Exploring Patient Pain Experiences during and after Conventional Red Light and Simulated Daylight Photodynamic Therapy for Actinic Keratosis: A Qualitative Interview Study.

Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.

Mobile health technologies in an interventional hybrid study on actinic keratosis: Results from an early phase randomized controlled trial investigating the safety and efficacy of a cytosolic phospholipase A2 inhibitor gel in photodamaged skin.

Hybrid trials are a new trend in dermatological research that leverage mobile health technologies to decentralize a subset of clinical trial elements and thereby reduce the number of in-clinic visits. In a Phase I/IIa randomized controlled hybrid trial, the safety and efficacy of an anti-proliferative and anti-inflammatory drug inhibiting cytosolic phospholipase A2 (AVX001) was tested using 1%, 3% or vehicle gel in 60 patients with actinic keratosis (AK) and assessed in-clinic as well as remotely. Over the course of 12 weeks, patients were assessed in-clinic at baseline, end of treatment (EOT) and end of study (EOS), as well as 9 times remotely on a weekly to biweekly basis. Safety outcomes comprising local skin reactions (LSR; 0-5), adverse events (AE) and cosmesis, were graded in-clinic and remotely using patient-obtained smartphone photographs (PSPs) and questionnaires; efficacy was assessed in-clinic based on clinically visible clearance of AK target area of >50%. A total of 55 participants (91.7%) completed the treatment course. The average submission rate of PSPs was high (≥85%), of which 93% were of sufficient quality. No serious AE were reported and only two experienced temporary LSR >2 (scale 0-4) and cosmesis remained stable throughout the study. Based on the mild AE and LSR profile, daily application of AVX001 gel for 1 month appears safe, tolerable, and cosmetically acceptable for use in patients with AK. At EOT, AVX001 achieved a subtle treatment response with clearance of AK target area of >50% in 18% of patients. Remote and in-clinic assessments of LSRs were in high agreement, suggesting that the use of mobile health technologies in early-phase hybrid studies of AK does not compromise patient safety.

Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura / Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review / Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

Systematic review of randomized controlled trials of topicals for actinic keratosis field therapy.

Cutaneous field cancerization in dermatology describes the anatomic region of photodamaged skin with actinic keratoses (AKs) or cutaneous squamous cell carcinoma (cSCC) that is surrounded by cellular atypia, forming a dysplastic field. The concept of field cancerization is especially relevant in dermatology, as actinic keratoses and the surrounding dysplastic region can progress to carcinomas, necessitating the treatment of the field. Recent research has focused on field-directed therapy using topical agents. This study aims to systematically review randomized controlled trials on topical treatments for actinic keratosis field cancerization, following the PRISMA guidelines. Clinical recommendations were based on the Oxford Centre for Evidence-Based Medicine. We identified 20 original randomized controlled trials for topical cutaneous field therapy. 0.5% 5-Fluorouracil/salicylic acid and 0.5% 5-fluorouracil received a clinical recommendation grade of A, while diclofenac sodium received a clinical recommendation grade of B. Calcipotriol/5-fluorouracil, Imiquimod, sunscreen combination therapies, and tirbanibulin received a recommendation grade of C. This review provides a framework for clinicians when considering topical treatments for patients with field cancerization.

Tirbanibulin 1% Ointment for Actinic Keratosis: Results from a Real-Life Study.

Background and Objectives: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods: We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients-28 males (73%) and 10 females (26%)-aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results: Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs.

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review.

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role. Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients. This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.

A Review of the Dermatologic Clinical Applications of Topical Photodynamic Therapy.

Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients.

Combination of vitamin D and photodynamic therapy enhances immune responses in murine models of squamous cell skin cancer.

Improved treatment outcomes for non-melanoma skin cancers can be achieved if Vitamin D (Vit D) is used as a neoadjuvant prior to photodynamic therapy (PDT). However, the mechanisms for this effect are unclear. Vit D elevates protoporphyrin (PpIX) levels within tumor cells, but also exerts immune-modulatory effects. Here, two murine models, UVB-induced actinic keratoses (AK) and human squamous cell carcinoma (A431) xenografts, were used to analyze the time course of local and systemic immune responses after PDT ± Vit D. Fluorescence immunohistochemistry of tissues and flow analysis (FACS) of blood were employed. In tissue, damage-associated molecular patterns (DAMPs) were increased, and infiltration of neutrophils (Ly6G+), macrophages (F4/80+), and dendritic cells (CD11c+) were observed. In most cases, Vit D alone or PDT alone increased cell recruitment, but Vit D + PDT showed even greater recruitment effects. Similarly for T cells, increased infiltration of total (CD3+), cytotoxic (CD8+) and regulatory (FoxP3+) T-cells was observed after Vit D or PDT, but the increase was even greater with the combination. FACS analysis revealed a variety of interesting changes in circulating immune cell levels. In particular, neutrophils decreased in the blood after Vit D, consistent with migration of neutrophils into AK lesions. Levels of cells expressing the PD-1+ checkpoint receptor were reduced in AKs following Vit D, potentially counteracting PD-1+ elevations seen after PDT alone. In summary, Vit D and ALA-PDT, two treatments with individual immunogenic effects, may be advantageous in combination to improve treatment efficacy and management of AK in the dermatology clinic.

Pharmacokinetics, Safety, and Tolerability of a Single 5-Day Treatment of Tirbanibulin Ointment 1% in 100 cm2 : A Phase 1 Maximal-Use Trial in Patients with Actinic Keratosis.

Tirbanibulin ointment 1% is approved in the United States and Europe for the treatment of actinic keratosis with demonstrated efficacy, safety, and tolerability when applied over a field up to 25 cm2 . This Phase 1 maximal-use trial determines the plasma pharmacokinetics, safety, and tolerability of tirbanibulin ointment 1% applied to 100 cm2 of the face or balding scalp in adults with actinic keratosis. Twenty-eight patients self-applied tirbanibulin once daily for a single 5-day treatment course. On Day 5, the mean maximum plasma concentration was 1.06 ng/mL and area under the plasma concentration-time curve during a dosing interval was 16.2 ng â€¢ h/mL. Systemic exposure was approximately 4-fold higher than in a previous pharmacokinetic study with a 25 cm2 field, consistent with the increase in the treated area. Tirbanibulin applied to a 100-cm2 treatment field showed favorable safety and tolerability. The most common treatment-emergent adverse events were application site reactions (in 35.7% of patients). All treatment-emergent adverse events and most of the tolerability signs were mild/moderate and resolved or returned to baseline by Day 29. In summary, under maximal-use conditions, tirbanibulin ointment 1% was safe and well tolerated supporting its potential use over a field up to 100 cm2 .

Photodynamic therapy with BF-200 ALA gel for the treatment of actinic keratosis, Bowen´s disease and basal cell carcinoma in long term immunosuppressed patients after organ transplantation.

Continuous immunosuppression after organ transplantation is associated with an increased risk of developing keratinocyte neoplastic lesions. Topical photodynamic therapy represents a therapeutic approach for different keratinocyte neoplastic lesions. However, the specific efficacy and safety of this treatment in this immunocompromised population remains largely unknown. In this case report series, we show the efficacy and safety of photodynamic therapy with BF-200 ALA gel using red-light and daylight in immunocompromised patients. Out of 8 patients presented here, 1 was treated for 8 basal cell carcinomas, 1 for 2 Bowen´s disease lesions and 6 were treated for field cancerization including 4 to 10 actinic keratoses. Treatment response rates were above 75 %. The adverse events, including pain, did not differ from those already described for PDT. These data suggest that PDT with BF-200 ALA gel could be an effective and safe option to add to the treatment portfolio for neoplastic keratinocyte lesions in this high-risk population.

Painless photodynamic therapy for facial actinic keratoses: A retrospective cohort study of the post-treatment inflammatory response.

INTRODUCTION: Photodynamic therapy (PDT) is a safe, non-mutagenic, and non-scarring treatment for actinic keratoses (AK). BACKGROUND: 'Painless' photodynamic therapy (p-PDT) is a regimen for AK that employs simultaneous aminolevulinate incubation and blue light illumination. The efficacy of p-PDT resembles that of traditional PDT, but detailed mechanisms of action for p-PDT are not well understood. METHODS: To characterize the inflammatory effects of the p-PDT procedure 48 h following treatment and determine the association of inflammation with precancer burden, we performed a retrospective cohort study of 104 patients with AK of face or scalp treated with p-PDT between 2017 and 2019. Patients self-reported their side effects 48 h following p-PDT and took photographs of their face and scalp. Photographs were edited to define seven anatomic regions, and erythema was scored by four investigators. RESULTS: Ninety-eight patients provided photographs suitable for erythema evaluation. Most patients experienced 2 or more side effects and some pain 48 h post-procedure. Females experienced more pain (p = 0.01) and side effects (p = 0.002) compared to males. AK burden was positively associated with post p-PDT erythema response (p < 0.0001) at all sites, but particularly in the temples (p = 0.002) and supralabial area (p = 0.009). DISCUSSION: This study confirms a strong clinical inflammatory response after p-PDT. Severity of inflammation is positively associated with AK tumor burden, suggesting that post-treatment inflammation may be a pre-requisite for p-PDT efficacy. Interestingly, the results also identify certain gender-related differences in the severity of side effects experienced by patients post-PDT.

Keratolytics can replace curettage in daylight photodynamic therapy for actinic keratosis on the face/scalp: A randomized clinical trial.

BACKGROUND: Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is commonly used for field treatment of actinic keratoses (AKs). In standard natural daylight PDT (n-DL-PDT) the first step, after the application of chemical solar filter, is removal of crusts and scales by curettage, followed by the application of MAL cream. Some patients experience intense pain during curettage and stinging after application of the photosensitizer to just curettaged skin. OBJECTIVES: To evaluate whether n-DL-PDT without curettage, but preceded by application of keratolytics, would maintain a similar efficacy, based on clinical, dermoscopic, reflectance confocal microscopy (RCM) assessments, safety and patient satisfaction as standard n-DL-PDT with curettage. METHODS: Forty patients with multiple AKs on the face and/or scalp were enrolled in this study. Patients were randomized into two groups of treatment as follows: (i) MAL n-DL-PDT without previous curettage, preceded by skin preparation at home with keratolytics (30% urea cream, twice a day for 7 days; -Cur group) and (ii) MAL n-DL-PDT preceded by skin preparation at the hospital with curettage (+Cur group). RESULTS: Thirty-nine participants completed the study. Four hundred and twenty-one AKs in -Cur group and 337 AKs in +Cur group were treated. The mean reduction in the number of AK lesions 3 months after the treatment was 10.7 (-54.7%) in the -Cur and 10.4 (-58.7%) in the +Cur group. We found that the differences in terms of efficacy and patient satisfaction comparing the two treatment regimens were not statistically significant. The pain score reported during and after daylight exposure was similar and low in both groups. Moreover, no unexpected adverse events occurred during the trial period. CONCLUSIONS: According to our results, curettage is not necessary to obtain the full treatment effect of n-DL-PDT. We experienced in a real-life setting that n-DL-PDT protocol could be changed by replacing curettage with keratolytics.

Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.

BACKGROUND: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. OBJECTIVES: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. METHODS: Summary of presentations given at the EADV Congress. RESULTS: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. CONCLUSIONS: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.

Full-face ALA-PDT for facial actinic keratosis: Two case reports.

We reported two cases of full-face 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) for facial multiple actinic keratosis (AK). After the full-face ALA-PDT, we observed that the AK lesions on the faces of the patients were completely cleared and facial rejuvenation was achieved. In our follow-up, one patient was free of recurrence for over 13 months and the other one for over 28 months. The experience of these two cases may indicate that full-face ALA-PDT has an excellent therapeutic effect while potentially preventing the recurrence of AK.

Inflammation of actinic keratosis from chemotherapy in a relapsed multiple myeloma patient.

A man in his 60 s with a history of actinic keratosis (AK) and relapsed IgG kappa multiple myeloma (MM) recently received VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) chemotherapy and presented with numerous haemorrhagic, scaly lesions on his scalp and face. He also had sepsis from methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. Since the lesions were only present in the areas of pre-existing AK, a diagnosis of inflammation of AK secondary to chemotherapy was made. Sepsis was treated with appropriate antibiotics, and inflammation of AK was managed with topical steroids, leading to complete recovery.

The impact of photodynamic therapy on skin homeostasis in patients with actinic keratosis: A prospective observational study.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AKs), but there is little information on how PDT affects skin barrier function. The objectives of this study are: To compare skin barrier function between skin with AKs and healthy skin and to evaluate the impact of PDT on skin homeostasis in patients with AKs. METHODS: A prospective observational study was conducted in patients with AKs to evaluate epidermal barrier function and skin homeostasis before and 1 ek after receiving PDT. RESULTS: A total of 21 subjects were included in the study, male/female ratio was 17:4, mean age was 75.86 years. The number of AKS observed before starting treatment was reduced with respect to those diagnosed 1 month after starting PDT (14.83 vs. 1.91, p < 0.0001). Application of PDT for treating AKs modifies epidermal barrier function. Immediately after the first session temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH) and total antioxidant capacity (TAC) increased while pH decreased on lesional skin. After 1-month follow-up, the only remained change was the increased in SCH. Higher increases in temperature were observed when using occlusive PDT compared to mixed modality. 5-ALA and M-ALA seem to have a similar impact on skin barrier. CONCLUSIONS: PDT can improve skin barrier function in patients with AKs. Skin homeostasis parameters can be used to assess efficacy and optimize dosing.

Evaluating the Efficacy and Safety of 4% 5-Fluorouracil Cream in Patients with Actinic Keratosis: An Expert Opinion.

Actinic keratosis is a lesion that develops in sun-exposed areas of the skin and is considered to be a precancerous condition or an early in situ squamous cell carcinoma. Treatment of actinic keratosis is important for reducing skin cancer risk, with treatment choice based on patient-, lesion- and treatment-related considerations. Of the topical treatments used for field-directed therapy, those containing 5-fluorouracil are among the most effective and widely prescribed. The most recently developed topical 5-fluorouracil preparation (Tolak®; Pierre Fabre, France) contains 4% 5-fluorouracil in an aqueous cream. This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors' expert opinion on issues associated with it use. The effect of the cream has been evaluated in phase 2 and 3 trials of adult patients with actinic keratosis on the face, ears or scalp. These trials included patients with severe baseline disease, defined by high lesion counts and large-size treatment fields, which possibly affected the proportion of patients who were able to achieve complete clearance. Other efficacy parameters (e.g. percentage change in lesion count, ≥ 75% clearance of lesions or clinically significant changes in validated severity scales) should also be assessed to fully evaluate 4% 5-fluorouracil treatment efficacy in these patients. Nevertheless, 4% 5-fluorouracil is associated with high efficacy, a low level of recurrence and a satisfactory safety profile.

Association between calcium channel blockers and the severity of actinic keratosis on face and scalp: a cross-sectional study.

BACKGROUND: Actinic keratosis (AK) is a skin condition associated with age, sun exposure, and immunosuppression. Certain drugs, such as photosensitizing medications and calcium channel blockers (CCBs), have been linked to AK. This study explores the impact of individual, behavioral, and exposure factors on the severity of AKs on the face and scalp. METHODS: A multicenter cross-sectional study was conducted on immunocompetent individuals with at least one AK on their face or scalp and assessed demographic factors, sun exposure and protection, history of skin cancer, and medication use within the last 6 months. The primary outcome was the Actinic Keratosis Area and Severity Index (AKASI) score, and a hierarchical generalized linear model was used to evaluate the variation in AKASI scores, adjusting for gender, age, and skin phototype. RESULTS: Two hundred seventy subjects between 39 and 92 years were evaluated. The majority had phototype I or II (77%), male gender (51%), personal history of skin cancer (55%), and low adherence to sunscreen use (29%). The use of photosensitizing medications was reported by 61%. Through multivariate analysis, older age (ßSE = 0.14; P < 0.01), lighter skin phototype (ßSE = 0.15; P = 0.01), history of skin cancer (ßSE = 0.12; P < 0.01), sunburning (ßSE = 0.12; P < 0.01), and use of CCBs (ßSE = 0.11; P = 0.02) were identified as independent risk factors for AK severity. Photosensitizing drugs were not identified as risk factors. CONCLUSION: Older age, lower skin phototype classifications, and a personal history of skin cancer were confirmed as severity risk factors for AK, while the use of CCBs was associated with more severe AK.