Pruritus in Keloid Scars: Mechanisms and Treatments

Authors

  • 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

DOI:

https://doi.org/10.2340/00015555-3923

Keywords:

keloid, pruritus, therapeutics, neuropathy

Abstract

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.

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References

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.

https://doi.org/10.1016/j.jaad.2004.07.054 DOI: https://doi.org/10.1016/j.jaad.2004.07.054

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.

https://doi.org/10.1111/ijd.14610 DOI: https://doi.org/10.1111/ijd.14610

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.

https://doi.org/10.4081/dr.2020.8312 DOI: https://doi.org/10.4081/dr.2020.8312

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.

https://doi.org/10.2340/00015555-2498 DOI: https://doi.org/10.2340/00015555-2498

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

https://doi.org/10.1016/S0733-8635(18)30653-3 DOI: https://doi.org/10.1016/S0733-8635(18)30653-3

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.

https://doi.org/10.1111/j.1365-2133.2012.11190.x DOI: https://doi.org/10.1111/j.1365-2133.2012.11190.x

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

https://doi.org/10.3390/ijms18030606 DOI: https://doi.org/10.3390/ijms18030606

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

https://doi.org/10.1089/wound.2013.0457 DOI: https://doi.org/10.1089/wound.2013.0457

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.

https://doi.org/10.1097/00004630-198703000-00008 DOI: https://doi.org/10.1097/00004630-198703000-00008

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.

https://doi.org/10.1016/S1359-6101(03)00047-9 DOI: https://doi.org/10.1016/S1359-6101(03)00047-9

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.

https://doi.org/10.1016/j.yexcr.2017.12.011

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

https://doi.org/10.3389/fimmu.2014.00614 DOI: https://doi.org/10.3389/fimmu.2014.00614

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.

https://doi.org/10.1016/j.yexcr.2017.12.011 DOI: https://doi.org/10.1016/j.yexcr.2017.12.011

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.

https://doi.org/10.4049/jimmunol.172.3.1848 DOI: https://doi.org/10.4049/jimmunol.172.3.1848

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.

https://doi.org/10.1097/CM9.0000000000000949 DOI: https://doi.org/10.1097/CM9.0000000000000949

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.

https://doi.org/10.2340/00015555-3702 DOI: https://doi.org/10.2340/00015555-3702

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.

https://doi.org/10.3389/fimmu.2020.597741 DOI: https://doi.org/10.3389/fimmu.2020.597741

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

https://doi.org/10.1111/bjd.16173 DOI: https://doi.org/10.1111/bjd.16173

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.

https://doi.org/10.1080/2000656X.2019.1612752 DOI: https://doi.org/10.1080/2000656X.2019.1612752

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.

https://doi.org/10.1111/j.1365-2133.2007.08401.x DOI: https://doi.org/10.1111/j.1365-2133.2007.08401.x

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.

https://doi.org/10.2340/00015555-1336 DOI: https://doi.org/10.2340/00015555-1336

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.

https://doi.org/10.1016/S0022-4804(03)00188-4 DOI: https://doi.org/10.1016/S0022-4804(03)00188-4

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.

https://doi.org/10.1016/0091-6749(88)90971-2 DOI: https://doi.org/10.1016/0091-6749(88)90971-2

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

https://doi.org/10.1046/j.1523-1747.2003.12428.x DOI: https://doi.org/10.1046/j.1523-1747.2003.12428.x

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.

https://doi.org/10.1111/j.1524-475X.2010.00589.x DOI: https://doi.org/10.1111/j.1524-475X.2010.00589.x

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.

https://doi.org/10.1016/j.ajpath.2015.02.011 DOI: https://doi.org/10.1016/j.ajpath.2015.02.011

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.

https://doi.org/10.1111/j.1365-2133.2008.08449.x DOI: https://doi.org/10.1111/j.1365-2133.2008.08449.x

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.

https://doi.org/10.1097/BCR.0b013e3182223c32 DOI: https://doi.org/10.1097/BCR.0b013e3182223c32

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.

https://doi.org/10.1007/s00403-019-01972-3 DOI: https://doi.org/10.1007/s00403-019-01972-3

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.

https://doi.org/10.1016/j.immuni.2020.06.023 DOI: https://doi.org/10.1016/j.immuni.2020.06.023

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

https://doi.org/10.1111/ijd.15159 DOI: https://doi.org/10.1111/ijd.15159

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.

https://doi.org/10.2147/CCID.S133672 DOI: https://doi.org/10.2147/CCID.S133672

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.

https://doi.org/10.1016/j.clim.2015.02.014 DOI: https://doi.org/10.1016/j.clim.2015.02.014

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.

https://doi.org/10.1093/rheumatology/keaa195 DOI: https://doi.org/10.1093/rheumatology/keaa195

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.

https://doi.org/10.1111/exd.14279 DOI: https://doi.org/10.1111/exd.14279

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.

https://doi.org/10.1016/j.jaci.2015.12.1323 DOI: https://doi.org/10.1016/j.jaci.2015.12.1323

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.

https://doi.org/10.1111/j.1365-2230.2007.02631.x DOI: https://doi.org/10.1111/j.1365-2230.2007.02631.x

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.

https://doi.org/10.1111/jocd.12690 DOI: https://doi.org/10.1111/jocd.12690

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.

https://doi.org/10.1097/00006534-200208000-00031 DOI: https://doi.org/10.1097/00006534-200208000-00031

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

https://doi.org/10.1111/j.1524-4725.2007.34036.x DOI: https://doi.org/10.1111/j.1524-4725.2007.34036.x

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

https://doi.org/10.1007/s00266-007-9030-9 DOI: https://doi.org/10.1007/s00266-007-9030-9

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.

https://doi.org/10.1016/j.bjps.2008.03.022 DOI: https://doi.org/10.1016/j.bjps.2008.03.022

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.

https://doi.org/10.1080/09546630310016808 DOI: https://doi.org/10.1080/09546630310016808

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.

https://doi.org/10.1007/s00402-014-1942-7 DOI: https://doi.org/10.1007/s00402-014-1942-7

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.

https://doi.org/10.1007/s00266-011-9690-3 DOI: https://doi.org/10.1007/s00266-011-9690-3

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.

https://doi.org/10.1007/s00266-009-9423-z DOI: https://doi.org/10.1007/s00266-009-9423-z

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.

https://doi.org/10.3889/oamjms.2019.783 DOI: https://doi.org/10.3889/oamjms.2019.783

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.

https://doi.org/10.1016/j.pain.2010.02.024 DOI: https://doi.org/10.1016/j.pain.2010.02.024

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.

https://doi.org/10.1007/s00266-009-9334-z DOI: https://doi.org/10.1007/s00266-009-9334-z

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

https://doi.org/10.1159/000051830 DOI: https://doi.org/10.1159/000051830

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.

https://doi.org/10.1007/s00266-007-9109-3 DOI: https://doi.org/10.1007/s00266-007-9109-3

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.

https://doi.org/10.1097/GOX.0000000000000348 DOI: https://doi.org/10.1097/GOX.0000000000000348

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.

https://doi.org/10.1097/01.PRS.0000056868.42679.05 DOI: https://doi.org/10.1097/01.PRS.0000056868.42679.05

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.

https://doi.org/10.1046/j.1365-4362.2001.01117.x DOI: https://doi.org/10.1046/j.1365-4362.2001.01117.x

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.

https://doi.org/10.1038/bjc.1993.100 DOI: https://doi.org/10.1038/bjc.1993.100

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.

https://doi.org/10.1111/j.1473-2165.2008.00360.x DOI: https://doi.org/10.1111/j.1473-2165.2008.00360.x

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.

https://doi.org/10.1097/00042728-200101000-00007 DOI: https://doi.org/10.1097/00042728-200101000-00007

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.

https://doi.org/10.1002/lsm.22334 DOI: https://doi.org/10.1002/lsm.22334

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.

https://doi.org/10.1002/lsm.23363 DOI: https://doi.org/10.1002/lsm.23363

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

https://doi.org/10.1080/14628830050516407 DOI: https://doi.org/10.1080/14628830050516407

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.

https://doi.org/10.1111/j.1524-4725.2004.30303.x DOI: https://doi.org/10.1111/j.1524-4725.2004.30303.x

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

https://doi.org/10.1016/j.anai.2019.01.016 DOI: https://doi.org/10.1016/j.anai.2019.01.016

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.

https://doi.org/10.2340/00015555-2811 DOI: https://doi.org/10.2340/00015555-2811

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.

https://doi.org/10.1016/j.jaad.2016.10.030 DOI: https://doi.org/10.1016/j.jaad.2016.10.030

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.

https://doi.org/10.1111/jdv.16097 DOI: https://doi.org/10.1111/jdv.16097

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.

https://doi.org/10.1136/bmjopen-2018-022865 DOI: https://doi.org/10.1136/bmjopen-2018-022865

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.

https://doi.org/10.1080/00015550410032941 DOI: https://doi.org/10.1080/00015550410032941

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.

https://doi.org/10.2340/00015555-2177 DOI: https://doi.org/10.2340/00015555-2177

Published

2021-10-28

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. https://doi.org/10.2340/00015555-3923