Cutaneous pathological scars are fibrotic lesions that grow continuously, invade the adjacent skin, and are erythematous, itchy, and painful. Their etiology remains unclear but may involve genetic, local mechanical, and systemic factors. Here, we will summarize the main systemic factors that shape cutaneous pathological scarring, especially keloid formation and aggravation. They include circulating cytokines, chemokines, growth factors, particular cell types, sex hormones, the systemic renin‐angiotensin system, and vitamin D, all of which directly shape the angiogenesis, inflammation, fibrosis, and remodeling in pathological scars. There are also several environmental factors that more indirectly influence pathological scar formation or progression, namely diet, smoking, psychological stress, and exercise. Notably, much of the evidence on these systemic factors focus on their effects on one pathological scar characteristic, namely their fibrosis. However, systemic factors probably also shape other pathological scar characteristics. We describe two new avenues of keloid research that may greatly improve our understanding of pathological scarring and the systemic factors that affect it. One is the multiple similarities between keloids and tumors; the other is the different stem‐cell populations in keloids. We expect this research will greatly aid the development of diagnostic biomarkers for cutaneous pathological scars and drugs/techniques/regimens that prevent, improve, or cure these scars.

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形成皮肤病理性瘢痕形成的系统因素

皮肤病理性瘢痕是纤维化病变，不断生长，侵入邻近皮肤，呈红斑、瘙痒、疼痛。它们的病因尚不清楚，但可能涉及遗传、局部机械和全身因素。在这里，我们将总结形成皮肤病理性瘢痕形成的主要全身因素，尤其是瘢痕疙瘩的形成和加重。它们包括循环细胞因子、趋化因子、生长因子、特定细胞类型、性激素、全身性肾素-血管紧张素系统和维生素 D，所有这些都直接影响病理性瘢痕的血管生成、炎症、纤维化和重塑。还有一些环境因素更间接地影响病理性疤痕的形成或进展，即饮食、吸烟、心理压力和运动。尤其，关于这些全身性因素的大部分证据都集中在它们对一种病理性瘢痕特征的影响上，即它们的纤维化。然而，全身因素也可能影响其他病理性瘢痕特征。我们描述了瘢痕疙瘩研究的两种新途径，它们可能会大大提高我们对病理性瘢痕形成及其影响的系统性因素的理解。一是瘢痕疙瘩与肿瘤的多重相似性；另一个是瘢痕疙瘩中不同的干细胞群。我们预计这项研究将极大地帮助开发皮肤病理性疤痕的诊断生物标志物以及预防、改善或治愈这些疤痕的药物/技术/方案。全身因素也可能塑造其他病理性瘢痕特征。我们描述了瘢痕疙瘩研究的两种新途径，它们可能会大大提高我们对病理性瘢痕形成及其影响的系统性因素的理解。一是瘢痕疙瘩与肿瘤的多重相似性；另一个是瘢痕疙瘩中不同的干细胞群。我们预计这项研究将极大地帮助开发皮肤病理性疤痕的诊断生物标志物以及预防、改善或治愈这些疤痕的药物/技术/方案。全身因素也可能塑造其他病理性瘢痕特征。我们描述了瘢痕疙瘩研究的两种新途径，它们可能会大大提高我们对病理性瘢痕形成及其影响的系统性因素的理解。一是瘢痕疙瘩与肿瘤的多重相似性；另一个是瘢痕疙瘩中不同的干细胞群。我们预计这项研究将极大地帮助开发皮肤病理性疤痕的诊断生物标志物以及预防、改善或治愈这些疤痕的药物/技术/方案。