IgG4-associated disease in differential diagnosis of inflammatory orbitopathy

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IgG4-associated disease (IgG4-RD) is a systemic inflammatory disease characterized by tumorlike sclerosing masses in different organs. Differential diagnosis in orbital IgG4-RD includes majority of conditions, such as thyroid eye disease (TED), sarcoidosis, granulomatosis with polyangiitis, idiopatic orbital inflammation, limphoproliferative diseases and others. A case of IgG4-RD with different organs involvement and complicated differential diagnosis is presented. This case demonstrates very uncommon manifestation of IgG4-RD, when orbital involvement was very similar with TED. Systemic process was not recognized during a long period of time and diagnosis of IgG4-RD was established only after biopsy of abnormally increased lacrimal gland. Differential diagnosis included other systemic diseases, first of all sarcoidosis, GPA, and lymphoma. Biopsy results were consistent with the gold standard of diagnosis, e. g. more than 40% of plasma cells were IgG4 positive. This case demonstrates the necessity of orbital biopsy before starting immunosuppression to avoid inappropriate treatment strategy.

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About the authors

Yaroslav O. Grusha

Research institute of eye diseases; I.M. Sechenov first Moscow state medical university (Sechenov University)

Email: grusha-y@mail.ru
ORCID iD: 0000-0002-6461-8243
SPIN-code: 6595-4029

Russian Federation, 11A, Rossolimo street, Moscow, 119021; 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

Dilyara S. Ismailova

Research institute of eye diseases

Email: d_ismailova@bk.ru
ORCID iD: 0000-0003-3460-9191
SPIN-code: 1244-6539

Russian Federation, 11A, Rossolimo street, Moscow, 119021


Natalya Yu. Sviridenko

Endocrinology Research Centre

Author for correspondence.
Email: natsvir@inbox.ru
ORCID iD: 0000-0002-8538-5354
SPIN-code: 5889-6484

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036


Pavel I. Novikov

I.M. Sechenov first Moscow state medical university (Sechenov University)

Email: novikov-pavel@mail.ru
ORCID iD: 0000-0003-0148-5655
SPIN-code: 9876-3122

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992


Alla M. Kovrigina

National research center for hematology

Email: kovrigina.alla@gmail.com
ORCID iD: 0000-0002-1082-8659
SPIN-code: 3702-8208

Russian Federation, 4, Novyi Zykovsky pr., Moscow, 125167



  1. Stone JH, Khosroshahi A, Deshpande V, et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum. 2012;64(10):3061-3067. doi: https://doi.org/10.1002/art.34593.
  2. Sedyshev SKh, Vasiliev VI, Kovrigina AM, Nasonov EL. IgG4-linked systemic disease. Modern outlook on «old» disease. Science-practical rheumatology. 2012;(5):64-72.
  3. Hamano H, Arakura N, Muraki T, et al. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41(12):1197-1205. doi: https://doi.org/10.1007/s00535-006-1908-9
  4. Takuma K, Kamisawa T, Anjiki H, et al. Metachronous extrapancreatic lesions in autoimmune pancreatitis. Intern Med. 2010; 49(6):529−533. doi: https://doi.org/10.2169/internalmedicine.49.3038
  5. Ferry JA, Klepeis V, Sohani AR, et al. IgG4-related orbital disease and its mimics in a western population. Am J Surg Pathol. 2015;39(12):1688-1700. doi: https://doi.org/10.1097/pas.0000000000000497
  6. Masaki Y, Kurose N, Umehara H. IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century. J Clin Exp Hematop. 2011;51(1):13-20. doi: https://doi.org/10.3960/jslrt.51.13
  7. Sah RP, Chari ST. Serologic issues in IgG4-related systemic disease and autoimmune pancreatitis. Curr Opin Rheumatol. 2011;23(1): 108–113. doi: https://doi.org/10.1097/bor.0b013e3283413469
  8. Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol. 2011;64(3):237-243. doi: https://doi.org/10.1136/jcp.2010.085613
  9. Berry-Brincat A, Rose GE. Idiopathic orbital inflammation: a new dimension with the discovery of immunoglobulin G4-related disease. Curr Opin Ophthalmol. 2012;23(5):415-419. doi: https://doi.org/10.1097/ICU.0b013e32835563ec
  10. Tiegs-Heiden CA, Eckel LJ, Hunt CH, et al. Immunoglobulin G4-related disease of the orbit: imaging features in 27 patients. AJNR Am J Neuroradiol. 2014;35(7):1393-1397. doi: https://doi.org/10.3174/ajnr.A3865
  11. Siakallis LC, Uddin JM, Miszkiel KA. Imaging investigation of thyroid eye disease. Ophthalmic Plast Reconstr Surg. 2018; 34(4S Suppl 1):S41-S51. doi: https://doi.org/10.1097/IOP.0000000000001139.
  12. Hagiya C, Tsuboi H, Yokosawa M, et al. Clinicopathological features of IgG4-related disease complicated with orbital involvement. Mod Rheumatol. 2014;24(3):471-476. doi: https://doi.org/10.3109/14397595.2013.844307
  13. Detiger SE, Karim AF, Verdijk RM, et al. The treatment outcomes in IgG4-related orbital disease: a systematic review of the literature. Acta Ophthalmol. 2019;97(5):451-459. doi: https://doi.org/10.1111/aos.14048

Supplementary files

Supplementary Files Action
Fig. 1. The appearance of the patient before treatment: a - the kind of anphas, bilateral exophthalm (more pronounced on the right), esotropy on the left; B - view with head thrown.

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Fig. 1. The appearance of the patient before treatment: a - the kind of anphas, bilateral exophthalm (more pronounced on the right), esotropy on the left; B - view with head thrown.

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Fig. 2. MCCT orbits (axial projection) prior to treatment. Pronounced thickening of the external straight muscle, increase of lacrimal glands (arrows).

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Fig. 3. Lymphoid infiltration of lacrimal gland tissue is represented by numerous secondary follicles.

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Fig. 4. Areas of mature cell plasma cell infiltration with an impurity of eosinophilic granulocytes.

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Fig. 5. Lymphoid follicles are represented by clearly defined B cell structures. Reaction with anti-CD20 antibodies.

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Fig. 6. Interfollikulyarno T-cages prevail. Reaction with anti-CD3 antibodies.

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Fig. 7. Formations of mature plasma cells express IgG.

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Fig. 8. Formations of mature plasma cells express IgG4 (IgG/IgG4>40%).

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Fig. 9. Patient 's appearance 10 months after starting therapy.

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Fig. 9. Patient 's appearance 10 months after starting therapy.

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Fig. 10. CT orbits (axial projection) at the treatment period of 10 months. Significant reduction of the cross-arm of external straight muscles and lacrimal glands (arrows).

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Copyright (c) 2020 Grusha Y.O., Ismailova D.S., Sviridenko N.Y., Novikov P.I., Kovrigina A.M.

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