Dr Kash Bhatti highlights recent updates to the PCDS pathway on actinic keratosis and considerations when assessing and managing this common condition
Read this article to learn more about:
- diagnosing actinic keratosis (AK) and grading of lesions
- the natural course of AK and implications for treatment decisions
- treatment updates and advice.
Actinic keratosis (AK), also known as solar keratosis, is a common cutaneous presentation. It is a manifestation of ultraviolet-induced change within the epidermis of skin that is most frequently sun-exposed, such as the face, neck, balding scalp, and dorsal hands and arms.1 As a marker of excessive or cumulative solar irradiation, it is most often seen with increasing age and outdoor exposure.2,3 It is also found with greater prevalence in people who are more susceptible to ultraviolet damage, such those with fairer skin types, and in immune-suppressed patients, such as transplant recipients.2,3
General practitioners will be familiar with managing actinic keratosis, using modalities including cryotherapy, topical treatments such as diclofenac 3% gel, surgery, or referring for secondary care management. The big news in management is the recent suspension of topical ingenol mebutate by the European Medicines Agency, which is conducting a review into the safety of this treatment.4
In light of this change, guidance developed by the Primary Care Dermatology Society (PCDS) was updated in February 2020, with topical ingenol mebutate removed as a treatment option for the time being.5 This article summarises the recommendations made in the PCDS primary care treatment pathway for AK, and provides a timely refresher for diagnosing and managing this common condition.
Diagnosing actinic keratosis
Actinic keratosis can manifest as a solitary macular lesion, or in clusters of lesions, or in widespread confluent areas of damage known as field change or field cancerisation.3,6 The archetypal AK is an erythematous macule that is scaly and feels rough to touch. Individual lesions may vary in size from millimetres to up to 2 centimetres.3 Though generally asymptomatic, AKs may be noticed as unsightly scaly lesions, or be symptomatic with itchiness, or feel sore.2,6
Actinic keratoses can be classified into differing grades based on appearance:7
- grade 1 AKs are flat macules; more easily felt than seen
- grade 2 AKs are thicker, with more scale, and easily felt and seen
- grade 3 AKs have much thicker scale, and here an important differential diagnosis is squamous cell carcinoma (SCC) (Figure 1); grade 3 AKs should be referred to secondary care to explore for this
- field change would manifest as large areas of multiple AKs on a background of sun damage with other abnormalities, such as pigmentary changes and atrophic-appearing skin.
The thickness of scale and distribution have bearing on subsequent management.
The differential diagnosis for a single erythematous macule can range from benign conditions, such as solar lentigo and seborrhoeic keratosis, to other malignancies, such as basal cell carcinoma (BCC) and SCC. Dermoscopy can help differentiate AK from other conditions (see Figure 2).7
Are actinic keratoses a cause for concern?
Actinic keratoses present two important considerations. Firstly, as a marker of ultraviolet-induced damage, they are a sign that other ultraviolet-related malignancies, including BCC and SCC, or melanoma, may either be present or develop. Therefore, the assessment should involve examining the rest of the skin for the presence of other lesions.5,3,8 Secondly, any individual AK has the possibility of progressing into SCC.1–3 As a result, this somewhat alters the conversation as to whether any individual AK should be treated or not, or what to do with multiple lesions.
To understand the latter point, it is important to remember what AK is; ultraviolet-induced cell damage within the epidermis.3 DNA damage results in abnormal keratinocytes proliferating through the epidermis, in a patchy distribution. When the full thickness of the epidermis is involved it is called bowenoid AK. Invasion of the dermis by these abnormal cells appears, and behaves, as SCC. Hence, for several authorities, AK is thought to be epidermal SCC, in other words, a superficial SCC in situ.7,9 Though it is difficult to find a consensus figure, estimates for progression of AK to SCC range from 0.025% to 20% per year.2,8 By itself, AK is not going to cause death, but treating it is thought to reduce the likelihood of SCC developing.2
There is an alternative view that AKs are pre-cancerous (or pre-malignant) rather than cancerous. This is a previously held, but still valid, viewpoint.2 Although there is a risk of an AK becoming an SCC, there are greater likelihoods of it either persisting and not deteriorating, or of spontaneous resolution.2,3,6,8 Exact figures for resolution can range from 15% to over 50%.3,8 Studies show that the majority of SCCs develop in fields of actinic damage; however, SCCs can arise de novo in previously unaffected skin.6,8
Whichever argument is true (in situ versus pre-cancerous), the risk of progression to SCC increases with the number of lesions, and the rate of spontaneous remission reduces.10,11
There is currently no reliable way of knowing which individual AK will turn into an SCC, and which will spontaneously resolve.9,10 Equally, morphologic grading of AK does not seem to have a bearing on its invasive potential.9
Finally, field cancerisation is an important concept.7,9,10 In areas of widespread actinic damage, visible AKs will be present with subclinical AKs, all with the potential of transformation to SCC. Overall, with lesions appearing, persisting, relapsing, and remitting, AK is a dynamic chronic disease, so treatment is not necessarily a one-and-done deal.10
The science and art of managing actinic keratosis
Knowing the natural history of AK is important in framing the discussion for management. The PCDS treatment pathway simplifies the confusing array of what is available and what can be used for which lesion.5 From a GP perspective, what can be used depends very much on what is commissioned by the local CCG (5%-fluorouracil or imiquimod, for example). Equally, the guidance advises where treatment should not be instituted in primary care and therefore when patients should be referred.
The science and art of treating AK comes in determining the right modality for the right patient. There are many factors to consider; practitioners should assess the patient in front of them and engage with them in shared management, taking into account that this is a chronic disease. Factors to consider are the age and general health of the patient, risk factors for skin cancer, and patient preferences.
Equally, an awareness is needed of how treatments work and what result is envisaged. For example, the treatment pathway explains that treatments will cause cutaneous reactions; these are to be expected and one should consider skin reactions the norm, not the exception. Warning patients of these reactions increases acceptance and tolerability and it may be helpful to show the patient images from the internet of reactions people have experienced—do make sure to show them ‘before’ and ‘after’ pictures too!5
It is also worth warning patients that the effects of the treatment may not be evident for several weeks after a course of treatment, that AK is a chronic disease, and that treatments may need to be employed again in the future. Sun protection advice should round out any discussion.5
Treatment, of course, is not mandated in all cases, as lesions can spontaneously resolve, and indeed, with ongoing sun protection, fewer lesions may arise over time.3,6 Some, especially those with multiple co-morbidities, may just choose an emollient to improve roughness and be watchful for any deterioration. Safety-net these patients robustly and advise them to seek medical advice if anything is growing, changing, causing symptoms such as pain or bleeding, or lesions they are concerned about. Patients could also be offered written information, such as the BAD AK patient information leaflet.
The PCDS treatment pathway also discusses treating field change (cancerisation), rather than purely lesion-based therapy. This is important as often treatments such as 5% fluorouracil can be used on large areas, in which case it may help to treat different areas sequentially (e.g. by applying treatment to one side of the scalp for 4 weeks, then to the other side for the next 4 weeks, etc), to reduce the overall burden of expected reaction. There are other combination regimens people employ, such as ‘2 weeks on, 2 weeks off, 2 weeks on’, to reduce morbidity and improve concordance. Be flexible and adapt advice to what the patient is likely to tolerate. If, on occasion, a patient suffers a severe reaction, treatment can be suspended and a mild topical steroid employed, for 2–4 weeks, to help settle down any inflammation. The patient may be reviewed several weeks later to see if their skin has cleared or still requires therapy. Further details can be found in the PCDS webpages on AK.12
High-risk lesions, which should be referred urgently, include those that are:5,10
- rapidly growing
- larger than 1 cm
- ulcerating, thickened, or bleeding
- firm and fleshy at the base
- not responding to treatment.
Be wary of high-risk sites, such as the lips and ears, which carry a higher risk for disease progression and metastases than other sun-exposed sites.10 Patients who have a past history of skin cancer, extensive UV damage, or who are immunosuppressed or very young, should be considered for referral to secondary care or an accredited GP with Extended Role (GPwER) for assessment and surveillance.5
Actinic keratosis is common and practitioners are likely to encounter it more as time goes on, because of the relationship between cumulative sun exposure and an ageing population. Most cases can be diagnosed and managed in primary care and the PCDS two-page guidance provides clear advice on general measures, grading, and treatment options, and red flags for referral.5 Be aware of treatment effects: informing patients early about what is to be expected with treatment and beyond will reduce patient (and practitioner!) angst. Remember that this is a chronic disease with a relapsing-remitting course.
Dr Kash Bhatti
GP and Trainer, GPwER Dermatology; Leeds, UK
Executive committee member, Primary Care Dermatology Society
With the constantly developing knowledge around COVID-19, it is difficult to find definitive evidence or guidance for treating AK in the current (April 2020) situation. High-risk lesions should be managed as they would be normally. Depending on locality, facilities may exist for teledermatology or advice and guidance, or it may be necessary to fall back on 2-week-wait clinics; bear in mind that many of these patients may be the very same ones that should be shielded from the virus.
For low-risk disease, my personal view is to suggest managing with sun protection (for those out in their gardens) and moisturisers until conditions improve. Guidance for or against the use of active topicals during the pandemic is not available yet; low-risk disease does not immediately need to be treated and can be deferred.
Of course, one should have a discussion with the patient and come to an agreed shared decision; it is unlikely, theoretically, that any risk is present, but the absence of evidence should be considered.
Implementation actions for STPs and ICSs
written by Dr David Jenner, GP, Cullompton, Devon
The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources.
- Read and reflect on the PCDS pathway for the management of actinic keratoses
- Review local care pathways against the PCDS pathway and update and adapt them as required
- Ensure that during the COVID-19 pandemic there are local tele dermatology services to help primary care clinicians with diagnosis and to provide them with support
- Publish locally agreed choices for topical chemotherapies in local formularies
- Identify in referral guidelines lesions that should be referred under the 2-week-wait rules (suspected SCC) and those for more routine referral
STP=sustainability and transformation partnership; ICS=integrated care system; PCDS=Primary Care Dermatology Society; SCC=squamous cell carcinoma
- Conforti C, Beninati E, Dianzani C. Are actinic keratoses really squamous cell cancer? How do we know if they would become malignant? Clin Dermatol 2018; 36 (3): 430–432.
- Berker D, McGregor J, Mohd Mustapa M et al. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol 2017; 176 (1): 20–43.
- Gupta G, Madan V, Lear J. Squamous cell carcinoma and its precursors. In: Griffiths C, Barker J, Bleiker T et al, editors. Rook’s Textbook of Dermatology. 9th ed. Chichester: Wiley, 2016: 1–11.
- European Medicines Agency. EMA suspends Picato as a precaution while review of skin cancer risk continues. Press release. European Medicines Agency, 17 January 2020. Available at: www.ema.europa.eu/en/news/ema-suspends-picato-precaution-while-review-skin-cancer-risk-continues (accessed 27 April 2020).
- Cunliffe T, Peace J. Actinic (solar) keratosis primary care treatment pathway. Primary Care Dermatology Society, 2020. Available at: www.pcds.org.uk/ee/images/uploads/general/AK_guidelines_2020-new-web-v01.pdf
- Wheller L, Soyer H. Clinical features of actinic keratoses and early squamous cell carcinoma. In: Soyer H, Prow T, Jemec G, editors. Actinic keratosis. Current Problems in Dermatology vol. 46. Basel: Karger, 2015: 58–63.
- Zalaudek I, Piana S, Moscarella E et al. Morphologic grading and treatment of facial actinic keratosis. Clin Dermatol 2014; 32 (1): 80–87.
- Siegel J, Korgavkar K, Weinstock M. Current perspective on actinic keratosis: a review. Br J Dermatol 2017; 177 (2): 350–358.
- Fernandez Figueras M. From actinic keratosis to squamous cell carcinoma: pathophysiology revisited. J Eur Acad Dermatol Venereol 2017; 31 (S2): 5–7.
- Rigel D, Stein Gold L. The importance of early diagnosis and treatment of actinic keratosis. J Am Acad Dermatol 2013; 68 (1 Suppl 1): S20–S27.
- Ruiz E, Schmults C. Risk stratification: should all actinic keratoses in all patients be treated? Curr Derm Rep 2018; 7: 99–104.
- Primary Care Dermatology Society. Actinic keratosis (syn. solar keratosis). www.pcds.org.uk/clinical-guidance/actinic-keratosis-syn.-solar-keratosis (accessed 29 April 2020).