Multifactorial: genetic predisposition + stimulus (trauma, surgery, piercings, acne, burns, inflammation) + topographic factors (areas of tension) → dysregulated scarring. Limandjaja 2020 , Chike-Obi 2009 , Kim 2021

Genetics: There is evidence of susceptibility loci (linkage and GWAS), supporting a hereditary/predisposing phenotype in subgroups. Marneros 2004 , Nakashima 2010

Mechanobiology: Skin tension and mechanical signaling promote profibrotic pathways (conceptually relevant in terms of prevention, surgical closure, and offloading). Feng 2022

• scar plaque/nodule firm, raised, shiny; pink/erythematous or even hyperpigmented; may be painful or itchy. Kim Xnumx

• More frequent in areas of tension: sternal region, deltoid/shoulders, upper back; also earlobe (piercings). Kim Xnumx, Chike-Obi 2009

• History of injury + progressive growth that overflows borders of the original wound, with symptoms (itching/pain) and a high tendency to recur after incomplete treatments. Kim Xnumx, Andrews 2016

• “Active edge”: the perimeter It may be the most proliferative area (useful for deciding biopsy site or for intralesional therapies). Limandjaja 2020

• They tend to persist and grow slowly; there may be spontaneous regression in a minority (in some series). Smith 2014

• "Flat" phenotypes (spreading/flat) vs "high" (bulging/raised), and intra-lesion heterogeneity (center vs periphery). Limandjaja 2020

Hypertrophic scar : raised, but confined to the wound area; with a greater tendency to flatten over time. Andrews 2016 , Kim 2021

Post-inflammatory fibrous dermatoses/nodules (e.g., sequelae of acne/folliculitis): These typically follow the follicle pattern and do not show claw-like overgrowth beyond the wound margin. Chike-Obi 2009

Cutaneous fibrous tumors (if atypical growth/ulceration is present): consider biopsy to rule out other entities. Kim 2021

• Reticular dermis with exuberant fibrosis (fibroproliferative lesion), with variation by depth and by areas of activity. Andrews 2016, Jiao 2017

• Bundles/bands of thick, densely packed collagen (“cheloidal collagen”) with areas of different cellularity; the overlying epidermis may also show changes. Limandjaja 2020, Andrews 2016

• Masson's Trichrome: highlights collagen and fibrotic architecture (useful for documentation). Andrews 2016
• Stains for elastin (e.g., Verhoeff–Van Gieson type): can support the analysis of dermal remodeling (depending on diagnostic doubt). Limandjaja 2020
• α-SMA (myofibroblasts): has been proposed in the differential diagnosis with hypertrophic scar, but there are conflicting results and it is not a “single proof”. Limandjaja 2020

• They are not routine for diagnosis; genetics is more for research/risk stratification. Nakashima 2010, Marneros 2004

• Type of biopsy
  • If the diagnosis is uncertain or there are atypical findings: deep punch o incisional that includes reticular dermis (and, if a deep lesion is suspected, extend the biopsy to include it). Kim Xnumx, Chike-Obi 2009
• Technical considerations
  • Prefer to sample the active edge when looking for correlation with activity/proliferation. Limandjaja 2020
  • Avoid taking samples immediately after recent infiltrations if this may distort inflammation/necrosis caused by drugs (practical tip: document previous treatments). Walsh 2023
• Contraindications
  • The usual ones for any biopsy (uncorrected coagulopathy, uncontrolled local infection, etc.); individualize. Kim Xnumx
• Fixing and shipping
  • Formalin 10% for standard histopathology; label with anatomical site, evolution time and previous therapies. Chike-Obi 2009

• Silicones (gel or sheets)
  • Useful for improving symptoms/recurrence and as an adjunct; recommended in practical guidelines. Meaume 2014, Walsh 2023
  • Specific systematic evidence in keloid: variable; in general they are considered a reasonable non-invasive option, especially combined. Tian 2023
• Intralesional corticosteroid (eg, triamcinolone)
  • Considered an initial pillar (reduces inflammation/fibroproliferation; improves itching/pain and volume). Kim Xnumx, Walsh 2023
• Compression / Pressure (especially in earlobes and selected scars)
  • It is used as an adjunct to reduce recurrence, although the quality of evidence varies by indication/device. Kim Xnumx, Walsh 2023

• Combined infiltration with antimetabolites
  • Triamcinolone + 5-fluorouracil (5-FU): RCTs show clinical efficacy and support its use when the response to steroids is partial. Darougheh 2009, Hietanen 2019
• Intralesional bleomycin
  • An effective alternative in some scenarios (including pigmented skin), with evidence from controlled trials. Payapvipapong 2015, Walsh 2023
• Cryotherapy (especially intralesional) ± infiltrations
  • Useful in selected injuries; frequently combined with steroids to improve results and reduce recurrence. Kim Xnumx, Walsh 2023
• Laser as an adjunct (e.g., to facilitate penetration/optimize texture and erythema)
  • It is usually indicated as part of a combination (laser + topical/occlusive or intralesional steroid). Walsh 2023
• Surgery (excision) + adjuvant therapy (key to preventing recurrence)
  • La single split It has high recurrence; the best-supported strategy is split + early adjuvant radiotherapy in recalcitrant/bulky keloids. Walsh 2023, Hsieh 2021, foot 2023
  • Timing: “Immediate” radiotherapy (typically within the first 24–72 h) is associated with lower recurrence in timing meta-analyses. Hsieh 2021
  • Dose/energy: In electron radiotherapy, the biologically effective dose It has been associated with recurrence (useful for discussing plans with radiation oncology). Hwang 2022

• Before infiltrating: Document phototype, personal tendency to keloids, previous treatments, and realistic expectations (control > “cure”). Kim Xnumx
• Common adverse effects
  • Intralesional corticosteroid: skin atrophy, telangiectasias, hypopigmentation, local pain. Kim Xnumx
  • 5-FU/intralesional bleomycin: pain, local ulceration/superficial necrosis (depending on technique and dose). Hietanen 2019, Payapvipapong 2015
  • Radiotherapy: hyperpigmentation, textural changes, theoretical long-term risk (individualized discussion). Walsh 2023, Hwang 2022

• Pregnancy/breastfeeding and certain intralesional therapies (e.g., antimetabolites): individualize and prefer non-invasive measures or defer. Kim Xnumx
• Radiotherapy: special caution in minors and in locations where the risk/benefit balance is not favorable; discuss in committee according to case. Walsh 2023

Persistent ulceration , bleeding, very rapid growth , or morphology that does not correspond to a scar (especially if there is no clear history of injury). Kim 2021

Repeated recurrence despite standard combinations → consider a multimodal approach (e.g., surgery + radiotherapy) and review of mechanical factors (tension). Walsh 2023 , Feng 2022

Key fact: A keloid scar, by definition, extends beyond the edge of the original wound (the most distinguishing feature compared to hypertrophic scars). Kim 2021

Heterogeneity: the periphery may be more active (useful for targeted infiltration/biopsy). Limandjaja 2020

• Comprehensive review of clinical and histopathological heterogeneity, mechanisms (immunity, cells, matrix) and experimental models; very useful for understanding why studies and therapeutic responses are variable.

Andrews JP, Marttala J, Macarak E, Rosenbloom J, Uitto J. Keloids: The paradigm of skin fibrosis – Pathomechanisms and treatment. Matrix Biol. 2016;51:37-46. DOI: 10.1016/j.matbio.2016.01.013. PMID: 26844756. PubMed

• Mechanistic review focused on cutaneous fibrosis: profibrotic cytokines, ECM, inflammation and therapeutic rationale; includes clinicopathological correlation.

Chike-Obi CJ, Cole PD, Brissett AE. Keloids: pathogenesis, clinical features, and management. Semin Plast Surg. 2009;23(3):178-184. DOI: 10.1055/s-0029-1224797. PMID: 20676312. PubMed

• Classical, practical and surgical review: clinical, pathophysiology and therapeutic overview; useful as a general framework and for integration with reconstructive surgery.

Feng F, et al. Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis. Front Pharmacol. 2022;13:906212. DOI: 10.3389/fphar.2022.906212. PMID: 35614943. PubMed

• Review on mechanotransduction and skin tension: integrates mechanical signaling, profibrotic pathways and therapeutic targets; key for prevention and surgical planning.

Jiao H, et al. The Superficial Dermis May Initiate Keloid Formation: Histological Analysis of the Keloid Dermis at Different Depths. Front Physiol. 2017;8:885. DOI: 10.3389/fphys.2017.00885. PMID: 29163221. PubMed

• Histological study by depth that supports heterogeneity in superficial vs deep dermis; provides a basis for understanding “active zones” and biopsy variability.

Nakashima M, et al. A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population. Nat Genet. 2010;42(9):768-771. DOI: 10.1038/ng.645. PMID: 20711176. PubMed

• Multicenter GWAS in Japanese population identifies susceptibility loci; strengthens genetic basis and opens doors to biological stratification.

Marneros AG, Norris JEC, Watanabe S, Reichenberger E, Olsen BR. Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23 and 7p11. J Invest Dermatol. 2004;122(5):1126-1132. DOI: 10.1111/j.0022-202X.2004.22327.x. PMID: 15140214. PubMed

• Family linkage (two families) with evidence of genetic heterogeneity; a foundational piece for understanding hereditary susceptibility.

Liu AH, et al. Epidemiological and clinical features of hypertrophic scar and keloid in Chinese college students: a cross-sectional study. 2023. DOI: 10.1016/j.jas.2022.11.004. PMID: 37123979. PubMed

• Cross-sectional study in university population that provides contemporary epidemiological data and an example of ICD-11 coding in research.

Swenson A, Paulus JK, Jung Y, et al. Natural History of Keloids: A Sociodemographic Analysis Using Structured and Unstructured Data. Dermatol Ther (Heidelb). 2024;14(1):131-149. DOI: 10.1007/s13555-023-01070-3. PMID: 38066233. PubMed

• Large retrospective cohort (real data) describing characteristics, severity, and sociodemographic patterns; useful for understanding population burden.

Walsh LA, Wu E, Pontes D, et al. Keloid treatments: an evidence-based systematic review of recent advances. Syst Rev 2023;12(1):42. DOI: 10.1186/s13643-023-02192-7. PMID: 36918908. PubMed

• Systematic review focused on prospective studies (2010–2020); synthesizes comparative evidence and supports the use of combinations (silicone + steroid; surgery + RT, etc.).

Kim SW. Management of keloid scars: noninvasive and invasive treatments. Arch Plast Surg. 2021;48(2):149-157. DOI: 10.5999/aps.2020.01914. PMID: 33765731. PubMed

• Clear clinical-surgical review: non-invasive and invasive therapies, practical considerations and stepwise approach; very useful for daily decision making.

Meaume S, Le Pillouer-Prost A, Richert B, Roseeuw D, Vadoud J. Management of scars: updated practical guidelines and use of silicones. Eur J Dermatol. 2014;24(4):435-443. DOI: 10.1684/ejd.2014.2356. PMID: 25141160. PubMed

• Updated practical guide focusing on silicones and scar management; useful for protocols and patient education.

Tian F, et al. Silicone gel sheeting for treating keloid scars. Cochrane Database Syst Rev. 2023;1(1):CD013878. DOI: 10.1002/14651858.CD013878.pub2. PMID: 36594476. PubMed

• Cochrane review on silicone sheets for keloids; analyzes quality of evidence and limits strong conclusions, but guides prudent use as an adjunct.

Hietanen KE, Järvinen TAJ, Huhtala H, et al. Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections – a randomized controlled trial. J Plast Reconstr Aesthet Surg. 2019;72(1):4-11. DOI: 10.1016/j.bjps.2018.05.052. PMID: 30448246. PubMed

• Randomized trial evaluating infiltrations (combination/strategy) and clinical outcomes; basis for escalating therapy in refractory patients.

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(2):219-223. DOI: 10.1111/j.1365-2230.2007.02631.x. PMID: 19018794. PubMed

• RCT comparing triamcinolone alone vs combination with 5-FU; supports combination in selected pathological scars.

Payapvipapong K, Niumpradit N, Piriyanand C, et al. The treatment of keloids and hypertrophic scars with intralesional bleomycin in skin of color. J Cosmet Dermatol. 2015;14(1):83-90. DOI: 10.1111/jocd.12132. PMID: 25626920. PubMed

• Controlled trial in pigmented skin; evidence for intralesional bleomycin as an alternative/adjuvant with relevant clinical results.

Hsieh CL, Chi KY, Lin WY, Lee LT-J. Timing of Adjuvant Radiotherapy After Keloid Excision: A Systematic Review and Meta-Analysis. Dermatol Surg. 2021;47(11):1438-1443. DOI: 10.1097/DSS.0000000000003165. PMID: 34417379. PubMed

• Meta-analysis on radiotherapy time after excision; useful for surgical-oncological coordination and for reducing recurrence.

Fu S, et al. Comparison of surgical excision followed by adjuvant radiotherapy and laser combined with intralesional steroids for the treatment of keloids: a meta-analysis. 2023. DOI: 10.1111/iwj.14449. PMID: 37967571. PubMed

• Comparative meta-analysis between combined strategies (surgery+RT vs laser+steroids); guides therapeutic choice according to severity/recurrence.

Hwang NH, Chang JH, Lee NK, Yang KS. Effect of the biologically effective dose of electron beam radiation therapy on recurrence rate after keloid excision: A meta-analysis. Radiother Oncol. 2022;173:146-153. DOI: 10.1016/j.radonc.2022.06.003. PMID: 35688397. PubMed

• Meta-analysis relating electron BED and recurrence; useful for planning schemes and discussing risk/benefit.

Smith OJ, McGrouther DA. The natural history and spontaneous resolution of keloid scars. J Plast Reconstr Aesthet Surg. 2014;67(1):87-92. DOI: 10.1016/j.bjps.2013.10.014. PMID: 24184068. PubMed

• Describes natural history and cases of spontaneous resolution; helps to advise on expectations and individualize therapeutic aggressiveness.