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Current Opinion in Rheumatology Jan 2011An enlarged salivary gland or lacrimal gland raises a wide differential diagnosis that includes both benign inflammatory conditions and malignant disorders. This review... (Review)
Review
PURPOSE OF REVIEW
An enlarged salivary gland or lacrimal gland raises a wide differential diagnosis that includes both benign inflammatory conditions and malignant disorders. This review aims to address the numerous controversies that have arisen regarding inflammatory diseases of the salivary gland over the past two centuries and more specifically address the relevance of IgG4 in this setting.
RECENT FINDINGS
A significant percentage of cases previously classified as Mikulicz disease, Küttner tumor, and orbital pseudotumor (idiopathic orbital inflammation) show elevated numbers of IgG4-positive plasma cells, and some of these cases also show elevated levels of serum IgG4. These data support the evolving concept of IgG4-associated sialadenitis/dacroadenitis. The disease presents with enlargement of one of more salivary gland(s) and/or lacrimal gland(s). Histologically this disease is characterized by a dense polyclonal lymphoplasmacytic infiltrate, and is frequently associated with germinal centers, fibrosis and obliterative phlebitis. IgG4-bearing plasma cells are virtually always present, as is an elevated ratio of IgG4 to IgG containing plasma cells.
SUMMARY
IgG4-related sialadenitis belongs to the IgG4-related systemic disease spectrum and shows a swift response to immunosuppression.
Topics: Autoimmune Diseases; Diagnosis, Differential; Female; Humans; Immunoglobulin G; Lymphoma, Non-Hodgkin; Male; Mikulicz' Disease; Orbital Pseudotumor; Pancreatitis; Plasma Cells; Salivary Gland Neoplasms; Sialadenitis; Sjogren's Syndrome
PubMed: 21124091
DOI: 10.1097/BOR.0b013e3283413011 -
Investigative Ophthalmology & Visual... Jun 2000To characterize lacrimal gland function and lymphocyte infiltration in patients with Mikulicz's disease (MD) and Sjögren's syndrome (SS).
PURPOSE
To characterize lacrimal gland function and lymphocyte infiltration in patients with Mikulicz's disease (MD) and Sjögren's syndrome (SS).
METHODS
Four patients with MD and 5 with SS were recruited, on whom were performed Schirmer test I (Schirmer test without anesthesia), Schirmer test with nasal stimulation, and vital staining of the ocular surface. The lacrimal gland was then biopsied and the tissues stained with CD3, CD4, CD8, B220, APO2.7, Fas, and Fas ligand (Fas-L) antibodies.
RESULTS
Although regular Schirmer test results in the MD group were less than 10 mm, those with nasal stimulation, 38.1 +/- 3.4 mm, were significantly greater than the SS group. There were minimal ocular surface changes in MD. Morphologic staining with hematoxylin and eosin was identical in both groups, but the acinar cells were stained with APO2.7 only in the SS group. There was strong Fas and Fas-L staining in SS patients but not in those with MD.
CONCLUSIONS
Lacrimal gland acinar cells in those with MD maintained their function and were not programmed for cell death. The sicca syndrome was not observed in MD patients. Although the pathology is similar for MD and SS, the difference in acinar cell apoptosis and function can explain clinical differences.
Topics: Adult; Aged; CD3 Complex; CD4 Antigens; CD8 Antigens; Fas Ligand Protein; Female; Humans; Immunoenzyme Techniques; Lacrimal Apparatus; Lymphocytes; Male; Membrane Glycoproteins; Middle Aged; Mikulicz' Disease; Sjogren's Syndrome; Tears; fas Receptor
PubMed: 10845583
DOI: No ID Found -
Clinical Oral Investigations Dec 2013Mikulicz's disease (MD) was considered to be a subtype of Sjögren's syndrome (SS), based on histopathological similarities. However, recent studies have indicated that...
OBJECTIVES
Mikulicz's disease (MD) was considered to be a subtype of Sjögren's syndrome (SS), based on histopathological similarities. However, recent studies have indicated that patients with MD show high serum IgG4 concentration, and suggested that MD is one of "IgG4-related disease" and distinguishable from SS. Therefore, we clinically and histopathologically examined the disease states of MD and SS in detail.
MATERIALS AND METHODS
Twenty patients with Mikulicz's disease and 18 with SS were comparatively studied to determine clinical characteristics in MD patients.
RESULTS
Sialography in MD patients did not show the "apple-tree sign" typically seen in SS. Serologically, high serum IgG4 levels but not anti-SS-A or anti-SS-B antibodies were observed in MD. SS showed lymphocytic infiltration of various subsets with atrophy or severe destruction of the acini, while MD showed selective infiltration of IgG4+ plasma cells with hyperplastic germinal centers and mild acini destruction. Corticosteroid treatment of MD reduced IgG and IgG4 levels and improved salivary function. A negative correlation between disease duration and increasing rate of salivary flow was observed in MD.
CONCLUSIONS
These results suggested that the pathogenesis of MD might be different from those of SS.
CLINICAL RELEVANCE
early diagnosis and treatment of MD is important for the improvement of salivary function.
Topics: Adrenal Cortex Hormones; Aged; Female; Humans; Immunoglobulin G; Male; Middle Aged; Mikulicz' Disease; Saliva
PubMed: 23242814
DOI: 10.1007/s00784-012-0905-z -
BMC Ophthalmology Jul 2023Sjögren's Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz's disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in...
BACKGROUND
Sjögren's Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz's disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in middle-aged female, and the dry eyes could be presented in both of them with different degree. The MD patients are characterized by symmetrical swelling of the lacrimal glands which also can occur in the early stage of SS. And the imaging findings between early stage of SS and MD are lack of specificity. Therefore, SS and MD have similarities in the clinical manifestations, imaging and pathological findings and are confused in diagnosis.
CASE PRESENTATION
A 51-year-old female patient presented with bilateral swelling of the upper eyelids for 2 years. She also reported having dry mouth and dry eyes which could be tolerated. The Schirmer's test result is positive and the laboratory tests indicate serum total IgG increased. In the bilateral lacrimal gland area could palpate soft masses. The orbital magnetic resonance imaging (MRI) examination showed bilateral lacrimal gland prolapse. While the histopathological result was considered as MD. The immunohistochemical (IHC) staining results were positive for IgG and negative for IgG4. To clarify the diagnosis, SS-related laboratory tests were performed: anti-SSA antibody (+++), anti-SSB antibody (+++), anti-Ro-52 antibody (+++). With a comprehensive consideration, the final diagnosis was SS.
CONCLUSION
When the clinical manifestations are atypical, it is necessary to pay attention to the differential diagnosis of SS and MD.
Topics: Middle Aged; Humans; Female; Mikulicz' Disease; Sjogren's Syndrome; Salivary Glands; Edema; Immunoglobulin G; Diagnostic Errors
PubMed: 37501055
DOI: 10.1186/s12886-023-03090-1 -
Nature Reviews. Rheumatology Mar 2014Recognition of IgG4-related disease as an independent chronic inflammatory disorder is a relatively new concept; previously, the condition was thought to represent a... (Review)
Review
Recognition of IgG4-related disease as an independent chronic inflammatory disorder is a relatively new concept; previously, the condition was thought to represent a subtype of Sjögren's syndrome. IgG4-related disease is characterized by elevated serum levels of IgG4 and inflammation of various organs, with abundant infiltration of IgG4-bearing plasma cells, storiform fibrosis and obliterative phlebitis representing the major histopathological features of the swollen organs. The aetiology and pathogenesis of this disorder remain unclear, but inflammation and subsequent fibrosis occur due to excess production of type 2 T-helper-cell and regulatory T-cell cytokines. The disease can comprise various organ manifestations, such as dacryoadenitis and sialadenitis (also called Mikulicz disease), type 1 autoimmune pancreatitis, kidney dysfunction and lung disease. Early intervention using glucocorticoids can improve IgG4-related organ dysfunction; however, patients often relapse when doses of these agents are tapered. The disease has also been associated with an increased incidence of certain malignancies. Increased awareness of IgG4-related disease might lead to consultation with rheumatologists owing to its clinical, and potentially pathogenetic, similarities with certain rheumatic disorders. With this in mind, we describe the pathogenic mechanisms of IgG4-related disease, and outline considerations for diagnosis and treatment of the condition.
Topics: Autoimmune Diseases; Dacryocystitis; Glucocorticoids; Humans; Immunoglobulin G; Mikulicz' Disease; Pancreatitis; Rheumatic Diseases; T-Lymphocytes, Helper-Inducer
PubMed: 24296677
DOI: 10.1038/nrrheum.2013.183 -
Seminars in Diagnostic Pathology Nov 2012Lymphoid infiltrates are relatively common in the ocular adnexa and the salivary glands. They are of a variety of types and include both reactive processes and... (Review)
Review
Lymphoid infiltrates are relatively common in the ocular adnexa and the salivary glands. They are of a variety of types and include both reactive processes and lymphomas. Within the ocular adnexa in years past, lymphoid proliferations were classified as inflammatory pseudotumor, reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma. With improvements in diagnostic techniques and with advances in lymphoma subclassification, it became clear that many of the dense lymphoid infiltrates, including cases classified as lymphoma and likely some classified as atypical lymphoid hyperplasia, represented low-grade B-cell lymphomas, the most common of which by far were extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas. Ocular adnexal inflammatory pseudotumor, reactive lymphoid hyperplasia, and chronic sclerosing sialadenitis were recognized, but the focus in diagnosis had been on avoiding misdiagnosis as a neoplastic process and in planning appropriate therapy. Recently, it has become clear that many cases of these reactive processes fall into the spectrum of immunoglobulin G4 (IgG4)-related disease, offering new insight into the pathogenesis of inflammatory lesions occurring in the ocular adnexa and the salivary glands. The majority of entities previously classified as chronic sclerosing sialadenitis, Mikulicz disease, orbital pseudolymphoma, and eosinophilic angiocentric fibrosis are now considered a part of the IgG4-related disease spectrum. In this review, we discuss the histologic and immunohistochemical features of IgG4-related disease of the head and neck and provide guidance for distinguishing this disease from its many mimics.
Topics: Autoimmune Diseases; Biomarkers; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Immunoglobulin G; Lymphoma, B-Cell, Marginal Zone; Male; Orbital Diseases; Sialadenitis; Sjogren's Syndrome
PubMed: 23068303
DOI: 10.1053/j.semdp.2012.07.008 -
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 -
European Journal of Radiology Mar 2021Immunoglobulin G4-related disease (IgG4-RD) is a newly defined fibro-inflammatory multisystemic condition defined by a triad of diagnostic criteria based on clinical... (Review)
Review
PURPOSE
Immunoglobulin G4-related disease (IgG4-RD) is a newly defined fibro-inflammatory multisystemic condition defined by a triad of diagnostic criteria based on clinical presentation, biochemical and histopathological findings. Whereas some subsites of this disease have been well described in the literature so far (e.g. pancreas, kidneys, retroperitoneum, salivary glands), more recently identified anatomical sites of involvement in the head and neck are less well understood (e.g. nose, paranasal sinuses).
METHOD
This pictorial review details the imaging appearances of extracranial IgG4-RD in the Head & Neck. Multimodality imaging appearance and features are presented, with reference to the published literature to date.
RESULTS
Following a subsite-based approach, we present both the most common and the more rarely encountered imaging patterns of IgG4-RD in the extracranial head and neck, along with the relevant differential diagnoses to consider. Our institutional experience not only cements what is already known in the existing literature on this topic, but also reveals new imaging features of IgG4-RD, notably in the sinonasal tract.
CONCLUSIONS
This pictorial review of extracranial head & neck IgG4-RD will enable radiologists to recognise the features of this condition and propose it as a differential diagnosis to include alongside other probable entities. It establishes the place of the radiologist in the diagnosis and management of IgG4-RD.
Topics: Autoimmune Diseases; Head; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Neck
PubMed: 33524920
DOI: 10.1016/j.ejrad.2021.109560 -
Eye Science Mar 2014To report an unusual case of IgG4-related Mikulicz's disease associated with thyroiditis. (Review)
Review
PURPOSE
To report an unusual case of IgG4-related Mikulicz's disease associated with thyroiditis.
CASE REPORT
We describe a 25-year-old Chinese man who presented with bilateral, painless swellings of the lachrymal glands, parotid glands, and thyroid nodules. The patient underwent left-sided dacryoadenectomy and the diagnosis of IgG4-related Mikulicz's disease was pathologically confirmed. The size of the right-sided lachrymal gland and parotid glands recovered fundamentally after one month of glucocorticoid therapy.
CONCLUSION
IgG4-related Mikulicz's disease associated with thyroiditis should be considered in the differential diagnosis of bilateral swellings of lachrymal glands, salivary glands, and thyroid nodules. Surgical excision is recommended in order to treat the tumor and to ensure the pathological diagnosis. Glucocorticoid therapy should be considered in association with surgery after removal.
Topics: Adult; Autoimmune Diseases; Diagnosis, Differential; Glucocorticoids; Humans; Immunoglobulin G; Lacrimal Apparatus; Male; Mikulicz' Disease; Salivary Glands; Thyroiditis
PubMed: 26016066
DOI: No ID Found -
Endokrynologia Polska 2016We present a case of Mikulicz's Disease with hypophysitis. This is a rare clinical association as part of the group of IgG4- related diseases, a group of disorders which...
INTRODUCTION
We present a case of Mikulicz's Disease with hypophysitis. This is a rare clinical association as part of the group of IgG4- related diseases, a group of disorders which can have multiorgan involvement.
METHODS
A 55-year-old male patient was diagnosed with Mikulicz's disease. He was treated with oral steroids for six months with complete resolution. After two years the patient presented with fatigue, generalised weakness, and weight loss of 11 kg over six months. On evaluation he was found to have panhypopituitarism. MRI pituitary revealed homogeneously enlarged, well enhancing pituitary with thickening of the stalk. Serum IgG4 levels were significantly elevated. The patient was treated with methyl prednisolone pulse therapy followed by oral steroids for three months. He developed diabetes insipidus after starting steroid therapy. There was a significant resolution in the enlargement of the pituitary and stalk thickening at three months.
RESULTS
The clinical, biochemical, and radiological findings of hypophysitis associated with Mikulicz's disease are presented with a brief review of literature.
CONCLUSIONS
IgG4-related diseases are rare and have recently been recognised as a cause of hypophysitis. They can have multiorgan involvement. A high index of suspicion is required for clinching this rare diagnosis, which can be confirmed by measurement of serum levels of IgG4. Steroid therapy can reverse the inflammatory changes in IgG4 hypophysitis. (Endokrynol Pol 2016; 67 (6): 622-626).
Topics: Anti-Inflammatory Agents; Autoimmune Hypophysitis; Humans; Hypopituitarism; Male; Methylprednisolone; Middle Aged; Mikulicz' Disease; Pituitary Gland
PubMed: 28042654
DOI: 10.5603/EP.2016.0071