Colchicine is an age-old medication used to treat a variety of conditions. This article explores its history, mechanisms of action, traditional uses, and emerging applications, particularly focusing on the question: “What Is Colchicine Used For?”.
A Brief History of Colchicine
Colchicine’s roots trace back millennia, derived from the Colchicum autumnale plant, also known as the autumn crocus. Evidence suggests its use as an herbal remedy for joint pain as early as 1500 BCE in ancient Egypt, as documented in the Ebers Papyrus (Figure 1). The active ingredient, colchicine (Figure 2), was isolated in the early 1800s and continues to be utilized as a purified natural product. Despite its long history, the U.S. Federal Drug Administration didn’t approve colchicine until 2009.
Figure 1.
Figure 2.
How Does Colchicine Work? Understanding the Mechanism of Action
While its use spans thousands of years, the precise mechanism of action of colchicine is still under investigation. Research in the 1950s and 1960s identified the microtubule (MT) as a primary cellular target. Microtubules are essential components of the cellular cytoskeleton, critical for processes like mitosis and intracellular transport. Colchicine binds to tubulin dimers, the building blocks of microtubules, disrupting their dynamics and inhibiting cell function (Figure 3).
Figure 3.
Colchicine also impacts neutrophil function, key players in inflammatory responses. It reduces neutrophil recruitment, impairs their migration, and suppresses superoxide production, all of which contribute to the inflammatory process. Furthermore, colchicine interferes with vesicular trafficking, reducing TNF-α receptor expression on macrophages and preventing mast cell degranulation. These actions lead to decreased levels of pro-inflammatory cytokines, explaining colchicine’s potential in treating various inflammatory conditions.
Traditional Uses of Colchicine
Colchicine has been a mainstay in treating certain conditions for centuries:
Gout and Pseudogout
Colchicine’s use in gout treatment dates back millennia. It targets the inflammatory pathways involved in gout, including neutrophil and macrophage activation, leukocyte adhesion, inflammasome activation, and IL-1β production. Studies have demonstrated its efficacy in reducing pain and inflammation during acute gout flares. Additionally, colchicine is used as a prophylactic agent to prevent flares in patients with chronic gout, especially when starting urate-lowering therapy. It is also recommended for both acute flares and prophylaxis in pseudogout, or calcium pyrophosphate crystal arthritis.
Familial Mediterranean Fever (FMF)
Colchicine is the primary treatment for Familial Mediterranean Fever (FMF), a genetic disorder characterized by recurrent episodes of fever, arthritis, and serositis. FMF is caused by mutations affecting pyrin, a protein regulating inflammasome activation, leading to excessive IL-1β production and inflammatory attacks. Colchicine effectively reduces the frequency and severity of these attacks. Moreover, it prevents the development of amyloid A amyloidosis, a serious complication of FMF that can lead to kidney failure. Colchicine is considered safe for long-term use, even in children, pregnant women, and nursing mothers.
Emerging Uses of Colchicine: A New Horizon
Recent research has broadened the potential applications of colchicine across various medical fields, including oncology, immunology, cardiology, and dermatology. These new applications stem from observations in large groups of gout patients taking colchicine for extended periods.
Colchicine in Dermatology
Colchicine has shown promise in treating a range of dermatological conditions, though most evidence is based on small case reports and series (See Table 1).
Table 1: Dermatologic Diseases with Reported Colchicine Use
| Disease | Level of evidence | Reference(s) |
|---|---|---|
| Actinic keratosis | 1^ | 30–32 |
| Behcet’s disease | 1 | 22 |
| Chronic urticaria | 2 | 27 |
| Epidermolysis bullosa acquisita | 2/3 | 23,24,41 |
| Granuloma annulare | 3 | 42 |
| Henoch-Schonlein purpura | 3 | 43 |
| Hidradenitis suppurativa | 3* | 44 |
| Idiopathic plantar eccrine hidradenitis | 3 | 45 |
| Linear IgA | 3 | 46,47 |
| Leukocytoclastic vasculitis | 1* | 25 |
| Neutrophilic urticaria | 3 | 48 |
| Nodular vasculitis | 3 | 49 |
| Purpura annularis telangiectoides | 3 | 50 |
| Pyoderma gangrenosum | 3 | 51,52 |
| Recurrent apthous stomatitis | 1/2 | 28,29 |
| Relapsing polychondritis | 3 | 53,54 |
| Scleredema | 3 | 55 |
| Sclerederma diabeticorum | 3 | 56 |
| Sweet’s syndrome | 2 | 26 |
| Urticarial vasculitis | 3 | 57 |
*No significant effect observed or not efficacious
^Topical colchicine was used
1= Prospective controlled trial
2= Retrospective trial or larger case series (>20 patients)
3= Small series or individual reports
Specific Dermatologic Applications:
- Behçet’s Syndrome: Colchicine has demonstrated efficacy in managing mucosal, cutaneous, pleuropericardial, and abdominal complications of Behçet’s syndrome.
- Epidermolysis Bullosa Acquisita (EBA): Colchicine has been reported as a first-line therapy for EBA due to its low side effect profile, potentially inhibiting antibody secretion.
- Leukocytoclastic Vasculitis (LCV): While some case reports suggest benefit, a randomized controlled trial showed no significant effect of colchicine on LCV.
- Sweet’s Syndrome: Colchicine has been used to treat Sweet’s syndrome, a neutrophilic dermatosis.
- Chronic Urticaria: Some patients with chronic urticaria have shown partial to complete response to colchicine treatment.
- Recurrent Apthous Stomatitis: Colchicine has demonstrated potential in reducing the frequency and duration of lesions in severe apthous stomatitis.
- Actinic Keratosis: Topical colchicine has shown promise in reducing the size of actinic keratoses, premalignant skin lesions.
Other Potential Uses
- Cancer: Studies suggest a potential link between colchicine use and lower incidence of certain cancers, particularly prostate and colorectal cancers.
- Cardiovascular Disease: Research indicates that colchicine may reduce the risk of myocardial infarction and other cardiovascular events.
- Pericarditis: Colchicine is recommended for the treatment and prevention of acute and recurrent pericarditis.
Conclusion
Colchicine, a drug with ancient origins, continues to evolve in its therapeutic applications (Figure 4). From its established role in gout and FMF to its emerging potential in dermatology, oncology, and cardiology, colchicine offers a wide range of benefits. As research deepens our understanding of its mechanisms and expands its clinical uses, colchicine promises to remain a valuable tool in medicine.
