Keywords• actinic keratoses • betulin • betulinic acid • oleogel • skin cancer Summary Background: Actinic keratoses (AK) are squamous cell carcinomas in situ and require treatment. Betulin-based oleogel prepared from a standardized triterpene dry extract from birch bark represents a new topical agent with antiinflammatory and anti-tumor potential. Patients and Methods: In the prospective, randomized, monocentric phase 2a study 45 patients with ≤ 10 AK were included and randomly assigned to one of the three treatment groups. Intervention consisted of topical betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin-based oleogel. Treatment response was assessed clinically after three months. The clinical response was graded into complete clearing (100 %), therapy responders (≥ 75 % clearing of the lesions) and non-responders (< 75 % clearing). Additionally, punch biopsies were obtained from some patients before and at the end of treatment. Results: Therapy with betulin-based oleogel was well tolerated. Three patients discontinued therapy because of personal reasons. After three months, the 100 % (and > 75 %) clearing rates of the lesions were as follows: 64 % (86 %) with betulin-based oleogel (n = 14), 79 % (93 %) with cryotherapy (n = 14), and 71 % (71 %) with the combined therapy (n = 14). Histological analysis of biopsies taken before and after treatment (n = 8) showed a reduced degree of dysplasia in the epidermis in all study arms. Conclusions: Betulin-based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses. However, the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers.

Botanical extracts and single compounds are increasingly used in cosmetics but also in over-the-counter drugs and food supplements. The focus of the present review is on controlled clinical trials with botanicals in the treatment of acne, inflammatory skin diseases, skin infections, UV-induced skin damage, skin cancer, alopecia, vitiligo, and wounds. Studies with botanical cosmetics and drugs are discussed, as well as studies with botanical food supplements. Experimental research on botanicals was considered to a limited extent when it seemed promising for clinical use in the near future. In acne therapy, Mahonia, tea tree oil, and Saccharomyces may have the potential to become standard treatments. Mahonia, Hypericum, Glycyrrhiza and some traditional Chinese medicines appear promising for atopic dermatitis. Some plant-derived substances like dithranol and methoxsalen (8-methoxypsoralen) [in combination with UVA] are already accepted as standard treatments in psoriasis; Mahonia and Capsicum (capsaicin) are the next candidates suggested by present evidence. Oral administration and topical application of antioxidant plant extracts (green and black tea, carotenoids, coffee, and many flavonoids from fruits and vegetables) can protect skin from UV-induced erythema, early aging, and irradiation-induced cancer. Hair loss and vitiligo are also traditional fields of application for botanicals. According to the number and quality of clinical trials with botanicals, the best evidence exists for the treatment of inflammatory skin diseases, i.e. atopic dermatitis and psoriasis. However, many more controlled clinical studies are needed to determine the efficacy and risks of plant-derived products in dermatology. Safety aspects, especially related to sensitization and photodermatitis, have to be taken into account. Therefore, clinicians should not only be informed of the beneficial effects but also the specific adverse effects of botanicals used for dermatologic disorders and cosmetic purposes.

Keywords• acne vulgaris • atopic dermatitis • phytotherapy • psoriasis vulgaris • randomized clinical trials Summary Plant extracts and isolated compounds are increasingly used in cosmetics and food supplements to improve skin conditions. We first introduce the positive plant monographs with dermatological relevance of the former German Commission E. Subsequently clinical studies with botanicals for atopic dermatitis, psoriasis, acne, condylomata acuminata and herpes simplex are discussed. The best studies have been conducted with atopic dermatitis and psoriasis patients. Mahonia aquifolium, Hypericum perforatum, Glycyrrhiza glabra and certain traditional Chinese therapies have been shown to be effective in the treatment of atopic dermatitis. Mahonia aquifolium, Indigo naturalis and Capsicum frutescens are effective treatments for psoriasis. Green tea extract and tea tree oil have been investigated in the treatment of acne. Podophyllin and green tea extract are effective treatments for condylomata acuminata. Balm mint and a combination of sage and rhubarb have been shown to be effective in the treatment of herpes simplex in proof of concept studies.

The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.