Systemic inflammatory and autoimmune diseases and myelodysplastic syndromes have been linked in individual patients and in larger case series for at least 25 years. These associations frequently include thyroid disease, neutrophilic dermatoses, polyarthritis, connective tissue diseases, vasculitis, and autoimmune cytopenias. Studies have found that autoimmune disease (or its therapy) is a risk factor for the development of myelodysplastic syndromes, but such syndromes might also be an instigator of autoimmune disease. Epidemiological studies examining disease risk in myelodysplastic syndromes with and without comorbid autoimmune illness have reached mixed conclusions. The pathophysiology of myelodysplastic syndromes is tightly linked to excessive inflammatory activity in the bone marrow microenvironment, which could promote systemic inflammatory and autoimmune diseases directly or by stimulation of the adaptive immune response. Alternatively, autoimmune diseases could promote clonal evolution and disordered bone marrow growth, promoting the development of myeloid malignancy. Additionally, therapy-related myeloid neoplasms—including myelodysplastic syndromes—have been diagnosed after treatment of autoimmune diseases with immunosuppressant therapies. These associations raise the following question: are myelodysplastic syndromes and systemic inflammatory and autoimmune diseases two sides of the same coin—that is, do they share an underlying disease state that can manifest as a myeloid neoplasm, an autoinflammatory illness, or both? VEXAS syndrome, which was first reported in 2020, is caused by a mutation that affects myeloid-restricted cells and manifests with both myelodysplasia and autoinflammation, and could give insight into this biological possibility. We note that systemic inflammatory and autoimmune diseases are often steroid-dependent; however, studies have also evaluated the roles of other immunomodulating therapies. In this Viewpoint, we critically appraise and review the literature on the epidemiology, pathophysiology, and management of systemic inflammatory and autoimmune diseases that are associated with myelodysplastic syndromes and related diseases.

至少 25 年以来，系统性炎症和自身免疫性疾病以及骨髓增生异常综合征在个体患者和更大的病例系列中一直存在关联。这些关联通常包括甲状腺疾病、中性粒细胞性皮肤病、多关节炎、结缔组织疾病、血管炎和自身免疫性血细胞减少症。研究发现，自身免疫性疾病（或其治疗）是发生骨髓增生异常综合征的危险因素，但此类综合征也可能是自身免疫性疾病的诱因。对伴有和不伴有自身免疫性疾病的骨髓增生异常综合征的疾病风险进行流行病学研究得出了不同的结论。骨髓增生异常综合征的病理生理学与骨髓微环境中过度的炎症活动密切相关，它可以直接或通过刺激适应性免疫反应来促进全身性炎症和自身免疫性疾病。或者，自身免疫性疾病可以促进克隆进化和骨髓生长紊乱，促进髓系恶性肿瘤的发展。此外，在使用免疫抑制剂治疗自身免疫性疾病后，已诊断出与治疗相关的骨髓肿瘤（包括骨髓增生异常综合征）。这些关联引发了以下问题：骨髓增生异常综合征和全身性炎症和自身免疫性疾病是同一枚硬币的两个方面吗？也就是说，它们是否具有共同的潜在疾病状态，可以表现为髓系肿瘤、自身炎症性疾病或两者兼而有之？2020 年首次报道的 VEXAS 综合征，是由影响骨髓限制性细胞的突变引起的，并表现为骨髓发育不良和自身炎症，并且可以深入了解这种生物学可能性。我们注意到全身性炎症和自身免疫性疾病通常依赖于类固醇。然而，研究还评估了其他免疫调节疗法的作用。在这个观点中，我们批判性地评估和回顾了与骨髓增生异常综合征和相关疾病相关的全身性炎症和自身免疫性疾病的流行病学、病理生理学和管理的文献。研究还评估了其他免疫调节疗法的作用。在这个观点中，我们批判性地评估和回顾了与骨髓增生异常综合征和相关疾病相关的全身性炎症和自身免疫性疾病的流行病学、病理生理学和管理的文献。研究还评估了其他免疫调节疗法的作用。在这个观点中，我们批判性地评估和回顾了与骨髓增生异常综合征和相关疾病相关的全身性炎症和自身免疫性疾病的流行病学、病理生理学和管理的文献。