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Proceedings of the Royal Society of... 1916
PubMed: 19979432
DOI: No ID Found -
Proceedings of the Royal Society of... 1912
PubMed: 19975642
DOI: No ID Found -
International Heart Journal 2014Immunoglobulin4 (IgG4)-related disease is a systemic inflammatory disease characterized by elevation of serum IgG4. It involves various organs such as the pancreas... (Review)
Review
Immunoglobulin4 (IgG4)-related disease is a systemic inflammatory disease characterized by elevation of serum IgG4. It involves various organs such as the pancreas (autoimmune pancreatitis), lacrimal gland (Mikulicz's disease), retroperitoneum (retroperitoneal fibrosis), aorta (aortic aneurysm and aortitis), heart (constrictive pericarditis), and pseudotumors around the coronary arteries. These disorders often coexist in accordance with progression of the disease. Because IgG4-related cardiovascular disorder affects the patient's prognosis, early detection and treatment is important. Coronary CT imaging and echocardiography accidentally detect IgG4-related disorders and (18)FDG-PET imaging can identify active inflammation in the lesions. Measurement of serum IgG4 levels and tissue biopsy are necessary for diagnosis. Minor salivary gland biopsy is recommended even though (18)FDG uptake is not detected when it is difficult to obtain a biopsy specimen from IgG4-related cardiovascular lesions. The first-line treatment is high-dose corticosteroid therapy, however, relapse is often reported. Corticosteroids suppress the development of active inflammatory diseases such as aortitis, pericarditis, and pseudotumors, but already-developed lesions do not respond. A large developed aneurysm can rupture even during or after corticosteroid therapy, therefore, additional surgical treatment may be needed. Treatment of IgG4-related cardiovascular disorders might require higher doses of corticosteroids than IgG4-related extracardiovascular disorders. The adequate dose of corticosteroid, type and dose of immunosuppressant, and surgical intervention should be carefully considered on a case-by-case basis.
Topics: Antibodies, Anti-Idiotypic; Autoimmune Diseases; Autoimmunity; Cardiovascular Diseases; Humans; Immunoglobulin G
PubMed: 24898599
DOI: 10.1536/ihj.13-321 -
Head and Neck Pathology Mar 2015IgG4 related disease of the head and neck region represents one of the more common manifestations of IgG4 related disease. Involvement of the submandibular and parotid... (Review)
Review
IgG4 related disease of the head and neck region represents one of the more common manifestations of IgG4 related disease. Involvement of the submandibular and parotid glands, the orbit and thyroid represent some of the more common sites involved by IgG4 related disease. Eosinophilic angiocentric fibrosis, Mikulicz disease and Riedel thyroiditis are also members of the family of IgG4 related disease. Clinically, the disease is characterized by tumefactive lesions, often multicentric, that show a swift response to immunosuppressive therapy. An elevated serum IgG4 represents the only validated blood based biomarker. However, elevated serum IgG4 is detected in only half the patients with this disease. Histology continues to represent the gold standard for the diagnosis of IgG4 related disease: storiform-type fibrosis and obliterative phlebitis constitute characteristic features of this disease. A definitive diagnosis of IgG4 related disease also requires the presence of elevated numbers of IgG4 positive plasma cells as well as an IgG4 to IgG ratio of greater than 40 %. In isolation, elevated numbers of IgG4 positive plasma cells represents a non-specific feature, detected in a variety of other inflammatory as well as neoplastic diseases. Attention to the clinical context, histological features, as well as an elevated IgG4 to IgG ratio is critical to avoiding overdiagnosis of IgG4 related disease.
Topics: Head; Humans; Immunoglobulin G; Neck
PubMed: 25804380
DOI: 10.1007/s12105-015-0620-6 -
Medicine Dec 2022IgG4-related diseases cause lesions in various organs throughout the body. In otorhinolaryngology, IgG4-related Mikulicz's disease is suspected and diagnosed based on... (Review)
Review
RATIONALE
IgG4-related diseases cause lesions in various organs throughout the body. In otorhinolaryngology, IgG4-related Mikulicz's disease is suspected and diagnosed based on the presence of lesions of the head and neck, salivary and lacrimal gland enlargement, and bilateral sinus opacity concentrated on the maxillary sinuses. However, in some cases, it is necessary to consider about differentiation between IgG4-related Mikulicz's disease and Sjögren syndrome.
PATIENT CONCERNS AND DIAGNOSIS
A 75-years-old male patient visited our hospital with bilateral otitis media with effusion, which was resistant to conservative treatment. Other symptoms at presentation included enlarged bilateral submandibular and sublingual glands marked oral dryness, severe decrease in saliva secretion (1 mL/10 minutes), and dry eyes. We conducted a Schirmer's and fluorescent dye tests, both of which were positive. High serum IgG4 levels were observed, and although the Sjögren syndrome (SS)-A/SS-B antibodies were negative, marked hypolacrimation and tear secretion were observed. Therefore, a detailed examination considering both IgG4-related Mikulicz's disease and SS was conducted. Salivary gland scintigraphy performed prior to the salivary gland biopsy revealed a marked decrease in uptake, which satisfied the diagnostic criteria for SS; however, it was difficult to diagnose IgG4-related disease based on the diagnostic definition.
INTERVENSIONS
Although a definitive diagnosis of SS was made, the persistent otitis media with effusion that was resistant to conservative treatment and bilateral mixed hearing loss were confirmed. As mixed hearing loss is considered an otological symptom of IgG4-related disease, oral steroid treatment was administered.
OUTCOME
Thereafter, marked recovery of hearing and reduced swelling and induration of the bilateral parotid and submandibular glands were observed. Clinically, IgG4-related Mikulicz's disease was strongly suspected, but a definite diagnosis of SS was made.
LESSONS
In the absence of an IgG4-related Mikulicz's disease diagnosis, careful differentiation between IgG4-related Mikulicz's disease and 2 diseases and their diagnostic criteria was essential.
Topics: Male; Humans; Aged; Sjogren's Syndrome; Mikulicz' Disease; Immunoglobulin G4-Related Disease; Hearing Loss, Mixed Conductive-Sensorineural; Otitis Media with Effusion; Immunoglobulin G
PubMed: 36596084
DOI: 10.1097/MD.0000000000032617 -
Cells Feb 2023Diverse immune cell subsets have been described in IgG4-related disease (IgG4-RD). If there is a different immunophenotype according to clinical phenotype and activity...
Diverse immune cell subsets have been described in IgG4-related disease (IgG4-RD). If there is a different immunophenotype according to clinical phenotype and activity status is not known. Levels of IL-4-, IL-13-, IL-5-, and IL-21-producing CD4 T cells (Th2 subsets), CD4 cytotoxic T lymphocytes (CD4CTLs), T helper 9 cells, T follicular helper cells (Tfh; Tfh1/Tfh2/Tfh17/Tf regulatory [Tfr]), Foxp3 regulatory T cells, Type 1 regulatory T cells (Tr1), T helper 3 regulatory cells (Th3), IL-10-producing regulatory B cells (Bregs), IL-10-expressing regulatory plasmacytoid dendritic (pDC IL-10) cells, and M1 and M2 monocytes were determined by flow cytometry in 43 IgG4-RD patients and 12 controls. All immune subsets were higher in patients vs. controls. CD4/IL-4, CD4/IL-5, CD4CTLs, Tfh2, Tfh17, Tfr, and M1 monocyte cell number was different among IgG4-RD clinical phenotypes. The pancreato-hepato-biliary phenotype was characterized by a higher CD4CTLs, Tfh17, Tfh2, and Tfr and lower M1 cell number. An increased CD4CTLs and Th3 cell number distinguished the head and neck-limited phenotype, while the retroperitoneal/aortic and Mikulicz/systemic phenotypes were characterized by increased Th2 subsets. Tfh17, Tr1, Th3, pDC, M1, and M2 monocytes were augmented in active patients. In summary, the clinical heterogeneity of IgG4-RD might be driven by the participation of different immunophenotypes and, consequently, by a different fibroinflammatory process.
Topics: Humans; Interleukin-10; Immunoglobulin G4-Related Disease; Interleukin-4; Interleukin-5; Phenotype
PubMed: 36831337
DOI: 10.3390/cells12040670 -
Nihon Rinsho Men'eki Gakkai Kaishi =... Feb 2008Mikulicz's disease represents persistent enlargement of the lacrimal and salivary glands, and autoimmune pancreatitis is shown with diffuse pancreatic swelling. Both... (Review)
Review
Mikulicz's disease represents persistent enlargement of the lacrimal and salivary glands, and autoimmune pancreatitis is shown with diffuse pancreatic swelling. Both diseases are characterized with elevated IgG4 concentrations in the serum and prominent infiltration by plasmacytes expressing IgG4 in the glands. Clinical analyses were performed in 40 patients with systemic IgG4-related plasmacytic syndrome (SIPS) who consulted the doctors in Sapporo Medical University Hospital. Our patients were mainly middle-aged or elderly females. The average age was 58.9 years. The diagnosis was following ; 33 cases with Mikulicz's disease, 3 cases with Küttner's tumor, and 4 cases with IgG4-related dacryoadenitis. Slight dysfunction of lacrimal and salivary gland was observed in about 60% of them. Antinuclear antibodies were detected in only 15% of the cases with SIPS. Almost all, except one case, did not have anti-SS-A or anti-SS-B antibodies. Interestingly, hypocomplementemia was revealed in 30% of them. The complications of SIPS include autoimmune pancreatitis, tubulointerstitial nephritis, retroperitoneal fibrosis, prostatitis, and so on. SIPS is mainly treated by the administration of steroids. We started to prescribe much quantity of prednisolone to the patients with organ failure. The recurrence was admitted in the 3 patients for the followed 16 years. We present here the problems and prospects in SIPS.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunoglobulin G; Male; Middle Aged; Mikulicz' Disease; Plasma Cells; Sjogren's Syndrome; Syndrome
PubMed: 18311037
DOI: 10.2177/jsci.31.1 -
Reumatologia Clinica 2017IgG4-related disease is the term used to refer to a condition characterized by a lymphoplasmacytic infiltrate, fibrosis and an increased number of IgG4+ cells present in... (Review)
Review
IgG4-related disease is the term used to refer to a condition characterized by a lymphoplasmacytic infiltrate, fibrosis and an increased number of IgG4+ cells present in tissue, in most cases, with an elevated serum IgG4 level. This disease frequently affects the pancreas, salivary glands and lymph nodes, but can involve almost any tissue. Its etiology and the exact role of the different inflammatory cells in the damage to the target organ is still unclear. As yet, there is no international consensus about diagnostic criteria for the disease, but there are important advances in its treatment and in the quest to achieve remission. We include a review of the history, possible pathogenesis, clinical manifestations, diagnostic approach and available therapeutic approaches.
Topics: Autoimmune Diseases; Biomarkers; Global Health; Humans; Immunoglobulin G; Incidence; Prevalence
PubMed: 27329319
DOI: 10.1016/j.reuma.2016.05.009 -
Canadian Medical Association Journal Apr 1948
Topics: Humans; Mikulicz' Disease
PubMed: 18916111
DOI: No ID Found -
Clinical and Experimental Immunology Aug 2015Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4(+) plasma cells in... (Review)
Review
Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4(+) plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed.
Topics: Adaptive Immunity; B-Lymphocytes; Cell Communication; Collagen; Gene Expression; Granuloma, Plasma Cell; Humans; Immunity, Innate; Immunoglobulin G; Inflammation; Mikulicz' Disease; Retroperitoneal Fibrosis; T-Lymphocytes, Regulatory; Th2 Cells
PubMed: 25865251
DOI: 10.1111/cei.12641