Systemic retinoid therapy - informing about opportunities and risks

Oral isotretinoin can be very effective in treating severe forms of acne that do not respond sufficiently to topical and systemic antibiotic therapy. In advance, patients should be informed about side effect risks and possible countermeasures. Most side effects are reversible and dose-dependent, with regular medical follow-up.

While patients with mild acne vulgaris are primarily treated topically, moderate to severe cases often require the use of systemically acting preparations (oral antibiotics, hormone treatments, oral isotretinoin). The current European guidelines recommend the use of oral isotretinoin especially in moderate or severe papulopustular/nodular acne (Fig. 1) and in acne conglobata [1]. In Europe, isotretinoin has been a well-established substance in acne therapy for more than two decades and, in sufficient dosage and treatment duration, often leads to a permanent absence of symptoms after the end of therapy [2]. In Switzerland, oral isotretinoin has been successfully used for severe forms of acne since the 1980s [4].

Highly effective weapon in the fight against severe acne

An essential component in the management of acne patients is to educate them about the opportunities and risks of isotretinoin treatment [3]. Prof. Vincenzo Bettoli, MD, Università di Ferrara (I), advised a differentiated risk-benefit assessment and pointed out that timely, effective acne treatment is useful and important in many respects – not least to minimize the risk of permanent physical scarring, and to improve the quality of life of those affected [5,7]. Isotretinoin is a vitamin A derivative with a broad spectrum of activity. It permanently inhibits the activity of the sebaceous glands and regulates the keratinization of the top layer of the skin, which is causally involved in the development of acne. Several key pathogenetic factors of acne are affected: intrafollicular hyperkeratosis, androgen-dependent seborrhea, microbial hypercolonization with Propionibacterium acnes (Fig. 2), and inflammation and immune response. Study findings confirm that it is a very effective treatment option. Most isotretinoin side effects can be easily prevented and/or treated; it is important to consider individual patient characteristics. A review of the benefit-risk profile of oral isotretinoin based on randomized trials involving a total of 760 patients found that only 12 study participants discontinued treatment due to adverse effects [6].

Individual dosing regimen for sustainable therapy results

The European guidelines suggest a dose of 0.3-0.5 mg/kg/day for oral isotretinoin in moderate or severe papulopustular/nodular acne and ≥0.5 mg/kg/day for acne conglobata [1]. Prof Bettoli, referring to scientific findings, reports that a low initial dose of 0.1-0.2 mg/kg/day or about 10 mg daily and a gradual increase to the highest dose tolerated by the patient is a successful way to achieve good clinical results while minimizing side effects compared to a standard dose of 0.5 mg/kg/day [5,7,8]. With this approach, it takes a little longer for treatment effects to become visible, but the side effects are less.

Treatment with oral isotretinoin should be continued for one month after freedom from appearance to achieve long-term “clearance.” In general, a duration of use of at least six months and a target dose (total cumulative dose, TCD) of 120-150 mg/kg bw is recommended [3]. In a study by Borghi et al. it made no significant difference whether the target dose was 120 or 150 mg/kg bw [10].

Adequate side effect management promotes compliance

A possible complication that may occur with oral isotretinoin is a worsening of the skin condition at the beginning of treatment. In most cases, this “flare” subsides within two to three weeks. Moreover, since isotretinoin inhibits sebum production, dry skin and mucosal changes (cheilitis sicca, dermatitis facialis) may occur. Topical lipid-replenishing therapy can compensate for skin dryness, and patients should be given recommendations for lip care and measures to combat dry eyes. Cheilitis is a typical side effect of isotretinoin and an indication that the treatment is effective. It is a dose-dependent side effect. Study findings show that cheilitis does not affect the quality of life for the majority of acne patients [11]. Patients should also be informed that the skin is prone to photosensitivity during isotretinoin treatment, which is why it is important to ensure adequate sun protection (e.g. preparations with sun protection factor 50+). A summary of recommended accompanying skin/body care measures is shown in Table 1 [5].

Regarding laboratory controls, liver enzymes and serum lipids (cholesterol, triglycerides) should be checked at the beginning of treatment, one month afterward, and at three-monthly intervals during therapy, because an increase in transaminases and serum lipids is possible with isotretinoin treatment [3]. Due to teratogenic potential, retinoids are contraindicated in pregnant women and contraception is important in childbearing age.

No causal relationship to depressive disorders

A causal relationship between isotretinoin and depression or suicidality has not been empirically proven to date [3,9,12] (Box) . Among other things, prospective cohort studies show that suicidal thoughts and depression in acne patients are more likely to be due to other factors (e.g., stigmatization) than to therapy-induced effects [3]. Prof. Bettoli has not observed a disproportionate accumulation of psychological complaints in patients treated with isotretinoin. To screen acne patients for psychological symptoms, the speaker recommended asking questions about general health before and during treatment with oral isotretinoin, as well as after therapy ends. This allows psychological symptoms to be recorded as well.

Kongress: Schweizerische Gesellschaft für Dermatologie und Venerologie (SGDV)

Literature:

European evidence-based (S3) guideline for the treatment of acne – update 2016 – short version. J Eur Acad Dermatol Venereol 2016; 30(8): 1261-1268.
Plewig G, et al.: Systemische Behandlung der Akne mit Isotretinoin: Aktueller Stand. Hautarzt 1997; 48: 881–885.
Nägeli MC, Läuchli S: Acne vulgaris: Aktuelle Erkenntnisse zur Pathogenese und Therapieempfehlungen. Schweiz Med Forum 2017;17(39): 833–837.
Swissmedic: Health Professional Communication (HPC): Sichere Anwendung von Retinoiden, Januar 2017.
Bettoli V, et al.: Challenges and Solutions in Oral Isotretinoin in Acne: Reflections on 35 Years of Experience. Clin Cosmet Investig Dermatol 2019; 12: 943–951.
Vallerand IA, et al.: Effficacy and adverse events of oral isotretinoin for acne: a systematic review. Br J Dermatol 2018; 178: 76.
«The difficult acne patient: How to use Spironolactone and Isotretinoin», Prof. Dr. med. Vincenzo Bettoli, SGDV Jahresversammlung 09.11.2022.
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Borghi A, et al.: Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: efficacy in achieving stable remission. J Eur Acad Dermatol Venereol 2011; 25(9): 1094–1098.
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Spring LK, et al.: Isotretinoin and timing of procedural interventions: a systematic review with consensus recommendations. JAMA Dermatol 2017; 153(8): 802–809.
Waldman A, et al.: ASDS guidelines task force: consensus recommendations regarding the safety of lasers, dermabrasion, chemical peels, energy devices, and skin surgery during and after isotretinoin use. Dermatol Surg 2017; 43(10): 1249–1262.