• Case report
• Diagnosis
• Immunoglobulin G4-related disease
• Older adults
• Pleura

• Humans
• Female
• Aged, 80 and over
• Immunoglobulin G4-Related Disease/diagnosis
• Immunoglobulin G4-Related Disease/drug therapy
• Immunoglobulin G4-Related Disease/pathology
• Immunoglobulin G4-Related Disease/complications
• Immunoglobulin G/blood
• Pleural Effusion/etiology
• Biopsy
• Pleura/pathology
• Pleural Diseases/diagnosis

• COVID-19
• bioinformatics analysis
• common genes
• immunology
• pericarditis

• Humans
• COVID-19 Vaccines
• COVID-19/genetics
• Computational Biology
• Systems Biology
• Pericarditis/genetics

• Humans
• Immunoglobulin G
• Immunologic Tests
• Pericarditis, Constrictive/diagnosis

• 6th cranial (abducens) nerve palsy
• Diabetes insipidus
• Hypopituitarism
• IgG4-related disease (IgG4-RD)
• IgG4-related hypophysitis (IgG4-RH)

• Autoimmune Hypophysitis/diagnostic imaging
• Humans
• Hypophysitis/diagnostic imaging
• Iran
• Pituitary Diseases/diagnosis
• Pituitary Gland/diagnostic imaging

• Classification
• Diagnosis
• Diagnostic criteria
• IgG4
• IgG4-related disease
• Pericarditis

• IgG4-related disease
• chylothorax
• pleuritis
• rituximab

• Aged
• Chylothorax/diagnosis
• Chylothorax/drug therapy
• Humans
• Immunoglobulin G
• Immunoglobulin G4-Related Disease
• Male
• Pleura/diagnostic imaging
• Pleural Effusion/drug therapy
• Pleurisy

• IgG4-related disease
• Multiple pleural nodules
• Thoracoscopy

A 75‐year‐old woman underwent thoracoscopic right upper lobectomy for lung cancer. A histopathological examination showed adenocarcinoma, pT1aN0M0 stage IA1. At six months after surgery, chest computed tomography (CT) revealed pericardial nodules that had not been detected before pulmonary resection. Postoperative CT performed two months later revealed that the nodules were growing and F¹⁸ fluorodeoxyglucose‐positron emission tomography showed a maximum standardized uptake of 9.87. Blood tests revealed no elevated tumor markers, with the exception of a mildly elevated interleukin‐2. Based on the above results, thoracoscopic biopsy was performed due to the suspected recurrence of lung cancer or malignant lymphoma. The histopathological examination of the nodule revealed immunoglobulin G4 (IgG4)‐related inflammatory pseudotumor. The serum IgG4 levels were elevated (358 mg/dL, normal: 4.5–117.0 mg/dL). No additional treatment was required because all nodules were observed to have disappeared naturally on a follow‐up CT scan performed two months after the surgical biopsy. The patient has been followed‐up for two years without recurrence.

We report a case of pericardial immunoglobulin G4‐related inflammatory pseudotumor that appeared after right upper lobectomy for lung cancer, and which naturally disappeared without any treatment.

There was an immunoglobulin G4‐related inflammatory pseudotumor which appeared as multiple nodules in the pericardial space, and this should be kept in mind when considering the differential diagnosis of intrapericardial nodules.

• Immunoglobulin G4-related (IgG4-related) inflammatory pseudotumor
• lung cancer
• pericardial tumor

• CP, constrictive pericarditis
• IgG4 related disease
• IgG4-RD, immunoglobulin G4–related disease
• TTE, transthoracic echocardiogram
• constrictive pericarditis

The causes of exudative pleural effusions are diverse and frequently remain unclear despite exhaustive examinations. Recently recognized IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that can affect nearly any organ including the lungs. This review will focus on the involvement of IgG4 in exudative pleural effusion of unknown cause.

IgG4 is found to be involved in a proportion of patients with undiagnosed pleural effusions. Pleural involvement in IgG4-RD can be seen in isolation or association with other organ disease. Pleural thickening and/or effusion are common clinical features of IgG4-related pleural lesions, and this condition is histologically characterized by a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells in the pleura. Although the pathogenesis of IgG4-RD is poorly understood, there is a growing body of evidence that indicates an antigen-driven process requiring T-cell and B-cell interaction in which autoantibodies, plasmablasts, follicular helper T cells and CD4+ cytotoxic T lymphocytes participate.

The possibility of IgG4-related pleural lesion should be considered in patients with pleural effusion of unexplained cause when lymphoplasmacytic infiltration is seen in a pleural biopsy specimen. This condition is responsive to systemic steroid therapy.

In general, we have to assume tuberculous pleurisy when a patient presents with pleural effusion and elevated adenosine deaminase (ADA). However, other diseases need to be considered, including immunoglobulin (Ig)G4-related disease (IgG4-RD). This case involved a 65-year-old asymptomatic man with right pleural effusion showing elevated ADA. He had no articular findings or rashes. Results were negative for all autoantibodies. Pleura, mediastinal lymph nodes, and areas around the aorta and vertebra showed high uptake of ¹⁸F-fluorodeoxyglucose (FDG) on positron-emission tomography-computed tomography (PET-CT). These findings were specific for IgG4-RD. Based on the results of FDG-PET-CT, we performed thoracoscopy under local anesthesia and bronchoscopy. Pleural biopsy and culture, and other examinations including sputum and blood yielded negative findings for tuberculous pleurisy. A pleural biopsy specimen showed IgG4-positive plasma cells and fibrosis without obliterative phlebitis or storiform fibrosis, and serum IgG4 was also high. The ratio of IgG4-to IgG-positive plasma cells was under 40%, and >10 IgG4-positive cells were seen in high-power fields. This case was classed as ‘possible IgG4-RD’ on the comprehensive diagnostic criteria for IgG4-RD, but did not meet the diagnostic criteria for IgG4-related respiratory disease. Prednisolone proved effective against the pleural effusion. We therefore clinically diagnosed IgG4-RD with pleural effusion based on the 2019 classification criteria for IgG4-RD in the United States. Although few cases of IgG4-RD with pleural effusion have been reported, this disease needs to be considered among the differential diagnoses for high-ADA pleural effusion. FDG-PET-CT and thoracoscopy under local anesthesia may be helpful for diagnosis.

•

ImmunoglobulinG4-related disease (IgG4-RD) with pleural effusion is rare.

• Adenosine deaminase
• IgG4-related disease
• PET-CT
• Pleural effusion
• Thoracoscopy

• IgG4-related disease
• Periaortitis
• Pleural disease
• Submandibular gland

• IgG4-related disease
• pleural effusion
• thoracoscopy

• Humans
• Immunoglobulin G/blood
• Immunoglobulin G4-Related Disease/diagnosis
• Immunoglobulin G4-Related Disease/diagnostic imaging
• Immunoglobulin G4-Related Disease/pathology
• Lymphocytes/metabolism
• Male
• Middle Aged
• Plasma Cells/metabolism
• Pleura/pathology
• Pleural Effusion/pathology
• Pleurisy/diagnosis
• Pleurisy/diagnostic imaging
• Pleurisy/pathology
• Thoracoscopy

IgG4-related disease, described around the years 2000 as a form of autoimmune pancreatitis, is now increasingly accepted as a systemic syndrome. The diagnosis is based on both comprehensive and organ-specific criteria. For the kidney, Mayo clinic classification and the guidelines of the Japanese Nephrology Society are used. Ultimately, together with parameters that characterize every organ or apparatus involved, the key element is the confirmation of growing levels of IgG4 in blood or in tissues.

We describe a male patient with chronic renal failure associated to hypertension without proteinuria. IgG4-related disease was diagnosed through renal biopsy. After an initial positive response to steroids, he presented tinnitus, and histological assessment showed cerebral and subsequently cardiac damage, both IgG4-related. This case appears unique for the type of histologically documented cardiac and neurological parenchymal involvement, and at the same time, exemplifies the subtle and pernicious course of the disease. Frequently, blurred and non-specific signs prevail. Here, kidney damage was associated with minimal urinary findings, slowly progressive renal dysfunction and other factors that can be equivocated in the differential diagnosis. Neurological involvement was represented by tinnitus alone, while cardiac alterations were completely asymptomatic.

This report is representative of the neurological and cardiac changes described in the literature for IgG4-related disease, which may be correlated or not with the renal form and highlights the need, in some cases, of targeted therapeutic approaches. In addition to glucocorticoids, as in this case, rituximab may be necessary.

• B-lymphocytes
• IgG4-related disease
• Kidney
• Nervous system
• T-lymphocytes

Pleural effusion is a relatively rare feature of IgG4-related disease (IgG4-RD). Here, we report a case of a 72-year-old woman who presented with pleural effusion. Although the pleural adenosine deaminase level was increased, surgical biopsy of the pleura and left inguinal lymph node indicated that the effusion was due to IgG4-RD. Active surveillance was initiated because serum IgG4 and pleural effusion naturally decreased and then completely disappeared. The patient has shown no recurrence for >4 years. This case suggests that pleural biopsy can be used to distinguish IgG4-RD from tuberculosis; moreover, some cases with pleural effusion could improve without treatment.

• Adenosine deaminase
• IgG4-related disease
• Pleural biopsy
• Pleural effusion
• Spontaneous remission

• IgG4-related disease
• IgG4-related respiratory disease
• diagnostic criteria
• nonspecific interstitial pneumonia
• pulmonary manifestations

• Corticosteroid therapy
• IgG4-related pleuritis
• No other organ involvement

• IgG4-related disease
• autoimmune pancreatitis

• Adrenal Cortex Hormones/therapeutic use
• Autoimmune Diseases/drug therapy
• Autoimmune Diseases/immunology
• Autoimmune Diseases/physiopathology
• Humans
• Immunoglobulin G/blood
• Pancreatitis/immunology
• Recurrence

• Immunoglobulin G4-related lung disease (IgG4-RLD)
• diagnosis
• histopathology
• inflammation

• heart failure
• cardiomyopathy, restrictive
• pleural diseases
• heart diseases
• pleural effusion
• edema

• Adult
• Autopsy
• Cardiomyopathy, Restrictive/complications
• Cardiomyopathy, Restrictive/diagnosis
• Edema/complications
• Edema/diagnosis
• Fatal Outcome
• Humans
• Male
• Pericarditis, Constrictive/complications
• Pericarditis, Constrictive/diagnosis
• Pleural Diseases/complications
• Pleural Diseases/diagnosis
• Pleural Effusion

• IgG4-related disease
• fibrinous pleuritis
• free light chain
• pleural effusion

• IgG4-related disease
• Pericardium
• Peritoneum
• Pleura

• Immunoglobulin G (IgG)
• constrictive
• pericarditis

• Adenosine deaminase
• IL-10
• IgG4-related disease
• Pericarditis

Immunoglobulin G4-related disease (IgG4-RD) can involve any organ. The majority of reported cases involve IgG4-RD of the biliary tract or pancreas, while only two cases of pericarditis have been reported. A 58-year-old man visited the outpatient clinic of our institution with a seven-day history of progressive dyspnea. Based on his transthoracic echocardiogram and transesophageal echocardiogram, he was diagnosed with constrictive pericarditis. The histopathology of his pericardiectomy revealed the cause of constrictive pericarditis to be IgG4-RD. Prednisolone (40 mg) was initiated after the pericardiectomy. As the patient's symptoms resolved, he was discharged and followed-up on an outpatient basis. This is the first case report of constrictive pericarditis caused by IgG4-RD in Korea.

• Immunoglobulin G
• Inflammation
• Pericarditis, constrictive

• Autoimmune Diseases/complications
• Autoimmune Diseases/diagnostic imaging
• Autoimmune Diseases/metabolism
• C-Reactive Protein/metabolism
• Female
• Fever/etiology
• Fluorodeoxyglucose F18/administration & dosage
• Fluorodeoxyglucose F18/metabolism
• Glucocorticoids/administration & dosage
• Humans
• Immunoglobulin G/blood
• Lymph Nodes/immunology
• Lymph Nodes/metabolism
• Mediastinum
• Middle Aged
• Multimodal Imaging/methods
• Pericarditis/complications
• Pericarditis/diagnostic imaging
• Pericarditis/immunology
• Pericarditis/metabolism
• Pericardium/metabolism
• Plasma Cells/immunology
• Positron-Emission Tomography
• Radiopharmaceuticals/metabolism
• Tomography, X-Ray Computed
• Treatment Outcome

• Aged
• Autoimmune Diseases/immunology
• Humans
• Immunoglobulin G/immunology
• Male
• Pancreatitis/immunology
• Pericarditis, Constrictive/immunology
• Pericardium/immunology
• Tomography, X-Ray Computed

IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease.

• IgG4-related disease
• Autoimmune pancreatitis
• Gastric ulcer

• Acute Disease
• Aged
• Autoimmune Diseases/blood
• Autoimmune Diseases/diagnosis
• Autoimmune Diseases/immunology
• Autoimmune Diseases/surgery
• Biomarkers/blood
• Drainage
• Esophagostomy
• Gastrectomy
• Gastric Fistula/blood
• Gastric Fistula/diagnosis
• Gastric Fistula/immunology
• Gastric Fistula/surgery
• Heart Diseases/blood
• Heart Diseases/diagnosis
• Heart Diseases/immunology
• Heart Diseases/surgery
• Humans
• Immunoglobulin G/blood
• Jejunostomy
• Male
• Pericardium/surgery
• Stomach Ulcer/blood
• Stomach Ulcer/diagnosis
• Stomach Ulcer/immunology
• Stomach Ulcer/surgery
• Tomography, X-Ray Computed
• Treatment Outcome

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21^st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD.

Whipple’s disease is a rare, multisystemic, chronic infectious disease which classically presents as a wasting illness characterized by polyarthralgia, diarrhea, fever, and lymphadenopathy. Pleuropericardial involvement is a common pathologic finding in patients with Whipple’s disease, but rarely causes clinical symptoms. We report the first case of severe fibrosing pleuropericarditis necessitating pleural decortication in a patient with Whipple’s disease.

Our patient, an elderly gentleman, had a chronic inflammatory illness dominated by constrictive pericarditis and later severe fibrosing pleuritis associated with a mildly elevated serum IgG4 level. A pericardial biopsy showed dense fibrosis without IgG4 plasmacytic infiltration. The patient received immunosuppressive therapy for possible IgG4-related disease. His poor response to this therapy prompted a re-examination of the diagnosis, including a request for the pericardial biopsy tissue to be stained for Tropheryma whipplei.

Despite a high prevalence of pleuropericardial involvement in Whipple’s disease, constrictive pleuropericarditis is rare, particularly as the dominant disease manifestation. The diagnosis of Whipple’s disease is often delayed in such atypical presentations since the etiologic agent, Tropheryma whipplei, is not routinely sought in histopathology specimens of pleura or pericardium. A diagnosis of Whipple’s disease should be considered in middle-aged or elderly men with polyarthralgia and constrictive pericarditis, even in the absence of gastrointestinal symptoms. Although Tropheryma whipplei PCR has limited sensitivity and specificity, especially in the analysis of peripheral blood samples, it may have diagnostic value in inflammatory disorders of uncertain etiology, including cases of polyserositis. The optimal approach to managing constrictive pericarditis in patients with Whipple’s disease is uncertain, but limited clinical experience suggests that a combination of pericardiectomy and antibiotic therapy is of benefit.

• Humans
• Immune System Diseases/complications
• Immunoglobulin G
• Pleurisy/immunology