Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease‐driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease‐modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment‐induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long‐term, therapy‐free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease‐driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long‐lasting disease remission, target disease‐driving mechanisms, reduce mast cell‐activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL‐4 and IL‐13. Future therapies could prevent CSU signs and symptoms, achieve long‐term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.

中文翻译：

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慢性自发性荨麻疹的疾病调整


慢性自发性荨麻疹 (CSU) 是一种使人衰弱的炎症性皮肤病，其特征是免疫细胞浸润。可用的治疗仅限于改善体征和症状。目前尚未满足开发针对肥大细胞激活上游疾病驱动途径的治疗方法的需求，以抑制或延缓 CSU 及相关合并症的进展。在这里，我们的目标是根据治疗干预和疾病缓解治疗 (DMT) 在 CSU 必须满足的标准来定义疾病缓解。我们将 CSU 的疾病缓解定义为治疗引起的潜在病理生理学的有利变化，从而改变病程，这在临床上是有益的且持久的。 DMT 必须满足以下标准：(1) 预防或延缓 CSU 的进展，(2) 诱导长期、无需治疗的临床缓解，即无需治疗即可持续消除 CSU 体征和症状，以及(3) 影响 CSU 的潜在机制，如对疾病驱动信号和/或生物标志物的影响所证明的那样。 CSU 中的 DMT 应减缓疾病进展，实现持久的疾病缓解，针对疾病驱动机制，减少肥大细胞激活 IgE 自身抗体，针对细胞因子谱极化，并使肠道微生物组和屏障正常化。在免疫系统水平上治疗 CSU 可以为 CSU 管理中的药物治疗提供有价值的替代方案。 CSU 中的特定 DMT 尚未开发，但其中一些显示出潜在的益处，例如布鲁顿酪氨酸激酶、IL-4 和 IL-13 的抑制剂。未来的疗法可以预防 CSU 的体征和症状，在停止治疗后实现长期临床获益，并预防相关的伴随疾病。