration can lead to common side effects like diarrhea.
Mechanism of Action and Side Effects
Despite decades of use, the exact mechanism by which gold compounds alleviate RA symptoms is not fully understood, but it is known to involve complex anti-inflammatory and immunomodulatory effects. Researchers believe the compounds suppress the immune system by inhibiting certain cell activities. The gold ions accumulate in the lysosomes of immune cells, particularly macrophages, and interfere with their function. This process inhibits key signaling pathways, reducing the production of pro-inflammatory cytokines such as TNF-alpha and interleukins. Gold compounds also inhibit enzymes like thioredoxin reductase, which plays a role in cellular redox balance and the overall immune response.
The most common side effects of chrysotherapy include skin rashes, mouth ulcers, diarrhea, and a metallic taste. More serious, albeit rare, side effects can occur, impacting various organ systems.
Potential Side Effects of Gold Therapy
| Organ System | Side Effects |
|---|---|
| Skin | Pruritus (itching), dermatitis, urticaria (hives), chrysiasis (blue/gray skin discoloration) |
| Gastrointestinal | Diarrhea, loose stools, abdominal pain, nausea, stomatitis (mouth sores) |
| Renal | Proteinuria (protein in urine), inflammation (nephritis), potential kidney damage |
| Hematologic | Anemia, leukopenia (low white blood cells), thrombocytopenia (low platelets) |
| Hepatic | Liver dysfunction, elevated liver enzymes |
| Pulmonary | Interstitial pneumonitis, lung damage (rare) |
Decline and Modern Alternatives
Beginning in the 1990s, the use of gold therapy began to decline dramatically with the introduction of newer, more effective, and safer DMARDs and biologic drugs. Methotrexate, for instance, became the preferred first-line treatment for RA due to its superior efficacy and better safety profile. The inconvenience of frequent injections and the potential for severe, long-term toxicity made gold therapy a less favorable option. The discontinuation of injectable gold products further cemented its status as a second- or third-line, or even obsolete, treatment.
Modern alternatives to gold compounds for treating rheumatoid arthritis include:
- Methotrexate (MTX): A powerful, widely used DMARD.
- Hydroxychloroquine: An antimalarial drug also used for RA.
- Sulfasalazine: An anti-inflammatory agent.
- Biologics: A class of drugs that target specific parts of the immune system, including TNF inhibitors (e.g., adalimumab, etanercept, infliximab).
- Janus kinase (JAK) inhibitors: A newer class of oral medications that block signals in the immune system.
Emerging Applications of Gold in Medicine
While traditional gold salts have faded from common use, the unique properties of gold are being explored in a new frontier: nanomedicine. Gold nanoparticles (GNPs) possess distinct physical and chemical characteristics that make them promising for a variety of advanced medical applications.
Modern research into gold nanoparticles includes:
- Cancer Therapy: GNPs are being developed for applications such as photothermal therapy, where they are used to heat and destroy cancer cells. They are also investigated as radiosensitizers to enhance the effect of radiation therapy.
- Drug Delivery: The surface of GNPs can be functionalized with drugs, antibodies, or other molecules, allowing for the targeted delivery of therapeutics to specific cells or tissues, such as tumors.
- Imaging and Diagnostics: Due to their high density and light-absorbing properties, GNPs can be used as contrast agents in imaging techniques like X-ray and photoacoustic imaging.
Conclusion
In summary, the primary illness historically treated with gold compounds is rheumatoid arthritis, with gold salts serving as an early form of disease-modifying therapy. While gold therapy, or chrysotherapy, provided significant benefits for many patients, it was ultimately overshadowed by safer and more effective modern alternatives due to its toxicity and delayed onset of action. The legacy of medicinal gold continues, not in the form of traditional salts, but in the exciting and highly targeted field of nanomedicine, where gold nanoparticles are being developed for advanced drug delivery, imaging, and cancer treatments. This shift represents a fascinating evolution in pharmacology, from a broad-spectrum anti-inflammatory agent to a highly precise tool of targeted medicine.
