Diagnosis Of IgG4-related Systemic Disease Research Articles

Клиническое наблюдение пациента с хроническим риносинуситом и редкой формой первичного иммунодефицита

The article tentatively reviewed such rare immuno-dependent conditions as: IgG4-linked primary immunodeficiency (PI) and general variable immunodeficiency. Over the past two decades, more and more data has been accumulating about this subject, due to which several previously known nosological forms were combined into a new group of IgG4-associated diseases (IgG4-SZ), and in order to establish a diagnosis of IgG4-related systemic disease, two or more lesions of organs are required. This group of diseases has a common serological sign – an increase in the concentration of IgG4 subclass in serum. Histologically in organs and tissues, plasmocytes infiltration secreting IgG4, eosinophils are formed, fibrosclerosis and obliterating phlebitis develop. Laboratory and immunological examination of patients with PI helps to identify a specific violation of the immune system. Primary diagnosis is usually done using a panel of screening laboratory tests. A high risk of developing IgG4-C3 is in patients with pancreatitis with unknown etiology, sclerosing cholangitis, bilateral enlargement of the salivary and lacrimal glands, in the presence of multiple nodes in the lungs. Predisposing factors are middle age and male gender. The article presents a clinical observation of a patient suffering from a rare combination of primary immunodeficiency and chronic bilateral rhinosinusitis, special attention on laboratory and instrumental examinations and treatment.

Protein Electrophoretic Findings Suggest IgG4-Related Systemic Disease

Serum protein electrophoresis (SPEP) is routinely performed to detect monoclonal gammopathies. Large polyclonal increases in IgG4 subclass produce a distinctive, relatively broad restriction in the anodal portion of the gamma globulin region. In this study, we sought to determine whether more subtle polyclonal increases in IgG4 detectable by SPEP were associated with a diagnosis of IgG4-related systemic disease (IgG4-RSD). A …

Diagnosis of IgG4-related systemic disease by cytology of large pericardial effusion with fine needle aspiration

IgG4-related disease has characteristic features as follows; Serum IgG4 is prominently elevated, IgG4-positive plasma cells infiltrate in involved tissues and various mass-forming lesions with fibrosis, such as the autoimmune pancreatitis, salivary gland and retroperitoneum. As this disease comes to attention, the reports of IgG4-related disease have been increasing, but the pathogenesis and exact frequency of the disease remain unknown. We present the case of a 69 year-old male who was admitted to our hospital for evaluation of lower legs edema in July, 2010. He first noticed lower legs edema in 2009 and visited a local clinic, and was diagnosed deep vein thrombosis, received anti-coagulation therapy. However, his edema was getting worth and hydrocele testis was appeared. When he visited our office, he complained of trouble in walking with lower legs edema. On physical examination, his body temperature was 36.2 °C, blood pressure 152/82 mm Hg, and pulse rate 60 per minute. There was no murmur in his cardiac sounds and lungs were clear. On abdominal examination, it was slightly swelling but not any mass were noted. His trunk was edematous, especially in lower legs. The thyroid gland, salivary glands and lymph nodes were not palpable. He had never experienced dry eye and dry mouth. Laboratory findings were as follows: WBC 4390/μL, hemoglobin 10.6 g/dL, platelet 27.3×10/μL, BUN 10 mg/dL, creatinine 1.04 mg/dL, BNP 119.0 pg/mL, CRP b0.10 μg/L. Liver function test was normal. Urinalysis did not demonstrate any protein on dipstick. Rheumatoid factor, anti-nuclear antibody, anti SS-A and anti SS-B, antibodies and antineutrophil cytoplasmic antibody were all negative. IgG, IgA, IgM and IgE were 1769.0 mg/dL, 272.7 mg/dL, 74.8 mg/dL and 276 mg/dL, respectively. Serum level of IgG4 was elevated by 408 mg/dL. A chest radiograph revealed marked cardiomegaly. Echocardiography revealed marked pleural effusion with slightly collapsed right atrium. Computed tomography (CT) revealed also large pericardial effusion (Fig. 1A) and low density area around the aorta (Fig. 1B). The mass, which was suspected retroperitoneal fibrosis (RPF), compressed inferior vena cava and right urinary duct, and induced lower legs edema and right hydronephrosis. After admission, a ureteral stent was placed in order to treat the hydronephrosis. Lip biopsy was done, but there was no significant pathological change. Gallium scintigraphy showed no hot lesions. Autoimmune pancreatitis was ruled out by magnetic resonance pancreatic cholangiopancreatography. Then,we performedpericardiocentesis byfineneedle aspiration on 9 days after admission. The specimen was light yellow, cloudy, TP 5.2 g/dL, albumin 3.0 g/dL, IgG 1604.3 mg/dL, IgG4 451 mg/dL and abundant small sized lymphocytes, rich in IgG4-positive cells (Fig. 2). There was no malignancy. Culture of the pericardial fluid revealed no bacterial infection. Therefore, we diagnosed this case as IgG4-related disease and treated with prednisolone 50 mg/day. Then his edema was rapidly improved. One month after starting steroid therapy, the CT revealed disappearance of pericardial effusion and regression of retroperitoneal mass (Fig. 1C and D). To our knowledge, this is the first case report diagnosed by fine needle aspiration cytology of large pericardial effusion. The pathological characteristic of this disease is rich in IgG4-positive plasma cells with typical fibrosis or sclerosis in the tissue [1]. IgG4related disease sometimes shows retroperitoneal fibrosis (RPF) and caused hydronephrosis as in our case. A biopsy for the retroperitoneal mass is necessary to provide a definitive diagnosis, but is considerably invasive. The major reasons of pericardial effusion are idiopathic pericarditis, infection included tuberculosis and malignancy [2,3]. Secondary to malignancy are frequently observed in lung cancer, breast cancer, and malignant lymphoma. Malignant lymphoma is considered of differential diagnosis in both RPF and pericardial effusion. Fine needle aspiration of pericardial effusion is less invasive compared to retroperitoneal biopsy. Although Sugimoto et al. reported IgG4-related disease caused constrictive pericarditis diagnosed by pericardiectomy [4], pericardial effusion is not a major complication. We showed that the cytology of pericardial effusion was rich in IgG4-positive cells similar to serum, suggesting that IgG4-related disease caused pericardial exudation of the plasma cell. Thus, it is necessary to consider the possibility of IgG4-related disease in the differential diagnosis of pericardial effusion. A pericardiocentesis will be useful to diagnose a IgG4related disease. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5].

Long-term clinical course of IgG4-related systemic disease accompanied by hypophysitis

A 70-year old man with a 14 year history of Sjögren syndrome, interstitial pneumonia, and autoimmune hepatitis (AIH) was admitted to our hospital due to hyponatremia with a one month history of fatigue, thirst, and nausea. Laboratory tests on admission revealed that this patient had a central adrenal insufficiency. Pituitary magnetic resonance imaging (MRI) further showed swelling of the stalk and posterior lobe of his pituitary, suggesting infundibulo-hypophysitis. Based on his past history of autoimmune disease, his serum IgG4 levels were measured and found to be remarkably high (924 mg/ dL). Previous biopsy specimens from his liver, lung, and parotid gland were immunostained for IgG4, which revealed a marked infiltration of IgG4-positive plasma cells. As a result of our tests, we made a diagnosis of IgG4-related systemic disease. Interestingly, a subsequent MRI scan at three weeks after the patient commenced glucocorticoid replacement therapy for adrenal insufficiency showed that the swelling of his pituitary stalk was reduced. This finding suggested that IgG4-related hypophysitis may improve either as a result of a supplemental dose of glucocorticoid or possibly spontaneously. Although six cases of IgG4-related hypophysitis have been reported in the scientific literature published in English, our current case is the first in which IgG4-related hypophysitis likely occurred as a result of a long-term history of IgG4-related systemic disease. We report this case herein and review the relevant literature.

Hypophysitis presented as inflammatory pseudotumor in immunoglobulin G4-related systemic disease

Immunoglobulin (Ig) G4-related systemic disease is a recently characterized entity. The best-known manifestation is pancreatitis. Other systemic involvements are also described. Three cases of this disease with hypophyseal involvement have been reported in the literature, all diagnosed clinically. We herein present the first case of IgG4-related hypophysitis diagnosed histopathologically. The patient is a 77-year-old Chinese man with a pituitary tumor. Histologic examination of the resected tumor showed hypophysitis with features of inflammatory pseudotumor. Clinical review showed history of pancreatitis and cholecystitis 4 years ago. The pancreatic biopsy and gall bladder specimens obtained previously had the same pathologic features of inflammatory pseudotumor. Immunohistochemistry highlighted abundant IgG4-positive plasma cells in all 3 specimens. Serum IgG4 level was also elevated. A diagnosis of IgG4-related systemic disease was confirmed. This is the first case of intracranial inflammatory pseudotumor shown to be associated with IgG4-related systemic disease.