What are the effects of alitretinoin on eczema?

Which form of eczema does alitretinoin target?

Eczema is a chronic inflammatory skin condition characterised by itching, redness, blisters, and significant skin dryness, referred to as xerosis. Eczema can be widespread or focused on certain parts of the body, such as the hands. According to an article published in the Revue Médicale Suisse in 2012, hand eczema is a fairly common form affecting approximately 15% of the European population. Both men and women are almost equally affected, with hand eczema being slightly more prevalent in women.

This form of eczema often resembles contact eczema. This occurs when the skin is exposed to a specific environmental allergen that it cannot tolerate. Feeling attacked, it responds by releasing chemical mediators of inflammation. Contact eczema is generally associated with occupational eczema, caused by a substance present in the workplace. Among the most affected professions, we find notably construction jobs (cement, paint), healthcare professions (gloves, resin) and agricultural jobs (pesticides, fertilisers).

Alitretinoin is a medication utilised as a second-line treatment in instances of severe chronic hand eczema.

How does alitretinoin contribute to the management of eczema?

Naturally present in the human body, alitretinoin is a hormone related to vitamin A capable of binding to all known subtypes of retinoic acid receptors, namely RAR-α, RAR-β, RAR-ɣ, RXR-α, RXR-β and RXR-ɣ, unlike other retinoids which are specific agonists to RAR or RXR receptors. Once these receptors are activated by binding with alitretinoin, they behave as transcription factors that regulate the expression of certain genes, particularly those controlling the processes of cell differentiation and proliferation and angiogenesis, that is, the formation of new blood vessels.

Furthermore, alitretinoin has immunomodulatory and anti-inflammatory effects that are beneficial in combating eczema. It notably aids in regulating inflammation in eczema by reducing the expression of certain molecules involved in the immune response, such as CXCR3 ligands and the chemokine CCL20, which are overexpressed in skin lesions. Alitretinoin acts by moderating their production in keratinocytes exposed to cytokines and in the dermal endothelial cells. Moreover, this compound limits the activation and proliferation of leukocyte subsets stimulated by cytokines, as well as antigen-presenting cells, thus helping to decrease the inflammatory response.

Alitretinoin is available in the form of capsules to be swallowed. The treatment typically starts with a dose of 30 mg per day, after which the dosage is adjusted between 10 and 30 mg per day based on tolerance and effectiveness, for a duration of 12 to 24 weeks.

A closer look at the clinical evidence of the efficacy of alitretinoin.

Alitretinoin is a molecule that has been the subject of numerous clinical studies, demonstrating its effectiveness in managing hand eczema. Here are a few examples:

Study	Treatment Plan	Results
BOLLAG & al. (1999)	38 patients received alitretinoin 20 or 40 mg for a period of 1 to 5 months	89% (34/38) of patients had a response deemed good or very good; 5.5% (2/38) had a moderate response and 5.5% (2/38) did not respond. The average reduction in the overall severity score was 86%
RUZICKA & al. (2004)	Placebo (n=78), 10 mg of alitretinoin (n=80), 20 mg of alitretinoin (n=80) or 40 mg of alitretinoin (n=81) once daily for 12 weeks	27% (21/78) with placebo, 39% (31/80) with 10 mg of alitretinoin, 41% (32/80) with 20 mg of alitretinoin, and 53% (43/81) with 40 mg of alitretinoin had healthy hands according to the PGA score
BISONNETTE & al. (2010)	Double-blind study: 117 patients who have previously tried alitretinoin but did not respond or relapsed were randomised to receive either 10 or 30 mg or a placebo for a period of 12 to 24 weeks.	An 80% (39/49) response rate was observed in the group treated with 30 mg of alitretinoin, compared to 8% (2/24) in the placebo group. Similarly, a 48% (10/21) response rate was noted in the group treated with 10 mg of alitretinoin, as opposed to 10% (1/10) in the placebo group.
RUZICKA & al. (2008)	Placebo (n=205), 10 mg of alitretinoin (n=418) or 30 mg of alitretinoin (n=409) once daily for 24 weeks	33.3% (344/1032) of patients had healthy hands according to the PGA score, of which 16.6% (34/205) were with placebo, 27.5% (115/418) with 10 mg of alitretinoin, and 47.7% (195/409) with 30 mg of alitretinoin.

Findings from several clinical studies on the effectiveness of alitretinoin in cases of hand eczema.

Source: RICHARD M. A. & others. Alitretinoin and chronic hand eczema: synthesis of clinical trials. Annals of Dermatology and Venereology (2010).

What precautions should be taken when using alitretinoin?

Like any medication, alitretinoin is associated with risks and usage precautions. It is first important to note that this medication is strictly contraindicated in pregnant women or those who could become pregnant if they do not follow a strict pregnancy prevention programme. Due to its high teratogenic potential, contraception must be implemented before, during and up to one month after stopping the treatment. Regular pregnancy tests are also required and breastfeeding is prohibited during the treatment, due to the risk of alitretinoin passing into breast milk.

Another contraindication: alitretinoin should not be prescribed in cases of severe hepatic or renal insufficiency, hypercholesterolemia, as this substance tends to increase LDL levels, or hypervitaminosis A. It is also associated with an increased risk of psychiatric disorders, particularly depression, hence the importance of closely monitoring the patient's psychological state, especially in individuals with a history of mood disorders. Other notable side effects include musculoskeletal damage, significant skin and lip dryness, as well as a risk of photosensitivity requiring avoidance of excessive sun exposure and proper protection.

In the event of a severe reaction, such as pancreatitis, an inflammatory bowel disease, a persistent increase in transaminases, or symptoms of intracranial hypertension, it is necessary to discontinue the treatment.