Pruritus in Keloid Scars: Mechanisms and Treatments


  • Ahmed A. Hawash
  • Giuseppe Ingrasci
  • Keyvan Nouri
  • Gil Yosipovitch Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami, 1600 NW 10th Ave RMSB Building 2067B, FL, USA



keloid, pruritus, therapeutics, neuropathy


Keloids are scars that extend beyond the margins of an insulting cutaneous injury. Keloids are often thought to be primarily a cosmetic issue, as they are typically quite raised and pigmented. However, these scars also present with functional symptoms of pruritus and pain that significantly impact quality of life. The symptom of pruritus is frequently overlooked by dermatologists, and treatments are often primarily focused on the gross appearance of the scar. This review describes the prevalence and importance of pruritus in keloids. In addition, the putative mechanisms underlying the development of keloid pruritus, which include neuronal and immunological mechanisms, are discussed. Furthermore, this review describes keloid treatments that have been shown to reduce pruritus, treatments that specifically target the itch, and emerging therapies.


Download data is not yet available.


Lee S-S, Yosipovitch G, Chan Y-H, Goh C-L. Pruritus, pain, and small nerve fiber function in keloids: a controlled study. J Am Acad Dermatol 2004; 51: 1002-1006. DOI:

Kouotou EA, Nansseu JR, Omona Guissana E, Mendouga Menye CR, Akpadjan F, Tounkara TM, et al. Epidemiology and clinical features of keloids in black Africans: a nested case-control study from Yaoundé, Cameroon. Int J Dermatol 2019; 58: 1135-1140. DOI:

Komenan K, Kanga K, Alexandre K, Ange A, Isidore K, Sarah K, et al. Quality of life in black African patients with keloid scars. Dermatol Rep 2020; 12: 8312. DOI:

Bijlard E, Kouwenberg CAE, Timman R, Hovius S, Busschbach J, Mureau M. Burden of keloid disease: a cross-sectional health-related quality of life assessment. Acta Derm Venereol 2017; 97: 225-229. DOI:

Kelly AP. Keloids. Dermatol Clin 1988; 6: 413-424. DOI:

Jumper N, Paus R, Bayat A. Functional histopathology of keloid disease. Histol Histopathol 2015; 30: 1033-1057.

Bagabir R, Byers RJ, Chaudhry IH, Müller W, Paus R, Bayat A. Site-specific immunophenotyping of keloid disease demonstrates immune upregulation and the presence of lymphoid aggregates. Br J Dermatol 2012; 167: 1053-1066. DOI:

Ogawa R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci 2017; 18: 606. DOI:

Wilgus TA, Wulff BC. The importance of mast cells in dermal scarring. Adv Wound Care (New Rochelle) 2014; 3: 356-365. DOI:

Smith CJ, Smith JC, Finn MC. The possible role of mast cells (allergy) in the production of keloid and hypertrophic scarring. J Burn Care Rehabil 1987; 8: 126-131. DOI:

Micera A, Puxeddu I, Aloe L, Levi-Schaffer F. New insights on the involvement of nerve growth factor in allergic inflammation and fibrosis. Cytokine Growth Factor Rev 2003; 14: 369-374. DOI:

Jin Q, Gui L, Niu F, Yu B, Lauda N, Liu J, et al. Macrophages in keloid are potent at promoting the differentiation and function of regulatory T cells. Exp Cell Res 2018; 362: 472-476.

Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol 2014; 5: 614. DOI:

Jin Q, Gui L, Niu F, Yu B, Lauda N, Liu J, et al. Macrophages in keloid are potent at promoting the differentiation and function of regulatory T cells. Exp Cell Res 2018; 362: 472-476. DOI:

Ishida Y, Kondo T, Takayasu T, Iwakura Y, Mukaida N. The essential involvement of cross-talk between IFN-gamma and TGF-beta in the skin wound-healing process. J Immunol 2004; 172: 1848-1855. DOI:

Yin S-L, Qin Z-L, Yang X. Role of periostin in skin wound healing and pathologic scar formation. Chin Med J 2020; 133: 2236-2238. DOI:

Hashimoto T, Nattkemper LA, Kim HS, Kursewicz CD, Fowler E, Shah SM, et al. Dermal periostin: a new player in itch of prurigo nodularis. Acta Derm Venereol 2021; 101: adv00375. DOI:

Wu J, Del Duca E, Espino M, Gontzes A, Cueto I, Zhang N, et al. RNA Sequencing keloid transcriptome associates keloids with Th2, Th1, Th17/Th22, and JAK3-skewing. Front Immunol 2020; 11: 597741. DOI:

Chen Z, Zhou L, Won T, Gao Z, Wu X, Lu L. Characterization of CD45RO. Br J Dermatol 2018; 178: 940-950. DOI:

Maeda D, Kubo T, Kiya K, Kawai K, Matsuzaki S, Kobayashi D, et al. Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-beta 1 secretion in abnormal scar formation. J Plast Surg Hand Surg 2019; 53: 288-294. DOI:

Hochman B, Nahas FX, Sobral CS, Arias V, Locali RF, Juliano Y, et al. Nerve fibres: a possible role in keloid pathogenesis. Br J Dermatol 2008; 158: 651-652. DOI:

Tey HL, Maddison B, Wang H, Ishiju Y, McMichael A, Marks M, et al. Cutaneous innervation and itch in keloids. Acta Derm Venereol 2012; 92: 529-531. DOI:

Chen W, Fu X, Sun X, Sun T, Zhao Z, Sheng Z. Analysis of differentially expressed genes in keloids and normal skin with cDNA microarray. J Surg Res 2003; 113: 208-216. DOI:

Tomioka M, Stead RH, Nielsen L, Coughlin MD, Bienenstock J. Nerve growth factor enhances antigen and other secretagogue-induced histamine release from rat peritoneal mast cells in the absence of phosphatidylserine. J Allergy Clin Immunol 1988; 82: 599-607. DOI:

Kanda N, Watanabe S. Histamine enhances the production of nerve growth factor in human keratinocytes. J Invest Dermatol 2003; 121: 570-577. DOI:

Jing C, Jia-Han W, Hong-Xing Z. Double-edged effects of neuropeptide substance P on repair of cutaneous trauma: double-edged effects of neuropeptide substance P. Wound Repair Regen 2010; 18: 319-324. DOI:

Leal EC, Carvalho E, Tellechea A, Kafanas A, Tecilazich F, Kearney C, et al. Substance P promotes wound healing in diabetes by modulating inflammation and macrophage phenotype. Amer J Pathol 2015; 185: 1638-1648. DOI:

Cheng B, Liu HW, Fu XB, Sheng ZY, Li JF. Coexistence and upregulation of three types of opioid receptors, mu, delta and kappa, in human hypertrophic scars. Br J Dermatol 2008; 158: 713-720. DOI:

Cheng B, Liu H-W, Fu X-B. Update on pruritic mechanisms of hypertrophic scars in postburn patients: the potential role of opioids and their receptors. J Burn Care Rehabil 2011; 32: 118-125. DOI:

Nguyen JK, Austin E, Huang A, Mamalis A, Jagdeo J. The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res 2020; 312: 81-92. DOI:

Xu J, Zanvit P, Hu L, Tseng P-Y, Liu N, Wang F, et al. The cytokine TGF-β induces interleukin-31 expression from dermal dendritic cells to activate sensory neurons and stimulate wound itching. Immunity 2020; 53: 371-383. DOI:

Ekstein SF, Wyles SP, Moran SL, Meves A. Keloids: a review of therapeutic management. Int J Dermatol 2021; 60: 661-671. DOI:

Coppola MM, Salzillo R, Segreto F, Persichetti P. Triamcinolone acetonide intralesional injection for the treatment of keloid scars: patient selection and perspectives. Clin Cosmet Investig Dermatol 2018; 11: 387-396. DOI:

Cedeno-Laurent F, Singer EM, Wysocka M, Benoit BM, Vittorio CC, Kim EJ, et al. Improved pruritus correlates with lower levels of IL-31 in CTCL patients under different therapeutic modalities. Clin Immunol 2015; 158: 1-7. DOI:

Yaseen B, Lopez H, Taki Z, Zafar S, Rosario H, Abdi BA, et al. Interleukin-31 promotes pathogenic mechanisms underlying skin and lung fibrosis in scleroderma. Rheumatology (Oxford) 2020; 59: 2625-2636. DOI:

Hashimoto T, Nattkemper LA, Kim HS, Kursewicz CD, Fowler E, Shah SM, et al. Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta. Exp Dermatol 2021; 30: 804-810. DOI:

Brunner PMMD, Khattri SMD, Garcet SP, Finney RMD, Oliva MBA, Dutt RS, et al. A mild topical steroid leads to progressive anti-inflammatory effects in the skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol 2016; 138: 169-178. DOI:

Darougheh A, Asilian A, Shariati F. Intralesional triamcinolone alone or in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. Clin Exp Dermatol 2009; 34: 219-223. DOI:

Song H, Tan J, Fu Q, Huang L, Ao M. Comparative efficacy of intralesional triamcinolone acetonide injection during early and static stage of pathological scarring. J Cosmet Dermatol 2019; 18: 874-878. DOI:

Mustoe TA, Cooter RD, Gold MH, Richard Hobbs FD, Ramelet A-A, Shakespeare PG, et al. International clinical recommendations on scar management. Plast Reconstr Surg (1963) 2002; 110: 560-571. DOI:

Bhatt N, Alster TS. Laser Surgery in Dark Skin. Dermatol Surg 2008; 34: 184-195. DOI:

Mustoe TA. Evolution of silicone therapy and mechanism of action in scar management. Aesthetic Plast Surg 2008; 32: 82-92. DOI:

Tandara AA, Mustoe TA. The role of the epidermis in the control of scarring: evidence for mechanism of action for silicone gel. J Plast Reconstr Aesthet Surg 2008; 61: 1219-1225. DOI:

Eishi K, Bae SJ, Ogawa F, Hamasaki Y, Shimizu K, Katayama I. Silicone gel sheets relieve pain and pruritus with clinical improvement of keloid: possible target of mast cells. J Dermatolog Treat 2003; 14: 248-252. DOI:

Kong CG, Kim GH, Kim DW, In Y. The effect of topical scar treatment on postoperative scar pain and pruritus after total knee arthroplasty. Arch Orthop Trauma Surg 2014; 134: 555-559. DOI:

Xiao Z, Zhang M, Liu Y, Ren L. Botulinum toxin type a inhibits connective tissue growth factor expression in fibroblasts derived from hypertrophic scar. Aesthetic Plast Surg 2011; 35: 802-807. DOI:

Xiao Z, Zhang F, Lin W, Zhang M, Liu Y. Effect of botulinum toxin type A on transforming growth factor beta1 in fibroblasts derived from hypertrophic scar: a preliminary report. Aesthetic Plast Surg 2010; 34: 424-427. DOI:

Scala J, Vojvodic A, Vojvodic P, Vlaskovic-Jovicevic T, Peric-Hajzler Z, Matovic D, et al. Botulin toxin use in scars/keloids treatment. Open Access Maced J Med Sci 2019; 7: 2979-2981. DOI:

Carmichael NME, Dostrovsky JO, Charlton MP. Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin. Pain (Amsterdam) 2010; 149: 316-324. DOI:

Xiao Z, Zhang F, Cui Z. Treatment of hypertrophic scars with intralesional botulinum toxin type A injections: a preliminary report. Aesthetic Plast Surg 2009; 33: 409-412. DOI:

Gupta S, Kalra A. Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids. Dermatol 2002; 204: 130-132. DOI:

Goldan O, Weissman O, Regev E, Haik J, Winkler E. Treatment of postdermabrasion facial hypertrophic and keloid scars with intralesional 5-fluorouracil injections. Aesthetic Plast Surg 2008; 32: 389-392. DOI:

Li WB, Liu S, Zhang MZ, Liu H, Dong XH, Hao Y, et al. Hyperbaric oxygen therapy relieved pruritus and pain of keloid patients. Am J Transl Res 2020; 12: 574-582.

Van Leeuwen MC, Bulstra AE, Ket JC, Ritt MJ, Van Leeuwen PA, Niessen FB. Intralesional cryotherapy for the treatment of keloid scars: evaluating effectiveness. Plast Reconstr Surg Glob Open 2015; 3: 437. DOI:

Goldenberg G, Luber AJ. Use of intralesional cryosurgery as an innovative therapy for keloid scars and a review of current treatments. J Clin Aesthet Dermatol 2013; 6: 23-26.

Har-Shai Y, Amar M, Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. Plast Reconstr Surg 2003; 111: 1841-1852. DOI:

Gupta S, Kumar B. Intralesional cryosurgery using lumbar puncture and/or hypodermic needles for large, bulky, recalcitrant keloids. Int J Dermatol 2001; 40: 349-353. DOI:

Hendricks T, Martens MF, Huyben CM, Wobbes T. Inhibition of basal and TGF β-induced fibroblast collagen synthesis by antineoplastic agents. Implications for wound healing. Br J Cancer 1993; 67: 545-550. DOI:

Aggarwal H, Saxena A, Lubana PS, Mathur RK, Jain DK. Treatment of keloids and hypertrophic scars using bleom. J Cosmet Dermatol 2008; 7: 43-49. DOI:

España A, Solano T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg 2001; 27: 23-27. DOI:

Zhu R, Yue B, Yang Q, Ma Y, Huang G, Guan M, et al. The effect of 595 nm pulsed dye laser on connective tissue growth factor (CTGF) expression in cultured keloid fibroblasts. Lasers Surg Med 2015; 47: 203-209. DOI:

Patel PM, Bakus AD, Garden BC, Lai O, Jones VA, Garden JM. Treatment of pain in keloids using only a long-pulsed 1064 nm Nd:YAG laser. Lasers Surg Med 2021; 53: 66-69. DOI:

Connell PG, Harland CC. Treatment of keloid scars with pulsed dye laser and intralesional steroid. J Cutan Laser Ther 2000; 2: 147-150. DOI:

Chan HH, Wong DSY, Ho WS, Lam LK, Wei W. The use of pulsed dye laser for the prevention and treatment of hypertrophic scars in Chinese persons. Dermatol Surg 2004; 30: 987-994. DOI:

Fowler E, Yosipovitch G. Chronic itch management: therapies beyond those targeting the immune system. Ann Allergy Asthma Immunol 2019; 123: 158-165. DOI:

Zheng L, Bing Z, Wei L, Qiang W. [Clinical effects of gabapentin on the treatment of pruritus of scar resulting from deep partial-thickness burn]. Zhonghua Shao Shang Za Zhi 2015; 31: 177-180 (in Chinese).

Jaller JA, Yosipovitch G. Successful treatment of epidermal nevus-associated pruritus with topical ketamine-amitriptyline-lidocaine. Acta Derm Venereol 2018; 98: 121-122. DOI:

Lee HG, Grossman SK, Valdes-Rodriguez R, Berenato F, Korbutov J, Chan YH, et al. Topical ketamine-amitriptyline-lidocaine for chronic pruritus: a retrospective study assessing efficacy and tolerability. J Am Acad Dermatol 2017; 76: 760-761. DOI:

Diaz A, Tan K, He H, Xu H, Cueto I, Pavel AB, et al. Keloid lesions show increased IL-4/IL-13 signaling and respond to Th2-targeting dupilumab therapy. J Eur Acad Dermatol Venereol 2020; 34: 161-164. DOI:

Lu Y-Y, Lu C-C, Yu W-W, Zhang L, Wang Q-R, Zhang C-L, et al. Keloid risk in patients with atopic dermatitis: a nationwide retrospective cohort study in Taiwan. BMJ open 2018; 8: 022865. DOI:

Willebrand M, Low A, Dyster-Aas J, Kildal M, Andersson G, Ekselius L, et al. Pruritus, personality traits and coping in long-term follow-up of burn-injured patients. Acta Derm Venereol 2004; 84: 375-380. DOI:

Schut C, Mollanazar NK, Kupfer J, Gieler U, Yosipovitch G. Psychological Interventions in the treatment of chronic itch. Acta Derm Venereol 2016; 96: 157-161. DOI:



How to Cite

Hawash, A. A., Ingrasci, G., Nouri, K., & Yosipovitch, G. (2021). Pruritus in Keloid Scars: Mechanisms and Treatments. Acta Dermato-Venereologica, 101(10), adv00582.