S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Classifying Actinic Keratosis: What the Reality of Everyday Clinical Practice Shows Us.

Difficulties faced by clinicians in routine clinical practice when selecting the appropriate treatment for patients with actinic keratosis (AK) include: the independent evaluation of AK lesions, the absence of a standardized definition of field cancerization (FC), and the lack of a reproducible classification to grade the entire AK-affected area. Moreover, to assess the severity of AK, most guidelines rely on lesion count, which is often not reproducible among specialists. The present work has 2 main objectives: first, to review and highlight some of the issues clinicians tackle when classifying and monitoring AK lesions and the status of FC, looking in more detail at some of the most commonly used clinical scales for classifying AK lesions. Second, we pose questions that we encounter in daily clinical practice, and whose answers or comments help to deal with cases of AK, facilitating the work of clinicians: How should we approach AK diagnosis? How do the challenges of clinical studies on the evaluation of treatment efficacy translate into clinical practice? We review the literature on the clinical classifications and management of AK, and propose how to guide the diagnosis, management, and monitoring of patients with AK. J Drugs Dermatol. 2022;21(8):845-849. doi:10.36849/JDD.6704.

Wound Care With a Porcine Extracellular Matrix After Surgical Treatment of Rhinophyma.

BACKGROUND: Rhinophyma surgery is commonly associated with prolonged wound healing and the need for multiple wound dressings. OBJECTIVES: To evaluate clinical outcome with a porcine extracellular matrix (ECM) after shave excision of rhinophyma compared with common wound care procedure. MATERIALS AND METHODS: Retrospective analysis of patients with common dressings (CD) compared with patients with additional ECM (OASIS) application. Clinical findings were assessed prior to treatment and at follow-up visit using the Patient and Observer Scar Assessment Scale (POSAS), Vancouver Scar Scale (VSS), and Rhinophyma Severity Index (RHISI). RESULTS: Overall, 28 patients (67.5 ±9.0 years) with a mean wound area of 33.9 (±8.5) cm² were included. After a mean follow-up period of 132 (±73) days, scales of POSAS, VSS, and RHISI showed significant (P< .0001) reductions of 47.0% (±11.1), 56.0% (±12.0), and 62.3% (±14.3), respectively. Subgroup analysis showed no significant differences of aforementioned parameters between the ECM group (n= 17) and CD group (n= 11). In contrast, the number of dressing changes were significantly (P< .006) less in the ECM group (1.4 ±0.8) compared with CD group (4.1 ±2.6). The ECM group showed a significant (P< .017) shorter time to re-epithelization (10.5 ±1.7 days) than the CD group (13.1 ±2.2 days). CONCLUSIONS: The application of porcine ECM is practicable and reduces the number of dressing changes and time to re-epithelization clearly. Crusts are scaling off spontaneously without any aggressive action needed. Our findings indicate that ECM application is a promising approach for rhinophyma wound care.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators.

Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) - short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow-up, prevention and occupational disease.

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.

Diclofenac Sodium 3% in Hyaluronic Acid 2.5% Gel Significantly Diminishes the Actinic Keratosis Area and Severity Index.

BACKGROUND/AIMS: Actinic keratosis area and severity index (AKASI) is a new assessment tool to quantify the severity of actinic damage on the head. Thus far, it has not been evaluated in monitoring the efficacy of field-directed topical treatments in actinic keratosis (AK) in routine clinical practice. Thus, the aim of this study was to determine treatment outcomes by using AKASI 3 months after the initiation of topical application of diclofenac sodium 3% in hyaluronic acid 2.5% gel (DFS) in patients with AKs on the head. METHODS: We performed a retrospective analysis of patients with AKs who had AKASI scores prior to and after treatment with DFS. RESULTS: Of the 24 patients included, 20 (83.3%) showed an improvement in AKASI, 2 (8.3%) a stable AKASI, and 2 (8.3%) a worsening of AKASI after a median (interquartile range) follow-up period of 91.5 days (89.8-104.3). The median AKASI reduction was 31.4% (16.7-59.1). The Wilcoxon test showed significant differences (p = 0.0008) between baseline and posttreatment AKASI values. CONCLUSIONS: AKASI is an easy-to-use quantitative tool for assessing the treatment outcome of field-directed therapies. Field-directed therapies of AK should no longer be monitored by assessments based on lesion counts alone.

Nonmelanoma skin cancer - from actinic keratosis to cutaneous squamous cell carcinoma.

Actinic keratoses (AKs) are defined as intraepithelial proliferation of atypical keratinocytes. Given their potential for progression to invasive squamous cell carcinoma, they may eventually evolve into a life-threatening disease. In recent decades, there has been a significant increase in the incidence of AKs, primarily due to changes in recreational activities and demographic trends in industrialized countries. As it is currently impossible to predict if and when a given AK might progress to invasive carcinoma, rigorous treatment of field cancerization is a key component in preventing potential progression. In addition to a broad armamentarium of procedures as well as pharmaceutical treatment options, primary prevention through diligent UV protection likewise plays a crucial role. New clinical, histomorphological, or molecular classifications are needed to be able to reliably stratify patients based on their individual risk. Especially in light of socio-economic aspects, such a step might prevent over- and undertreatment of an ever-growing patient population and help develop treatment concepts based on individual patient needs.

Histological intralesional heterogeneity of actinic keratoses relates to field cancerization.

BACKGROUND/OBJECTIVES: Histological heterogeneity within distinct actinic keratosis (AK) lesions has been described and might serve as an additional feature of AKs. We aimed to investigate and quantify the histological heterogeneity of AKs regarding different grading systems. METHODS AND MATERIAL: We assessed the histology of 3 mm biopsies of AK lesions located on the scalp or face. We documented basal proliferation (PRO I-III), histological grade (AK I-III) and determined the overall classification of each lesion. RESULTS: Of the 305 lesions included, 48 (15.7 %) lesions were classified as AK I, 152 (49.8 %) as AK II and 105 (34.4 %) as AK III. 33 AKs (10.8 %) showed no basal proliferation, 94 (30.8 %) were graded as PRO I, 99 (32.5 %) as PRO II and 79 (25.9 %) as PRO III. One histological grade and basal growth pattern per lesion was observed in 94 (30.8 %) and 104 (34.1 %) cases respectively, two grades in 170 (55.7 %) and 168 (55.1 %) cases, and three grades in 41 (13.4 %) and 33 (10.8 %) cases (Chi-squared test, p < 0.0001). CONCLUSIONS: By analogy with the clinical heterogeneity of field cancerization, AKs show a high histological grade heterogeneity even within small lesions. Variations in AK grading reflect the heterogeneity of the cancerization field and might serve as additional feature.

Expression of PD-L1 in keratoacanthoma and different stages of progression in cutaneous squamous cell carcinoma.

BACKGROUND: Programmed cell death 1 (PD-1) and its ligands (PD-L1) play a major role in the immune responses of a variety of cancers. OBJECTIVES: To investigate the expression of PD-L1 in different progression forms of cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma (KA). METHODS: We performed immunohistochemical staining of 21 KA, 26 actinic keratoses (AK), 20 Bowen´s diseases (BD), and 26 high-risk cSCC. The staining patterns were assessed using the tumour proportion score and staining intensity evaluation. Immunohistology scores were statistically analysed. RESULTS: PD-L1 expression of tumour cells as well as tumour-infiltrating cells (TILs) was significantly higher in KA and cSCC when compared to AK and BD (P = 0.00028 and P = 0.00033, respectively). We observed a very strong positive correlation between the PD-L1 protein expression of tumour cells of KA and the PD-L1 protein expression of TILs (r = 0.97; P < 0.0001). A similar correlation was also found for cSCC (r = 0.86; P < 0.0001). The percentage of PD-L1 + tumours was 33.3% for KA and 26.9% for cSCC. Similarly, the percentage of PD-L1 + TILs in KA and cSCC was 33.3 and 34.6%, respectively. CONCLUSIONS: PD-L1 is differently expressed in cSCC and closely related non-melanoma skin cancer. cSCC exhibit PD-L1 expression in a fourth of cases, indicating that PD1/PD-L1 inhibitors might be beneficial in a proportion of patients with an inoperable or metastatic cSCC. Unlike AK and BD, TILs and tumour cells of KA and cSCC present very similar PD-L1 expression profiles indicating a common immune escape mechanism.

A Sequential Approach to the Treatment of Severe Papulopustular Rosacea Not Responding to Traditional Treatment.

We report the case of a German female patient presenting with papulopustular rosacea (PPR) with a high count of facial inflammatory lesions and severe erythema who had not responded well to treatment with traditional therapies for a decade. In this patient, a sequential therapy consisting of oral modified-release doxycycline 40 mg (initially as monotherapy, then in combination with topical metronidazole), followed by topical ivermectin 10 mg/g was both rapidly active and effective. Following reduction of the inflammation with modified-release doxycycline 40 mg upfront and the disease becoming moderate in severity, the dose of this agent could be reduced and combination therapy with metronidazole 7.5 mg/g lotion started to continue decreasing inflammatory lesions count and erythema severity, before treatment with the recently approved agent ivermectin 10 mg/g was implemented to provide almost complete clearance. This sequential treatment was effective in reducing both the number of papules and pustules and the severity of erythema, with a good safety profile. In addition, a large improvement was documented in the patient's DLQI score, contributing to her overall wellbeing.

J Drugs Dermatol. 2016;15(6):769-771.

Brain changes associated with postural training in patients with cerebellar degeneration: a voxel-based morphometry study.

Recent research indicates that physiotherapy can improve motor performance of patients with cerebellar degeneration. Given the known contributions of the cerebellum to motor learning, it remains unclear whether such observable changes in performance are mediated by the cerebellum or cerebral brain areas involved in motor control and learning. The current study addressed this question by assessing the increase in gray matter volume due to sensorimotor training in cerebellar patients using voxel-based morphometry. Nineteen human subjects with pure cerebellar degeneration and matched healthy controls were trained for 2 weeks on a balance task. Postural and clinical assessments along with structural magnetic resonance imaging were performed pretraining and post-training. The main findings were as follows. First, training enhanced balance performance in cerebellar patients. Second, in contrast to controls patients revealed significantly more post-training gray matter volume in the dorsal premotor cortex. Third, training-related increase in gray matter volume was observed within the cerebellum and was more pronounced in controls than in patients. However, statistically cerebellar changes were at the trend level and thus require additional, independent confirmation. We conclude that sensorimotor training of patients with cerebellar neurodegeneration induces gray matter changes primarily within nonaffected neocortical regions of the cerebellar-cortical loop. Residual function of the cerebellum appears to be exploited suggesting either a recovery from degeneration or intact processes of cerebellar plasticity in the remaining healthy tissue.

Optical coherence tomography: its role in daily dermatological practice.

Optical coherence tomography (OCT) is a non-invasive, tomographic imaging technique which generates high-resolution in-vivo images up to mid-dermal layers. Due to continuous technological improvements, OCT is moving from research projects into daily dermatological practice. It can complement other imaging methods like high-frequency ultrasound or confocal microscopy. There is a wide variety of indications for OCT. In addition to aiding in the diagnosis and clinical monitoring of inflammatory dermatoses, OCT is a very useful and feasible technique in dermato-oncology.