When acne becomes severe, nodular, or resistant to topical treatments, despite good adherence, oral retinoids, specifically isotretinoin, represent the most effective option currently available. Their effectiveness is based on their ability to act on all mechanisms related to acne. In addition to normalising cell renewal and having an anti-inflammatory action, isotretinoin has a sebostatic effect not found in topical retinoids. Indeed, this molecule inhibits the activity of the sebaceous glands, thus reducing sebum production. Furthermore, some studies have shown that it is capable of causing them to atrophy, a property particularly interesting for preventing acne relapse in oily skin.
Isotretinoin also exerts an indirect antibacterial effect by altering the follicular environment. Indeed, by inhibiting the proliferation of sebocytes and inducing their dedifferentiation into keratinocytes, it significantly reduces sebum production, which is the main nutritional substrate of C. acnes. This reduction in sebum limits the colonisation of the hair canal by the bacteria, although the molecule does not have a bactericidal or bacteriostatic action. Moreover, unlike oral antibiotics frequently used in acne, isotretinoin does not lead to bacterial resistance.
A systematic review analysed data from 11 randomised clinical trials on the efficacy of isotretinoin in the treatment of acne, involving a total of 760 patients. The participants most often had moderate to severe acne. Across all studies, isotretinoin proved more effective than control treatments (placebo, oral antibiotics or others), with a significant and clinically relevant reduction in the number of acne lesions. However, this benefit is accompanied by an increased risk of adverse effects: their frequency was twice as high in the isotretinoin groups (751 events) than in the control groups (388 events). The majority of reported effects were skin-related and linked to dryness (xerosis, cheilitis), but some more severe cases led to treatment discontinuation, particularly following an elevation of liver enzymes.
Isotretinoin is prescribed at doses ranging from 0.5 to 1 mg/kg/day, with a cumulative target around 120 to 150 mg/kg, achievable after several months of treatment. To limit the purge and side effects associated with isotretinoin, it is possible to start with a low dosage (0.2 mg/kg/day) and gradually increase it. Reaching the cumulative dose maximises the chances of long-term remission. An insufficient cumulative dose is indeed associated with an increased risk of relapse after stopping treatment. In this case, a new course of treatment may be considered.
While isotretinoin is currently the most effective solution for combating acne, it is far from free of side effects, as mentioned earlier. The most common is xerosis, affecting the skin and mucous membranes: dry lips, ocular, nasal or skin dryness are almost systematic. Joint and muscle pains also occur quite frequently, as does an increase in cholesterol levels and transaminases, liver enzymes, that is, present in the liver. Blood tests are thus prescribed every three months to monitor these parameters. That said, one of the most significant risks of isotretinoin is its high teratogenic potential : a pregnancy under isotretinoin exposes to a major malformation risk (up to 35% according to a FELDMAN study), which requires rigorous contraception throughout the duration of the treatment and one month after stopping, as well as a monthly blood test to verify the absence of pregnancy.
Isotretinoin is currently the only molecule that offers a potential for prolonged acne relief.