Cryosurgery as a Single Agent and in Combination with Intralesional Corticosteroids Is Effective on Young, Small Keloids and Induces Characteristic Histological and Immunohistological Changes: A Prospective Randomized Trial
Christos C. Zouboulis, Eftychia Zouridaki
Abstract
BACKGROUND: As the pathogenesis of keloids is poorly understood, there is no sound biological basis of keloid management. Few controlled therapeutic studies have been published, and recurrences are a major reason for treatment failure. OBJECTIVE: To detect efficacy and safety of cryosurgery regimens on keloids and the occurring biological changes caused by the treatment. METHODS: This prospective randomized study compared efficacy and tolerability as well as histological/immunohistochemical effects of liquid nitrogen contact cryosurgery as a single regimen (group A) and combined with intralesional corticosteroids (group B) on young (<2 years old), small (≤10 cm2) keloids in 40 patients (2-sided effect, α-error 1%, power 95%). RESULTS: Marked flattening of the lesions was achieved by both regimens. Median lesional volumes decreased from 106 to 7 mm3 in group A (p = 0.001) and from 138 to 6 mm3 in group B (p < 0.0001; ns, between groups). Good to excellent responses were registered in 83.3 and 90% of patients in groups A and B, respectively, by evaluating the lesional volume, in 80 and 95% of patients by the physician's evaluation and in 95% of patients in either group by the patient's assessment. Follow-up of 6-36 months revealed no further significant changes. Cryosurgery was generally well tolerated, with minor pain during treatment not requiring (27.5%) or requiring local anaesthesia (5%) - but not analgesics -, and hypopigmentation (25%). Histological examination showed increased vessel number and lumen dilatation after treatment in group B and reduction of rete ridge length in both groups with more prominent changes in group A. Tenascin C staining demarcated keloids from normal skin before therapy, while after therapy the entire treated tissue was labelled. Interferon-γ expression was significantly decreased after therapy both regarding positively stained cells and intensity in both groups. CONCLUSION: Cryosurgery without and with intralesional corticosteroids is effective and safe on young, small keloids not only as a destructive physical procedure, but also by inducing biochemical and immunological scar rejuvenation.