Tarun Mehra1*, Claudia Borelli1*, Walter Burgdorf2, Martin Röcken1 and Martin Schaller1

Departments of Dermatology, 1Eberhard Karls University, Liebermeisterstr. 25, DE-72076 Tübingen, and 2Ludwig-Maximilians-Universität, München, Germany. E-mail: tarun.mehra@med.uni-tuebingen.de

Accepted December 3, 2011.

*These authors contributed equally and should be considered as first authors.

Acne vulgaris is the most common skin disorder with possibly significant social consequences for those affected. Acne conglobata is a severe, inflammatory, nodulocystic form of acne (1), and acne fulminans is a severe, ulcerative form of acne with an acute onset and systemic symptoms (2). Acne has a complex pathogenesis with likely factors including increased seborrhoea, ductal cornification, and colonization of the pilosebaceous ducts by Propionibacterium acnes with ensuing inflammation, as well as elevated insulin-like growth factor 1 (IGF-1 levels (3) and increased signalling via the fibroblast growth factor receptor 2 pathway (4). Inflammation seems to result ultimately from an increased production of interleukin 1 beta and tumour necrosis factor-α (5). A wide array of treatment options, including systemic isotretinoin are available (6).

The aim of this study was to show that a low-dose isotretinoin therapy, 0.1–0.3 mg/kg daily, can be effective in treating severe forms of acne.

METHODS

A retrospective analysis of 4 patients with acne conglobata or acne fulminans treated with low-dose isotretinoin (0.1–0.3 mg/kg/day) was performed. The primary endpoint was the photodocumented improvement of the skin lesions during therapy, quantified using Cook’s grading scale for acne (7), a method grading the severity of skin lesions on a scale from 0 (≤ 3 comedones/papules) to 8 (most severe, i.e. highly inflammatory acne, acne conglobata) using photographic standards. Secondary endpoints were the occurrence of side-effects, therapy duration and cumulative isotretinoin dose. The use of topical therapeutics or other medication for acne treatment was reviewed. Before starting treatment, pregnancy of female patients was ruled out. Patients had been informed of the strict necessity to use reliable methods of contraception until one month after treatment cessation. Patients underwent routine laboratory checks including a full blood count, liver function tests, and a serum lipid profile before treatment initiation and during treatment, as well as routine clinical examination for the monitoring of side-effects.

RESULTS

The study sample comprised 4 patients; all were between 14 and 18 years of age at the start of treatment (Table I). All patients initially had a Cook’s grading scale acne score of 8 and received isotretinoin 10–20 mg daily; 3 were also treated intermittently with oral corticosteroids for 7–9 weeks. The patients were treated for a mean of 10.4 months, with a mean daily isotretinoin dose of 0.19 mg/kg, and a mean cumulative dose of 65.8 mg/kg. Three of four patients also recieved topical treatment (adapalene, clindamycin in combination with benzoyl peroxide or erythromycin). After treatment, one patient had a Cook’s grading scale acne score of 0, two of 2 and one patient of 4 (Fig. 1). The side-effects were mild. Except for one patient with persistently elevated serum cholesterol and creatine kinase, the laboratory findings normalized during treatment without further intervention.

Fig. 1. Patient 2. (a) Before treatment, Cook’s grading scale acne score of 8. (b) After treatment, 0.18 mg/kg/day for 10.0 months, score 2. Patient 4. (c) Before treatment, score of 8. (d) After treatment, 0.16 mg/kg/day for 16.2 months, score 2.

DISCUSSION

Isotretinoin is indicated for severe nodular acne that is unresponsive to combined oral therapy with antibiotics and topical therapy, or under special clinical circumstances as a first-line therapy in individual cases, at a dose of 0.5–1.0 mg/kg/day, with a cumulative dosage of 120–150 mg/kg over 4–6 months (8). Adverse effects include dry skin and mucosa (9), elevated liver enzymes and an increase in serum lipids, especially triglycerides (10), most of the side-effects being dose-dependent. Isotretinoin is highly teratogenic, with a reported 40% incidence of birth defects occurring in children who have been exposed to isotretinoin during the first trimester of pregnancy (9). Most of the side effects, such as dryness of the lips and skin, are dose-dependent, although this can not be asserted for isotretinoin’s teratogenicity (12, 14). Moreover, isotretinoin of less than 0.2 mg/kg is reported to reduce the risk of acne flare upon initiation of therapy (11). This study clearly shows that severe forms of acne can be treated effectively with low-dose isotretinoin (0.1–0.3 mg/kg), if necessary in combination with oral prednisolone, all 4 treated patients improving significantly. Our results are supported by the findings of Plewig et al. (12) and of Lee et al. (13), who demonstrated the effectiveness of low-dose isotretinoin in the treatment of acne conglobata and moderate acne, respectively. Karvonen et al. (14) demonstrated the effectiveness of combining long-term isotretinoin therapy with an initial course of systemic prednisolone in cases of cystic acne. Strong indirect evidence supports the mechanism of action of isotretinoin through the upregulation of FoxO transcription factors, thus dampening promotive effects in the pathogenesis of acne (15). Our patients did not experience a flare of acne upon treatment initiation, nor did any patients show signs of neuropsychiatric problems. None complained about dry eyes or skin, although all developed a mild cheilitis. The laboratory findings were mild and in all but one case resolved spontaneously. None of the patients had to stop isotretinoin therapy due to side-effects. In conclusion, the efficacy and favourable side-effect profile strongly support the use of low-dose isotretinoin treatment, 10–20 mg/day, as first-line therapy for acne conglobata, and in combination with a short-term course of oral corticosteroids, also for acne fulminans. Larger studies are necessary to validate our findings. Moreover, it will be interesting to determine the rate of recurrence of severe forms of acne treated with low-dose isotretinoin.

The authors declare no conflicts of interest.

REFERENCES