G. Gupta

Management of field change in actinic keratosis.

Field cancerization was first described in 1953 as histologically altered mucosa surrounding tumours removed from the upper gastro‐intestinal tract. Over the years the definition has changed to include an area which is clinically occult but has multifocal preneoplastic changes, showing genetic mutations and which precedes the development of second primary tumours and local recurrences. Field cancerization has been described in the oropharynx, oesophagus, stomach, lung, colon, anus, cervix, bladder and skin. Various molecular techniques have been developed to look for genetic mutations and clonality in areas of field change. These studies have highlighted the need for early detection and treatment in order to prevent the development of tumours and local recurrences. In this article we examine the concept of field cancerization and treatments available to manage field change.

Adherence to topical dermatological therapy: lessons from oral drug treatment

Patients are remarkably nonadherent to medical treatment regimens across all diseases and classes of therapy, and it has been estimated that nonadherence to drug treatment is responsible for as many as 10% of all hospital admissions. Nonadherence to treatment also has significant negative effects on treatment outcomes across a wide range of diseases. Patient‐related factors such as age, ethnicity, literacy (including health literacy), health beliefs, and socioeconomic conditions have been shown to influence adherence to oral therapy. Medication‐related factors, such as regimen complexity and duration of treatment, also impact on adherence. Variables that significantly influence adherence to oral drugs have similar effects on adherence to topical therapy. Both educational and psychological interventions along with simplification of dosing regimens can significantly improve adherence to oral therapy and limited evidence indicates that these approaches are also effective in patients receiving topical therapy. There is very little information about the effects of dosing regimens on adherence to topical medical therapy. The advent of new drug formulations that permit once‐daily or single‐dose drug application will, however, permit evaluation of different topical treatment regimens on adherence and treatment outcomes in patients with dermatological disease.

Reduction in lesions from Lmax: a new concept for assessing efficacy of field-directed therapy for actinic keratosis. Results with imiquimod 3.75%

BackgroundCurrent parameters for assessing the efficacy of actinic keratosis (AK) treatments compare clinical lesions at the start and end of a study. However, the sun-exposed field also contains subclinical lesions which may become detectable during treatment. Lmax, the maximum lesion count during treatment, is a new concept to better assess the efficacy of field-directed AK therapies. Measuring efficacy using the reduction in lesions from Lmax includes for the first time the clearance of both subclinical and clinical lesions.ObjectivesTo evaluate the reduction of lesions from Lmax to study end and compare the results with traditional efficacy endpoints using imiquimod 3.75% (IQ3.75%) as an example of field-directed AK therapy.Materials & MethodsPooled analysis of data from two 14-week, vehicle-controlled, double-blind studies of IQ3.75%.ResultsWith IQ3.75%, the median number of lesions increased from 10 at baseline to an Lmax of 22. The median absolute reduction in lesions to study end was 18 from Lmax versus 7 from baseline. The median percentage reduction in AK lesions to study end was 92.2% from Lmax compared with 81.8% from baseline.ConclusionsThe reduction in lesion count from Lmax is a novel efficacy parameter that should become the new way of evaluating field-directed AK therapies since it enables their efficacy against both clinical and subclinical lesions to be accurately determined. Together, the Lmax concept and IQ3.75% represent a newapproach for the management ofAKacross a large sun-exposed field.

A proposed scoring system for assessing the severity of actinic keratosis on the head: actinic keratosis area and severity index.

Actinic keratosis (AK) severity is currently evaluated by subjective assessment of patients.

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.

Real-world approach to actinic keratosis management: practical treatment algorithm for office-based dermatology

Abstract Actinic keratosis (AK) is a chronic skin disease in which multiple clinical and subclinical lesions co-exist across large areas of sun-exposed skin, resulting in field cancerisation. Lesions require treatment because of their potential to transform into invasive squamous cell carcinoma. This article aims to provide office-based dermatologists and general practitioners with simple guidance on AK treatment in daily clinical practice to supplement existing evidence-based guidelines. Novel aspects of the proposed treatment algorithm include differentiating patients according to whether they have isolated scattered lesions, lesions clustered in small areas or large affected fields without reference to specific absolute numbers of lesions. Recognising that complete lesion clearance is rarely achieved in real-life practice and that AK is a chronic disease, the suggested treatment goals are to reduce the number of lesions, to achieve long-term disease control and to prevent disease progression to invasive squamous cell carcinoma. In the clinical setting, physicians should select AK treatments based on local availability, and the presentation and needs of their patients. The proposed AK treatment algorithm is easy-to-use and has high practical relevance for real-life, office-based dermatology.

The role of digital photography and electronic referral in the triage of patients with suspected skin cancer

SIR, Most patients with suspected skin cancer, fast-tracked to dermatology departments, eventually turn out to have benign lesions. To improve the skin cancer capture rate, we redesigned our service to use digital images taken by a medical photographer, in conjunction with an electronic referral letter, in order to triage patients. Patients suspected of having skin cancer by their general practitioner (GP) were referred using a structured electronic letter. The referral was sent to Monklands Hospital via the Scottish Care Initiative referral pathway. This is a secure Scotland-wide web-based electronic referral system (Electronic Clinical Communications Implementation, ECCI) open to all GPs linked to the National Health Service boards’ intranet systems. The referral letter was received and vetted by the dermatologist (C.D.E., G.G) on-line with the help of digital images. The GP arranged an appointment for photography at the Department of Medical Illustration in Monklands Hospital by telephone, at a time to suit the patient. Images showing the location and a close-up shot of the lesion were taken. In addition, a digital dermoscopy image was included for pigmented lesions. The digital images and the electronic letter were vetted in conjunction. Patients suspected of having skin cancer, including basal cell carcinoma (BCC), were given an urgent appointment. Patients were also given an urgent appointment if premalignant lesions were suspected or where the diagnosis was uncertain. All others were seen routinely. At the time of vetting the diagnosis based on photographic evaluation was recorded. All patients were offered an outpatient appointment. Patients given an urgent priority by the dermatologist were offered an appointment within 2 weeks of referral. Data collected from the case notes included patient demographics, GP diagnosis and referral priority, change in lesion noted by GP based on the Scottish Intercollegiate Guidelines Network seven-point checklist score, referral priority by dermatologist based on photographic triage, waiting times for photography, first appointment and treatment initiation, type of treatment and details of histology, where obtained. Fifty patients (19 male, 31 female) with a median age of 41 years (range 11–87) were referred using the ECCI system. Thirty patients were referred routinely by their GP; seven were given a ‘soon’ priority and 13 were referred urgently. Thirtyfive (70%) patients were referred with a suspected skin cancer. In 28 cases, a diagnosis of melanoma was selected from a drop-down list as the referring diagnosis. Of these suspected melanoma cases, 10 referrals were graded by the GP as ‘urgent’, two as ‘soon’ and 16 as ‘routine’. Six patients were suspected of having a BCC, of whom four were referred routinely and two urgently. One patient was suspected of having a squamous cell carcinoma and was referred urgently. Of the remaining 15 (30%) patients, 13 were referred with possible benign naevi and two with premalignant disease. Forty-one (82%) patients were referred with a pigmented lesion. Of these, 19 (46%) had a seven-point score of > 3, 11 (27%) had a score of 2 and 11 (27%) had a score of 0 or 1. Of the 28 patients referred with suspected melanoma, 12 had a seven-point score of ‡ 3 (43%), six had a score of 2 (21%) and 10 had a score of 0 or 1 (36%). On the basis of the digital image, 38 of 50 patients (76%) were given a routine priority and 12 (24%) an urgent priority by the dermatologist. The median waiting time for digital photography was 1 day (range 0–23) and 0 days (range 0–17) for urgent and routine cases, respectively. Table 1 shows the diagnosis by the dermatologist after photographic evaluation and at clinic visit. Photographic diagnosis matched the clinical impression exactly in 88% of cases, with the majority of patients suspected of having benign lesions. The median waiting time for first appointment was 7 days for a patient given an urgent priority (range 3–14) and 14 days for routine priority (range 4–39). There were no cases of missed malignancy in the patients given a routine priority by the dermatologist. Thirty-three (66%) patients received treatment: 21 with surgery alone and nine with cryotherapy alone. One patient was prescribed a topical steroid. One patient had both cryotherapy and surgery and one patient was entered into a clinical trial of topical therapy. The overall median wait for treatment was 0 days (range 0–100). The median wait for surgery was 0 days (range 0–100) and the median wait for treatment of urgent cases was 0 days (range 0–100). The two patients with suspected melanoma had surgery on the same day as their clinic visit.

Long‐term sustained lesion clearance from Lmax with imiquimod 3.75%, a new field‐directed treatment for actinic keratosis

In patients with actinic keratosis (AK), subclinical and clinical lesions coexist across large areas of sun‐exposed skin. The long‐term efficacy of AK treatments depends on their ability to eradicate both types of lesions across the entire field.

Imiquimod 3.75% in actinic keratosis: efficacy in patients with and without rest periods during treatment

and alleviated his discomfort. Direct sequencing of the coding regions of KRT16 and KRT6C was performed on his DNA. He was found to have a heterozygous T>C transversion at nucleotide 1406 of KRT6C. This results in a leucine to proline amino acid substitution at residue 469, located in the 2B domain of the K6c protein (p.Leu469Pro; c.1406T>C). This c.1406T>C mutation is located in the helix boundary motif region of keratin 6c, which is a recognized mutation hotspot in keratin genes. The analogous mutation in KRT6A has been reported in a few cases. The classification of PC is now based on the gene involved (PC-K6a, PC-K6b, PC-K6c, PC-K16, PC-K17) due to the considerable phenotypic overlap between the two previous subtypes (PC-1 and PC-2). We report on a novel mutation of KRT6C and highlight the inclusion of focal PPK secondary to KRT16 and KRT6C mutations as a milder phenotype within the spectrum of PC.

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma

Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy‐to‐use tool to assess the severity of AKs on the head.