Therapeutic Hotline: Facial skin rejuvenation in a patient treated with photodynamic therapy for actinic keratosis

The aim of the most used treatments of actinic keratoses (AKs) is to avoid the conversion into invasive squamous cell carcinoma through the destruction of the lesion; a lot of therapeutic modalities (imiquimod, 5-fluorouracil, electrosurgery with curettage, cryosurgery) are effective and safe in this field, but not many can do it with excellent cosmetic results like treatment with photodynamic therapy (PDT). We have treated with this technique an old patient, whose AK was resistant to other treatments; the most interesting feature of our case comes from the esthetic effects of the PDT employing a methyl-ester of 5-aminolevulinic acid as topical photosensitizer. This kind of therapy has removed not only the lesion but also the photoaging manifestations like the wrinkles and the ugly lines, leaving a smooth skin, as we have proved with 3D-profilometry technique.     

Predicting which patients with actinic keratosis are at high risk of keratinocyte carcinoma (non-melanoma skin cancer)

An actinic keratosis (AK) is an area (lesion) of sun-damaged skin, mainly found on sun-exposed parts of the body, particularly the forearms, backs of the hands, face, ears, bald scalp and the lower legs. Left untreated, there is a small risk that an AK could progress into a type of keratinocyte carcinoma (also called non-melanoma skin cancer) called cutaneous squamous cell carcinoma, and patients with AK are at increased risk for keratinocyte carcinoma development in general, including basal cell carcinoma. In the Netherlands, 23·5% of the population aged 50 years or older has one or multiple AKs. It is unclear which AK-patients will develop KCs and how high this risk rate is. This study aimed to develop a prediction model - a way of analysing data to help predict outcomes - to identify high risk AK-patients for KC occurrence. The authors, based at the dermatology department of the Erasmus MC in the Netherlands, included 1,169 participants with AK from the Rotterdam Study cohort and added known risk factors for KC, such as caused by phenotype (physical characteristics), genes or lifestyle, to their model. 176 participants (15.1%) developed a KC after a median follow-up of 1·8 years. The final model with significant KC predictors was obtained by so called “backward stepwise selection”, where the individual effect of each predictor on KC development is analysed while at the same time the effect of all other variables is corrected for. The authors found that (1) the presence of 4 to 9 AKs or 10 or more AKs, (2) AK-localization on upper extremities of the body, and (3) AK-localization elsewhere except the head, increased the risk of KC, and (4) coffee consumption decreased the risk of KC in patients with AK. While this study enables clinicians to calculate the KC risk in AK-patients with the use of four easily assessable predictors, internal validation of the model showed a moderate discriminative ability; this means that there are still unknown predictor variables for KC development in this patient group. Linked Article:   Tokez et al. Br J Dermatol 2020; 183 :495–502 .     

DNA-repair after UV-irradiation in skin fibroblasts from patients with actinic keratosis

Summary Autoradiographic counting technique was utilized to measure the ultraviolet-induced unscheduled DNA synthesis of skin fibroblasts from 12 patients with chronic actinic keratosis and from 12 healthy donors of about the same age. In order to reveal a possible regional difference of DNA repair between the parts of the body ordinarily exposed and those parts unexposed to sunlight, two cell strains were used for each examined subject; one developed from the forehead skin and the other from the abdominal or axillary skin. Unscheduled DNA synthesis appeared depressed in actinic keratosis patients, as compared with controls. In all examined subjects however cell strains from exposed skin showed a DNA repair more active than cell strains from unexposed skin. These findings show that skin cancer may be promoted in actinic keratosis patients by a defect of DNA repair. The exalted DNA repair of chronically sun exposed skin is probably the consequence of a defensive process caused by enzymatic induction.     

The development of Hodgkin's disease in a patient with actinic reticuloid

A 6o-year-old man with actinic reticuloid developed Hodgkin's disease after an interval of 6 years. This is the second case reported of an association between actinic reticuloid and malignant lymphoma.     

Uncommon skin lesion in a patient with ataxia-telangiectasia

A 20‐year‐old African‐American man, with a history of ataxia‐telangiectasia diagnosed at the age of one year, presented to the hospital with fever, cough, and headache of 2 days’ duration. The fever was of high grade, associated with chills and rigors. The headache was frontal in location, constant, pounding in nature, and associated with photophobia and phonophobia; there was no neck pain, no neck stiffness, and no blurring of vision. The patient complained of facial pain. There were no relieving or aggravating factors. The family denied any change in mental status. The cough was productive of yellowish sputum. There was associated rhinorrhea. The patient complained of nausea and vomiting with the headache. A review of other systems was negative. On presentation in the emergency room, the patient was tachypneic, febrile, and tachycardic. He was oriented to time, place, and person. His neck was supple and meningeal signs were negative. He had maxillary sinus tenderness. Neurologic examination revealed nystagmus, ocular telangiectasia ( Fig. 1 ), ataxia, and globally decreased muscle strength. Skin examination showed hypopigmented areas on all four extremities, the face, and neck ( Figs 1–4 ), without involvement of the trunk. The rest of the physical examination was unremarkable.

Figure 1 Open in figure viewer PowerPoint Area of vitiligo on the neck with premature graying of the hair     

Awareness, knowledge and attitudes to non-melanoma skin cancer and actinic keratosis among the general public

BACKGROUND: The incidence of nonmelanoma skin cancer (NMSC) has dramatically increased worldwide. In areas of high incidence this will place a significant burden on the health system. Objectives To establish the awareness, knowledge and attitudes of the general public to NMSC and provide an overview on their level of understanding and knowledge of preventative measures. METHODS: Two thousand and one hundred Caucasian and Hispanic individuals, aged 40-75 years, from the UK, Italy, Germany, Spain, France, the USA and Australia were randomly selected to participate in this market research survey. In a structured telephone interview lasting approximately 10 min, respondents answered questions on NMSC, specifically actinic keratosis (AK) and basal cell carcinoma (BCC). RESULTS: Overall, 6% of respondents had been diagnosed with NMSC, of which the incidence was highest in Australia and the USA. The frequency of skin cancer detection examinations was also greater within these populations. Countries with a high incidence of NSMC had greater awareness of the condition, with more awareness of BCC than AK. The majority of respondents believed there was a correlation between skin cancer and sun exposure, however, a minority of respondents associated skin cancer with 'moderate' tanning. Overall, 86% of respondents claimed that they always took precautions against ultraviolet exposure when in the sun, but only 26% applied sunscreen most or all of the time when they were exposed to the sun for more than 1 h. In most of the countries, outside workers reported lower sunscreen use than other respondents. CONCLUSION: Nonmelanoma skin cancer awareness and prevention behaviors varied significantly among the countries studied. Improved population-specific documentation of skin cancer knowledge and prevention behaviors will facilitate the development and assessment of public health campaigns.     

The natural history of actinic keratosis: a systematic review

Knowledge about the development of untreated actinic keratosis (AK) and risk of progression into squamous cell carcinoma (SCC) is important. Therefore, we set out to synthesize primary data on the natural history of AK. We carried out a systematic literature search (Medline, Medline in Process, Embase, Cochrane) of studies on the natural course of AK, regarding (i) progression and regression rates per lesion‐year, (ii) changes in total lesion counts over time, and (iii) spontaneous field regression and recurrence rates, taking into account studies on participants without immunosuppression and history of skin cancer, immunosuppressed patients and participants with a history of skin cancer and sunscreen use. Twenty‐four eligible studies were identified providing data on at least one of the outcomes. Progression rates of AK to SCC ranged from 0% to 0·075% per lesion‐year, with a risk of up to 0·53% per lesion in patients with prior history of nonmelanoma skin cancer. Rates of regression of single lesions ranged between 15% and 63% after 1 year. The data available on recurrence rates of single lesions 1 year after regression indicate a recurrence rate of 15–53%. Data on the relative change of total AK count over time are heterogeneous, and range from ?53% to +99·1%. Spontaneous complete field regression rates range from 0% to 21%, with recurrences in 57%. In general, the available data are limited. Important methodological limitations apply. Currently, no reliable estimates concerning the frequency of AK developing into invasive carcinoma can be given, and further studies are needed.     

Update on actinic keratosis in clinical trial experience with imiquimod

Actinic keratoses (AK) is a sun induced cutaneous lesion, currently considered as a squamous cell carcinoma in situ that has the potential to progress to invasive SCC. To treat them, numerous, ablative and no ablative, therapeutic approaches exist. Among them, imiquimod, a toll like receptor agonist, recently approved to treat them in the US and Europe, has demonstrated to be effective and safe with an acceptable tolerability in the treatment of these lesions. In this article the results of several high quality RCT are analysed.     

Prevalence and risk factors of actinic keratosis in patients attending Italian dermatology clinics

Background

Actinic keratosis (AK) is a common keratinocyte intraepidermal neoplasia.

Objective

To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics.

Materials & methods

This retrospective study was conducted on clinical data from consecutive white outpatients aged ≥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented.

Results

AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p<0.001). Independent AK risk factors in 4,604 patients were: age (OR: 4.8 [95% CI: 3.5-6.5] for 46-60 years, increasing with older age to OR: 41.5 [95% CI: 29.5-58.2] for >70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI ≥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors.

Conclusions

AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes.

     

Melan-A: not a helpful marker in distinction between melanoma in situ on sun-damaged skin and pigmented actinic keratosis

Pigmented actinic keratosis is one of the simulators of early melanoma in situ from severely sun-damaged skin. Close scrutiny of the hematoxylin and eosin stained section does not always allow an unequivocal diagnosis, because it is sometimes difficult to distinguish pigmented keratinocytes from melanocytes. Immunohistochemical stains, such as S-100 and HMB-45, are used routinely to address this problem. Melan-A, also known as MART-1, is an additional melanocytic marker and has proved to be useful in identifying metastatic tumors of melanocytic origin. The usefulness of this marker to discriminate pigmented actinic keratosis from early melanoma in situ, however, has not yet been a subject of investigation. In this study we evaluated Melan-A expression in ten unequivocal cases of pigmented actinic keratosis and compared the staining pattern with that of S-100, HMB-45, and tyrosinase. In all ten cases the number of cells highlighted with Melan-A was by far larger than those labeled with S-100, HMB-45, and tyrosinase. Four cases showed clusters of Melan-A positive cells being suggestive of melanocytic nests. Even areas of normal skin adjacent to the actinic keratosis featured prominent staining of Melan-A, but only inconsistent labeling of intraepidermal melanocytes with S-100, HMB-45, and tyrosinase. We therefore believe that Melan-A is a more sensitive marker for intraepidermal melanocytes than S-100, HMB-45, and tyrosinase. In addition there may be expression of Melan-A in keratinocytes and nonmelanocytic cells. To avoid an erroneous diagnosis of malignant melanoma one should therefore interpret results obtained from Melan-A stained slides carefully and in the context with other melanocytic markers.