唾液腺超声对干燥综合征的诊断价值

doi:10.19723/j.issn.1671-167X.2022.06.011

摘要/Abstract

摘要：

目的: 评估唾液腺超声(salivary gland uhrasonography，SGUS)对干燥综合征(Sj?gren’s syndrome，SS)的诊断价值。方法: 收集2019年12月至2022年1月就诊于上海交通大学医学院附属第九人民医院风湿免疫科门诊及住院部的246例表现为口干和/或眼干燥的患者，均完善SGUS，并采用2019年风湿病临床试验结果指标(outcome measures in rheumatology clinical trial，OMERACT)工作组超声评分系统对患者唾液腺进行评分，记录患者一般资料、未刺激唾液流率(unstimulated saliva flow rate, USFR)、Schirmer试验及血清学检查结果，193例完善唇腺活检检查。采用2016年美国风湿病学会(American College of Rheumatology，ACR)/欧洲抗风湿病联盟(European League Against Rheumatism，EULAR)共识作为SS诊断金标准。采用χ²检验比较两组唾液腺超声评分的差异，用受试者工作特征(receiver operating characteristic，ROC)曲线评估SGUS诊断SS的准确性，并比较SS患者中SGUS阳性组与阴性组的临床特征。结果: 共175例患者符合2016年ACR/EULAR共识为SS组，余71例不符合ACR/EULAR共识为非SS患者，两组患者年龄[(54.2±11.8)岁 vs.(53.4±14.9)岁，P=0.705]、女性(94.4% vs.93.1%，P=1.000)比较差异均无统计学意义。共109例患者SGUS阳性(≥2分)，其中104例符合SS诊断，5例不符合SS诊断，SS组SGUS阳性率明显高于非SS组(59.4% vs.7.0%，P < 0.001)。2019年OMERACT超声评分系统诊断SS的曲线下面积为0.762(95%CI 0.701~0.823)，SGUS评分与ACR/EULAR共识的绝对一致性为69.1%(170/246)，敏感性为59.4%(104/175)，特异性为93.0%(66/71)，阳性预测值为95.4%(104/109)，阴性预测值为48.2% (66/137)。共81例患者SGUS、抗干燥综合征A (Sj?gren’s syndrome A, SSA)抗体双阳性，均符合ACR/EULAR共识，阳性符合率为100%(81/81)；85例患者SGUS阴性且无抗SSA抗体，60例未达到ACR/EULAR共识，阴性符合率为70.6% (60/85)。在SS患者中，SGUS阳性组有更高的抗核抗体(antinuclear antibody, ANA)阳性率(83.1%对98.1%，P < 0.001)。结论: 2019年OMERACT超声评分系统在诊断SS中有重要价值，与抗SSA抗体联合可进一步提高诊断性能。

关键词: 干燥综合征, 唾液腺, 超声

Abstract:

Objective: To evaluate the diagnostic performances of salivary gland ultrasonography(SGUS)in Sj?gren's syndrome(SS). Methods: A total of 246 patients with dry mouth and/or eyes who were treated in the outpatient department and inpatient department of Rheumatology and Immunology Department of the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine from December 2019 to January 2022 were collected. All patients received SGUS examination and scored by 2019 outcome measures in rheumatology clinical trial (OMERACT)ultrasonic scoring system.Their general information, unstimulated saliva flow rate(USFR), Schirmer test and serological test results were recorded. In the study, 193 cases had lip gland biopsy. The 2016 American College of Rheumatology(ACR)/ European League Against Rheumatism(EULAR)classification criteria were adopted as the diagnostic standard of SS. χ² test was used to compare the difference of salivary gland ultrasonic scores between the two groups. The receiver operating characteristic(ROC) curve was used to evaluate the accuracy of SGUS in diagnosing SS, and the disease characteristics of SGUS positive group and negative group in the SS patients were compared. Results: A total of 175 patients were SS group according to the ACR/EULAR classification, and the remaining 71 patients were non-SS group.There was no significant difference in age [(54.2±11.8) years vs. (53.4±14.9) years, P=0.705] and female (94.4% vs.93.1%, P=1.000) between SS and non-pSS groups. A total of 109 patients were SGUS positive (≥ 2 points), of whom 104 patients met the SS diagnosis and 5 patients did not meet the SS diagnosis. The positive rate of SGUS in SS group was significantly higher than that in non-SS group (59.4% vs. 7.0%, P < 0.001). The accuracy of 2019 OMERACT ultrasonic scoring system to predict ACR/EULAR classification was good, with an area under the curve of 0.762 (95%CI 0.701-0.823). The absolute agreement between the SGUS outcome and ACR-EULAR classification was 69.1%(170/246), with a sensiti-vity of 59.4%(104/175), specificity of 93%(66/71), positive predictive value of 95.4%(104/109) and negative predictive value of 48.2% (66/137). A total of 81 patients were positive SGUS combined with anti-SSA antibody, 100% (81/81) fulfilled the ACR-EULAR criteria, 85 patients were negative SGUS and anti SSA antibody, and 60 patients(70.6%, 60/85) did not fulfil the ACR-EULAR criteria. SGUS positive group had higher antinuclear antibody(ANA) positive rate(83.1% vs. 98.1%, P < 0.001) in the patients with SS. Conclusion: The OMERACT ultrasonic scoring system has high diagnostic value in SS. The combination of SGUS and anti-SSA antibody can improve the diagnostic value.

Key words: Sj?gren's syndrome, Salivary gland, Ultrasound

中图分类号:

R593.2

刘杨,程昉,王艳玲,艾香艳,朱振航,赵福涛. 唾液腺超声对干燥综合征的诊断价值[J]. 北京大学学报（医学版）, 2022, 54(6): 1123-1127.

Yang LIU,Fang CHENG,Yan-ling WANG,Xiang-yan AI,Zhen-hang ZHU,Fu-tao ZHAO. Diagnostic performances of salivary gland ultrasonography for Sjögren's syndrome[J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1123-1127.

图/表 3

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参考文献 23

1	Shiboski CH , Shiboski SC , Seror R , et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts[J]. Arthritis Rheumatol, 2017, 69 (1): 35- 45. doi: 10.1002/art.39859
2	Theander E , Mandl T . Primary Sjögren's syndrome: Diagnostic and prognostic value of salivary gland ultrasonography using a simplified scoring system[J]. Arthritis Care Res (Hoboken), 2014, 66 (7): 1102- 1107. doi: 10.1002/acr.22264
3	Salaffi F , Carotti M , Iagnocco A , et al. Ultrasonography of salivary glands in primary Sjögren's syndrome: A comparison with contrast sialography and scintigraphy[J]. Rheumatology (Oxford), 2008, 47 (8): 1244- 1249. doi: 10.1093/rheumatology/ken222
4	Lee KA , Lee SH , Kim HR , et al. Diagnostic and predictive eva-luation using salivary glandultrasonography in primary Sjögren's syndrome[J]. Clin Exp Rheumatol, 2018, 112 (3): 165- 172.
5	Jousse-Joulin S , Gatineau F , Baldini C , et al. Weight of salivary gland ultrasonography compared toother items of the 2016 ACR/EULAR classification criteria for Primary Sjögren's syndrome[J]. J Intern Med, 2020, 287 (2): 180- 188. doi: 10.1111/joim.12992
6	van Nimwegen JF , Mossel E , Delli K , et al. Incorporation of salivary gland ultrasonography into the ACR EULAR criteria for primary Sjögren's syndrome[J]. Arthritis Care Res (Hoboken), 2020, 72 (4): 583- 590. doi: 10.1002/acr.24017
7	Takagi Y , Nakamura H , Sumi M , et al. Combined classification system based on ACR/EULAR and ultrasonographic scores for improving the diagnosis of Sjögren's syndrome[J]. PLoS One, 2018, 13 (4): e0195113. doi: 10.1371/journal.pone.0195113
8	Jousse-Joulin S , D'Agostino MA , Nicolas C , et al. Video clip assessment of a salivary gland ultrasound scoring system in Sjögren's syndrome using consensual definitions: An OMERACT uhrasound working group reliability exercise[J]. Ann Rheum Dis, 2019, 78 (7): 967- 973. doi: 10.1136/annrheumdis-2019-215024
9	Zhou M , Song S , Wu S , et al. Diagnostic accuracy of salivary gland ultrasonography with different scoring systems in Sjögren's syndrome: A systematic review and meta-analysis[J]. Sci Rep, 2018, 8 (1): 17128. doi: 10.1038/s41598-018-35288-5
10	Ramsubeik K , Motilal S , Sanchez-Ramos L , et al. Diagnostic accuracy of salivary gland ultrasound in Sjögren's syndrome: A systematic review and meta-analysis[J]. Ther Adv Musculoskelet Dis, 2020, 12, 1- 21.
11	Jousse-Joulin S , Milic V , Jonsson MV , et al. Is salivary gland ultrasonography a useful tool in Sjögren's syndrome? A systematic review[J]. Rheumatology (Oxford), 2016, 55 (5): 789- 800. doi: 10.1093/rheumatology/kev385
12	Carotti M , Sala F , Di Carlo M , et al. Diagnostic value of major salivary gland ultrasonography in primary Sjögren's syndrome: The role of grey-scale and colour/power Doppler sonography[J]. Gland Surg, 2019, 8 (Suppl 3): S159- S167.
13	Mossel E , Arends S , van Nimwegen JF , et al. Scoring hypoechogenic areas in one parotid and one submandibular gland increases feasibility of ultrasound in primary Sjögren's syndrome[J]. Ann Rheum Dis, 2018, 77 (4): 556- 562. doi: 10.1136/annrheumdis-2017-211992
14	Izzetti R , Fulvio G , Nisi M , et al. Reliability of OMERACT scoring system in ultra-high frequency ultrasonography of minor salivary glands: Inter-rater agreement study[J]. J Imaging, 2022, 8 (4): 111. doi: 10.3390/jimaging8040111
15	Al Tabaa O , Gouze H , Hamroun S , et al. Normal salivary gland ultrasonography could rule out the diagnosis of Sjögren's syndrome in anti-SSA-negative patients with sicca syndrome[J]. RMD Open, 2021, 7 (1): e001503. doi: 10.1136/rmdopen-2020-001503
16	Fana V , Dohn UM , Krabbe S , et al. Application of the OMERACT grey-scale ultrasound scoring system for salivary glands in a single-centre cohort of patients with suspected Sjögren's syndrome[J]. RMD Open, 2021, 7 (2): e001516. doi: 10.1136/rmdopen-2020-001516
17	Robin F, Albert JD, Lescoat A, et al. Diagnostic performances of ultrasound evaluation of major salivary glands according to the 2019 OMERACT US scoring system[J/OL]. Arthritis Care Res (Hoboken), 2021, 5 (2021-05-10)[2022-04-15]. https://onlinelibrary.wiley.com/doi/10.1002/acr.24631.
18	Gazeau P , Cornec D , Jousse-Joulin S , et al. Time-course of ultrasound abnormalities of major salivary glands in suspected Sjögren's syndrome[J]. Joint Bone Spine, 2018, 85 (2): 227- 232. doi: 10.1016/j.jbspin.2017.02.007
19	Zandonella-Callegher S , Zabotti A , Giovannini I , et al. Normal-appearing salivary gland ultrasonography identifies a milder phenotype of primary Sjögren's syndrome[J]. Front Med (Lausanne), 2020, 7, 602354.
20	Mossel E , Delli K , Nimwegen GF , et al. Ultrasonography of major salivary glands compared with parotid and labial gland biopsy and classification criteria in patients with clinically suspected primary Sjögren's syndrome[J]. Ann Rheum Dis, 2017, 76 (11): 1883- 1889. doi: 10.1136/annrheumdis-2017-211250
21	Kim JW , Lee H , Park SH , et al. Salivary gland ultrasonography findings are associated with clinical, histological, and serologic features of Sjögren's syndrome[J]. Scand J Rheumatol, 2018, 47 (4): 303- 310. doi: 10.1080/03009742.2017.1374451
22	Jousse-Joulin S , Devauchelle-Pensec V , Cornec D , et al. Brief report: Ultrasonographic assessment of salivary gland response to rituximab in primary Sjögren's syndrome[J]. Arthritis Rheumatol, 2015, 67 (6): 1623- 1628. doi: 10.1002/art.39088
23	Lorenzon M , Spina E , Di Franco FT , et al. Salivary gland ultrasound in primary Sjögren's syndrome: Current and future perspectives[J]. Open Access Rheumatol, 2022, 14, 147- 160. doi: 10.2147/OARRR.S284763

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Items	Non-SS (n=71)	SS (n=175)	t/χ²/Z	P
Age/years, ${\bar x}$±s	54.2±11.8	53.4±14.9	0.860	0.391
Female, n (%)	67 (94.4)	163 (93.1)	0.005	0.946
Course of disease/months，M(P₂₅, P₇₅)	12 (3, 24)	36 (6, 96)	-3.332	0.001
Enlargement of salivary gland, n (%)	3 (4.2)	33 (18.9)	8.656	0.003
Schirmer test, n (%)	52 (73.2)	147 (84.0)	3.784	0.052
USFR/(mL/15 min)，${\bar x}$±s	3.8±3.6	1.7±1.4	-5.716	< 0.001
ANA, n (%)	40 (56.3)	161 (92.0)	42.977	< 0.001
Anti-SSA antibody, n (%)	6 (8.5)	127 (72.6)	81.618	< 0.001
Anti-SSB antibody, n (%)	0 (0)	40 (22.9)	19.380	< 0.001
Anti-centrometric antibody, n (%)	5 (7.0)	31 (17.7)	4.605	0.032
RF，n (%)	8 (11.3)	71 (40.6)	19.895	< 0.001
IgG, n (%)	13 (18.3)	97 (55.4)	28.150	< 0.001
ESR/(mm/h), ${\bar x}$±s	17.5±14.2	31.1±21.2	5.039	< 0.001
SGUS, n (%)	5 (7.0)	104 (59.4)	56.172	< 0.001
Lip biopsy (n =193), n (%)	4(6.7) (n=58)	112(83) (n=135)	97.894	< 0.001

Items	SGUS negative (n=71)	SGUS positive (n=104)	t/χ²/Z	P
Age/years, ${\bar x}$±s	53.9±15.1	53.0±14.9	0.396	0.693
Female, n (%)	66 (93.0)	97 (93.3)	0.000	1.000
Course of disease/months，M(P₂₅, P₇₅)	36 (6, 120)	36 (12, 60)	-0.087	0.931
Schirmer test, n (%)	58 (81.7)	89 (85.6)	0.474	0.491
ANA, n (%)	59 (83.1)	102 (98.1)	12.862	< 0.001
Anti-SSA antibody, n (%)	46 (64.8)	81 (77.9)	3.635	0.057
Anti-SSB antibody, n (%)	12 (16.9)	28 (26.9)	2.403	0.121
Anti-centrometric antibody, n (%)	9 (12.7)	22 (21.2)	2.081	0.149
RF, n (%)	30 (42.3)	41 (39.7)	0.140	0.708
IgG, n (%)	35 (49.3)	61 (59.6)	1.819	0.177
ESR/(mm/h), ${\bar x}$±s	20.8±18.2	31.2±23.1	-0.118	0.906
USFR/(mL/15 min)，${\bar x}$±s	1.8±1.5	1.7±1.3	0.574	0.567
Lip biopsy, n (%) (n=135)	50/61 (82) (n=61)	62/74 (83.8) (n=74)	0.780	0.780

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