What is Acitretin?
Acitretin is an oral synthetic retinoid, a compound related to vitamin A. Marketed as Soriatane, it treats severe skin conditions in adults by modulating gene expression that regulates skin cell growth and differentiation. This action helps normalize the rapid cell turnover seen in conditions like psoriasis. Unlike immunosuppressants, acitretin offers an alternative for patients with certain other health concerns. Significant improvement may take several months of treatment.
Primary Uses of Acitretin
Acitretin's main application is in managing severe, difficult-to-treat skin diseases, most notably psoriasis.
Treatment for Severe Psoriasis
Acitretin is a key treatment for various severe forms of psoriasis, especially when other options have failed. This includes extensive plaque psoriasis, generalized and localized pustular psoriasis, palmoplantar pustulosis, and nail psoriasis. For generalized pustular psoriasis, it is often a first-line treatment.
Other Dermatological Conditions
Acitretin is also effective for other disorders where keratinization is abnormal. These include Darier's disease, Ichthyoses, Lichen planus, and Pityriasis Rubra Pilaris (PRP).
Chemoprevention
The medication has also shown potential in preventing non-melanoma skin cancers in individuals at high risk, such as those with a history of numerous skin cancers or organ transplant recipients.
How Acitretin Works in the Body
Acitretin's mechanism involves interacting with nuclear retinoid receptors (RAR and RXR) in skin cells. This binding modifies gene transcription, which in turn regulates cell growth and differentiation, helping to normalize the skin's growth cycle. Additionally, acitretin exhibits anti-inflammatory effects by inhibiting molecules involved in conditions like psoriasis, thus reducing redness and scaling. It also slows down the excessive proliferation of keratinocytes.
Comparison of Acitretin and Methotrexate
Acitretin and methotrexate are both systemic options for psoriasis, but they differ in mechanism, indications for psoriatic arthritis, and specific risks.
| Feature | Acitretin | Methotrexate |
|---|---|---|
| Drug Class | Systemic Retinoid (Vitamin A derivative) | Antimetabolite, Immunosuppressant |
| Mechanism | Modulates gene transcription to normalize skin cell proliferation and differentiation | Inhibits cell growth by blocking the enzyme dihydrofolate reductase |
| Psoriatic Arthritis | Not indicated for joint symptoms | Effective for joint inflammation associated with psoriatic arthritis |
| Liver Risk | Hepatotoxicity risk, requires regular monitoring of liver function tests (LFTs). Contraindicated with severe liver disease. | Hepatotoxicity risk, especially with long-term use. Contraindicated with active liver disease. |
| Birth Defect Risk | Severe teratogenic risk. Women of childbearing potential must use two forms of contraception for the duration of treatment and for 3 years after stopping. | Severe teratogenic risk. Women of childbearing potential should not use this drug during pregnancy and must be carefully monitored. |
| Speed of Effect | Slower onset, may take 2-3 months for full benefit | Generally faster-acting than acitretin |
Important Safety Considerations
Acitretin carries a black box warning due to significant risks, particularly related to pregnancy and alcohol consumption.
- Pregnancy and Contraception: Acitretin poses an extremely high risk of severe birth defects and is contraindicated during pregnancy. Women of childbearing age must use two effective forms of contraception for one month before, throughout treatment, and for at least three years after discontinuing the medication. Blood donation is also restricted during and for three years post-treatment.
- Alcohol Consumption: Alcohol consumption must be strictly avoided during treatment and for at least two months after discontinuation. Alcohol can convert acitretin into etretinate, a substance with a longer half-life and prolonged teratogenic effects.
- Liver Function: Monitoring of liver function tests is essential due to the risk of abnormal results and rare severe hepatotoxicity.
- Lipid Levels: Acitretin can increase blood levels of cholesterol and triglycerides, requiring regular monitoring to mitigate risks of cardiovascular issues or pancreatitis.
- Visual Disturbances: Dry eyes and decreased night vision are potential side effects, and rarely, increased intracranial pressure can occur. Eye examinations are advisable.
Combination Therapy with Acitretin
Combining acitretin with other treatments can improve effectiveness and potentially reduce required amounts of each therapy. This includes phototherapy, such as Re-UVB or Re-PUVA, where acitretin is used alongside UV light. Topical agents like corticosteroids or calcipotriol can also be used concurrently. In severe cases, it may be used in rotation or combination with other systemic agents like biologics or cyclosporine under strict medical supervision. You can find more detailed information in the Guidelines for the Use of Acitretin in Psoriasis.
Conclusion
Acitretin is a potent systemic retinoid used primarily for severe psoriasis and other hyperkeratotic skin conditions that haven't responded to other treatments. It works by normalizing skin cell growth and reducing inflammation. Due to significant risks, especially the severe risk of birth defects, careful patient selection, adherence to safety protocols like long-term contraception, and regular monitoring are crucial. With proper management by a dermatologist, acitretin can be an effective part of a treatment plan for debilitating skin conditions.
