国际口腔医学杂志

国际口腔医学杂志 ›› 2024, Vol. 51 ›› Issue (2): 193-200.doi: 10.7518/gjkq.2024005

• 综述 • 上一篇    下一篇

免疫球蛋白G4相关性唾液腺炎临床特点及诊疗进展

张宇1(),贾志宇2,唐慧芳1,张志勇1,李文静1,田松波1()   

  1. 1.河北医科大学第二医院口腔内科 石家庄 050000
    2.河北医科大学第二医院口腔颌面外科 石家庄 050000
  • 收稿日期:2023-02-18 修回日期:2023-08-18 出版日期:2024-03-01 发布日期:2024-03-11
  • 通讯作者: 田松波
  • 作者简介:张宇，硕士，Email：zhangyuzy99@126.com
  • 基金资助:
    河北省自然科学基金(H2019206129)

Diagnosis and treatment progress and clinical characteristics of immunoglobulin G4-related sialadenitis

Yu Zhang1(),Zhiyu Jia2,Huifang Tang1,Zhiyong Zhang1,Wenjing Li1,Songbo Tian1()   

  1. 1.Dept. of Oral Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
    2.Dept. of Oral and Maxillofacial Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Received:2023-02-18 Revised:2023-08-18 Online:2024-03-01 Published:2024-03-11
  • Contact: Songbo Tian
  • Supported by:
    Hebei Provincial Natural Science Foundation(H2019206129)

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摘要：

免疫球蛋白G4相关性唾液腺炎（IgG4-RS）是一种与IgG4密切相关的慢性自身免疫性疾病，其发病率低，病因和发病机制尚不明确，以唾液腺尤其是颌下腺无痛性持续性肿大为主要临床表现，多数患者血清IgG4升高，淋巴浆细胞浸润，后期全身多器官可继发病变，组织病理学是该病最可靠的诊断方法。临床上倾向于传统糖皮质激素作为首选用药，现阶段可尝试应用生物制剂进行靶向治疗。本文根据国内外文献，对IgG4-RS的病因、临床表现、诊断与鉴别诊断、治疗和预后的研究进展作一综述，以期为该病的临床诊疗和研究提供帮助。

关键词: 免疫球蛋白G4, 唾液腺炎, 免疫反应, 诊断, 治疗

Abstract:

Immunoglobulin G4-related sialadenitis (IgG4-RS) is a chronic autoimmune disease closely associated with IgG4. This disease is an uncommon disorder in the clinical setting, and its etiology is unknown. The major clinical features of IgG4-RS is a painless, persistent enlargement of the salivary gland, especially the submandibular gland. Periphe-ral blood examination show that IgG4 levels are elevated in the serum of most patients, and their lymphoplasmic cells are infiltrated. In the advanced stage of the disease, tissue lesions can present in various organs of the body. Histopathology is the most reliable diagnostic method. Glucocorticoids are recommended as the primary clinical treatment. Biologics can also be used as targeted therapy at this stage. Based on domestic and international literature, we review herein the etiology, clinical manifestations, diagnosis and differential diagnosis, and treatment and prognosis of IgG4-RS to aid the diagnosis, treatment, and subsequent research of the disease.

Key words: immunoglobulin G4, sialadenitis, immunoreaction, diagnosis, treatment

中图分类号: 

  • R781.7+2

表 1

IgG4-RS的鉴别诊断"

项目IgG4-RSEHLGSSCOSS
好发人群中老年人，无明显性别差异中年男性中年女性中青年
临床特点易累及下颌下腺，通常双侧1对或1对以上唾液腺持续肿大，易累及泪腺腮腺常见，皮肤粗糙、有瘙痒感，常有过敏症状多个外分泌腺反复肿大，以腮腺最常见，口干症状严重，多有复发性腮腺炎病史多发生于单侧下颌下腺，常在进食后腺体肿大，部分可自行消退，常见导管阻塞症状或导管结石、腺体急性感染病史，无口干症状
实验室检查IgG4水平多升高，自身抗体均为阴性嗜酸性粒细胞增高，IgE水平升高IgG4和IgE 水平常无升高，抗SS-A和抗SS-B抗体和其他自身抗体常阳性IgG及IgG4水平不高
影像学表现B超见低回声不均质团块；CT示腺体浅层密度增高，腺叶不均匀肿胀CT示腺体弥漫性斑片高密度影及结节，皮下脂肪密度增高B超见内部多发小囊状病变，未见腺体浅部低回声带；腮腺造影示末梢导管点、球状扩张B 超见导管内强回声，导管增宽，结石后段导管扩张；X线或CT示高密度结石影
病理组织学大量淋巴浆细胞浸润，部分可见淋巴滤泡形成，腺泡萎缩，编织样纤维化、地图样生发中心；IgG4阳性浆细胞大量浸润同心圆状纤维化，规则生发中心，嗜酸性微脓肿；免疫组织化学结果IgG4阳性淋巴细胞浸润，肌上皮岛形成，无明显纤维组织增生；免疫组织化学结果IgG4阴性导管周围淋巴细胞浸润；免疫组织化学结果IgG4阴性
1 Basyal B, KC P. Autoimmune pancreatitis[M]. Treasure Island (FL): StatPearls Publishing, 2023.
2 Bozzalla Cassione E, Stone JH. IgG4-related disease[J]. Curr Opin Rheumatol, 2017, 29(3): 223-227.
3 Takahashi Y, Mizushima I, Konishi M, et al. Involvement of two or more sets of lacrimal glands and/or major salivary glands is related to greater systemic disease activity due to multi-organ involvement in IgG4-related dacryoadenitis/sialadenitis[J]. Mod Rheumatol, 2021, 31(6): 1164-1170.
4 Karadeniz H, Vaglio A. IgG4-related disease: a contemporary review[J]. Turk J Med Sci, 2020, 50(SI-2): 1616-1631.
5 Hong X, Li W, Su JZ, et al. Internal organ involvement in IgG4-related sialadenitis: a systemic review[J]. Chin J Dent Res, 2015, 18(2): 85-94.
6 Borges T, Silva S. IgG4-related disease: how to place it in the spectrum of immune-mediated and rheumatologic disorders[J]. Mod Rheumatol, 2020, 30(4): 609-616.
7 Hsieh SC, Shen CY, Liao HT, et al. The cellular and molecular bases of allergy, inflammation and tissue fibrosis in patients with IgG4-related disease[J]. Int J Mol Sci, 2020, 21(14): 5082.
8 Yoshikawa T, Watanabe T, Minaga K, et al. Cytokines produced by innate immune cells in IgG4-related disease[J]. Mod Rheumatol, 2019, 29(2): 219-225.
9 Kubo S, Nakayamada S, Tanaka Y. Immunophenotype involved in IgG4-related disease[J]. Mod Rheumatol, 2019, 29(2): 226-230.
10 Haldar D, Hirschfield GM. Deciphering the biology of IgG4-related disease: specific antigens and di-sease[J]. Gut, 2018, 67(4): 602-605.
11 Liu JC, Yin W, Westerberg LS, et al. Immune dysregulation in IgG4-related disease[J]. Front Immunol, 2021, 12: 738540.
12 Tsuboi H, Honda F, Takahashi H, et al. Pathogenesis of IgG4-related disease. Comparison with sjögren’s syndrome[J]. Mod Rheumatol, 2020, 30(1): 7-16.
13 Della-Torre E, Rigamonti E, Perugino C, et al. B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease[J]. J Allergy Clin Immunol, 2020, 145(3): 968-981.e14.
14 闵赛南, 吴立玲, 俞光岩, 等. IgG4相关性疾病发病机制的研究进展[J]. 中国病理生理杂志, 2019, 35(12): 2290-2298.
Min SN, Wu LL, Yu GY, et al. Research progress on underlying mechanism of IgG4-related disease[J]. Chin J Pathophysiol, 2019, 35(12): 2290-2298.
15 俞光岩, 柳登高, 李巍, 等. 3类新型慢性唾液腺炎的诊断和治疗[J]. 北京大学学报(医学版), 2022, 54(1): 13-17.
Yu GY, Liu DG, Li W, et al. Studies on newly recognized chronic sialadenitis[J]. J Peking Univ (Heath Sci), 2022, 54(1): 13-17.
16 Michailidou D, Schwartz DM, Mustelin T, et al. Allergic aspects of IgG4-related disease: implications for pathogenesis and therapy[J]. Front Immunol, 2021, 12: 693192.
17 Wei TW, Lien CF, Hsu TY, et al. Chronic sclerosing sialadenitis of the submandibular gland: an entity of IgG4-related sclerosing disease[J]. Int J Clin Exp Pathol, 2015, 8(7): 8628-8631.
18 Vu DL, Thieu-Thi TM, Pham MT, et al. A case report of Mikulicz’s disease[J]. Pan Afr Med J, 2020, 37: 252.
19 Wallace ZS, Zhang YQ, Perugino CA, et al. Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts[J]. Ann Rheum Dis, 2019, 78(3): 406-412.
20 俞光岩, 洪霞, 李巍, 等. IgG4相关唾液腺炎的临床病理特点及诊断[J]. 北京大学学报(医学版), 2019, 51(1): 1-3.
Yu GY, Hong X, Li W, et al. Clinicopathological characteristics and diagnosis of IgG4-related siala-denitis[J]. J Peking Univ (Heath Sci), 2019, 51(1): 1-3.
21 Puxeddu I, Capecchi R, Carta F, et al. Salivary gland pathology in IgG4-related disease: a comprehensive review[J]. J Immunol Res, 2018, 2018: 6936727.
22 Tang HQ, Yang HX, Zhang PP, et al. Malignancy and IgG4-related disease: the incidence, related factors and prognosis from a prospective cohort study in China[J]. Sci Rep, 2020, 10(1): 4910.
23 Moriyama M, Tanaka A, Maehara T, et al. T helper subsets in Sjögren’s syndrome and IgG4-related dacryoadenitis and sialoadenitis: a critical review[J]. J Autoimmun, 2014, 51: 81-88.
24 Watanabe T, Minaga K, Kamata K, et al. Mechanistic insights into autoimmune pancreatitis and IgG4-related disease[J]. Trends Immunol, 2018, 39(11): 874-889.
25 Chen LYC, Mattman A, Seidman MA, et al. IgG4-related disease: what a hematologist needs to know[J]. Haematologica, 2019, 104(3): 444-455.
26 Mattoo H, Mahajan VS, Maehara T, et al. Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease[J]. J Allergy Clin Immunol, 2016, 138(3): 825-838.
27 Li W, Chen Y, Sun ZP, et al. Clinicopathological characteristics of immunoglobulin G4-related siala-denitis[J]. Arthritis Res Ther, 2015, 17(1): 186.
28 Takano K, Okuni T, Yamamoto K, et al. Potential utility of core needle biopsy in the diagnosis of IgG4-related dacryoadenitis and sialadenitis[J]. Mod Rheumatol, 2019, 29(2): 393-396.
29 Puxeddu I, Capecchi R, Carta F, et al. Salivary gland pathology in IgG4-related disease: a comprehensive review[J]. J Immunol Res, 2018, 2018: 1-7.
30 Moriyama M, Ohta M, Furukawa S, et al. The diagnostic utility of labial salivary gland biopsy in IgG4-related disease[J]. Mod Rheumatol, 2016, 26(5): 725-729.
31 Sakamoto M, Moriyama M, Shimizu M, et al. The diagnostic utility of submandibular gland sonography and labial salivary gland biopsy in IgG4-related dacryoadenitis and sialadenitis: its potential application to the diagnostic criteria[J]. Mod Rheumatol, 2020, 30(2): 379-384.
32 Abraham M, Khosroshahi A. Diagnostic and treatment workup for IgG4-related disease[J]. Expert Rev Clin Immunol, 2017, 13(9): 867-875.
33 Onda K, Fukuhara T, Matsuda E, et al. Impact of screening for salivary gland by ultrasonography[J]. Yonago Acta Med, 2020, 63(1): 42-46.
34 Komori T, Inoue D, Izumozaki A, et al. Ultrasono-graphy of IgG4-related dacryoadenitis and sialadenitis: imaging features and clinical usefulness[J]. Mod Rheumatol, 2022, 32(5): 986-993.
35 Liu Y, Wang Z, Ren L, et al. Sonographic findings of immunoglobulin G4-related sialadenitis and differences from Sjögren’s syndrome[J]. Scand J Rheumatol, 2022, 51(2): 128-134.
36 Martín-Nares E, Ángeles-Ángeles A, Hernandez-Molina G. Major salivary gland enlargement in IgG4-related disease is associated with multiorgan involvement and higher basal disease activity[J]. Mod Rheumatol, 2020, 30(1): 172-177.
37 张雪, 谢海琴, 陈芸. 超声在IgG4相关性颌下腺炎早期诊断中的作用[J]. 影像研究与医学应用, 2021, 5(11): 10-11, 14.
Zhang X, Xie HQ, Chen Y. The role of ultrasound in the early diagnosis of IgG4-associated submaxillaritis[J]. J Imag Res Med Appl, 2021, 5(11): 10-11, 14.
38 Qian XJ, Ma T, Yu MY, et al. Multi-functional ultrasonic micro-elastography imaging system[J]. Sci Rep, 2017, 7(1): 1230.
39 王知俊, 张蔚蒨, 郑凌艳, 等. 超声弹性成像技术在IgG4相关唾液腺炎诊断和随访中的应用[J]. 中国口腔颌面外科杂志, 2019, 17(3): 225-229.
Wang ZJ, Zhang WQ, Zheng LY, et al. Ultrasound elastography in diagnosis and follow-up for patients with IgG4-related sclerosing sialadenitis[J]. China J Oral Maxillofac Surg, 2019, 17(3): 225-229.
40 宁晓然, 王子乔, 张珊珊, 等. 超声评分系统在IgG4相关涎腺炎评估中的应用[J]. 北京大学学报(医学版), 2019, 51(6): 1032-1035.
Ning XR, Wang ZQ, Zhang SS, et al. Application of ultrasonography scoring system in the assessment of IgG4-related sialadenitis[J]. J Peking Univ (Heath Sci), 2019, 51(6): 1032-1035.
41 Wang ZW, Feng RE, Chen Y, et al. CT features and pathologic characteristics of IgG4-related systemic disease of submandibular gland[J]. Int J Clin Exp Pathol, 2015, 8(12): 16111-16116.
42 Kurowecki D, Patlas MN, Haider EA, et al. Cross-sectional pictorial review of IgG4-related disease[J]. Br J Radiol, 2019, 92(1103): 20190448.
43 Lanzillotta M, Mancuso G, Della-Torre E. Advances in the diagnosis and management of IgG4 related disease[J]. BMJ, 2020, 369: m1067.
44 曹颖, 王冰莹, 杜鸿, 等. 血清IgG4与IgG比率在IgG4相关性疾病中的诊断价值[J]. 临床检验杂志, 2021, 39(2): 123-125.
Cao Y, Wang BY, Du H, et al. Diagnostic value of serum IgG4 and IgG ratio in IgG4 related diseases[J]. Chin J Clin Lab Sci, 2021, 39(2): 123-125.
45 Thompson LDR. IgG4-related sialadenitis[J]. Ear Nose Throat J, 2021, 100(): 531S-532S.
46 Zhang KF, Hong X, Li W, et al. Natural developing process of immunoglobulin G4-related sialadenitis after submandibular gland excision: a retrospective cohort study[J]. Clin Rheumatol, 2021, 40(12): 4969-4976.
47 Moriyama M, Tanaka A, Maehara T, et al. Clinical characteristics of Mikulicz’s disease as an IgG4-related disease[J]. Clin Oral Investig, 2013, 17(9): 1995-2002.
48 Khosroshahi A, Wallace ZS, Crowe JL, et al. International consensus guidance statement on the ma-nagement and treatment of IgG4-related disease[J]. Arthritis Rheumatol, 2015, 67(7): 1688-1699.
49 李洁琼, 张文. 糖皮质激素在IgG4相关性疾病中的应用[J]. 中华临床免疫和变态反应杂志, 2019, 13(6): 464-467.
Li JQ, Zhang W. Glucocorticoids therapy in IgG4-related disease[J]. Chin J Allergy Clin Immunol, 2019, 13(6): 464-467.
50 Sasaki T, Akiyama M, Kaneko Y, et al. Risk factors of relapse following glucocorticoid tapering in IgG4-related disease[J]. Clin Exp Rheumatol, 2018, 36(3): 186-189.
51 Liu YY, Zeng QZ, Zhu LJ, et al. Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort[J]. Rheumatology, 2020, 59(8): 2115-2123.
52 Hong X, Zhang YY, Li W, et al. Treatment of immunoglobulin G4-related sialadenitis: outcomes of glucocorticoid therapy combined with steroid-sparing agents[J]. Arthritis Res Ther, 2018, 20(1): 12.
53 Adam Z, Dastych M, Čermák A, et al. Therapy of immunoglonuline IgG4 related disease (IgG4-RD)[J]. Vnitr Lek, 2022, 68(E-6): 15-22.
54 Wang YW, Zhao Z, Gao D, et al. Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: a randomized clinical trial[J]. Semin Arthritis Rheum, 2020, 50(6): 1513-1520.
55 张霞, 张文. 传统免疫抑制剂在IgG4相关性疾病中的应用[J]. 中华临床免疫和变态反应杂志, 2019, 13(6): 468-472.
Zhang X, Zhang W. Traditional immunosuppressive agents in treatment of IgG4-related disease[J]. Chin J Allergy Clin Immunol, 2019, 13(6): 468-472.
56 Yamamoto M. New strategies for the treatment of IgG4-related disease[J]. Jpn J Clin Immunol, 2016, 39(6): 485-490.
57 Barbier L, Ebbers HC, Declerck P, et al. The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review[J]. Clin Pharmacol Ther, 2020, 108(4): 734-755.
58 Kaegi C, Wuest B, Schreiner J, et al. Systematic review of safety and efficacy of rituximab in treating immune-mediated disorders[J]. Front Immunol, 2019, 10: 1990.
59 滕菲, 张文. 生物制剂在IgG4相关性疾病中的临床应用: 现状与前景[J]. 中华临床免疫和变态反应杂志, 2019, 13(6): 473-476.
Teng F, Zhang W. Biological agents in IgG4-related disease: advances and future[J]. Chin J Allergy Clin Immunol, 2019, 13(6): 473-476.
60 Ji ZF, Chen RY, Cui XM, et al. In vitro IL-6/IL-6R trans-signaling in fibroblasts releases cytokines that may be linked to the pathogenesis of IgG4-related disease[J]. Front Immunol, 2020, 11: 1272.
61 Honda F, Tsuboi H, Ono Y, et al. Pathogenic roles and therapeutic potential of the CCL8-CCR8 axis in a murine model of IgG4-related sialadenitis[J]. Arthritis Res Ther, 2021, 23(1): 214.
62 Zhu MQ, Min SN, Mao XD, et al. Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis[J]. Int J Oral Sci, 2022, 14(1): 29.
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[2] 王昆润. 下颔骨成形术用网状钛板固定植骨块[J]. 国际口腔医学杂志, 1999, 26(04): .
[3] 陈晓 蒋文晖 王文梅. 念珠菌性白斑的研究概况[J]. 国际口腔医学杂志, 2004, 31(02): 138 -140 .
[4] 轩东英,张建波 金岩. 胚胎发育期TGF-β超家族成员与腭裂发生的关系[J]. 国际口腔医学杂志, 2004, 31(02): 132 -134 .
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[7] 黄君斐,王敏. 全瓷修复体颜色效果的影响因素[J]. 国际口腔医学杂志, 2008, 35(S1): .
[8] 叶年嵩 王晟综述 赖文莉审校. 非综合征性先天缺牙相关基因的研究进展[J]. 国际口腔医学杂志, 2011, 38(4): 416 -418 .
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