Scleroderma (systemic sclerosis, SSc) is an autoimmune fibrosing connective tissue disease of unknown etiology. SSc patients show increased levels of autoantibodies, profibrotic cytokines, and extracellular matrix remodeling enzymes that collectively cause activated (myo)fibroblasts, the effector cell type of fibrosis. Despite these impacts, no disease-modifying therapy exists; individual symptoms are treated on a patient-to-patient basis. SSc research has been principally focused on symptoms observed in the lung and skin. However, SSc patients display significant oral complications that arise due to fibrosis of the not only skin, causing microstomia, but also the gastrointestinal tract, causing acid reflux, and the oral cavity itself, causing xerostomia and gingival recession. Due to these complications, SSc patients have impaired quality of life, including periodontitis, tooth loss, reduced tongue mobility, and malnutrition. Indeed, due to their characteristic oral presentation, SSc patients are often initially diagnosed by dentists. Despite their clinical importance, the oral complications of SSc are severely understudied; high-quality publications on this topic are scant. However, SSc patients with periodontal complications possess increased levels of matrix metalloproteinase-9 and chemokines, such as interleukin-6 and chemokine (C-X-C motif) ligand-4. Although many unsuccessful clinical trials, mainly exploring the antifibrotic effects of anti-inflammatory agents, have been conducted in SSc, none have used oral symptoms, which may be more amenable to anti-inflammatory drugs, as clinical end points. This review summarizes the current state of knowledge regarding oral complications in SSc with the goal of inspiring future research in this extremely important and underinvestigated area.

中文翻译：

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结缔组织病系统性硬化症的口面部并发症


硬皮病（系统性硬化症，SSc）是一种病因不明的自身免疫性纤维化结缔组织疾病。 SSc 患者的自身抗体、促纤维化细胞因子和细胞外基质重塑酶水平升高，这些酶共同导致激活的（肌）成纤维细胞（纤维化的效应细胞类型）。尽管存在这些影响，但尚不存在缓解疾病的疗法；个别症状根据患者情况进行治疗。 SSc 研究主要集中在肺部和皮肤中观察到的症状。然而，SSc 患者表现出明显的口腔并发症，这些并发症不仅是由于皮肤纤维化引起的小口，而且是胃肠道纤维化引起的胃酸反流，以及口腔本身的纤维化引起的口腔干燥和牙龈退缩。由于这些并发症，SSc 患者的生活质量受损，包括牙周炎、牙齿脱落、舌头活动能力下降和营养不良。事实上，由于其独特的口腔表现，SSc 患者通常最初是由牙医诊断的。尽管 SSc 的口腔并发症具有临床重要性，但对其的研究却严重不足。关于这一主题的高质量出版物很少。然而，患有牙周并发症的 SSc 患者的基质金属蛋白酶 9 和趋化因子（例如白细胞介素 6 和趋化因子（CXC 基序）配体 4）水平升高。尽管在 SSc 中进行了许多不成功的临床试验，主要探讨抗炎药物的抗纤维化作用，但没有一项使用口腔症状作为临床终点，而口腔症状可能更适合抗炎药物。 本综述总结了有关 SSc 口腔并发症的当前知识状况，旨在启发这一极其重要且研究不足的领域的未来研究。