类风湿关节炎患者接受 TNF 抑制剂治疗后出现干眼：眼表杯状细胞作为早期眼生物标志物。
Dry eye in rheumatoid arthritis patients under TNF-inhibitors: conjunctival goblet cell as an early ocular biomarker.
机构信息
Department of Ophthalmology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Rheumatology Division, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
出版信息
Sci Rep. 2020 Aug 20;10(1):14054. doi: 10.1038/s41598-020-70944-9.
Dry eye disease (DED) is common in Rheumatoid Arthritis (RA) patients. The application of conjunctival goblet cell count as a clinical biomarker to diagnose and respond to treatment can take place in rheumatoid arthritis patients under TNF-inhibitors (TNFi) therapy. This study aimed to investigate the ocular surface parameters and the long-term effects of TNFi therapy on ocular surface features and goblet cell count of rheumatoid arthritis patients. At baseline, rheumatoid arthritis patients eligible to TNFi were compared to healthy controls (similar age/gender), regarding Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, tear break-up time test, vital dye staining of the ocular surface, and conjunctival impression cytology. DED severity grade, impression cytology score, and goblet cell count were analyzed. Rheumatoid arthritis patients were followed after three (3 M) and 12 months (12 M), during TNFi treatment. Sixteen rheumatoid arthritis patients and 24 controls were compared: a higher frequency of abnormal OSDI (68.8% vs. 16.7%, p = 0.002), Schirmer's test < 10 mm (37.5% vs. 8.3%, p = 0.042), meibomian gland dysfunction (50% vs. 8.3%, p = 0.007), abnormal impression cytology (75% vs. 8.3%, p < 0.001), and mild to moderate DED (81.3% vs. 4.2%, p < 0.001) were observed in rheumatoid arthritis patients, who also had lower goblet cell count [325 (274-707) cells/mm vs. 742 (562-863) cells/mm, p = 0.004]. The presence of Meibomian gland dysfunction was associated with higher disease activity scores (p < 0.05). The prospective early observation of these patients at 3 M showed an increase improvement in tear production by Schirmer's test [13 (7.5-17.5) vs. 23.5 (16-35); p = 0.001], and an improvement in impression cytology score [1 (0.5-2) vs. 1 (0-1), p = 0.031] and in goblet cell count [325 (274-707) vs. 931 (656-1,244), p < 0.001]. Eight RA responders to TNFi were also re-evaluated at 12 M with further improvement in goblet cell count [393 (275-827) vs. 872 (502-1,185) vs. 1,079 (867-1,244), p = 0.047]. Multifactorial DED is frequent in RA patients, comprising aqueous, lipid, and mucin components. TNFi prompt improves tear production and recovers the goblet cells, which can be a biomarker of the pathological process and response to therapy in this population.
干燥性角结膜炎（DED）在类风湿关节炎（RA）患者中很常见。使用结膜杯状细胞计数作为一种临床生物标志物来诊断和应对治疗，可以应用于接受肿瘤坏死因子抑制剂（TNFi）治疗的类风湿关节炎患者。本研究旨在调查 TNFi 治疗对类风湿关节炎患者眼表特征和杯状细胞计数的长期影响。在基线时，将符合 TNFi 治疗条件的类风湿关节炎患者与健康对照组（年龄/性别相似）进行比较，评估眼表疾病指数（OSDI）问卷、Schirmer I 试验、泪膜破裂时间试验、眼表活体染色和结膜印片细胞学。分析 DED 严重程度分级、印片细胞学评分和杯状细胞计数。类风湿关节炎患者在接受 TNFi 治疗后 3 个月（3M）和 12 个月（12M）时进行随访。比较了 16 例类风湿关节炎患者和 24 例对照组：异常 OSDI 的频率更高（68.8% vs. 16.7%，p=0.002），Schirmer 试验<10mm（37.5% vs. 8.3%，p=0.042），睑板腺功能障碍（50% vs. 8.3%，p=0.007），异常印片细胞学（75% vs. 8.3%，p<0.001）和轻度至中度 DED（81.3% vs. 4.2%，p<0.001）在类风湿关节炎患者中更常见，他们的杯状细胞计数也更低[325（274-707）个/毫米 vs. 742（562-863）个/毫米，p=0.004]。睑板腺功能障碍的存在与更高的疾病活动评分相关（p<0.05）。对这些患者的前瞻性早期 3M 观察显示，Schirmer 试验的泪液产生改善[13（7.5-17.5）vs. 23.5（16-35）；p=0.001]，印片细胞学评分改善[1（0.5-2）vs. 1（0-1），p=0.031]和杯状细胞计数改善[325（274-707）vs. 931（656-1,244），p<0.001]。8 例对 TNFi 有反应的 RA 患者在 12M 时再次接受评估，杯状细胞计数进一步改善[393（275-827）vs. 872（502-1,185）vs. 1,079（867-1,244），p=0.047]。多因素 DED 在 RA 患者中很常见，包括水液、脂质和粘蛋白成分。TNFi 可迅速改善泪液产生并恢复杯状细胞，这可能是该人群病理过程和治疗反应的生物标志物。
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