Manifestation Of IgG4-related Disease Research Articles

Raised Numbers of IgG4-Positive Plasma Cells Are a Common Histopathological Finding in Orbital Xanthogranulomatous Disease

ABSTRACTPurpose: To determine the relation of orbital xanthogranuloma with IgG4-related disease.Methods: Retrospective consecutive case series over a period of 25 years. We searched our charts for histologically confirmed orbital xanthogranuloma. Patient files were reviewed for clinical and follow up data including presence or absence of systemic non-ophthalmic manifestations of IgG4 related disease. Slides were re-examined and histopathological classification was re-assessed. Sixteen cases of orbital xanthogranuloma were evaluated. Immunohistochemical stains for IgG and IgG4 were performed. Positive immunohistochemical staining required increased IgG4-positive plasma cells in the involved tissues scored as >50 per high-power field, with IgG4/IgG ratio >0.40.Results: According to the criteria described above 8/16 (50%) cases showed increased numbers of IgG4-positive plasma cells in the specimens. Two of these patients may have had signs of systemic diseaseConclusion: Raised numbers of IgG4-positive plasma cells are a common finding in histopathological specimens of xanthogranulomatous disease of the orbit and are often not indicative for IgG4 related systemic disease.

Cutaneous plasmacytosis as a skin manifestation of IgG4-related disease

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a fibro-inflammatory condition that has distinctive clinical features involving multiple organs, such as the pancreas, salivary and lacrymal glands (Mikulicz's disease), biliary tract, peritoneum, pituitary gland, lung, kidney and aorta [1, 2]. Mass-forming, sclerosing lesions are commonly seen in affected organs and systemic corticosteroids are effective for these conditions. Histopathologically, dense lymphoplasmacytic infiltration, storiform [...]

Membranous glomerulonephritis is a manifestation of IgG4-related disease

IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that typically manifests as fibro-inflammatory masses that can affect nearly any organ system. Renal involvement by IgG4-RD usually takes the form of IgG4-related tubulointerstitial nephritis, but cases of membranous glomerulonephritis (MGN) have also been described. Here we present a series of 9 patients (mean age at diagnosis 58 years) with MGN associated with IgG4-RD. All patients showed MGN on biopsy, presented with proteinuria (mean 8.3 g/day), and most had elevated serum creatinine (mean 2.2 mg/dl). Seven patients had known extrarenal involvement by IgG4-RD, with 5 patients having concurrent IgG4-related tubulointerstitial nephritis. Immunohistochemical analysis for the phospholipase A2 receptor, a marker of primary MGN, was negative in all 8 biopsies so examined. Six of 7 patients with available follow-up (mean 39 months) were treated with immunosuppressive agents; one untreated patient developed end-stage renal disease and underwent transplantation, without recurrence at 12 years after transplant. All 6 treated patients showed decreased proteinuria (mean 1.2 g/day), and most showed decreased serum creatinine (mean 1.4 mg/dl). Thus, MGN should be included in the spectrum of IgG4-RD and should be suspected in proteinuric IgG4-RD patients. Conversely, patients with MGN and an appropriate clinical history should be evaluated for IgG4-RD.

Teaching Neuro Images : Multifocal neurologic involvement as the only manifestation of IgG4-related disease

A 46-year-old man with progressive visual loss underwent brain MRI showing multifocal nodular pachymeningeal thickening involving optic nerve meninges bilaterally and internal acoustic meatus dura mater (figure 1). Diffuse meningiomatosis was diagnosed and radiation therapy was given with symptom stabilization. Four years later, left hearing loss and right hypoacusia occurred, with slight transient improvement after high-dose dexamethasone. Serum immunoglobulin (Ig)G4 was increased. CSF analysis showed increased protein, oligoclonal IgG, plasma cells, and lymphocytes. Cerebral biopsy showed meningeal plasma-cell granuloma with IgG4-positive polyclonal plasma cells and B-lymphocyte infiltration (figure 2). IgG4-related disease was diagnosed.1 Rituximab was unsuccessful. IgG4-related disease is a fibroinflammatory, multiorgan condition characterized by tumefactive lesions and lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells that may affect every organ; serum IgG4 may be elevated. Although IgG4-related disease with exclusive multifocal CNS localization is extremely rare and often misdiagnosed,2–4 it should be considered in the differential diagnosis of tumor-like intracranial lesions and hyperthrophic pachymeningitis.

Nasal manifestations of immunoglobulin G4‐related disease

Immunoglobulin (Ig)G4-related disease is a systemic syndrome, characterized by sclerosing lesions that mainly affect the exocrine tissue. Although some patients with IgG4-related disease complain of nasal symptoms, there are few reports concerning the nasal manifestations of this disease. We investigated the clinical and pathological features of the nasal manifestations of IgG4-related disease. Retrospective review in a tertiary referral hospital. Twenty-three consecutive patients with IgG4-related disease, six allergic rhinitis (AR) patients, and eight healthy subjects (HS) were evaluated. Nasal symptoms, local findings of the nasal cavity, and laboratory data were examined. Mucosal tissues from the inferior turbinate were obtained from all subjects before treatment. The level of IgG4-positive plasma cells and other infiltrating cells, and the number of nasal glands in the nasal subjects were compared among the three groups. Ten (43.4%) of 23 cases had some nasal symptoms, such as nasal obstruction and nasal crusting. Thirteen cases (56.5%) had numerous IgG4-positive plasma cell infiltration in the nasal mucosa. IgG4-positive plasma cells, CD3, and CD4 were significantly higher in the IgG4-related disease group than in the HS and AR groups, whereas the number of nasal glands in the IgG4-related disease group was significantly lower than in the HS and AR groups. The inflammatory lesions associated with IgG4-related disease exist on the nasal membrane. Thus, the nasal manifestations of IgG4-related disease were thought to be different from AR.

Retroperitoneal and aortic manifestations of immunoglobulin G4-related disease

Retroperitoneal fibrosis is one of the prototypic manifestations of immunoglobulin G4 (IgG4)-related disease (IgG4-RD), but there is growing evidence that the aorta is also involved. These 2 conditions are closely linked, and based on the epicenter of the disease, the clinical manifestations can be classified as retroperitoneal fibrosis, inflammatory abdominal aortic aneurysm (including a combination of the 2), and thoracic aortitis. IgG4-RD is responsible for only a subset (∼50%) of cases of retroperitoneal fibrosis and inflammatory aortic aneurysms. Histological features include an extensive lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, fibrosis arranged in a storiform pattern, moderate tissue eosinophilia, and partially or completely obliterated veins. Among the 3 layers comprising the aorta, the adventitia is most susceptible to IgG4-related inflammation. The inflammatory process can also disrupt the lamellar elastic fibers in the media, which is seemingly a critical event leading to aneurysmal transformation. Steroid therapy is effective for both retroperitoneal and aortic lesions, as it is for the other manifestations of IgG4-RD. The risk of rupture appears to be low in patients with IgG4-related aortic aneurysms, but immunosuppressive therapy may trigger this critical complication by reducing the wall thickness.

IgG4‐related sclerosing mesenteritis: A rare mesenteric disease of unknown etiology

Sclerosing mesenteritis is a rare inflammatory and fibrosing disorder of unknown etiology, while IgG4-related disease (IgG4-RD) consists of mass-forming, fibroinflammatory lesions characterized by high serum IgG4 levels and tissue infiltration of many IgG4-positive plasma cells; obliterative phlebitis is common. This report describes a case of sclerosing mesenteritis that was considered a manifestation of IgG4-RD. A 53-year-old man underwent right hemicolectomy because of an ileocecal mass that did not improve with conservative therapy. The ill-defined fibroinflammatory lesion extended in the mesentery with storiform fibrosis, obliterative phlebitis, and infiltration of many IgG4-positive plasma cells. The ratio of IgG4-positive/IgG-positive cells was 64%, and the ratio of forkhead box protein 3 (FOXP3)-positive/CD4-positive cells was elevated (13%). It is likely that at least some cases of sclerosing mesenteritis are a manifestation of IgG4-RD. It is important to investigate this relationship because steroid therapy may benefit such cases.

The Clinical and Pathological Features of IgG4-Related Disease

The rapidly emerging disorder now known as IgG4-related disease (IgG4-RD) includes a variety of clinical entities once regarded as being entirely separate diseases. Manifestations of IgG4-RD have now been reported in essentially all organ systems. Regardless of which organ is involved, tissue biopsies reveal striking histopathological similarities. The hallmark pathology findings are diffuse lymphoplasmacytic infiltrates, abundant IgG4-positive plasma cells, modest tissue eosinophilia, and extensive fibrosis. Tumorous swelling and obliterative phlebitis are other frequently observed features. Polyclonal elevations of serum IgG4 are found in approximately 70% of patients. Many questions pertaining to the etiology, pathophysiology, epidemiology, clinical features, therapy, disease monitoring, and long-term outcomes remain to be addressed. This paper focuses on the clinical and pathological features of IgG4-RD.

Vertebral basilar system dolichoectasia with marked infiltration of IgG4‐containing plasma cells: A manifestation of IgG4‐related disease?

We report the histopathological features of vertebral basilar system dolichoectasia (VBD) in a 68-year-old man who died as a result of accompanying infarction of the medulla oblongata on day 6 of admission. During hospitalization, the patient was also found to have an elevated serum IgG level and tumors of the renal pelvis. A possible clinical diagnosis of VBD associated with IgG4-related disease was considered postmortem. Autopsy examination, limited to the intracranial tissues, revealed marked infiltration of IgG4-containing plasma cells in the adventitia and media of the vertebral and basilar arteries. Multiple fibrous nodules forming pseudotumors were also evident on the outer surface of the affected arteries. These histological features were very similar to those of arteriopathy, such as inflammatory aortic aneurysm, which has been described in patients with IgG4-related disease, suggesting that autoimmune mechanisms, known to be involved in the pathogenesis of visceral lesions in the disease, also played a role in the etiology of VBD in the present patient. In conclusion, we consider that the present case may represent VBD as a manifestation of IgG4-related disease.