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Clinical features and mechanistic insights regarding IgG4-related dacryoadenitis and sialoadenitis: a review. Immunoglobulin G4-related disease (IgG4-RD), recognized only recently as a single diagnostic entity, is a chronic inflammatory condition of unknown etiology. The diagnosis of IgG4-RD relies heavily on histopathological analysis and the correlation of histology findings with clinical, serological, and radiological data. CD4+ T and B cells, including IgG4-expressing plasmablasts (...) of the interactions between these CD4+ T cells and cells of the B lymphocyte lineage is critical to understanding the pathophysiology of IgG4-RD. The establishment of pathogenic T cell clones and the identification of antigens specific to these clones constitute the first steps in determining the pathogenesis of this disease. This review focuses on clinical features and mechanistic insights regarding IgG4-related dacryoadenitis and sialoadenitis, from a perspective suitable for oral and maxillofacial
Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of SjÃ¶gren Syndrome Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sjögren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role (...) in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines (Cxcl9, Ccl19) and other
Bilateral Dacryoadenitis: Don't Forget Tuberculosis! Tuberculous dacryoadenitis occurs rarely. It should be suspected in children presenting with unremitting inflammation of the lacrimal gland despite standard antibiotic and/or anti-inflammatory treatment, and a thorough systemic evaluation should be undertaken to identify a primary infectious site. We present an adolescent girl in whom bilateral dacryoadenitis was the first sign of pulmonary tuberculosis.
Bilateral subacute lacrimal gland enlargement mimicking dacryoadenitis in a 7-year-old boy: a rare adverse effect of valproic acid (sodium valproate). A healthy 7-year-old boy presented with bilateral symmetrical lacrimal gland enlargement; a week later salivary gland enlargement was also noted. Clinical investigations suggested no diagnosis, and surgical biopsy was considered. Valproic acid (sodium valproate), which he was taking for absence seizures, has been reported to cause salivary gland
Mesenchymal stem cells for treating autoimmune dacryoadenitis Autoimmune dacryoadenitis, such as Sjögren syndrome, comprises multifactorial and complex diseases. Inflammation of the lacrimal gland plays a key role in the pathogenesis of diseases. Unfortunately, current treatment strategies, including artificial tears, anti-inflammatory drugs, punctual occlusion, and immunosuppressive drugs, are only palliative, and long-term administration of these strategies is associated with adverse effects (...) that limit their utility. Hence, an effective and safe treatment for autoimmune dacryoadenitis is urgently needed. Mesenchymal stem cells (MSCs) have emerged as a promising tool for treating autoimmune dacryoadenitis, owing to their immunosuppressive properties, tissue repair functions, and powerful differentiation capabilities. A large number of studies have focused on the effect of MSCs on autoimmune diseases, such as autoimmune uveitis, inflammatory bowel disease, and collagen-induced arthritis
Dacryoadenitis with Ptosis and Diplopia as the Initial Presentation of Granulomatosis with Polyangiitis A 77-year-old Japanese woman presented to an ophthalmologist with an erythematous swollen upper eyelid and diplopia which was initially diagnosed to be idiopathic dacryoadenitis on the basis of a histological evaluation of an orbital mass that was in remission following a 3.5-month period of systemic corticosteroid therapy. She subsequently developed respiratory symptoms, and was finally (...) diagnosed with systemic granulomatosis with polyangiitis (GPA) based on the clinical and histological features. She was successfully treated with corticosteroids and azathioprine. Dacryoadenitis in the form of an orbital inflammatory pseudotumor may be an initial presenting feature of GPA, sometimes as the limited phenotype, and occasionally progressing to systemic disease.
Bilateral dacryoadenitis as initial presentation of a locally aggressive and unresponsive limited form of orbital granulomatosis with polyangiitis Limited orbital granulomatosis with polyangiitis (GPA) is uncommon and its diagnosis may be delayed, especially when isolated lacrimal involvement is the initial presentation, because clinical manifestations are non-specific and systemic diagnostic criteria are not applicable. Making an early diagnosis despite the absence of systemic progression (...) is extremely important because in some cases the disease is locally destructive, with irreversible visual and functional loss, and it can be refractory to corticosteroids and conventional immunosuppressive drugs to induce remission. The authors report an unusual limited form of orbital GPA in a 35-year-old woman presenting with bilateral dacryoadenitis, evolving later to locally aggressive bilateral orbital pseudotumour leading to proptosis, extraocular myositis, diplopia and medial deviation of the nasal
Adipose-Derived Mesenchymal Stem Cells Reduce Lymphocytic Infiltration in a Rabbit Model of Induced Autoimmune Dacryoadenitis. To investigate the immunoregulatory roles of adipose-derived mesenchymal stem cells (ADSCs) in autoimmune dacryoadenitis.Rabbits were treated with ADSCs or phosphate-buffered solution on days 1, 3, 5, 7, and 9 after injection of activated peripheral blood lymphocytes, and clinical scores were determined by assessing tear production, break-up time, and fluorescein (...) of their lacrimal gland was restored significantly. Treatment with ADSCs downregulated the Th1 and Th17 responses but enhanced Tregs function. In addition, ADSC treatment noticeably suppressed the expression of matrix metalloproteinase (MMP)-9, MPP-2, IL-1β, and IL-6, whereas it enhanced the expression of the anti-inflammatory cytokine IL-10.Our results demonstrated that ADSC administration efficiently ameliorates autoimmune dacryoadenitis mainly via modulating Th1/Th17 responses.
The pathological features of ectopic lymphoid neogenesis in idiopathic dacryoadenitis. Lymphoid neogenesis has been reported in various diseases but not in idiopathic dacryoadenitis. The aim of this paper is to discuss the pathological features of lymphoid neogenesis in idiopathic dacryoadenitis.20 cases of idiopathic dacryoadenitis were collected retrospectively. Lymphoid neogenesis was graded by lymphocytic aggregates and germinal center-like structure formation. T and B cell (...) and grades of lymphoid neogenesis.Ectopic lymphoid neogenesis participates in the pathogenesis of idiopathic dacryoadenitis and appears as a dynamic process.
Relationship between dacryoadenitis subtype of idiopathic orbital inflammatory pseudotumor and paranasal sinusitis To determine the clinical features of the dacryoadenitis subtype of idiopathic orbital inflammatory pseudotumor and its relationship with paranasal sinusitis.A retrospective analysis of 46 patients who received surgical treatment at the Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University for the dacryoadenitis subtype of idiopathic orbital inflammatory (...) pseudotumor from October 2010 to December 2012. Each patient underwent magnetic resonance imaging (MRI) of the orbits and the 4 paranasal sinuses. Disease status and the level of serum immunoglobulin G4 (IgG4) was measured before and 6mo after surgery.The initial clinical feature of the idiopathic dacryoadenitis type of orbital inflammatory pseudotumor was redness or swelling of the eyelids. Masses were palpated in the area of the lacrimal gland in some patients. Of the 46 patients, 16 also suffered from
Acute Painful Ptosis Secondary to IgG4 Dacryoadenitis A 48-year-old lorry driver presented with 3 weeks of blurred vision, pain and diplopia. There was a right upper lid ptosis with some restriction of eye movements. A CT revealed an enlarged lacrimal gland and lacrimal gland biopsy showed IgG4-positive plasma cells. The patient responded to oral prednisolone and fully recovered. As a condition which mimics a number of diseases, an IgG4-related disease presents a diagnostic challenge and ought
Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis. IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis (...) of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites.Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjögren's syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were
First case report of isolated aspergillus dacryoadenitis We report a case of isolated Aspergillus dacryoadenitis. A 23-year-old male presented with dull ache, diffuse swelling in superolateral quadrant of the right orbit and proptosis for 4 months. Ocular examination showed conjunctival congestion, discharge in the fornix and palpable lacrimal gland (LG) mass. Routine hematological investigations followed by computed tomography scan of orbits were done. He did not respond to a course
Idiopathic dacryoadenitis: clinical features, histopathology, and treatment outcomes. To review the clinical and histologic features of idiopathic dacryoadenitis, and to assess prognostic factors associated with disease recurrence, treatment recalcitrance, and incomplete treatment response.Retrospective interventional case series.setting: Tertiary referral centers.Seventy-nine cases of biopsy-confirmed idiopathic dacryoadenitis.The following data were reviewed: age, sex, laterality, symptom (...) onset, clinical presentation, histopathology, treatment response, and recurrence.Rates of treatment recalcitrance, incomplete treatment response, and recurrence.Idiopathic dacryoadenitis patients had a mean age of 50 years, 57% were female, and 16% of cases were bilateral. Fifty-two percent had inflammation extending to adjacent structures on imaging. Twenty percent were recalcitrant to treatment, 17% had an incomplete treatment response, and 15% of patients had a recurrence during a mean follow-up
The many facets of dacryoadenitis. To review the spectrum of lacrimal gland inflammation, with particular reference to the old condition, idiopathic dacryoadenitis, and the new, immunoglobulin G4 (IgG4)-related dacryoadenitis.Idiopathic dacryoadenitis remains the most common inflammatory lesion of the lacrimal gland, for which surgical treatment is successful. There is mounting evidence that the presence of IgG4-positive plasma cells in a lacrimal gland specimen is nonspecific, for being found (...) in other inflammatory lacrimal gland lesions, even lymphoproliferative ones. To identify IgG4-related dacryoadenitis, particularly when there is no documented disease elsewhere, the criteria have been strengthened toward abundant IgG4-positive plasma cell counting.The gold standard of diagnosis of noninfectious lacrimal gland inflammation is tissue biopsying, which is commonly therapeutic in the case of idiopathic dacryoadenitis. Although it was initially suggested that IgG4-related dacryoadenitis
Innate Immune Signaling Induces IL-7 Production, Early Inflammatory Responses, and Sjögren's-Like Dacryoadenitis in C57BL/6 Mice. Innate immune signaling elicited by polyinosinic-polycytidylic acid (poly I:C) induces IL-7 production and early inflammatory responses in the salivary gland and accelerates the development of Sjögren's syndrome (SS)-like sialadenitis. Whether poly I:C can induce similar responses in the lacrimal gland (LAC) has not been characterized. In this study, we examined (...) mice over an 8-day period caused leukocytic infiltration and caspase-3 activation in the LAC, antinuclear antibody production, and impaired tear secretion.Poly I:C induces IL-7 production, early inflammatory responses, and characteristic pathologies of SS-like dacryoadenitis in non-autoimmune-prone C57BL/6 mice. These findings provide new evidence that viral infection-elicited innate immune signaling may be one of the early triggers of SS-like dacryoadenitis.
A case of marginal zone B cell lymphoma mimicking IgG4-related dacryoadenitis and sialoadenitis IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease, is characterized by elevated serum IgG4 and infiltration of IgG4-positive plasma cells in glandular tissues. Recently, several studies reported both malignant lymphoma developed on the background of IgG4-associated conditions and IgG4-producing malignant lymphoma (non-IgG4-related disease).We report on the case
T helper subsets in Sjögren's syndrome and IgG4-related dacryoadenitis and sialoadenitis: a critical review. IgG4-related disease (IgG4-RD) is a systemic disease characterized by the elevation of serum IgG4 and infiltration of IgG4-positive plasma cells in multiple target organs, including the pancreas, kidney, biliary tract and salivary glands. In contrast, Mikulicz's disease (MD) has been considered a subtype of Sjögren's syndrome (SS) based on histopathological similarities. However (...) , it is now recognized that MD is an IgG4-RD distinguishable from SS and called as IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS). Regarding immunological aspects, it is generally accepted that CD4+ T helper (Th) cells play a crucial role in the pathogenesis of SS. Since it is well known that IgG4 is induced by Th2 cytokines such as interleukin (IL)-4 and IL-13, IgG4-DS is speculated to be a unique inflammatory disorder characterized by Th2 immune reactions. However, the involvement of Th cells
The diagnostic utility of biopsies from the submandibular and labial salivary glands in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease. IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is characterized by serum IgG4 elevation and the infiltration of IgG4-positive plasma cells in glandular tissues. For definitive diagnosis of IgG4-DS, biopsies of local lesions are recommended to exclude Sjögren's syndrome (SS), malignant tumours, and similar disorders