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Special Considerations Use in the Treatment of Actinic Keratoses.
Source publication
There are currently several reputable guidelines on the treatment of actinic keratosis (AK) from groups in Canada, the United Kingdom, and Europe. These recommendations, based on evidence or expert consensus, offer clinicians a variety of treatment options for the different clinical presentations of AKs. Although the guidelines are similar in some...
Contexts in source publication
Context 1
... for destructive and field therapies are highlighted in Tables 1 and 2. Special cases of AK and their management are outlined in Table 3. Available and unavailable treatments for each region are outlined in Table 4. ...Context 2
... Field Therapies 5-FU. The Canadian guidelines currently recommend using 5% 5-FU twice daily for up to 4 weeks as a treatment for Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Laser resurfacing Evidence and recommendation Provided for special cases in Table 3 Recommendation B, quality of evidence I Provided for special cases in Table 3 Other Evidence and recommendation Provided for special cases in Table 3 Recommendation-A, quality of evidence-I ...Context 3
... Field Therapies 5-FU. The Canadian guidelines currently recommend using 5% 5-FU twice daily for up to 4 weeks as a treatment for Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Laser resurfacing Evidence and recommendation Provided for special cases in Table 3 Recommendation B, quality of evidence I Provided for special cases in Table 3 Other Evidence and recommendation Provided for special cases in Table 3 Recommendation-A, quality of evidence-I ...Context 4
... Field Therapies 5-FU. The Canadian guidelines currently recommend using 5% 5-FU twice daily for up to 4 weeks as a treatment for Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Laser resurfacing Evidence and recommendation Provided for special cases in Table 3 Recommendation B, quality of evidence I Provided for special cases in Table 3 Other Evidence and recommendation Provided for special cases in Table 3 Recommendation-A, quality of evidence-I ...Context 5
... Field Therapies 5-FU. The Canadian guidelines currently recommend using 5% 5-FU twice daily for up to 4 weeks as a treatment for Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Laser resurfacing Evidence and recommendation Provided for special cases in Table 3 Recommendation B, quality of evidence I Provided for special cases in Table 3 Other Evidence and recommendation Provided for special cases in Table 3 Recommendation-A, quality of evidence-I ...Context 6
... Field Therapies 5-FU. The Canadian guidelines currently recommend using 5% 5-FU twice daily for up to 4 weeks as a treatment for Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Laser resurfacing Evidence and recommendation Provided for special cases in Table 3 Recommendation B, quality of evidence I Provided for special cases in Table 3 Other Evidence and recommendation Provided for special cases in Table 3 Recommendation-A, quality of evidence-I ...Context 7
... for special cases in Table 3 Imiquimod 2.5% imiquimod: once-daily application for 2 weeks followed by rest period of 2 weeks (with 1 or 2 treatment cycles). ...Context 9
... B, quality of evidence I Provided for special cases in Table 3 Ingenol Mebutate Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Other topicals discrete AKs. The frequency of application is restricted due to its erosive nature. 1 The UK guidelines also recommend the use of 5% 5-FU twice daily, but for 3 weeks, for similar reasons. ...Context 10
... B, quality of evidence I Provided for special cases in Table 3 Ingenol Mebutate Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Other topicals discrete AKs. The frequency of application is restricted due to its erosive nature. 1 The UK guidelines also recommend the use of 5% 5-FU twice daily, but for 3 weeks, for similar reasons. ...Context 11
... B, quality of evidence I Provided for special cases in Table 3 Ingenol Mebutate Evidence and recommendation Provided for special cases in Table 3 Recommendation A, quality of evidence I Provided for special cases in Table 3 Other topicals discrete AKs. The frequency of application is restricted due to its erosive nature. 1 The UK guidelines also recommend the use of 5% 5-FU twice daily, but for 3 weeks, for similar reasons. ...Similar publications
Actinic keratoses (AK) are common lesions of the skin that can be effectively treated with several lesion- and field-directed treatments. Clinical practice guidelines assist physicians in choosing the appropriate treatment options for their patients. Here, we aimed to systematically identify and evaluate the methodological quality of currently avai...
Simple Summary
Actinic keratoses (AKs) are extremely common in the elderly population; they are universally recognized as precursors of invasive squamous cell carcinoma, and their risk of progression relates to the basal growth pattern of keratinocytes in the histological slides, based on a model called “PRO” classification. Since AKs can be invest...
Citations
... Але недоліком даного методу лікування являється утруднене його проведення на великих ділянках, уражених АК (займають більше 30% обличчя). [22,13]. ...
The subject of the work is to study modern methods of treatment of actinic keratosis (AK) and compare their effectiveness. Materials and methods. 34 international studies on the treatment of AK after 2018 were analyzed. The inclusion criteria for the review were studies with proven efficacy in the treatment of AK. Exclusion criteria were review articles with proven effectiveness of treatment methods. Results and discussions. Due to the increase in cases of AK and its neoplastic transformation (PCC), this problem remains relevant and requires increased monitoring of modern treatment methods. There are several treatment options for AK, both alone and in combination. The main therapeutic tasks in the management of patients with AK include the elimination of clinical and subclinical manifestations of the disease, prevention of transformation into PCC, and reduction of the number of relapses. Both hardware (surgical, cryosurgical, laser, photodynamic (PDT)) and applied (5-FU, imiquimod, diclofenac, tirbanibulin) treatment methods have been proven effective. Conclusions. AK is a fairly common precancerous skin disease, which increases the urgency of the problem in the development of effective treatment methods. Based on the conducted scientific screening, it was concluded that there are various methods of treating AK, with different percentages of positive dynamics and absence of relapses. Combined methods of treatment, which included the hardware method of treatment with the subsequent use of application methods, showed the greatest effectiveness.
... In addition to benign changes in the skin, there are several precancerous and malignant lesions that emerge with the aging process. The incidence of all types of malignant skin tumours, both melanoma and non-melanoma types, as well as precancerous lesions, increases with age [4][5][6]. The most common precancerous lesion is actinic keratosis (AK, also referred to as solar keratosis), which may affect up to 25% of the elderly population [4]. ...
... The incidence of all types of malignant skin tumours, both melanoma and non-melanoma types, as well as precancerous lesions, increases with age [4][5][6]. The most common precancerous lesion is actinic keratosis (AK, also referred to as solar keratosis), which may affect up to 25% of the elderly population [4]. Without adequate treatment, AK can transform into squamous cell carcinoma (SCC), which can metastasise [4]. ...
... The most common precancerous lesion is actinic keratosis (AK, also referred to as solar keratosis), which may affect up to 25% of the elderly population [4]. Without adequate treatment, AK can transform into squamous cell carcinoma (SCC), which can metastasise [4]. Among malignant lesions, basal cell carcinoma (BCC) is the most prevalent and is the most common human malignancy in the Caucasian race [7]. ...
The incidence of all types of malignant skin tumours, including both melanoma and non-melanoma types, has increased in recent decades, while basal cell carcinoma is the most common human malignancy in the Caucasian race. The aging of the skin is associated with an increase in both benign and malignant tumours. As the population ages and life expectancy extends, mostly in developed countries, dermatologists are likely to face growing numbers of patients seeking therapy for such abnormalities. It is primarily UV irradiation that is responsible for the development of skin cancers, although there are other risk factors, including air pollution and X-ray irradiation. Seborrhoeic keratosis, solar lentigo and other benign lesions, despite their harmless nature, may cause distress to patients, such as itching or aesthetic issues. This review article summarises the features of the most common benign and malignant lesions of aging skin.
... Surgical excision or a biopsy of AK should always be considered in cases of diagnostic uncertainty or treatment-resistant lesions [90]. In such instances, histological examination may be useful to rule out an incipient invasive cutaneous SCC, and deep shave or surgical excision should be preferred to include the deep skin layers to establish the presence of dermal invasion [75]. ...
Actinic keratosis (AK) is a chronic skin disease in which clinical and subclinical cutaneous lesions coexist on sun-exposed areas such as the head and neck region and the extremities. The high prevalence of AK means the disease burden is substantial , especially in middle-aged and elderly populations. Evidence indicates that AK may progress into invasive cutaneous squamous cell carcinoma, so the European guidelines recommend treatment of any AK regardless of clinical severity. Given the aging population and therefore the increasing incidence of AK and cutaneous field carcinogenesis, further updates on the long-term efficacy of current therapies and new investigational agents are critical to guide treatment choice. Patients often have difficulty adequately applying topical treatments and coping with adverse local skin reactions, leading to less than optimum treatment adherence. The development of associated local skin symptoms and cosmetic outcomes for the area of interest are also relevant to the choice of an appropriate therapeutic strategy. Treatment is always individually tailored according to the characteristics of both patients and lesions. This review focuses on the therapeutic approaches to AK and illustrates the currently available home-based and physician-managed treatments. Key Points This article illustrates the scientific evidence driving the clinical management of patients affected by actinic keratosis, aiming to provide a patient-tailored treatment program. Phase II/III clinical trials are showing promising results from new topical agents. The goals of actinic keratosis treatment are to eradicate as many clinical and subclinical lesions as possible, achieve as prolonged a clinical remission as possible, provide a good cosmetic result, and prevent progression to invasive squamous cell carcinoma.
... cryosurgery, excision) to the treatment of the wider field (e.g. topical therapies, photodynamic therapy) [1,[9][10][11] and depends on patient preference and their clinical circumstances. The number of visible AKs is a poor indicator of the real number of lesions present in the field of cancerisation, underlying the importance of treating the whole field of cancerisation using field-directed treatments for multiple AKs [12]. ...
IntroductionActinic keratoses (AK) are epithelial lesions caused by chronic skin exposure to ultraviolet light that can progress into squamous cell carcinoma. Although several treatments are effective, they are associated with severe skin reactions, which might be related to the extent of the disease. This study aimed to examine the relationship between the severity of local skin reactions during treatment with 5-fluorouracil 4% cream and the number of AK lesions at baseline.Methods
This post hoc analysis pooled data from two multicentre randomised phase III studies (HD-FUP3B-048, HD-FUP3B-049) in patients with AK treated with topical 5-fluorouracil 4% once daily (OD) or 5% twice daily (BID) for 4 weeks. First, we compared the severity, assessed using a numerical rating scale, of the local skin reactions between 5-fluorouracil 4% and 5%. Then, we investigated the relationship between the number of lesions at baseline and severe skin reactions with 5-fluorouracil 4% OD.ResultsSafety data were included from 397 patients who had received 5-fluorouracil 4% (348 in study HD-FUP3B-048, 49 in study HD-FUP3B-049) OD and 342 (HD-FUP3B-048) who had received 5-fluorouracil 5% BID. For most skin reactions, severe ones were more common in patients treated with 5-fluorouracil 5% cream BID than in those treated with 5-fluorouracil 4% cream OD (P < 0.05). With 5-fluorouracil 4% OD, the incidence of severe erythema was significantly higher in patients with at least 10 lesions (46%) than in patients with 5–10 lesions (28%; P < 0.001). Similar results were observed for the other local skin reactions.Conclusion
Treatment with 5-fluorouracil 4% cream OD was associated with less severe local skin reactions than 5-fluorouracil 5% BID. The number of AK lesions at baseline seems to have predictive value regarding the severity of local skin reactions that appear during treatment.
... AKs are keratotic lesions occurring on skin areas extensively damaged by sunlight. 1 They should be classified as in situ carcinomas that may lead to the development of invasive squamous cell carcinomas, with a likelihood of progression varying from 0.025 to 20%. 2 , 3 The progression risk increases in patients with multiple ( > 5) AKs. 4 Although AK can occur as a single lesion, the more common clinical picture is multiple visible/nonvisible AKs within a chronically photodamaged area or field such as the front or scalp. 5 The area is also influenced by subclinical (eg, nonvisible and nonpalpable) lesions, giving rise to the field cancerization concept; that is, a whole area affected by premalignant cells surrounding the visible lesions, and providing the rationale for field-directed therapies. ...
Actinic keratoses (AKs) are keratotic lesions occurring on skin areas extensively damaged by sunlight. Using data from a previously published Phase III randomized, controlled clinical trial in patients with at least 5 AKs, we explored the potential link between the number of visible AK lesions before any treatment and the total number of lesions of the field cancerization as revealed by 5-fluorouracil cream. Our analysis suggests that the baseline number of visible AKs is a poor indicator of the real number of lesions in the field of cancerization, reinforcing the need to explain the field cancerization concept to patients.
... In general, cryotherapy is the most widely recommended treatment for isolated AKs, whereas field therapies (5-FU, imiquimod, PDT with a photosensitizing agent, and likely tirbanibulin when added to guidelines) are recommended for multiple AKs. 13 PDT for AK is considered highly effective, with efficacy at least comparable to other FDAapproved treatments. It is associated with improved cosmetic outcomes compared with cryotherapy. ...
... Treatments with a "B" recommendation include laser resurfacing, chemical peels, dermabrasion, and other topical agents. 3,13 Tirbanibulinapproved by the FDA for AK treatment in December 2020-is not yet included in treatment guidelines. 14 Some guidelines suggest that treating AK is not always required; however, experts are divided on this issue. ...
Actinic keratoses (AK) are lesions with potential to transform into nonmelanoma skin cancers. Numerous methods are available for treatment of AK. Here, we review clinical trial data on the use of photodynamic treatment combined with the sensitizing agent aminolevulinic acid 20% solution (ALA-PDT) for AK management. Although treatment guidelines for AK vary in their specific recommendations, efficacy of ALA-PDT is considered comparable or better relative to other FDA-approved treatments for AK. It is generally well tolerated and has a very acceptable long-term safety profile. ALA-PDT is typically recommended for patients who have multiple AKs and is associated with improved cosmetic outcomes compared with cryotherapy. Patients who undergo treatment with ALA-PDT should receive thorough education regarding the risks and benefits of treatment, the treatment regimen and the importance of adhering to it, how to manage local reactions, and signs and symptoms that warrant further evaluation. J Drugs Dermatol. 2021;20(11):1239-1244. doi:10.36849/JDD.6166.
... Actinic keratoses (AKs) are common precancerous cutaneous lesions that typically present on sun-exposed or ultraviolet damaged areas with gritty, scaly, and erythematous papules. 1,2 Histopathologically, they are identified through irregular hyperchromatic nuclei, epidermal keratinocyte crowding, and dysplastic keratinocytes. 2,3 AKs may progress to squamous cell carcinoma in situ (SCCis). ...
... 1,2 Histopathologically, they are identified through irregular hyperchromatic nuclei, epidermal keratinocyte crowding, and dysplastic keratinocytes. 2,3 AKs may progress to squamous cell carcinoma in situ (SCCis). 4 This progression is difficult to predict, and it is widely accepted that all forms of AKs should be treated in order to prevent progression to SCCis. 1 AKs currently affect about 58 million individuals in the United States and have a predilection for elderly males and/ or fair skinned individuals. ...
... Field-directed therapies include tirbanibulin ointment, ingenol mebutate gel, diclofenac gel, imiquimod cream, and 5-fluorouracil cream. 2,5 Ingenol mebutate has been discontinued in the European, Canadian, and US markets because of its association with increased risk of nonmelanoma skin cancer (NMSC). 6 Diclofenac gel, imiquimod, ingenol mebutate, and 5-fluorouracil have similar efficacies in treating AKs. ...
Objective
Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration.
Data Sources
The PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri.
Data Extraction
Phase 2 and phase 3 clinical trials were reviewed.
Data Synthesis
In phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile.
Relevance to Patient Care and Clinical Practice
Tirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias.
Conclusion
With a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.
... AK favour sun-exposed areas, such as the head, as chronic sun exposure increases their risk as well as high age, fair skin and immunosuppressive medication (3). Photodynamic therapy (PDT) is considered a first-line treatment for patients with multiple AKs (4). In PDT, a light-sensitizer containing a substrate of protoporphyrin IX (PpIX) is applied to the skin. ...
Previous research presents pulsed dye laser-mediated photodynamic therapy as a promising alternative to conventional red-light photodynamic therapy. In this study, 60 patients with 2 or more actinic keratoses randomly received either of these treatments on each side of the head. A physician blinded to the treatment evaluated treatment response at 6 months for each lesion, as completely, partially or not healed. Significantly lower complete clearance rates (10.3% vs 44.9%) and lesion-specific complete clearance rates were found for pulsed dye laser-mediated photodynamic therapy (47.9%) vs conventional red-light photodynamic therapy (73.4%). Significantly lower pain scores were found for pulsed dye laser-mediated photodynamic therapy, with a mean numerical rating of 2.3, compared with 4.1 for conventional red-light photodynamic therapy. The study population averaged 7.9 lesions, and 78% of patients had been treat-ed previously for actinic keratoses on the treatment area. To conclude, in a population with severe sun damage, pulsed dye laser-mediated photodynamic therapy seems less effective than conventional red-light photo-dynamic therapy. Pulsed dye laser-mediated photodynamic therapy may still be a treatment option for patients who are not compliant with conventional red-light photodynamic therapy.
... Als Behandlungsoptionen stehen chirurgische, physikalisch destruierende Maßnahmen oder topische arzneimittelbasierte Verfahren zur Verfügung. Zur Entwicklung eines allgemeingültigen Therapiestandards haben verschiedene Arbeitsgruppen eigene Leitlinien entwickelt [3,6,13]. Die aktuelle deutsche S3-Leitlinie "Aktinische Keratose und Plattenepithelkarzinom der Haut" [14] wurde im März 2020 (Leitlinienreport; Juni 2019) erstellt und hat eine angedachte Gültigkeit von 5 Jahren. ...
Zusammenfassung
Hintergrund
Aktinische Keratosen (AK) zeichnen sich durch einen chronischen Verlauf aus, und häufig ist ein ganzes Hautareal betroffen (Feldkanzerisierung). Die patientenindividuelle Abwägung therapiespezifischer Vor- und Nachteile einer feldgerichteten Therapie ist herausfordernd.
Fragestellung
Ziel der vorliegenden Arbeit war die Entwicklung und Evaluierung patientenorientierter Entscheidungskriterien, die sich für die pragmatische Einordnung einer AK-Feldtherapie im Behandlungsalltag bei Patienten mit besonderer Prädisposition zur Feldkanzerisierung eignen (Patiententyp 1 bis 3).
Material und Methoden
Die Entwicklung der Entscheidungskriterien und der Patiententypologie erfolgte im Rahmen eines nominalen bzw. strukturierten Multi-level-Gruppenprozesses. Anhand der patientenrelevanten Entscheidungskriterien, der verfügbaren Evidenz aus klinischen Studien und entlang der Patiententypologie wurde ein Bewertungsalgorithmus etabliert, und feldgerichtete AK-Therapieoptionen wurden systematisch evaluiert.
Ergebnisse
Als patientenrelevante Kriterien für die Therapieentscheidung wurden u. a. Effektivität, Sicherheit, Praktikabilität der Therapie, Adhärenz, Kosmetik, Patientenpräferenz und Komorbiditäten identifiziert und näher spezifiziert. In Bezug auf diese Entscheidungskriterien und Patiententypen, bei denen eine Feldtherapie vorrangig indiziert ist, erfüllte die photodynamische Therapie mit Tageslicht das therapiebezogene Anforderungsprofil in besonderem Maße.
Schlussfolgerung
Die Definition von patientenrelevanten und therapiebezogenen Entscheidungskriterien in der AK-Feldtherapie erlaubt eine strukturierte und gleichzeitig praxisorientierte Herangehensweise, um spezifische Therapieoptionen einzuordnen und individuelle Therapieentscheidungen herzuleiten.
... Several guidelines and consensus papers on how to manage patients with AKs have been published recently. [1][2][3][4][5][6][7][8][9][10] However, given the continuing introduction of new treatments and the rising amount of literature on the topic, updated recommendations are warranted. ...
... 49,50 A regular use of sunscreens is recommended by all guidelines and consensus recommendations on this topic. [1][2][3][4][5][6][7][8][9][10] Evidence also suggests the chemopreventive effect of nicotinamide and systemic retinoids in highrisk patients. 47,48,51 Finally, managing adverse events and LSR is a consistent part of patient care when dealing with some of the available topicals. ...
Purpose
To reach a consensus, among experts, on the management of patients with actinic keratosis (AK).
Methods
Two round tables involving experts were organized: in the first, seven clinical questions were selected and analyzed by a systematic literature review, using a Population, Intervention, Control, and Outcomes (PICO) framework; in the second, the experts discussed relevant evidences and a consensus statement for each question was developed.
Results
Lesion‐directed treatments are preferred in patients with few AKs. Patients with multiple AKs are challenging, with more than one treatment usually needed to achieve complete lesion clearance or a high lesion response rate, therapy should be personalized, based on previous treatments, patient and lesion characteristics. Photodynamic therapy (PDT) is the most studied treatment for AKs on the arms. Oral nicotinamide 500 mg twice daily, systemic retinoids and regular sunscreen use were demonstrated to reduce the number of new squamous cell carcinomas in patients with AKs. MAL (Methyl aminolevulinate)‐PDT, DL (day light) PDT, and imiquimod (IMQ) cream were demonstrated to have the lowest percentage of new AKs after post treatment follow up. Regular sunscreen use helps preventing new AKs. For IMQ 5% and 3.75% a higher intensity of skin reactions is associated with higher efficacy. Limited evidence is available for the treatment of AKs in organ transplant recipients (OTRs). There is no evidence in favor or against the use of any of the available treatments in patients suffering from hematological cancer.
Conclusions
Consensus was reached among experts on how to best treat AK patients with respect to different clinical scenarios and special populations.
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