Mikulicz's disease combined with IgG4-related hypophysitis: a case report.

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.

Primary Sjögren's syndrome misdiagnosed as Mikulicz's disease: a case report.

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.

Immunoglobulin G4-Related Disease: A Case Report.

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.

IgG4-Related Dacryoadenitis in Egyptian Patients: A Retrospective Study.

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.

IgG4-related sialadenitis - a rare bilateral submandibular gland enlargement: case report.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition of unknown etiology. Although the salivary glands are currently considered among the most commonly affected among them, oral and maxillofacial surgeons are generally not familiar with the condition. Enlargement of the major salivary glands may be the first identifiable sign of IgG4-RD. A salivary gland biopsy along with IgG4 serum level assessment may help differentiate IgG4-related sialadenitis (IgG4-RS) from malignancies, infectious diseases, and obstructive conditions. Greater knowledge and higher levels of awareness of IgG4-RS may contribute to the expansion of differential diagnostic and treatment approaches. This case report describes a patient with bilateral submandibular salivary gland swelling who was diagnosed as having IgG4-RS on the basis of the histopathologic findings of a submandibular salivary gland biopsy and subsequent IgG4 levels.

[Immunoglobulin G (IgG) 4-related diseases]. / Immunglobulin-G4(IgG4)-assoziierte Erkrankungen.

Immunoglobulin G (IgG) 4­related diseases are fibrosing inflammatory systemic diseases that can affect almost every organ system. Typical disease manifestations include autoimmune pancreatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory orbitopathy and involvement of the salivary and lacrimal glands. Organ involvements can occur either isolated or in combination with other disease manifestations. Before diagnosing IgG4-related diseases, malignancies and other inflammatory diseases have to be excluded. The diagnosis requires a combination of laboratory findings, histological and radiological results. Typically, IgG4-related diseases respond well to glucocorticosteroids. In cases of relapse or severe organ involvement a longer term immunosuppression is often required, whereas watch and wait can also be sufficient in milder cases.

Clinical Perspectives on IgG4-Related Disease and Its Classification.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease. Since its discovery nearly two decades ago, our understanding of its pathophysiology and clinical manifestations has grown substantially. Early diagnosis and treatment of this elusive disease can prevent substantial organ damage from end-stage fibrosis, emphasizing the need for prompt recognition and accurate characterization of IgG4-RD. The classification criteria endorsed by the American College of Rheumatology and the European Alliance of Associations for Rheumatology in 2019 provide a framework for establishing the diagnosis in the clinical setting. This process involves recognizing the typical manifestations of the disease and incorporating clinical, radiological, serological, and histopathological information as well as excluding disease mimickers. Glucocorticoids and rituximab are effective at inducing remission in IgG4-RD in most patients, but the optimal approach to long-term management of IgG4-RD remains an area of active clinical research.

Enfermedad relacionada con IgG4, según criterios ACR/EULAR 2019 sin evidencia de IgG4 en sangre / IgG4-related disease according to ACR/EULAR 2019 criteria without evidence of IgG4 in blood

INTRODUCCIÓN. La enfermedad relacionada con IgG4 es una patología fibroinflamatoria multiorgánica, de origen desconocido, que simula trastornos malignos, infecciosos e inflamatorios. Los criterios del American College of Rheumatology y la European League against Rheumatism 2019, son útiles para el diagnóstico diferencial de ésta enfermedad cuando se no se cuenta con evidencia de inmunoglobulina G4 en sangre. CASO CLÍNICO. Paciente hombre de 45 años de edad, nacido en Ambato-Ecuador, con ingreso en noviembre del 2017, en emergencias del Hospital de Especialidades Carlos Andrade Marín, con presencia de tos con hemoptisis leve, febrícula, astenia, pérdida de peso e hiporexia de dos semanas de evolución. Se realizó múltiples exámenes, tras observar infiltrados pulmonares intersticiales, con elevación de inmunoglobulina G en suero, negativas para malignidad; se sospechó de enfermedad relacionada a inmunoglobulina G4. Se ampliaron los estudios para descartar otras patologías más prevalentes y cuyo diferencial es primordial. Se inició tratamiento con prednisona y micofenolato con buena respuesta clínica; durante dos años. DISCUSIÓN. La evidencia científica registró que el hallazgo más importante en la enfermedad relacionada con inmunoglobulina G4 fue un aumento de sus niveles séricos. La recurrencia de la enfermedad en un órgano afectado o la aparición de un nuevo órgano involucrado pudo conducir al diagnóstico en el caso presentado. CONCLUSIÓN. La enfermedad relacionada con inmunoglobulina G4 al ser una patología heterogénea, inmunomediada, al simular otras afecciones puede retrasar el diagnóstico; se debe tener una alta sospecha clínica, si al excluir otros procesos infecciosos, autoinmunes y/o eoplásicos, hay evidencia de patología fibroesclerosante multiorgánica sin causa establecida.

INTRODUCTION. IgG4-related disease is a multiorgan fibroinflammatory pathology of unknown origin that mimics malignant, infectious, and inflammatory disorders. The criteria of the American College of Rheumatology and the European League against Rheumatism 2019 are useful for the differential diagnosis of this disease when there is no evidence of immunoglobulin G4 in blood. CLINICAL CASE. 45-year-old male patient, born in Ambato-Ecuador, with admission in November 2017, in the emergency room of the Hospital de Especialidades Carlos Andrade Marín, with the presence of cough with mild hemoptysis, fever, asthenia, weight loss and hyporexia of two weeks of evolution. Multiple tests were performed, after observing interstitial pulmonary infiltrates, with elevated serum immunoglobulin G, negative for malignancy; immunoglobulin G4-related disease was suspected. Studies were extended to rule out other more prevalent pathologies whose differential is paramount. Treatment with prednisone and mycophenolate was started with good clinical response; for two years. DISCUSSION. The scientific evidence recorded that the most important finding in immunoglobulin G4-related disease was an increase in its serum levels. Recurrence of the disease in an affected organ or the appearance of a new involved organ could have led to the diagnosis in the presented case. CONCLUSION. Immunoglobulin G4-related disease, being a heterogeneous, immune-mediated pathology, by simulating other conditions may delay diagnosis; a high clinical suspicion should be maintained if, when other infectious, autoimmune and/or neoplastic processes are excluded, there is evidence of multiorgan fibrosclerosing pathology without established cause.

Enfermedad relacionada con IgG4: reporte de un caso y revisión de la literatura / IgG4-related disease: a case report and literature review

Immunoglobulin G4 (IgG4-RD) -related disease is a regional or systemic fibroinflammatory disease of unknown etiology. It has a characteristic histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4 positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or swollen lesions. This entity frequently affects the pancreas, salivary glands, and lymph nodes, but it can compromise almost any structure in the human anatomy. This new disease entity includes a wide variety of diseases such as Mikulicz disease, autoimmune pancreatitis, Riedel's thyroiditis, interstitial nephritis, and retroperitoneal fibrosis. Glucocorticoid therapy can resolve clinical and pathologic abnormalities and impaired organ function. IgG4-RD was internationally recognized in 2011, and new evidence has accumulated on its pathogenesis, clinical characteristics, and treatment. However, much is still unknown about the behavior of IgG4 in vivo, the participation of this molecule in disease, and whether its role in IgG4-related disease is primary or secondary. The text below is based on a brief review of the most recent literature on this entity in relation to a clinical case.

Imaging of IgG4-related disease in the extracranial head and neck.

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.

The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.

Phenotyping of IgG4-related diseases based on affected organ pattern: A multicenter cohort study using cluster analysis.

OBJECTIVES: Immunoglobulin G4-related disease (IgG4-RD) is a systemic, multiorgan disease of unknown etiology. We aimed to classify IgG4-RD by a combination pattern of affected organs and identify the clinical features, including the comorbidities of each subgroup. METHODS: Patients diagnosed with IgG4-RD between April 1996 and June 2018 were enrolled from three institutes. Hierarchical cluster analysis was performed using six frequently affected organs (lacrimal gland and/or orbit, salivary gland, lung, pancreas, kidney, and retroperitone and/or aorta). Clinical features, such as comorbidities and outcomes, were compared between clusters. RESULTS: In total, 108 patients enrolled in this cohort could be stratified into five distinct subgroups: group 1, lung dominant group; group 2, retroperitoneal fibrosis and/or aortitis dominant group; group 3, salivary glands limited group; group 4, Mikulicz's disease dominant group; and group 5, autoimmune pancreatitis with systemic involvement group. There were significant between-group differences in sex (male dominant in group 1, 2, and 5), history of asthma and allergies on the respiratory tract (most frequent in group 5), and malignancy (most frequent in group 5). CONCLUSION: IgG4-RD can be classified into subgroups according to the pattern of affected organs. Group 5 may have frequent complications with allergies and malignancies.

IgG4-related disease with multiple organs involvement was effectively controlled by glucocorticoids: a case report.

Immunoglobulin G4 (IgG4) related disease is a rare autoimmune disease involving multiple organs and tissues. A diagnosis of IgG4-related disease (IgG4-RD) is mainly based on serum IgG4 concentration, imaging, pathology, and effective glucocorticoids therapy. In this paper, we report a 53-year-old male with typical signs and symptoms of IgG4-RD successfully treated with glucocorticoids. This patient had experienced bilateral mumps for more than 8 months and intermittent abdominal pain spreading to his lower back for 2 months before his admission. During his hospitalization, based on the characteristic appearance of magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and computed tomography with positron emission tomography, a diagnosis of autoimmune pancreatitis (AIP), cholangitis with biliary obstruction, lachrymal adenitis, and submandibular adenitis was made. A high serum IgG4 concentration further supported a diagnosis of IgG4-RD. Then, the treatment was promptly initiated with corticosteroids. MRI, MRCP, and IgG4 concentration were re-examined during his follow up, suggesting that glucocorticoid treatment resulted in a resolution of his disease. The dosage of glucocorticoid had been gradually decreased. Now, he is stable with oral low-dose glucocorticoids. Certainly, long-term follow up of this patient with such a rare disease is very essential to observe the possibility of disease recurrence and glucocorticoids related complications.

Mikulicz's disease and Küttner's tumor as manifestations of IgG4-related diseases: a review of the literature.

According to a new concept for the classification and division of autoimmune diseases, Mikulicz's disease and Küttner's tumor belong to immunoglobulin G4-related diseases (IgG4-RD) and fulfil their diagnostic criteria. The aim of this study was to summarize the new classification concepts of IgG4-RD in the head and neck area and to review their clinical, histopathological and serologic criteria and the methods used in the diagnostic workup with respect to their advantages, limitations and differentiative value. The PubMed, Web of Science, Google Scholar, and Scopus databases were searched for articles published between 2009 and 2019 using the following key words: IgG4-related diseases, Mikulicz's disease, Küttner's tumor, salivary glands, xerostomia. Results of the review of the literature revealed that Mikulicz's disease and Küttner's tumor fulfil the same diagnostic criteria but may manifest different clinical symptoms which determine the choice of the different diagnostic tools.

Immunoglobulin G4 (IgG4)-Related Sialadenitis and Dacryoadenitis With Chronic Rhinosinusitis.

Immunoglobulin G4-related disease (IgG4-RD) is a new disease entity of rare and complex immune-mediated fibroinflammatory conditions that can affect any organ. The concomitance of IgG4 sclerosing sialadenitis and dacryoadenitis with rhinosinusitis is extremely rare. We report a case of IgG4 sclerosing sialadenitis and dacryoadenitis (Mikulicz's disease) diagnosed in a middle-aged African American man with a long-standing history of chronic rhinosinusitis who presented with progressively worsening bilateral salivary and lacrimal glands swelling. Imaging revealed pansinusitis, symmetric enlargement of the lacrimal glands, parotid glands, and submandibular glands. Serological IgG4 level was significantly elevated and the diagnosis of IgG4 sclerosing sialadenitis was confirmed by histopathology. A robust clinical response in the facial swelling and nasal manifestations was noted after the initiation of immunotherapy with corticosteroids.

Review of a novel disease entity, immunoglobulin G4-related disease.

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.

Immunoglobulin G4-related chronic sclerosing sialadenitis: An emerging entity.

Chronic sclerosing sialadenitis is associated with the immunoglobulin G4 (IgG4)-related disease (RD) spectrum. IgG4-RD is a newly recognized immunomediated fibroinflammatory condition characterized by several features: a tendency to form tumefactive lesions at multiple sites, lymphoplasmacytic infiltrate, fibrosis and obliterative phlebitis. Often but not always, the serum IgG4 concentrations are also elevated. Immunohistochemistry for IgG4 is helpful to clinch the diagnosis. Here, we describe a case of 65-year-old male with IgG4-related chronic sclerosing sialadenitis of the s ubmandibular gland. We have discussed the histopathological criteria to diagnose this entity.

A case report of Mikulicz's disease.

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.

Review of a novel disease entity, immunoglobulin G4-related disease

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.

Mikulicz's Disease With Immune Thrombocytopenia: A New Immunoglobulin G4-Mediated Disorder and Literature Review.

Mikulicz's disease (MD), an immunoglobulin G4 (IgG4)-related disease, is a fibrosis-associated inflammatory disease characterized by painless bilat- eral swelling of lacrimal and salivary glands. Although thrombocytopenia is associated with many rheumatologic disorders, it is rare in IgG4-related MD. This novel study aims to report a rare case of IgG4-related MD complicated with severe autoimmune thrombocytopenia without any hemato- logical malignancies and review all cases of IgG4-related disease associated with thrombocytopenia in the literature.