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Hoffmann C, Oksenhendler E, Littler S, Grant L, Kanhai K, Fajgenbaum DC. The clinical picture of Castleman disease: a systematic review and meta-analysis. Blood Adv 2024; 8:4924-4935. [PMID: 38985311 PMCID: PMC11421328 DOI: 10.1182/bloodadvances.2024013548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/11/2024] Open
Abstract
ABSTRACT Castleman disease (CD) encompasses a spectrum of rare disorders, including unicentric CD (UCD), idiopathic multicentric CD (iMCD), and human herpesvirus 8-associated MCD (HHV8+ MCD). We performed a systematic review of publications reporting ≥5 cases of CD between 1995 and 2021, following preferred reporting items for systematic reviews and meta-analyses guidelines, to describe and compare subtypes. We extracted data on clinical symptoms and laboratory parameters as stated in international consensus diagnostic criteria for iMCD and estimated the frequency of each criterion using meta-analyses. We analyzed 32 studies describing 559 UCD, 1023 iMCD, and 416 HHV8+ MCD cases. Although many symptoms and laboratory abnormalities occurred at similar rates in patients with iMCD and HHV8+ MCD, patients with HHV8+ MCD had significantly higher rates of constitutional symptoms (46.6% vs 98.6%; P = .038) and splenomegaly (48.2% vs 89.2%; P = .031). Renal dysfunction was significantly more common in patients with iMCD than in patients with HHV8+ MCD before adjustment (36.9% vs 17.4%; P = .04; adjusted P = .1). Patients with UCD had lower rates of symptoms and laboratory abnormalities, although these were present in 20% of patients and were particularly pronounced in pediatric UCD. There are many similarities in the symptomatology of iMCD and HHV8+ MCD; many patients experience constitutional symptoms and organ dysfunction. Differences between these subtypes likely reflect differences in pathophysiology and/or comorbidity burdens.
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Affiliation(s)
- Christian Hoffmann
- Infektionsmedizinisches Centrum Hamburg Study Center, Hamburg, Germany
- Department of Medicine, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Eric Oksenhendler
- Department of Clinical Immunology, Hôpital Saint-Louis, Paris, France
| | | | - Lisa Grant
- TVF Communications, London, United Kingdom
| | - Karan Kanhai
- Medical Affairs, Recordati Pharma Ltd, Hemel Hempstead, United Kingdom
| | - David C. Fajgenbaum
- Department of Medicine, Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Xu J, Zhai J, Zhao J. Pathogenic roles of follicular helper T cells in IgG4-related disease and implications for potential therapy. Front Immunol 2024; 15:1413860. [PMID: 38911857 PMCID: PMC11190345 DOI: 10.3389/fimmu.2024.1413860] [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: 04/08/2024] [Accepted: 05/27/2024] [Indexed: 06/25/2024] Open
Abstract
IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4+ plasma cells in multiple organ systems. Recent advancements have significantly enhanced our understanding of the pathological mechanism underlying this immune-mediated disease. T cell immunity plays a crucial role in the pathogenesis of IgG4-RD, and follicular helper T cells (Tfh) are particularly important in germinal center (GC) formation, plasmablast differentiation, and IgG4 class-switching. Apart from serum IgG4 concentrations, the expansion of circulating Tfh2 cells and plasmablasts may also serve as novel biomarkers for disease diagnosis and activity monitoring in IgG4-RD. Further exploration into the pathogenic roles of Tfh in IgG4-RD could potentially lead to identifying new therapeutic targets that offer more effective alternatives for treating this condition. In this review, we will focus on the current knowledge regarding the pathogenic roles Tfh cells play in IgG4-RD and outline potential therapeutic targets for future clinical intervention.
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Affiliation(s)
- Jingyi Xu
- Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China
| | - Jiayu Zhai
- Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China
- Center for Rare Disease, Peking University Third Hospital, Beijing, China
| | - Jinxia Zhao
- Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China
- Center for Rare Disease, Peking University Third Hospital, Beijing, China
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Rodriguez Merino L, Pomares AA, Arce JR, Montes-Moreno S. From Castleman disease histopathological features to idiopathic multicentric Castleman disease: a multiparametric approach to exclude potential iMCD histopathological mimickers. J Clin Pathol 2024; 77:318-323. [PMID: 36690434 DOI: 10.1136/jcp-2022-208696] [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: 11/23/2022] [Accepted: 01/12/2023] [Indexed: 01/24/2023]
Abstract
AIMS International consensus diagnostic criteria for idiopathic multicentric Castleman disease (iMCD) includes lymph node Castleman disease (CD) histopathological features as major criteria. Our aim was to apply those criteria in a series of 42 cases with CD to find differences among unicentric CD, iMCD, HHV-8+multicentric CD (HHV-8+MCD) and POEMS/plasma cell neoplasia (PCN)-associated CD. METHODS Available clinical and laboratory criteria were collected. Histopathological features (germinal centre hyperplasia/regression, plasmacytosis, hypervascularity and follicular dendritic cell (FDC) prominence) were graded and immunohistochemistry with antibodies against CD20, CD3, CD138, HHV-8, Ig isotype (IgG, IgG4, IgA, IgM, IgD), kappa, lambda was performed in all cases. RESULTS Fourteen cases had hyaline-vascular type unicentric CD, 15 were HHV-8+MCD, 7 cases PCN/POEMS-associated CD and 5 cases were iMCD. One case was consistent with systemic lupus erythematosus (SLE) lymphadenopathy. Differences in grading of the CD-associated histopathological features showed that FDC proliferation was prominent in unicentric CD, hypervascularity was increased in HHV-8 positive MCD and germinal centre hyperplasia was restricted to iMCD cases and SLE. Monotypic plasma cells were readily identifiable in the lymph node biopsies in 43% of PCN/POEMS-associated CD. All three cases had lambda light chain restriction with IgA (two cases) and IgG (one case) isotypes. CONCLUSIONS HHV-8+ MCD and PCN/POEMS-related CD are the major mimickers of iMCD in lymph node biopsies. Grading of the five histopathological features for CD might be useful to, in conjunction with complete ancillary testing, suggest for specific disease entities.
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Affiliation(s)
| | - Aitana Avendaño Pomares
- Translational Hematopathology/IDIVAL, Hospital Universitario Marques de Valdecilla, Santander, Spain
| | - Jose Revert Arce
- Pathology Department, Hospital Universitario Marques de Valdecilla, Santander, Spain
| | - Santiago Montes-Moreno
- Anatomic Pathology, Hospital Universitario Marques de Valdecilla, Universidad de Cantabria (UNICAN), Santander, Spain
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Tsuge S, Mizushima I, Horita M, Kawahara H, Sanada H, Yoshida M, Takahashi Y, Zoshima T, Nishioka R, Hara S, Suzuki Y, Ito K, Kawano M. High serum IgA levels in patients with IgG4-related disease are associated with mild inflammation, sufficient disease-specific features, and favourable responses to treatments. Mod Rheumatol 2024; 34:621-631. [PMID: 37307433 DOI: 10.1093/mr/road056] [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: 10/03/2022] [Revised: 12/21/2022] [Accepted: 06/08/2023] [Indexed: 06/14/2023]
Abstract
OBJECTIVES Although elevated serum immunoglobulin A (IgA) levels are thought to exclude a diagnosis of IgG4-related disease (IgG4-RD), IgG4-RD has been definitively diagnosed in some patients despite elevated serum IgA levels. This study aimed to clarify the prevalence of elevated IgA levels in patients with IgG4-RD and to compare the clinical features of IgG4-RD patients with and without elevated IgA levels. METHODS The clinical features of 169 IgG4-RD patients were retrospectively compared among those with and without elevated serum IgA levels. RESULTS Of the 169 patients with IgG4-RD, 17 (10.1%) had elevated serum IgA levels. Those with elevated serum IgA levels showed higher serum C-reactive protein levels and lower prevalence of relapse than those without. Other clinical features did not differ significantly, including inclusion scores of the American College of Rheumatology/European League Against Rheumatism classification criteria. Cox regression analysis showed that elevated serum IgA levels were associated with a lower incidence of relapse. Moreover, patients with elevated serum IgA levels showed prompt improvement in response to glucocorticoids in the IgG4-RD responder index. CONCLUSIONS Some patients diagnosed with IgG4-RD have high serum IgA levels. These patients may form a subgroup, characterized by good response to glucocorticoids, less frequent relapse, mildly elevated serum C-reactive protein levels, and possible complications of autoimmune diseases.
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Affiliation(s)
| | | | - Makoto Horita
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Hiroyuki Kawahara
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Hajime Sanada
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Misaki Yoshida
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | | | - Takeshi Zoshima
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Ryo Nishioka
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Satoshi Hara
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Yasunori Suzuki
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Kiyoaki Ito
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Mitsuhiro Kawano
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
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Park BU, Lee HE, Zhang L. Mimickers of immunoglobulin G4-related hepatobiliary disease on biopsy. Semin Diagn Pathol 2024; 41:95-107. [PMID: 38238218 DOI: 10.1053/j.semdp.2024.01.009] [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: 12/11/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 03/24/2024]
Abstract
With the growing recognition of IgG4-related hepatobiliary disease, establishing a definitive diagnosis relies mainly on a combination of clinical findings, serological markers, and imaging modalities. However, the role of histopathological evaluation remains indispensable, particularly in cases necessitating differential diagnosis or malignancy exclusion. While diagnosing IgG4-related hepatobiliary disease through surgical resection specimens is often straightforward, pathologists encounter substantial challenges when evaluating biopsies. The increasing rarity of surgical interventions exacerbates this due to improved disease recognition and suspicion. Numerous confounding factors, including the absence of the characteristic histologic features, limited tissue sample size, biopsy artifacts, and the limited value of IgG4 counts, further complicate the diagnostic process. Additionally, many other disorders exhibit clinical and histological features that overlap with IgG4-related disease, intensifying the complexity of interpreting biopsy specimens. This article explores the clinical and histomorphologic features of IgG4-related hepatobiliary disease and its potential mimickers. It offers valuable insights for pathologists and clinicians when confronted with biopsy specimens from hepatobiliary organs.
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Affiliation(s)
- Byoung Uk Park
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Hee Eun Lee
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Lizhi Zhang
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States.
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Mukhopadhyay S. Differential diagnosis of IgG4-positive plasma cells in the lung. Semin Diagn Pathol 2024; 41:72-78. [PMID: 37993385 DOI: 10.1053/j.semdp.2023.11.006] [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: 09/24/2023] [Accepted: 11/14/2023] [Indexed: 11/24/2023]
Abstract
The recognition of immunoglobulin G4-related disease (IgG4-RD) as an entity in the pancreaticobiliary tract was followed by a slew of papers describing inflammation and fibrosis containing IgG4-positive plasma cells in a variety of sites including the respiratory tract, leading to the hypothesis that these abnormalities were attributable to IgG4-RD. Predictably, pathologists began to see requests from clinicians to perform IgG4 immunohistochemistry in lung biopsies "to rule out IgG4-RD". Several years later, the notion that IgG4-RD would prove to be the underlying cause of a wide array of fibroinflammatory lesions in the lung has not panned out as promised. To the contrary, it has become clear that IgG4-positive plasma cells are not specific for IgG4-RD, and that large numbers of IgG4-positive plasma cells can be encountered in other well-defined entities, including inflammatory myofibroblastic tumor and nodular lymphoid hyperplasia, as well as in lymphoplasmacytic infiltrates in other entities, including connective tissue disease and idiopathic forms of interstitial lung disease. It has also become clear that raised serum IgG4 levels can occur in settings other than IgG4-RD. These observations suggest that true IgG4-RD of the lung is far less common than previously surmised. Pathologists must familiarize themselves with mimics of IgG4-RD in the lung and exercise caution before attributing lymphoplasmacytic infiltrates in the lung to IgG4-RD.
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Affiliation(s)
- Sanjay Mukhopadhyay
- Department of Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue/L25, Cleveland, OH 44195, United States.
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Sawada E, Shioda Y, Ogawa K, Iwashita T, Ono Y, Hasegawa H, Maeshima A. A Case of Castleman's Disease with a Marked Infiltration of IgG4-Positive Cells in the Renal Interstitium. Diagnostics (Basel) 2024; 14:476. [PMID: 38472948 DOI: 10.3390/diagnostics14050476] [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: 02/07/2024] [Revised: 02/19/2024] [Accepted: 02/19/2024] [Indexed: 03/14/2024] Open
Abstract
Multicentric Castleman's disease (MCD) is a benign lymphoproliferative disorder with heterogenous clinical symptoms, and involves systemic organs in addition to lymph nodes. Herein, we present the case of a 55-year-old man with MCD characterized by an extensive infiltration of IgG4+ plasma cells in the kidneys. The patient presented to our hospital with a high fever and diarrhea. On admission, laboratory analysis revealed anemia, renal dysfunction (eGFR 30 mL/min/1.73 m2), polyclonal gammopathy (IgG 7130 mg/dL), elevated serum IgG4 level (2130 mg/dL), and increased C-reactive protein (8.0 mg/dL). An enlargement of lymph nodes in the axillary, mediastinal, para-aortic, and inguinal regions was observed on abdominal computed tomography. Axillary lymph node biopsy revealed interfollicular expansion due to dense plasma cell infiltration. Renal biopsy demonstrated significant plasma cell infiltration into the tubulointerstitium. Immunohistochemical analysis showed a 40% IgG4-positive/IgG-positive plasma cell ratio, meeting the diagnostic criteria for an IgG4-related disease. Amyloid A deposition was observed along vessel walls, and immunofluorescence analysis indicated granular positivity of IgG and C3 along the glomerular capillary wall. Elevated levels of interleukin-6 (21 pg/mL) and vascular endothelial growth factor (VEGF; 1210 pg/mL) were noted. Based on these findings, and the histological finding of the lymph node biopsy, idiopathic MCD was diagnosed. Corticosteroid monotherapy was only partially effective. Subsequently, tocilizumab administration was initiated, leading to sustained remission, even after discontinuation of prednisolone. Due to the diverse responses to steroid therapy and the varying prognoses observed in MCD and IgG4-related disease, it is essential to carefully diagnose MCD by thoroughly assessing the organ distribution of the disease, its response to steroid therapy, and any additional pathological findings.
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Affiliation(s)
- Erika Sawada
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
| | - Yuya Shioda
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
| | - Kohki Ogawa
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
| | - Takatsugu Iwashita
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
| | - Yuko Ono
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
| | - Hajime Hasegawa
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
| | - Akito Maeshima
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
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Guo M, Nong L, Wang M, Zhang Y, Wang L, Sun Y, Wang Q, Liu H, Ou J, Cen X, Ren H, Dong Y. Retrospective cohort evaluation of non-HIV Castleman disease from a single academic center in Beijing, China. Ann Hematol 2024; 103:153-162. [PMID: 37749319 DOI: 10.1007/s00277-023-05472-3] [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: 05/03/2023] [Accepted: 09/20/2023] [Indexed: 09/27/2023]
Abstract
The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).
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Affiliation(s)
- Meiyu Guo
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Lin Nong
- Department of Pathology, Peking University First Hospital, Beijing, China
| | - Mingyue Wang
- Department of Dermatology, Peking University First Hospital, Beijing, China
| | - Yang Zhang
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Lihong Wang
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Yuhua Sun
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Qingyun Wang
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Huihui Liu
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Jinping Ou
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Xinan Cen
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Hanyun Ren
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China
| | - Yujun Dong
- Department of Hematology, Peking University First Hospital, No. 7 Xishiku St. Xicheng District, Beijing, 100034, China.
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9
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Whitehair RM, Aguilera NS, Pramoonjago P, Craig JW. Increased IgG4+ plasma cells are common in excised lymph nodes from children and adolescents without IgG4-related disease. J Hematop 2023; 16:209-216. [PMID: 38175435 DOI: 10.1007/s12308-023-00565-4] [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: 09/18/2023] [Accepted: 10/30/2023] [Indexed: 01/05/2024] Open
Abstract
Lymphadenopathy is a common finding in patients with IgG4-related disease (IgG4-RD) and often associated with increased IgG4+ plasma cells in this setting. The histologic features of so-called IgG4-related lymphadenopathy (IgG4-LAD) have seldom been investigated in children and adolescents, and step-wise progression to extranodal IgG4-RD has not been described. This study was performed to further evaluate the frequency, pathologic features, and clinical significance of IgG4-LAD-like histologic changes in the pediatric setting. We analyzed 37 benign lymph nodes collected semi-consecutively from children aged 0-18 years at our institution for both absolute and relative IgG4+ plasma cell abundance and recurrent histomorphologic patterns associated with IgG4-LAD. The combination of IgG4+/IgG+ plasma cell ratio >40% and IgG4+ plasma cell count ≥50 were considered as IgG4-LAD-like per expert consensus guidelines. Seven cases (19%) met both diagnostic criteria. The dominant histomorphologic patterns were follicular hyperplasia (n = 6), interfollicular expansion (n = 3), and progressive transformation of germinal centers (n = 3). Extranodal manifestations of IgG4-RD were not identified in this cohort (38 months average follow-up). Instead, clinical and laboratory findings indicated that lymph node enlargement in most patients could likely be attributed to alternative processes including antecedent dentistry, concurrent infection, and incipient Crohn's disease. Our findings suggest that the histologic features of IgG4-LAD are likely much more common in children and adolescents than previously recognized, often existing in complex with common reactive lymphadenopathies. The diagnostic value of routine immunohistochemical assessment for IgG4+ plasma cells in benign lymph nodes from pediatric patients without established extranodal IgG4-RD and/or other supportive clinical and laboratory data is therefore uncertain.
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Affiliation(s)
- Rachel M Whitehair
- Department of Pathology, University of Virginia Health System, Charlottesville, VA, 22908-0904, USA
| | - Nadine S Aguilera
- Department of Pathology, University of Virginia Health System, Charlottesville, VA, 22908-0904, USA
| | - Patcharin Pramoonjago
- Department of Pathology, University of Virginia Health System, Charlottesville, VA, 22908-0904, USA
| | - Jeffrey W Craig
- Department of Pathology, University of Virginia Health System, Charlottesville, VA, 22908-0904, USA.
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10
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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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11
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Kawano M, Saeki T, Ubara Y, Matsui S. Recent advances in IgG4-related kidney disease. Mod Rheumatol 2023; 33:242-251. [PMID: 35788361 DOI: 10.1093/mr/roac065] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/01/2022] [Accepted: 06/21/2022] [Indexed: 11/14/2022]
Abstract
Recent advances in the management and understanding of immunoglobulin (Ig)G4-related kidney disease (RKD) have emphasized the importance of urgent treatment in IgG4-related tubulointerstitial nephritis. On the other hand, to avoid long-term glucocorticoid toxicity, strategies for early withdrawal of steroids or combination of immunosuppressants, such as rituximab, and the minimum dose of steroids have been pursued. However, disease recurrence after reducing or stopping steroid therapy hampers early withdrawal of glucocorticoid maintenance therapy. In addition, knowledge has accumulated in diagnostic approaches including differential diagnosis of anti-neutrophil cytoplasmic antibodies-associated vasculitis, idiopathic multicentric Castleman's disease, and Rosai-Dorfman disease with kidney lesion, which leads to earlier and precise diagnosis of IgG4-RKD. This review summarizes recent progress in the differential diagnosis of IgG4-RKD and related treatment strategies and recent topics of hypocomplementaemia, membranous glomerulonephritis, and IgG4-related pyelitis and periureteral lesion.
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Affiliation(s)
- Mitsuhiro Kawano
- Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
| | - Takako Saeki
- Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Yoshifumi Ubara
- Department of Nephrology and Rheumatology, Toranomon Hospital, Kawasaki, Japan
| | - Shoko Matsui
- Health Administration Center, University of Toyama, Toyama, Japan
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Abstract
Lymphadenopathy occurring in patients with immunoglobulin G4 (IgG4)-related disease, termed IgG4-related lymphadenopathy, shows morphologic heterogeneity and overlap with other nonspecific causes of lymphadenopathy including infections, immune-related disorders, and neoplasms. This review describes the characteristic histopathologic features and diagnostic approach to IgG4-related disease and IgG4-related lymphadenopathy, with comparison to nonspecific causes of increased IgG4-positive plasma cells in lymph nodes, and with emphasis on distinction from IgG4-expressing lymphoproliferative disorders.
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Affiliation(s)
- Jacob R Bledsoe
- Department of Pathology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
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13
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Kogami M, Abe Y, Ando T, Makiyama A, Yamaji K, Tamura N. Performance of classification and diagnostic criteria for IgG4-related disease and comparison of patients with and without IgG4-related disease. Sci Rep 2023; 13:2509. [PMID: 36782006 PMCID: PMC9925424 DOI: 10.1038/s41598-023-29645-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/08/2023] [Indexed: 02/15/2023] Open
Abstract
IgG4-related disease (IgG4-RD) was recently described in Japan. It is characterised by extensive organ involvement with tissue fibrosis. We assessed the performance of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria as well as differences between patients with and without IgG4-RD. In this retrospective, single-centre study of 50 patients admitted with suspected IgG4-RD, we evaluated the sensitivity and specificity of both criteria. We also compared clinical characteristics and laboratory data of patients with IgG4-RD (n = 42) and patients without IgG4-RD (n = 8). The ACR/EULAR classification criteria had 88.1% sensitivity and 87.5% specificity for IgG4-RD diagnosis. The RCD criteria had 100% sensitivity and 50% specificity. Patients with IgG4-RD had significantly more affected organs (p = 0.002). Patients with a single affected organ and IgG4-RD had significantly higher serum IgG4/IgG ratios (p = 0.027), lower serum C-reactive protein levels (p = 0.020), and lower total haemolytic complement activity (p = 0.044) than those without IgG4-RD. The ACR/EULAR classification criteria have high specificity and the RCD criteria have high sensitivity for diagnosing IgG4-RD. The number of affected organs is important for diagnosing IgG4-RD.
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Affiliation(s)
- Masahiro Kogami
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan.
| | - Yoshiyuki Abe
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan
| | - Taiki Ando
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan
| | - Ayako Makiyama
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan
| | - Ken Yamaji
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan
| | - Naoto Tamura
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, Japan
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14
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Yoshida M, Mizushima I, Tsuge S, Takahashi Y, Zoshima T, Nishioka R, Hara S, Ito K, Kawano M. Development of IgG4-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy: A case report. Mod Rheumatol Case Rep 2023; 7:192-196. [PMID: 35950792 DOI: 10.1093/mrcr/rxac065] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/17/2022] [Accepted: 08/05/2022] [Indexed: 06/15/2023]
Abstract
This report describes a patient diagnosed with immunoglobulin G4 (IgG4)-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy. A 48-year-old Japanese woman presented with fatigue and leg oedema. Computed tomography showed perigastric lymphadenopathy, for which she underwent a laparoscopic biopsy of the perigastric lymph nodes. Although histopathological examination of the lymph nodes did not lead to a definitive diagnosis, serological tests revealed elevated serum IgG4 levels (558 mg/dl) and IgG4 immunostaining of the lymph nodes showed IgG4-positive plasma cell infiltration, leading to the suspicion of IgG4-related disease. Further workup revealed no organ lesion other than lymphadenopathy. At age 55 years, despite having no subjective symptoms, contrast-enhanced computed tomography showed low-density lesions in the tail of the pancreas and the left kidney. Histopathological examination showed lymphocyte infiltration, consisting of a mixture of plasma cells and eosinophils, in both organs and obliterative phlebitis in the pancreas. IgG4 immunostaining of the kidney specimens showed 160 IgG4-positive cells per high-powered field, with the IgG4+/IgG+ cell ratio being almost 100%, leading to a diagnosis of IgG4-related pancreatitis and kidney disease. Treatment with prednisolone for 2 months resulted in lesion improvement. Although the diagnosis of IgG4-related lymphadenopathy is often challenging in patients with lymphadenopathy alone, findings in the present patient emphasise the importance of long-term follow-up, as it may allow early detection of involvement of other organs by IgG4-related disease.
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Affiliation(s)
- Misaki Yoshida
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Ichiro Mizushima
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Shunsuke Tsuge
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | | | - Takeshi Zoshima
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Ryo Nishioka
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Satoshi Hara
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Kiyoaki Ito
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Mitsuhiro Kawano
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
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15
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Idiopathic Multicentric Castleman Disease with Strikingly Elevated IgG4 Concentration in the Serum and Abundant IgG4-Positive Cells in the Tissue: A Case Report. Diagnostics (Basel) 2022; 12:diagnostics12092261. [PMID: 36140662 PMCID: PMC9498249 DOI: 10.3390/diagnostics12092261] [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: 08/12/2022] [Revised: 09/07/2022] [Accepted: 09/17/2022] [Indexed: 11/16/2022] Open
Abstract
Idiopathic multicentric Castleman disease (iMCD) can be challenging to distinguish clinically and histopathologically from Immunoglobulin G4-related disease (IgG4RD). A 73-year-old man was referred to a rheumatologist for suspected autoimmune-related polyclonal hypergammaglobulinemia. The patient had a history of multiple lymphadenopathies in the neck for over 20 years. Laboratory data showed elevated serum immunoglobulin G4 (IgG4) levels, hypergammaglobulinemia, high C-reactive protein (CRP) levels, marked anemia, and positivity for several autoantibodies. Additionally, imaging studies revealed multiple enlarged lymph nodes and multifocal, ill-defined, small patchy opacities over the lung. Biopsies of the neck lymph node and right lung revealed typical features of multicentric Castleman disease (MCD). Immunohistochemical staining was negative for human herpesvirus-8 (HHV-8) in both lymph nodes and the right lung, sub-classified as iMCD, whereas the IgG4/IgG ratio was >40%, which raised the suspicion of IgG4RD. However, serological cytokine analysis demonstrated an increased interleukin-6 (IL-6) level, alongside systemic inflammatory and histopathological features, distinguishing MCD from IgG4RD in this patient. The patient was treated with short-term glucocorticoids and regular infusion of an anti-IL-6 receptor monoclonal antibody (tocilizumab), with satisfactory clinical and radiographic responses. Notably, differentiating MCD from IgG4RD is crucial for optimal treatment. Clinical and pathological features may assist in distinguishing between these two diseases.
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16
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Zhang S, Zhang J, Li Y, Jiao J. From Suspicion to Diagnosis: Analysis on the Clinical Characteristics of 37 Cases of IgG4-Related Disease (IgG4-RD) in Northeast China. J Inflamm Res 2022; 15:4487-4497. [PMID: 35966001 PMCID: PMC9365018 DOI: 10.2147/jir.s367211] [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: 03/23/2022] [Accepted: 07/08/2022] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION IgG4-related disease (IgG4-RD) mimics a variety of disorders, the final diagnosis is heavily dependent on the doctor's familiarity with the disease, most patients are expected to get a good prognosis by early diagnosis and timely treatment. METHODS Retrospective analysis was carried out on 147 patients tested for serum IgG4 because of suspected IgG4-RD. These cases were grouped as the IgG4-RD group and non-IgG4-RD group according to the diagnostic criteria proposed by the Japanese IgG4-RD research group and the American College of Rheumatology and the European Union of Rheumatology. Characteristics of these patients were investigated and analyzed. RESULTS The onset age of IgG4-RD was 57.29 ± 14.03 years old, male to female ratio of IgG4-RD was 1.31:1. The most commonly affected organs were the pancreas (48.6%), lymph nodes (40.5%) and biliary tract (35.1%), the proportion of patients with simultaneous involvement of multiple organs is as high as 83.2%. A history of allergy is more common in IgG4-RD patients (32.4% vs 14.5%), the optimal critical value of serum IgG4/IgG ratio for diagnosis of IgG4-RD was 0.09 (sensitivity 94.7%, specificity 91.7%) and the optimal threshold for IgG diagnosis of IgG4-RD was 15.25g/L (sensitivity 73.7%, specificity 77.8%) in this study. CONCLUSION IgG4-RD is often manifested as multiple organ involvement, and is most likely to involve the pancreas, biliary tract and lymph nodes. Most patients were diagnosed in other departments instead of rheumatology. Serum IgG4 level, especially IgG4/IgG ratio has a higher predictive value for IgG4-RD. Early diagnosis is the key point to improve the prognosis.
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Affiliation(s)
- Shanshan Zhang
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
| | - Jun Zhang
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
| | - Yifang Li
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
| | - Jian Jiao
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
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17
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Covelli C, Carosi I, Graziano P, Ascani S. When idiopathic retroperitoneal fibrosis mimics Castleman disease: a challenging differential diagnosis. BMJ Case Rep 2022; 15:e248051. [PMID: 35393274 PMCID: PMC8990696 DOI: 10.1136/bcr-2021-248051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/29/2022] [Indexed: 11/04/2022] Open
Affiliation(s)
- Claudia Covelli
- Pathology Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Illuminato Carosi
- Pathology Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Paolo Graziano
- Pathology Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Stefano Ascani
- Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, Terni, Italy
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18
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Two cases of refractory IgG4-related disease successfully treated with tocilizumab. Ann Hematol 2022; 101:1593-1594. [DOI: 10.1007/s00277-022-04787-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 02/02/2022] [Indexed: 11/01/2022]
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19
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Duggal L, Singh BG, Patel J, Gupta M, Grover AK, Jain N. IgG4-Related Disease: A Clinical Case Series From a Tertiary Care Center in India. J Clin Rheumatol 2022; 28:e56-e62. [PMID: 33105313 DOI: 10.1097/rhu.0000000000001591] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
AIM Immunoglobulin G4-related disease (IgG4-RD) is often an unrecognized, rare fibroinflammatory condition that can involve various organ systems. This study aimed to identify the different clinical patterns of this disease in a single center in North India. METHODS Patients were diagnosed on the basis of published diagnostic criteria for IgG4-RD. Patients' presenting complaints; epidemiologic profiles; and laboratory, radiologic, and histologic findings along with the treatment and outcomes were collected and analyzed. RESULTS In total, 70 patients were diagnosed with the disease. The female-to-male ratio was 0.94:1, and it increased with multiorgan involvement. The mean age of patients was 41.4 years, and the majority of the patients (65.7%) were younger than 50 years. Patients were diagnosed as possible (38.57%), probable (32.85%), and definite (28.57%) IgG4-RD. The incidence of the involvement of orbital and periorbital tissues was the highest (52.9%); however, 13% of the patients had multiple organ involvement. Patients with involvement of the retroperitoneal tissues and the lymph nodes were 8.5% and 5.7%, respectively. Increased serum IgG4 levels were found in 74.3% of the patients with single-organ involvement, whereas all patients with multiorgan involvement had increased IgG4 levels. The majority of patients (94.3%) required immunosuppressive medications along with corticosteroids. Azathioprine was the most commonly used (72.8%) immunosuppressive medication. Rituximab was used in 17.1% of the patients, of whom only one had multisystem involvement. CONCLUSIONS This study depicts the most common patterns of organ involvement, along with the epidemiologic, laboratory, histologic, and radiologic data and response to treatment, in IgG4-RD, with a definite ophthalmology referral bias.
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20
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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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21
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[Immunoglobulin G (IgG) 4-related diseases]. Z Rheumatol 2021; 81:225-235. [PMID: 34851443 DOI: 10.1007/s00393-021-01130-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/03/2021] [Indexed: 10/19/2022]
Abstract
Immunoglobulin G (IgG) 4‑related diseases are fibrosing inflammatory systemic diseases that can affect almost every organ system. Typical disease manifestations include autoimmune pancreatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory orbitopathy and involvement of the salivary and lacrimal glands. Organ involvements can occur either isolated or in combination with other disease manifestations. Before diagnosing IgG4-related diseases, malignancies and other inflammatory diseases have to be excluded. The diagnosis requires a combination of laboratory findings, histological and radiological results. Typically, IgG4-related diseases respond well to glucocorticosteroids. In cases of relapse or severe organ involvement a longer term immunosuppression is often required, whereas watch and wait can also be sufficient in milder cases.
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22
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Zhou T, Wang HW, Pittaluga S, Jaffe ES. Multicentric Castleman disease and the evolution of the concept. Pathologica 2021; 113:339-353. [PMID: 34837092 PMCID: PMC8720411 DOI: 10.32074/1591-951x-351] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 08/25/2021] [Indexed: 12/29/2022] Open
Abstract
The term multicentric Castleman disease (MCD) encompasses a spectrum of conditions that share some overlapping clinicopathological manifestations. The fundamental pathogenetic mechanism involves dysregulated cytokine activity, causing systemic inflammatory symptoms as well as lymphadenopathy. Some of the histological changes in lymph nodes resemble the histology of unicentric Castleman disease (UCD). However, based on current knowledge, the use of this shared nomenclature is unfortunate, since these disorders differ in pathogenesis and prognosis. In Kaposi sarcoma-associated herpesvirus (KSHV)-associated MCD, cytokine overactivity is caused by viral products, which can also lead to atypical lymphoproliferations and potential progression to lymphoma. In idiopathic MCD, the hypercytokinemia can result from various mechanisms, which ultimately lead to different constellations of clinical presentations and varied pathology in lymphoid tissues. The authors review the evolving concepts and definitions of the various conditions under the eponym of multicentric Castleman disease.
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Affiliation(s)
- Ting Zhou
- Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hao-Wei Wang
- Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Stefania Pittaluga
- Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Elaine S Jaffe
- Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
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23
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Unique Ultrasonographic Findings of Isolated IgG4-Related Lymphadenopathy. Diagnostics (Basel) 2021; 11:diagnostics11122213. [PMID: 34943450 PMCID: PMC8700604 DOI: 10.3390/diagnostics11122213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/18/2021] [Accepted: 11/22/2021] [Indexed: 12/04/2022] Open
Abstract
IgG4-related disease is a rare immune-mediated disease that can involve many organs in the body. The lymph node is also where IgG4-related diseases occur, but its histological structure is different from that of other organs. For this reason, pathologists have difficulty diagnosing IgG4-related lymphadenopathy. If there were specific imaging findings of IgG4-related lymphadenopathy, it would be of great help to pathologists. A 64-year-old male visited our hospital with right ankle pain. On physical examination, the right lower extremity showed severe swelling with wound dehiscence, and infection was suspected. On CT (128-MDCT, Somatom Definition Flash, Siemens Healthcare) taken at the lower extremity, multiple enlarged lymph nodes were incidentally noted in the right inguinal area. On ultrasonography, a “starry night sign” resembling hyperechoic follicles was observed in the enlarged lymph node. A core needle biopsy was performed, and IgG4-related lymphadenopathy was diagnosed. Laboratory examination showed hypergammaglobulinemia with marked elevated serum IgG4, corresponding to IgG4-related disease. Chest and abdominal imaging were evaluated, but there was no extranodal IgG4-related disease. IgG4-related lymphadenopathy showed a very unique ultrasonography imaging finding. The cortex was filled with diffusely scattered hyperechoic foci and some bright foci gathered to form a follicle. This imaging finding may help diagnose IgG4-related lymphadenopathy.
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24
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Nishikori A, Nishimura MF, Nishimura Y, Notohara K, Satou A, Moriyama M, Nakamura S, Sato Y. Investigation of IgG4-positive cells in idiopathic multicentric Castleman disease and validation of the 2020 exclusion criteria for IgG4-related disease. Pathol Int 2021; 72:43-52. [PMID: 34762752 PMCID: PMC9299129 DOI: 10.1111/pin.13185] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 10/21/2021] [Indexed: 01/09/2023]
Abstract
Patients with plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) often show elevated serum IgG4 levels and IgG4-positive cell infiltration in tissues due to overproduction of interleukin-6, and may meet the diagnostic criteria for IgG4-related disease (IgG4-RD). Although PC-iMCD has been listed as a major exclusion disease for IgG4-RD, distinguishing between these diseases is challenging due to a lack of highly specific diagnostic biomarkers. In 2020, we proposed exclusion criteria of IgG4-RD mimickers. In this paper, we validated the accuracy of the criteria in excluding one of the mimickers, PC-iMCD, from IgG4-RD. Validation was performed on 57 PC-iMCD patients (39 presenting lymph node lesions and 19 with lung lesions) and 29 IgG4-RD patients (22 presenting lymph node lesions and seven with lung lesions). According to our results, 20.5% of the PC-iMCD patients with lymph node lesions and 42.1% of those with lung lesions met the diagnostic criteria for IgG4-RD. All these patients with PC-iMCD were excluded from a diagnosis of IgG4-RD by the proposed criteria. Additionally, 6.9% of IgG4-RD patients met the exclusion criteria. Thus, if the exclusion criteria are met, diagnosis should be made based on a combination of findings including organ distribution of disease, response to steroid therapy, and other pathological findings.
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Affiliation(s)
- Asami Nishikori
- Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan.,The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-Related Disease, Tokyo, Japan
| | - Midori Filiz Nishimura
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-Related Disease, Tokyo, Japan.,Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshito Nishimura
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.,Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, Hawaii, USA
| | - Kenji Notohara
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-Related Disease, Tokyo, Japan.,Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Akira Satou
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-Related Disease, Tokyo, Japan.,Department of Surgical Pathology, Aichi Medical University Hospital, Aichi, Japan
| | - Masafumi Moriyama
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-Related Disease, Tokyo, Japan.,Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Seiji Nakamura
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-Related Disease, Tokyo, Japan.,Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Yasuharu Sato
- Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan.,The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-Related Disease, Tokyo, Japan.,Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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25
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Sasaki T, Akiyama M, Kaneko Y, Takeuchi T. IgG4-related disease and idiopathic multicentric Castleman's disease: confusable immune-mediated disorders. Rheumatology (Oxford) 2021; 61:490-501. [PMID: 34363463 DOI: 10.1093/rheumatology/keab634] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/13/2021] [Accepted: 08/02/2021] [Indexed: 11/13/2022] Open
Abstract
IgG4-related disease (IgG4-RD) and idiopathic multicentric Castleman's disease (iMCD) are both rare systemic immune-mediated disorders. However, pathogenesis differs markedly between the two diseases, and differing therapeutic strategies are adopted: IgG4-RD is treated using a moderate dose of glucocorticoids or rituximab, while iMCD therapy involves an interleukin (IL)-6 targeted approach. Nonetheless, some clinical features of IgG4-RD and iMCD overlap, so differential diagnosis is sometimes difficult, even though the classification and diagnostic criteria of the diseases require careful exclusion of the other. The key findings in IgG4-RD are high IgG4/IgG ratio, allergic features, and germinal centre expansion involving T follicular helper cells, while iMCD involves polyclonal antibody production (high IgA and IgM levels), sheet-like mature plasma cell proliferation, and inflammatory features driven by IL-6. The distribution of organ involvement also provides important clues in both diseases. Particular attention should be given to differential diagnosis using combined clinical and/or pathological findings, because single features cannot distinguish IgG4-RD from iMCD. In the present review, we discuss the similarities and differences between IgG4-RD and iMCD, as well as how to distinguish the two diseases.
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Affiliation(s)
- Takanori Sasaki
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Mitsuhiro Akiyama
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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26
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Kinugawa Y, Uehara T, Iwaya M, Asaka S, Kobayashi S, Nakajima T, Komatsu M, Yasuo M, Yamamoto H, Ota H. IL-6 expression helps distinguish Castleman's disease from IgG4-related disease in the lung. BMC Pulm Med 2021; 21:219. [PMID: 34246246 PMCID: PMC8272341 DOI: 10.1186/s12890-021-01603-6] [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: 04/05/2021] [Accepted: 05/31/2021] [Indexed: 11/26/2022] Open
Abstract
Background It is difficult to distinguish between multicentric Castleman’s disease (MCD) and IgG4-related lung disease (IgG4-LD), an IgG4-related disease (IgG4-RD) in the lung. Methods We focused on IL-6, which is elevated in MCD, to distinguish between MCD and IgG4-LD by RNAscope, a highly sensitive RNA in situ method. Six cases of MCD and four cases of IgG4-LD were selected. Results In all cases of MCD and IgG4-LD, 10 or more IgG4-positive cells were found in one high-power field. All MCD cases were inconsistent with the pathological IgG4-related comprehensive diagnostic criteria, but 2 of 6 cases had an IgG4/IgG ratio greater than 40%. In all IgG4-LD cases, histological features were consistent with the pathological IgG4-RD comprehensive diagnostic criteria. IL-6 expression was observed in all MCD and IgG4-LD cases except for one IgG4-LD biopsy. IL-6-expressing cells were mainly identified in the stroma. Sites of IL-6 expression were not characteristic and were sparse. IL-6 expression tended to be higher in MCD compared with IgG4-LD. A positive correlation was found between the IL-6 H-score and serum IL-6 level. Conclusion Differences in IL-6 expression may help distinguish between MCD and IgG4-LD. In addition, the presence of high IL-6 levels may help elucidate the pathological mechanisms of IgG4-LD.
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Affiliation(s)
- Yasuhiro Kinugawa
- Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
| | - Mai Iwaya
- Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Shiho Asaka
- Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Shota Kobayashi
- Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Tomoyuki Nakajima
- Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
| | - Masamichi Komatsu
- First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masanori Yasuo
- First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hiroshi Yamamoto
- First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hiroyoshi Ota
- Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.,Department of Biomedical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
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27
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Nakai S, Murano M, Hiramatsu T, Matsushima S, Uto T, Sato J, Imokawa S, Suda T. Multicentric Castleman disease with infiltration of eosinophils to the lung. Respir Med Case Rep 2021; 34:101458. [PMID: 34381678 PMCID: PMC8339229 DOI: 10.1016/j.rmcr.2021.101458] [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: 03/27/2021] [Accepted: 06/15/2021] [Indexed: 11/30/2022] Open
Abstract
A 41-year-old man presented with multiple superficial lymph nodes (LNs) swollen with elevated levels of serum immunoglobulin (Ig)G4 and C-reactive protein. Histological findings of his left inguinal LN revealed lymphoplasmacytic infiltration with numerous IgG4-positive plasma cells; IgG4+/IgG+ plasma cell ratio >40%. Chest computed tomography (CT) showed poorly defined centrilobular nodules, interlobular septal thickening, consolidations, and mediastinal LNs swelling. Bronchoalveolar lavage fluid (BALF) showed elevated eosinophils. A surgical lung biopsy showed focal dense eosinophil infiltration, in addition to lymphoplasmacytic infiltration, but few IgG4+ plasma cells. The diagnosis of multicentric Castleman disease (MCD) was made because of serum interleukin-6elevation. Treatment with prednisolone and tocilizumab improved his symptoms and lung lesions. This case shows that overlapping clinical and pathological features of MCD and IgG4-related disease may present in a single patient, showing the difficulty in distinguishing between these two diseases.
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Affiliation(s)
- Shogo Nakai
- Division of Respiratory Medicine, Iwata City Hospital, 512-3 Ookubo, Iwata, Shizuoka, 438-8550, Japan
| | - Moeko Murano
- Division of Respiratory Medicine, Iwata City Hospital, 512-3 Ookubo, Iwata, Shizuoka, 438-8550, Japan
| | - Toshiya Hiramatsu
- Division of Respiratory Medicine, Iwata City Hospital, 512-3 Ookubo, Iwata, Shizuoka, 438-8550, Japan
| | - Sayomi Matsushima
- Division of Respiratory Medicine, Iwata City Hospital, 512-3 Ookubo, Iwata, Shizuoka, 438-8550, Japan
| | - Tomohiro Uto
- Division of Respiratory Medicine, Iwata City Hospital, 512-3 Ookubo, Iwata, Shizuoka, 438-8550, Japan
| | - Jun Sato
- Division of Respiratory Medicine, Iwata City Hospital, 512-3 Ookubo, Iwata, Shizuoka, 438-8550, Japan
| | - Shiro Imokawa
- Division of Respiratory Medicine, Iwata City Hospital, 512-3 Ookubo, Iwata, Shizuoka, 438-8550, Japan
| | - Takafumi Suda
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
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28
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Zhu LP, Khan S, Hui YY, Yang B, Wang SY, Sun KD, Yu ZH, Zhao JW, Wang BM, Chen X. IgG4-Related Disease with Ascites: Report of a Case Simulating Primary Peritoneal Papillary Serous Carcinoma. Dig Dis Sci 2021; 66:1751-1756. [PMID: 32556817 DOI: 10.1007/s10620-020-06376-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 05/30/2020] [Indexed: 12/27/2022]
Affiliation(s)
- Lan-Ping Zhu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Samiullah Khan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Yang-Yang Hui
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Bo Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Sai-Yu Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Kai-di Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Zi-Han Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Jing-Wen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
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29
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Kawano M, Hara S, Yachie A, Inoue D, Sato Y, Fajgenbaum DC. HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease. Rheumatology (Oxford) 2021; 60:e3-e4. [PMID: 32772106 DOI: 10.1093/rheumatology/keaa362] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/10/2020] [Accepted: 05/28/2020] [Indexed: 12/21/2022] Open
Affiliation(s)
| | | | | | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa
| | - Yasuharu Sato
- Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan
| | - David C Fajgenbaum
- Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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30
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IgG4-related Lymphadenopathy: A Comparative Study of 41 Cases Reveals Distinctive Histopathologic Features. Am J Surg Pathol 2021; 45:178-192. [PMID: 32889888 DOI: 10.1097/pas.0000000000001579] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Lymphadenopathy is common in patients with immunoglobulin G4-related disease (IgG4-RD). However, the described histopathologic features of IgG4-related lymphadenopathy have been shown to be largely nonspecific. In an attempt to identify features specific for nodal IgG4-RD we examined the histopathologic features of lymph nodes from 41 patients with established IgG4-RD, with comparison to 60 lymph nodes from patients without known or subsequent development of IgG4-RD. An increase in immunoglobulin (Ig) G4-positive plasma cells >100/HPF and IgG4/IgG ratio >40% was identified in 51% of IgG4-RD cases and 20% of control cases. Localization of increased IgG4-positive plasma cells and IgG4/IgG ratio to extrafollicular zones was highly associated with IgG4-RD, particularly when identified in regions of nodal fibrosis (P<0.0001; specificity: 98.3%), or in the context of marked interfollicular expansion (P=0.022; specificity: 100%). Other features characteristic of IgG4-RD included frequent eosinophils associated with IgG4-positive plasma cells, phlebitis (P=0.06), and perifollicular granulomas (P=0.16). The presence of an isolated increase in intrafollicular IgG4-positive plasma cells and IgG4/IgG ratio was more frequently present in control cases than IgG4-RD (P<0.0001). This study confirms that increased IgG4-positive plasma cells and IgG4/IgG ratio are neither sensitive nor specific for the diagnosis of IgG4-related lymphadenopathy, and most described morphologic patterns are nonspecific. In contrast, nodal involvement by IgG4-rich fibrosis akin to extranodal IgG4-RD or diffuse interfollicular expansion by IgG4-positive plasma cells are highly specific features of true IgG4-related lymphadenopathy. Our findings provide for a clinically meaningful approach to the evaluation of lymph nodes that will assist pathologists in distinguishing IgG4-related lymphadenopathy from its mimics.
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31
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Hindilerden F, Yonal-Hindilerden I, Gulturk E, Yuksel M, Ozturkmen AY, Sakız D. IgG4 producing POEMS syndrome: A rarely recognized subtype. INDIAN J PATHOL MICR 2021; 64:584-586. [PMID: 34341279 DOI: 10.4103/ijpm.ijpm_995_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Serum IgG4 is typically measured for Immunoglobulin G4-related Disease (IgG4-RD), a fibroinflammatory condition associated with polyclonal increase in serum IgG4. Yet, increased IgG4 may still be monoclonal, and little is known about IgG4 POEMS syndrome. We present a case of 40-year-old male with a mass lesion in the left sacral ala. The mass was composed of non-neoplastic fibrous tissue and dense infiltrate of mature plasmacytes with dense eosinophilic cytoplasm and eccentrically placed nuclei that express monoclonal Lambda free light chains and show diffuse positivity for IgG and IgG4. We discuss clinical manifestations and challenges encountered in the diagnosis and treatment of this rare coexistence.
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Affiliation(s)
- Fehmi Hindilerden
- University of Health Sciences Bakırkoy Dr. Sadi Konuk Training and Research Hospital, Hematology Clinic, Istanbul, Turkey
| | - Ipek Yonal-Hindilerden
- Istanbul University Istanbul Medical Faculty, Department of Internal Medicine, Division of Hematology, Istanbul, Turkey
| | - Emine Gulturk
- University of Health Sciences Bakırkoy Dr. Sadi Konuk Training and Research Hospital, Hematology Clinic, Istanbul, Turkey
| | - Mahmut Yuksel
- Altınbas University Faculty of Medicine, Department of Nuclear Medicine, Istanbul, Turkey
| | - Asli Yuksel Ozturkmen
- University of Health Sciences Bakırkoy Dr. Sadi Konuk Training and Research Hospital, Hematology Clinic, Istanbul, Turkey
| | - Damlanur Sakız
- University of Health Sciences Bakırkoy Dr. Sadi Konuk Training and Research Hospital, Pathology Clinic, Istanbul, Turkey
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32
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Nishimura MF, Igawa T, Gion Y, Tomita S, Inoue D, Izumozaki A, Ubara Y, Nishimura Y, Yoshino T, Sato Y. Pulmonary Manifestations of Plasma Cell Type Idiopathic Multicentric Castleman Disease: A Clinicopathological Study in Comparison with IgG4-Related Disease. J Pers Med 2020; 10:jpm10040269. [PMID: 33321725 PMCID: PMC7768369 DOI: 10.3390/jpm10040269] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 02/06/2023] Open
Abstract
Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage.
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Affiliation(s)
- Midori Filiz Nishimura
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan; (M.F.N.); (T.I.); (T.Y.)
| | - Takuro Igawa
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan; (M.F.N.); (T.I.); (T.Y.)
| | - Yuka Gion
- Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama 700-8558, Japan;
| | - Sakura Tomita
- Department of Pathology, Tokai University School of Medicine, Kanagawa 259-1193, Japan;
| | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8641, Japan; (D.I.); (A.I.)
| | - Akira Izumozaki
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8641, Japan; (D.I.); (A.I.)
| | - Yoshifumi Ubara
- Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa 213-0015, Japan;
| | - Yoshito Nishimura
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan;
| | - Tadashi Yoshino
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan; (M.F.N.); (T.I.); (T.Y.)
| | - Yasuharu Sato
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan; (M.F.N.); (T.I.); (T.Y.)
- Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama 700-8558, Japan;
- Correspondence: ; Tel.: +81-86-235-7150
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33
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Vasilyev VI, Palshina SG, Pavlovskaya AI, Kokosadze NV, Chaltsev BD, Shornikova LA. [Idiopathic multicentric Castleman's disease]. TERAPEVT ARKH 2020; 92:78-84. [PMID: 32598779 DOI: 10.26442/00403660.2020.05.000440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Indexed: 11/22/2022]
Abstract
Idiopathic multicentric Castlemans disease is a rare lymphoproliferative disorder that has many similar laboratory, radiological, clinical and pathological manifestations with various conditions, including IgG4-related disease. Increased activity of cytokines, especially interleukin-6, leads to systemic inflammatory symptoms with the development of lymphadenopathy and rarely extranodal lesions. Histological changes in the lymph nodesin hyaline vascular and plasma cell variants of Castlemans disease are hardly distinguishable from the pattern of reactive, tumor and IgG4-related lymphadenopathy. Idiopathic multicentric Castlemans disease can be diagnosed only when infection with human herpesvirus-8 type and human immunodeficiency virus is excluded. In the article, the authors describe two cases of idiopathic multicentric Castlemans disease, including the first world literature description of extranodal damage of the hip muscle in this disorder. In addition, the authors gave a review of the literature on the main clinical, laboratory and morphological manifestations, which allow confirming the diagnosis of Castlemans disease.
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Affiliation(s)
| | | | | | - N V Kokosadze
- Blokhin National Medical Research Center of Oncology
| | | | - L A Shornikova
- Yevdokimov Moscow State University of Medicine and Dentistry
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34
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Sotier M, Stern JB, Brian E, Wyplosz B, Validire P, Lenoir S, Gayraud M, Cosserat J, Deroux A. [Weight loss and cervical mass in a 50 year-old man]. Rev Med Interne 2020; 41:641-643. [PMID: 32362367 DOI: 10.1016/j.revmed.2020.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 03/03/2020] [Indexed: 11/25/2022]
Affiliation(s)
- M Sotier
- Service de Médecine Interne, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France
| | - J-B Stern
- Institut du thorax, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France
| | - E Brian
- Institut du thorax, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France
| | - B Wyplosz
- Service Pathologie infectieuse, Hôpital Bicêtre, 78 rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France
| | - P Validire
- Service d'Anatomie Pathologique, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France
| | - S Lenoir
- Service de Radiologie, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France
| | - M Gayraud
- Service de Médecine Interne, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France
| | - J Cosserat
- Service de Médecine Interne, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France.
| | - A Deroux
- Service de Médecine Interne, CHU de Grenoble, Avenue Maquis du Grésivaudan, 38700 La Tronche, France
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35
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IgG4-related disease with elevated adenosine deaminase in pleural effusion diagnosed clinically using thoracoscopy under local anesthesia and FDG-PET-CT. Respir Med Case Rep 2020; 30:101066. [PMID: 32373457 PMCID: PMC7193316 DOI: 10.1016/j.rmcr.2020.101066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 04/16/2020] [Accepted: 04/21/2020] [Indexed: 12/20/2022] Open
Abstract
In general, we have to assume tuberculous pleurisy when a patient presents with pleural effusion and elevated adenosine deaminase (ADA). However, other diseases need to be considered, including immunoglobulin (Ig)G4-related disease (IgG4-RD). This case involved a 65-year-old asymptomatic man with right pleural effusion showing elevated ADA. He had no articular findings or rashes. Results were negative for all autoantibodies. Pleura, mediastinal lymph nodes, and areas around the aorta and vertebra showed high uptake of 18F-fluorodeoxyglucose (FDG) on positron-emission tomography-computed tomography (PET-CT). These findings were specific for IgG4-RD. Based on the results of FDG-PET-CT, we performed thoracoscopy under local anesthesia and bronchoscopy. Pleural biopsy and culture, and other examinations including sputum and blood yielded negative findings for tuberculous pleurisy. A pleural biopsy specimen showed IgG4-positive plasma cells and fibrosis without obliterative phlebitis or storiform fibrosis, and serum IgG4 was also high. The ratio of IgG4-to IgG-positive plasma cells was under 40%, and >10 IgG4-positive cells were seen in high-power fields. This case was classed as ‘possible IgG4-RD’ on the comprehensive diagnostic criteria for IgG4-RD, but did not meet the diagnostic criteria for IgG4-related respiratory disease. Prednisolone proved effective against the pleural effusion. We therefore clinically diagnosed IgG4-RD with pleural effusion based on the 2019 classification criteria for IgG4-RD in the United States. Although few cases of IgG4-RD with pleural effusion have been reported, this disease needs to be considered among the differential diagnoses for high-ADA pleural effusion. FDG-PET-CT and thoracoscopy under local anesthesia may be helpful for diagnosis.
ImmunoglobulinG4-related disease (IgG4-RD) with pleural effusion is rare. We should assume IgG4-RD as one of the differential diagnoses of pleural effusion with high level of adenosine deaminase. Thoracoscopy under local anesthesia and 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) may be useful as an adjunctive tool for making a diagnosis of IgG4-RD. We could diagnosed as IgG4-RD with pleural effusion based on findings of FDG-PET-CT and thoracoscopy, and the responsiveness to prednisolone.
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36
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Satou A, Notohara K, Zen Y, Nakamura S, Yoshino T, Okazaki K, Sato Y. Clinicopathological differential diagnosis of IgG4-related disease: A historical overview and a proposal of the criteria for excluding mimickers of IgG4-related disease. Pathol Int 2020; 70:391-402. [PMID: 32314497 DOI: 10.1111/pin.12932] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/16/2020] [Accepted: 03/30/2020] [Indexed: 12/15/2022]
Abstract
IgG4-related disease (RD) is a relatively new entity, which was first proposed in 2001. Since then, clinical and pathological characteristics of the disease have been investigated. As IgG4-RD has been studied extensively, the diagnostic criteria for IgG4-RD of each organ and the comprehensive diagnostic criteria for IgG4-RD have also been developed. However, one of the biggest challenges in the field is distinguishing between IgG4-RD and mimickers, which show overlapping features with IgG4-RD. It is now known that some non-IgG4-RDs may meet the diagnostic criteria of IgG4-RD and can be misdiagnosed as IgG4-RD. However, accurate diagnosis is crucial, as the treatments for IgG4-RD and those for other diseases that may be misdiagnosed as IgG4-RD are different. This prompted us to create and propose comprehensive exclusion criteria for IgG4-RD. In this review, we have described the comprehensive exclusion criteria for IgG4-RD, with a historical overview of the disease. These exclusion criteria were recently created by the Research Program for Intractable Disease of the Ministry of Health, Labor, and Welfare of Japan, All Japan IgG4 team, to support correct and accurate diagnosis of IgG4-RD.
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Affiliation(s)
- Akira Satou
- Department of Surgical Pathology, Aichi Medical University Hospital, Aichi, Japan.,The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-related Disease, Tokyo, Japan
| | - Kenji Notohara
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-related Disease, Tokyo, Japan.,Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Yoh Zen
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-related Disease, Tokyo, Japan.,Institute of Liver Studies, King's College Hospital & King's College London, London, UK
| | - Shigeo Nakamura
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-related Disease, Tokyo, Japan.,Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Aichi, Japan
| | - Tadashi Yoshino
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-related Disease, Tokyo, Japan.,Department of Pathology, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Kazuichi Okazaki
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-related Disease, Tokyo, Japan.,The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Yasuharu Sato
- The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Japanese Pathology Study Group of IgG4-related Disease, Tokyo, Japan.,Department of Pathology, Okayama University Graduate School of Medicine, Okayama, Japan.,Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan
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37
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Hu YH, Yu CT, Chen CJ, Wen MC. Calcifying fibrous tumour: An IgG4-related disease or not? Int J Exp Pathol 2020; 101:38-44. [PMID: 32090409 DOI: 10.1111/iep.12339] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 11/09/2019] [Accepted: 11/17/2019] [Indexed: 12/17/2022] Open
Abstract
Calcifying fibrous tumour (CFT) has some of the histopathological features, such as abundant plasma cells and stromal fibrosis, that are exhibited by IgG4-related diseases (IgG4-RD). The possible role of IgG4-positive plasma cells in calcifying fibrous tumour was investigated. The aim of this study was to determine any potential relationship between IgG4-RD and CFT. Thirteen cases with a total of 16 CFTs were reviewed. Lesion samples were immunostained with anti-IgG4 and anti-IgG antibodies. The number of IgG4-positive and IgG-positive plasma cells (IgG + PC) and their ratios were estimated. Plasma cells were found in all tumours. IgG4-positive plasma cells ranged from 0 to 71 per high-power field (HPF; mean 17.8/HPF), and IgG + PC ranged from 2 to 93/HPF (mean 42.6/HPF). The IgG4/IgG ratio ranged from 0% to 80% (mean 29%). There were seven tumours with the ratio of IgG4/IgG + PC that exceeded 40%. Various degrees of stromal fibrosis were present in eight tumours. All tumours have variable calcification. The histopathological features of CFT were found to be similar to those of IgG4-RD. Some CFT also showed a high number of IgG4-positive plasma cells, and the ratio of IgG4/IgG + PC exceeded 40%, most notably in patients with concomitant inflammatory or autoimmune disease. The long-term follow-up showed no evidence of IgG4-RD in any of these patients. Our findings suggest that while CFT overlaps morphologically with IgG4-RD, it probably should not be classified as an IgG4-RD.
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Affiliation(s)
- Yu-Hsuan Hu
- Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chen-Tang Yu
- Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan
| | - Chih-Jung Chen
- Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Mei-Chin Wen
- Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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38
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Tille L, Schnabel A, Laass MW, Hahn G, Taut H, Leszczynska A, Pablik J, Berner R, Brück N, Hedrich CM. Orbital inflammation and colitis in pediatric IgG4-related disease: A case report and review of the literature. Eur J Rheumatol 2020; 7:S21-S27. [PMID: 31804176 PMCID: PMC7004272 DOI: 10.5152/eurjrheum.2019.19165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 10/03/2019] [Indexed: 01/13/2023] Open
Abstract
IgG4-related disease (IgG4-RD) is an inflammatory disorder characterized by tumor-like swelling in one or more organs, elevated serum IgG4 levels, and histological alterations with infiltration of IgG4-positive plasma cells. IgG4-RD is rare and likely underdiagnosed in children. We report a case of a 16-year-old girl with IgG4-positive colitis that developed weeks after IgG4-related ophthalmic disease and discuss diagnosis and treatment in the context of the literature available. Since the pathophysiology of IgG4-RD is unknown, treatment options are empiric and, for the most part, untargeted. Systemic corticosteroid treatment is the basis of anti-inflammatory treatment in IgG4-RD and induced early remission in our patient. During corticosteroid taper, the patient developed weight loss and intestinal inflammation. Histopathological assessment of the intestinal walls confirmed IgG4-positive colitis. Immune-modulating treatment with non-biologic (e.g., methotrexate (MTX) and mycophenolate mofetil) or biologic (rituximab) disease-modifying antirheumatic drugs has been reported in treatment refractory or corticosteroid-dependent patients. The patient responded to treatment with anti-inflammatory therapy with food rich in TGF-β2 (modulen) and MTX. This is one of the first pediatric patients reported with IgG4-related colitis extending the phenotype of pediatric IgG4-RD. International collaboration to prospectively document clinical presentation and treatment responses may help to further establish the phenotype and treatment options and to raise awareness for IgG4-RD.
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Affiliation(s)
- Lissy Tille
- Department of Pediatrics, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Anja Schnabel
- Department of Pediatrics, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Martin W. Laass
- Department of Pediatrics, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Gabriele Hahn
- Department of Radiology, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Heike Taut
- Department of Pediatrics, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Anna Leszczynska
- Department of Ophthalmology, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Jessica Pablik
- Department of Pathology, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Reinhard Berner
- Department of Pediatrics, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Normi Brück
- Department of Pediatrics, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
| | - Christian M. Hedrich
- Department of Pediatrics, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Germany
- Department of Women’s and Children’s Health, Institute of Translational Medicine, University of Liverpool School of Life Sciences, Liverpool, UK
- Department of Paediatric Rheumatology, Alder Hey Children’s NHS Foundation Trust Hospital, Liverpool, UK
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van den Elshout-den Uyl D, Spoto CPE, de Boer M, Leiner T, Leavis HL, Leguit RJ. First Report of IgG4 Related Disease Primary Presenting as Vertebral Bone Marrow Lesions. Front Immunol 2019; 10:1910. [PMID: 31456806 PMCID: PMC6700296 DOI: 10.3389/fimmu.2019.01910] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 07/29/2019] [Indexed: 12/24/2022] Open
Abstract
IgG4-related disease is a fibro-inflammatory disorder characterized by swelling of tissues and affected organs accompanied by the development of scar tissue (fibrosis) and infiltration by IgG4 positive plasma cells. Almost any organ can be affected, including, but rarely, bone marrowinvolvement. Here we present a case of a 76-year-old male with IgG4-related disease presenting primarily with vertebral bone marrow lesions. Histopathology showed the typical features of storiform fibrosis, and increased IgG4 positive plasma cells. Treatment with corticosteroids significantly improved wellbeing and resolved lesion size on MRI.
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Affiliation(s)
| | - Clothaire P E Spoto
- Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Mirthe de Boer
- Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Tim Leiner
- Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Helen L Leavis
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Roos J Leguit
- Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
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Kawano M, Saeki T, Nakashima H. IgG4-related kidney disease and retroperitoneal fibrosis: An update. Mod Rheumatol 2019; 29:231-239. [DOI: 10.1080/14397595.2018.1554321] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Mitsuhiro Kawano
- Division of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Kanazawa, Japan
| | - Takako Saeki
- Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Hitoshi Nakashima
- Faculty of Medicine, Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University, Fukuoka, Japan
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Lishchuk SV, Kazantseva IA, Dubova EA, Pavlov KA, Katunina OR, Borbat AM, Udalov YD. [Morphological features of IgG4-related lesions at various sites]. Arkh Patol 2019; 81:22-29. [PMID: 31626201 DOI: 10.17116/patol20198105122] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
OBJECTIVE To determine the morphological features of IgG4-related lesions and to improve pathomorphological criteria for diagnosing various clinical variants of IgG4-related disease. MATERIAL AND METHODS Biopsy and surgical materials from 100 patients with tumor-like lesions at various sites (63 cases of IgG4-related lesion and 37 cases of non-IgG4-related inflammatory processes) were studied. Histological and immunohistochemical studies were conducted to determine the absolute counts of CD138+ cells, IgG+ and IgG4+ in the inflammatory infiltrates, as well as IgG4/IgG and IgG4/CD138 cell ratios. RESULTS When IgG4-related disease manifested, pancreatic, lacrimal, and salivary gland lesions prevailed. Brisk lymphoplasmacytic infiltration is characteristic for tissue damage in the eye, salivary glands, thyroid, pancreas, and skin. The formation of moiré fibrosis was specific to damages to the pancreas, liver and bile ducts, and eye tissues. Obliterative phlebitis is most often observed in pancreatic and salivary gland lesions. According to international criteria, the frequency of achieving the required level of IgG4+ plasma cells in each organ was high in lesions of the pancreas, bile ducts, and lymph nodes and that was low in lesions of the salivary and lacrimal glands and skin. The IgG4+/CD138+ and IgG4+/IgG+ cell ratios exceeded 40% in all cases. CONCLUSION The morphologic diagnosis of IgG4-related disease is based on the detection of lymphoplasmacytic infiltration, moiré fibrosis, and obliterative phlebitis, as well as on the calculation of the absolute number of IgG4+ plasma cells in the inflammatory infiltrate and on the determination of IgG4+/IgG+ and IgG4+/CD138+ cell ratios. The number of IgG4+ plasma cells depends on the location of the lesion and on the phase of the process.
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Affiliation(s)
- S V Lishchuk
- A.I. Burnazyan Federal Medical and Biophysical Center, Federal Biomedical Agency of Russia, Moscow, Russia
| | - I A Kazantseva
- M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia
| | - E A Dubova
- A.I. Burnazyan Federal Medical and Biophysical Center, Federal Biomedical Agency of Russia, Moscow, Russia
| | - K A Pavlov
- A.I. Burnazyan Federal Medical and Biophysical Center, Federal Biomedical Agency of Russia, Moscow, Russia
| | - O R Katunina
- A.I. Burnazyan Federal Medical and Biophysical Center, Federal Biomedical Agency of Russia, Moscow, Russia
| | - A M Borbat
- A.I. Burnazyan Federal Medical and Biophysical Center, Federal Biomedical Agency of Russia, Moscow, Russia
| | - Yu D Udalov
- A.I. Burnazyan Federal Medical and Biophysical Center, Federal Biomedical Agency of Russia, Moscow, Russia
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Kurose N, Futatsuya C, Mizutani KI, Kumagai M, Shioya A, Guo X, Aikawa A, Nakada S, Fujimoto S, Kawabata H, Masaki Y, Takai K, Aoki S, Kojima M, Nakamura S, Yamada S. The clinicopathological comparison among nodal cases of idiopathic multicentric Castleman disease with and without TAFRO syndrome. Hum Pathol 2018; 77:130-138. [PMID: 29684500 DOI: 10.1016/j.humpath.2018.04.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 04/05/2018] [Accepted: 04/13/2018] [Indexed: 01/09/2023]
Abstract
Multicentric Castleman disease (MCD) is a systemic inflammatory disease potentially caused by an increase in the serum interleukin-6 (IL-6) level. Idiopathic MCD (iMCD) is histopathologically classified into three types: plasmacytic (PC), mixed, and hypervascular (hyperV) types. Recently, a unique clinical phenotype with a poor prognosis overlap with iMCD, thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly (TAFRO syndrome), has been reported from Japan, but its detailed clinicopathological features remain unclear. In this study, we performed a clinicopathological analysis of 70 nodal cases of iMCD with and without TAFRO syndrome (n = 37 versus n = 33). Compared with iMCD without TAFRO, iMCD with TAFRO showed more atrophic lymphoid follicles (LF), greater distances between follicles, increased glomeruloid vascular proliferation within the germinal center, and increased follicular dendritic cells. In addition, the hyperV type in particular demonstrated severe atrophic LF and interfollicular vascular proliferation. Among the mixed-type cases, the serum IL-6 levels in iMCD with TAFRO were significantly higher than those in iMCD without TAFRO. Furthermore, compared to iMCD without TAFRO, the numbers of immunoglobulin G4 (IgG4)-positive and CD38-positive plasma cells were significantly decreased in iMCD with TAFRO.
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Affiliation(s)
- Nozomu Kurose
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Chizuru Futatsuya
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Ken-Ichi Mizutani
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Motona Kumagai
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Akihiro Shioya
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Xin Guo
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Akane Aikawa
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Satoko Nakada
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Shino Fujimoto
- Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan
| | - Hiroshi Kawabata
- Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan
| | - Yasufumi Masaki
- Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan
| | - Kazue Takai
- Division of Hematology, Niigata City General Hospital, Niigata, Japan
| | - Sadao Aoki
- Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan
| | - Masaru Kojima
- Department of Anatomic and Diagnostic Pathology, Dokkyo University School of Medicine, Tochigi, Japan
| | - Shigeo Nakamura
- Department of Pathology and Biological Response, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Sohsuke Yamada
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan.
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Bledsoe JR, Della-Torre E, Rovati L, Deshpande V. IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach. APMIS 2018; 126:459-476. [PMID: 29924455 DOI: 10.1111/apm.12845] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 04/20/2018] [Indexed: 02/06/2023]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is an uncommon disorder that demonstrates characteristic clinicopathologic features including sclerosing lesions with storiform fibrosis, increased IgG4+ plasma cells with an increased IgG4+/IgG+ plasma cell ratio, obliterative phlebitis, and often an increased serum IgG4 level. This review summarizes the characteristic histopathologic and clinical features of IgG4-RD with detailed discussion of the histopathologic characteristics of the most commonly involved anatomic sites. We also present recent advances in our understanding of the pathophysiologic mechanisms of IgG4-RD and discuss updates on the treatment, prognosis, and outcomes of this rare disease, including discussion of the possible association between IgG4-RD and malignancy.
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Affiliation(s)
- Jacob R Bledsoe
- Department of Pathology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA
| | - Emanuel Della-Torre
- Unit of Immunology, Rheumatology, Allergy, and Rare Diseases (UnIRAR), Università Vita-Salute San Raffaele - San Raffaele Scientific Institute, Milan, Italy.,Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA, USA
| | - Lucrezia Rovati
- Unit of Immunology, Rheumatology, Allergy, and Rare Diseases (UnIRAR), Università Vita-Salute San Raffaele - San Raffaele Scientific Institute, Milan, Italy.,Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA, USA
| | - Vikram Deshpande
- The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, MA, USA
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Kasashima S, Kawashima A, Kasashima F, Endo M, Matsumoto Y, Kawakami K. Inflammatory features, including symptoms, increased serum interleukin-6, and C-reactive protein, in IgG4-related vascular diseases. Heart Vessels 2018; 33:1471-1481. [DOI: 10.1007/s00380-018-1203-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 06/15/2018] [Indexed: 12/15/2022]
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Zhang X, Zhang P, Peng L, Fei Y, Zhang W, Feng R, Zhang W. Clinical characteristics of a concurrent condition of IgG4-RD and Castleman's disease. Clin Rheumatol 2018; 37:3387-3395. [PMID: 29948354 DOI: 10.1007/s10067-018-4165-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Revised: 05/09/2018] [Accepted: 05/31/2018] [Indexed: 12/17/2022]
Abstract
IgG4-related disease (IgG4-RD) and Castleman's disease (CD) share similar clinical manifestations. When the histopathology coincides with the diagnosis of both IgG4-RD and CD, it is hard to depart the two disease entities utterly; here we call it IgG4-CD provisionally. In this study, we aim to review the clinical features of IgG4-CD. This study is based on a retrospective analysis of a prospectively acquired database. IgG4-CD was defined histopathologically in patients who fulfilled the diagnosis of both IgG4-RD and CD. Forty-five definite IgG4-RD and 16 multicentric CD (MCD) patients were recruited as controls. Clinical features including organ involvement, serum IgG4, IgG, IgE, ESR, CRP, and IL-6 levels were collected and analyzed. Fifteen patients (2.8%) out of 534 patients with IgG4-RD in China's largest prospective IgG4-RD and Mimicry cohort fulfilled the definition of IgG4-CD. There were 14 males and 1 female, whose mean age was 47 ± 18 years old, and the median disease duration before diagnosis was 12 (1-132) months. Eight patients have allergic disease history. IgG4-CD patients had more lymph node involvement (100 vs 57.8%, P < 0.01), while IgG4-RD patients had more submandibular (33.3 vs 77.1%, P < 0.01) and parotid gland (13.3 vs 40.9%, P < 0.05) affected. IgG4-CD patients had significantly higher levels of ESR, CRP, IgG, IgG1, IgG3, IgG4, and IgE than IgG4-RD patients. Compared with MCD patients, IgG4-CD patients showed higher incidence of salivary gland and paranasal sinus involvement, higher hemoglobin, eosinophil count, serum IgG4 level and IgG4/IgG ratio, and lower CRP, IL-6 levels, and IgG1/IgG, IgG2/IgG ratio. All patients with IgG4-CD exhibited relatively favorable outcomes. Both IgG4-RD and CD can involve multiple organs. There are a small group of patients who had clinical and pathological characteristics of both CD and IgG4-RD showed better clinical outcome. In the long-term prognosis of these patients, the relationship of CD and IgG4-RD is waiting to be further elucidated.
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Affiliation(s)
- Xia Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Panpan Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Linyi Peng
- Department of Rheumatology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Yunyun Fei
- Department of Rheumatology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Wei Zhang
- Department of Hematology, Peking Union Medical College Hospital, Beijing, China
| | - Ruie Feng
- Department of Pathology, Peking Union Medical College Hospital, Beijing, China.
| | - Wen Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
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Hamano H, Tanaka E, Ishizaka N, Kawa S. IgG4-related Disease - A Systemic Disease that Deserves Attention Regardless of One's Subspecialty. Intern Med 2018; 57:1201-1207. [PMID: 29279491 PMCID: PMC5980798 DOI: 10.2169/internalmedicine.9533-17] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
IgG4-related disease (IgG4-RD) is an inflammatory condition characterized by a high serum IgG4 concentration and the abundant infiltration of lymphocytes and IgG4-positive plasma cells in the tissue, as well as spatial (diverse clinical manifestations) and temporal (the possibility of recurrence) multiplicities. Since the initial documentation of IgG4-related disease in patients with autoimmune pancreatitis in 2001, a growing body of evidence has been accumulating to suggest that various-virtually all-organs can be affected by IgG4-RD. In general, steroid therapy is effective and is considered to be the first-line treatment for IgG4-RD. The precise mechanism underlying this systemic disorder has remained unknown. Considering that IgG4-RD was specified as being an intractable disease in 2015, further studies are needed to clarify whether IgG4-RD is indeed a distinct disease entity or a complex of disorders of different etiologies and clinical conditions.
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Affiliation(s)
- Hideaki Hamano
- Division of Medical Informatics, Shinshu University Hospital, Japan
- Department of Internal Medicine, Gastroenterology, Shinshu University School of Medicine, Japan
| | - Eiji Tanaka
- Department of Internal Medicine, Gastroenterology, Shinshu University School of Medicine, Japan
| | | | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Japan
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Tong X, Bai M, Wang W, Han Q, Tian P, Fan H. IgG4-related disease involving polyserous effusions with elevated serum interleukin-6 levels: a case report and literature review. Immunol Res 2018; 65:944-950. [PMID: 28710703 DOI: 10.1007/s12026-017-8934-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a recently described immune-mediated fibroinflammatory disease with a characteristic histopathologic appearance that can affect various organs. We report a 43-year-old Chinese female patient with IgG4-RD involving polyserous effusions with reports of worsening exertional dyspnea for 3 months. Laboratory blood tests revealed that serum interleukin (IL)-6, carbohydrate antigens (CA-199 and CA-125), and alpha-fetoprotein levels were significantly increased, but serum IgG4 levels were normal. Repeat pleural effusion and ascite analysis showed lymphocyte-predominant exudates. In addition, computed tomography scan showed massive pleural effusion in the right pleural cavity, abdominal effusion, and some pericardial effusion with a partial compression atelectasis. Further, medical thoracoscopy was performed to examine the pleural cavity and found multiple nodules on the pleura and partly thickened pleura with a reddish color. Histopathologic and immunohistochemical examination revealed marked lymphocytes and IgG4-positive plasma cell infiltration. The patient was finally diagnosed with IgG4-RD according to the comprehensive diagnostic criteria, although the patient presented similar serological and pathological manifestations of Castleman disease (CD). Our case suggests that IgG4-RD may be one of the causes of polyserous effusions and shows the difficulties in differentiating between IgG4-RD and CD.
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Affiliation(s)
- Xiang Tong
- Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Guoxuexiang 37, Chengdu, Sichuan, 610041, China
| | - Min Bai
- Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Guoxuexiang 37, Chengdu, Sichuan, 610041, China
| | - Weiya Wang
- Department of Pathology, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, 610041, China
| | - Qingbing Han
- Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Guoxuexiang 37, Chengdu, Sichuan, 610041, China
| | - Panwen Tian
- Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Guoxuexiang 37, Chengdu, Sichuan, 610041, China. .,Lung Cancer Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, 610041, China.
| | - Hong Fan
- Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Guoxuexiang 37, Chengdu, Sichuan, 610041, China.
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Hibi A, Mizuguchi K, Yoneyama A, Kasugai T, Kamiya K, Kamiya K, Ito C, Kominato S, Miura T, Koyama K. Severe refractory TAFRO syndrome requiring continuous renal replacement therapy complicated with Trichosporon asahii infection in the lungs and myocardial infarction: an autopsy case report and literature review. RENAL REPLACEMENT THERAPY 2018; 4:16. [PMID: 34171004 PMCID: PMC7149248 DOI: 10.1186/s41100-018-0157-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 02/22/2018] [Indexed: 01/09/2023] Open
Abstract
Background TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal failure, and organomegaly) syndrome is a systemic inflammatory disorder and unique clinicopathological variant of idiopathic multicentric Castleman disease that was proposed in Japan. Prompt diagnosis is critical because TAFRO syndrome is a progressive and life threating disease. Some cases are refractory to immunosuppressive treatments. Renal impairment is frequently observed in patients with TAFRO syndrome, and some severe cases require hemodialysis. Histological evaluation is important to understand the pathophysiology of TAFRO syndrome. However, systemic histopathological evaluation through autopsy in TAFRO syndrome has been rarely reported previously. Case presentation A 46-year-old Japanese man with chief complaints of fever and abdominal distension was diagnosed with TAFRO syndrome through imaging studies, laboratory findings, and pathological findings on cervical lymph node and bone marrow biopsies. Interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were remarkably elevated in both blood and ascites. Methylprednisolone (mPSL) pulse therapy was initiated on day 10, followed by combination therapy with PSL and cyclosporine A. However, the amount of ascites did not respond to the treatment. The patient became anuric, and continuous renal replacement therapy was initiated from day 50. However, the patient suddenly experienced cardiac arrest associated with myocardial infarction (MI) on the same day. Although the emergent percutaneous coronary intervention was successfully performed, the patient died on day 52, despite intensive care. Autopsy was performed to ascertain the cause of MI and to identify the histopathological characteristics of TAFRO syndrome. Conclusions Bacterial peritonitis, systemic cytomegalovirus infection, and Trichosporon asahii infection in the lungs were observed on autopsy. In addition, sepsis-related myocardial calcification was suspected. Management of infectious diseases is critical to reduce mortality in patients with TAFRO syndrome. Although the exact cause of MI could not be identified on autopsy, we considered embolization by fungal hyphae as a possible cause. Endothelial injury possibly caused by excessive secretion of IL-6 and VEGF contributed to renal impairment. Fibrotic changes in anterior mediastinal fat tissue could be a characteristic pathological finding in patients with TAFRO syndrome.
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Affiliation(s)
- Arata Hibi
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Ken Mizuguchi
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Akiko Yoneyama
- Deaprtment of Pathology, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Takahisa Kasugai
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Keisuke Kamiya
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Keisuke Kamiya
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Chiharu Ito
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Satoru Kominato
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Toshiyuki Miura
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
| | - Katsushi Koyama
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya, Aichi 448-8505 Japan
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Upregulated interleukins (IL-6, IL-10, and IL-13) in immunoglobulin G4-related aortic aneurysm patients. J Vasc Surg 2018; 67:1248-1262. [DOI: 10.1016/j.jvs.2016.12.140] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 12/16/2016] [Indexed: 12/18/2022]
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Abstract
TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Thrombocytopenia and severe anasarca accompanied by relatively low serum immunoglobulin levels are characteristic clinical findings of TAFRO syndrome that are not present in iMCD-not otherwise specified (iMCD-NOS). Lymph node biopsy is recommended to exclude other diseases and to diagnose TAFRO syndrome, which reveals characteristic histopathological findings similar to hyaline vascular-type CD. TAFRO syndrome follows a more aggressive course, compared with iMCD-NOS, and there is no standard treatment.
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Affiliation(s)
- Takuro Igawa
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Yasuharu Sato
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; Division of Pathophysiology, Okayama University Graduate School of Health Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
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