Keloid treatment is challenging because of the high likelihood of recurrence and a lack of definitive treatment combinations. The treatment of bulky and recurrent keloids is particularly difficult. We investigated the administration of extralesional cryotherapy (EL) in conjunction with intralesional (IL) triamcinolone (TA) injections as adjuvant therapy after surgical excision for the management of keloids.
Among all patients who visited our scar laser center between January 2016 and August 2017, 54 patients who underwent IL keloid excision with EL cryotherapy and IL TA injection as adjuvant therapy were included in this retrospective study. We examined sex, site, the number of cryotherapy sessions and TA injections, symptoms after surgery, and recurrence. The Vancouver Scar Scale (VSS) was used as to quantify treatment outcomes.
Among 54 cases of IL keloid excision, after an average of 6.26 cryotherapy sessions and IL TA injections as combined adjuvant treatment, the lesion was controlled without recurrence in 49 cases. Relapse occurred in five patients, requiring additional treatment and reoperation. For 49 patients with photographic data, the average VSS score before and after treatment improved from 10.1 to 5.0. In 17 patients in whom symptoms recurred after surgery, all symptoms were controlled and maintained with adjuvant therapy.
Initial direct surgical excision, followed by a combination of EL cryotherapy and IL TA injections, was shown to be effective in challenging cases of large and recurring keloids.
Keloids originate from skin overgrowth beyond the original wound’s boundaries [
Several methods are used for keloid treatment, including surgical excision, silicone sheets, pressure therapy, intralesional (IL) corticosteroids, IL 5-fluorouracil, and radiation therapy. However, none of these modalities can completely eliminate keloids. Cryotherapy was first described for skin lesions by Weshahy [
A keloid scar with a narrow base is the ideal target for this treatment modality, as the narrow base concentrates the cooling effect on the small soft-tissue pedicle to maximize the freezing effect [
Existing cryotherapy applicators that use liquid nitrogen often cause undesirable hypopigmentation or scarring, since their freezing point is below –196 °C; the CryoPen’s freezing point is below –79 °C. The CryoPen prevents tissue destruction and epidermal damage, while potentially inducing fibroblast inactivation and facilitating ease of handling due to device miniaturization [
IL triamcinolone (TA) injection constitutes the first-line therapy for keloids; it effectively reduces alpha-globulin deposition in keloid tissue and inhibits fibroblast growth [
Herein, we present the clinical application of the CryoPen for keloids in combination with IL TA injections as adjuvant therapy after surgical excision.
Among all patients who visited our scar laser center between January 2016 and August 2017, 528 patients received extralesional (EL) cryotherapy with the CryoPen and simultaneous IL TA injections for keloids. A chart review was performed for these patients. Patient data were obtained after acquiring written informed consent and following a protocol approved by the institutional board (IRB No. 2021-4625-001). The study was performed in accordance with the tenets of the Declaration of Helsinki of 1975.
The inclusion criteria were as follows: (1) having undergone initial IL keloid excision with EL cryotherapy and IL TA injections as adjuvant therapy; (2) age ≥19 years; and (3) provision of informed consent to photography and data usage for research purposes. The exclusion criteria were (1) age <19 years and (2) unwillingness to consent for research for reasons such as language problems (e.g., foreign patients).
Indications for excision surgery were a history of recurrence, existing symptoms, and bulky cases. All excisions were performed by a single surgeon. For EL cryotherapy, all procedures were performed using a portable, spray-type CryoPen (L&C BIO). Disposable nitrous oxide cartridges weigh 8 g, and the maximum spraying time per cartridge bottle is 120 seconds. A disposable nitrous oxide cartridge and filter are included in one set. After mounting the cartridge and filter in the device, when we press the spray button at a distance of 1 cm from the center of the keloid lesion, nitrous oxide at –79 °C is immediately sprayed and cryotherapy is performed. Anesthesia was not performed because the treatment took no longer than a few seconds and caused little pain. In the case of skin abrasion after cryotherapy, conservative treatment was concurrently performed and cryotherapy was postponed to the next time. The solution’s concentration for IL TA injections was 10–40 mg/mL. The follow-up interval was 3 weeks and was increased from 3 to 6 months during the later part of treatment.
As a measure of the final outcome judgments before and after treatment, the Vancouver Scar Scale (VSS) score was calculated by retrospectively analyzing lesion images from photographs in the outpatient clinic.
In total, 53 patients with 54 keloid lesions were included in this retrospective interventional study (
Among the 54 instances of keloid lesions treated with 4.42 cycles (range, 1–11 cycles) of cryotherapy and IL TA injections, 31 cases maintained flatness without recurrence of the remnant keloid after surgery. In the remaining 23 cases, locally palpable lesions in the residual keloids were observed during treatment. For this focal relapsed remnant lesion, approximately four cycles of additional adjuvant therapy were administered. On average, the total number of sessions after surgery for all patients was 6.26. Among the 23 cases considered to have local regrowth, 18 cases (78.3%) were relieved during the additional treatment period, and no specific symptoms were observed. Five cases (9.3%) experienced relapse even after surgery and additional adjuvant treatment. Reoperation was performed for one of these patients.
Of the 54 patients, the VSS score was calculated for 45 patients with available photographs from both the start and end of treatment. The mean value at the start of treatment was 10.1 (range, 7–13) and that at the end was 5.0 (range, 1–8). Considering the specific items of the VSS, vascularity improved from 2 to 1.1, pigmentation from 1.9 to 1.6, pliability from 3.8 to 1.3, and height from 2.4 to 1 after treatment.
In 17 patients (31.5%), symptoms including pain, tenderness, erythema, itching, hardness, and pigmentation were observed after surgery, but these symptoms were controlled and maintained through adjuvant therapy.
In one patient, delayed healing and wound dehiscence occurred after keloidectomy and three sessions of adjuvant therapy of the anterior chest wall. After 6 months of conservative treatment, the wound healed, and cryotherapy was restarted with satisfactory results. Skin abrasion that occurred immediately after treatment was resolved with conservative treatments such as hydrocolloid agents or self-dressing with antibiotic ointment, and based on the chart review, there were no cases of delay or discontinuation of the next treatment session attributed to this reason. In addition, there were no cases of hypopigmentation, necrosis, abscess formation, blistering, or infection due to adjuvant therapy. The following sections present three cases of excision.
A 59-year-old woman visited our hospital with a keloid that appeared following abdominal surgery performed 5 years ago (
A 32-year-old woman presented with a keloid on the left shoulder caused by inoculation 20 years ago (
A 22-year-old woman presented with a keloid of the left helix caused by a piercing 5 years ago (
Globally, many studies have discovered monotherapies for keloids. This has led to a change of thought regarding combinations of multiple treatments in cases wherein one treatment has limited effectiveness.
The reason for hesitating to perform surgical resection is that it is an invasive act; thus, there is a limit to what a dermatologist can perform. Moreover, the operating surgeon is likely to have concerns regarding the high recurrence rate [
In the case of large, bulky, or recurrent keloids, surgical excision should be considered. Staged excision should be considered if blood circulation in the surrounding tissues is likely to decrease after excision, if there is a possibility that the skin will be insufficient, or that tension may occur due to locational characteristics. Rather than trying to solve everything simultaneously, it is also important to reduce the patient’s anxiety regarding their results by reminding them from the outset that treatment will take place over several sessions.
Cryotherapy using the CryoPen not only physically damages blood vessels and destroys tissues, but also increases CD163+ M2 macrophages and matrix metalloproteinase-9, which is molecularly and biologically involved in fibrotic resolution. Nevertheless, since the CryoPen has a freezing point of –79 °C, it can reduce side effects by enabling selective treatment compared to the traditional cryogun method [
In our study, recurrence after surgery was observed in 23 out of 54 patients, which is not significantly different from the results previously published in the literature. Recurrence after IL keloidectomy was considered impossible to prevent completely, as there would be a residual unresected keloid. If the size of the keloid after surgery is similar to the size before surgery, reoperation should be considered. If there is a focal or partial relapse that has not increased to the size of the previous keloid, the lesion is considered to be responsive to adjuvant therapy, and an average of six cycles should be performed and the progress should be monitored. Excluding two cases where treatment was stopped due to transfer to other hospitals, the final recurrence rate was three out of 52 cases (5.8%), which is a satisfactory result.
TA injections, when used alone, were found to be effective as the first-line treatment for keloids; however, studies on combination therapy are being actively conducted because of the possibility of recurrence or side effects. According to Yosipovitch et al. [
The main limitation of this study is the absence of a control group. Additionally, the VSS for all cases could not be calculated because there were cases where photographs of patients were omitted, and there was no description of subjective indicators from the start to end of keloid treatment. Although the length of the keloid was measured in this study, measuring the volume reduction three-dimensionally would be more effective for proving the therapeutic effect. In subsequent studies, it will be necessary to produce objective results through the calculation of various indicators along with the inclusion of a control group.
Keloids, irrespective of their size, are difficult to treat and are inherently prone to recurrence. Owing to the lack of a definitive monotherapy regimen, all treatment methods should be pursued within limits that are useful, safe, and acceptable to both physicians and patients. This is especially true in challenging cases with large or recurrent keloids. The current study showed that initial direct surgical excision, followed by combined treatment with EL cryotherapy and IL TA injections, was effective in the management of such challenging cases. Additionally, EL cryotherapy using the CryoPen was found to be superior to conventional IL cryotherapy, as its application is safer, easier, and faster. Still, further studies with larger samples and long-term follow-up are required.
No potential conflict of interest relevant to this article was reported.
The study was approved by the Institutional Review Board of Severance Hospital (IRB No. 2021-4625-001) and performed in accordance with the principles of the Declaration of Helsinki.
The patients provided written informed consent for the publication and use of their images.
A 59-year-old woman presented with abdominal keloids due to postoperative scarring. Images of the lesion before treatment (A), at a 6-month follow-up (B), and at a 1-year follow-up (C).
A 32-year-old woman presented with a left shoulder keloid secondary to vaccination. Images of the lesion before treatment (A), after partial keloid excision (B), at a 3-month follow-up (C), and at an 8-month follow-up (D).
A 22-year-old woman presented with a left ear keloid arising from a helix piercing. Images of the lesion before treatment (A), after partial keloid excision (B), at a 9-month follow-up (C), and at a 2-year follow-up (D).
Patient demographics
Variable | No. of keloid lesion |
---|---|
Sex | |
Female | 42 |
Male | 12 |
Age (yr) | 34 (19–79) |
Site of keloid | |
Head & neck | 21 |
Trunk | 20 |
Extremities | 13 |
Cause of keloid | |
Postoperative scar | 26 |
Acne | 5 |
Burn | 3 |
Piercing | 9 |
Trauma | 7 |
Vaccine | 4 |
Length of keloid (cm) | 6.14 (1–20) |
No. of treatment sessions (times) | 6.26 (1–20) |
Values are presented as number or mean (range).