Skip to main content
Top
Published in:

01-10-2024 | Keloid | Review

Systematic review of dupilumab safety and efficacy for treatment of keloid scars

Authors: David Bitterman, Paras Patel, Jennifer Y. Wang, Margaret Kabakova, Kayla Zafar, Austin Lee, Jessica Mineroff Gollogly, Marc Cohen, Evan Austin, Jared Jagdeo

Published in: Archives of Dermatological Research | Issue 8/2024

Login to get access

Abstract

Keloids, characterized by excessive scar formation following dermal inflammation, pose a therapeutic challenge due to high recurrence rates. Radiation therapy, contraindicated in children, can minimize recurrence post-surgical removal. Dupilumab, which inhibits the pro-fibrotic interleukin-4/interleukin-13 axis, may effectively manage keloids when intralesional corticosteroid injections are unsuccessful. It may also prevent recurrence post-surgery in pediatric patients. This systematic review assesses the efficacy and safety of dupilumab for the treatment of keloids. Through a systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we identified and analyzed outcomes from three case reports and three case series studies, totaling 15 patients. Results indicate variable responses to treatment, including significant improvements, no clinical change, and worsening of keloid symptoms. Additional research is needed to recommend using dupilumab to treat keloids (Grade D). Treatment response variability may be linked to differences in interleukin-4/interleukin-13 activity between active and inactive keloids. Additionally, the unintended promotion of T helper 17 cell differentiation by dupilumab may worsen keloids.
Literature
2.
go back to reference Ogawa R (2017) Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci, 18(3) Ogawa R (2017) Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci, 18(3)
4.
go back to reference Bijlard E et al (2017) Burden of Keloid Disease: a cross-sectional health-related quality of Life Assessment. Acta Derm Venereol 97(2):225–229CrossRefPubMed Bijlard E et al (2017) Burden of Keloid Disease: a cross-sectional health-related quality of Life Assessment. Acta Derm Venereol 97(2):225–229CrossRefPubMed
5.
go back to reference Lu W, Chu H, Zheng X (2021) Effects on quality of life and psychosocial wellbeing in Chinese patients with keloids. Am J Transl Res 13(3):1636–1642PubMedPubMedCentral Lu W, Chu H, Zheng X (2021) Effects on quality of life and psychosocial wellbeing in Chinese patients with keloids. Am J Transl Res 13(3):1636–1642PubMedPubMedCentral
6.
go back to reference Mustoe TA et al (2002) International clinical recommendations on scar management. Plast Reconstr Surg 110(2):560–571CrossRefPubMed Mustoe TA et al (2002) International clinical recommendations on scar management. Plast Reconstr Surg 110(2):560–571CrossRefPubMed
7.
go back to reference Yin Q et al (2023) Intralesional Corticosteroid Administration in the treatment of keloids: a scoping review on injection methods. Dermatology 239(3):462–477CrossRefPubMed Yin Q et al (2023) Intralesional Corticosteroid Administration in the treatment of keloids: a scoping review on injection methods. Dermatology 239(3):462–477CrossRefPubMed
9.
go back to reference Fredman R, Tenenhaus M (2013) Cushing’s syndrome after intralesional triamcinolone acetonide: a systematic review of the literature and multinational survey. Burns 39(4):549–557CrossRefPubMed Fredman R, Tenenhaus M (2013) Cushing’s syndrome after intralesional triamcinolone acetonide: a systematic review of the literature and multinational survey. Burns 39(4):549–557CrossRefPubMed
10.
go back to reference Ogawa R (2022) The most current algorithms for the Treatment and Prevention of Hypertrophic Scars and keloids: a 2020 update of the algorithms published 10 years ago. Plast Reconstr Surg 149(1):79e–94eCrossRefPubMed Ogawa R (2022) The most current algorithms for the Treatment and Prevention of Hypertrophic Scars and keloids: a 2020 update of the algorithms published 10 years ago. Plast Reconstr Surg 149(1):79e–94eCrossRefPubMed
11.
go back to reference Ekstein SF et al (2021) Keloids: a review of therapeutic management. Int J Dermatol 60(6):661–671CrossRefPubMed Ekstein SF et al (2021) Keloids: a review of therapeutic management. Int J Dermatol 60(6):661–671CrossRefPubMed
13.
go back to reference Min MS et al (2023) Successful treatment of keloids and hypertrophic scars with systemic and Intralesional Dupilumab. J Drugs Dermatol 22(12):1220–1222CrossRefPubMed Min MS et al (2023) Successful treatment of keloids and hypertrophic scars with systemic and Intralesional Dupilumab. J Drugs Dermatol 22(12):1220–1222CrossRefPubMed
14.
go back to reference Ogawa R et al (2009) Is radiation therapy for keloids acceptable? The risk of radiation-induced carcinogenesis. Plast Reconstr Surg 124(4):1196–1201CrossRefPubMed Ogawa R et al (2009) Is radiation therapy for keloids acceptable? The risk of radiation-induced carcinogenesis. Plast Reconstr Surg 124(4):1196–1201CrossRefPubMed
15.
go back to reference Nguyen JK et al (2020) The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res 312(2):81–92CrossRefPubMed Nguyen JK et al (2020) The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res 312(2):81–92CrossRefPubMed
16.
go back to reference Muromoto R, Oritani K, Matsuda T (2022) Current understanding of the role of tyrosine kinase 2 signaling in immune responses. World J Biol Chem 13(1):1–14CrossRefPubMedPubMedCentral Muromoto R, Oritani K, Matsuda T (2022) Current understanding of the role of tyrosine kinase 2 signaling in immune responses. World J Biol Chem 13(1):1–14CrossRefPubMedPubMedCentral
17.
go back to reference Yin Q et al (2023) The JAK-STAT pathway in keloid pathogenesis: a systematic review with qualitative synthesis. Exp Dermatol 32(5):588–598CrossRefPubMed Yin Q et al (2023) The JAK-STAT pathway in keloid pathogenesis: a systematic review with qualitative synthesis. Exp Dermatol 32(5):588–598CrossRefPubMed
18.
go back to reference Diaz A et al (2020) Keloid lesions show increased IL-4/IL-13 signaling and respond to Th2-targeting dupilumab therapy. J Eur Acad Dermatol Venereol 34(4):e161–e164CrossRefPubMed Diaz A et al (2020) Keloid lesions show increased IL-4/IL-13 signaling and respond to Th2-targeting dupilumab therapy. J Eur Acad Dermatol Venereol 34(4):e161–e164CrossRefPubMed
22.
go back to reference Tirgan MH, Uitto J (2022) Lack of efficacy of dupilumab in the treatment of keloid disorder. J Eur Acad Dermatol Venereol 36(2):e120–e122CrossRefPubMed Tirgan MH, Uitto J (2022) Lack of efficacy of dupilumab in the treatment of keloid disorder. J Eur Acad Dermatol Venereol 36(2):e120–e122CrossRefPubMed
23.
go back to reference Luk K, Fakhoury J, Ozog D (2022) Nonresponse and progression of diffuse keloids to Dupilumab Therapy. J Drugs Dermatol 21(2):197–199CrossRefPubMed Luk K, Fakhoury J, Ozog D (2022) Nonresponse and progression of diffuse keloids to Dupilumab Therapy. J Drugs Dermatol 21(2):197–199CrossRefPubMed
25.
go back to reference Cooney LA et al (2011) Sensitivity and resistance to regulation by IL-4 during Th17 maturation. J Immunol 187(9):4440–4450CrossRefPubMed Cooney LA et al (2011) Sensitivity and resistance to regulation by IL-4 during Th17 maturation. J Immunol 187(9):4440–4450CrossRefPubMed
26.
go back to reference Lee SY et al (2022) IL-17 induces Autophagy Dysfunction to promote inflammatory cell death and fibrosis in keloid fibroblasts via the STAT3 and HIF-1α Dependent Signaling pathways. Front Immunol 13:888719CrossRefPubMedPubMedCentral Lee SY et al (2022) IL-17 induces Autophagy Dysfunction to promote inflammatory cell death and fibrosis in keloid fibroblasts via the STAT3 and HIF-1α Dependent Signaling pathways. Front Immunol 13:888719CrossRefPubMedPubMedCentral
27.
go back to reference Lee YI et al (2022) WNT5A drives interleukin-6-dependent epithelial-mesenchymal transition via the JAK/STAT pathway in keloid pathogenesis. Burns Trauma 10:tkac023CrossRefPubMedPubMedCentral Lee YI et al (2022) WNT5A drives interleukin-6-dependent epithelial-mesenchymal transition via the JAK/STAT pathway in keloid pathogenesis. Burns Trauma 10:tkac023CrossRefPubMedPubMedCentral
28.
go back to reference Zhang Q et al (2009) Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. PLoS ONE 4(11):e7798CrossRefPubMedPubMedCentral Zhang Q et al (2009) Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. PLoS ONE 4(11):e7798CrossRefPubMedPubMedCentral
29.
go back to reference Bridgewood C et al (2022) Helper 2 IL-4/IL-13 dual blockade with Dupilumab is linked to some Emergent T Helper 17–Type diseases, including Seronegative Arthritis and Enthesitis/Enthesopathy, but not to Humoral Autoimmune diseases. J Invest Dermatol 142(10):2660–2667CrossRefPubMed Bridgewood C et al (2022) Helper 2 IL-4/IL-13 dual blockade with Dupilumab is linked to some Emergent T Helper 17–Type diseases, including Seronegative Arthritis and Enthesitis/Enthesopathy, but not to Humoral Autoimmune diseases. J Invest Dermatol 142(10):2660–2667CrossRefPubMed
Metadata
Title
Systematic review of dupilumab safety and efficacy for treatment of keloid scars
Authors
David Bitterman
Paras Patel
Jennifer Y. Wang
Margaret Kabakova
Kayla Zafar
Austin Lee
Jessica Mineroff Gollogly
Marc Cohen
Evan Austin
Jared Jagdeo
Publication date
01-10-2024
Publisher
Springer Berlin Heidelberg
Keywords
Keloid
Dupilumab
Published in
Archives of Dermatological Research / Issue 8/2024
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-024-03277-6

Other articles of this Issue 8/2024

Archives of Dermatological Research 8/2024 Go to the issue