Pruritus in Keloid Scars: Mechanisms and Treatments

Hawash, Ahmed; Ingrasci, Giuseppe; Nouri, Keyvan; Yosipovitch, Gil

doi:10.2340/00015555-3923

Cited by 50 publications

(45 citation statements)

References 72 publications

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“…Keloid is a common dermatofibrotic disease with main characteristics of excessive skin fibroblast proliferation and extracellular matrix accumulation [ 1 ]. Keloid is usually regarded as a benign skin tumor according to clinical manifestation, gene phenotype, pathological features, and prognosis [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Suppresses Skin Fibroblast Proliferation via Oxidative Stress Alleviation and Necroptosis Inhibition

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Keloid is a common dermatofibrotic disease with excessive skin fibroblast proliferation. Hydrogen sulfide (H2S) as the third gasotransmitter improves fibrosis of various organs and tissues. Our study is aimed at investigating the effects and possible mechanisms of H2S on skin fibroblast proliferation. Scar tissues from six patients with keloid and discarded skin tissue from six normal control patients were collected after surgery, respectively. Plasma H2S content and skin H2S production in patients with keloid were measured. Keloid fibroblasts and transforming growth factor-β1- (TGF-β1, 10 ng/mL) stimulated normal skin fibroblasts were pretreated with H2S donor as NaHS (50 μM) for 4 h. Cell migration after scratch was assessed. The expressions of α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), collagen I, and collagen III were detected by immunofluorescence, real-time PCR, and/or Western blot. Intracellular superoxide anion and mitochondrial superoxide were evaluated by dihydroethidium (DHE) and MitoSOX staining, respectively. Mitochondrial membrane potential was detected by JC-1 staining. Apoptotic cells were detected by TDT-mediated dUTP nick end labeling (TUNEL). The expressions of receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) were measured by Western blot. We found that H2S production was impaired in both the plasma and skin of patients with keloid. In keloid fibroblasts and TGF-β1-stimulated normal skin fibroblasts, exogenous H2S supplementation suppressed the expressions of α-SMA, PCNA, collagen I, and collagen III, reduced intracellular superoxide anion and mitochondrial superoxide, improved the mitochondrial membrane potential, decreased the positive rate of TUNEL staining, and inhibited RIPK1 and RIPK3 expression as well as MLKL phosphorylation. Overall, H2S suppressed skin fibroblast proliferation via oxidative stress alleviation and necroptosis inhibition.

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Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Suppresses Skin Fibroblast Proliferation via Oxidative Stress Alleviation and Necroptosis Inhibition

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“… 12 Corticosteroids are the traditional treatment of keloids, which can effectively improve the flexibility of the tissue, reduce its thickness, relieve pruritus and pain in patients. 13 The most commonly used corticosteroid is triamcinolone acetonide, with an efficiency of 50–100% in different studies. 6 However, after long-term observation, it has been found that the recurrence rate of corticosteroids is up to 50%, and 63% of the patients have local side effects, including skin atrophy, hypopigmentation and telangiectasia.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Combination Therapy Involving Excision Followed by Intralesional 5-Fluorouracil and Betamethasone, and Radiotherapy in the Treatment of Keloids: A Randomized Controlled Trial

Zhang

Hang

et al. 2022

CCID

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Background Combined therapy for keloids is currently recommended. Surgery is one of the main options, but the measures to prevent recurrence after excision are still being explored. Objective The randomized controlled study aimed at evaluating the efficacy of excision followed by intralesional low concentrations of 5-fluorouracil (5-FU)(12.5 mg/mL) and betamethasone. Methods Sixty patients were randomly assigned to three groups. Patients in group A had excision followed by 5-FU and betamethasone intralesional injections, group B had 5-FU and betamethasone intralesional injections, and group C had excision followed by radiotherapy. Efficacy parameters were assessed from 8 to 12 months, including improvement on the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Scale (POSAS), as well as side effects and recurrence. Trial registration number: ChiCTR2100046025. Results After 4 months’ treatment, the improvement of the VSS and POSAS scores in group A was not different from that in group C ( P > 0.05) but was superior to that in group B ( P < 0.05); the pain and pruritus of the three groups were relieved more than 50%. After 8 to 12 months’ follow-up, there was no statistical difference in the incidence of side effects and recurrence among the groups ( P > 0.05). Conclusion Excision followed by intralesional low concentrations of 5-FU (12.5mg/mL) with betamethasone is a safe and sustainable treatment for keloid, with no significant difference from excision followed by radiotherapy.

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“…Psychotherapy for really itchy keloids is another factor for future therapy. Although there is no evidence supporting the use of psychological psychotherapy to treat keloid-associated pruritus, there is evidence connecting personality characteristics and coping techniques to the persistence of pruritus in post-burn patients [100]. Moreover, there are a lot of pathways, cytokines, and growth factors that are found to be upregulated or downregulated in keloids compared to normal tissues.…”

Section: Discussionmentioning

confidence: 99%

Keloids: A Review of the Diseases, Causes, and Current Treatments

Anirudh¹,

Gomathi²,

Sujatha³

et al. 2022

JPRI

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Keloids are benign tumors that grow as a result of excessive collagen release from overexpressed fibroblasts. Keloids and hypertrophic scars are distinguished by the fact that keloids develop beyond the site of the original lesion, but hypertrophic scars do not. It is still unclear why this mechanism operates, mainly when aberrant scarring occurs. Despite several treatments' availability, the keloids' recurrence rate remains high. Here, we summarize recent narrative reviews, systematic reviews, and meta-analyses to give a general overview of the condition, its underlying causes, and available therapies for keloids. To undertake a comprehensive investigation of the disease, over 100 publications were reviewed utilizing Google Scholar and Pubmed. We also shed light on using phytochemicals as a natural alternative to prevent keloid scarring, which occurs when the body responds abnormally to external injuries by producing scar tissue. We also summarize the available current treatments.

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Pruritus in Keloid Scars: Mechanisms and Treatments

Cited by 50 publications

References 72 publications

Hydrogen Sulfide Suppresses Skin Fibroblast Proliferation via Oxidative Stress Alleviation and Necroptosis Inhibition

Hydrogen Sulfide Suppresses Skin Fibroblast Proliferation via Oxidative Stress Alleviation and Necroptosis Inhibition

The Efficacy of Combination Therapy Involving Excision Followed by Intralesional 5-Fluorouracil and Betamethasone, and Radiotherapy in the Treatment of Keloids: A Randomized Controlled Trial

Keloids: A Review of the Diseases, Causes, and Current Treatments

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