Ablative fractional laser intensifies treatment outcome of scalp actinic keratoses with ingenol mebutate: a case report

Editor Actinic keratoses (AK) are pre-malignant lesions caused by cumulative exposure to ultraviolet radiation. AK may progress into invasive squamous cell carcinoma and thus treatment is recommended. Treatment compliance is a considerable issue when striving to achieve optimal treatment outcomes. Presently available topical AK treatments are time-consuming, and cryotherapy may cause disturbing hypopigmentation disorders. Ingenol mebutate (IngMeb) is a topical agent approved for fielddirected treatment of AK with only 2–3 daily treatments. Pretreating the skin with ablative fractional CO2 laser (AFXL) has shown promise as an anti-cancer treatment, whereby uptake of topical photosensitizers is increased, and clinical outcome from photodynamic therapy is enhanced. AFXL pretreatment may have the same potential to enhance treatment outcome with IngMeb, and it is therefore essential to evaluate safety and efficacy of treating AK with IngMeb delivered through AFXL channels. Three male patients with AK on hairless scalp were treated. Treatment area was divided, and one side received AFXL before one single application of IngMeb 150 lg/g (AFXL-IngMeb); the other similar side received 3 days of application with 150 lg/g IngMeb, which follows conventional, approved treatment regimens (IngMeb-conv) (Fig. 1a). AFXL preparation of the skin was performed with the UltraPulse fractional CO2 laser system using DeepFx handpiece to deliver pulse energy of 10 mJ/pulse at a density of 5% (Lumenis Inc, Santa Clara, CA, USA). Ablative fractional CO2 laser was lesion-directed towards individual AK (patient 1 and 2) and covering the entire field cancerized area as field-directed AFXL (patient 3) (Fig. 1b). Local skin reactions on day 3 appeared similar in the lesiondirected AFXL-IngMeb and IngMeb-conv areas for patient 1 and patient 2. The field-directed AFXL-IngMeb of patient 3 responded with intensified local skin reactions compared to the IngMeb-conv area (Fig. 1c). Eight weeks after treatment, efficacy of AK clearances were enhanced on the AFXL pretreated side as compared to the IngMeb-conv in all three patients. The lesion-directed AFXL-IngMeb treatment of patient 1 cleared AKs 100% (Baseline n = 5 vs. 8 weeks n = 0). Less reduction in AK (60%) was achieved in the IngMeb-conv area (Baseline n = 5 vs. 8 weeks n = 2). The same trend was noticed in patient 2, presenting 62.5% AK reduction on AFXL-IngMeb side (Baseline n = 8 vs. 8 weeks n = 3) vs. 50% clearance on IngMeb-conv (Baseline n = 8 vs. 8 weeks n = 4). A total clearance (100%) of AK was documented in the field-directed AFXL-IngMeb area of patient 3 (Baseline: n = 6 vs. 8 weeks: n = 0). Furthermore, rejuvenation was noticed in skin exposed to the combination of AFXL and IngMeb (Fig. 1d). The IngMeb-conv area had less reduction in AK (Baseline: n = 6 vs. 8 weeks: n = 2) (new AK n = 1). All three patients reported no difference in pain on the two differently treated areas. This case report indicates that a one-time AFXL-assisted IngMeb treatment may be advantageous over conventional IngMeb triple self-application. Local skin reactions were more pronounced, but tolerable, with low fluence and low-density