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Mendoza-Vargas LÁ, Sevilla-Fuentes S, Bautista-Becerril B, Berthaúd-González B, Falfán-Valencia R, Félix-Martínez LP, Avila-Páez M, Manilla-González J. IgG4-RD-Associated Mikulicz Syndrome Without Classic Systemic Involvement-A Case Report. J Clin Med 2025; 14:958. [PMID: 39941629 PMCID: PMC11818687 DOI: 10.3390/jcm14030958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/27/2025] [Accepted: 01/30/2025] [Indexed: 02/16/2025] Open
Abstract
Background: IgG4-related disease is a rare, chronic inflammatory disorder characterized by lymphoplasmacytic infiltration, 'storiform' fibrosis, and elevated IgG4 levels in affected tissues. This disease has a broad and heterogeneous clinical spectrum that includes four main phenotypes: pancreatic-hepatobiliary disease, retroperitoneal/aortic fibrosis, head and neck disease, and Mikulicz syndrome. Case Description: An 85-year-old male patient with a clinical presentation, which is unusual outside Asia, of IgG4-related disease phenotype Mikulicz syndrome, characterized by bilateral dacryoadenitis, orbital pseudotumor, and no evidence of significant systemic participation. Despite extensive involvement in the orbital and glandular region, the patient did not develop serious organ complications, a behavior rarely documented in the literature. Despite the serum IgG4 levels being normal (<135 mg/dL), the clinical and radiological picture suggested IgG4-RD, emphasizing the need for a biopsy for a definitive diagnosis. Histopathological examination revealed a dense lymphoplasmacytic infiltrate, storiform fibrosis, and more than 40% IgG4-positive cells, confirming the diagnosis. Results: Treatment with prednisone was initiated alongside azathioprine for long-term control. Calcium and vitamin D3 supplementation were added to prevent glucocorticoid-induced osteoporosis. Remarkable clinical improvement was observed within 24 h, with progressive orbital and glandular symptoms resolution. Over a year, the patient exhibited complete resolution of the orbital tumors, total recovery of vision, and no relapses. The only sequelae observed were dry eye. Conclusions: This case highlights the need to consider IgG4-RD with normal serum IgG4 levels, the importance of histopathology for diagnosis, and the efficacy of steroids as first-line treatment. A multidisciplinary approach is essential for timely treatment.
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Affiliation(s)
| | | | - Brandon Bautista-Becerril
- Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico;
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | | | - Ramcés Falfán-Valencia
- Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico;
| | | | - Mauricio Avila-Páez
- Facultad de Medicina, Universidad Nacional Autónoma de México, Campus Ciudad Universitaria, Mexico City 04510, Mexico
| | - Jennifer Manilla-González
- Facultad de Medicina, Universidad Popular Autónoma del Estado de Puebla, Campus Puebla, Puebla 72410, Mexico
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Kamekura R, Sakamoto H, Yajima R, Yamamoto K, Okuni T, Yamamoto M, Takahashi H, Ichimiya S, Takano K. Recent Evidence of the Role of CD4 + T Cell Subsets in IgG4-related Disease. JMA J 2025; 8:40-47. [PMID: 39926068 PMCID: PMC11799721 DOI: 10.31662/jmaj.2024-0096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 09/30/2024] [Indexed: 02/11/2025] Open
Abstract
CD4+ T cells, the so-called T helper cells, are one of the main players in the human immune system, which can regulate acquired immunity. Dysfunction of the acquired immune system induces various chronic inflammatory diseases such as malignancies and autoimmune diseases. IgG4-related disease (IgG4-RD) is also a chronic inflammatory disease that is characterized by elevated serum IgG4 concentration and infiltration of IgG4-positive plasma cells in affected tissues. Despite that remarkable advances in understanding the pathogenesis of IgG4-RD have been on the rise, the detailed mechanisms by which IgG4-RD develops are still unknown. In fact, CD4+ T cells abundantly infiltrate at lesions of IgG4-RD, and they are also associated with the pathogenesis of other refractory chronic inflammatory diseases. Therefore, our focus was on CD4+ T cells, and we previously reported the roles of their subsets including regulatory T cells, CD4 cytotoxic T lymphocytes, T follicular helper (Tfh) cells, T follicular regulatory cells, and T peripheral helper (Tph) cells in IgG4-RD. Among the subsets, Tph cells play an important role in generating ectopic lymphoid structures at inflammatory sites. Moreover, we found that circulating Tph cells are increased in IgG4-RD patients. Unlike Tfh cells, Tph cells express high levels of chemokine receptors and cytotoxic molecules. Thus, they can infiltrate affected tissues and exert a cytotoxic function. Additionally, our latest observations demonstrated that Tph cells interact with extrafollicular B cells in affected tissues. Hence, Tph cells may collaborate with a specific B-cell subset, and they play a role in the maintenance of persistent fibroinflammation in lesions of IgG4-RD. Tph cells may have an important role to play in the pathogenesis of not only IgG4-RD but also other chronic inflammatory diseases. This review summarizes and discusses the possible pathologic roles of CD4+ T cell subsets including Tph cells in IgG4-RD.
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Affiliation(s)
- Ryuta Kamekura
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Human Immunology, Research Institute for Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hiroshi Sakamoto
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ryoto Yajima
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keisuke Yamamoto
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tsuyoshi Okuni
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Motohisa Yamamoto
- Division of Rheumatology, Center for Antibody and Vaccine Therapy, Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hiroki Takahashi
- Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shingo Ichimiya
- Department of Human Immunology, Research Institute for Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Kenichi Takano
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
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Shah M, Bajan K, Samant R. Navigating the labyrinth: Phenotypes of IgG4-related disease. J Postgrad Med 2025; 71:45-48. [PMID: 40085066 PMCID: PMC12011329 DOI: 10.4103/jpgm.jpgm_757_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/08/2025] [Accepted: 01/20/2025] [Indexed: 03/16/2025] Open
Abstract
ABSTRACT We report a case of an elderly female with subacute submental neck swelling, dry cough, and a history of significant weight loss. Unexpectedly, a left submandibular chronic sialadenitis was noted on ultrasound of the neck, along with a thyroid nodule that, on biopsy, showed lymphocytic infiltration. High-resolution computed tomography of the lungs revealed multifocal irregular consolidations with lymphadenopathy, and possible infective causes, including tuberculosis, were ruled out after a thorough microbiological evaluation. It was only after a positron emission tomography-guided lung biopsy with specialized immunohistochemical staining was performed that the diagnosis of IgG4-related disease (IgG4-RD) was confirmed. Our patient exhibited overlapping features of head and neck-limited and Mikulicz/systemic phenotype of IgG4. In this case report, we highlight the clinical phenotypes of IgG4-RD, their respective differential diagnoses, and discuss our approach to this challenging case.
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Affiliation(s)
- M Shah
- Department of Internal Medicine, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
| | - K Bajan
- Department of Critical Care Medicine, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
| | - R Samant
- Department of Rheumatology, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
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Badshah MB, Khan QA, Kazi N, Ansari RA, Verma R. IgG4-related retroperitoneal fibrosis presenting as a peripancreatic mass: a case series. Ann Med Surg (Lond) 2025; 87:36-42. [PMID: 40109592 PMCID: PMC11918540 DOI: 10.1097/ms9.0000000000002749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 11/05/2024] [Indexed: 03/22/2025] Open
Abstract
Introduction IgG4-related disease (IgG4-RD) is a chronic, immune-mediated disorder characterized by widespread inflammation and fibrosis, leading to potential organ dysfunction if untreated. Often underdiagnosed due to subtle and varied symptoms, the disease can affect multiple organ systems. This case series highlights two patients who were diagnosed as cases of IgG4-related retroperitoneal fibrosis. Methods A total of two patients were included in this prospective case series who presented to the gastroenterology department of a tertiary care hospital with the same signs and symptoms and were diagnosed with IgG4-related retroperitoneal fibrosis (IgG4-RPF). Case summary Two patients were included in our case series, aged 25 and 26 years. The chief complaints included dull, radiating epigastric pain, other symptoms include diffuse abdominal pain, intensified, accompanied by nausea, vomiting, and episodic diarrhea, and a history of B-cell lymphoproliferative disorder. Endoscopic ultrasound (EUS)-)-guided biopsies were performed, showing findings consistent with (IgG4-RPF). Both patients were started on a regimen of prednisolone, pantoprazole, and vitamin D, which they tolerated well without adverse effects. They were advised to follow up with a CT scan after one month. Conclusion IgG4-related disease (IgG4-RD) is a rare, chronic condition often presenting as retroperitoneal fibrosis (RPF) and affecting multiple organs. Serum IgG4 levels can be normal in certain cases, histopathological and radiological investigations are necessary for the correct diagnosis. Early initiation of immunosuppressive drugs are necessary for the disease control.
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Affiliation(s)
| | | | - Naima Kazi
- Khyber Girls Medical College, Peshawar, Pakistan
| | | | - Ravina Verma
- St. George's University School of Medicine, True Blue, Grenada
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Agarwal K, Jain S, Kaushal S. Immunoglobulin G4-related disease of the testis masquerading as a testicular mass: a clinical dilemma. BMJ Case Rep 2024; 17:e262636. [PMID: 39675791 DOI: 10.1136/bcr-2024-262636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2024] Open
Abstract
Immunoglobulin G4 (IgG4)-related disease is a rare immune-mediated fibro-inflammatory disorder with many clinical manifestations. Most commonly affected sites include the pancreas, salivary glands, kidneys, lachrymal glands, biliary tree, aorta and retroperitoneum; testicular involvement is a rare entity. This report describes a man in his 20s who presented with a persistent painless mass in his left testis. After a thorough examination he underwent orchiectomy to rule out any malignancy of the testis. Histopathology and immunohistochemistry were suggestive of IgG4-related disease. Systemic evaluation showed normal IgG4 levels with no other site of involvement. This is a unique presentation of this rare diagnosis and remains a diagnostic challenge which is difficult to distinguish from the more common testicular malignancy. We conducted a review of the current literature regarding IgG4-related disease to complement the case discussion and provide a comprehensive review regarding this diagnostic dilemma.
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Affiliation(s)
- Keshav Agarwal
- Urology, All India Institute of Medical Sciences New Delhi, New Delhi, Delhi, India
| | - Siddharth Jain
- Urology, All India Institute of Medical Sciences New Delhi, New Delhi, Delhi, India
| | - Seema Kaushal
- Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, India
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Yamamoto M, Kanda M, Mizushima I, Kanno A, Umemura T, Ikeura T, Kodama Y, Dobashi H, Tanaka Y, Masamune A, Moriyama M, Saeki T, Matsui S, Origuchi T, Masaki Y, Asada M, Umehara H, Seno H, Naitoh I, Yamamoto S, Iwasaki E, Kubota K, Tanoue S, Nishino T, Tsuboi H, Matsumoto Y, Isayama H, Goto H, Notohara K, Uchida K, Kawabe K, Yamada K, Kasashima S, Takahira M, Sato Y, Kawachi I, Yamaguchi I, Okazaki K, Nakamura S, Matsuda F, Ishikawa H, Kawano M. Clinical profile of IgG4-related disease in Japan based on the rare disease data registry. Immunol Med 2024:1-11. [PMID: 39607031 DOI: 10.1080/25785826.2024.2430812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 10/14/2024] [Indexed: 11/29/2024] Open
Abstract
We started a registry for cases of immunoglobulin (Ig)G4-related disease (IgG4-RD) in December 2019 to clarify the clinical profile of IgG4-RD. In this study, clinical information from 854 cases registered by February 16, 2024 was analyzed from multiple perspectives. Diagnosis of IgG4-RD was made in 808 cases, comprising 638 definite, 38 probable, and 132 possible. The mean ± SD age at time of enrollment of the 808 cases was 67.9 ± 11.3 years, with 68.8% being male. The pancreas was the most frequently affected organ (49.8%), followed by the submandibular glands (46.2%) and lacrimal glands (30.6%). This study reconfirmed the pancreas and head-and-neck region as major affected areas in IgG4-RD. Clinically, submandibular adenitis and autoimmune pancreatitis often occur together in the same patient, but no association between the two organs was observed in our analysis. Regarding diagnosis, the comprehensive diagnostic criteria were most commonly used (63.6%). Storiform fibrosis and phlebitis obliterans were detected at different frequencies in different organs. In summary, this registry study identified clinical, imaging, hematologic, and pathologic findings in 808 Japanese patients with IgG4-RD. The frequency of affected organs and their characteristic pathological findings will be particularly useful for future practice.
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Affiliation(s)
- Motohisa Yamamoto
- The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | | | | | | | | | | | | | | | - Yoshiya Tanaka
- University of Occupational and Environmental Health, Fukuoka, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Takayoshi Nishino
- Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan
| | | | - Yasushi Matsumoto
- National Hospital Organization Kanazawa Medical Center, Ishikawa, Japan
| | | | | | - Kenji Notohara
- Kurashiki Central Hospital, Ohara Health Care Foundation, Okayama, Japan
| | | | - Ken Kawabe
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | | | | | | | | | | | | | | | | | | | | | - Mitsuhiro Kawano
- Kanazawa University, Ishikawa, Japan
- Kanazawa Medical University, Ishikawa, Japan
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Buglioni A, Jenkins SM, Nasr SH, Zhang P, Gibson IW, Alexander MP, Herrera Hernandez LP, Fidler ME, Takahashi N, Hogan MC, Cornell LD. Clinicopathologic Features of IgG4-Related Kidney Disease. Kidney Int Rep 2024; 9:2462-2473. [PMID: 39156178 PMCID: PMC11328570 DOI: 10.1016/j.ekir.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 04/29/2024] [Accepted: 05/06/2024] [Indexed: 08/20/2024] Open
Abstract
Introduction IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that can involve nearly any organ. IgG4-RD can affect the kidney in different disease patterns, collectively referred to as IgG4-related kidney disease (IgG4-RKD). Methods We conducted a tissue-based cohort study with clinicopathological correlation in 125 patients with IgG4-RKD. Results The mean age at biopsy (n = 120) or nephrectomy (n = 5) was 63 years; 80% were male. One hundred eighteen patients (94%) had IgG4-related tubulointerstitial nephritis (IgG4-TIN); 20 patients (16%) had IgG4-related membranous glomerulonephritis (IgG4-MGN; 13 with concurrent IgG4-TIN). The primary clinical indication for biopsy/nephrectomy was acute or chronic renal failure in 78%, proteinuria in 17%, and mass lesion(s) in 15% (with overlap in primary indication). Fifty-two percent patients (41/79) had abnormal radiographic findings, including masses in 30% (24/79). All patients with IgG4-MGN had proteinuria. Extrarenal involvement by IgG4-RD was present in 79%. Median serum creatinine at presentation was 2.5 mg/dl (range 0.7-12). Serum IgG and/or IgG4 was increased in 91% (53/58); hypocomplementemia was present in 56% (43/77). Light microscopy showed plasma cell-rich interstitial nephritis in all cases of IgG4-TIN. Ninety-two percent of patients showed increased IgG4+ plasma cells. Seven percent showed an acute interstitial nephritis (AIN) pattern, and 5% showed non-necrotizing arteritis. Tubular basement membrane immune deposits were present in 83% of IgG4-TIN. Treatment information was available for 71 patients; 62 were treated with immunosuppression. Of those with elevated creatinine, 72% (41/57) showed a treatment response. Conclusion This largest tissue-based series more clearly defines the disease phenotype of IgG4-RKD.
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Affiliation(s)
- Alessia Buglioni
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Sarah M. Jenkins
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota, USA
| | - Samih H. Nasr
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Pingchuan Zhang
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ian W. Gibson
- Department of Pathology, University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada
| | - Mariam P. Alexander
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Loren P. Herrera Hernandez
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Mary E. Fidler
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Naoki Takahashi
- Division of Abdominal Imaging, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Marie C. Hogan
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Minnesota, USA
| | - Lynn D. Cornell
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
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Alkan A, Durhan G, Yardimci GK, Ozden Sertcelik U, Farisogullari B, Ariyurek M, Karadag O, Koksal D. Immunoglobulin G4-related thoracic disease: clinical and radiological findings of a Turkish cohort. SARCOIDOSIS, VASCULITIS, AND DIFFUSE LUNG DISEASES : OFFICIAL JOURNAL OF WASOG 2024; 41:e2024030. [PMID: 38940718 PMCID: PMC11275537 DOI: 10.36141/svdld.v41i2.14165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 02/08/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND AND AIM Thoracic involvement of Immunoglobulin G4-related disease (IgG4-RD) is relatively rare and may be disregarded at the time of initial diagnosis due to its asymptomatic nature. This study aimed to ascertain the prevalence and patterns of thoracic involvement in a retrospective cohort of Turkish patients with IgG4-RD. METHODS A total of 90 patients (47 males and 43 females, with a mean age of 57.7±15.5 years) diagnosed with IgG4-RD were reviewed retrospectively. All computed tomography (CT) scans were re-evaluated by two thoracic radiologists and IgG4-related thoracic disease was assessed on four compartments: The mediastinum, pulmonary parenchyma, airways, and pleura. IgG4-related thoracic disease was categorized as: definite, highly probable, probable or possible. RESULTS There were 64 patients who had undergone at least one thorax CT examination, and 18 (28%) were diagnosed with IgG4-related thoracic disease. The rate of IgG4-related thoracic disease increased by 20% and reached a ratio of 48.4% (n=31) after a thorough reevaluation of registry data specifically to thoracic findings. The mediastinum was the most frequently involved compartment, affecting 16 (51.6%) patients, followed by pulmonary parenchyma in 14 (45.2%) patients, and airways and pleura in 10 (32.3%) patients each. Other organ involvements were more prevalent and IgG4 levels were higher in patients with thoracic involvement. Eosinophils were significantly elevated in patients with thoracic involvement (p=0.023). CONCLUSIONS IgG4-related thoracic disease is heterogeneous and likely to be more prevalent than currently recognized. The mediastinum is the most frequently involved compartment. It is important to assess IgG4-related thoracic disease at the time of initial diagnosis. Elevated levels of serum IgG4 and eosinophils, as well as a greater number of organ involvements may serve as indicators of thoracic involvement.
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Affiliation(s)
- Asli Alkan
- Yildirim Beyazit University, Yenimahalle Training and Research Hospital, Chest Diseases Clinic, Ankara, Turkey
- Formerly Hacettepe University Faculty of Medicine, Department of Chest Diseases
| | - Gamze Durhan
- Hacettepe University Faculty of Medicine, Department of Radiology, Ankara, Turkey
| | - Gozde Kubra Yardimci
- Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Hacettepe University Vasculitis Research Centre, Ankara, Turkey
| | - Umran Ozden Sertcelik
- Ankara City Hospital, Chest Diseases Clinic, Ankara, Turkey
- Formerly Hacettepe University Faculty of Medicine, Department of Chest Diseases
| | - Bayram Farisogullari
- Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Hacettepe University Vasculitis Research Centre, Ankara, Turkey
| | - Macit Ariyurek
- Hacettepe University Faculty of Medicine, Department of Radiology, Ankara, Turkey
| | - Omer Karadag
- Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Hacettepe University Vasculitis Research Centre, Ankara, Turkey
| | - Deniz Koksal
- Hacettepe University Faculty of Medicine, Department of Chest Diseases, Ankara, Turkey
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Towheed ST, Zanjir W, Ren KYM, Garland J, Clements-Baker M. Renal Manifestations of IgG4-Related Disease: A Concise Review. Int J Nephrol 2024; 2024:4421589. [PMID: 38957780 PMCID: PMC11217581 DOI: 10.1155/2024/4421589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 04/28/2024] [Accepted: 06/10/2024] [Indexed: 07/04/2024] Open
Abstract
IgG4-related disease (IgG4-RD) is an immune-mediated disorder marked by fibro-inflammatory masses that can infiltrate multiple organ systems. Due to its relatively recent discovery and limited understanding of its pathophysiology, IgG4-related disease may be difficult to recognize and is consequently potentially underdiagnosed. Renal involvement is becoming regarded as one of the key features of this disease. To date, the most well-recognized renal complication of IgG4-related disease is tubulointerstitial nephritis, but membranous glomerulonephritis, renal masses, and retroperitoneal fibrosis have also been reported. This concise review has two objectives. First, it will briefly encapsulate the history, epidemiology, and presentation of IgG4-related disease. Second, it will examine the reported renal manifestations of IgG4-related disease, exploring the relevant histology, imaging, clinical features, and treatment considerations. This synthesis will be highly relevant for nephrologists, rheumatologists, general internists, and renal pathologists to raise awareness and help improve early recognition of IgG4-related kidney disease (IgG4-RKD).
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Jain AK, Sundaram S, Tyagi U, Kale A, Patkar S, Patil P, Deodhar K, Ramadwar M, Yadav S, Chaudhari V, Shrikhande S, Mehta S. IgG4-related disorders of the gastrointestinal tract: Experience from a tertiary care centre with systematic review of Indian literature. Indian J Gastroenterol 2024; 43:548-556. [PMID: 37823986 DOI: 10.1007/s12664-023-01437-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/24/2023] [Indexed: 10/13/2023]
Abstract
INTRODUCTION IgG4-related disease (IgG4-RD) is a rare disease entity in India. We aimed at studying the clinical profile of IgG4-RD of gastrointestinal tract (GIT) from our centre, while systematically reviewing data from India. METHODS Retrospective review of IgG4-RD of GIT was done using electronic medical records between January 2013 and July 2022. Literature search was done for studies of IgG4-RD of the GIT reported from India from 2000 till January 2023. Case series, case reports of IgG4-RD of GIT and case reports describing GIT with multi-organ involvement were included in the review. Primary outcome measure was response to treatment. Secondary outcome measure was relapse after remission. RESULTS Thirty-one patients were included with 71% (22/31) having autoimmune pancreatitis. The diagnosis was achieved on surgical specimen in 35% (11/31) patients. Steroid was given to 64% (20/31) patients with remission achieved in 70% (14/20) patients. Four patients exhibitted response to prolonged course of steroids with maintenance azathioprine. Relapse was seen in four (20%) patients who achieved remission. Of 731 articles screened, 48 studies (four case series and 44 case reports) were included in the literature review. Of 95 patients described, steroids were given to 65.2% (62/95), while surgery was done in 33.6% (32/95). Remission was seen in 96.6% (85/88) with relapse occurring in 11.4% (10/88) patients on follow-up. CONCLUSION One-third patients of IgG4-RD of GIT are diagnosed after surgery. Response to steroids is good with relapse occurring in up to 12% patients.
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Affiliation(s)
- Aadish Kumar Jain
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Sridhar Sundaram
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India.
| | - Unique Tyagi
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Aditya Kale
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Shraddha Patkar
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Prachi Patil
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Kedar Deodhar
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Mukta Ramadwar
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Subhash Yadav
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Vikram Chaudhari
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Shailesh Shrikhande
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Shaesta Mehta
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
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Czarnywojtek A, Agaimy A, Pietrończyk K, Nixon IJ, Vander Poorten V, Mäkitie AA, Zafereo M, Florek E, Sawicka-Gutaj N, Ruchała M, Ferlito A. IgG4-related disease: an update on pathology and diagnostic criteria with a focus on salivary gland manifestations. Virchows Arch 2024; 484:381-399. [PMID: 38316669 DOI: 10.1007/s00428-024-03757-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/12/2024] [Accepted: 01/29/2024] [Indexed: 02/07/2024]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality. Given its broad clinical spectrum, physicians of all specialties may be the first clinicians facing this diagnostic challenge. Outside the pancreatobiliary system, the head and neck represents the major site of IgG4-RD with variable organ-specific diffuse or mass-forming lesions. In up to 75% of cases, elevated serum IgG4 levels are observed, but this figure possibly underestimates the fraction of seronegative cases, as the disease manifestations may present metachronously with significant intervals. Together with negative serology, this can lead to misdiagnosis of seronegative cases. A standardized nomenclature and diagnostic criteria for IgG4-RD were established in 2012 and revised in 2020 facilitating scientific research and expanding the range of diseases associated with IgG4 abnormalities. In addition to orbital pseudotumor, dacryoadenitis, Riedel thyroiditis, sinonasal manifestations, and rare miscellaneous conditions, IgG4-related sialadenitis is one of the most frequent presentations in the head and neck region. However, controversy still exists regarding the relationship between sialadenitis and IgG4-RD. This review focuses on the clinicopathological features of IgG4-related sialadenitis and its contemporary diagnostic criteria.
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Affiliation(s)
- Agata Czarnywojtek
- Department of Pharmacology, Poznan University of Medical Sciences, 60-806, Poznan, Poland
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Abbas Agaimy
- Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany
| | | | - Iain J Nixon
- Department of Otorhinolaryngology Head and Neck Surgery, NHS Lothian, Edinburgh, EH8 9YL, UK
| | - Vincent Vander Poorten
- Otorhinolaryngology-Head and Neck Surgery, KU Leuven University Hospitals, 3000, Leuven, Belgium
- Department of Oncology, Section Head and Neck Oncology, KU Leuven, 3000, Leuven, Belgium
| | - Antti A Mäkitie
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, and the Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland
| | - Mark Zafereo
- Department of Head & Neck Surgery, MD Anderson Cancer Center, Houston, TX, 77005, USA
| | - Ewa Florek
- Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, 60-806, Poznan, Poland.
| | - Nadia Sawicka-Gutaj
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Alfio Ferlito
- International Head and Neck Scientific Group, 35100, Padua, Italy
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Korkmaz C, Yıldırım R, Dinler M, Cansu DU. Coexistence of IgG4-related disease and ANCA-associated vasculitis: case report and review of the literature. Rheumatol Int 2024; 44:557-572. [PMID: 37634133 DOI: 10.1007/s00296-023-05419-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 08/03/2023] [Indexed: 08/29/2023]
Abstract
IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that is characterized by storiform fibrosis, infiltration of IgG4-positive lymphocytes, obliterative phlebitis, and high IgG4 levels. Since IgG4-RD affects a wide variety of organs, a differential diagnosis must include multiple conditions. IgG4-RD is also believed to coexist with certain diseases. In recent years, case reports and case series describing the co-occurrence of IgG4-RD and ANCA-associated vasculitis (AAV) have been published. We intended to evaluate patients with IgG4-RD and AAV overlap in the literature using a case similar to one that was diagnosed and monitored in our department. We searched the databases of Web of Science, Scopus, and Google Scholar as well as PubMed with the keywords ANCA, IgG4, IgG4-RD, granulomatosis with polyangiitis, Wegener's granulomatosis, microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis, and Churg-Strauss syndrome. Cases and Case series addressing the coexistence of IgG4-RD and AAV have been selected. Comprehensive diagnostic criteria are used to diagnose IgG4-RD. The Chapel Hill Consensus Conference nomenclature criteria were used for the inclusion of AAV. Out of a total of 910 publications, 20 articles, including 65 cases, were found to be eligible. Forty-seven cases with IgG4-RD were evaluated as definitive (71.2%), 10 cases as probable (15.1%), and 9 cases as possible IgG4-RD (13.6%). 26 patients were diagnosed with GPA, 1 patient with localized GPA, 23 patients with MPA, and 4 patients with EGPA. The aorta, lacrimal tissue, pancreas, and retroperitoneum are the sites of IgG4-RD rather than AAV. AAV and IgG4-RD might coexist in the same patient. IgG4-RD is mainly associated with GPA.
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Affiliation(s)
- Cengiz Korkmaz
- Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.
- Department of Rheumatology, Faculty of Medicine, Eskişehir Osmangazi University, 26480, Eskisehir, Turkey.
| | - Reşit Yıldırım
- Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey
| | - Mustafa Dinler
- Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey
| | - Döndü U Cansu
- Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey
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Mizushima I, Saeki T, Kobayashi D, Sawa N, Hayashi H, Taniguchi Y, Nakata H, Yamada K, Matsui S, Yasuno T, Masutani K, Nagasawa T, Takahashi H, Ubara Y, Yanagita M, Kawano M. Improved Renal Function in Initial Treatment Improves Patient Survival, Renal Outcomes, and Glucocorticoid-Related Complications in IgG4-Related Kidney Disease in Japan. Kidney Int Rep 2024; 9:52-63. [PMID: 38312790 PMCID: PMC10831353 DOI: 10.1016/j.ekir.2023.10.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/26/2023] [Accepted: 10/16/2023] [Indexed: 02/06/2024] Open
Abstract
Introduction We aimed to clarify long-term renal prognosis, complications of malignancy, glucocorticoid (GC) toxicity, and mortality in immunoglobulin G4 (IgG4)-related kidney disease (IgG4-RKD). Methods Reviewing the medical records of 95 patients with IgG4-RKD, we investigated clinical and pathologic features at baseline, the course of renal function, complications of malignancy, GC toxicity, and mortality during follow-up (median 71 months). The standardized incidence ratio (SIR) of malignancy and standardized mortality ratio were calculated using national statistics. Factors related to outcomes were assessed by Cox regression analyses. Results At diagnosis, the median estimated glomerular infiltration rate (eGFR) was 46 ml/min per 1.73 m2. GC achieved initial improvement. Additional renal function recovery within 3-months of initial treatment occurred in patients with highly elevated serum IgG and IgG4 levels and hypocomplementemia. During follow-up, 68%, 17%, and 3% of the patients had chronic kidney disease (CKD), >30% eGFR decline, and end-stage renal disease (ESRD), respectively. Age-adjusted and sex-adjusted Cox regression analyses indicated that eGFR (hazard ratio [HR], 0.71) and extensive fibrosis (HR, 2.58) at treatment initiation had a significant impact on the time to CKD. Ten patients died, and the standardized mortality ratio was 0.94. The SIR of malignancy was 1.52. The incidence rate (IR) of severe infection was 1.80/100 person-years. Cox regression analyses showed that the best eGFR within 3 months after treatment initiation were associated with lower mortality (HR 0.67) and fewer severe infections (HR 0.63). Conclusion This study suggests that more renal function recovery through early treatment initiation may improve patient survival, renal outcomes, and some GC-related complications in IgG4-RKD.
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Affiliation(s)
- Ichiro Mizushima
- Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
| | - Takako Saeki
- Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Daisuke Kobayashi
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan
| | - Naoki Sawa
- Department of Nephrology Center, Toranomon Hospital, Kawasaki, Japan
| | - Hiroki Hayashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Yoshinori Taniguchi
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi University, Nankoku-shi, Japan
| | - Hirosuke Nakata
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto City, Japan
| | - Kazunori Yamada
- Department of Hematology and Immunology, Kanazawa Medical University, Kahoku-gun, Japan
| | - Shoko Matsui
- Health Administration Center, University of Toyama, Toyama City, Japan
| | - Tetsuhiko Yasuno
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Jonan-Ku, Japan
| | - Kosuke Masutani
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Jonan-Ku, Japan
| | - Tasuku Nagasawa
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan
| | - Hiroki Takahashi
- Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yoshifumi Ubara
- Department of Nephrology Center, Toranomon Hospital, Kawasaki, Japan
| | - Motoko Yanagita
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto City, Japan
| | - Mitsuhiro Kawano
- Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
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Gader G, Hamza M, Jaziri F, Chelly I, Zammel I, Rkhami M, Badri M. Intracranial inflammatory pseudotumour related to IgG4: A very rare case. CASPIAN JOURNAL OF INTERNAL MEDICINE 2024; 15:354-359. [PMID: 38807725 PMCID: PMC11129071 DOI: 10.22088/cjim.15.2.354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/17/2022] [Accepted: 09/05/2022] [Indexed: 05/30/2024]
Abstract
Background Intracranial inflammatory pseudotumours (IPT) are rare entities that frequently lead to misdiagnosis with malignant lesions. The identification of these lesions is difficult, but important to avoid inadvertent iatrogenicity and to adjust therapeutic protocols. Case Presentation We report the case of a 30-year-old man who presented a single tonic-clonic seizure. Brain imaging showed a right frontal lesion with intra and extra axial components. Facing the radiologic presentation, a brain tumor was suspected, thus the patient underwent surgery. Pathological exam concluded to a plasma cell granuloma. A whole-body CT-scan showed only a thoracic aortitis. Complete blood work studies came back negative. The patient was also tested for an array of antibodies among which antinuclear antibodies were positive (blood level superior to 1/100). CSF evaluation revealed clear fluid with normal glucose concentration, normal protein levels and lymphocytic pleocytosis. Finally, IgG-4 plasma levels were elevated which led to the diagnosis of an IgG4-RD. The patient was put under prednisolone with a favorable outcome. Conclusion IPT have several etiologies, among which IgG4 related disease may be one of the less known as only 2 cases have previously been reported. Herein, we report a new case of a young man who presented for seizures related to an intracranial lesion of an IgG4 related disease. The challenge is to suspect such conditions to avoid unnecessary surgeries.
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Affiliation(s)
- Ghassen Gader
- Department of Neurosurgery, Trauma and Burns Center, University of Tunis-El Manar, Faculty of Medicine of Tunis, Ben Arous, Tunisia
| | - Meissa Hamza
- Department of Neurosurgery, Trauma and Burns Center, University of Tunis-El Manar, Faculty of Medicine of Tunis, Ben Arous, Tunisia
| | - Ftima Jaziri
- Department of Internal Medicine, Sadok Mokaddem Hospital of Jerba, Ben Arous, Tunisia
| | - Ines Chelly
- Department of Pathology, La Rabta Hospital, University of Tunis-El Manar, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Ihsèn Zammel
- Department of Neurosurgery, Trauma and Burns Center, University of Tunis-El Manar, Faculty of Medicine of Tunis, Ben Arous, Tunisia
| | - Mouna Rkhami
- Department of Neurosurgery, Trauma and Burns Center, University of Tunis-El Manar, Faculty of Medicine of Tunis, Ben Arous, Tunisia
| | - Mohamed Badri
- Department of Neurosurgery, Trauma and Burns Center, University of Tunis-El Manar, Faculty of Medicine of Tunis, Ben Arous, Tunisia
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Yu Y, Wang QQ, Jian L, Yang DC. Infrequent organ involvement in immunoglobulin G4-related prostate disease: A case report. World J Clin Cases 2023; 11:7485-7491. [PMID: 37969446 PMCID: PMC10643058 DOI: 10.12998/wjcc.v11.i30.7485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 08/26/2023] [Accepted: 09/25/2023] [Indexed: 10/25/2023] Open
Abstract
BACKGROUND Immunoglobulin G4-related prostate disease (IgG4-RPD) characterized by a high count of IgG4-positive plasma cells has distinctive serological and radiological findings. Here we report a case of a patient who was successfully treated for IgG4-RPD, which manifested as frequent micturition, dysuric, and systemic lymphadenopathy. CASE SUMMARY The patient was a 33-year-old man who was referred to our hospital because of urinary tract symptoms that had persisted for 4 years. A physical examination revealed systemic lymphadenopathy and blood tests showed hyperglobulinemia with an IgG level of 18.90 g/L and an IgG4 level of 18.40 g/L. Computed tomography (CT) revealed bilateral lacrimal gland, right parotid gland and prostatic enlargement. Based on these findings, IgG4-RD was suspected, and further pathological examination and follow-up results showed expected results. Finally, the patient was diagnosed with IgG4-RPD based on clinical symptoms, pathological examination, therapeutic effects, and follow-up results. He received 50 mg oral prednisolone (the dose was gradually reduced and a low dose was used for long-term maintenance) in combination with cyclophosphamide 1.0 g via an intravenous drip for 6 mo. One year after the treatment was initiated, he was free of urinary or other complaints and his serum IgG4 level normalized. CONCLUSION In IgG4-RPD with severe urinary tract symptoms, radiological findings should be carefully examined. IgG4-RPD prognosis is good because the disease responds well to glucocorticoids. Furthermore, it is urgent for clinicians and pathologists to improve their understanding of IgG4-RPD.
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Affiliation(s)
- Yi Yu
- Department of Critical Care Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Qian-Qian Wang
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
| | - Li Jian
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Deng-Can Yang
- Anesthesiology Department, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China
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16
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Chen L, Nong L, Liu J, Chen L, Shao Y, Sun X. Value of High-Frequency Ultrasonography in the Qualitative and Semi-Quantitative Assessment of Immunoglobulin G4-Related Submandibular Sialadenitis. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2023; 42:2235-2246. [PMID: 37162711 DOI: 10.1002/jum.16240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 04/06/2023] [Accepted: 04/09/2023] [Indexed: 05/11/2023]
Abstract
OBJECTIVE To assess the value of high-frequency ultrasonography in the evaluation of immunoglobulin G4-related submandibular sialadenitis (IgG4-SS). METHODS Thirty-four submandibular glands in 17 patients with IgG4-SS were retrospectively enrolled, as well as 34 submandibular glands in 17 healthy control subjects. Qualitative ultrasonic features including submandibular gland size, border, echogenicity, and vascularity were reviewed. Two different scoring systems (0-16 and 0-48, respectively) were used for semi-quantitative analysis of imaging features. Comparison of both qualitative and semi-quantitative ultrasonic analysis were made between patients with IgG4-SS and healthy controls. Spearman correlation was used to explore relationships between variables. RESULTS The submandibular glands with IgG4-SS presented with enlarged size, rough border, increased vascularity, and abnormal echogenicity (All P < .05). The most common echogenicity pattern for IgG-SS was diffuse hypoechoic foci pattern (44.1%), followed by superficial hypoechoic pattern (20.6%), tumor-like pattern (14.7%), and diffuse hypoechogenicity pattern (11.8%). Most IgG4-SS glands presented linear hyperechogenicity in parenchyma (91.2%). Based on both scoring system, scores of IgG4-SS were significantly higher than those of the controls (All P < .05). Association analysis of both scoring systems showed positive correlation of scores with vascularity in the gland parenchyma (All P < .05). CONCLUSION The ultrasonic features of IgG4-SS comprise enlarged gland, rough border, increased vascularity, and abnormal echogenicity, which correlate with its pathological characteristics. The most common echogenicity pattern for IgG4-SS was diffuse hypoechoic foci pattern. Semi-quantitative analysis systems could be useful in the assessment of IgG4-SS. Ultrasound is a potential, valuable, and non-invasive tool for the diagnosis and evaluation of IgG4-SS.
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Affiliation(s)
- Lei Chen
- Department of Ultrasound, Peking University First Hospital, Beijing, China
| | - Lin Nong
- Department of Pathology, Peking University First Hospital, Beijing, China
| | - Jumei Liu
- Department of Pathology, Peking University First Hospital, Beijing, China
| | - Luzeng Chen
- Department of Ultrasound, Peking University First Hospital, Beijing, China
| | - Yuhong Shao
- Department of Ultrasound, Peking University First Hospital, Beijing, China
| | - Xiuming Sun
- Department of Ultrasound, Peking University First Hospital, Beijing, China
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Bararia A, Das A, Mitra S, Banerjee S, Chatterjee A, Sikdar N. Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways. World J Gastrointest Oncol 2023; 15:1505-1519. [PMID: 37746645 PMCID: PMC10514732 DOI: 10.4251/wjgo.v15.i9.1505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/29/2023] [Accepted: 08/01/2023] [Indexed: 09/13/2023] Open
Abstract
Pancreatic cancer (PanCa) presents a catastrophic disease with poor overall survival at advanced stages, with immediate requirement of new and effective treatment options. Besides genetic mutations, epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target. Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails. Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients. Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies. Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance. Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions, and novel pharmacological strategies that target these components could potentially lead to breakthroughs. We aim to highlight the possibilities that exist and the potential therapeutic interventions.
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Affiliation(s)
- Akash Bararia
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India
| | - Amlan Das
- Department of Biochemistry, Royal Global University, Assam 781035, India
| | - Sangeeta Mitra
- Department of Biochemistry and Biophysics, University of Kalyani, West Bengal 741235, India
| | - Sudeep Banerjee
- Department of Gastrointestinal Surgery, Tata Medical Center, Kolkata 700160, India
| | - Aniruddha Chatterjee
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand
- School of Health Sciences and Technology, University of Petroleum and Energy Studies, Dehradun 248007, India
| | - Nilabja Sikdar
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India
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18
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Farook S, Jilani MSA, Islam MK, Rahman S, Ashraf R, Mendiratta N, Rawal SK. IgG4-related retroperitoneal fibrosis: A case report of a challenging disease. Clin Case Rep 2023; 11:e7865. [PMID: 37663821 PMCID: PMC10468584 DOI: 10.1002/ccr3.7865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/19/2023] [Accepted: 08/21/2023] [Indexed: 09/05/2023] Open
Abstract
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a multi-organ immune-mediated fibroinflammatory disorder that may imitate malignancy, infectious or any other inflammatory disorder. IgG4-related retroperitoneal fibrosis (IgG4-RPF) is a rare form of IgG4-RD, diagnosis of which is often relied on radiological technology. Herein, we describe a case of 60 year old male, presenting with low back pain and weight loss for a period of 2 months and 15 days. Imaging studies showed a retroperitoneal tumorous mass along with bilateral hydroureteronephrosis, which was later confirmed to be IgG4-related retroperitoneal fibrosis on the basis of extensive histopathological analysis. Immunosuppressive therapy resulted in a decrease in fibrosis and restoration of renal function.
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Affiliation(s)
- Saika Farook
- Department of MicrobiologyIbrahim Medical CollegeDhakaBangladesh
| | | | - Md. Kamrul Islam
- Department of UrologyDhaka Medical College and Hospital & Department of Urology, Centre for Kidney Disease & HospitalDhakaBangladesh
| | - Shamima Rahman
- Department of Obstetrics and Gynecology, Colonel Malek Medical College and Hospital, ManikganjUniversity of DhakaDhakaBangladesh
| | - Rumana Ashraf
- Department of Obstetrics and GynecologyDr. Sirajul Islam Medical College & Hospital LtdDhakaBangladesh
| | - Naval Mendiratta
- Department of RheumatologyFortis Memorial Research InstituteGurugramIndia
| | - Sudhir Kumar Rawal
- Department of Urogenital OncologyRajeev Gandhi Cancer Hospital and Research CentreNew DelhiIndia
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19
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Xu C, Du L, Guo Y, Liang Y. TCN1 Expression Is Increased in Asthma. Int Arch Allergy Immunol 2023; 184:1135-1142. [PMID: 37586352 DOI: 10.1159/000531073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 04/19/2023] [Indexed: 08/18/2023] Open
Abstract
INTRODUCTION Asthma is a chronic disease that affects populations worldwide. The purpose of this study was to investigate the expression of TCN1 in sputum and its correlation with inflammation and lung function in asthma. METHODS We recruited 141 subjects, detected TCN1 mRNA level by quantitative reverse transcription polymerase chain reaction, detected TCN1 protein expression by Western blot, detected TCN1 protein level by enzyme-linked immunosorbent assay, and analyzed the correlation between TCN1 and fraction of exhaled nitric oxide (FeNO), IgE, EOS%, lung functions, and some Th2 cytokines. The diagnostic value of TCN1 was evaluated by receiver operating characteristics curve. The expression of TCN1 was further confirmed by human bronchial epithelial cell in vitro. RESULTS Compared with the health group, the expression of TCN1 in induced sputum cells increased in asthma group and was correlated with FeNO, IgE, and EOS%. TCN1 level was also elevated in the induced sputum supernatant of asthma patients. The protein level of TCN1 in induced sputum supernatant was correlated with FeNO, IgE and PC-20, forced expiratory volume in the first second (FEV1)%pred, FEV1/FVC, and some cytokines (IL-4, IL-5, IL-10, IL-13, MUC5AC). TCN1 was also differentially expressed in patients with different severity of asthma. Four weeks after ICS treatment, the expression of TCN1 in induced sputum supernatant increased. In vitro, the protein level of TCN1 in human bronchial epithelial cells' supernatant increased after stimulated with IL-4 and IL-13. CONCLUSION The expression of TCN1 was increased in asthma patients' sputum, and was positively correlated with some inflammatory markers, negatively correlated with lung function. TCN1 may be used as a potential biomarker for the diagnosis and treatment of asthma.
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Affiliation(s)
- Changyi Xu
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
- Institute of Respiratory Diseases of Sun Yat-Sen University, Guangdong, China
- Department of Clinical Laboratory, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lijuan Du
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
- Institute of Respiratory Diseases of Sun Yat-Sen University, Guangdong, China
| | - Yubiao Guo
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
- Institute of Respiratory Diseases of Sun Yat-Sen University, Guangdong, China
| | - Yuxia Liang
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
- Institute of Respiratory Diseases of Sun Yat-Sen University, Guangdong, China
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20
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Rathinam A, Gupta S, Khan M. A Case of Immunoglobulin G4-Related Disease Presenting as a Parapharyngeal Mass. Cureus 2023; 15:e41764. [PMID: 37575773 PMCID: PMC10416673 DOI: 10.7759/cureus.41764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2023] [Indexed: 08/15/2023] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by tissue infiltration with lymphocytes and IgG4-secreting plasma cells. The presentation of IgG4-RD is heterogenous, making it difficult to diagnose. IgG4-RD presenting as a parapharyngeal mass is extremely rare. This report discusses the case of a 69-year-old African American female presenting with intermittent bilateral frontal headaches. Initial imaging revealed an ill-defined parapharyngeal mass encasing the left internal carotid artery and left internal jugular vein. Subsequent biopsy and immunohistochemistry showed a high concentration of IgG4-positive plasma cells with storiform fibrosis, despite normal serum IgG4 levels. The patient opted for conservative management. The localized parapharyngeal mass has remained stable over two years on annual imaging. This case report highlights that IgG4-RD can have varied and nonspecific presentations requiring high clinical suspicion to diagnose. Histopathology and IgG4 staining are vital to confirm the diagnosis of IgG4-RD, particularly in atypical cases not meeting the standard inclusion criteria.
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Affiliation(s)
- Arun Rathinam
- Internal Medicine, Carle Foundation Hospital, Urbana, USA
| | - Sushan Gupta
- Internal Medicine, Carle Foundation Hospital, Urbana, USA
| | - Mehwish Khan
- Rheumatology, Carle Foundation Hospital, Urbana, USA
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21
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Gader G, Atig FB, Jemel N, Bourgou M, Slimane A, Ghedira K, Badri M, Zammel I. Epiduritis related to IgG4 disease: A very rare cause for spinal cord compression. Surg Neurol Int 2023; 14:205. [PMID: 37404483 PMCID: PMC10316182 DOI: 10.25259/sni_400_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 05/27/2023] [Indexed: 07/06/2023] Open
Abstract
Background Inflammatory pseudotumors are rare, and those attributed to immunoglobulin G4 (IgG4) diseases are even less frequently encountered. Here, we reviewed 41 cases from the literature of spinal inflammatory pseudotumors due to IgG4 and have added our single new case. Case Presentation A 25-year-old male presented with progressive back pain, bilateral paraparesis, and sphincter dysfunction. His deficit was attributed to MR-documented posterolateral lesion between the T5 and T10 levels for which he levels underwent a T1-T1010 laminectomy. The pathology revealed an immunoglobulin G4-related inflammatory pseudotumor. Postoperatively, the patient additionally required systemic and epidural administration of glucocorticoids. Conclusion IgG4-related disease is an emerging clinical condition that rarely involves the central nervous system. Spinal inflammatory pseudotumors, including IgG4 disease, should be more commonly considered among the potential differential diagnoses of lesions compressing the spinal cord.
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Affiliation(s)
- Ghassen Gader
- Department of Neurosurgery, Trauma and Burns Center, Ben Arous, Tunisia
| | - Fatma Ben Atig
- Department of Neurosurgery, National Institute of Neurology, Tunis, Tunisia
| | - Nesrine Jemel
- Department of Neurosurgery, Trauma and Burns Center, Ben Arous, Tunisia
| | - Malek Bourgou
- Department of Neurosurgery, Trauma and Burns Center, Ben Arous, Tunisia
| | | | - Khalil Ghedira
- Department of Neurosurgery, National Institute of Neurology, Tunis, Tunisia
| | - Mohamed Badri
- Department of Neurosurgery, Trauma and Burns Center, Ben Arous, Tunisia
| | - Ihsèn Zammel
- Department of Neurosurgery, Trauma and Burns Center, Ben Arous, Tunisia
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22
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Tornel-Avelar AI, Velarde Ruiz-Velasco JA, Pelaez-Luna M. Pancreatic cancer, autoimmune or chronic pancreatitis, beyond tissue diagnosis: Collateral imaging and clinical characteristics may differentiate them. World J Gastrointest Oncol 2023; 15:925-942. [PMID: 37389107 PMCID: PMC10302998 DOI: 10.4251/wjgo.v15.i6.925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/21/2023] [Accepted: 04/28/2023] [Indexed: 06/14/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related death. Often, the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses, such as autoimmune pancreatitis (AIP) and mass-forming chronic pancreatitis (MFCP), making its diagnosis challenging. Differentiating AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic implications. Current diagnostic criteria and tools allow the precise differentiation of benign from malignant masses; however, the diagnostic accuracy is imperfect. Major pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate diagnosis. It is not unusual that after a thorough diagnostic evaluation, the clinician is confronted with a pancreatic mass with uncertain diagnosis. In those cases, a re-evaluation must be entertained, preferably by an experienced multispecialty team including radiologists, pathologists, gastroenterologists, and surgeons, looking for disease-specific clinical, imaging, and histological hallmarks or collateral evidence that could favor a specific diagnosis. Our aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP, PDAC, and MFCP and to highlight those disease-specific clinical, radiological, serological, and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.
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Affiliation(s)
- Ana I Tornel-Avelar
- Department of Gastroenterology, Hospital Civil of Guadalajara “Fray Antonio Alcalde”, Guadalajara 44340, Jalisco, Mexico
| | | | - Mario Pelaez-Luna
- Research Division School of Medicine/Department of Gastroenterology, Universidad Nacional Autonoma de México/National Institute of Medical Sciences and Nutrition “Salvador Zubiran”, Tlalpan 14000, Mexico City, Mexico
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23
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Katsuo C, Kubota K, Tanaka K, Kurita Y, Nakajima A. Combined REGN-COV2 Antibody Therapy Immediately Prevented a Patient with Refractory Type 1 Autoimmune Pancreatitis from Contracting SARS-CoV-2 during the Sixth Wave in Japan. Intern Med 2023; 62:1765-1770. [PMID: 37316279 PMCID: PMC10332964 DOI: 10.2169/internalmedicine.1421-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 02/20/2023] [Indexed: 06/16/2023] Open
Abstract
A 51-year-old man who had been receiving steroid therapy for type 1 autoimmune pancreatitis (AIP) for 3 years contracted coronavirus disease 2019 (COVID-19). As he had a high-grade fever and dry cough, and because his SpO2 level had dropped below 95% in the supine position, he was considered as being at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); therefore, he received combined REGN-COV2 antibody therapy. The patient's fever resolved immediately after this treatment, and he went into remission. A high cumulative steroid dose is associated with an increased susceptibility to infection. Early antibody cocktail therapy may be effective and rewarding for steroid-dependent type 1 AIP patients with a potential risk for SARS-CoV-2.
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Affiliation(s)
- Chihiro Katsuo
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan
| | - Kensuke Kubota
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan
| | - Katsushi Tanaka
- Division of Respiratory, Yokohama City University Graduate School of Medicine, Japan
| | - Yusuke Kurita
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan
| | - Atsushi Nakajima
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan
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24
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Lee JE, Hwang SH. A Case of IgG4-Related Disease With Sinonasal Involvement Presenting With Decreased Visual Acuity. JOURNAL OF RHINOLOGY 2023; 30:48-52. [PMID: 39664706 PMCID: PMC11524364 DOI: 10.18787/jr.2023.00008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 01/30/2023] [Accepted: 02/01/2023] [Indexed: 04/01/2023] Open
Abstract
IgG4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by IgG4-positive plasma cell and T lymphocyte infiltration of multiple organs. It commonly involves the pancreas, lacrimal glands, and salivary glands, and it has been rarely reported in the sinonasal cavity. We herein report the case of a 47-year-old male patient whose chief complaint was decreased visual acuity. A tumefactive mass was found on imaging studies, originating from the sinonasal cavity and invading the orbit, kidney, and meninges. The mass was resected through endoscopic sinus surgery and was pathologically confirmed to be IgG4-RD. The patient was treated with steroid therapy and showed clinical improvement.
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Affiliation(s)
- Ju Eun Lee
- Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Se Hwan Hwang
- Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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25
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Gyawali S, Pokhrel B, Uprety P, Gnawali A. IgG4-related sclerosing cholangitis, a mimicker of the cholangiocarcinoma: A case report. Clin Case Rep 2023; 11:e6935. [PMID: 36789321 PMCID: PMC9909256 DOI: 10.1002/ccr3.6935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/25/2022] [Accepted: 01/23/2023] [Indexed: 02/11/2023] Open
Abstract
An 83-year-old-male patient presented with obstructive jaundice, whose imagings were consistent with the cholangiocarcinoma of the distal common bile duct. The tumor markers were within normal limits. IgG4 level was raised; therefore, IgG4-sclerosing cholangitis was made as the provisional diagnosis. Steroid therapy was started to which he responded well.
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Affiliation(s)
- Siddinath Gyawali
- Department of GastroenterologyTribhuvan University Teaching Hospital, Institute of MedicineKathmanduNepal
| | - Biraj Pokhrel
- Department of GastroenterologyTribhuvan University Teaching Hospital, Institute of MedicineKathmanduNepal
| | - Pratik Uprety
- Department of Internal MedicineB.P. Koirala Institute of Health ScienceDharanNepal
| | - Arun Gnawali
- Department of GastroenterologyTribhuvan University Teaching Hospital, Institute of MedicineKathmanduNepal
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26
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Zhang XD, Zhang Y, Zhao YZ, Zhou CH, Zou DW. Autoimmune pancreatitis: A bibliometric analysis from 2002 to 2022. Front Immunol 2023; 14:1135096. [PMID: 36911675 PMCID: PMC9992966 DOI: 10.3389/fimmu.2023.1135096] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 02/09/2023] [Indexed: 02/24/2023] Open
Abstract
Background/Objectives Autoimmune pancreatitis (AIP) is a distinct form of pancreatic inflammatory disease that responds well to glucocorticoid therapy. Knowledge on AIP has rapidly evolved over the past two decades. Based on bibliometric analysis, this study aimed to assess the research status of AIP over the past two decades and determine the research focus and emerging topics. Methods AIP-related publications published between January 1, 2002, and June 6, 2022, were retrieved from the Web of Science Core Collection. Bibliometric data were analyzed using HisCite, VOSviewer, CiteSpace, and bibliometrix package. Annual output, leading countries/regions, active institutions and authors, core journals and references, and keywords of AIP were evaluated. Results Overall, 1,772 publications were retrieved from 501 journals by 6,767 authors from 63 countries/regions. Japan published articles on AIP the most (n=728, 41.1%), followed by the United States (n=336, 19%), Germany (n=147, 8.3%), China (n=127, 7%), and Italy (n=107, 6%). The top three most prolific authors were Terumi Kamisawa from Tokyo Metropolitan Komagome Hospital (n=117), Kazuichi Okazaki from Kansai Medical University (n=103), and Shigeyuki Kawa from Matsumoto Dental University (n=94). Pancreas was the most productive journal regarding AIP research (n=95), followed by the Journal of Gastroenterology (n=67), Internal Medicine (n=66), Pancreatology (n=63), and World Journal of Gastroenterology (n=62). "Diagnosis" was the most mentioned keyword. "Risk," "malignancy," "outcome," "22-gauge needle," and "fine-needle aspiration" were recognized as emerging topics. Conclusion Japan was the leading country in AIP research. Research papers were mainly published in specialized journals. Diagnosis was the research focus. Long-term outcomes and pancreatic tissue acquisition were recognized as research frontiers for AIP.
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Affiliation(s)
- Xian-Da Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yao Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi-Zhou Zhao
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chun-Hua Zhou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Duo-Wu Zou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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27
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Olejarz M, Szczepanek-Parulska E, Ostałowska-Klockiewicz A, Antosik P, Sawicka-Gutaj N, Helak-Łapaj C, Stopa M, Ruchala M. High IgG4 serum concentration is associated with active Graves orbitopathy. Front Endocrinol (Lausanne) 2023; 14:1083321. [PMID: 36936165 PMCID: PMC10014914 DOI: 10.3389/fendo.2023.1083321] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 02/07/2023] [Indexed: 03/05/2023] Open
Abstract
BACKGROUND The aim of the study was to evaluate the differences in clinical profile, laboratory parameters, and ophthalmological signs, and symptoms between patients with high IgG4 Graves orbitopathy and patients with normal IgG4 Graves orbitopathy. METHODS This was a prospective observational study. We recruited adult patients with Graves Orbitopathy(GO) referred to our clinic for further diagnostics and treatment. Eventually, 60 patients with GO were enrolled in the study. All patients underwent ophthalmological assessment, magnetic resonance imaging (MRI) of the orbits, and laboratory tests, including IgG4 serum concentration measurement. High IgG4 GO was diagnosed if the IgG4 concentration exceeded 135 mg/dl. We used both the clinical activity score (CAS) and magnetic resonance imaging (MRI) to assess the activity of GO. Eventually, active GO was defined according to MRI results. RESULTS Among 60 GO patients, 15 (25%) patients had elevated IgG4 levels. Patients in the high IgG4 group had a higher prevalence of active GO by MRI than patients with normal IgG4 (100% vs. 64.44%, P=0.006). They also had a higher eosinophile count in peripheral blood, a lower bilirubin level, a more frequent lower eyelid retraction, and a lower prevalence of glaucoma. There were no statistically significant differences between the groups in CAS. Patients with active GO, had higher median IgG4 level [89.95 (55.48; 171.1) vs 43.45 (32.48; 49.68) mg/dl, P<0.001]. The receiver operating characteristic (ROC) analysis for IgG4 as a marker of active GO revealed the following results: AUC 0.848 for the cut-off value of 54.2 mg/dl, sensitivity 79.5%, specificity 87.5%, positive predictive value 94.6%, negative predictive value 59.1%. CONCLUSIONS We demonstrated that IgG4 is a marker of GO activity. Certain differences in the clinical profile of patients with high IgG4 GO, and normal IgG4 GO were observed. More data is needed to establish whether patients with high IgG4 GO are GO patients with particularly active disease or actually represent a distinct clinical entity related to IgG4-Related Disease.
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Affiliation(s)
- Michał Olejarz
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
- *Correspondence: Michał Olejarz,
| | - Ewelina Szczepanek-Parulska
- Department of Ophthalmology, Chair of Ophthalmology and Optometry, Poznan University of Medical Sciences, Poznan, Poland
| | - Anna Ostałowska-Klockiewicz
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
| | - Patrycja Antosik
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
| | - Nadia Sawicka-Gutaj
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
| | - Celina Helak-Łapaj
- Department of Ophthalmology, Chair of Ophthalmology and Optometry, Poznan University of Medical Sciences, Poznan, Poland
| | - Marcin Stopa
- Department of Ophthalmology, Chair of Ophthalmology and Optometry, Poznan University of Medical Sciences, Poznan, Poland
| | - Marek Ruchala
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
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28
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Lv Z, Wu L, Lu Y, Liu S, Li Q. Bibliometric analysis of IgG4-related disease research from 2003 to 2022 based on Web of Science Core Collection Databases. Clin Rheumatol 2023; 42:15-27. [PMID: 36121577 DOI: 10.1007/s10067-022-06377-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/10/2022] [Accepted: 09/13/2022] [Indexed: 01/11/2023]
Abstract
This study aimed to perform a bibliometric analysis of the IgG4-related disease (IgG4-RD) research field over the past 20 years to explore its research hotspots and trends. The literature of IgG4-RD published in the Web of Science Core Collection databases was reviewed from January 1, 2003, to April 30, 2022. A bibliometric analysis was carried out using CiteSpace software to evaluate and visualize the evolving dynamics and hotspots in the field of IgG4-RD. A total of 3174 IgG4-RD articles were reviewed. Since 2011, there has been a rapid increase in published literature. Japan is the highest yielding country and Kanazawa University the highest yielding institution. The USA has the highest centrality (0.34) and plays a critical role in cooperation and communication of IgG4-RD research. Nine highly connected clusters of IgG4-RD were observed by keyword analysis. Research hotspots included IgG4-RD involved organs and differentiation from Rosai-Dorfman disease and primary sclerosing cholangitis. Further research topics include pathogenesis, relapse, and malignancy. As a cross-discipline systemic disease, IgG4-RD requires attention by clinicians in multiple fields. This bibliometric analysis can help researchers grasp trends and provide new perspectives for future research on IgG4-RD.
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Affiliation(s)
- Zhijie Lv
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China
| | - Li Wu
- Center of Clinical Evaluation, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China. .,Center of Clinical Evaluation, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, 310006, Zhejiang, China.
| | - Yan Lu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - Shan Liu
- Center of Clinical Evaluation, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China.,Center of Clinical Evaluation, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, 310006, Zhejiang, China
| | - Qiushuang Li
- Center of Clinical Evaluation, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China.,Center of Clinical Evaluation, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, 310006, Zhejiang, China
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29
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Differential CpG DNA methylation of peripheral B cells, CD4 + T cells, and salivary gland tissues in IgG4-related disease. Arthritis Res Ther 2023; 25:4. [PMID: 36609529 PMCID: PMC9824958 DOI: 10.1186/s13075-022-02978-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 12/12/2022] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVES Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease manifesting as chronic inflammation and tissue fibrosis. Since the role of DNA methylation in the pathogenesis of IgG4-RD is still unclear, we conduct this study to investigate epigenetic modifications in IgG4-RD. METHODS A genome-wide DNA methylation study was conducted with B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients and matched controls by using the Illumina HumanMethylation 850K BeadChip. We further performed pyrosequencing and immunohistochemistry assays to validate the methylation status of some targets of interest. RESULTS We identified differentially methylated CpG sites including 44 hypomethylated and 166 hypermethylated differentially methylated probes (DMPs) in B cells and 260 hypomethylated and 112 hypermethylated DMPs in CD4+ T cells from 10 IgG4-RD patients compared with 10 healthy controls. We also identified 36945 hypomethylated and 78380 hypermethylated DMPs in salivary gland tissues of 4 IgG4-RD patients compared with 4 controls. DPM2 (cg21181453), IQCK (cg10266221), and ABCC13 (cg05699681, cg04985582) were hypermethylated and MBP (cg18455083) was hypomethylated in B cells, CD4+ T cells, and salivary gland tissues of IgG4-RD patients. We also observed the hypomethylated HLA-DQB2 in CD4+ T cells from IgG4-RD patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DMPs in salivary gland tissues of IgG4-RD patients revealed enrichment of pathways involved in the regulation of immune cell responses and fibrosis. CONCLUSION This is the first DNA methylation study in peripheral B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients. Our findings highlighted the role of epigenetic modification of DNA methylation and identified several genes and pathways possibly involved in IgG4-RD pathogenesis.
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30
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Manifestaciones otológicas de la enfermedad relacionada con IgG4. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2022. [DOI: 10.1016/j.otorri.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
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31
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Cytotoxic CD8 + T cells may be drivers of tissue destruction in Sjögren's syndrome. Sci Rep 2022; 12:15427. [PMID: 36104369 PMCID: PMC9475031 DOI: 10.1038/s41598-022-19397-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 08/29/2022] [Indexed: 01/14/2023] Open
Abstract
Sjögren's syndrome is a chronic autoimmune disorder whose pathogenesis is poorly understood and that lacks effective therapies. Detailed quantitative and spatial analyses of tissues affected by Sjögren's syndrome were undertaken, including the quantitation of the frequency of selected cell-cell interactions in the disease milieu. Quantitative analyses of CD4+ T cell subsets and of CD8+ T cells in the labial salivary glands from untreated patients with primary Sjögren's syndrome revealed that activated CD8+ cytotoxic T cells (CD8+CTLs) were the most prominent T cells in these infiltrates. An accumulation of apoptotic glandular epithelial cells, mainly ductal and acinar cells, was observed, consistent with the impaired salivary secretion often observed in patients with this disease. FasL expressing activated CD8+ T cells were seen to accumulate around Fas expressing apoptotic epithelial cells. Quantitative analyses of apoptotic cell types and of conjugates between cytotoxic T cells and epithelial cells undergoing apoptosis suggest that Sjögren's syndrome is primarily driven by CD8+CTL mediated execution of epithelial cells mainly represented by ductal and acinar cells.
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32
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Yim SH, Yoon JS, Lee CH, Kim J. Hypertrophic Pachymeningitis and Interstitial Lung Disease in IgG4-Related Disease. J Clin Neurol 2022; 18:481-483. [PMID: 35796274 PMCID: PMC9262458 DOI: 10.3988/jcn.2022.18.4.481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/30/2022] [Accepted: 03/31/2022] [Indexed: 11/17/2022] Open
Affiliation(s)
- So Hyun Yim
- Department of Neurology, BioMedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Jae Seob Yoon
- Department of Neurology, BioMedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Chang Hun Lee
- Department of Pathology, BioMedical Research Institute, Pusan National University Hospital, Busan, Korea.,Department of Pathology, Pusan National University School of Medicine, Busan, Korea
| | - Jiyoung Kim
- Department of Neurology, BioMedical Research Institute, Pusan National University Hospital, Busan, Korea.,Department of Neurology, Pusan National University School of Medicine, Busan, Korea.
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33
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Doersch KM, Barnett D, Chase A, Johnston D, Gabrielsen JS. The contribution of the immune system to genitourinary fibrosis. Exp Biol Med (Maywood) 2022; 247:765-778. [PMID: 35531654 PMCID: PMC9134766 DOI: 10.1177/15353702221090872] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023] Open
Abstract
Fibrotic diseases of the genitourinary tract are devastating and incompletely understood pathologies. These diseases include urethral and ureteral strictures, retroperitoneal fibrosis, and Peyronie's disease. They can contribute to obstructive uropathy and sexual dysfunction. Poor understanding of the pathophysiology of these diseases severely limits our ability to prevent and treat them. Genitourinary fibrotic diseases likely represent related pathologies that share common underlying mechanisms involving wound healing in response to injury. These diseases share the common feature of extracellular matrix abnormalities-such as collagen deposition, transforming growth factor-β accumulation, and dysregulation of collagen maturation-leading to abnormal tissue stiffness. Given the association of many of these diseases with autoimmunity, a systemic pro-inflammatory state likely contributes to their associated fibrogenesis. Herein, we explore the immunologic contribution to fibrogenesis in several fibrotic diseases of the genitourinary system. Better understanding how the immune system contributes to fibrosis in these diseases may improve prevention and therapeutic strategies and elucidate the functions of immunologic contributors to fibrosis in general.
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Affiliation(s)
- Karen M Doersch
- Department of Urology, University of
Rochester Medical Center, Rochester, NY 14642, USA
| | - Daniel Barnett
- Department of Pediatrics, University of
Toledo, Toledo, OH 43614, USA
| | - Abbie Chase
- Department of Urology, University of
Rochester Medical Center, Rochester, NY 14642, USA
| | - Daniel Johnston
- Department of Urology, University of
Rochester Medical Center, Rochester, NY 14642, USA
| | - J Scott Gabrielsen
- Department of Urology, University of
Rochester Medical Center, Rochester, NY 14642, USA
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34
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Kubo S, Kanda R, Nawata A, Miyazaki Y, Kawabe A, Hanami K, Nakatsuka K, Saito K, Nakayamada S, Tanaka Y. Eosinophilic granulomatosis with polyangiitis exhibits T cell activation and IgG4 immune response in the tissue; comparison with IgG4-related disease. RMD Open 2022; 8:rmdopen-2021-002086. [PMID: 35260476 PMCID: PMC8906049 DOI: 10.1136/rmdopen-2021-002086] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 02/16/2022] [Indexed: 12/25/2022] Open
Abstract
Objective To study the pathophysiological differences of EGPA and IgG4-related disease (RD) by clarifying their clinical, pathological and immunological features. Methods Clinical and pathological findings were compared in patients with EGPA and IgG4-RD. Peripheral blood mononuclear cells were used for comprehensive flow cytometric analysis. Results An elevation of the IgG4 level was found in all EGPA cases, with the accompanying pathological findings of lymphocytic infiltration and fibrosis observed in 30.8% patients, and the elevation of IgG4/IgG ratio in 61.5% patients. However, actual IgG4 levels, as well as the degree of the infiltration of IgG4-positive plasma cells, were still higher in patients with IgG4-RD than patients with EGPA. Examination by ACR/EULAR classification criteria showed only 13.6% of the EGPA patients met entry criteria, while all of them met the exclusion criteria. In regard to the immunophenotyping, EGPA patients had increases in activated CD4 and CD8 T cells compared with the healthy controls. However, no such similar changes occurred in IgG4-RD patients. On the other hand, both the EGPA and IgG4-RD patient groups had correlated increased plasmablasts and Tfh. These results indicate the presence of two axes: namely, the activation of T cells and that of B cells. Both axes are present in EGPA, but the T cell activation axis was not observed in IgG4-RD. Conclusions The elevation of serum IgG4 as well as pathological IgG4 infiltration are not specific. Meanwhile, EGPA and IgG4-RD differ in immunological phenotypes, indicating the possible importance of the predominant activation of T cells in the development of vasculitis.
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Affiliation(s)
- Satoshi Kubo
- First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
| | - Ryuichiro Kanda
- First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
| | - Aya Nawata
- First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan.,Department of Pathology and Oncology, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
| | - Yusuke Miyazaki
- First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
| | - Akio Kawabe
- First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
| | - Kentaro Hanami
- Department of Rheumatology and Diabetology, Wakamatsu Hospital of the University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
| | - Keisuke Nakatsuka
- Department of Internal Medicine, Fukuoka Yutaka Central Hospital, Nogata, Fukuoka, Japan
| | - Kazuyoshi Saito
- Department of Clinical Immunology and Rheumatology, Tobata General Hospital, Kitakyushu, Fukuoka, Japan
| | - Shingo Nakayamada
- First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
| | - Yoshiya Tanaka
- First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
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Maslinska M, Dmowska-Chalaba J, Jakubaszek M. The Role of IgG4 in Autoimmunity and Rheumatic Diseases. Front Immunol 2022; 12:787422. [PMID: 35145508 PMCID: PMC8821096 DOI: 10.3389/fimmu.2021.787422] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/23/2021] [Indexed: 12/15/2022] Open
Abstract
The distinguishing of the IgG4-related disease (IgG4-RD) from among other rheumatic diseases has brought attention to the IgG4 subclass of immunoglobulins. It is the least numerous subclass among immunoglobulins G. In general, IgG4 is considered to be non-inflammatory and tolerance inducing, due to its unique structure. However, in IgG4-RD this antibody plays a pathogenic role in activation of the fibrinogenesis and of the inflammatory process; there are also suggestions that it may be a marker of an abnormal inflammatory response. The importance of IgG4 for the pathogenesis of allergic diseases, with a vital role of its ratio to immunoglobulin E (IgE/IgG4 ratio), has been known for years. The role of IgG4 in the course and pathogenesis of rheumatic diseases is still being researched and is not yet fully understood. Increased IgG4 levels have been revealed in rheumatoid arthritis, although no clear link between this phenomenon and disease activity has been demonstrated. There are articles on the potential importance of IgG4 concentration (of both elevated and decreased serum levels) in Sjogren’s syndrome. Additionally, anti-nuclear IgG4 antibody significant titers have been detected in SLE patients, and it has been suggested that the effect of these antibodies on complement consumption and the production of proinflammatory cytokines may play a role in inhibiting the progression of SLE. IgG4 plays a role in autoimmune diseases other than rheumatic diseases, such as pemphigus, bullous pemphigoid, idiopathic membranous glomerulonephritis, or myasthenia gravis, but also in helmints infections. Research shows the importance of IgG4 in malignancy of neoplasms. Melanoma cells are known to stimulate IgG4 production through a modified Th2-based inflammatory response. The role of this immunoglobulin in cholangiocarcinoma is also considered as possible. The aim of this review article is to discuss the current knowledge of IgG4 not only from the perspective of the IgG4-RD but also from a point of view of other autoimmune diseases with particular emphasis on rheumatic diseases.
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Kamisawa T. Immunoglobulin G4-related Disease: A New Systemic Disease Emerging in Japan. JMA J 2022; 5:23-35. [PMID: 35224257 PMCID: PMC8826784 DOI: 10.31662/jmaj.2021-0113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 10/05/2021] [Indexed: 11/16/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by organ enlargement and elevated serum IgG4 levels. In 2003, IgG4-RD was proposed as a distinct form of IgG4-related systemic disease based on a histopathological study involving patients with autoimmune pancreatitis. IgG4-RD occurs mainly in older men and can affect almost any organ simultaneously or metachronously. Pathophysiologically, IgG4-RD occurs when an autoantigen triggers an immune response characterized by Th2 predominance with increased production of cytokines, such as interleukin 4 (IL-4), IL-5, IL-10, IL-13, and tumor growth factor-β (TGF-β), in the affected organ. IL-10 and TGF-β produced by the increased number of regulatory T cells induce a switch from B cells to IgG4-producing plasma cells and fibrosis, respectively. The characteristic histological features consist of dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD is diagnosed based on a combination of clinical, serological, radiological, and histopathological findings. Differentiating IgG4-RD from malignant tumors or similar inflammatory diseases in the affected organs is important. The 2019 America College of Rheumatology/European League against Rheumatism classification criteria for IgG4-RD have high diagnostic sensitivity and specificity. IgG4-RD generally responds well to treatment with steroids, and a swift response is reassuring and provides further diagnostic confirmation. However, relapses are common during tapering or after cessation of steroids. In Japan, low-dose steroid maintenance therapy is usually given to prevent a relapse. B-cell depletion with rituximab is effective in patients resistant to or dependent on steroids. Most patients with IgG4-RD who receive steroid therapy show good short-term clinical, morphological, and functional outcomes. However, long-term outcomes, such as relapse, fibrosis development, and associated malignancies, have not been clearly defined. Therefore, novel treatment strategies, including rituximab, need to be tested in international randomized controlled clinical trials.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
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Endmayr V, Tunc C, Ergin L, De Rosa A, Weng R, Wagner L, Yu TY, Fichtenbaum A, Perkmann T, Haslacher H, Kozakowski N, Schwaiger C, Ricken G, Hametner S, Klotz S, Dutra LA, Lechner C, de Simoni D, Poppert KN, Müller GJ, Pirker S, Pirker W, Angelovski A, Valach M, Maestri M, Guida M, Ricciardi R, Frommlet F, Sieghart D, Pinter M, Kircher K, Artacker G, Höftberger R, Koneczny I. Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study. Front Immunol 2022; 12:785247. [PMID: 35095860 PMCID: PMC8795769 DOI: 10.3389/fimmu.2021.785247] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/15/2021] [Indexed: 12/18/2022] Open
Abstract
Background IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features. Methods We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD. Results A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD. Conclusion Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.
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Affiliation(s)
- Verena Endmayr
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Cansu Tunc
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Lara Ergin
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Anna De Rosa
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Rosa Weng
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Lukas Wagner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Thin-Yau Yu
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Andreas Fichtenbaum
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Helmuth Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Carmen Schwaiger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Gerda Ricken
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Simon Hametner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Sigrid Klotz
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Lívia Almeida Dutra
- Department of Neurology and Neurosurgery, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Christian Lechner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Pediatric Neurology, Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Désirée de Simoni
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Department of Neurology, University Hospital St. Poelten, St. Poelten, Austria
| | - Kai-Nicolas Poppert
- Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
| | - Georg Johannes Müller
- Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria
| | - Susanne Pirker
- Department of Neurology, Klinik Hietzing, Vienna, Austria
| | - Walter Pirker
- Department of Neurology, Klinik Ottakring, Vienna, Austria
| | | | - Matus Valach
- Department of Pathology, Klinik Landstrasse, Vienna, Austria
| | - Michelangelo Maestri
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Melania Guida
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Roberta Ricciardi
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Florian Frommlet
- Center for Medical Statistics, Informatics and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria
| | - Daniela Sieghart
- Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Miklos Pinter
- Wiener Privatklinik – Health Center, Vienna, Austria
| | - Karl Kircher
- Department of Ophthalmology, Medical University of Vienna, Vienna, Austria
| | - Gottfried Artacker
- Department of Pediatrics and Adolescent Medicine, Klinik Donaustadt, Vienna, Austria
| | - Romana Höftberger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Inga Koneczny
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
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Pereira FG, Nogueira R, Pataca I, Sampaio R. Chronic sclerosing sialadenitis (Küttner's tumour) of the submandibular gland: a neoplastic mimic. BMJ Case Rep 2022; 15:e245518. [PMID: 35022201 PMCID: PMC8756289 DOI: 10.1136/bcr-2021-245518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2021] [Indexed: 11/03/2022] Open
Abstract
A 74-year-old man was referred for a plastic surgery consultation for two previous acute episodes of right submandibular sialadenitis. Physical examination revealed a lump in the right submandibular region, painful on palpation. The initial impression on clinical examination was of sialolithiasis. The sonography demonstrated a structural heterogeneity of the submandibular gland with a hypoechogenic and vascularised nodular formation (1.5×1.2 cm), suggestive of a mixed tumour of the right maxillary gland, requiring histological evaluation. He underwent a right submandibulectomy and an IgG4-positive chronic sclerosing sialadenitis was diagnosed. The patient's condition evolved favourably, resulting in a full recovery. The clinical features and differential diagnosis of this entity are debated in light of relevant literature.
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Affiliation(s)
- Filipa Galante Pereira
- Pathology Department, Western Lisbon Hospital Center EPE Hospital de Egas Moniz, Lisbon, Portugal
| | - Ruben Nogueira
- Plastic Surgery Department, Western Lisbon Hospital Center EPE Hospital de Egas Moniz, Lisbon, Portugal
| | - Iris Pataca
- Radiology Department, Western Lisbon Hospital Center EPE Hospital de Egas Moniz, Lisbon, Portugal
| | - Rita Sampaio
- Pathology Department, Western Lisbon Hospital Center EPE Hospital de Egas Moniz, Lisbon, Portugal
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Adam Z, Zeman D, Čermák A, Dastych M, Doubková M, Horváth T, Skorkovská Š, Adamová Z, Řehák Z, Koukalová R, Pour L, Štork M, Krejčí M, Sandecká V, Ševčíková S, Král Z. IgG4-related disease. Clinical manifestation differential diagnosis and recent International Diagnostic Criteria for IgG4-related disease. VNITRNI LEKARSTVI 2022; 68:4-19. [PMID: 36283812 DOI: 10.36290/vnl.2022.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder. Autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum, prostate and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD and in 2019 four Clinical phenotypes of IgG4-related disease were described. Diagnosis is based on morphological examination with typical findings of lymphoplasmocellular inflammation, storiform fibrosis and obliterative phlebitis in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. New diagnostic criteria for IgG4-RD have been published recently in 2019 and 2021. This review summarizes current knowledge on pathophysiology, clinical manifestations, diagnosis and differential diagnosis of IgG4-RD from the point of view 2022 and in next article brings overview of the IgG4-RD therapy.
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40
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Huang M, Yin Z. Adolescent IgG4-related retroperitoneal fibrosis with left lower extremity edema as the first symptom: A case report. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2021; 46:1437-1441. [PMID: 35232916 PMCID: PMC10930578 DOI: 10.11817/j.issn.1672-7347.2021.200773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Indexed: 06/14/2023]
Abstract
IgG4-related retroperitoneal fibrosis is a type of IgG4-related diseases. The etiology is still unclear. It is often classified as idiopathic retroperitoneal fibrosis, but the pathological process and clinical results between them are different. Therefore, the differential diagnosis of them is very important. An 18-year-old patient was admitted to the Second Xiangya Hospital of Central South University due to "left lower extremity edema for 1 and a half month" on December 19, 2019. In examination of PET/CT, the starting point of the left aorta-intra-thoracic artery showed a soft tissue density lump with increased sugar metabolism, which indicated a suspected malignant tumor, and dilatation of the left renal pelvis and ureter. On January 8, 2020, the patient was performed pelvic edema excision, ureterectomy and anastomosis. The postoperative examination results were considered as IgG4-related disease. As a rare systemic disease, early correct diagnosis and precise and individualized treatment can alleviate the suffering of patients and ensure that patients are minimally traumatized.
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Affiliation(s)
- Mengjun Huang
- Department of Urology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
| | - Zhuo Yin
- Department of Urology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
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41
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Drazilova S, Veseliny E, Lenartova PD, Drazilova D, Gazda J, Grgurevic I, Janicko M, Jarcuska P. IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease. Can J Gastroenterol Hepatol 2021; 2021:1959832. [PMID: 34970512 PMCID: PMC8714375 DOI: 10.1155/2021/1959832] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 11/08/2021] [Accepted: 12/01/2021] [Indexed: 11/30/2022] Open
Abstract
IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.
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Affiliation(s)
- Sylvia Drazilova
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Eduard Veseliny
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Patricia Denisa Lenartova
- Department of Infectology and Travel Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Rastislavova 43, 040 01 Kosice, Slovakia
| | - Dagmar Drazilova
- 1 Faculty of Medicine, Charles University, Katerinska 1660/32, 121 08 Nove Mesto, Prague, Czech Republic
| | - Jakub Gazda
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University of Zagreb School of Medicine and University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia
| | - Martin Janicko
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Peter Jarcuska
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
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Asano Y, Kashiwagi S, Kawano Y, Tanaka S, Kuwae Y, Takashima T, Ohsawa M, Hirakawa K, Ohira M. IgG4-related mastitis requiring differentiation from breast cancer: a case report. J Surg Case Rep 2021; 2021:rjaa240. [PMID: 34858570 PMCID: PMC8634083 DOI: 10.1093/jscr/rjaa240] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 06/15/2020] [Indexed: 01/13/2023] Open
Abstract
Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a group of chronic relapsing inflammatory conditions. Although IgG4-RD can occur in various organs, it is rarely observed in mammary glands. Here, we report a case of IgG4-related mastitis (IgG4-RM) that needed to be differentiated from breast cancer. A 54-year-old woman was examined for a tumor in her left breast. Mammary ultrasonography revealed an irregular hypoechoic tumor measuring 45.0 × 43.0 × 32.0 mm in size. A core-needle biopsy of the left breast tissue revealed a high degree of mixed T and B lymphocytic and plasma cell infiltration, as well as interstitial fibrosis. IgG4-RD was diagnosed based on hematological examination that revealed an abnormal IgG4 value of 332 mg/dl. All the clinical diagnostic criteria for IgG4 were met, resulting in a definitive diagnosis of IgG4-RM.
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Affiliation(s)
- Yuka Asano
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Shinichiro Kashiwagi
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Yuko Kawano
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Sayaka Tanaka
- Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Yuko Kuwae
- Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Tsutomu Takashima
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Masahiko Ohsawa
- Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Kosei Hirakawa
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Masaichi Ohira
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
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Sankowski R, Lützen N, Hubbe U, Prinz M, Urbach H, Erny D, Taschner CA. Freiburg Neuropathology Case Conference : A 56-year-old Man Presenting with Progressive Gait Disorder, Neck Pain, and Lower Cranial Nerve Palsy. Clin Neuroradiol 2021; 31:1215-1221. [PMID: 34767051 PMCID: PMC8648702 DOI: 10.1007/s00062-021-01114-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2021] [Indexed: 11/30/2022]
Affiliation(s)
- R Sankowski
- Department of Neuropathology, University of Freiburg, Freiburg, Germany
- Medical Centre, University of Freiburg, Freiburg, Germany
| | - N Lützen
- Department of Neuroradiology, University of Freiburg, Breisacherstraße 64, 79106, Freiburg, Germany
- Medical Centre, University of Freiburg, Freiburg, Germany
| | - U Hubbe
- Department of Neurosurgery, University of Freiburg, Freiburg, Germany
- Medical Centre, University of Freiburg, Freiburg, Germany
| | - M Prinz
- Department of Neuropathology, University of Freiburg, Freiburg, Germany
- Medical Centre, University of Freiburg, Freiburg, Germany
| | - H Urbach
- Department of Neuroradiology, University of Freiburg, Breisacherstraße 64, 79106, Freiburg, Germany
- Medical Centre, University of Freiburg, Freiburg, Germany
| | - D Erny
- Department of Neuropathology, University of Freiburg, Freiburg, Germany
- Medical Centre, University of Freiburg, Freiburg, Germany
| | - C A Taschner
- Department of Neuroradiology, University of Freiburg, Breisacherstraße 64, 79106, Freiburg, Germany.
- Medical Centre, University of Freiburg, Freiburg, Germany.
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Li J, Liu R, Sun M, Wang J, Wang N, Zhang X, Ge X, Ma J. The FcεRI signaling pathway is involved in the pathogenesis of lacrimal gland benign lymphoepithelial lesions as shown by transcriptomic analysis. Sci Rep 2021; 11:21853. [PMID: 34750466 PMCID: PMC8576038 DOI: 10.1038/s41598-021-01395-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 10/06/2021] [Indexed: 01/30/2023] Open
Abstract
This study aimed to analyze the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland (LGBLEL). Transcriptomic analysis was performed on LGBLEL and orbital cavernous hemangioma (CH) patients diagnosed via histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013. Four LGBLEL and three orbital CH patients, diagnosed between October 2018 and August 2019, were randomly selected as experimental and control groups, respectively. RT-PCR, immunohistochemical staining, and western blotting were used to verify genes and proteins related to the FcεRI signaling pathway. Transcriptomic analysis showed that the FcεRI signaling pathway was upregulated in the LGBLEL compared with the CH group. The mRNA expression levels of important genes including SYK, p38, JNK, PI3K, and ERK were significantly increased in the LGBLEL group (P = 0.0066, P = 0.0002, P = 0.0003, P < 0.0001, P < 0.0001, respectively). Immunohistochemical staining results showed that SYK, p38, and ERK were positively expressed in LGBLEL, while JNK and PI3K were not. The protein contents of P-SYK, P-p38, P-JNK, P-PI3K, and P-ERK were significantly higher in the LGBLEL than in the CH group (P = 0.0169, P = 0.0074, P = 0.0046, P = 0.0157, P = 0.0156, respectively). The FcεRI signaling pathway participates in the pathogenesis of LGBLEL.
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Affiliation(s)
- Jing Li
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
| | - Rui Liu
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
| | - Mei Sun
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
| | - Jinjin Wang
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
| | - Nan Wang
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
| | - Xuan Zhang
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
| | - Xin Ge
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
| | - Jianmin Ma
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China.
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45
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Kimura T, Umino S, Kitamura M, Yatsuga S. Increased Serum-Immunoglobulin G4 Levels in a 12-Year-Old Male Patient With Central Diabetes Insipidus. Cureus 2021; 13:e17362. [PMID: 34567902 PMCID: PMC8454289 DOI: 10.7759/cureus.17362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2021] [Indexed: 11/24/2022] Open
Abstract
Immunoglobulin G4 (IgG4)-related disorders are characterized by tissue hypertrophy due to IgG4-positive cell infiltration and increased serum IgG4 levels. IgG4-related hypophysitis (IgG4-RH) is characterized by pituitary hypertrophy, IgG4-positive cell infiltration, central diabetes insipidus, and increased serum IgG4 levels. IgG4-RH is diagnosed through diagnostic criteria. A few cases of IgG4-RH in children have been reported. We report a case of CDI with increased serum IgG4 levels that failed to meet the diagnostic criteria of IgG4-RH. The patient developed polyuria and polydipsia at age 11 and was diagnosed as having idiopathic CDI at age 12. The patient was not treated with steroids and is well controlled with antidiuretic hormones. It has been reported that pediatric IgG4-RH differs from that of adults in several respects. We believe that the pediatric IgG4-RH may not fit the diagnostic criteria of adults. There may be also other cases of increased serum IgG4 levels in pediatric patients with idiopathic CDI. We do not know if they are subtypes of IgG4-RH or if serum IgG4 levels are by chance raised in CDI, however, we report them here because IgG4-RH in children may be different from that in adults.
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Affiliation(s)
- Takuro Kimura
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, JPN.,Department of Neonatology, St. Mary's Hospital, Kurume, JPN
| | - Satoko Umino
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, JPN
| | - Miyuki Kitamura
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, JPN
| | - Shuichi Yatsuga
- Department of Pediatrics, Aso Iizuka Hospital, Iizuka City, JPN.,Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, JPN
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46
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Ukai K. Two cases of IgG4-related disease accompanied by many cerebral microbleeds and a review of the literature: can IgG4-related disease cause cerebral small vessel vasculitis/vasculopathy? NAGOYA JOURNAL OF MEDICAL SCIENCE 2021; 83:649-654. [PMID: 34552297 PMCID: PMC8437991 DOI: 10.18999/nagjms.83.3.649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 12/25/2020] [Indexed: 11/30/2022]
Abstract
IgG4-related disease (IgG4-RD) is a condition of unknown cause, which involves marked tissue infiltration by IgG4-positive plasma cells into various organs throughout the body. Histopathological examinations based on biopsy examinations are essential for obtaining a definitive clinical diagnosis of IgG4-RD. However, there are only a limited number of organs from which biopsy samples can be easily obtained. Furthermore, it is impossible even for recently developed imaging techniques to directly detect abnormalities affecting small organs, such as the cerebral small vessel system. Due to these limitations, the clinical diagnosis of so-called “IgG4-related cerebral small vessel vasculitis/vasculopathy” is very difficult. In this report, two cases of IgG4-RD involving elderly patients are presented, together with their cranial magnetic resonance imaging features, especially those seen on T2* imaging. Both patients exhibited many cerebral microbleeds (CMB) on T2* imaging. I consider that it is possible to indirectly detect abnormalities of the small cerebral vessels by searching for CMB because they are caused by the failure of small cerebral vessels. Of course, the fact that many CMB were seen in both cases might be considered to be a coincidence. However, the chances of this are low because a rapid increase in the number of CMB, as was seen in case 1, and the occurrence of so many CMB, as was seen in case 2, are rare. Based on my clinical experiences and the detailed findings of the IgG4-RD cases described in this report, I present the hypothesis that “IgG4-related cerebral small vessel vasculitis/vasculopathy” exists.
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Affiliation(s)
- Katsuyuki Ukai
- Department of Psychogeriatrics, Kamiiida Daiichi General Hospital, Nagoya, Japan.,Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
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47
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Pyae PK, Cama R, Nicholson AG, Vancheeswaran R. Curious case of the unexplained exudative pleural effusion. BMJ Case Rep 2021; 14:e245796. [PMID: 34544724 PMCID: PMC8454451 DOI: 10.1136/bcr-2021-245796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2021] [Indexed: 11/03/2022] Open
Abstract
We report a case of a 74-year-old male patient who was referred to the respiratory clinic with an incidental finding of a left sided pleural effusion. He was initially being treated by the general practitioner for chest infection with productive cough that had limited resolution after course of oral antibiotics. At the pleural clinic, 1.5 L of serosanguineous fluid was drained and sent for diagnostics. However, the diagnosis only reached as far as idiopathic exudative effusion with lymphocytes and plasma cells. He was then referred for video-assisted thoracoscopic surgery pleural biopsy and pleurodesis. It revealed black pleura with abundant IgG4 positive cells. He is followed up in respiratory clinic where further discussion and treatment has commenced.
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Affiliation(s)
- Phyoe Kyaw Pyae
- Respiratory Medicine, West Hertfordshire Hospitals NHS Trust, Watford, UK
| | - Rigers Cama
- Respiratory Medicine, West Hertfordshire Hospitals NHS Trust, Watford, UK
| | - Andrew G Nicholson
- Department of Histopathology, Royal Brompton and Harefield NHS Trust, London, UK
| | - Rama Vancheeswaran
- Respiratory Medicine, West Hertfordshire Hospitals NHS Trust, Watford, UK
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48
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Akazawa T, Sekido M, Adachi K, Aihara Y, Myojo R. A tumor of IgG4-related skin disease on a forehead with relapse 3 years after resection. JAAD Case Rep 2021; 16:9-11. [PMID: 34504926 PMCID: PMC8413660 DOI: 10.1016/j.jdcr.2021.07.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Affiliation(s)
- Toshifumi Akazawa
- Department of Plastic and Reconstructive Surgery, Tsukuba Gakuen Hospital, Tsukuba, Ibaraki, Japan
| | - Mitsuru Sekido
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Koji Adachi
- KANEKI Dermatology Clinic, Iwaki, Fukushima, Japan
| | - Yukiko Aihara
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Risa Myojo
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
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49
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Soputro NA, Kapoor J, Popa I, Katz D. Testicular-sparing excision for benign paratesticular IgG4-related disease. BMJ Case Rep 2021; 14:14/9/e243450. [PMID: 34493553 PMCID: PMC8424693 DOI: 10.1136/bcr-2021-243450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 28-year-old male was referred by his local general practitioner due to recurrence of painful right scrotal mass, first noted 8 years prior. The mass was further characterised with ultrasound and then was locally excised via an inguinal approach, sparing the testicle, without any postoperative complication. Immunoperoxidase staining of the excised lesion confirmed paratesticular IgG4-related disease.
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Affiliation(s)
| | - Jada Kapoor
- Department of Urology, Western Health, Footscray, Victoria, Australia
| | - Ioana Popa
- Department of Urology, Western Health, Footscray, Victoria, Australia
| | - Darren Katz
- Men's Health Melbourne, Melbourne, Victoria, Australia.,Department of Surgery, The University of Melbourne Faculty of Medicine Dentistry and Health Sciences, Parkville, Victoria, Australia
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50
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Ikebe S, Minami S, Ihara S, Yasuoka H, Komuta K. Pulmonary Adenosquamous Cell Carcinoma With Systemic Lymphadenopathy due to Immunoglobulin G4-Related Disease: A Case Report. J Med Cases 2021; 12:164-171. [PMID: 34434452 PMCID: PMC8383661 DOI: 10.14740/jmc3649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 01/27/2021] [Indexed: 11/11/2022] Open
Abstract
A 75-year-old man with diabetes mellitus showed elevated C-reactive protein (CRP) level at his regular visit. Computed tomography scan showed a lung tumor in his left lower lobe and systemic lymphadenopathy including abdominal lymph nodes. The patient was diagnosed as primary pulmonary squamous cell carcinoma with systemic lymph node metastasis. Thereafter, unexpected steroid pulse therapy for accidental acute exacerbation of interstitial pneumonia rapidly shrank lymphadenopathy. At this time, we also found elevated serum immunoglobulin G4 (IgG4) level (385 mg/dL). Considering these findings, we doubted the lymph nodes metastases at the initial staging, and then corrected cancer-staging (C-staging) from inferior vena cava (IVC) to inferior abdomen (IA). In addition, during the steroid tapering, sudden onset and uncontrollable left pneumothorax required surgical approach. Curative-intent left lower lobectomy with lymphadenectomy was performed for the lung cancer. Pathological findings revealed coexistence of adenosquamous carcinoma and infiltration of IgG4-positive plasma cells in the resected mediastinal lymph node. We detected 384 IgG4-positive cells per high power field. IgG4/IgG-positive cell ratio was 54%. Based on these findings, the diagnosis of IgG4-related disease with primary adenosquamous carcinoma (p-stage IIIA) was confirmed. The patient died 24 days after surgery because of another acute exacerbation of interstitial pneumonia. Our case alerts oncologists to IgG4-related disease as a possible underlying comorbidity which may confuse pretreatment clinical stage.
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Affiliation(s)
- Saori Ikebe
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan
| | - Seigo Minami
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan.,Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasuga-tuji, Tennoji-ku, Osaka 543-0042, Japan
| | - Shouichi Ihara
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan.,Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasuga-tuji, Tennoji-ku, Osaka 543-0042, Japan
| | - Hironao Yasuoka
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan
| | - Kiyoshi Komuta
- Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasuga-tuji, Tennoji-ku, Osaka 543-0042, Japan
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