Keloid treatment

• Keloids revisited: Current concepts in treatment and differential diagnosis
• New Anti-Fibrotic Strategies for Keloids: Insights From Single-Cell Multi-Omics
• Post-operative KEloids iRradiation (POKER): does the surgery/high-dose interventional radiotherapy association make a winning hand?
• Advances and future directions in keloid research: Pathogenesis, diagnosis and personalized treatment strategies
• Comparative Efficacy of Intralesional Triamcinolone Acetonide and 5-Fluorouracil for Keloid Scars: Retraction
• Comparative Efficacy of Intralesional Triamcinolone Acetonide and 5-Fluorouracil for Keloid Scars
• Identification of Hub Genes of Keloid Fibroblasts by Coexpression Network Analysis and Degree Algorithm
• The Efficacy of Local Flaps in the Treatment of Traumatic Scalp Defects

Keloid treatment remains a clinical challenge due to high recurrence rates and the variable response to therapy. The ideal treatment would not only remove or reduce the keloid but also minimize recurrence and improve the patient's quality of life.

- Intralesional Corticosteroids:

1. Mechanism: Reduce inflammation and fibroblast proliferation.
2. Usage: Often considered the first-line therapy.
3. Limitations: May require multiple injections and can lead to side effects like skin atrophy or hypopigmentation.

- Surgical Excision:

1. Approach: Removal of the keloid tissue.
2. Adjuvant Therapies: Surgery is usually combined with other treatments (e.g., corticosteroids or radiation) to reduce recurrence.
3. Challenges: High recurrence rates if used as a standalone therapy.

- Cryotherapy:

1. Mechanism: Freezes and destroys keloid tissue.
2. Combination: Often used in conjunction with other modalities.
3. Side Effects: Risk of pigmentation changes, especially in darker skin types.

- Radiation Therapy:

1. Usage: Post-excision radiation can help reduce the likelihood of recurrence.
2. Considerations: Long-term risks include potential radiation-induced malignancies, though these are rare.

### 2. Adjunctive Therapies

- Laser Therapy:

1. Types: Pulsed dye lasers and other fractional lasers.
2. Benefits: Can reduce redness and improve texture.
3. Limitations: May require multiple sessions, and not all patients respond equally.

- Silicone Gel Sheets and Pressure Therapy:

1. Mechanism: Help to flatten and soften keloids through hydration and pressure.
2. Usage: Often recommended as a low-risk adjunct after primary treatments.
3. Compliance: Success depends heavily on patient adherence.

- 5-Fluorouracil (5-FU):

1. Usage: Intralesional injections, sometimes combined with corticosteroids.
2. Rationale: Inhibits fibroblast proliferation.
3. Evidence: Shows promise but may need further studies to establish optimal protocols.

### 3. Emerging and Targeted Therapies

- Molecular and Cellular Targets: Recent research, including single-cell transcriptomics studies, has identified distinct fibroblast subpopulations involved in keloid formation. For instance, studies have shown that:

1. POSTN-positive (POSTN+) mesenchymal fibroblasts exhibit enhanced transforming growth factor β (TGF-β) signaling, which drives fibrosis.
2. IGFBP2-positive (IGFBP2+) fibroblasts appear to have anti-fibrotic properties and might limit excessive tissue repair.
3. Implications: Targeting these specific cell populations or their signaling pathways (such as TGF-β inhibitors) could provide more effective, personalized treatments that reduce recurrence.

- Other Investigative Approaches:

1. Gene Therapy and RNA Interference: Experimental strategies aimed at modulating gene expression involved in keloid pathogenesis.
2. Immunomodulators: Given the role of inflammation in keloid formation, therapies that modulate the immune response are also under investigation.

### 4. Challenges and Future Directions

- High Recurrence: Despite many available treatments, recurrence remains a major issue. Combining therapies (e.g., surgery with adjuvant radiation or corticosteroid injections) tends to yield better outcomes than monotherapy. - Patient-Specific Factors: Skin type, genetic predisposition, and the location of the keloid all influence treatment efficacy. - Research Needs:

1. Larger clinical studies to validate emerging therapies.
2. More detailed exploration of the molecular mechanisms driving keloid formation.
3. Development of biomarkers to predict treatment response and recurrence risk.

### Conclusion

Keloid treatment is multifaceted, often requiring a combination of surgical, pharmacological, and physical therapies. While traditional treatments remain the cornerstone, ongoing research into the molecular underpinnings of keloid formation—such as the role of distinct fibroblast populations—offers hope for more targeted and effective interventions in the future. Clinicians must balance efficacy with potential side effects and tailor treatment plans to each patient’s unique clinical presentation.

Despite various treatment options available, the treatment of keloids remains a major clinical challenge due to high recurrence rates and inconsistent therapeutic outcomes. By collecting three keloid tissues and three normal skin samples and utilizing single-cell RNA sequencing (scRNA-seq), Zhao et al. delved into the cellular heterogeneity and molecular mechanisms of keloids. The study identified multiple fibroblast subpopulations within keloid tissue. Enrichment and cell-cell communication analyses revealed that POSTN-positive mesenchymal fibroblasts (POSTN+ mesenchymal fibs) are more prevalent in keloids and exhibit higher transforming growth factor β (TGF-β) signaling activity, potentially playing a central role in excessive fibrosis. In contrast, IGFBP2-positive fibroblasts (IGFBP2+ fibs) are more abundant in normal skin, insensitive to TGF-β and Periostin signaling, and possess anti-fibrotic potential, possibly related to limited tissue repair and regenerative capacity. Trajectory analysis inferred the differentiation states and patterns of different fibroblast subpopulations. Additionally, they explored the heterogeneity of endothelial cells, finding an endothelial cell subpopulation (EC10) exhibiting mesenchymal activation characteristics, which may work with specific fibroblasts to promote abnormal angiogenesis and endothelial-to-mesenchymal transition processes. Spatial transcriptomics analysis has shown that the proportion of IGFBP2+ fibroblasts relatively increases in acne keloidalis after hormonal treatment, further demonstrating their value as potential therapeutic targets. Ultimately, they separated these two subpopulations using flow cytometry, highlighting their opposing roles in the secretion of the ECM. These findings provide new insights into the pathogenesis of keloids and lay the theoretical foundation for developing innovative anti-fibrotic treatment strategies ¹⁾.

Zhao et al. have provided a noteworthy contribution to the field of fibrosis and keloid research by leveraging cutting-edge single-cell technologies to dissect the cellular and molecular heterogeneity of keloid tissues. The identification of distinct fibroblast subpopulations with opposing roles in fibrosis is particularly promising for the development of targeted anti-fibrotic therapies. However, the study’s limitations—chiefly the small sample size and the need for further functional validation—underscore the importance of cautious interpretation of these findings. Future research that addresses these issues and explores the interplay between multiple cell types in a broader patient cohort will be crucial for translating these insights into effective clinical interventions.

Intralesional triamcinolone acetonide (TAC; a synthetic corticosteroid) and 5-fluorouracil (5-FU; a cytotoxic chemotherapy drug) are the medications most commonly used to treat keloid scars. We investigated the clinical efficacy of TAC compared with 5-FU. We included 40 patients in the study and divided them into two equal groups (n = 20 Group A; n = 20 Group B). Group A patients received 4 mg/cm2 or 0.1 ml/cm2 of intralesional TAC (40 mg/ml) at 3-week intervals. Group B patients received 10 mg/cm2 or 0.2 ml/cm2 of intralesional 5-FU (50 mg/ml) at 3-week intervals. We assessed the scar using the Vancouver Scar Scale (VSS), visual analog scale (VAS), and patient satisfaction score (PSS). We found that Group A patients had a lower VAS than Group B patients (2.09 vs. 3.18). We saw a reduction in the VSS in both treatment arms; however, we found that Group B patients had a more marked reduction in the VSS compared with Group A patients (2.57 vs. 2.68). The PSS was higher in Group A than in Group B (1.97 vs. 1.78). We concluded that intralesional 5-FU elicits a better response than intralesional TAC. Although 5-FU is less well tolerated and has more side effects than TAC, we found that 5-FU was more effective in resolving keloid scars. Notably, the PSS was higher in the TAC group, but the VSS and VAS were better in Group B ²⁾.