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Clinical Ophthalmology (Auckland, N.Z.) 2022To report clinical, serological, and histopathological findings in Egyptian patients with dacryoadenitis associated with ImmunoglobulinG4-related disease (IgG4-RD).
PURPOSE
To report clinical, serological, and histopathological findings in Egyptian patients with dacryoadenitis associated with ImmunoglobulinG4-related disease (IgG4-RD).
METHODS
We retrospectively revised medical records of patients presented to Al-Azhar University Hospitals with lacrimal gland (LG) swelling between June 2016 and February 2022. We included patients with definite IgG4-related disease (IgG4-RD) diagnosis and excluded those with possible, probable, or unlikely IgG4-RD based on The Japanese Ministry of Health, Labour, and Welfare's 2011 guidelines.
RESULTS
Sixteen cases were included in the study (Fourteen females and two males, mean age 39.2±12.2 years); Seven cases met the criteria of Mikulicz disease, and nine cases met full clinical, serological, and histopathological criteria. Mean reported serum IgG was 1792.5 ± 313.7 (range 1063-2134) mg/dl, mean serum IgG4 was 576.25±215.3 (range 112-841) mg/dl, and mean Serum IgG4/IgG ratio was 31.9 ± 12.4%. The mean number of IgG4+ plasma cells/HPF was 74 ± 21.2, and the mean IgG4+ plasma cell percentage was 55 ± 9.7%. Serum IgG4 level showed a positive correlation to tissue IgG4+plasma cell percentage, while serum IgG4/IgG ratio positively correlated to both percentage and number of IgG4+plasma cells. Steroids had a good initial response, but recurrences were common.
CONCLUSION
A considerable proportion of patients with lacrimal gland swelling fall within the range of IgG4-RD. Proper diagnosis requires clinical, serological, and histopathologic correlation. Patients require long follow-up periods.
PubMed: 36039106
DOI: 10.2147/OPTH.S378583 -
Acta Otorhinolaryngologica Italica :... Apr 2017Autoimmune diseases of major salivary glands include Sjögren's syndrome and a complex of disorders classified as immunoglobulin G4-related diseases. These pathologies... (Review)
Review
Autoimmune diseases of major salivary glands include Sjögren's syndrome and a complex of disorders classified as immunoglobulin G4-related diseases. These pathologies are characterised by an autoimmune reaction mediated by T-helper lymphocytes that targets the ducts of exocrine glands in Sjögren's syndrome and glandular parenchyma in immunoglobulin G4-related diseases. Immunoglobulin G4-related diseases represent recently introduced multi-organ diseases that also involve the salivary glands. However, the morbid conditions once known as Mikulicz's disease and Kuttner's tumour were recently considered as two variants of immunoglobulin G4-related diseases affecting the major salivary glands ( immunoglobulin G4-related sialadenitis). This review briefly summarises the pathogenesis and clinical features of autoimmune diseases of the major salivary glands, focusing on the diagnostic and therapeutic role of sialendoscopy.
Topics: Autoimmune Diseases; Endoscopy; Humans; Immunoglobulin G; Sialadenitis; Sjogren's Syndrome
PubMed: 28516978
DOI: 10.14639/0392-100X-1605 -
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 -
Clinical and Experimental Rheumatology Dec 2023Recent studies have implicated cytotoxic CD4 and CD8 T cells in primary Sjögren's syndrome (pSS) and IgG4-related disease (IgG4-RD), but their association with immune...
OBJECTIVES
Recent studies have implicated cytotoxic CD4 and CD8 T cells in primary Sjögren's syndrome (pSS) and IgG4-related disease (IgG4-RD), but their association with immune aging and organ-specific clinical features remain unclear. CX3CR1 is expressed on cytotoxic CD4 and CD8 T cells. The aim of this study was to determine associations of peripheral CX3CR1+CD4 and CX3CR1+CD8 T cells with aging and clinical features.
METHODS
Whole blood samples were freshly obtained from consecutive patients with active, treatment-naïve pSS (n=57), IgG4-RD (n=54), and healthy individuals (n=40) and analysed by flow cytometry for CX3CR1+CD4 and CX3CR1+CD8 proportions. Associations of those T cells with aging and clinical features were determined.
RESULTS
CX3CR1+CD4 and CX3CR1+CD8 T cells selectively expressed perforin and granzyme B. Proportions of CX3CR1+CD4 and CX3CR1+CD8 T cells were significantly higher in pSS and IgG4-RD than in healthy individuals. Higher proportions of CX3CR1+CD8 T cells were associated with aging in pSS and IgG4-RD but not in healthy individuals. Sex differences were not associated with proportions of CX3CR1+CD8 T cells. Furthermore, patients with pSS with interstitial lung disease showed higher proportions of CX3CR1+CD8 T cells than those without interstitial lung disease. IgG4-RD patients with retroperitoneal fibrosis and/or aortitis exhibited higher proportions of CX3CR1+CD8 T cells compared with those with Mikulicz's disease. Moreover, proportions of CX3CR1+CD8 T cells were decreased following glucocorticoid treatment in paralleled with clinical improvements in IgG4-RD.
CONCLUSIONS
CX3CR1+CD8 T cells might be involved in immune aging and distinct clinical phenotypes of patients with pSS or IgG4-RD.
Topics: Humans; Male; Female; Sjogren's Syndrome; Immunoglobulin G4-Related Disease; CD8-Positive T-Lymphocytes; Aging; Lung Diseases, Interstitial; CX3C Chemokine Receptor 1
PubMed: 37812481
DOI: 10.55563/clinexprheumatol/kfsd65 -
Journal of the Korean Association of... Feb 2020Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related... (Review)
Review
Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.
PubMed: 32158675
DOI: 10.5125/jkaoms.2020.46.1.3 -
Cells Sep 2023Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential... (Review)
Review
Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential role as a specific marker in breast cancer. PIP binds to aquaporin-5 (AQP5), CD4, actin, fibrinogen, β-tubulin, serum albumin, hydroxyapatite, zinc α2-glycoprotein, and the Fc fragment of IgGs, and the expression of PIP has been demonstrated to be modulated by various cytokines, including IL4/13, IL1, and IL6. PIP gene expression has been extensively studied due to its captivating nature. It is influenced by various factors, with androgens, progesterone, glucocorticosteroids, prolactin, and growth hormone enhancing its expression while estrogens suppress it. The regulatory mechanisms involve important proteins such as STAT5A, STAT5B, Runx2, and androgen receptor, which collaborate to enhance PIP gene transcription and protein production. The expression level of PIP in breast cancer is dependent on the tumor stage and subtype. Higher expression is observed in early-stage tumors of the luminal A subtype, while lower expression is associated with luminal B, basal-like, and triple-negative subtypes, which have a poorer prognosis. PIP expression is also correlated with apocrine differentiation, hormone receptor positivity, and longer metastasis-free survival. PIP plays a role in supporting the immune system's antitumor response during the early stages of breast cancer development. However, as cancer progresses, the protective role of PIP may become less effective or diminished. In this work, we summarized the clinical significance of the PIP molecule in breast cancer and its potential role as a new candidate for cell-based therapies.
PubMed: 37759471
DOI: 10.3390/cells12182252 -
Journal of Otolaryngology - Head & Neck... Jun 2015Immunoglobulin G4 related disease (IgG4-RD) is a poorly understood chronic inflammatory disorder affecting the middle-aged and elderly that can present to the... (Review)
Review
BACKGROUND
Immunoglobulin G4 related disease (IgG4-RD) is a poorly understood chronic inflammatory disorder affecting the middle-aged and elderly that can present to the otolaryngologist. We aim to summarize the current literature regarding the manifestations and management of IgG4-RD in the head and neck.
METHODS
Pubmed and EMBASE were searched using the term relevant search algorithm utilizing keywords such as: IgG4 related disease, head and neck, orbit, salivary glands, sialadenitis, Kuttner, angiocentric eosinophilic fibrosis, submandibular, lacrimal, thyroid, dacryoadenitis, nasal, sinus, and Mikulicz's. Reference lists were searched for identification of relevant studies. Case reports, original research and review articles published in English from 1964 to 2014 whose major topic was IgG4-RD affecting the head and neck were included. Data regarding patient demographics, presentation, histopathology, management and treatment outcomes of IgG4-RD were extracted. Level of evidence was also assessed and data were pooled where possible. Three independent reviewers screened eligible studies; extracted relevant data and discrepancies were resolved by consensus, where applicable. Descriptive and comparative statistics were performed.
RESULTS
Fourty-three articles met our inclusion criteria. IgG4-RD most often presents as a mass lesion in the head and neck region. Common diagnostic features include: (1) elevated serum IgG4 level, (2) marked infiltration of exocrine glands by IgG4-positive plasma cells with fibrosis, and (3) marked improvement with corticosteroid therapy and additional immunosuppressive therapy in corticosteroid refractory cases. Early diagnosis and involvement of rheumatology is important in management.
CONCLUSIONS
IgG4-RD is a challenging non-surgical disease that has multiple manifestations in the head and neck. It must be distinguished from various mimics including malignancy, systemic diseases, and infectious. Otolaryngology-Head and Neck surgeons should be aware of this condition and its management.
Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Chronic Disease; Diagnosis, Differential; Humans; Immunoglobulin G; Inflammation; Otorhinolaryngologic Diseases
PubMed: 26092582
DOI: 10.1186/s40463-015-0071-9 -
Cureus Nov 2022Immunoglobulin G4-related disease (IgG4 RD) has a fair prognosis but its diagnosis has been difficult due to the condition's wide range of clinical manifestations,...
Immunoglobulin G4-related disease (IgG4 RD) has a fair prognosis but its diagnosis has been difficult due to the condition's wide range of clinical manifestations, limited awareness among common practitioners, and various differentials. Here, we present a case of an elderly male who presented with recurrent dental caries, recurrent sinusitis, persistent dry mouth, and dry eyes along with bilateral parotid gland enlargement without any lymphadenopathy. The patient was evaluated further and found to have elevated levels of IgG4 and on histopathological examination of the parotid gland showed lymphocytic infiltrate with germinal centers without any granulomatous lesions and IgG4-positive plasma cells on immunohistochemistry (IHC). The patient was diagnosed with IgG4 RD and was started on corticosteroids, after which there was a symptomatic improvement.
PubMed: 36524963
DOI: 10.7759/cureus.31403 -
The Pan African Medical Journal 2020Mikulicz's disease is a unique condition involving the enlargement of the lacrimal and salivary glands, similar to that observed in Sjogren's syndrome; however,...
Mikulicz's disease is a unique condition involving the enlargement of the lacrimal and salivary glands, similar to that observed in Sjogren's syndrome; however, Mikulicz's disease is clinically characterized by infrequent autoimmune reactions and responsiveness to glucocorticoid treatment. The ultrasound features of the lacrimal and salivary glands in patients with IgG4-Mikulicz's disease were characterized by multiple hypoechoic areas of varying sizes within the enlarged glands. IgG4 serum level was also elevated, in contrast to the detection of normal levels in Sjogren's syndrome. In this article, we intended to illustrate a case of Mikulicz's disease with clinical and imaging features.
Topics: Adult; Diagnosis, Differential; Female; Humans; Immunoglobulin G; Lacrimal Apparatus; Mikulicz' Disease; Salivary Glands; Sjogren's Syndrome; Ultrasonography
PubMed: 33598067
DOI: 10.11604/pamj.2020.37.252.26835 -
BMC Geriatrics Jun 2024IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
BACKGROUND
IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
CASE PRESENTATION
A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size.
CONCLUSION
Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.
Topics: Humans; Aged; Female; Mikulicz' Disease; Immunoglobulin G4-Related Disease; Autoimmune Hypophysitis; Immunoglobulin G; Prednisolone; Magnetic Resonance Imaging
PubMed: 38880897
DOI: 10.1186/s12877-024-05142-7