{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:01:28Z","timestamp":1781143288368,"version":"3.54.1"},"reference-count":17,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg\/dL, estimated glomerular filtration rate of 16 mL\/min\/1.73 m2, and proteinuria of 2874 mg\/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg\/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease.<\/jats:p>","DOI":"10.3390\/reports9020181","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:48:35Z","timestamp":1781138915000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mikulicz Disease Revealing IgG4-Related Tubulointerstitial Nephritis: A Case Report and Literature Review"],"prefix":"10.3390","volume":"9","author":[{"given":"Lissethkaren","family":"Alvarez Vargas","sequence":"first","affiliation":[{"name":"Department of Nephrology, Peruvian University Cayetano Heredia and Cayetano Heredia National Hospital, Lima 15102, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9873-3043","authenticated-orcid":false,"given":"Celia","family":"Rodr\u00edguez Tudero","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital Universitario de Salamanca, 37007 Salamanca, Spain"},{"name":"PhD Program in Surgery, Faculty of Medicine, University of Salamanca, Faculty of Medicine, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3005-7039","authenticated-orcid":false,"given":"Elena","family":"Jim\u00e9nez Mayor","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital Santa B\u00e1rbara, 42005 Soria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0633-6325","authenticated-orcid":false,"given":"Avinash","family":"Chandu Nanwani","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital General de Fuerteventura, 35600 Canarias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3690-6598","authenticated-orcid":false,"given":"Esperanza","family":"Moral Berrio","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital General Universitario de Ciudad Real, 13005 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Daniel D\u00edaz","family":"D\u00edaz Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Villalobos Navarro","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation, Hospital Barros Luco Trudeau, Santiago de Chile 8900091, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Rosario Chamorro","family":"Chamorro Asto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Instituto Nacional de Salud del Ni\u00f1o, Lima 1399, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-7231","authenticated-orcid":false,"given":"Michael","family":"Cieza Terrones","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Peruvian University Cayetano Heredia and Cayetano Heredia National Hospital, Lima 15102, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9346-2279","authenticated-orcid":false,"given":"Jos\u00e9 C.","family":"De La Flor","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital Central de la Defensa G\u00f3mez Ulla, 28047 Madrid, Spain"},{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine, Alcal\u00e1 University of Alcal\u00e1, 28805 Madrid, Spain"},{"name":"Health Sciences Doctoral Program, Faculty of Medicine, Alcala University, 28805 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/S0140-6736(14)60720-0","article-title":"IgG4-related disease","volume":"385","author":"Kamisawa","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"m1067","DOI":"10.1136\/bmj.m1067","article-title":"Advances in the diagnosis and management of IgG4-related disease","volume":"369","author":"Lanzillotta","year":"2020","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/modpathol.2012.72","article-title":"Consensus statement on the pathology of IgG4-related disease","volume":"25","author":"Deshpande","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/mr\/roae096","article-title":"The 2023 revised diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis","volume":"35","author":"Kanda","year":"2025","journal-title":"Mod. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1136\/annrheumdis-2018-214603","article-title":"Clinical phenotypes of IgG4-related disease: An analysis of two international cross-sectional cohorts","volume":"78","author":"Wallace","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3109\/s10165-011-0571-z","article-title":"Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011","volume":"22","author":"Umehara","year":"2012","journal-title":"Mod. Rheumatol."},{"key":"ref_7","first-page":"2313","article-title":"Clinicopathologic features of IgG4-related kidney disease","volume":"9","author":"Buglioni","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1053\/j.semdp.2023.12.001","article-title":"IgG4-related kidney disease: Clinicopathologic features, differential diagnosis, and mimics","volume":"41","author":"Gilani","year":"2024","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1002\/art.34593","article-title":"Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations","volume":"64","author":"Stone","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1053\/j.semdp.2012.07.008","article-title":"IgG4-related disease in the head and neck","volume":"29","author":"Ferry","year":"2012","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/art.41120","article-title":"The 2019 American College of Rheumatology\/European League Against Rheumatism classification criteria for IgG4-related disease","volume":"72","author":"Wallace","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41584-020-0500-7","article-title":"IgG4-related disease: An update on pathophysiology and implications for clinical care","volume":"16","author":"Perugino","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1681\/ASN.2011010062","article-title":"Diagnosis of IgG4-related tubulointerstitial nephritis","volume":"22","author":"Raissian","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Capecchi, R., Giannese, D., Moriconi, D., Bonadio, A.G., Pratesi, F., Croia, C., Egidi, M.F., Puxeddu, I., Tavoni, A.G., and Migliorini, P. (2021). Renal involvement in IgG4-related disease: From sunlight to twilight. Front. Med., 8.","DOI":"10.3389\/fmed.2021.635706"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1002\/art.39132","article-title":"International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease","volume":"67","author":"Khosroshahi","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1093\/mr\/roac093","article-title":"Glucocorticoids in the treatment of IgG4-related disease: Past, present, and future","volume":"33","author":"Kobayashi","year":"2023","journal-title":"Mod. Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1136\/annrheumdis-2014-206605","article-title":"Rituximab for IgG4-related disease: A prospective, open-label trial","volume":"74","author":"Carruthers","year":"2015","journal-title":"Ann. Rheum. Dis."}],"container-title":["Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-841X\/9\/2\/181\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T01:24:14Z","timestamp":1781141054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-841X\/9\/2\/181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":17,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["reports9020181"],"URL":"https:\/\/doi.org\/10.3390\/reports9020181","relation":{},"ISSN":["2571-841X"],"issn-type":[{"value":"2571-841X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]}}}