A Comparison of Cryotherapy and Imiquimod for Treatment of Actinic Keratoses: Lesion Clearance, Safety, and Skin Quality Outcomes

December 2011 | Volume 10 | Issue 12 | Original Article | 1432 | Copyright © December 2011


Background: There is limited direct comparative data on imiquimod versus cryotherapy to treat actinic keratoses.
Objective: Compare lesion response through 12 months post-initial treatment.
Methods: Patients with ≥10 lesions on the face or scalp were randomized to cryotherapy (up to 10 lesions per session, up to 4 sessions, every 3 months) or imiquimod (3—times—per—week for 3—4 weeks, up to 2 courses) with repeat treatment depending on response.
Results: In 36 patients assigned to cryotherapy and 35 to imiquimod, lesion complete response rates were 85.0 percent (306/360) and 66.9 percent (234/350) for cryotherapy and imiquimod, respectively (P‹0.0002). For completely cleared lesions, global skin quality was excellent in 82 percent (250/306) versus 100 percent (234/234) for cryotherapy and imiquimod, respectively (P‹0.0001). More cryotherapy than imiquimod patients had hypopigmentation (54.8% versus 24.0%, P=0.0197), as well as blister formation, redness/erythema, flaking/scaling/dryness, and scabbing/crusting (P‹0.05).
Conclusion: 12-month lesion complete clearance rate was higher with repeated cryotherapy, but cosmetic outcome was better with imiquimod.

J Drugs Dermatol. 2011;10(12):1432-1438.


Cryotherapy is the most common treatment used globally to manage actinic keratoses (AK). This provider-administered treatment primarily treats individual lesions; field treatment is occasionally performed using wide spray patterns. Patients with extensive sun damage often require several clinic visits to treat multiple AK. Frequently lesions will fail to clear or will recur, requiring additional treatment sessions.1 Other treatment options include patient-applied topical agents such as 5-fluorouracil, diclofenac, and imiquimod, as well as provider-administered photodynamic therapy. Studies have compared treatments for AK, including cryotherapy versus photodynamic therapy as well as imiquimod versus 5-fluorouracil.1-5 Imiquimod may offer some advantages over cryotherapy in that it can treat "fields" containing multiple AK, as well as possibly treating subclinical lesions that are not easily visualized and treatable with cryotherapy.6 We herein report a prospective, randomized, comparison of cryotherapy versus imiquimod for the treatment of AK evaluating lesion clearance, safety, and skin quality outcomes up to 12 months following initial treatment.


Adult patients with at least 10 AK lesions in one anatomical area (both cheeks, forehead and temples, or scalp) were enrolled at a single center. The study was approved by the Human Research Ethics Committee of Saint Vincen's Hospital Melbourne. All patients provided written informed consent prior to conducting any study procedures.
At baseline, each AK in the target area was graded: 1 (mild= slightly palpable, better felt than seen); 2 (moderate=moderately thick, easily felt and seen); or 3 (severe=very thick and/or obvious lesion).7 Participants were randomly assigned to either cryotherapy or imiquimod (1:1 ratio, Figure 1). Each cryotherapy patient had 10 lesions in the target area identified, recorded, and outlined with a surgical marker. If there were more than 10 suitable lesions within the area, grade 3 lesions were treated first, followed by grade 2, and then grade 1 lesions. Each lesion was treated with liquid nitrogen using a spray applicator to produce