Application of sialography in diagnosis and differential diagnosis of igg4-related sialadenitis. A systematic review.
DOI:
https://doi.org/10.51168/sjhrafrica.v7i3.2505Keywords:
Salivary glands, IgG4-related sialadenitis, Chronic obstructive submandibular sialadenitis, Differential diagnosis, Ultrasound, Sialography, Benign salivary gland obstructionAbstract
Background:
Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition frequently involving salivary glands. IgG4-related sialadenitis often mimics neoplastic and other inflammatory disorders, creating diagnostic difficulty. Sialography provides detailed visualization of salivary ductal architecture and may aid in differentiation.
Methodology:
A systematic review was conducted using PubMed, Scopus, Embase, Web of Science, and LILACS databases for studies published between 2020 and 2024. Original research articles focusing on imaging or diagnosis of IgG4-related sialadenitis were included. Study selection and data extraction were performed independently by two reviewers. Extracted variables included study design, sample size, imaging modality, and diagnostic findings. Study quality was assessed using STROBE criteria. Due to heterogeneity, a narrative synthesis was undertaken.
Results:
A total of 11 studies met the inclusion criteria. Sialography demonstrated characteristic ductal changes such as ductal irregularities, segmental narrowing, and sialectasis. These features were useful in differentiating IgG4-related sialadenitis from conditions such as Sjögren’s syndrome and obstructive sialadenitis. Diagnostic accuracy improved when sialography was combined with other imaging modalities including ultrasound, CT, and MRI. Evidence quality was low to moderate due to observational study designs and heterogeneity.
Conclusion:
Sialography serves as a valuable adjunctive imaging modality for evaluating ductal morphology in IgG4-related sialadenitis. However, it is not sufficient as a standalone diagnostic tool and should be interpreted alongside clinical, serological, and histopathological findings.
Recommendation:
A multimodal diagnostic approach integrating imaging, serology, and histopathology is recommended for accurate diagnosis. Future studies with standardized imaging protocols and larger sample sizes are required to establish the definitive diagnostic role of sialography.
References
Silvers AR, Som PM. Salivary glands. Radiologic clinics of north America. 1998 Sep 1;36(5):941-66. doi: 10.1016/s0033-8389(05)70070-1.
Virmani N, Dabholkar J. Primary tubercular sialadenitis–A diagnostic dilemma. Iranian Journal of Otorhinolaryngology. 2019 Jan;31(102):45. PMID: 30783598
Lucarelli A, Perandini S, Borsato A, Strazimiri E, Montemezzi S. Iodinated contrast-induced sialadenitis: a review of the literature and sonographic findings in a clinical case. Journal of Ultrasonography. 2018 Dec 31;18(75):359. doi: 10.15557/JoU.2018.0053
Steiger R, Storck C. CME ORL 5. Bilateral pre-auricular swelling. Sialadenitis of all salivary glands in bulimia. Praxis. 2012 May 1;101(11):748-9. doi: 10.1024/1661-8157/a000951.
Mauz PS, Mörike K, Kaiserling E, Brosch S. Valproic acid-associated sialadenosis of the parotid and submandibular glands: diagnostic and therapeutic aspects. Acta oto-laryngologica. 2005 Apr 1;125(4):386-91. doi: 10.1080/00016480410024460.
Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. The American journal of surgical pathology. 2010 Dec 1;34(12):1812-9. doi: 10.1097/PAS.0b013e3181f7266b.
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Yoshino T, Nakamura S, Kawa S, Hamano H. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Modern rheumatology. 2012 Feb 1;22(1):21-30. doi: 10.1007/s10165-011-0571-z.
Stone JH. IgG4-related disease: pathophysiologic insights drive emerging treatment approaches. Clin Exp Rheumatol. 2016 Jul 1;34(4 Suppl 98):66-8. PMID: 27586808
Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. The Lancet. 2015 Apr 11;385(9976):1460-71. doi: 10.1016/S0140-6736(14)60720-0.
Kanno A, Nishimori I, Masamune A, Kikuta K, Hirota M, Kuriyama S, Tsuji I, Shimosegawa T, Research Committee on Intractable Diseases of the Pancreas. Nationwide epidemiological survey of autoimmune pancreatitis in Japan. Pancreas. 2012 Aug 1;41(6):835-9. doi: 10.1097/MPA.0b013e3182480c99.
Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH. Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts. Annals of the rheumatic diseases. 2019 Mar 1;78(3):406-12. doi: 10.1136/annrheumdis-2018-214603
Mattoo H, Stone JH, Pillai S. Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease. Autoimmunity. 2017 Jan 2;50(1):19-24. doi: 10.1080/08916934.2017.1280029
Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, Deshpande V, Stone JH, Pillai S. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. Journal of allergy and clinical immunology. 2014 Sep 1;134(3):679-87. doi: 10.1016/j.jaci.2014.03.034
Doorenspleet ME, Hubers LM, Culver EL, Maillette de Buy Wenniger LJ, Klarenbeek PL, Chapman RW, Baas F, van de Graaf SF, Verheij J, van Gulik TM, Barnes E. Retracted: Immunoglobulin G4+ B‐cell receptor clones distinguish immunoglobulin G 4‐related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies. Hepatology. 2016 Aug;64(2):501-7. doi: 10.1002/hep.28568
Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, Klöppel G, Heathcote JG, Khosroshahi A, Ferry JA, Aalberse RC. Consensus statement on the pathology of IgG4-related disease. Modern pathology. 2012 Sep;25(9):1181-92. doi: 10.1038/modpathol.2012.72.
Stone JH, Zen Y, Deshpande V. IgG4-related disease. New England Journal of Medicine. 2012 Feb 9;366(6):539-51. DOI: 10.1056/NEJMra1104650
Mattoo H, Mahajan VS, Maehara T, Deshpande V, Della-Torre E, Wallace ZS, Kulikova M, Drijvers JM, Daccache J, Carruthers MN, Castelino FV. Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease. Journal of Allergy and Clinical Immunology. 2016 Sep 1;138(3):825-38. doi: 10.1016/j.jaci.2015.12.1330
Wallace ZS, Mattoo H, Carruthers M, Mahajan VS, Della Torre E, Lee H, Kulikova M, Deshpande V, Pillai S, Stone JH. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Annals of the rheumatic diseases. 2015 Jan 1;74(1):190-5. doi: 10.1136/annrheumdis-2014-205233
Brito-Zerón P, Ramos-Casals M, Bosch X, Stone JH. The clinical spectrum of IgG4-related disease. Autoimmunity reviews. 2014 Dec 1;13(12):1203-10. doi: 10.1016/j.autrev.2014.08.013.
Li W, Chen Y, Sun ZP, Cai ZG, Li TT, Zhang L, Huang MX, Hua H, Li M, Hong X, Su JZ. Clinicopathological characteristics of immunoglobulin G4-related sialadenitis. Arthritis Research & Therapy. 2015 Jul 21;17(1):186. doi: 10.1186/s13075-015-0698-y
Della-Torre E, Feeney E, Deshpande V, Mattoo H, Mahajan V, Kulikova M, Wallace ZS, Carruthers M, Chung RT, Pillai S, Stone JH. B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease. Annals of the Rheumatic Diseases. 2015 Dec 1;74(12):2236-43. doi: 10.1136/annrheumdis-2014-205799.
Maehara T, Mattoo H, Ohta M, Mahajan VS, Moriyama M, Yamauchi M, Drijvers J, Nakamura S, Stone JH, Pillai SS. Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis. Annals of the Rheumatic Diseases. 2017 Feb 1;76(2):377-85. doi: 10.1136/annrheumdis-2016-209139.
Kubo S, Nakayamada S, Zhao J, Yoshikawa M, Miyazaki Y, Nawata A, Hirata S, Nakano K, Saito K, Tanaka Y. Correlation of T follicular helper cells and plasmablasts with the development of organ involvement in patients with IgG4-related disease. Rheumatology. 2018 Mar 1;57(3):514-24. doi: 10.1093/rheumatology/kex455.
Kamekura R, Takano K, Yamamoto M, Kawata K, Shigehara K, Jitsukawa S, Nagaya T, Ito F, Sato A, Ogasawara N, Tsubomatsu C. Cutting edge: a critical role of lesional T follicular helper cells in the pathogenesis of IgG4-related disease. The Journal of Immunology. 2017 Oct 15;199(8):2624-9. doi: 10.4049/jimmunol.1601507.
Hennessey JV. Riedel's thyroiditis: a clinical review. The Journal of Clinical Endocrinology & Metabolism. 2011 Oct 1;96(10):3031-41. doi: 10.1210/jc.2011-0617.
Kamisawa T, Okamoto A. IgG4-related sclerosing disease. World journal of gastroenterology: WJG. 2008 Jul 7;14(25):3948. doi: 10.3748/wjg.14.3948.
Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R, Azumi A, Bloch DB, Brugge WR, Carruthers MN, Cheuk W. IgG4-related disease: recommendations for the nomenclature of this condition and its individual organ system manifestations. Arthritis and rheumatism. 2012 Oct;64(10):3061. doi: 10.1002/art.34593
Tanabe T, Tsushima K, Yasuo M, Urushihata K, Hanaoka M, Koizumi T, Fujimoto K, Kubo K, Uehara T, Shigematsu S, Hamano H. IgG4-associated multifocal systemic fibrosis complicating sclerosing sialadenitis, hypophysitis, and retroperitoneal fibrosis, but lacking pancreatic involvement. Internal medicine. 2006;45(21):1243-7. doi: 10.2169/internalmedicine.45.1759
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Sumida T, Mimori T, Tanaka Y, Tsubota K. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Modern rheumatology. 2012 Feb 1;22(1):1-4. doi: 10.1007/s10165-011-0508-6.
Zen Y, Nakanuma Y. Pathogenesis of IgG4-related disease. Current opinion in rheumatology. 2011 Jan 1;23(1):114-8. doi: 10.1097/BOR.0b013e3283412f4a.
Umehara H, Okazaki K. Comprehensive diagnostic criteria for IgG4-related disease. InIgG4-related disease 2013 Oct 12 (pp. 35-39). Tokyo: Springer Japan. https://doi.org/10.1007/978-4-431-54228-5_6
Cheuk W, Chan JK. IgG4-related sclerosing disease: a critical appraisal of an evolving clinicopathologic entity. Advances in anatomic pathology. 2010 Sep 1;17(5):303-32. doi: 10.1097/PAP.0b013e3181ee63ce.
Della-Torre E, Mattoo H, Mahajan VS, Deshpande V, Krause D, Song P, Pillai S, Stone JH. IgG4-related midline destructive lesion. Annals of the rheumatic diseases. 2014 Jul 1;73(7):1434-6. doi: 10.1136/annrheumdis-2014-205187
Stone JH. IgG4-related disease: nomenclature, clinical features, and treatment. InSeminars in diagnostic pathology 2012 Nov 1 (Vol. 29, No. 4, pp. 177-190). WB Saunders. doi: 10.1053/j.semdp.2012.08.002.
Deshpande V. The pathology of IgG4-related disease: critical issues and challenges. InSeminars in diagnostic pathology 2012 Nov 1 (Vol. 29, No. 4, pp. 191-196). WB Saunders. doi: 10.1053/j.semdp.2012.08.001
Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-related disease. Annual Review of Pathology: Mechanisms of Disease. 2014 Jan 24;9(1):315-47. doi: 10.1146/annurev-pathol-012513-104708.
Aalberse RC, Schuurman J. IgG4 breaking the rules. Immunology. 2002 Jan;105(1):9-19. doi: 10.1046/j.0019-2805.2001.01341.x
Ferry JA, Deshpande V. IgG4-related disease in the head and neck. InSeminars in diagnostic pathology 2012 Nov 1 (Vol. 29, No. 4, pp. 235-244). WB Saunders. doi: 10.1053/j.semdp.2012.07.008.
Li Y, Zhou G, Ozaki T, Nishihara E, Matsuzuka F, Bai Y, Liu Z, Taniguchi E, Miyauchi A, Kakudo K. Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease. Modern Pathology. 2012 Aug 1;25(8):1086-97. doi: 10.1038/modpathol.2012.68.
Deshpande V, Huck A, Ooi E, Stone JH, Faquin WC, Nielsen GP. Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease. Journal of clinical pathology. 2012 Aug 1;65(8):725-8. doi: 10.1136/jclinpath-2011-200485.
Geyer JT, Ferry JA, Harris NL, Stone JH, Zukerberg LR, Lauwers GY, Pilch BZ, Deshpande V. Chronic sclerosing sialadenitis (Küttner tumor) is an IgG4-associated disease. The American journal of surgical pathology. 2010 Feb 1;34(2):202-10. doi: 10.1097/PAS.0b013e3181c811ad.
Kitagawa S, Zen Y, Harada K, Sasaki M, Sato Y, Minato H, Watanabe K, Kurumaya H, Katayanagi K, Masuda S, Niwa H. Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Küttner's tumor). The American journal of surgical pathology. 2005 Jun 1;29(6):783-91. doi: 10.1097/01.pas.0000164031.59940.fc.
Deshpande V, Chicano S, Finkelberg D, Selig MK, Mino-Kenudson M, Brugge WR, Colvin RB, Lauwers GY. Autoimmune pancreatitis: a systemic immune complex mediated disease. The American journal of surgical pathology. 2006 Dec 1;30(12):1537-45. doi: 10.1097/01.pas.0000213331.09864.2c.
Pillai S, Perugino C, Kaneko N. Immune mechanisms of fibrosis and inflammation in IgG4-related disease. Current Opinion in Rheumatology. 2020 Mar 1;32(2):146-51. doi: 10.1097/BOR.0000000000000686.
Kamisawa T, Anjiki H, Egawa N, Kubota N. Allergic manifestations in autoimmune pancreatitis. European journal of gastroenterology & hepatology. 2009 Oct 1;21(10):1136-9. doi: 10.1097/meg.0b013e3283297417
Liu Y, Xue M, Wang Z, Zeng Q, Ren L, Zhang Y, Zhang S, Wang Y, Shen D, Xia C, Yu G. Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients. Rheumatology. 2020 Mar 1;59(3):634-40. doi: 10.1093/rheumatology/kez280.
Penfold CN. Mikulicz syndrome. Journal of oral and maxillofacial surgery. 1985 Nov 1;43(11):900-5. doi: 10.1016/0278-2391(85)90231-9.
Küttner H. Über entzündliche Tumoren der Submaxillar‐Speicheldüse. Beitr Klin Chir. 1896;15:815.(doi: not available)
Uhliarova B, Svec M. Kuttner tumor. Bratislavske Lekarske Listy. 2013 Jan 1;114(1):36-8. doi: 10.4149/bll_2013_009.
Skillington SA, Ogden MA. IgG4-related disease and the salivary glands: a review of pathophysiology, diagnosis, and management. Otolaryngologic Clinics of North America. 2021 Jun 1;54(3):497-508. doi: 10.1016/j.otc.2021.02.002.
Moriyama M, Furukawa S, Kawano S, Goto Y, Kiyoshima T, Tanaka A, Maehara T, Hayashida JN, Ohta M, Nakamura S. The diagnostic utility of biopsies from the submandibular and labial salivary glands in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease. International journal of oral and maxillofacial surgery. 2014 Oct 1;43(10):1276-81. doi: 10.1016/j.ijom.2014.06.014.
Yousem DM, Kraut MA, Chalian AA. Major salivary gland imaging. Radiology. 2000 Jul;216(1):19-29. doi: 10.1148/radiology.216.1.r00jl4519.
Hasson O. Modern sialography for screening of salivary gland obstruction. Journal of oral and maxillofacial surgery. 2010 Feb 1;68(2):276-80. doi: 10.1016/j.joms.2009.09.044.
Burke CJ, Thomas RH, Howlett D. Imaging the major salivary glands. British Journal of Oral and Maxillofacial Surgery. 2011 Jun 1;49(4):261-9. doi: 10.1016/j.bjoms.2010.03.002.
Thoeny HC. Imaging of salivary gland tumours. Cancer Imaging. 2007 Apr 30;7(1):52. doi: 10.1102/1470-7330.2007.0008
Nihara MZ, Chandrika KU, Sundari RV, Yi TS, Ramesh M. Investigation of Salivary Gland Pathology. Journal of Academy of Dental Education. 2016 Dec 31;2(1):29-31. doi:10.18311/jade/2015-2016/15955
Kalk WW, Vissink A, Spijkervet FK, Bootsma H, Kallenberg CG, Roodenburg JL. Parotid sialography for diagnosing Sjögren syndrome. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2002 Jul 1;94(1):131-7. doi: 10.1067/moe.2002.126017.
Elhalal M, Khattab Y, El-Sayed E, Habib R. Role of magnetic resonance sialography in diagnosis of salivary gland diseases. Internet J Radiol. 2018;21:1. DOI: 10.5580/IJRA.53225
Rahayu RF, Lillah SY, Yarso KY, Hariyono DC, Bellynda M. Simple and effective sialography with modification of contrast injection. International Journal of Surgery Case Reports. 2024 Apr 6;119:109626. doi: 10.1016/j.ijscr.2024.109626
Ivanović A, Mihalec D. Diagnostic imaging of sialolithiasis. Radiološki vjesnik: radiologija, radioterapija, nuklearna medicina. 2023 May 22;47(1):33-40. https://doi.org/10.55378/rv.47.1.4
Tokue A, Higuchi T, Arisaka Y, Nakajima T, Tokue H, Tsushima Y. Role of F-18 FDG PET/CT in assessing IgG4-related disease with inflammation of head and neck glands. Annals of nuclear medicine. 2015 Jul;29(6):499-505. doi: 10.1007/s12149-015-0969-3.
Witte T, Schulze-Koops H. IgG4-related sialadenitis: IgG4 is helpful, but biopsies are still crucial. Arthritis Research & Therapy. 2015 Dec 18;17(1):368. doi: 10.1186/s13075-015-0888-7
Shimizu M, Okamura K, Kise Y, Takeshita Y, Furuhashi H, Weerawanich W, Moriyama M, Ohyama Y, Furukawa S, Nakamura S, Yoshiura K. Effectiveness of imaging modalities for screening IgG4-related dacryoadenitis and sialadenitis (Mikulicz’s disease) and for differentiating it from Sjögren’s syndrome (SS), with an emphasis on sonography. Arthritis Research & Therapy. 2015 Aug 23;17(1):223. doi: 10.1186/s13075-015-0751-x.
Rastogi R, Bhargava S, Mallarajapatna GJ, Singh SK. Pictorial essay: Salivary gland imaging. Indian Journal of Radiology and Imaging. 2012 Oct;22(04):325-33. doi: 10.4103/0971-3026.111487.
Pniak T, Štrympl P, Staníková L, Zeleník K, Matoušek P, Komínek P. Sialoendoscopy, sialography, and ultrasound: a comparison of diagnostic methods. Open Medicine. 2016 Jan 1;11(1):461-4. doi: 10.1515/med-2016-0081.
Hong X, Li W, Xie XY, Zhang ZY, Chen Y, Gao Y, Peng X, Su JZ, Zhang YY, Wang Z, Cai ZG. Differential diagnosis of IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis. British Journal of Oral and Maxillofacial Surgery. 2017 Feb 1;55(2):179-84. doi: 10.1016/j.bjoms.2016.10.021.
Abdel Razek AA, Mukherji S. Imaging of sialadenitis. The neuroradiology journal. 2017 Jun;30(3):205-15. doi: 10.1177/1971400916682752
Capaccio P, Cuccarini V, Ottaviani F, Minorati D, Sambataro G, Cornalba P, Pignataro L. Comparative ultrasonographic, magnetic resonance sialographic, and videoendoscopic assessment of salivary duct disorders. Annals of Otology, Rhinology & Laryngology. 2008 Apr;117(4):245-52. doi: 10.1177/000348940811700402.
Kabenge C, Ng S, Muyinda Z, Ameda F. Diagnostic ultrasound patterns of parotid glands in human immunodeficiency virus-positive patients in Mulago, Uganda. Dentomaxillofacial Radiology. 2010 Oct 1;39(7):389-99. doi: 10.1259/dmfr/23992216
Yokosawa M, Tsuboi H, Nasu K, Hagiya C, Hagiwara S, Hirota T, Ebe H, Takahashi H, Asashima H, Kondo Y, Ogishima H. Usefulness of MR imaging of the parotid glands in patients with secondary Sjögren's syndrome associated with rheumatoid arthritis. Modern Rheumatology. 2015 May 4;25(3):415-20. doi: 10.3109/14397595.2014.958892
Wei Y, Xiao J, Pui MH, Gong Q. Tuberculosis of the parotid gland: computed tomographic findings. Acta Radiologica. 2008 May;49(4):458-61. doi: 10.1080/02841850801922912.
Ding C, Xing X, Guo Q, Liu D, Guo Y, Cui H. Diffusion-weighted MRI findings in Sjögren’s syndrome: a preliminary study. Acta Radiologica. 2016 Jun;57(6):691-700. doi: 10.1177/0284185115603245.
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