The Geoepidemiology and Clinical Aspects of IgG4-Related Disease

Opinion statementIgG4-related disease (IgG4-RD) is a multisystem inflammatory disorder. Early recognition of IgG4-RD is important to avoid permanent organ dysfunction and disability. Neurological involvement by IgG4-RD is relatively uncommon, but well recognised—hypertrophic pachymeningitis and hypophysitis are the most frequent manifestations. Although the nervous system may be involved in isolation, this more frequently occurs in conjunction with involvement of other systems. Elevated circulating levels of IgG4 are suggestive of the condition, but these are not pathognomonic and exclusion of other inflammatory disorders including vasculitis is required. Wherever possible, a tissue diagnosis should be established. The characteristic histopathological changes include a lymphoplasmacytoid infiltrate, storiform fibrosis and obliterative phlebitis. IgG4-RD typically responds well to treatment with glucocorticoids, although relapse is relatively common and treatment with a steroid-sparing agent or rituximab may be required. Improved understanding of the pathogenesis of IgG4-RD is likely to lead to the development of more specific disease treatments in the future.

show abstract

“…As with AIP, patients with IgG4-related hypophysitis tend to be middle-aged and older men [14, 71, 79–81]. …”

Section: Neurological Manifestations Of Igg4-rdmentioning

confidence: 99%

“…In addition, constitutional symptoms are often subtle or even absent, and patients often feel relatively well even in the setting of multi-organ disease [8, 79, 114]. However, a minority of patients have a more fulminant presentation characterised by constitutional symptoms, fever and multi-organ involvement from the outset [4, 8].…”

Section: Diagnostic Approachmentioning

confidence: 99%

Neurological Manifestations of IgG4-Related Disease

Baptista

Casian

Gunawardena

et al. 2017

Curr Treat Options Neurol

106

View full text Add to dashboard Cite

show abstract

“…The glandular infiltration was composed of mononuclear cells and the syndrome was named as Mikulicz's disease. 19,20 Similarly, Küttner (1896) reported tumor-like enlargement of the submandibular gland. 20 A spectrum of glandular infiltrative diseases was first proposed in the 1930s by Henrik Sjögren after identification of patients with Mikulicz's disease who were incorrectly diagnosed with Sjögren's syndrome.…”

Section: History Of Igg4-related Diseasementioning

confidence: 97%

“…It was concluded based on these two studies that there were $8,000 to 20,000 Japanese patients with the diagnosis of IgG4-RD. 19 The incidence of Ig4-RD in Japan was estimated to be 0.28 to 1.08 per 100,000, with 336 to 1,300 patients newly diagnosed per year. 3 IgG4-RD is most often diagnosed in middle-aged to elderly adults with a male predominance.…”

Section: Epidemiologymentioning

confidence: 99%

“…35 The male-to-female ratio and the age of disease onset vary slightly according to specific organ involvement at presentation. 19 Additional epidemiologic data on IgG4-RD come from cohort studies reported between 2012 and 2016, and included those from Europe (France, Spain, and Italy), United States, and China. 4,5,7,[36][37][38][39] Clinical manifestations, organ involvement, laboratory findings, treatment, and outcomes were described in these studies.…”

Section: Epidemiologymentioning

confidence: 99%

See 1 more Smart Citation

Thoracic Involvement in IgG4-Related Disease

Moura

Gripaldo

Baqir

et al. 2020

Semin Respir Crit Care Med

View full text Add to dashboard Cite

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

show abstract

Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundPathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP.MethodsBy using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells. Additionally, we obtained peripheral blood samples from 27 healthy subjects, 40 patients with type 1 AIP, 8 patients with alcoholic chronic pancreatitis, 10 patients with bronchial asthma, and 10 patients with atopic dermatitis, and analyzed activation of basophils by stimulating them with ligands of TLR1–9. We also compared TLR expression in basophils from the tissue and blood samples.ResultsBasophils were detected in pancreatic tissues from 10 of 13 patients with type 1 AIP. Flow cytometric analysis revealed that the ratios of basophils activated by TLR4 stimulation in type 1 AIP (9.875 ± 1.148%) and atopic dermatitis (11.768 ± 1.899%) were significantly higher than those in healthy subjects (5.051 ± 0.730%; P < 0.05). Levels of basophils activated by TLR2 stimulation were higher in seven type 1 AIP cases. Furthermore, stimulation of TLR2 and/or TLR4, which were expressed by basophils in pancreas, activated basophils in peripheral blood.ConclusionsBasophils activated via TLR signaling may play an important role in the pathophysiology of type 1 AIP.

show abstract

The Geoepidemiology and Clinical Aspects of IgG4-Related Disease

Cited by 7 publications

References 95 publications

Neurological Manifestations of IgG4-Related Disease

Neurological Manifestations of IgG4-Related Disease

Thoracic Involvement in IgG4-Related Disease

Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis

Contact Info

Product

Resources

About