Use of Retinoids in the Treatment of Psoriasis

The retinoids are derivatives of retinoic acid and their use is widespread in the treatment of various skin diseases, such as acne, eczema and psoriasis. Etretinate was the first compound of this kind to be used in the treatment of psoriasis and has yielded positive results, both as a monotherapy and in combination with PUVA and other treatment modalities.

However, its high teratogenicity and long elimination half-life (around 100 days) compared to the new retinoid, acitretin, which has an elimination half-life of 2 days, has led to its replacement. Topical application is the common route of administration. However, oral administration is a viable second option for the treatment of severe acne, psoriasisor cutaneous T-cell lymphoma.

How do retinoids act on psoriasis?

The mechanism of action of retinoids on psoriasis is not yet fully understood. Retinoids are believed to work by modulating the proliferation of epidermal keratinocytes. According to some authors, retinoids may also play a role in modulating the response of T lymphocytes, particularly Th1 and Th17 cells, inhibiting chemotaxis, and activating polymorphonuclear leukocytes. Other studies have also shown that retinoids have an antiproliferative action that can reduce scaling, erythema, and the overall thickness of the lesion. However, their mode of action has not been described.

The doctor will typically prescribe acitretin at a dosage of 10 to 25 mg per day. The acitretin dosage can be increased up to 50 mg per day, depending on the patient's tolerance, over a period of 3 to 4 months. The treatment should be taken during a meal or with milk to facilitate the absorption of the medication. In case of forgetting the treatment, there are no specific recommendations. If acitretin is combined with a phototherapy, the dosage will generally be maintained at 25 mg per day or less. A maintenance treatment can also be prescribed at a dosage of 25 mg/day.

The treatment of plaque psoriasis, the common form, with acitretin is considered to have moderate efficacy when used alone. The use of acitretin treatment may be considered when the severity of psoriasis requires a systemic treatment. However, a combination of acitretin and phototherapy in a dermatological cabin allows for an optimal effect in treating the disease. Convincing results are generally observed in about three to four months. Furthermore, acitretin can be administered for the management of less common forms of psoriasis. These include, among others, the pustular psoriasis whether generalised or localised, as well as cases of psoriasis in children.

The primary side effect of acitretin, as with all other retinoids, is skin and mucous membrane dryness. Additionally, at the start of treatment, some patients may report hair loss. Headaches, abdominal and muscular pains are also sometimes observed. These symptoms are generally temporary, but if you notice they persist, do not hesitate to discuss it with your doctor.

Acitretin treatment has been associated in some studies with hepatotoxicity, an increase in intracranial pressure, alterations in glucose tolerance, and photosensitivity. The simultaneous use of retinoids with other therapies having similar side effects may increase the risk of these adverse events.

The decision to take acitretin is based on certain contraindications.

• Pregnancy and breastfeeding.

  For women of childbearing age, it is essential to ensure appropriate contraception. The risks of foetal malformations and the need to continue contraception for three years after stopping the treatment must be taken into account. Foetal malformations associated with retinoid treatment include abnormalities of the central nervous system or facial dysmorphia, anomalies of the external ear, etc. Therefore, it is important to discuss with your doctor other therapeutic options if you are considering pregnancy. Breastfeeding is contraindicated during treatment due to the lack of data.

• Drug Interactions.

  One must be cautious of certain drug interactions. The simultaneous use of acitretin and methotrexate is contraindicated as there is a risk of increased hepatotoxicity from methotrexate. Additionally, concurrent use of antibiotics from the tetracycline family can lead to intracranial hypertension. It is also strongly advised against taking other retinoids at the same time as there is an increased risk of hepatotoxicity, raised intracranial pressure, alterations in glucose tolerance, and photosensitivity.

• The consumption of alcohol.

  A study on volunteer patients using acitretin treatment has shown that acitretin, when combined with alcohol, forms etretinate, the previously used retinoid which is highly teratogenic. However, the mechanism of action has not been elucidated.

• SAURAT J-H. Retinoids and psoriasis: Novel issues in retinoid pharmacology and implications for psoriasis treatment. The Journal of the American Academy of Dermatology (1999).

• KATZ H. I. & al. Acitretin in psoriasis: An overview of adverse effects. American Academy of Dermatology (1999).

• CARRETERO G. & al. Guidelines for the use of acitretin in psoriasis. Actas Dermo-Sifiliográficas (2013).

• Lettre d’information pour le traitement du psoriasis par acitrétine (SORIATANE®). Association France Psoriasis (2020).