Treatment of actinic keratoses with a novel betulin‐based oleogel. A prospective,randomized, comparative pilot study

Background: Actinic keratoses (AK) are squamous cell carcinomas in situ and require treatment. Betulin‐based oleogel prepared from a standardized triter‐pene dry extract from birch bark represents a new topical agent with anti‐inflammatory 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 dys‐plasia 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.     

Daylight methyl‐aminolevulinate photodynamic therapy versus ingenol mebutate for the treatment of actinic keratoses: an intraindividual comparative analysis

Daylight‐photodynamic therapy (D‐PDT) and ingenol mebutate (IM) are novel therapies directed to actinic keratoses (AK). The purpose of our study was to compare effectiveness, tolerability, cosmetic outcome and patient preference of D‐PDT versus IM in the treatment of grade I and II AK. Twenty‐seven patients with AK on the face or scalp were enrolled. Each patient received, in a 25 cm² target area, D‐PDT on right side and IM on left side. Overall 323 AK were treated. Both target areas achieved complete response in 40.47% of the cases and average AK clearance rate was similar for D‐PDT and IM (p=0.74). In D‐PDT areas mean grade II AK clearance rate was lower compared with that of grade I AK (p=0.015). In IM areas grade I and II AK average clearance rates were similar (p=0.28). At week 1 and month 1, mean local skin responses (LSR) score were higher in areas treated with IM. IM areas showed more severe pain and cosmetic sequelae. D‐PDT had similar effectiveness to IM, even if IM demonstrated higher grade II AK clearance rate. Tolerability profile was superior for D‐PDT in terms of LSR and pain. D‐PDT was more cosmetically acceptable. Patients preferred D‐PDT to IM in most cases.     

Treatment of actinic keratoses with birch bark extract: a pilot study

Background: Birch bark contains a variety of apoptosis‐inducing and anti‐inflammatory substances such as betulinic acid, betulin, oleanolic acid and lupeol. Therefore, birch bark extract may be effective in the treatment of actinic keratoses. To address this issue, a pilot study using a standardized birch bark ointment was performed. Methods: Twenty‐eight patients with actinic keratoses were enrolled in this prospective, non‐randomized pilot study. Fourteen patients were treated with birch bark ointment only; fourteen patients received a combination therapy with cryotherapy and birch bark ointment. Treatment response was assessed clinically after two months. Results: Clearing of more than 75 % of the lesions was seen in 79 % of the patients treated with birch bark ointment monotherapy. The response rate of the combined treatment modality was 93 %. Therapy with birch bark ointment was well tolerated. Conclusion: In this pilot study, a standardized birch bark extract was effective in the treatment of actinic keratoses. This therapy is easy to perform and it has no side effects. Birch bark ointment may be a new therapeutic option for actinic keratoses.     

Follow‐up of actinic keratoses after shave biopsy by in‐vivo reflectance confocal microscopy – a pilot study

Background Monitoring of treatment efficacy after shave biopsy of actinic keratoses (AK) is often difficult, as clinical and dermoscopic features may not be reliable. Objectives  We investigated the applicability of in‐vivo reflectance confocal microscopy (RCM) for the follow‐up of AK after shave biopsy. Methods A total of 10 lesions were investigated by RCM before shave biopsy, after 3 and 12 months by two observers in agreement blinded to location, patients and time interval. Results At baseline all lesions showed typical clinical, dermoscopic and RCM criteria of AK. Three months after shave biopsy, all lesions presented clinically as normal skin (NS), but two lesions showed features suspicious for AK by RCM. After 12 months, one lesion of these two lesions changed into NS in RCM, whereas the other lesion progressed into clinical visible AK. At baseline, the two observers diagnosed 10 of 10 lesions correctly in RCM, after 3 months eight of 10 lesions and after 12 months all lesions were diagnosed correctly. Conclusions Our results suggest that RCM might be a useful tool in the follow‐up of AK after shave biopsy and might be used in inconclusive clinical and dermoscopic presentations of lesions after surgery or other treatment modalities.     

A randomized,half‐side comparative study of aminolaevulinate photodynamic therapy vs. CO2 laser ablation in immunocompetent patients with multiple actinic keratoses

Background Photodynamic therapy (PDT) and laser ablation (LA) are frequently used treatment options for multiple actinic keratoses (AK), yet they have not been compared head to head. Objectives To compare PDT and carbon dioxide (CO₂) LA in the management of multiple AK using objective and subjective outcome measures. Methods A single‐centre, randomized, two‐treatment half‐side comparative study of PDT vs. CO₂ LA was performed. Patients with at least four bilateral (e.g., scalp, forearms) AK were included. The primary outcome measure was the reduction of AK 3 months (v3) after therapy. Secondary outcome measures included the reduction of AK 4 weeks (v2) after therapy, decrease of epidermal p53 and Ki‐67 protein expression, micromorphological changes as assessed by optical coherence tomography (OCT) in vivo, and investigators’ and patients’ satisfaction scoring. Results In total, 20 patients (18 men and 2 women) completed the study. Both treatments reduced AK quantity significantly. On v3, relative reduction of AK quantity was significantly higher following PDT (P = 0·0362). Ki‐67 and p53 protein expression was reduced significantly from baseline (Ki‐67, median 49·5%; p53, median 64·8%) to v2 by both procedures (PDT, median 18·5%, P < 0·0001; LA, median 16·2%, P < 0·0001). AK features as assessed by OCT imaging were also significantly reduced by both procedures. The investigators and patients rated the side‐effects and inconveniences of PDT as more severe, but both overall preferred PDT due to the superior clinical outcome. Conclusions CO₂ LA and PDT are both effective therapy options for multiple AK, yet PDT seems to be superior in terms of AK reduction and participants’ and investigators’ overall satisfaction.     

Photodynamische Therapie mit Methylaminooxopentanoat (Metvix®) und einer Breitbandlichtquelle (PhotoDyn 501): Praktische Erfahrungen bei Problem‐Patienten mit Aktinischen Keratosen und Basalzellkarzinomen

Background: Actinic keratoses (AK) and basal cell carcinomas (BCC) may represent a therapeutic challenge because of special subtypes, location, previous therapy or accompanying diseases. Photodynamic therapy (PDT) offers a semi‐conservative treatment option for selected indications. Patients and methods: 28 outpatients who had been admitted as complicated dermato‐oncologic cases because of AK (n = 22) and BCC (n = 6) were treated with PDT, using methylaminooxopentanoate (MAOP, Methyl‐Ala, Metvix®) and a broad band light source (PhotoDyn 501). The treatment was evaluated for efficacy and subjective tolerance (local discomfort and pain). Results: A complete remission (CR) was achieved in 11/22 AK (50 %) and 4/6 BCC (67 %) cases. All three cases of a superficial BCC subtype underwent a CR. Among responders, tolerance was good in 12/15 cases (80 %), as compared to 4/13 cases (31 %) in non‐responders. Focusing on 16/28 patients with good tolerance (57 %), there was a CR in 12 cases (75 % rate), whereas for the 12/28 patients with moderate to poor tolerance a CR was achieved in only 3 cases (25 % rate). In a subgroup of 8 patients who, partly due to secondary diseases, were taking systemic retinoids or immunosuppressive‐cytostatic medications, a CR was achieved in 3/8 cases (38 %) with a good tolerance in only 1/8 cases (13 %). Conclusion: These observations confirm a good efficacy and tolerance of PDT in ≥ 50 % of a AK/BCC problem patient cohort. We found indications for 1) a positive correlation between efficacy and subjective tolerance as well as 2) the presumptive existence of a retinoid‐dependent cutaneous PDT hyperalgesia. Effective pain control seems to be an essential cofactor for the success of PDT.     

Long‐term follow‐up of photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid patch: 12 months data

Background Photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid (5‐ALA) patch shows high efficacy rates in the treatment of mild to moderate actinic keratosis (AK) in short term trials. Objectives The purpose of the trial was to follow up patients after successful 5‐ALA patch‐PDT at 3 month intervals over a total period of 12 months. Patients who had received placebo‐PDT or cryosurgery served for comparison. Patients/methods Three months after therapy, 360 patients from two separate randomized parallel group phase III studies (one superiority trial vs. placebo‐PDT, one noninferiority trial vs. cryosurgery) were suitable for the follow‐up study. Patients had to show at least one successfully treated AK lesion after initial therapy. A total of 316 patients completed the follow‐up. Results Twelve months after a single treatment, 5‐ALA patch‐PDT still proved superior to placebo‐PDT and cryosurgery (P < 0·001 for all tests). On a lesion basis, efficacy rates were 63% and 79% for PDT, 63% for cryosurgery and 9% and 25% for placebo‐PDT. Recurrence rates of patch‐PDT proved superior to those of cryosurgery (per protocol set: P = 0·011, full analysis set: P = 0·049). While 31% of cryosurgery lesions were still hypopigmented after 1 year, the 5‐ALA patch‐PDT groups showed hypopigmentation in 0% (superiority trial) and 3% (noninferiority trial) of the treated lesions. Conclusion Twelve months after a single 5‐ALA patch‐PDT the majority of lesions were still cleared with an excellent cosmetic outcome. 5‐ALA patch‐PDT proved to be superior to cryosurgery in the noninferiority study setting.     

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 1: treatment delivery and established indications – actinic keratoses,Bowen's disease and basal cell carcinomas

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3‐h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well‐tolerated therapy although discomfort associated with conventional protocol may require pain‐reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.     

Single vs. fractionated photodynamic therapy for face and scalp actinic keratoses: a randomized,intraindividual comparison trial with 12‐month follow‐up

Objective To compare the efficacy and tolerability of a single ALA‐PDT illumination scheme with that of a fractionated ALA‐PDT illumination scheme in face and scalp actinic keratoses (AKs). Methods Eligible patients received either a single ALA‐PDT illumination or a fractionated illumination scheme randomly allocated to alternate sides of face/scalp. The side allocated to a single illumination received 75 J/cm². This side received 2 sessions performed 7 days apart. Lesions on the fractionated illumination scheme side received 20 and 80 J/cm², 4 and 6 hours after a single ALA application. Patients were evaluated at baseline, at 3 and 12 months after treatment. Efficacy end point included the individual AK lesion clearance rate. Results Thirty three patients with 266 lesions were enrolled in the study. Three months after treatment the overall lesion complete response rate was 89.05% for the single scheme and 96.12% for the fractionation scheme while at the 12‐months follow‐up response rate decreased to 85.4% for the single illumination and to 93.79% for the fractionated illumination group. Looking at lesion response based on lesion grade fractionated photodynamic therapy (PDT) resulted in larger rates of cured grade I as well as grade II lesions. Recorded adverse events were transient and did not demand additional therapy. Conclusions Our results demonstrate that higher responses are achieved with fractionated PDT compared with single illumination PDT. The study data indicate that fewer treatment sessions may be needed with fractionated PDT increasing that way the comfort of the patient regarding number of visits, treatment cost and treatment‐related downtime.     

Peeling with 70% glicolic acid followed by 5% 5‐fluorouracil as well as 5% 5‐fluorouracil cream are effective methods for the treatment of actinic keratoses on upper limbs: A randomized clinical trial

The 5% 5‐fluorouracil (5‐FU) cream, considered the gold standard topical treatment, and peeling using 70% glycolic acid (GA) followed by 5% 5‐FU are methods for the treatment of actinic keratoses (AKs). However, the comparison of these two treatments had not yet been described and therefore was the objective of this study. A randomized clinical trial, intrapatient study in which 17 patients received a type of treatment in the right and left upper limb with 5% 5‐FU cream (twice daily) or a peeling application of 70% GA (every 15 days) followed by 5% 5‐FU cream. There was a significant reduction of 75% and 85.71% in the mean number of AK lesions and of 74.5% and 85.71% in the size of lesions on the upper limbs of patients treated with peeling and 5% 5‐FU cream (P‐value ≤.001), respectively. Neither treatment was superior to the other since there was no significant difference (P‐value ≥.05) between the treatments, both at the post‐intervention period as well as when comparing the difference between the pre and post‐intervention periods. The peeling with 70% GA followed by 5% 5‐FU as well as 5% 5‐FU cream are effective methods for the treatment of AKs on upper limbs.     

Patient‐reported health outcomes in patients with non‐melanoma skin cancer and actinic keratosis: results from a large‐scale observational study analysing effects of diagnoses and disease progression

Background

Non‐melanoma skin cancer (NMSC) and actinic keratosis (AK) are very common among fair‐skinned individuals. A disease continuum from AK to squamous cell carcinoma (SCC) has been frequently postulated. AK and NMSC may influence quality of life (QL) of patients, and it can be suspected that disease progression entails a QL reduction. The purpose of this study was to document QL in patients with NMSC and AK using the health‐outcome questionnaire EQ‐5D‐5L.

Methods

The study was designed as a non‐interventional, prospective, cross‐sectional study. Patients with AK, SCC, basal cell carcinoma (BCC) or multiple diagnoses were enrolled in this study in 29 dermatological centres across Germany. Patients were asked to complete the EQ‐5D‐5L (compromising EQ Index and EQ VAS), and the dermatologists provided diagnosis, disease history and treatment data.

Results

A total of 1184 patients were enrolled and diagnosed as follows: 73% AK, 49% BCC and 17% SCC. 66% had a single diagnosis, 28% two different diagnoses and 6% three different diagnoses. QL was strongly associated with patients’ diagnosis. Patients with a single AK diagnosis had significantly higher mean EQ VAS (78) than patients with BCC (74), SCC (72), and BCC plus SCC (69), P < 0.050. When the effects of disease progression were calculated, patients with AK plus SCC reported significantly less mean EQ VAS (71) than patients with a single AK diagnosis (78), P < 0.011.

Conclusions

While rarely being imminently life‐threatening, NMSC and AK have an impact on QL as quantified by the EQ‐5D‐5L. This impact is associated with diagnosis (AK vs. NMSC) and clinical progression (AK vs. AK plus SCC). Both lead to a clear decline in QL. This shows that disease progression is perceived and judged as detrimental by patients and that AK and NMSC should be diligently treated to preserve and restore QL.     

Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas

Please cite this paper as: Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas. Experimental Dermatology 2010; 19: 151–153. Abstract: Epidermal growth factor receptor (EGFR) gene amplification and protein overexpression are common in several cancers. EGFR status has seldom been studied in cutaneous squamous carcinomas (SCCs), or their precursors, actinic keratoses (AKs). We evaluated the presence of EGFR genomic aberrations and EGFR protein overexpression in 25 AKs and 35 invasive SCCs by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. EGFR numerical aberrations were detected in 52% of AKs and 77.1% of SCCs (P = 0.042). EGFR amplification was identified in 12% of AKs and 20% of SCCs. No differences regarding EGFR numerical aberrations were observed when AKs with high‐grade dysplasia were compared with SCCs. A good correlation was observed between EGFR numerical aberrations and EGFR overexpression. Our results suggest that EGFR numerical aberrations occur in the early stages of epithelial carcinogenesis in skin, not playing a role in the progression from low‐grade SCCs into more aggressive phenotypes.     

Topical 3.0% diclofenac in 2.5% hyaluronic acid gel induces regression of cancerous transformation in actinic keratoses

Background Actinic keratoses (AKs) are frequently diagnosed in dermatological patients. As they represent in situ carcinomas, effective treatment is required. Objectives We investigated the effect of topical 3.0% diclofenac in 2.5% hyaluronic acid gel on AK. Methods Sixty‐five patients with AKs were clinically evaluated before and after 3 months’ treatment with topical 3.0% diclofenac in 2.5% hyaluronic gel. Biopsy specimens were taken and stained with haematoxylin‐eosin and immunohistological markers. Specimens were evaluated for histological type of AKs using the AK classification scheme suggested by Röwert‐Huber et al. [(early) in situ squamous cell carcinoma type AK Grade I–III], number of mitoses per high‐power field and expression of immunohistological markers. Results Complete clinical resolution was observed in 11 patients (16.9%). A significant (P < 0.001) downgrading of AK grade was observed. Complete histological resolution was achieved in 15 patients (23.1%). The number of mitoses per high‐power field was reduced significantly (P < 0.001). The expression of anti‐p53‐antibody decreased significantly (P = 0.009), as did the expression of anti‐MiB‐1 antibody (P = 0.021). Conclusions 3.0% diclofenac in 2.5% hyaluronic acid gel causes regression of signs of cancerous transformation after 3 months’ therapy.     

5-fluorouracil 0.5% cream for multiple actinic or solar keratoses of the face and anterior scalp

Carac (5-fluorouracil 0.5% cream, Aventis Pharma) was approved by the US FDA in October 2000, for the treatment of multiple actinic or solar keratoses involving the face and anterior scalp. The cream should be applied in a thin film once daily to the skin where actinic keratoses (AKs) are present. When it is applied for 1, 2, or 4 weeks, it is significantly more effective than a vehicle in the management of patients with five or more AKs at pretherapy. Pooled data from the two pivotal trials (n=384) indicate that following 4 weeks of therapy the number of subjects with total AK clearance in the Carac and vehicle groups was 52.9% and 1.6% respectively (p<0.001). Furthermore, the corresponding reduction of AK lesion counts in the Carac and vehicle groups was 82.5% and 19.3%, respectively (p<0.001). Treatment should be continued up to 4 weeks as tolerated by the patient. The most common adverse-effect is facial irritation.     

Die solare Keratose: Von der Präkanzerose zum präinvasiven Plattenepithelkarzinom – Therapeutischer Ansatz nach dem Bioinduktionsverfahren

Background: Solar keratoses are precancerous lesions in chronically UV‐damaged skin with histological features consistent with pre‐invasive squamous cell carcinoma. They require therapeutic intervention in order to prevent progression towards invasive carcinoma. Treatment options include topical medications and destructive methods. We report on a new approach – topical bioinductive therapy with imiquimod 5 % cream. Patients and methods: In a prospective case series, 7 patients with solar keratoses have been treated with topical imiquimod 5 %. The cream was applied 5 days/week over 2 weeks. After end of treatment, the outcome was assessed at regular control visits and, in some cases, histologically confirmed. One patient was followed up as untreated control. Results: In 6 of the 7 treated patients, the lesions cleared completely; one patient did not respond. The patients did not show new solar keratoses during a follow‐up period of about 2 years. The untreated patient showed spontaneous clearance of his keratoses. Local skin reactions during treatment included erythema, oedema and erosions in varying degrees, all of which completely resolved. Conclusions: Bioinductive therapy with imiquimod 5 % cream represents a promising therapeutic approach for cutaneous precancerous lesions such as solar keratoses.     

Successful treatment of actinic keratosis with imiquimod cream 5%: a report of six cases

BACKGROUND: Actinic keratoses (AK) are premalignant lesions, which are routinely treated by destructive procedures such as cryotherapy, electrodessication or topical 5-fluorouracil. OBJECTIVES: The aim of this study is to report six cases of AK treated with a potential new topical therapy, imiquimod. METHODS: Subjects included in this study had suffered with recurrent AK for between 5 and 16 years. All six men were treated with imiquimod 5% cream three times a week for 6-8 weeks. In the event of a local skin reaction treatment was modified to two times per week. RESULTS: All the AK lesions were successfully cleared after treatment with imiquimod cream 5% for 6-8 weeks. Histologically, no apparent signs of persisting AK could be detected, and no recurrences were reported during follow up. CONCLUSIONS: This study suggests that imiquimod may be useful as a new therapy for the treatment of actinic keratoses.     

Open label randomized study comparing 3 months vs. 6 months treatment of actinic keratoses with 3% diclofenac in 2.5% hyaluronic acid gel: a trial of the German Dermatologic Cooperative Oncology Group

Background  Actinic keratoses (AK) are carcinomata in situ with the potential to develop into invasive carcinoma. Several studies have demonstrated that 3% diclofenac in 2.5% hyaluronic acid gel (HA) is effective and well tolerated in the treatment of AK. To date there are no large randomized multicentre trials with treatment durations longer than 90 days and histopathological control of treatment outcome. Objective  The aim of this study was to investigate whether a prolonged treatment with diclofenac in HA of 6 vs. 3 months adds to the efficacy in treatment for AK and if this will influence tolerability and quality of life (QoL). Methods  This was a multicentre, randomized open‐label study in which 418 patients with mild to moderate AKs were randomized into two treatment groups. Group A received diclofenac in HA for 3 months and group B for 6 months. Treatment efficacy was assessed by size measurement and a final biopsy of a defined marker AK. Quality of life was measured using the Dermatology Life Quality Index questionnaire. Results  Clinical complete clearance was observed in 40% in group A and in 45% in group B (P = 0.38). Histopathological clearance was confirmed in 30% in group A and in 40% in group B (P = 0.16). Treatment was well tolerated and QoL was significantly improved after treatment in both treatment groups. Conclusion  Treatment with diclofenac in HA is effective and well tolerated during a treatment period of 3 months as well as 6 months. Prolongation of the treatment duration did not significantly affect treatment outcome.     

Actinic keratosis in the en‐face and slice imaging mode of high‐definition optical coherence tomography and comparison with histology

Background Optical coherence tomography (OCT) allows real‐time, in vivo examination of nonmelanoma skin cancer. An innovative high‐definition (HD)‐OCT with a horizontal (en‐face) and vertical (slice) imaging mode offers additional information in the diagnosis of actinic keratosis (AK) and may potentially replace invasive diagnostic biopsies. Objectives To define the characteristic morphological features of AK by using HD‐OCT in the two imaging modes compared with histopathology as gold standard. Methods In total, 20 AKs were examined by HD‐OCT in the en‐face and slice imaging modes and characteristic features were described and evaluated in comparison with the histopathological findings. Furthermore, the HD‐OCT images of a subgroup of AKs were compared with those of the clinically normal adjacent skin. Results The preoperative in vivo diagnostics showed the following features in the en‐face imaging mode of HD‐OCT: disruption of stratum corneum, architectural disarray, cellular/nuclear polymorphism in the stratum granulosum/stratum spinosum, and bright irregular bundles in the superficial dermis. In the vertical slice imaging mode the following characteristics were found: irregular entrance signal, destruction of layering, white streaks and dots, and grey areas. In contrast, the clinically healthy adjacent skin showed mainly a regular epidermal ‘honeycomb’ pattern in the en‐face mode and distinct layering of the skin in the slice mode. Conclusions HD‐OCT with both the en‐face and slice imaging modes offers additional information in the diagnosis of AK compared with conventional OCT and might enhance the possibility of the noninvasive diagnosis of AK prior to treatment procedures and possibly in the monitoring of noninvasive treatment strategies.     

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub‐clinical and clinical actinic keratosis during imiquimod treatment

Please cite this paper as: Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub‐clinical and clinical actinic keratosis during imiquimod treatment. Experimental Dermatology 2010; 19: 641–647. Background: During treatment of actinic keratosis (AK) lesions with imiquimod sub‐clinical lesions often become visible. It is, however, unclear whether these sub‐clinical lesions would be detectable beforehand. Objective: The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood’s lamp for their ability to detect sub‐clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Methodology: Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm² area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub‐clinical) at the screening visit and final counts at week 20. Results: The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 ± 3.4 vs 5.8 ± 1.3; P = 0.027) and week 20 (4.8 ± 2.4 vs 3.0 ± 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. Conclusion: The number of sub‐clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using the CPL method. This is only a preliminary study with a small number of patients and as a result it is difficult to conclude both statistical and clinical significance. However, results were encouraging and indicate that larger studies are needed to demonstrate the relevance of these two new methods for improved detection of clinical and especially sub‐clinical AK lesions.     

European guidelines for topical photodynamic therapy part 1: treatment delivery and current indications – actinic keratoses,Bowen’s disease,basal cell carcinoma

Topical photodynamic therapy (PDT) is a widely used non‐invasive treatment for certain non‐melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High efficacy is demonstrated for PDT using standardized protocols in non‐hyperkeratotic actinic keratoses, Bowen’s disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain‐minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses.