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evaluate the efficacy and safety of intralesional cryosurgery alone compared with intralesional cryosurgery combined with intralesional 5-fluorouracil and triamcinolone acetonide in the treatment of keloids.
Keloids are abnormal scars characterized by excessive collagen deposition that extends beyond the original wound boundaries, often leading to cosmetic disfigurement, pain, pruritus, and tenderness, significantly affecting patients' quality of life . Keloid formation is influenced by genetic predisposition, skin tension, wound location, and inflammatory responses, and they are notorious for high recurrence rates, with some reports indicating recurrence in up to 50-80% of cases after treatment .
Various therapeutic modalities have been used for the management of keloids. These treatment options can be broadly classified into intralesional therapies, topical therapies, and procedural interventions.
Despite the availability of multiple treatment options, no single therapy ensures complete resolution, and recurrence remains a significant challenge in keloid management .
Intralesional corticosteroids remain the first-line therapy, reducing fibroblast proliferation, collagen synthesis, and local inflammation. Clinical studies have shown flattening of keloids in 50-70% of patients with repeated injections . Another commonly used intralesional agent is 5-fluorouracil (5-FU), an antimetabolite that inhibits fibroblast proliferation and extracellular matrix deposition, with reported improvement in 70-80% of cases . Combination therapy of corticosteroids and 5-FU has demonstrated superior efficacy compared with monotherapy.
Among procedural modalities. Intralesional (IL) cryotherapy, is a technique in which a cryogen can be applied using a cryoneedle directly into the deeper dermis of the scar to produce rapid scar freezing from the core outwards, thus all the pathological tissue will be frozen and destructed, creating a new scar without keloidal characteristics, while sparing the surface epithelium. As a monotherapy, IL cryosurgery has yielded promising clinical results in terms of volume reduction and alleviation of pain and pruritus . Marked efficacy of a single intralesional cryosurgery session has been recorded even in voluminous keloids, which is an additional major advantage compared with the repeated sessions required in classical contact cryosurgery, However, on average, no complete scar eradication is attained and scar recurrence is seen. Also, persistent hypopigmentation remains problematic in nonwhite patients . These issues raise the question whether IL cryotherapy could be used in combination with nonsurgical therapies to augment the therapeutic effect and to lower the risk of hypopigmentation.
Weshahy and Abdel Hay and Stromps et combined IL cryotherapy with adjuvant therapy with silicone sheeting and triamcinolone injections, respectively .
Eisert and Nast reported good outcomes by initially using intralesional cryosurgery, followed by injection of triamcinolone, 5-fluorouracil and hyaluronidase, suggesting that such treatment also leads to significant softening of the keloid, which would otherwise be too firm to be treated with intralesional injections
Although several studies have evaluated the effectiveness of intralesional corticosteroids, 5-fluorouracil, and cryotherapy individually, data directly comparing intralesional cryotherapy with combined intralesional corticosteroid and 5-fluorouracil therapy remain limited in the literature .
The study aims to investigate whether intralesional injection of a mixture of 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC) as adjuvant therapy to intralesional cryosurgery produces superior outcomes in terms of scar improvement, recurrence reduction, and hypopigmentation control.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cryotherapy + Saline Injection (Placebo) | Experimental | Patients will receive a single session of intralesional cryotherapy followed by intralesional saline injection as a placebo. Saline injections will be repeated at 4-week intervals for a total of four sessions to maintain blinding and follow-up consistency with the experimental group. Patients and care providers are not blinded. Two independent blinded observers will evaluate scar characteristics using OSAS and VSS |
|
| Cryotherapy + TAC/5-FU Injection | Experimental | Patients will receive a single session of intralesional cryotherapy followed immediately by intralesional injection of a combination of triamcinolone acetonide (TAC, 40 mg/mL) and 5-fluorouracil (5-FU, 50 mg/mL) in a ratio of 1:9. Further intralesional injections of TAC and 5-FU will be administered at 4-week intervals for a total of four sessions. Patients and care providers are not blinded. Two independent blinded observers will evaluate scar characteristics using OSAS and VSS. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intralesional Cryotherapy + Saline Injection | Procedure | Patients will receive a single session of intralesional cryotherapy followed by intralesional saline injection as a placebo. Saline injections will be repeated at 4-week intervals for a total of four sessions to maintain blinding and follow-up consistency with the experimental group. Patients and care providers are not blinded. Two independent blinded observers will evaluate scar characteristics using OSAS and VSS |
| Measure | Description | Time Frame |
|---|---|---|
| Change in keloid size | Keloid severity will be assessed using the Vancouver Scar Scale (VSS), which evaluates vascularity, pigmentation, pliability, and height. Scores range from 0 to 13, with higher scores indicating more severe scarring. Assessment will be performed by blinded observers. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Patient Scar Assessment (PSAS) | Patient-reported outcomes will be evaluated using the Patient Scar Assessment Scale (PSAS), which assesses pain, pruritus, color, stiffness, thickness, and irregularity. Scores range from 6 to 60, with higher scores indicating worse scar quality. | up to 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in dermoscopic vascular patterns and pigmentation | Dermoscopy will be used to document and evaluate changes in vascular patterns, pigmentation, and structural features of the keloid. Observations will be compared between baseline and 12 weeks to assess changes | up to 12 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hadeer Ali Abouelela | Contact | 01092452868 | hadeer.abouelela1997@gmail.com | |
| Yasmin Moustafa Tawfiq | Contact | 01006033331 | yasminm.t@aun.edu.eg |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25442108 | Result | Abdel-Meguid AM, Weshahy AH, Sayed DS, Refaiy AE, Awad SM. Intralesional vs. contact cryosurgery in treatment of keloids: a clinical and immunohistochemical study. Int J Dermatol. 2015 Apr;54(4):468-75. doi: 10.1111/ijd.12667. Epub 2014 Nov 28. | |
| 22913446 | Result | Weshahy AH, Abdel Hay R. Intralesional cryosurgery and intralesional steroid injection: a good combination therapy for treatment of keloids and hypertrophic scars. Dermatol Ther. 2012 May-Jun;25(3):273-6. doi: 10.1111/j.1529-8019.2012.01456.x. |
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| ID | Term |
|---|---|
| D007627 | Keloid |
| ID | Term |
|---|---|
| D003095 | Collagen Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002921 | Cicatrix |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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Parallel Assignment
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"To ensure blinding, patients in the control group will receive intralesional saline injections as a placebo. Clinical and dermoscopic evaluations will be performed by two independent observers blinded to the treatment groups."
|
| Intralesional Cryotherapy + TAC/5-FU Injection | Procedure | Patients will receive a single session of intralesional cryotherapy followed immediately by intralesional injection of a combination of triamcinolone acetonide (TAC, 40 mg/mL) and 5-fluorouracil (5-FU, 50 mg/mL) in a ratio of 1:9. Further intralesional injections of TAC and 5-FU will be administered at 4-week intervals for a total of four sessions. Patients and care providers are not blinded. Two independent blinded observers will evaluate scar characteristics using OSAS and VSS. |
|
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017670 |
| Sodium Compounds |