IgG4-related disease is a protean condition that mimics many malignant, infectious, and inflammatory disorders. This multi-organ immune-mediated condition links many disorders previously regarded as isolated, single-organ diseases without any known underlying systemic condition. It was recognised as a unified entity only 10 years ago. Histopathology is the key to diagnosis. The three central pathology features of IgG4-related disease are lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. The extent of fibrosis is an important determinant of responsiveness to immunosuppressive therapies. IgG4-related disease generally responds to glucocorticoids in its inflammatory stage, but recurrent or refractory cases are common. Important mechanistic insights have been derived from studies of patients treated by B-cell depletion. Greater awareness of this disease is needed to ensure earlier diagnoses, which can prevent severe organ damage, disabling tissue fibrosis, and even death. Identification of specific antigens and T-cell clones that drive the disease will be the first steps to elucidate the pathogenesis of IgG4-related disease. 

IgG4-related disease

A. Khosroshahi, Z. S. Wallace, J. L. Crowe, T. Akamizu, A. Azumi, M. N. Carruthers, S. T. Chari, E. Della-Torre, L. Frulloni, H. Goto, P. A. Hart, T. Kamisawa, S. Kawa, M. Kawano, M. H. Kim, Y. Kodama, K. Kubota, M. M. Lerch, M. L€ ohr, Y. Masaki, S. Matsui, T. Mimori, S. Nakamura, T. Nakazawa, H. Ohara, K. Okazaki, J. H. Ryu, T. Saeki, N. Schleinitz, A. Shimatsu, T. Shimosegawa, H. Takahashi, M. Takahira, A. Tanaka, M. Topazian, H. Umehara, G. J. Webster, T. E. Witzig, M. Yamamoto, W. Zhang, T. Chiba, and J. H. Stone

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.39132

International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease

https://www.nejm.org/doi/pdf/10.1056/NEJMra1104650

Objective
IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect nearly any organ. Prior studies have focused on individual cases of IgG4-RD or small case series. This study was undertaken to report detailed clinical and laboratory findings in a larger group of patients with IgG4-RD whose diagnosis was established by strict clinicopathologic correlation.

Methods
The baseline features of 125 patients with biopsy-proven IgG4-RD were reviewed. The diagnosis was confirmed by pathologists’ review, based on consensus diagnostic criteria and correlation with clinicopathologic features. Disease activity and damage were assessed using the IgG4-RD Responder Index (RI). Flow cytometry was used to assess levels of circulating plasmablasts.

Results
Of the 125 patients, 107 had active disease and 86 were not receiving treatment for IgG4-RD. Only 51% of the patients with active disease had elevated serum IgG4 concentrations. However, patients with active disease and elevated serum IgG4 concentrations were older, had a higher IgG4-RD RI score, a greater number of organs involved, lower complement levels, higher absolute eosinophil counts, and higher IgE levels compared to those with active disease but normal serum IgG4 concentrations (P < 0.01 for all comparisons). The correlation between IgG4+ plasmablast levels and the IgG4-RD RI of disease activity (Spearman's ρ = 0.45, P = 0.003) was stronger than the correlation between total plasmablast levels and the IgG4-RD RI. Seventy-six (61%) of the patients were male, but no significant differences according to sex were observed with regard to disease severity, organ involvement, or serum IgG4 concentrations. Treatment with glucocorticoids failed to produce sustained remission in 77% of patients.

Conclusion
Nearly 50% of this patient cohort with biopsy-proven, clinically active IgG4-RD had normal serum IgG4 concentrations. Elevations in the serum IgG4 concentration appeared to identify a subset of patients with a more severe disease phenotype. In addition, the levels of IgG4+ plasmablasts correlated well with the extent of disease activity.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/art.39205

IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients.

High serum IgG4 concentrations in patients with sclerosing pancreatitis

Objective. Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a new disease entity that has only been identified this century. Clinical information is thus lacking. We established the Sapporo Medical University and Related Institutes Database for Investigation and Best Treatments of IgG4-related Disease (SMART) to clarify the clinical features of IgG4-RD and provide useful information for clinicians. Methods. Participants comprised 122 patients with IgG4-related dacryoadenitis and/or sialadenitis (IgG4-DS), representing lacrimal and/or salivary lesions of IgG4-RD, followed-up in December 2013. We analyzed the sex ratio, mean age at onset, organ dysfunction, history or complications of malignancy, treatments, rate of clinical remission, and relapse. Results. The sex ratio was roughly equal. Mean age at diagnosis was 59.0 years. Positron emission tomography revealed that the ratio of other organ involvements was 61.4%. Complications of malignancy were observed in 7.4% of cases. Glucocorticoid was used to treat 92.1% of cases, and the mean maintenance dose of prednisolone was 4.8 mg/day. Rituximab was added in three cases, and showed good steroid-sparing effect. The clinical remission rate was 73.8%, and the annual relapse rate was 11.5%. Half of the cases experienced relapses within 7 years of initial treatment. Conclusion. We analyzed the clinical features and treatments of IgG4-DS using SMART, providing useful information for everyday clinical practice.

Everyday clinical practice in IgG4-related dacryoadenitis and/or sialadenitis: results from the SMART database.

Objective. Despite ongoing research, the clinical and histopathological natural history of immunoglobulin (Ig) G4-related disease (IgG4-RD) remains unclear and the optimal time to initiate treatment is unknown. A focus on clinical symptoms rather than image finding is recommended for therapeutic initiation in autoimmune pancreatitis, but evidence for this approach is lacking. We aimed to retrospectively analyse disease duration, efficacy of treatment with glucocorticoids and results of histopathological examination of submandibular gland specimens to clarify the necessity for early intervention in IgG4-RD. Methods. Salivary secretions were assessed before and after treatment in 26 cases of IgG4-related Mikulicz’s disease (IgG4-MD). Relationships between disease duration, amount of salivary secretion before treatment, improvement of salivary secretion and ratios of areas of residual acini, fibrosis and lymphoid follicles in the involved submandibular gland specimens were analysed. Results. Salivary secretions were significantly reduced in cases with illness of >2 years (P < 0.05). An inverse correlation was seen between improved amount of salivary secretion and amount of salivary secretion before treatment (r =0.60). Improved amount of salivary secretion was also associated with each histological factor (acini, r = 0.29; fibrosis, r =0.23; lymphoid follicles, r =0.31), which showed interrelationships (acini and lymphoid follicles, r =0.23; acini and fibrosis, r = 0.42; lymphoid follicles and fibrosis, r = 0.30). Conclusion. Salivary secretion can be improved even in cases with lower levels of salivary secretion before treatment in IgG4-RD, but improvements in the amount of salivary secretion decrease with histological changes with delayed therapeutic intervention. These data suggest that early intervention is needed to improve outcomes in patients with IgG4-MD.

Necessity of early intervention for IgG4-related disease—delayed treatment induces fibrosis progression

Popular Tasks used by Researchers

How can I help with your research?

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

We encountered an error while loading the panel. Please try refreshing the page.

Something went wrong

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

Anyone with the link can view this chat. You can switch it back to private anytime.

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Ken Yamashita

Author Tools

Chat about Author

Papers

Everyday clinical practice in IgG4-related dacryoadenitis and/or sialadenitis: results from the SMART database.

Necessity of early intervention for IgG4-related disease—delayed treatment induces fibrosis progression