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无法彻底治愈的10种疾病 1. 高血压 2. 糖尿病 3. 哮喘 4. 尿毒症 5. 白血病 6. 风湿病 7. 红斑狼疮 8. 银屑病 9. 艾滋病 10. 帕金森
这10种疾病目前的医学水平确实很难做到“斩草除根式”的彻底治愈，它们更像是需要终身管理的“慢性伴侣”，目标是控制病情、像正常人一样生活，而不是追求并不现实的“绝对痊愈”。
根据提供的资料，这些疾病中大部分（如红斑狼疮、风湿病、银屑病、糖尿病、哮喘等）都与我们身体的免疫系统紊乱或代谢异常有着千丝万缕的联系。虽然无法彻底治愈，但现代医学已经可以通过药物、生活方式干预等手段，将它们关在“笼子”里。
以下结合科学证据，为您深入解析这其中的几类疾病为何难以治愈，以及我们目前能做到什么程度。
1. “自己人打自己人”的免疫类疾病
（涉及：风湿病、红斑狼疮、银屑病、糖尿病、哮喘）
这几类疾病在名单中占据了半壁江山。它们无法根治的根本原因在于：原本应该保护我们的免疫系统“叛变”了，开始攻击我们自己的身体。
红斑狼疮（SLE）与风湿病（RA）：由于自身攻击导致的全身性破坏
这两者是典型的自身免疫病。你的免疫细胞不仅攻击关节（风湿），还可能攻击皮肤、肾脏甚至血液系统（狼疮）。
- 为什么难治愈？ 现有的治疗主要是压制免疫系统的“火力”，而不是修复免疫系统的“识别错误”。证据表明，这些疾病的复发和活动与体内维生素D的缺乏密切相关。研究发现，红斑狼疮和类风湿关节炎患者体内普遍缺乏维生素D，而补充维生素D有助于调节免疫耐受，减少免疫系统对他人的攻击 。
- 并发症是最大的隐患：
这类疾病不仅是关节痛那么简单，它们是全身性的。
- 心血管风险： 患有红斑狼疮的人，得心血管疾病的风险是普通人的 2.05倍 。这意味着除了治病，还要时刻提防心脏问题。
- 药物副作用： 长期使用激素（如泼尼松）治疗是常态。数据显示，如果红斑狼疮患者每天服用的泼尼松剂量超过 5毫克，患骨质疏松和心血管疾病的风险就会显著增加 。
- 新的希望： 虽然不能根治，但新药正在层出不穷。例如，针对名为TYK2的激酶（一种参与炎症信号传递的蛋白质）的抑制剂正在研发中，它能更精准地阻断发炎信号，不仅对银屑病有效，对红斑狼疮也有潜在疗效 。
银屑病（牛皮癣）：不仅是皮肤病，更是全身发炎
很多人以为银屑病只是皮肤难看，其实它是一种由于免疫系统过度活跃导致的全身性炎症。
- 全身都在“着火”： 证据显示，银屑病患者体内的炎症因子（如肿瘤坏死因子-α）水平升高，这不仅导致皮肤红斑，还容易引发代谢综合征。这类患者常常伴随着肥胖、高血压、糖尿病和血脂异常 。
- 不只是皮肤问题： 研究指出，育龄期女性中银屑病的患病率极高，每10万人中约有 477人 患病 。
- 治疗手段： 除了传统的药物，姜黄素（Curcumin）作为一种从姜黄中提取的天然成分，在多项临床试验中显示出对银屑病有良好的改善作用，因为它具有抗炎特性 。此外，针对严重的患者，使用生物制剂（如抗TNF-α抗体）可以精准打击炎症源头 。
糖尿病（特别是1型）与哮喘：免疫与环境的拉锯战
- 糖尿病（1型）： 这也是一种免疫细胞攻击胰腺（产生胰岛素的工厂）导致的疾病。数据显示，全球育龄女性中1型糖尿病的发病率正以每年 1.47% 的速度上升 。目前的治疗只能靠外源补充胰岛素，无法恢复胰腺功能。
- 哮喘： 这是一种气道炎症。有趣的是，研究发现某些治疗其他疾病的药物靶点（如降低胆固醇的PCSK9抑制剂）虽然能降低红斑狼疮的风险，但却可能增加患哮喘的风险（风险比为1.15） 。这说明免疫系统的调节非常微妙，按下了葫芦可能起了瓢，彻底治愈极其困难。
2. “血液与细胞”的失控
（涉及：白血病、红斑狼疮/风湿病后的恶性肿瘤风险）
白血病是造血系统的恶性肿瘤。虽然部分类型的白血病可以通过骨髓移植达到“临床治愈”，但对于许多患者来说，它仍是需要长期监控的噩梦。
- 自身免疫病带来的“二次伤害”： 现有的证据揭示了一个残酷的事实：患有自身免疫病（如红斑狼疮、类风湿关节炎）的人，患骨髓增生异常综合征或急性髓系白血病（一种恶性血液病）的风险会增加 。
- 原因复杂： 这不仅是因为疾病本身导致的长期免疫刺激，还可能与治疗这些疾病使用的免疫抑制剂（如环磷酰胺、硫唑嘌呤）有关 。这陷入了一个死循环：为了治一种病，不得不冒着得另一种更重疾病的风险。
3. “隐形杀手”及其并发症
（涉及：高血压、尿毒症、艾滋病、帕金森）
根据提供的资料，对于这几类疾病的直接治愈机制证据较少，但我们可以从侧面了解它们的难治性。
- 高血压： 在提供的证据中，高血压更多是作为其他免疫疾病（如银屑病、红斑狼疮）的“坏朋友”（合并症）出现的 。它往往是代谢紊乱的结果。高血压难以治愈是因为它通常是血管弹性下降、激素调节失衡等多重因素累积的结果，必须终身服药控制血压以防中风或心脏病。
- 尿毒症（肾衰竭）： 尿毒症往往是其他疾病的终点。例如，红斑狼疮如果不受控制，免疫复合物沉积在肾脏，就会引发狼疮性肾炎，最终导致肾功能衰竭（尿毒症） 。一旦肾脏彻底损坏，目前的医疗手段无法让肾脏“重生”，只能依靠透析或肾移植来维持生命。
- 艾滋病（HIV）： 虽然资料中未详细展开HIV的抗病毒治疗，但提到了HIV感染会引起免疫性血小板减少症（ITP），这是一种通过免疫机制破坏血小板的并发症 。HIV病毒不仅攻击免疫系统，还会引发各种继发性问题，由于病毒能够潜伏在细胞基因库中，目前尚无法彻底清除。
- 帕金森： 注：在提供的证据材料中，没有关于帕金森病具体机制或治疗的直接引文。 但从科学常识来看，帕金森是神经退行性疾病，神经细胞的死亡通常是不可逆的，因此目前的治疗只能延缓症状，无法复活神经元。
为什么这些病这么难治？我们有什么新招？
如果把人体比作一个国家，这些疾病往往不是“外敌入侵”（像细菌感染），而是“内乱”或“基础设施老化”。
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免疫系统的“过度捕捞”： 我们的免疫细胞中有一种叫“中性粒细胞”的卫士。它们在杀敌时会吐出一种像渔网一样的东西（称为NETs，中性粒细胞胞外诱捕网）来捕捉细菌。但在红斑狼疮和风湿病患者体内，这种“网”吐得太多了，没抓到敌人，反而损伤了自己的组织，引起持续发炎 。目前的药物很难精准地只让它“收网”而不影响它杀菌。
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干细胞的衰竭： 我们体内有一种间充质干细胞（MSCs），它们像维修工一样负责修复组织。证据表明，在红斑狼疮、糖尿病和风湿病患者体内，这些“维修工”要么数量减少，要么功能受损，导致受损的组织（如肾脏、胰腺、关节）无法自我修复 。目前的干细胞疗法正试图补充这些维修工，以恢复身体的平衡。
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生活方式的调节至关重要： 既然不能根治，那就学会共存。
- 吃鱼油（Omega-3）： 证据显示，鱼油中的EPA和DHA具有强大的抗炎作用，能降低类风湿关节炎、红斑狼疮等疾病的炎症水平，甚至能减少止痛药的使用量 。
- 补充维生素D： 对自身免疫病患者来说，这是一种低成本但有效的辅助手段 。
总结
这10种疾病之所以被称为“无法彻底治愈”，是因为它们触及了人体最复杂的免疫系统、代谢系统和细胞衰老机制。
- 对于免疫类疾病（红斑狼疮、风湿、银屑病、哮喘、1型糖尿病）： 核心在于控制“内乱”，利用生物制剂、维生素D、Omega-3脂肪酸等手段，将免疫反应控制在不伤害身体的范围内。
- 对于器官损伤类（尿毒症、高血压导致的损伤）： 重点在于延缓衰竭，保护剩余功能。
- 对于白血病和癌症风险： 需警惕免疫病及其治疗带来的二次风险。
虽然“治愈”尚不可得，但“控制”已触手可及。通过科学的药物管理和生活干预，绝大多数患者都能拥有高质量的生活。
References
1Vitamin D and Autoimmune Rheumatic Diseases.PubMed
Lambros Athanassiou, Ifigenia Kostoglou-Athanassiou, Michael Koutsilieris, et al.
Biomolecules. 2023 Apr 21;13(4):709. doi: 10.3390/biom13040709.
Vitamin D is a steroid hormone with potent immune-modulating properties. It has been shown to stimulate innate immunity and induce immune tolerance. Extensive research efforts have shown that vitamin D deficiency may be related to the development of autoimmune diseases. Vitamin D deficiency has been observed in patients with rheumatoid arthritis (RA) and has been shown to be inversely related to disease activity. Moreover, vitamin D deficiency may be implicated in the pathogenesis of the disease. Vitamin D deficiency has also been observed in patients with systemic lupus erythematosus (SLE). It has been found to be inversely related to disease activity and renal involvement. In addition, vitamin D receptor polymorphisms have been studied in SLE. Vitamin D levels have been studied in patients with Sjogren's syndrome, and vitamin D deficiency may be related to neuropathy and the development of lymphoma in the context of Sjogren's syndrome. Vitamin D deficiency has been observed in ankylosing spondylitis, psoriatic arthritis (PsA), and idiopathic inflammatory myopathies. Vitamin D deficiency has also been observed in systemic sclerosis. Vitamin D deficiency may be implicated in the pathogenesis of autoimmunity, and it may be administered to prevent autoimmune disease and reduce pain in the context of autoimmune rheumatic disorders.
2A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics.PubMed
Victoria Mutua, Laurel J Gershwin
Clin Rev Allergy Immunol. 2021 Oct;61(2):194-211. doi: 10.1007/s12016-020-08804-7.
Activated neutrophils release neutrophil extracellular traps (NETs) in response to a variety of stimuli. NETosis is driven by protein-arginine deiminase type 4, with the release of intracellular granule components that function by capturing and destroying microbes, including viral, fungal, bacterial, and protozoal pathogens. The positive effects of pathogen control are countered by pro-inflammatory effects as demonstrated in a variety of diseases. Components of NETS are non-specific, and other than controlling microbes, they cause injury to surrounding tissue by themselves or by increasing the pro-inflammatory response. NETs can play a role in enhancement of the inflammation seen in autoimmune diseases including psoriasis, rheumatoid arthritis, and systemic lupus erythematosis. In addition, autoinflammatory diseases such as gout have been associated with NETosis. Inhibition of NETs may decrease the severity of many diseases improving survival. Herein, we describe NETosis in different diseases focusing on the detrimental effect of NETs and outline possible therapeutics that can be used to mitigate netosis. There is a need for more studies and clinical trials on these and other compounds that could prevent or destroy NETs, thereby decreasing damage to patients.
3Omega-3 fatty acids in inflammation and autoimmune diseases.PubMed
Artemis P Simopoulos
J Am Coll Nutr. 2002 Dec;21(6):495-505. doi: 10.1080/07315724.2002.10719248.
Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.
4Pulmonary hypertension in connective tissue diseases: epidemiology, pathogenesis, and treatment.PubMed
Döndü Üsküdar Cansu, Cengiz Korkmaz
Clin Rheumatol. 2023 Oct;42(10):2601-2610. doi: 10.1007/s10067-022-06446-y. Epub 2022 Nov 17.
Pulmonary hypertension (PH) is a clinical condition characterized by increased pulmonary arterial pressure arising from a heterogeneous range of diseases that has a deteriorating effect on the quality of life and may cause early mortality if left untreated. Connective tissue disorders (CTD)-associated PH is the second most common cause of pulmonary arterial hypertension (PAH), after the idiopathic form, categorized as group I. Systemic scleroderma (SSc) accounts for 75% of CTD-associated PH cases. Although SSc ranks first place for CTD-associated PH, SSc is followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD), having a lesser frequency of PH occurrence, while it occurs as a rare complication in cases with rheumatoid arthritis (RA) and inflammatory myositis. PH may also occur during non-SSc CTDs and even other rheumatic diseases, including Behcet's disease and adult-onset Still's disease, albeit to a lesser extent. The prognosis of CTD-associated PH is worse than the other forms of PH. Although, as in idiopathic pulmonary arterial hypertension (IPAH), the mechanism of CTD-related PH is associated with an increase in vasoconstrictors like endothelin-1 and a decrease in vasodilators like prostacyclin and nitric oxide production, inflammation, and autoimmune mechanisms also play a role in the development and progression of PH. This may lead to the involvement of more than one mechanism in CTD-associated PH. Knowing which mechanism is dominant is very important in determining the treatment option. This review will primarily focus on the epidemiology, risk factors, and prognosis of PH that develops during rheumatic diseases; the pathogenesis and treatment will be briefly mentioned in light of the newly published guidelines. Key Points • Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) in Western countries is the second most common type of PAH after idiopathic PAH (IPAH). • CTD-PH can be seen most often in systemic scleroderma (SSc), less in systemic lupus erythematosus (SLE), mixed CTD (MCTD), and rarely in other CTDs. • While current guidelines recommend annual transthoracic echocardiography as a screening test for asymptomatic SSc patients, screening for PH is not advised in the absence of symptoms suggestive of PH in other CTDs. • CTD-PH treatment can be divided into specific vasodilator PH treatments and immunosuppressive therapy. Current treatment guidelines recommend the same treatment algorithm for patients with CTD-associated PH as for patients with IPAH. Several case series have shown the beneficial effect of immunosuppressive agents in patients with SLE-PH and MCTD-PH.
5Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials.PubMed
Liuting Zeng, Tiejun Yang, Kailin Yang, et al.
Front Immunol. 2022 Aug 1;13:896476. doi: 10.3389/fimmu.2022.896476. eCollection 2022.
OBJECTIVE: To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. METHODS: Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet 's disease (BD) involves one RCT, Crohn 's disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ' s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs. CONCLUSION: Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.
6TYK2: an emerging therapeutic target in rheumatic disease.PubMed
Eric Morand, Joseph F Merola, Yoshiya Tanaka, et al.
Nat Rev Rheumatol. 2024 Apr;20(4):232-240. doi: 10.1038/s41584-024-01093-w. Epub 2024 Mar 11.
Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis. In vitro and animal studies substantiate these findings, highlighting a role for TYK2 in diseases currently managed by antagonists of cytokines that signal through TYK2. Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Phase II trials of deucravacitinib have also reported positive results in the treatment of psoriatic arthritis and systemic lupus erythematosus, with a preliminary safety profile that seems to differ from that of the JAK1, JAK2 and JAK3 inhibitors. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors.
7Causal relationship between PCSK9 inhibitor and autoimmune diseases: a drug target Mendelian randomization study.PubMed
Weijia Xie, Jiaxin Li, Hao Du, et al.
Arthritis Res Ther. 2023 Aug 14;25(1):148. doi: 10.1186/s13075-023-03122-7.
BACKGROUND: In addition to decreasing the level of cholesterol, proprotein convertase subtilis kexin 9 (PCSK9) inhibitor has pleiotropic effects, including immune regulation. However, the impact of PCSK9 on autoimmune diseases is controversial. Therefore, we used drug target Mendelian randomization (MR) analysis to investigate the effect of PCSK9 inhibitor on different autoimmune diseases. METHODS: We collected single nucleotide polymorphisms (SNPs) of PCSK9 from published genome-wide association studies statistics and conducted drug target MR analysis to detect the causal relationship between PCSK9 inhibitor and the risk of autoimmune diseases. 3-Hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitor, the drug target of statin, was used to compare the effect with that of PCSK9 inhibitor. With the risk of coronary heart disease as a positive control, primary outcomes included the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myasthenia gravis (MG), multiple sclerosis (MS), asthma, Crohn's disease (CD), ulcerative colitis (UC), and type 1 diabetes (T1D). RESULTS: PCSK9 inhibitor significantly reduced the risk of SLE (OR [95%CI] = 0.47 [0.30 to 0.76], p = 1.74 × 10) but increased the risk of asthma (OR [95%CI] = 1.15 [1.03 to 1.29], p = 1.68 × 10) and CD (OR [95%CI] = 1.38 [1.05 to 1.83], p = 2.28 × 10). In contrast, HMGCR inhibitor increased the risk of RA (OR [95%CI] = 1.58 [1.19 to 2.11], p = 1.67 × 10), asthma (OR [95%CI] = 1.21 [1.04 to 1.40], p = 1.17 × 10), and CD (OR [95%CI] = 1.60 [1.08 to 2.39], p = 2.04 × 10). CONCLUSIONS: PCSK9 inhibitor significantly reduced the risk of SLE but increased the risk of asthma and CD. In contrast, HMGCR inhibitor may be a risk factor for RA, asthma, and CD.
8Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in women of childbearing age from 1990 to 2019.PubMed
Fan Cao, Yi-Sheng He, Ni Sang, et al.
Autoimmun Rev. 2023 Nov;22(11):103450. doi: 10.1016/j.autrev.2023.103450. Epub 2023 Sep 21.
AIM: To estimate the age-standardized incidence, prevalence, and mortality rates of autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), asthma, and psoriasis in women of childbearing age from 1990 to 2019, and to further analyze their changing trends, at global, regional, and national levels. METHODS: Women of childbearing age was defined as 15-49 years old. The estimates and 95% uncertainty intervals (UIs) for case number of RA, IBD, MS, T1DM, asthma and psoriasis in seven age groups (15-19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49 years) were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age standardization by direct method was adopted to estimate the age-standardized incidence, prevalence, and mortality rates of these autoimmune diseases in women of childbearing age. Joinpoint regression analysis was utilized to analyze the changing trends of estimated age-standardized incidence, prevalence, and mortality rates from 1990 to 2019 by calculating the average annual percentage change (AAPC) and its 95% confidence intervals (CIs). RESULTS: In 2019, the estimated global age-standardized incidence, prevalence, and mortality rates of RA in women of childbearing age was 17.13 (95% UI: 12.39 to 22.60), 215.86 (95% UI: 179.04 to 259.70), and 0.06 (95% UI: 0.04 to 0.08); of IBD was 5.85 (95% UI: 4.72 to 7.12), 63.54 (95% UI: 53.50 to 74.37), and 0.11 (95% UI: 0.08 to 0.13); of MS was 1.63 (95% UI: 1.05 to 2.28), 28.74 (95% UI: 23.80 to 34.46), and 0.17 (95% UI: 0.14 to 0.27); of T1DM was 6.22 (95% UI: 2.75 to 11.50), 290.51 (95% UI: 221.39 to 370.19), and 0.63 (95% UI: 0.48 to 0.78); of asthma was 291.14 (95% UI: 157.06 to 468.78), 2796.25 (95%UI: 1987.07 to 3842.97), and 1.42 (95% UI: 1.12 to 1.75), respectively. The estimated global age-standardized incidence and prevalence rates of psoriasis in women of childbearing age was 58.68 (95% UI: 51.04 to 66.85) and 477.20 (95% UI: 440.30 to 515.76). Highest disease burden generally exists in Region of the Americas and European Region. From 1990 to 2019, the estimated global age-standardized incidence and prevalence rates of RA (AAPC: 0.18, 95% CI: 0.11 to 0.24; AAPC: 0.24, 95% CI: 0.18 to 0.30) and T1DM (AAPC: 1.47, 95% CI: 1.40 to 1.54; AAPC: 0.83, 95% CI: 0.79 to 0.88) in women of childbearing age showed significantly increasing trends whereas those of IBD (AAPC: -0.76, 95% CI: -0.80 to -0.73; AAPC: -0.65, 95% CI: -0.70 to -0.60), MS (AAPC: -0.20, 95% CI: -0.23 to -0.16; AAPC: -0.25, 95% CI: -0.26 to -0.23), asthma (AAPC: -0.53, 95% CI: -0.60 to -0.47; AAPC: -0.74, 95% CI: -0.81 to -0.68), and psoriasis (AAPC: -0.83, 95% CI: -0.85 to -0.82; AAPC: -0.99, 95% CI: -1.02 to -0.96) showed significantly decreasing trends. Favorably, the estimated global age-standardized mortality rate of RA (AAPC: -1.32, 95% CI: -1.63 to -1.01), IBD (AAPC: -0.95, 95% CI: -1.06 to -0.84), MS (AAPC: -0.96, 95% CI: -1.12 to -0.80), T1DM (AAPC: -1.05, 95% CI: -1.21 to -0.89), and asthma (AAPC: -2.27, 95% CI: -2.34 to -2.19) in women of childbearing age all declined. The changing trends of estimated age-standardized incidence, prevalence, and mortality rates varied significantly across 204 countries and territories. CONCLUSIONS: Our study provides an accurate estimation on the age-standardization of disease indicators of autoimmune diseases in women of childbearing age. There are remarkable disparities in the incidence, prevalence, and mortality burden related to autoimmune diseases in women of childbearing age, as well as their changing trends across the world, suggesting that each individual government should establish flexible health policies and make reasonable source allocation to address different needs for autoimmune diseases in this population.
9Autoimmunity in 2018.PubMed
Carlo Selmi
Clin Rev Allergy Immunol. 2019 Jun;56(3):375-384. doi: 10.1007/s12016-019-08745-w.
In the vast database of peer-reviewed articles, the number of 2018 papers published retrieved using the "autoimmunity" keyword remained unchanged compared with the brilliant results of 2017 while returning above a 5% share within the immunology field, after the brisk decrease of this ratio in 2017. As in the past 12 years, we have now searched PubMed for publications related to autoimmunity in the major immunology and autoimmunity peer-reviewed journals and provide here an arbitrary discussion of the major themes encountered. Once again, we are happy to notice that similarities between autoimmune diseases and the common mechanisms significantly outnumber differences. Some examples include data on Th17 cells, cytokines, or other mediators variably involved in the autoimmunity mechanisms such as BLIMP-1, IL-10, IFN, or NF-kB. The study of the microbiome remains central to autoimmunity development and data are being gathered in a growing number of conditions, similar to epigenetics and long non-coding RNA. In the cases of specific diseases, such as systemic lupus erythematosus, rheumatoid arthritis, or psoriatic arthritis, multiple encouraging findings underline the importance of a strict relationship between basic and clinical science to define new pathogenetic and therapeutic developments. Cumulatively, the present scenario of autoimmunity appears bright and should be regarded as one of the fastest growing in the scientific field of immunology, despite the enormous attention paid to cancer immune mechanisms. The parallel observation that the rheumatology therapeutic pipeline is second only to oncology increases the hopes that more and more patients will be satisfactorily treated in the near future.
10Myeloid disorders after autoimmune disease.PubMed
Prajwal C Boddu, Amer M Zeidan
Best Pract Res Clin Haematol. 2019 Mar;32(1):74-88. doi: 10.1016/j.beha.2019.02.002. Epub 2019 Feb 7.
Autoimmune diseases (ADs) are associated with an increased risk not only of lymphoproliferative disorders but also of myeloid malignancies. The excess risk of myelodysplastic syndromes and/or acute myeloid leukemia is observed across several AD types, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disorders, multiple sclerosis, among others. The risk of developing myeloid neoplasms (MNs) is dependent on several variables, including the specific AD type, chronicity and severity of the AD, type and duration of exposure of disease modifying anti-rheumatic drugs or cytotoxics/immunosuppressives, and genetic predisposition risk. Putative triggering factors linking AD to elevated MN risk include AD-directed medications, shared genetic susceptibilities between the two disease entities, and chronic immune stimulation or bone marrow infiltration by the AD. Molecular mechanisms underpinning leukemogenesis remain largely speculative and warrant further investigation. Leukemias arising in patients with AD are not always 'therapy-related' in that MNs may develop in certain AD subtypes even among patients with no prior therapy exposure. Only a few studies have attempted to determine factors associated with MN development in AD but failed to demonstrate consistent characteristic clinical or paraclinical features. These reports have failed to demonstrate a clear correlation between individual agent exposure and subsequent leukemia development due to the low rates of therapy exposure compounded by the rarity of MN occurrence. Notwithstanding, the leukemogenic potential is best documented with agents such as azathioprine, cyclophosphamide, and mitoxantrone; this risk of MN development does not appear to be shared by biologic approaches such as anti-tumor necrosis factors-alpha inhibitors. In this article, we discuss plausible biologic mechanisms underlying MN pathogenesis in AD and review the data available on the development of MNs in patients with AD.
11[The skin and rheumatism].PubMed
S Ständer, R J Ludwig, D Thaçi
Orthopade. 2019 Nov;48(11):905-910. doi: 10.1007/s00132-019-03811-9.
The skin is commonly affected in chronic inflammatory disorders and may act as a visual marker for internal or systemic inflammation. Frequent inflammatory skin diseases, like psoriasis and atopic dermatitis (AD), are associated with rheumatic and inflammatory bowel diseases. Metabolic, mental and cardiovascular comorbidity are frequent consequences of chronic inflammation. Further intersections between skin and joints are connective tissue diseases (collagenoses) and can be observed in complex diseases, e.g. systemic lupus erythematosus. Clinically, these diseases range from predominant cutaneous to severe systemic implication of several organs. Localized scleroderma should be clinically distinguished from systemic sclerosis and treated sufficiently to avoid long-term damage and disability. Thus, interdisciplinary disease management is of crucial importance.
12Other immune thrombocytopenias.PubMed
Howard Liebman
Semin Hematol. 2007 Oct;44(4 Suppl 5):S24-34. doi: 10.1053/j.seminhematol.2007.11.004.
Immune thrombocytopenic purpura (ITP) can be classified as primary (known also as idiopathic thrombocytopenic purpura) or as secondary to an underlying condition such as a malignant or nonmalignant disorder. Commonly occurring conditions associated with secondary ITP include lymphoproliferative disorders (chronic lymphocytic leukemia [CLL], Hodgkin's disease and non-Hodgkin's lymphomas), autoimmune collagen vascular diseases (systemic lupus erythematosus [SLE], thyroid disease, antiphospholipid syndrome [APS]), and chronic infections (human immunodeficiency virus [HIV], Helicobacter pylori, hepatitis C virus [HCV]). The mechanism of platelet destruction in thrombocytopenias associated with lymphoproliferative disorders and collagen vascular diseases is identical to the autoimmune mechanism seen in primary ITP. Drug-induced thrombocytopenias are uncommon and generally resolve quickly upon drug discontinuation, but are often attributed to other causes. Platelet destruction in infection-associated ITP occurs via various mechanisms including accelerated platelet clearance due to immune complex disease as seen in HIV infection or cross-reactivity of anti-platelet glycoprotein antibodies and viral antigens in HIV, HCV, and H pylori infections (antigenic mimicry). In patients with HCV-related cirrhotic liver disease, splenic sequestration secondary to portal hypertension and decreased production of thrombopoietin may further contribute to development of thrombocytopenia. The current treatment paradigm for secondary ITP varies according to the underlying condition. Standard treatments for primary ITP (corticosteroids, IVIG, anti-D, splenectomy) are often successful in secondary ITP. In cases of ITP with H pylori and HCV infection, treatment should focus on the underlying disorder.
13Psoriasis and metabolic syndrome.PubMed
Hidetoshi Takahashi, Hajime Iizuka
J Dermatol. 2012 Mar;39(3):212-8. doi: 10.1111/j.1346-8138.2011.01408.x. Epub 2011 Oct 31.
Psoriasis is a chronic inflammatory and immune-mediated disease associated with several comorbidities, such as obesity, hypertension, diabetes mellitus, dyslipidemia and cardiovascular disorder. These comorbidities are components of metabolic syndrome. The pathogenesis of metabolic syndrome is supposed to be related to increased levels of adipocytokines, such as tumor necrosis factor-α (TNF-α) and adiponectin. Recent study has revealed a high prevalence of metabolic syndrome in psoriatics compared with other skin diseases. Biologic agents, including anti-TNF-α antibodies, are recommended as the first-line treatment for psoriatics with metabolic syndrome. This article reviews the association of psoriasis and metabolic syndrome in terms of adipocytokines and evaluates the role of biologic agents in the treatment of psoriasis.
14Risk of cardiovascular comorbidities before and after the onset of rheumatic diseases.PubMed
Hanna-Kaisa Aaramaa, Nina Mars, Mika Helminen, et al.
Semin Arthritis Rheum. 2024 Apr;65:152382. doi: 10.1016/j.semarthrit.2024.152382. Epub 2024 Jan 26.
OBJECTIVES: To elucidate the risk and temporal relationship of cardiovascular (CV) comorbidities in rheumatic diseases. METHODS: Patients in the FinnGen study diagnosed between 2000 and 2014 with seropositive (n = 2368) or seronegative (n = 916) rheumatoid arthritis (RA), ankylosing spondylitis (AS, n = 715), psoriatic arthritis (PsA, n = 923), systemic lupus erythematosus (SLE, n = 190), primary Sjogren's syndrome (pSS, n = 412) or gout (n = 2034) were identified from healthcare registries. Each patient was matched based on age, sex, and birth region with twenty controls without any rheumatic conditions. Overall risk ratios (RR) were calculated by comparing the prevalence of seven CV diseases between patients and controls. Logistic regression models were used for estimating odds ratios (OR) for CV comorbidities before and after the onset of rheumatic diseases. RESULTS: The RR for 'any CVD' varied from 1.14 (95 % confidence interval [CI] 1.02-1.26) in PsA to 2.05 (95 % CI 1.67-2.52) in SLE. Patients with SLE or gout demonstrated over two-fold risks for several CV comorbidities. Among CV comorbidities, venous thromboembolism (VTE) showed the highest effect sizes in several rheumatic diseases. The ORs for CV comorbidities were highest within one year before and/or after the onset of the rheumatic disease. However, in gout the excess risk of CV disease was especially high before gout diagnosis. CONCLUSIONS: The risk of CV comorbidities was elevated in all studied rheumatic diseases, with highest risks observed in SLE and gout. The risk for CV diseases was highest immediately before and/or after rheumatic disease diagnosis, highlighting the increased risk for CV comorbidities across all rheumatic diseases very early on the disease course.
15Psoriasis as a systemic disease.PubMed
Ivan Grozdev, Neil Korman, Nikolai Tsankov
Clin Dermatol. 2014 May-Jun;32(3):343-50. doi: 10.1016/j.clindermatol.2013.11.001. Epub 2013 Nov 23.
Psoriasis is an inflammatory immune-mediated disease that affects the skin and has pathogenic effects with systemic impact. The relationship between psoriasis and comorbidities remains controversial. The hypothesis of a causative role of psoriasis in its cardiovascular and metabolic comorbidities is based on pathophysiologic concepts establishing a link between chronic inflammation in psoriasis, endothelial dysfunction, formation of atherosclerotic plaques, and the different compounds of metabolic syndrome. Psoriasis management has to be multidisciplinary. It implicates identification and treatment of psychological disorders, addictions, and associated cardiovascular and metabolic diseases, together with improvement of quality of life of patients.
16Pulmonary hypertension in connective tissue diseases, new evidence and challenges.PubMed
Madelon C Vonk, Els Vandecasteele, Arie P van Dijk
Eur J Clin Invest. 2021 Apr;51(4):e13453. doi: 10.1111/eci.13453. Epub 2020 Dec 5.
Pulmonary arterial hypertension is a lethal complication of different connective tissue diseases such as systemic sclerosis, mixed connective tissue disease and systemic lupus erythematosus. Although the treatment possibilities for patients with pulmonary arterial hypertension have increased in the last two decades and survival of patients with idiopathic pulmonary arterial hypertension has improved, the latter is not the case for patients with pulmonary arterial hypertension associated with connective tissue disease. In this narrative review, we review recent literature and describe the improvement of early diagnostic possibilities, screening modalities and treatment options. We also point out the pitfalls in diagnosis in this patient category and describe the unmet needs and what the focus of future research should be.
17Alicaforsen. Isis Pharmaceuticals.PubMed
A T Gewirtz, S Sitaraman
Curr Opin Investig Drugs. 2001 Oct;2(10):1401-6.
Alicaforsen (ISIS-2302) is an RNase H-dependent antisense inhibitor of the intercellular adhesion molecule ICAM-1 under development by Isis Pharmaceuticals, for the potential treatment of a variety of inflammatory disorders [175741]. As of April 1997 it was in phase III trials for Crohn's disease (CD); however, the trial failed and, in December 1999, the company suspended development for this indication [352801]. In October 2000, the company re-initiated development in CD [384820] and new phase III trials had begin by May 2001 [409704]. In August 2000, phase II studies of alicaforsen in an enema formulation for ulcerative colitis and a topical formulation for psoriasis were ongoing [378715]. Development of the compound for the potential treatment of rheumatoid arthritis (RA) was discontinued in 1999 [347579]. By the end of 1998, alicaforsen was in phase II trials for kidney transplant rejection. At this time, these trials were expected to finish in mid-1999 [343460]. However, they were ongoing in September 1999, although no further development has been reported for this indication since that time [338672]. In February 1995, Isis Pharmaceuticals and Boehringer Ingelheim (BI) signed a collaborative agreement on cell adhesion inhibitors, including alicaforsen [174111]. By early 1999, Isis and BI were to decide on the next developmental step for alicaforsen following further analyses of its performance against CD [292915], [315439]. Their joint development agreement was terminated in 1999; Isis regained rights to the product and by September 1999 was in talks to license alicaforsen to another partner for CD [338672]. In June 2000, Cytogenix entered into a sponsored research agreement with Baylor College of Medicine at the Texas Medical Center Houston for the use of its ssDNA expression system for the development of antisense strategies directed against intercellular adhesion molecules for the purpose of reducing lung inflammation and injury in disease states and conditions [369677]. US-05514788, and other patents, cover antisense cell adhesion molecule inhibitors [212289], [234792].
18Real-world treatment patterns in patients with systemic lupus erythematosus: associations with comorbidities and damage.PubMed
Tali Eviatar, Roni Yahalom, Idit Livnat, et al.
Lupus Sci Med. 2024 Sep 24;11(2):e001266. doi: 10.1136/lupus-2024-001266.
OBJECTIVE: To assess treatment patterns and the association between long-term glucocorticoid (GC) and hydroxychloroquine (HCQ) use and damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective study including patients with SLE using the computerised database of a large health maintenance organisation. Patients were matched with subjects from the general population. Multivariable logistic regression models were used to assess the association between GC cumulative daily doses, HCQ and comorbidities: Osteoporosis, cardiovascular disease (CVD), hypertension and diabetes mellitus. Models were adjusted for age, sex, socioeconomic status, smoking, disease duration and HCQ use. RESULTS: A total of 1073 patients with SLE were included, 87.79% were women. The age at first diagnosis was 37.23±14.36 and the SLE disease duration was 12.89±6.23 years. Initiation of HCQ within 12 months of SLE diagnosis increased from 51.02% in 2000 to 83.67% in 2010 and 93.02% in 2018. The annual usage of GC gradually decreased from 45.34% in 2000 to 30.76% in 2020. CVD and osteoporosis were more prevalent in SLE than in the general population. Multivariable logistic regression models revealed increased odds for comorbidities in patients receiving a mean daily dose of prednisone of more than 5 mg/day compared with those receiving 5 mg/day or less. CONCLUSIONS: CVD and osteoporosis were more prevalent in SLE than in the general population. The dose and frequency of GC treatment in patients with SLE have decreased over the years. Prednisone usage in doses exceeding 5 mg/day is associated with significantly increased odds of osteoporosis and CVD.
19Mesenchymal Stem Cells in Homeostasis and Systemic Diseases: Hypothesis, Evidences, and Therapeutic Opportunities.PubMed
Francisco J Vizoso, Noemi Eiro, Luis Costa, et al.
Int J Mol Sci. 2019 Jul 31;20(15):3738. doi: 10.3390/ijms20153738.
Mesenchymal stem cells (MSCs) are present in all organs and tissues, playing a well-known function in tissue regeneration. However, there is also evidence indicating a broader role of MSCs in tissue homeostasis. In vivo studies have shown MSC paracrine mechanisms displaying proliferative, immunoregulatory, anti-oxidative, or angiogenic activity. In addition, recent studies also demonstrate that depletion and/or dysfunction of MSCs are associated with several systemic diseases, such as lupus, diabetes, psoriasis, and rheumatoid arthritis, as well as with aging and frailty syndrome. In this review, we hypothesize about the role of MSCs as keepers of tissue homeostasis as well as modulators in a variety of inflammatory and degenerative systemic diseases. This scenario opens the possibility for the use of secretome-derived products from MSCs as new therapeutic agents in order to restore tissue homeostasis, instead of the classical paradigm "one disease, one drug".
20Interleukin-9 and T helper type 9 cells in rheumatic diseases.PubMed
F Ciccia, G Guggino, A Ferrante, et al.
Clin Exp Immunol. 2016 Aug;185(2):125-32. doi: 10.1111/cei.12807.
Interleukin (IL)-9 is a 28-30 kDa monomeric glycosylated polypeptide belonging to the IL-7/IL-9 family of proteins that bind to a composite receptor consisting of the private receptor IL-9R and the IL-2 receptor, gamma (IL-2RG), a common gamma subunit shared by the receptors of many different cytokines. The IL-9R is expressed widely and IL-9 impacts a number of effector cells, such as effector T cells, B cells, innate lymphoid cells, mast cells, polymorphonuclear cells, epithelial cells and smooth muscle cells, playing an important role in regulating inflammatory immunity. The critical role of IL-9 in promoting cellular and humoral immune responses makes it an important focus of potential therapeutic interventions. Recently, a defined subset of T helper type cells, Th9 cells, has been identified by the potent production of IL-9. The involvement of the Th9 cell subset has been described in many types of inflammatory diseases, namely atopic diseases, helminth infections, experimental autoimmune encephalomyelitis and ulcerative colitis. In this review, we summarize the IL-9 biological activities, highlighting roles for IL-9 and Th9 cells in rheumatoid and psoriatic arthritis, systemic vasculitis, systemic lupus erythematosus and systemic sclerosis.