Actinic keratosis (AK), also known as solar keratosis, are commonly referred to as pre-cancerous skin growths. In fact, they are the most common pre-cancerous growth of humans. Actinic keratoses (plural) are most commonly found on sun exposed areas, namely, the face, lips, bald scalp, and backs of hands and arms.
What do AK’s look like?
AK’s are usually small red slightly raised bumps with attached dry scaly skin or scab. The scab or crust is usually tightly adherent or concave like a corn flake, such that attempting to remove it yourself might cause pain or bleeding. Some patients report abnormal skin sensations such as pain, itching, burning, or tingling. Some patients only complain about the abnormal feel or texture of their skin such as granular, gritty, sandy, pointy, or like a nutmeg-grater.
AK’s are often numerous, and sometimes they can be felt more easily than seen. At times, they can be confused with other red scaly rashes that are benign, such as eczema, psoriasis, and seborrheic dermatitis. In such instances, a skin biopsy may be required to
establish the diagnosis.
What is the cause of AK’s?
Based on their typical locations, and their association with other skin cancers, the most obvious cause of AK’s is chronic excessive sunlight exposure accumulated over a period of many years. Less common causes of AK’s are X-rays (radiation) and industrial chemicals such as arsenic.
What is the risk of AK’s?
AK is the first step in the development of squamous cell carcinoma, a type of skin cancer that has the biologic potential to spread or metastasize. However, the majority of AK’s do not progress to skin cancer. Although it has been estimated that up to 10% of AK’s transform into squamous cell carcinoma, it is virtually impossible to predict which ones will progress, regress, or stay the same. Therefore, it is the dermatologist’s goal to treat all or as many AK’s as possible to prevent cancer.
How are AK’s treated?
We are fortunate that there are many effective treatments for AK’s. For patients who have several scattered well-defined AK’s, liquid nitrogen cryosurgical destruction is usually the treatment of choice. This method is quick, bloodless, and effective. The top layer of skin cells where the precancerous cells reside is killed by the extremely cold temperature of the liquid nitrogen. The only side effects are a temporary burning sensation and possibly some decreased pigmentation of the skin. Healing is complete in about 1-2 weeks, and the local after-care is straightforward.
There are now four different topical creams that have been FDA-approved and are marketed for the treatment of AK’s. Each one works well by a different mechanism of action. These medicines are more likely to be prescribed when a patient has too many lesions to count, or an entire area or segment of the body shows obvious severe sun damage (such as face, bald scalp, upper chest, backs of arms or hands), if the AK’s are not easy to delineate from normal skin, or if the patient simply cannot tolerate the discomfort of cryosurgery or declines to receive liquid nitrogen for other reasons. The four topical drugs are 5-fluorouracil (Efudex, Carac, Fluoroplex, and generic), diclofenac (Solaraze), imiquimod (Aldara, Zyclara), and ingenol mebutate (Picato).
Treatment of Actinic Keratoses
The three most commonly prescribed topical creams for actinic keratoses (AK’s) are:
1. 5-Fluorouracil (5-FU), “chemotherapy in a cream,” selectively kills the more rapidly dividing skin cells which are generally the precancer and cancer cells. Efudex or Carac cream is applied once or twice daily to the entire area of involvement for 2-4 weeks (face and scalp). Arms and legs generally require 6 weeks of treatment. It can cause quite a bit of redness, swelling, and crusting in the treated areas along with some stinging and burning. The reaction takes another 2-3 weeks to settle. I consider a “brisk” reaction to be desirable and predictive of a good outcome. I prefer to use the Carac brand because the 5-FU is incorporated into a porous microsphere allowing the concentration of drug to be lower (0.5%). The reaction is usually milder and easier to tolerate. A disadvantage is that it might be more expensive than Efudex or generics. However, the cure rate for all forms of 5-fluorouracil is high and usually yields an excellent end result.
2. Imiquimod stimulates the patient’s own immune system to produce the natural cancer fighting chemical interferon which destroys the abnormal cells. Aldara cream (5% imiquimod) is applied 2-3 times per week to the affected area for up to 16 weeks. It is recommended to treat limited areas of skin (2×2 inches) per course of treatment than with Efudex. Aldara may also cause a significant amount of redness, erosions,and pain, but it is generally well-tolerated and gives good results after healing. Patients will occasionally develop fever or swollen, tender lymph glands near the area of treatment, especially if there is a robust inflammatory reaction. This response is caused by interferon and is beneficial. A disadvantage of using Aldara is that it is only available in small one-use foil packets that contain only 250 mg of cream, so that it may be necessary to use more than one packet per application to cover the affected area.
3. Diclofenac (Solaraze gel), a non-steroidal anti-inflammatory drug, is combined with hyaluronic acid, a natural substance in the connective tissue of skin. Its mechanism of action in treating AK’s is not known, however, it produces much less inflammation in the skin than 5-FU or imiquimod. It also takes much longer to achieve results because it is applied twice daily for 2-3 months. My impression is that the results are inferior to the first two listed here, either because of the reduced inflammatory response or the lack of adherence by the patient to the protracted regimen.
What are the newer treatments for Actinic Keratoses?
The latest innovation for treating multiple AK’s is Photodynamic Therapy (PDT), which some patients have nick-named the “blue light special.” This treatment combines the application of a light sensitizing chemical called Levulan to the affected skin with a special blue light source. Neither treatment used alone would be effective. After the chemical incubates on the skin for an hour or longer, it is selectively taken up by the abnormal skin cells. The skin is then exposed to the blue light for 5 to 16 minutes depending on the lamp utilized, targeting the precancer and cancer cells for destruction. Patients may experience stinging and burning and eventually redness and swelling in the treated areas for several days followed by peeling. Sun exposure must be strictly avoided for the first 48 hours after the procedure. Healing is usually complete in about 10 days. Results are comparable to 5-FU with the added bonus of shorter healing time and some noticeable rejuvenation of the skin. A second PDT can be performed a month or two later for further improvement. Currently, blue light PDT is only approved in the US for AK’s of the face and scalp. AK’s on the chest, arms, hands, and legs would more likely be treated by one of the other methods described here.
Zyclara is imiquimod cream in lower concentrations of 2.5 and 3.75% than Aldara. It is intended to reduce the inflammatory reaction by application once daily for 2 weeks, followed by 2 weeks off, then applied once daily for 2 more weeks. A larger surface area may be treated such as a full face or scalp. Another advantage over Aldara is that Zyclara is available in both the small foil packets as well as larger pumps for more convenient dispensing.
Picato (ingenol mebutate) is a chemical derived from a plant that causes apoptosis or cell death. It is available as 0.015% cream for face and scalp and 0.05% cream for trunk and extremities. It is applied once daily for 2 or 3 days, respectively, to a limited contiguous area. The reactions described are similar to Efudex and Aldara. The obvious advantage over the other creams is the very short duration of treatment. However, potential disadvantages are limiting the treatment area to about 2×2 inches, and lower reported cure rates.
Prognosis and Prevention of Actinic Keratoses
The prognosis for treated actinic keratoses (AK’s) is excellent. However, the patients who have many AK’s have accumulated so much sun damage in their lifetimes that it is very likely they will eventually develop new or recurrent AK’s, especially if they do not change some habits. The treatments described in the previous paragraphs may have to be repeated several times and may even fail in some patients. A failure to respond may indicate that the precancerous AK has already progressed into a squamous cell cancer. Moreover, some patients may develop other skin cancer types such as basal cell carcinoma and melanoma directly from sun-damaged skin without first passing through the precancerous stage as AK’s. A skin biopsy will help to answer the question and determine the next step in treatment. It is safe to say that patients who have had numerous AK’s, with or without a history of skin cancer, are at increased of developing skin cancer.
Can AK’s and skin cancer be prevented? It is really never too late to begin practicing sun-safety habits.
- Seek the shade, especially between 10am and 4pm.
- Try not to get a sun burn. Remember that the sun rays are reflected off sand and are transmitted through water. You can also get sun burned on a cloudy day if you stay out long enough and are unprotected.
- Use a broad-spectrum (blocks both UVB and UVA rays) sunscreen with SPF #30 or higher daily.
- Apply the sunscreen 30 minutes before going out and reapply after swimming or perspiring heavily.
- Do not go to ultraviolet tanning salons.
- Cover up with clothing, broad-brimmed hat, and ultraviolet blocking sun glasses (protects the eyes too).
- Check your own skin head to toe every month in the mirror.
- Get a professional skin examination every year.
Can any of the treatments used for AK’s be used for skin cancer?
Yes. 5-Fluorouracil (Efudex) and imiquimod (Aldara) are also approved for the treatment of superficial basal cell carcinomas. This usually applies to tumors on the trunk, arms, or legs that are less than 2 cm in diameter. The treatment course is longer than that for AK’s: 6 weeks for Efudex twice daily and Aldara once daily Monday through Friday for 6 weeks. The usual inflammatory reactions are to be expected and may be more intense, but the success rate is high. This type of treatment is appropriate for patients who cannot tolerate or simply refuse surgery or radiation therapy. Although off-label, other types of skin cancer, such as nodular basal cell carcinoma and non-invasive squamous cell carcinoma and melanoma in situ, have been treated with these creams, albeit with a lower success rate. For this reason, a follow-up confirmatory skin biopsy is recommended after healing is completed.
Photodynamic therapy also has potential for treating skin cancer, especially when combined with curetting or debulking tumor prior to the application of the sensitizing chemical and red light exposure. Red light, which has a longer wavelength and therefore more energy than blue light, penetrates more deeply into skin, increasing the likelihood of reaching and destroying the “root” of the cancer cells.