R.A. Palmer S. Sidhu P.G. Goodwin
S ir, It is our experience that some adults with acne vulgaris respond to extremely low doses of isotretinoin. Such low doses, used continuously, may be a good way of treating patients who relapse quickly when they cease taking standard doses of isotretinoin.
The dose of isotretinoin used to treat acne vulgaris is often 0·5-1 mg kg 1 d 1, for approximately 4-6 months, to produce a cumulative dose of > 120 mg kg 1. 1 Adult patients with acne tend not to have severe disease and are often successfully treated with relatively low doses, such as 0·25 mg kg 1 d 1, 2 or 0·5 mg kg 1 d 1 taken 1 week in 4 for 6 months. 3 The lowest dose we could find in the literature is 0·1 mg 1 kg 1 d 1· 4 We retrospectively report eight patients with acne vulgaris, controlled by continuous treatment with a single 20 mg tablet, taken once or twice a week; we calculate they are receiving doses of 0·04-0·11 mg kg 1 d 1. Details of their treatment are shown in Table 1.
These patients developed acne between 14 and 32 years ago. Prior to treatment with oral isotretinoin they had acne of moderate severity. Two patients had predominantly truncal acne, which is known to be associated with a relatively high relapse rate after isotretinoin therapy. 5 With treatment (20 or 40 mg d 1), all patients became clear or almost clear of acne. At least six of our eight patients experienced side-effects, such as dry lips, which were severe in some cases.
After stopping treatment they relapsed, often within a few weeks, on several occasions, developing acne of mild severity. Usually, conventional measures of treating relapse (topical therapies and systemic antibiotics) were not used, because their efficacy was perceived by dermatologist and patient to be inferior to oral isotretinoin. Relapse was treated by restarting oral isotretinoin, at successively lower doses. All patients currently have no acne or minimal acne while taking a single 20 mg tablet once or twice per week. They report enormous psychological benefit. Stopping this treatment results in recurrence of mild acne.
Two of our patients have reported mild dry skin or eczema, thought to be due to treatment with ‘microdose’ isotretinoin; the others have no symptomatic side-effects. Isotretinoin therapy can elevate serum hepatic enzymes and lipids and cause adverse skeletal effects, including diffuse idiopathic skeletal hyperostosis. The latter may be detected with a lateral cervical or lumbar spine radiograph. The patients with the highest cumulative doses were investigated for these side-effects when their cumulative doses were between 174 mg kg 1 and 310 mg kg 1. In the four patients tested, no relevant abnormalities were found. However, a previously reported patient with perforating folliculitis 6 now treated with this regimen has a slightly raised serum cholesterol (5·79 mmol L 1, normal range 3·30-5·20); her pretreatment serum cholesterol is unknown. Treatment is on-going in all patients.
Continuous treatment with ‘microdose’ isotretinoin has several theoretical advantages over intermittent standard-dose treatment. In the latter type of regime, patients restart treatment when their symptoms return; therefore by definition, they are not continuously free of disease. The incidence and severity of symptomatic side-effects is very low. Continuous treatment with a 20-mg tablet once per week in a 70-kg adult produces a cumulative dose of under 15 mg kg 1 year 1, which is sufficiently low to be unlikely to cause long-term side-effects, but is an unlicensed method of administration. It costs approximately £52 per year, and can produce enormous psychological benefit.
We recommend that dermatologists consider the continuous use of very low doses of isotretinoin, particularly for adult patients who have repeatedly relapsed after stopping standard doses.