Ghent University, Ghent, Belgium.
Dig Dis. 2009;27(4):511-5. doi: 10.1159/000233290. Epub 2009 Nov 4.
Joint involvement associated with inflammatory bowel disease (IBD) belongs to the concept of spondyloarthritis (SpA) and includes two types of arthritis: a peripheral arthritis characterized by the presence of pauciarticular asymmetrical arthritis affecting preferentially joints of lower extremities and an axial arthropathy including inflammatory back pain, sacroiliitis and ankylosing spondylitis (AS). Treatment of arthritis includes a short-term use of NSAIDs associated with optimized treatment of gut inflammation. Safety concerns mean that long-term treatment with NSAIDs is best avoided if possible. Salazopyrine can be recommended for treatment of peripheral arthritis. Methotrexate and azathioprine are generally ineffective. Finally, efficacy of anti-TNF therapy (infliximab and adalimumab) is well established. However, use of etanercept is not recommended because of the increased risk for intestinal disease relapse. Pathogenesis of gut-joint iteropathy is not elucidated. Both inflammations are tightly related as suggested by human evidence of gut inflammation in patients with other forms of SpA and animal evidence of gut and joint inflammation in HLA-B27/human beta(2)-microglobulin transgenic rat model and TNF(DeltaARE) mice. Several clues for the linkage between gut and joint inflammation have been put forward including an altered recognition and handling of bacterial antigens, an aberrant trafficking of CD8+ T cells with an impaired T-helper type 1 cytokine profile and expression of aEb7 integrin, an altered trafficking of macrophages expressing CD163 and evidence of an increased angiogenesis. A transcriptome analysis of mucosal biopsies identified a set of 95 genes that are differentially expressed in both CD and SpA as compared with healthy controls suggesting common pathways. TNF plays a key role in the pathogenesis of various arthritic diseases and IBD. Mesenchymal/myofibroblast-like cells may represent the local primary targets of TNF in the induction of gut and joint pathology. Selective expression of TNFRI on these cells seems to be sufficient to orchestrate the complete development of SpA-related pathologies at least in TNF(DeltaARE) mice. Finally, genetic susceptibility is probably required to develop these pathologies. Genotyping of AS patients provided evidence for an important overlap between determinants of inherited predisposition to CD and AS. The best documented common association is with an IL-23R polymorphism, although the exact role remains unexplored. In addition, evidence suggests that a number of recently identified CD-susceptibility loci are associated with AS. Clinical, genetical, immunological and therapeutic evidence support the tight junction between gut and joint inflammation in two linked diseases, IBD and SpA, belonging to the 'immune-mediated inflammatory diseases'.
与炎症性肠病（IBD）相关的关节受累属于脊柱关节炎（SpA）的概念，包括两种类型的关节炎：一种是外周关节炎，表现为少关节炎，不对称性关节炎，主要影响下肢关节；另一种是轴性关节炎，包括炎症性背痛、骶髂关节炎和强直性脊柱炎（AS）。关节炎的治疗包括短期使用 NSAIDs，并优化肠道炎症的治疗。安全性考虑意味着如果可能的话，最好避免长期使用 NSAIDs。柳氮磺胺吡啶可推荐用于治疗外周关节炎。甲氨蝶呤和硫唑嘌呤通常无效。最后，抗 TNF 治疗（英夫利昔单抗和阿达木单抗）的疗效已得到充分证实。然而，由于肠道疾病复发的风险增加，不建议使用依那西普。肠道-关节病变的发病机制尚不清楚。两种炎症之间存在紧密联系，这一点从人类证据中可以看出，即其他形式的 SpA 患者存在肠道炎症，动物证据中也存在 HLA-B27/人β2-微球蛋白转基因大鼠模型和 TNF（DeltaARE）小鼠的肠道和关节炎症。已经提出了一些肠道和关节炎症之间联系的线索，包括对细菌抗原的识别和处理改变、CD8+T 细胞的异常迁移以及辅助性 T 细胞 1 细胞因子谱的损害和 aEb7 整合素的表达、表达 CD163 的巨噬细胞的异常迁移以及血管生成增加的证据。对黏膜活检的转录组分析确定了一组 95 个基因，这些基因在 CD 和 SpA 中与健康对照组相比有差异表达，提示存在共同的通路。TNF 在各种关节炎疾病和 IBD 的发病机制中起着关键作用。间充质/成纤维细胞样细胞可能是 TNF 在诱导肠道和关节病理中的局部主要靶标。在 TNF（DeltaARE）小鼠中，这些细胞上 TNFRI 的选择性表达似乎足以协调 SpA 相关病理的完全发展。最后，遗传易感性可能是发展这些病理的必要条件。对 AS 患者的基因分型提供了证据，证明 CD 和 AS 遗传易感性决定因素之间存在重要重叠。最有文献记载的共同关联是 IL-23R 多态性，尽管确切作用仍未被探索。此外，有证据表明，最近发现的一些 CD 易感性基因座与 AS 有关。临床、遗传、免疫和治疗证据支持两种相关疾病，即炎症性肠病（IBD）和脊柱关节炎（SpA）之间的肠道和关节炎症之间的紧密联系，属于“免疫介导的炎症性疾病”。
