Healing Wounds After Cryotherapy

By James Q. Del Rosso, D.O., F.A.O.C.D.

Actinic keratoses (AKs) are foci of cutaneous epithelial dysplasia that may develop into squamous cell carcinoma (SCC)
in situ or invasive SCC. Treatment for AK includes ablative techniques such as cryotherapy, and topical “field treatment” therapies such as 5-fluorouracil (Efudex, Carac, Fluoroplex), imiquimod (Aldara), and diclofenac sodium 3% (Solaraze). Cryotherapy typically leads to blistering and erosion of the treatment sites, and topical 5-fluorouracil and imiquimod to erythema, erosion and crusting. Post-procedure healing with all techniques generally requires 2 to 4 weeks.

Since AKs are frequently found in sun-exposed sites, patients often express concern about the appearance of treated areas and the extended time required for resolution of the treatment-induced lesions. To date, no specific therapy has been demonstrated in a large-scale clinical study to accelerate wound healing following AK treatment.

Trolamine-Containing Topical Emulsion

A trolamine-containing topical emulsion (Biafine) has been used in Europe for more than 25 years to expedite wound healing. This therapy is currently available by prescription in the United States for application to first- and second-degree burns (including sunburn and post-radiation therapy burns), dermal donor and graft sites, and wounds ranging in severity from superficial to full thickness.1


The formulation is reported to promote wound healing through both occlusive and hydrating properties, and by increasing the recruitment of macrophages to wound sites 3 to 10 times more than petrolatum.1,2 In comparative trials, the trolamine-containing topical emulsion has been shown to increase epithelial cell proliferation,3 reduce dermal edema,3 and accelerate wound healing.1

To assess the impact on healing time of a trolamine-containing topical emulsion (Biafine), a recent study was designed and conducted to compare it to a designated, non-medicated petrolatum-based ointment. Each therapy was applied twice daily to AKs right after they had been treated with liquid nitrogen cryotherapy. An additional objective of the study was to assess treatment safety and tolerability.1

How the Study Was Designed

This study was an investigator-blinded, randomized, split-body (target region) trial that lasted 4 weeks. The trial included adult patients with AKs in one of four target regions. Liquid nitrogen cryotherapy was performed on specified AK lesions; however, hyperkeratotic AKs were excluded.

Participants were excluded from the study if they had undergone treatment with liquid nitrogen cryotherapy within 4 months of study start for their AKs. In addition, they were not included if they had used any topical therapy other than sunscreen within 6 months of study start. At the time of the study, participants were not included if they had been using any systemic therapy known to affect wound healing, including systemic corticosteroids and chemotherapeutic or immunosuppressive agents.

Study Methods

Four target regions, consisting of the dorsal hands, dorsal forearms, forehead, and cheeks, were identified and matched for symmetric involvement of AK on each patient. Within each target region, AK lesions were treated with liquid nitrogen cryotherapy (each application did not exceed 6 seconds in duration). (See Table 1 for patients’ baseline characteristics.)


Following treatment, patients were instructed to apply a trolamine-containing topical emulsion twice daily to all treated target regions on one side of the body and a specified, non-medicated, petrolatum-based ointment twice daily to all treated target regions on the other side of the body.

Patients were instructed to maintain a daily diary and report the day on which they observed complete healing of all treated sites. Complete healing was defined as the point at which the skin was completely intact without any superficial erosion, crusting, or exudate and the point at which erythema had resolved (a residual light pink color or hypopigmentation was acceptable). Patients were instructed to avoid sun exposure over the 4-week duration of the trial and not to apply sunscreen or topical products other than those given them for the trial.

At 4 weeks, all patients were assessed by an investigator for extent of healing.

Study Results

All patients completed the study. Investigator observation confirmed that all treatment sites were completely healed at the 4-week follow-up with no adverse reactions reported. The mean time to complete healing for all target regions combined was 9.27 days for sides treated with trolamine-containing topical emulsion and 11.8 days for sides treated with the non-medicated petrolatum-based ointment, a difference of 2.53 days.

The mean time to complete healing varied by target region but, overall, was at least 2.3 days faster on the sides treated with trolamine-containing topical emulsion than on the sides treated with the non-medicated petrolatum-based ointment (see Figure 1).


Complete healing was a mean of 2.31 days faster on the dorsal hands, 2.87 days faster on the dorsal forearms, 3.20 days faster on the forehead, and 2.33 days faster on the cheeks for sides treated with trolamine-containing topical emulsion compared to sides treated with non-medicated petrolatum-based ointment (see Table 2).



No clear evidence exists that postoperative use of topical antibiotics such as bacitracin and neomycin decreases the risk of infection after office-based dermatologic surgical procedures such as biopsies, excisions, repairs and cryotherapy.4 However, both neomycin and bacitracin, found in multiple brand and generic over-the-counter topical antibiotic formulations, are common causes of allergic contact dermatitis.5

The widespread recommendation of having patients apply a topical antibiotic preparation after an office-based dermatologic surgery procedure is likely based more on “recycled habit” than scientific support. It may be time for clinicians performing office-based dermatologic surgery procedures to reconsider their approach, especially since many topical antibiotic preparations that contain neomycin and bacitracin are frequent contact allergens.

Summary of Point

• A trolamine-containing topical emulsion applied twice daily after liquid nitrogen cryotherapy of AK involving the hands, forearms, forehead, and cheeks demonstrated faster times to complete healing than twice-daily application of a non-medicated petrolatum-based ointment.
• The overall mean healing time was at least 2.3 days faster for lesions treated with trolamine-containing topical emulsion than for those treated with non-medicated petrolatum-based ointment.
• Treatment with both trolamine-containing topical emulsion and non-medicated petrolatum-based ointment was well tolerated.


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