ActinicKeratosesNet Spotlight Article
Benefits of Newer Treatment Options for Actinic Keratoses (AKs)

Imiquimod and photodynamic therapy (PDT), two newer treatment options approved by the U.S. Food and Drug Administration (FDA) for treating actinic keratoses (AKs), offer patients some unique benefits. Here is what published articles in medical journals are reporting:

Imiquimod
Approved in 2004 for treating AKs, dermatologists prescribe this cream to patients with multiple AKs. Meant for at-home use, patients apply imiquimod to affected skin as directed, typically a few times per week for a number of weeks or months.

What makes this cream so unique is that it stimulates the patient’s own immune system to attack the cells damaged by ultraviolet (UV) rays. As imiquimod works, it causes a brisk inflammatory reaction in most patients. Redness, swelling, and scabbing are common. This reaction means it is working.

As dermatologists continue to look at the safety and effectiveness of imiquimod, they have discovered that patients may experience:

• Less irritation. While imiquimod produces an inflammatory reaction, it is typically less intense and less painful than the reaction caused by 5-fluorouracil (5-FU), a topical chemotherapy often prescribed in the United States to treat multiple AKs.

• Fewer cosmetic side effects. While effective, older treatment options for AKs can cause skin discoloration or scarring. Cosmetic side effects are less frequently reported in patients using imiquimod. Skin discoloration (in the form of white spots developing after the scabs disappear) has been reported.

• Improved skin quality and texture. Patients often report these welcomed effects after using imiquimod to treat AKs. Imiquimod may partially reverse some of the damage caused by long-term exposure to UV rays, leading to improved skin.

• Prolonged clearance of AKs and reduction of new AKs. Once a patient develops multiple AKs, the patient typically sees new AKs for life. As imiquimod stimulates the patient’s immune system, imiquimod may create a type of “memory” in the patient’s immune system that makes AKs less likely to return. It also may reduce the incidence of new AKs.

• Decreased risk of squamous cell carcinoma. This “memory” created in the patient’s immune system also may reduce the risk of developing squamous cell carcinoma (SCC). AKs have the potential to progress to SCC, a type of skin cancer that can spread. One study found that 2 years after treatment, none of the 25 patients in the study developed SCC in the area treated with imiquimod. Of the 11 patients in this study who were treated with an inactive cream, 9 developed new AKs and 1 patient developed SCC in the treatment area.

It is important to keep in mind that imiquimod is not an appropriate treatment option for every patient with AKs. It is not meant to treat a single AK. If a patient has a compromised immune system, imiquimod will not be prescribed. Causes of a compromised immune system include HIV/AIDS or taking medication to prevent organ rejection after a transplant operation. Imiquimod also may be inappropriate for patients who work outdoors. When exposed to UV rays, imiquimod can cause a phototoxic reaction.

Photodynamic Therapy (PDT)
Used to treat widespread or multiple AKs, PDT can be performed in a dermatologist’s office. During this two-step process, a chemical solution is first applied to the skin affected by AKs. This makes the skin more reactive to light. After a prescribed time, which may be a few hours to overnight, the treated skin is exposed to light therapy. This brief exposure destroys AKs. While exposed to the light, the skin may burn. After therapy, the treated area may be painful for a brief time, showing redness, swelling, and crusting.

As more patients have received this treatment for AKs, dermatologists have observed the following benefits:

• May be as effective as 5-FU. 5-FU has long been used to effectively treat widespread AKs. Prescribed for at-home use, patients apply 5-FU for several weeks. Some patients discontinue 5-FU before the prescribed time due to severe redness, swelling, and pain.
  
  A study comparing the effectiveness of 5-FU with PDT found that the reduction in AKs was about the same. After six months of follow-up, the patients treated with 5-FU experienced a 70% reduction in AKs, and the patients treated with PDT had a 73% reduction in AKs.

• Reduced treatment time. While most therapies used to treat widespread AKs require the patient to apply a medication at home for a period of weeks or see a dermatologist for several treatment sessions, one PDT session can be completed in less than 24 hours. Some patients require 2 PDT treatment sessions.

• May reduce risk of nonmelanoma skin cancer and AKs in high-risk patients. Some people have an extremely high risk of developing skin cancer. Organ-transplant recipients take medication to prevent organ rejection. This medication suppresses the immune system, which dramatically increases the risk of developing skin cancer. People living with Gorlin’s syndrome, an inherited condition also known as basal cell nevus syndrome, often develop numerous basal cell skin cancers before they reach 30 years of age. For these and other high-risk patients, PDT may substantially reduce their risk, according to preliminary studies. More research is needed.

• Better cosmetic outcome than some therapies used to treat widespread AKs. During studies conducted to determine if the FDA would approve PDT for the treatment of AKs, patients were asked to rate the cosmetic effects of PDT. More than 90% rated the results as “excellent” or “good.” Studies also show that there is little risk of scarring or skin discoloration.

• Younger-looking skin. Some light sources and lasers used during PDT for AKs also are used to give patients younger-looking skin. When such a light source or laser is used to treat AKs, patients tend to see a younger-looking complexion. Reports of a decrease in wrinkles, improved skin texture, and reduced pore size are common.

While PDT offers patients a high cure rate and patients like the cosmetic outcome, this treatment option is not suitable for all patients with AKs. Patients who have a medical condition that causes sensitivity to light, such as lupus or porphyria, are not candidates for PDT.

Lifetime Checkups Crucial
No matter how effective the treatment, patients who develop AKs should receive regular checkups from a dermatologist for life. Most patients will develop more AKs. Those with extensive skin damage may see new AKs every year. For this reason, it is important that patients diagnosed with AKs also perform regular skin self-exams and constantly protect their skin from the sun. All recommendations are vital in long-term management of AKs.

References:
Braathen LR et al. “Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: An international consensus.” Journal of the American Academy of Dermatology. 2007. Jan;56(1):125-143.

Del Rosso JQ. “The Use of Topical Imiquimod for the Treatment of Actinic Keratoses: A Status Report.” Cutis. 2005. Oct;76(4):241-248.

Jorizzo JL. “Matching Patients with Therapy.” Cutis. 2004;74(suppl 6):5-8.

Lebwohl M et al. “Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.” Journal of the American Academy of Dermatology. 2004. May;50(5):714-721

Tutrone WD et al. “Topical Therapy for Actinic Keratoses, I: 5-Fluorouracil and Imiquimod.” Cutis. 2003. May;71(5):365-369.

Spencer JM et al. “Actinic Keratosis.” eMedicine. Last updated October 2, 2006. Available at http://www.emedicine.com/derm/topic9.htm. Last accessed May 31, 2007.

Yu TC et al. “Actinic Keratoses—Surgical and Physical Therapeutic Modalities.” Cutis. 2003. May;71(5):381-384.