From Lymph Nodes to Orbit: a Time Travel in IgG4-related Disease

Introduction Immunglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated fibroinflammatory condition that has emerged over the past two decades as a distinct clinical entity [ 1 ], [ 2 ], [ 3 ]. It is characterized histopathologically by dense lymphoplasmatic infiltrates rich of IgG4-positive plasma cells, storiform fibrosis, and often elevated serum IgG4 levels [ 1 ], [ 2 ], [ 4 ]. The first time IgG4-RD was identified in 2001, when Hamano et al. reported about 20 patients in Japan with autoimmune sclerosing pancreatitis and high serum levels of IgG4 [ 5 ]. Since then, there have been many reports about patients with high IgG4-levels and diverse organ involvement. Many single diseases have long been viewed as conditions confined to single organs that are now seen as part of the spectrum of IgG4-RD, i.e. Mikuliczʼs syndrome, Küttnerʼs tumor, Riedelʼs thyroiditis and Ormondʼs disease [ 2 ], [ 6 ]. The disease can affect virtually every organ system, with most common involvement of the pancreas, kidneys, lacrimal and salivary glands, retroperitoneum, orbit and lymph nodes [ 3 ], [ 6 ]. Commonly, the presentation is subacute due to the enlargement of organs and few are found incidentally during diagnostic imaging or laboratory work [ 1 ], [ 2 ]. IgG4-related autoimmune pancreatitis, retroperitoneal fibrosis and IgG4-related tubulointerstitial nephritis seem to occur more often in males, whereas head and neck involvement is more common in females [ 7 ]. In general, etiology and epidemiology knowledge is still limited [ 1 ], [ 3 ]. Orbital manifestations include dacryoadenitis, orbital masses, and extraocular muscle enlargement, which can mimic thyroid eye disease, idiopathic orbital inflammation, lymphoma, granulomatosis with polyangiitis or sarcoidosis [ 8 ], [ 9 ]. Involvement of lacrimal glands and orbital involvement occur at the rate of 17 – 23% [ 10 ], [ 11 ]. In a study of 38 patients diagnosed with chronic dacryoadenitis or orbital pseudotumor, 15 (39%) met definite criteria of IgG4-RD [ 12 ]. While IgG4-associated orbitopathy generally responds well to glucocorticoid therapy, delayed or missed diagnosis may result in irreversible tissue fibrosis and functional impairment [ 10 ], [ 13 ]. Increasing awareness among ophthalmologists is therefore crucial for timely recognition and management. We report a diagnostically challenging case of IgG4-associated orbitopathy in a female patient, illustrating the variable clinical presentation and emphasizing the importance of interdisciplinary evaluation and histological confirmation in establishing the diagnosis. Furthermore, this case highlights the importance of re-evaluating previously inconclusive diagnostic results and to specifically watch out for systemic involvement. Publication History Received: 21 October 2025 Accepted: 02 December 2025 Article published online: 29 January 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 14, 70469 Stuttgart, Germany