IgG4 sclerosing disease of the esophagus: a case-based review

Rheumatology International - IgG4-related disease (IgG4-RD) is an inflammatory and fibrosing disease which causes tumor-like swelling of organs and commonly mimics symptoms of malignancy. It has...     

An overlap of IgG4-related tubulointerstitial nephritis and microscopic polyangiitis-associated glomerulonephritis: a case-based review

Clinical Rheumatology - Because of some similarities in organ involvement, clinical manifestations, and histopathological features, IgG4-related disease (IgG4-RD) may occur concurrently with some...     

IgG4-related pleural disease with aortitis and submandibular glands involvement successfully treated with corticosteroid: case-based review

Rheumatology International - IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by increased serum IgG4 level, infiltration of lymphocytes and IgG4-positive (IgG4+)...     

IgG4相关性肺疾病二例并文献复习

目的 总结IgG4相关性肺疾病的临床特点及诊治经验,提高临床对该病的认识,减少误诊误治.方法 分析第二军医大学附属长海医院呼吸内科收治的两例IgG4相关性肺疾病的一般情况、临床表现、实验室检查、组织病理学、治疗及预后,并进行相关文献复习.结果 两例患者均为男性,血清IgG4水平均显著升高(2.25 g/L;10 g/L).1例肺部影像学呈实性结节型改变,并有回盲部受累,糖皮质激素治疗有效.另1例肺部影像学呈支气管血管束型改变,对糖皮质激素治疗依赖.文献复习69例IgG4相关性肺疾病,因呼吸道症状就诊者39例(56.5％),伴有肺外受累者41例(59.4％).48例检测了血清IgG4水平,均显著升高(307 ～ 52 500 mg/L).胸部影像学表现实性结节型35例(50.7％).31例(44.9％)患者接受了糖皮质激素治疗,预后良好.结论 IgG4相关性肺疾病是临床少见的免疫性疾病,临床表现缺乏特异性,临床诊断应综合分析其血清免疫学检查、影像学表现及组织病理学结果,糖皮质激素治疗效果良好.     

ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based review

Minocycline is a synthetic tetracycline-derived antibiotic with significant anti-inflammatory properties that may benefit patients with rheumatoid arthritis. Surprisingly, chronic exposure to minocycline can also cause a breach in immunologic tolerance resulting in a variety of autoimmune syndromes such as drug-induced lupus or autoimmune hepatitis. Vasculitis, most commonly resembling cutaneous polyarteritis nodosa, has also been seen in patients taking this drug. Herein, we present a case of biopsy-proven systemic vasculitis presenting as an ANA (+) ANCA (+) polyarteritis nodosa-like syndrome in a male patient who was taking minocycline for his acne for approximately 2 years. Patient initially presented with constitutional symptoms such as profound weight loss and fatigue, along with myalgias, oligoarticular arthritis, and livedo reticularis. About 2 months later, he developed a severe left testicular pain. Biopsy showed vasculitis complicated with the infarction of the left testis. Angiography revealed microaneurysms in the renal and splenic circulation. Stopping the offending drug, along with the short course of prednisone and hydroxychloroquine, resulted in prompt resolution of his symptoms. We additionally present a comprehensive review of biopsy-proven cases of vasculitis associated with chronic minocycline treatment focusing on its pathogenesis and clinical manifestations.     

IgG4-related sclerosing disease

Based on histological and immunohistochemical exami- nation of various organs of patients with autoimmune pancreatitis （AIP）, a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prosrate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AlP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4- related sclerosing diseases. This disease includes AlP, sclerosing cholangitis, cholecystitis, sialadenitis, retro-peritoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AlP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunos-taining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.     

Immunoglobulin G4-related cholangitis: a variant of IgG4-related systemic disease

IgG4-related sclerosing cholangitis as part of IgG4 systemic-related diseases is commonly associated with autoimmune pancreatitis. Major clinical manifestations of IgG4-related sclerosing diseases are apparent in the organs in which tissue fibrosis with obstructive phlebitis is pathologically induced. IgG4-related sclerosing cholangitis is included within the heterogeneous group of 'sclerosing cholangitis'. Sclerosing cholangitis may be associated with choledocholithiasis, infection or biliary malignancies. Sclerosing cholangitis of unknown etiology is called primary sclerosing cholangitis (PSC). Conservative therapy of PSC is usually unsuccessful, the disease involves extra- and/or intrahepatic biliary tree, and the end point of this disease is liver cirrhosis. Typically, PSC is identified at the age of 30 to 40 years, and the disease is frequently associated with inflammatory bowel diseases. On the other hand, IgG4-related sclerosing cholangitis is not associated with inflammatory bowel diseases. In patients with IgG4-related sclerosing cholangitis, a first symptom can be obstructive jaundice, whereas obstructive jaundice is rarely present in PSC. Clinically, patients with IgG4-related sclerosing cholangitis are older at diagnosis compared to patients with PSC. A typical diagnostic feature of IgG4-related sclerosing cholangitis is elevation of serum immunoglobulin G4. In patients with IgG4-related sclerosing cholangitis, response to steroid therapy is high; in patients with PSC corticosteroid therapy is unsuccessful. Histochemically abundant infiltration of IgG4-positive plasma cells is detected in the biliary duct wall. Histologically, we can identify dense lymphoplasmacytic infiltration of the bile duct wall, transmural fibrosis, lymphoplasmacytic infiltration and fibrosis in the periportal area of the liver - a typically obliterative phlebitis. The biliary epithelium is usually intact in contrast to PSC, where mucosal erosion is often present. Steroids are the first-choice therapy of IgG4-related sclerosing cholangitis. In the literature, cholangiocarcinoma in patients with IgG4- related sclerosing cholangitis was not described, whereas cholangiocarcinoma develops in up to 10-30% of patients with PSC.     

IgG4-related lung disease:analysis of 8 cases and literature review

正Objective To improve the understanding and treatment of Ig G4-related lung disease(Ig G-RLD).MethodsThe clinical characteristics,serum Ig G4 levels,pathological features,chest CT,therapy and prognosis of 8patients with Ig G4-RLD were retrospectively analyzed.These patients were admitted to the People’s Liberation Army General Hospital and the pathological diagnosis     

Hypocomplementemic urticarial vasculitis syndrome is associated with high levels of serum IgG4: a clinical manifestation that mimics IgG4-related disease

A 58-year-old Japanese woman presented with recurrent abdominal pain, chronic urticaria, and petechiae on her extremities, and hypocomplementemia, findings that were consistent with hypocomplementemic urticarial vasculitis syndrome (HUVS). A laboratory examination revealed that she had markedly elevated IgG levels (4,448 mg/dL; normal range, 870-1,700 mg/dL) with particularly high IgG4 levels (1,050 mg/dL; normal range, 48-105 mg/dL) and a high IgG4/total IgG ratio (0.22; normal range, 0.02-0.05). A skin biopsy demonstrated leukocytoclastic vasculitis with IgG4 deposition in the vascular lumen and vascular walls. A lymph node biopsy revealed reactive lymphoid hyperplasia with numerous IgG4-positive cells in the perifollicular area, but no sclerotic findings. A chromosomal analysis of an enlarged lymph node, without phytohemagglutinin (PHA) stimulation, demonstrated that one in every three analyzed cells had abnormalities, such as 44, XX, -13, add(15)(p11), -17, -17, and mar.     

Ophthalmic manifestations of IgG4-related disease: Single-center experience and literature review

Objectives

IgG4-related disease (IgG4-RD) is an inflammatory disorder responsible for fibrosing, tumefactive lesions that can involve the lacrimal gland as well as the extraocular muscles, orbital soft tissues, sclera, and local nerves. We reviewed IgG4-related ophthalmic disease (IgG4-ROD), including the natural history, pathology, and treatment, based on our center's experience and that reported in the literature.

Methods

We identified 27 patients with orbital manifestations from our IgG4-RD registry; six were excluded because no pathology was available for review. All 21 cases included had histopathologically confirmed diagnoses of IgG4-RD, 11 of which were of the orbital tissue. Other data were obtained by a retrospective medical records review. MEDLINE and PubMed literature searches in English were conducted to identify articles for a literature review on the topic.

Results

Patients with IgG4-ROD were predominantly male (57%) and had an average age at symptom onset of 50 years (range: 21–79 years). The lacrimal gland was the most commonly involved structure (62%). Most patients (71%) had bilateral disease and extra-orbital involvement (71%); these patients also had elevated serum IgG4 concentrations compared to those with unilateral disease and no extra-orbital disease. Ten patients improved following rituximab treatment.

Conclusions

Ophthalmic involvement is a common manifestation of IgG4-RD and can affect nearly every orbital structure. Consideration of IgG4-RD and accurate diagnosis by biopsy have important implications for prognosis and treatment following the distinction of this condition from the Sjögren syndrome (SjS), granulomatosis with polyangiitis (GPA, formerly Wegener's), sarcoidosis, lymphoma, infection, and other disorders. Rituximab holds promise as an effective steroid-sparing agent or therapy for steroid-resistant cases.     

IgG4相关间质性肺疾病

IgG4相关间质性肺疾病的提出是基于对系统性IgG4相关硬化性疾病的研究发现.IgG4相关间质性肺疾病的诊断需要临床医师结合临床-影像学-病理学特征疑及此病.IgG4相关间质性肺疾病对糖皮质激素治疗反应良好,监测随访对于发现复发是必要的.     

Treatment of IgG4-related disease

IgG4-related disease (IgG4-RD) is capable of causing great morbidity and even mortality if the condition remains undiagnosed or poorly treated, yet is typically a treatment-responsive disorder. Glucocorticoids have not been studied rigorously and practices with regard to dosing and duration of treatment remain largely empiric. In addition, IgG4-RD patients are often particularly susceptible to and intolerant of the deleterious effects of glucocorticoid therapy. B cell depletion with anti-CD20 monoclonal antibodies appears to be a rapid, effective means of obtaining disease control and limiting patients’ glucocorticoid exposure, but this option is frequently not available. Other therapies targeting the B cell lineage may also be efficacious, and one is under study. The means by which depletion or inhibition of B cells and their progeny ameliorate IgG4-RD is coming into focus now through careful mechanistic studies of samples from treated patients. The mechanistic understanding of IgG4-RD will bring an array of specific targets for therapeutic intervention. Plasmablast-directed therapy with a CD19 monoclonal antibody is currently in clinical trials. CD4?+ cytotoxic T lymphocytes and fibrosis, both observed nearly universally in the tissue of IgG4-RD patients, present two unexploited vulnerabilities in controlling and even reversing the effects of the disease. Further development of such therapies is a major goal of the next few years.     

The great mimicker: IgG4-related disease

IgG4-related disease is defined as a multi-organ systemic disorder with pathological findings affecting a wide range of organ systems. The condition unifies a large number of clinical diagnoses previously considered as being confined to single organ systems. At present, several issues related to its pathophysiology remained controversial, including the natural history of the disease, the pathogenic role of IgG4, and its use as a biomarker. Glucocorticoids are considered the treatment of choice for remission induction of IgG4-related disease manifestations; however, concerns regarding duration of therapy and management of refractory disease remained to be elucidated.     

IgG4相关性肺疾病1例及文献复习

目的提高对IgG4相关性肺疾病的临床特征、胸部影像学和病理组织学的认识。方法对1例经病理证实的IgG4相关性肺疾病的临床资料进行分析,并结合文献进行回顾总结。结果患者男,62岁,以胸腔积液起病,在外院先后行胸膜活检、胸腔镜肺活检等均未能明确诊断,后至我院行CT引导下经皮肺穿刺活检术,结果示活检组织内纤维组织增生伴淋巴细胞、浆细胞等炎症细胞浸润,免疫组化示大量浆细胞(+),IgG4阳性,浆细胞最密集计数约为40个/高倍视野,血清IgG4浓度示4.07 g/L(0.03 g/L~2 g/L)。诊断IgG4相关性肺疾病,给予糖皮质激素治疗,2个月后复查胸部CT示肺部病灶较前局部吸收、好转。结论IgG4相关性疾病是一种累及多器官、以血清IgG4水平升高、组织IgG4阳性浆细胞浸润为特点的淋巴浆细胞病。目前国内IgG4相关性肺疾病的报道很少,报道这一病例并进行文献复习有助于提高对IgG4相关性肺疾病的认识。     

Critical review of IgG4-related hypophysitis

Purpose

IgG4-related hypophysitis is a rare disease, with only 34 cases published in English (2015). Available short reviews may not present complete details of IgG4-related hypophysitis. We aimed to survey case reports of IgG4-related hypophysitis, including abstracts of scientific meetings, in English and Japanese.

Methods

We searched for information about IgG4-related hypophysitis in PubMed and Igakuchuozasshi (Japan Medical Abstracts Society). Among 104 case reports found, we reviewed 84 fulfilling Leporati’s diagnostic criteria.

Results

The mean ± ?SD age of onset was 64.2? ± ?13.9, 67.5? ± ?9.8, and 56.4? ± ?18.6 years for all subjects, men, and women, respectively. Men:women was 2.4:1. On magnetic resonance imaging, pituitary, stalk, and pituitary-stalk mass were observed at frequencies of 14.3, 21.4, and 64.3%, respectively. Manifestations were anterior hypopituitarism in 26.2% (22 cases), central diabetes insipidus in 17.9% (15 cases), and panhypopituitarism in 52.4% (44 cases). The median level of serum IgG4 was 264.5 mg/dL for all subjects, 405 mg/dL for men, and 226 mg/dL for women. The mean number of IgG4-related systemic diseases was 2.7? ± ?1.5 in all subjects, 3.0? ± ?1.5 in men, and 1.8? ± ?1.1 in women. Among the IgG4-related diseases, retroperitoneal fibrosis was the most frequent (26.2%), followed by salivary gland diseases (25%). Glucocorticoid therapy was generally effective, except for two cases that received replacement doses. There were significant differences between sexes in terms of age, serum IgG4 levels, and number of IgG4-related diseases.

Conclusion

IgG4-related hypophysitis may have different clinical characteristics between genders. This survey may lack some information because the Japanese abstracts did not contain certain details.

     

Vasculitis beyond aortitis in IgG4-related disease (IgG4-RD): case report and review of the literature

Clinical Rheumatology - IgG4-related disease (IgG4-RD) can affect almost every tissue/organ. Vascular involvement in the setting of IgG4-RD is increasingly being recognized with most of the cases...