新发关节炎患者牙周炎患病率异常高

一项对类风湿性关节炎(RA)患者口腔微生物群的分析研究显示，新发RA成人患者中至重度牙周炎患病率达75%。该结果发表在10月份出版的《关节炎与风湿病》杂志上。

长期以来认为RA与口腔微生物和牙周疾病有关，但未见有关RA患者龈下菌群的数据报告。为此，纽约大学关节病医院关节炎诊室主任Jose U. Scher博士及其同事通过确定RA患者和健康对照者牙周状况，首次分析了龈下菌群与RA状况的直接相关性。共计纳入31例连续新发RA成人患者，34例慢性RA成人患者[平均病程5年，多数接受口服生物性改善病情抗风湿药(DMARD)治疗]，18例与新发RA患者年龄、性别及种族相匹配的健康对照者。从所有受试者牙周疾病最严重的6个部位的龈下菌斑生物膜提取口腔标本，然后对标本中的DNA进行微生物鉴定。

结果显示，新发RA患者与慢性RA患者的中至重度牙周疾病患病率均为75%，明显高于健康对照者的39%，后者与一般人群30%~40%的患病率一致。研究者指出，该结果与普遍认可的牙周疾病可能是RA风险因素的观点相一致，也表明“具有明确毒性(如侵袭特点、高PAD酶活性)的卟啉单胞菌及其他菌类是易感人群RA触发因素”的推断是合理的(Arthritis Rheum. 2012;64:3083-94)。

研究者发现，许多新发RA患者标本中含有普氏菌属和纤毛菌属两类细菌，流行率分别为32.2%和25.8%，但对照者标本中均未发现。研究者认为，应进一步研究这两种细菌以及牙龈卟啉菌作为RA牙周触发因素的可能性。此外，新发RA患者上述3种最具毒力的牙周细菌数量多于慢性RA患者，研究者认为可能与慢性患者接受治疗，特别是使用甲氨蝶呤或羟化氯喹等具有抗菌作用的免疫调节剂导致上述细菌数量有所减少有关。

研究者指出，鉴于受试者为年轻人，大多为不吸烟者且从未接受具有潜在免疫抑作用的甾体类激素或DMARD治疗，因此他们的牙周疾病尤其值得关注。此外，研究结果还提示，牙龈和关节或许都是自身免疫反应的靶位，而牙周炎或许是RA关节以外的特征。研究者推测，肺部或小肠等人体其他部位细菌暴露也可能促使RA发生，他们计划将对小肠菌群在RA发病过程的作用进行研究。

该研究由美国国立关节炎肌肉骨骼与皮肤病研究所资助，研究者无利益冲突披露。

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By: MARY ANN MOON, Internal Medicine News Digital Network

Adults with new-onset rheumatoid arthritis showed a 75% prevalence of moderate to severe periodontal disease in a study profiling the oral microbiota in RA. The results were published in the October issue of Arthritis & Rheumatism.

The presence of periodontal disease was particularly striking because these study subjects were young, were mostly nonsmokers, and had never been treated with potentially immunosuppressive steroids or disease-modifying antirheumatic drugs (DMARDs), said Dr. Jose U. Scher, director of the arthritis clinic at New York University Hospital for Joint Diseases, and his associates.

The study finding is "consistent with the prevailing speculation" that Porphyromonas gingivalis and other species may be triggering factors for rheumatoid arthritis (RA) in susceptible people. But it also raises the intriguing alternative possibility that both the gums and the joints may be targets of the same autoimmune process and that periodontitis may be an extraarticular characteristic of RA, the investigators said.

RA has long been associated with both oral microbes and periodontal disease, but "data describing the subgingival microbiota in patients with RA are virtually nonexistent." Dr. Scher and his colleagues "aimed to determine the periodontal status of RA patients and healthy controls and to directly correlate, for the first time, the presence and abundance of subgingival microbiota with RA status."

They assessed 31 consecutive adults who presented to the university’s rheumatology clinics with new-onset RA; 34 adults who had chronic RA (mean duration, 5 years), most of whom were receiving oral and biologic DMARDs; and 18 healthy control subjects matched to the new-onset RA patients for age, sex, and ethnicity.

Oral samples were obtained from all study subjects using subgingival biofilm from the six sites with the greatest extent of periodontal disease. DNA was then extracted from the samples to identify the microorganisms that were present.

The prevalence of moderate to severe periodontal disease was 75% in patients with new-onset RA, equivalent to the 75% prevalence in patients with chronic RA and significantly higher than the 39% prevalence in the healthy controls. The rate in the control group was consistent with the 30%-40% rate found in the general population, the researchers said (Arthritis Rheum. 2012;64:3083-94).

This finding is consistent with the widely accepted idea that periodontal disease may be a risk factor for the development of RA. In fact, "it is reasonable to posit that a particular Porphyromonas species with defined virulent attributes (i.e., invasion properties, high PAD enzyme activity) might serve as a triggering factor for RA in susceptible individuals," they said.

Two species of bacteria, Prevotella and Leptotrichia, were found in many samples from patients with new-onset RA but in none of the samples from control subjects. The prevalence of Prevotella was 32.2% and that of Leptotrichia was 25.8% in new-onset RA. These organisms merit further study as possible periodontal triggers of RA, along with Porphyromonas gingivalis, Dr. Scher and his associates said.

Three of the most virulent periodontopathic bacteria – Tannerella, Treponema, and Porphyromonas – were more abundant in patients with new-onset RA than in those with chronic RA. It may be that these organisms diminish as patients begin therapeutic regimens, particularly those containing immunomodulatory agents that have antibacterial properties, such as methotrexate or hydroxychloroquine.

Dr. Scher and his colleagues noted that exposure to bacteria at other body sites, such as the lung or intestine, may also contribute to the development of RA. Their next project is to assess the role of the intestinal microbiota in the disease.

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No financial conflicts of interest were reported.