Supplementary Material for: 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

<b><i>Background:</i></b> 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. <b><i>Objective:</i></b> To detect efficacy and safety of cryosurgery regimens on keloids and the occurring biological changes caused by the treatment. <b><i>Methods:</i></b> 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 (&lt;2 years old), small (≤10 cm²) keloids in 40 patients (2-sided effect, α-error 1%, power 95%). <b><i>Results:</i></b> Marked flattening of the lesions was achieved by both regimens. Median lesional volumes decreased from 106 to 7 mm³ in group A (<i>p</i> = 0.001) and from 138 to 6 mm³ in group B (<i>p</i> &lt; 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. <b><i>Conclusion:</i></b> 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.