中医辨证治疗IgG4相关性米库利奇病1例体会

<正>免疫球蛋白G4相关疾病(IgG4-related disease,IgG4-RD)是以一个或多个器官局灶弥散性炎性细胞浸润和(或)受累脏器肿大为特征的自身免疫性疾病,多累及胰腺、唾液腺、泪腺、腹膜后组织等多个器官或组织,表现为血清IgG4细胞水平明显增高(> 1.35 g·L^-1),以及典型的组织病理学改变包括IgG4⁺浆细胞浸润、席状纤维化等,其中累及唾液腺和泪腺的被称为米库利奇病(Mikulicz disease,MD)^[1-2]。目前,IgG4-RD的发病机制尚不明确,女性患者更容易出现浅表器官受累,常见MD、甲状腺疾病等;     

IgG4相关性疾病累及肾盂疑诊肾盂癌1例报告

本文报道1例IgG4相关性疾病(IgG4-RD)累及肾盂病例。患者体检发现左肾盂占位, CTU、MRI、PET-CT检查均考虑左肾盂癌并多发淋巴结转移, 行CT定位左肾盂穿刺活检, 结合血清IgG4水平, 最终临床确诊IgG4-RD。口服甲泼尼龙治疗后肾盂病灶缩小, IgG4水平下降。IgG4-RD为一种新近认识的可累及全身多器官的纤维炎性疾病, 肾盂受累时易误诊为肾盂癌。结合多器官受累可能、血清学检查、影像学特征以及穿刺病理等结果, 能够获得正确诊断。本病对糖皮质激素治疗反应良好, 但易复发。     

IgG4相关性疾病泌尿系统损害分析

目的 总结IgG4相关性疾病泌尿系统损害的临床特点,以其提高对该疾病的认识.方法 回顾性分析出现泌尿系统损害的IgG4相关性疾病患者6例的临床表现、实验室检查、影像学资料、病理表现、治疗及预后情况.结果 诊断为IgG4相关性疾病患者中6例存在泌尿系统损害,男女比例为4:2,中位年龄59岁(36～ 72岁),中位病程为10.5个月.除肾脏、输尿管受累外,所有患者均同时存在泌尿系统外的多器官受累.泌尿系统损害临床表现多样,包括肾功能异常、水肿和腹痛.所有患者均存在高球蛋白血症、血清IgG(中位值23.3 g/L)及IgG4亚型(中位值4227.0 mg/L)升高,肾小管源性蛋白尿;5例患者Scr明显升高(中位值237 μmol/L).影像学表现可分为4类:肾脏弥漫增大、CT多发低密度灶可伴不均匀强化灶、肾盂和(或)输尿管积水、肾脏萎缩.肾脏病理显示为弥漫纤维化伴肾间质大量淋巴细胞、浆细胞浸润的间质性肾炎表现,伴淋巴细胞、浆细胞IgG4免疫组化染色阳性.患者对中至大剂量糖皮质激素治疗反应良好,经治疗,临床症状改善,IgG、IgG4及Scr均明显降低.结论 IgG4相关性疾病泌尿系统损害临床表现多样化,多同时合并其他器官受累;肾组织病理学以IgG4阳性的淋巴细胞和浆细胞浸润的间质性肾炎为其突出特点;糖皮质激素治疗有效.     

中西医结合治疗IgG4相关性肾脏病4例报告并文献复习

<正>IgG4相关性疾病(IgG4-related diseases, IgG4-RD)表现为受累器官肿大纤维化、血清IgG4升高、组织大量IgG4(+)浆细胞浸润等，是免疫介导的炎症性疾病[1]。2004年始国外相继报道IgG4-RD可累及肾小管间质、肾小球、肾盂、输尿管等，称之为IgG4相关性肾脏疾病(Igg4-related renal diseases, IgG4-RKD)。目前糖皮质激素(以下统称激素)是首选药物，但复发率高，     

IgG4相关性肾小管间质肾炎一例报告

IgG4相关性疾病（IgG4-relateddisease,IgG4-RD）是一类以血清IgG4升高、组织中IgG4阳性浆细胞浸润及组织纤维化为特征的全身性疾病,可累及多系统多器官,并对类固醇激素治疗有效。IgG4-RD累及肾脏时,称之为IgG4相关性肾病（IgG4-relatedkidneydisease,IgG4一RKD）,肾损害的主要特征是肾小管间质肾炎（tubuloimerstitialnephritis,TIN）,故又有学者称之为IgG4相关性肾小管间质性肾炎（IgG4-relatedtubulointerstitialnephritis,IgG4-TIN）。但是该病除肾小管间质肾病外,尚可累及肾小球（以膜性肾病多见）,     

以鼻窦起病的IgG4相关性疾病临床报告1例

<正>IgG4相关性疾病（IgG4-related disease,IgG4-RD）是一种自身免疫性疾病,以多发脏器肿大、血清中IgG4升高为特点。组织病理特征为IgG4阳性浆细胞浸润、席纹状纤维化和闭塞性静脉炎,可累及腺体、眼眶、鼻窦、腹膜后、胰腺等多个脏器。虽然大多数IgG4-RD为系统性疾病,但是以鼻窦起病的IgG4-RD临床较少见。其临床表现多为鼻出血、鼻塞、流脓涕等,相对于其他部位的IgG4-RD而言,鼻腔鼻窦的IgG4-RD是一种较为少见的类型。     

以泪腺、颌下腺肿大为表现的IgG4相关性疾病1例

IgG4相关性疾病(IgG4-RD)是一种与IgG4相关的,累及多器官、多系统的慢性进行性自身免疫性疾病.本病主要表现为受累器官或组织的无痛性肿大,临床较少见.很多医生对本病的认识不足,导致部分患者得不到及时诊断,或进行了不必要的手术,极大影响了患者的生活质量.本文报道我院1例以泪腺、颌下腺肿大为表现的IgG4-RD,...     

自身免疫性胰腺炎诊治进展

自身免疫性胰腺炎（AIP）是近年来逐渐被人们认知的一种少见病，属于血清免疫球蛋白G4（IgG4）相关性疾病的一种，病理学表现以胰腺炎症和纤维化为主。自身免疫性胰腺炎的病人在影像学上显示出胰腺“腊肠样肿大”或局部肿块形成，并伴随大量IgG4阳性浆细胞浸润和席纹状纤维化，此类病人对类固醇治疗反应良好。该疾病可通过检测血清IgG4，影像学改变和组织病理学特征进行诊断与鉴别。目前其一线治疗药物是皮质类固醇激素，对于激素不耐受的高风险病人可给予利妥昔单抗。自身免疫性胰腺炎复发率很高，IgG4对于激素治疗疗效评判尚未形成共识，IgG4在疗效评价上价值有限，建议参考临床症状及影像学表现评估治疗效果。     

1型自身免疫性胰腺炎临床分析（附9例报告）

目的:总结1型自身免疫性胰腺炎(autoimmune pancreatitis, AIP)的临床特点及诊治经验。方法 :本研究对2012年10月至2018年10月复旦大学附属中山医院收治的1型AIP病人9例,回顾性分析临床表现和实验室、影像学、组织病理学检查以及治疗、预后。结果:9例1型AIP病例临床表现为黄疸、腹胀、腹痛、体重减轻和食欲下降。胰腺外受累器官为胆管、淋巴结、肾脏和腹膜后组织。9例IgG4均升高,8例2倍正常值上限。上腹部MRI检查以全胰肿大为主(7例),2例提示胰腺内占位,3例见胰周包膜样边缘。2例胰腺细针穿刺组织学检查未得出诊断。所有病人均行类固醇治疗,疗效较好。治疗初期内镜逆行胰胆管造影放置胆道塑料支架,分别出现肝脓肿和胆总管结石各1例。复发病人使用激素或激素联合免疫抑制剂仍获缓解。结论:1型AIP仅部分病人有典型影像学表现,需慎重诊断并系统评估,激素治疗有效。     

特发性腹膜后纤维化并发肾积水

目的:探讨特发性腹膜后纤维化(IRF)并发肾积水的临床特征.方法:报告12例IRF并发肾积水患者的临床资料.12例均以腰、腹痛为首发症状.B超均发现肾积水及输尿管病变,3例发现腹膜后肿块.腹部CT均发现腹膜后肿块,对肿块的大小和部位均能明确.术前诊断准确率为83.3%.10例行输尿管松解 大网膜包裹或腹腔移位术,1例逆行置人输尿管支架管,1例肾穿刺造瘘.后2例情况好转后,仍行手术治疗.结果:10例随访无复发,1例因同侧肾积水复发行二次治疗,1例因对侧肾积水而行二次手术.结论:腰、腹痛患者应考虑到特发性腹膜后纤维化的可能;B超对肾积水敏感,腹膜后肿块依赖腹部CT检查,两者联合应用有利于诊断.输尿管松解 大网膜包裹或腹腔移位术是主要的有效的治疗手段.单侧腹膜后纤维化患者,随访应同时注意对侧发病的可能.     

IgG4相关性肾病的临床病理特征分析

目的探究本中心中国人群IgG4相关性肾病的发病情况、临床病理特征及预后。 方法回顾性分析2010年1月至2019年1月在东部战区总医院国家肾脏疾病临床医学研究中心行肾穿刺活检患者的临床病理资料，对肾组织中有大量浆细胞浸润的患者，重新测定肾活检时血清IgG4水平及肾组织IgG4阳性浆细胞浸润数目，结合肾外表现，筛选出确诊为IgG4相关性肾病的病例，并分析IgG4相关性肾病的临床特点、病理特征及肾脏预后。 结果44 784例肾活检患者中有22例确诊为IgG4相关性肾病。IgG4相关性肾病最常表现为蛋白尿(86.4%)及肾功能不全(81.8%)，约68.2%患者存在肾外累及。高IgG血症、高IgG4血症、低补体血症的发生率分别为86.4%、84.2%、45.5%。肾脏组织学最常见的病理类型为IgG4相关间质性肾炎(90.9%)，其次为膜性肾病(13.6%)。肾间质席纹状纤维化、鸟眼样改变分别占40.9%、54.5%。22例患者中，21例接受糖皮质激素治疗，2例失访，余20例中位随访时间为12个月，9例肾功能好转，10例肾功能平稳，1例肾功能减退并进展至终末期肾病。 结论IgG4相关性肾病发病率低，好发于中老年男性，最常表现为肾功能不全及蛋白尿。半数以上的患者有肾外表现。高IgG血症、高IgG4血症和低补体血症是其血清学特征。最常见的肾脏病理类型为间质性肾炎；大量IgG4阳性浆细胞浸润、肾间质席纹状纤维化或鸟眼样改变是其典型的病理特征。糖皮质激素仍是IgG4相关性肾病治疗首选的一线药物。     

Renal involvement in IgG4-related disease

IgG4-RD may affect several organs including kidneys. The kidney is involved in approximately 20% of patient with IgG4-RD. The most common intrinsic kidney disease is tubulointerstitial nephritis (IgG4-TIN). Retroperitoneal fibrosis (IgG4-RPF) may induce obstructive acute renal failure. More rarely, IgG4-RKD can manifest as a glomerular disease, in particular as a membranous nephropathy (MN). It mostly affects middle-aged to elderly men and causes acute or chronic renal dysfunction, multiple hypodense lesions on CT-Scan and various extra-renal lesions. Increased serum IgG4 and hypocomplementemia are the most important serological findings for the diagnosis of IgG4-RD and thus should be systematically assessed when IgG4-RKD is suspected. Specific diagnosis criteria for IgG4-TIN including interstitial infiltration of IgG4-positive plasma cells, storiform fibrosis and tubular basement membrane immune complex deposits have been proposed. Corticosteroids are effective and remain the first-line therapy but relapses or severe forms could respond to immunosuppressive therapy.     

Recurrent Mastoiditis Mimics IgG4 Related Disease: A Potential Diagnostic Pitfall

IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied—tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4–IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection.     

IgG4-related disease

The term “IgG4-related disease” encompasses several disorders described many years ago under various designations depending on the organ or system involved (e.g., Mikulicz syndrome, Riedel's thyroiditis, and retroperitoneal fibrosis). The clinical presentation varies widely, as one or more organs may be affected, usually in the same region of the body and either synchronously or metachronously. The main targets are the pancreas, bile ducts, salivary glands, lachrymal glands, mediastinal lymph nodes, and retroperitoneum. IgG4-related disease is rare, with an estimated incidence of 0.2 to 1/100 000 in Japan and no available incidence data in occidental countries. Men older than 50 years are predominantly affected. Serum IgG4 levels are often greater than 1.35 g/L. Enlargement of the involved organs, which may be pseudotumoral, is due to a combination of infiltration by T cells and IgG4-expressing plasma cells, storiform fibrosis, and obliterative thrombophlebitis. Glucocorticoid therapy is effective but may be followed by relapses requiring the use of immunomodulating agents such as azathioprine, methotrexate and, more recently, rituximab. IgG4-related disease is not an autoimmune condition related to IgG4 autoantibodies, and neither does it involve immune complexes. Specific joint involvement has been reported in a very small number of patients.     

Les atteintes uro-néphrologiques au cours de la maladie associée aux IgG4

Hyper-IgG4 syndrome, or IgG4-related disease, is an emerging disorder, involving one or more organ(s), and characterized by “storiform” fibrosis and inflammatory lesions with a predominance of IgG4+ plasma cells and increased IgG4 serum levels. Since the first report of auto-immune pancreatitis, numerous organ lesions have been reported and have been found to occur in a same patient including: sialadenitis, dacryoadenitis, lymphadenopathy, liver and biliary tract involvement, and renal and retroperitoneal lesions. Renal involvement was first described in 2004 and usually presents as functional and/or morphological abnormalities. In most cases, renal pathological analysis reveals tubulointerstitial nephritis that is rarely associated with glomerular lesions. Retroperitoneal fibrosis is also a typical feature that may be associated with periaortitis or inflammatory abdominal aortic aneurysm. First line treatment is based on corticosteroid therapy. Short-term outcome is usually favorable. However, patients should be carefully monitored for relapses and long-term complications. Although the multiple organ lesions share common clinical, biological, radiological and pathological features, no consensus diagnostic criteria have yet been validated for IgG4-related disease. Ruling out differential diagnoses is thus mandatory. Our literature review provides nephrologists, urologists and pathologists with key elements that will help in the early diagnosis and proper management of this new and emerging disorder.     

18F-FDG PET/CT诊断腹膜后纤维化

目的探讨~(18 )F-FDG PET/CT诊断腹膜后纤维化(RPF)的价值。方法回顾性分析因RPF接受~(18 )F-FDG PET/CT检查的12例患者,分析其病灶形态、分布范围和葡萄糖代谢活性最大标准摄取比值(SUV_(max))。结果 12例患者中,7例为初诊患者,5例为治疗后患者。7例初诊RPF患者中4例为继发性,病因分别为IgG4相关疾病、乳腺癌和前列腺癌。12例患者均可见腹主动脉和/或髂血管旁软组织密度病灶,91.67%(11/12)患者可见输尿管受累。初诊RPF患者腹膜后病灶SUV_(max)(4.21±1.76)显著高于治疗后患者(1.46±0.25;P0.05)。依据PET/CT检查结果,3例有代谢活性病灶的特发RPF患者接受激素和/或他莫昔芬等免疫抑制治疗,4例具有活性病灶的继发RPF患者接受针对病因治疗;5例治疗后患者,3例继续当前激素维持剂量治疗,2例未接受其他治疗。结论 PET/CT可用于评价RPF病灶活性和分布范围。     

Idiopathic retroperitoneal fibrosis associated with IgG4-positive-plasmacyte infiltrations and idiopathic chronic pancreatitis

Idiopathic retroperitoneal fibrosis (IRPF) is an inflammatory fibrosclerosing condition, leading to renal failure by obstruction of the ureters. Idiopathic chronic pancreatitis associated with marked inflammatory infiltrates has recently been referred to as autoimmune pancreatitis (AIP), and infiltrating plasmacytes carrying immunoglobulin-gamma type 4 (IgG4) are relevant to its pathogenesis. The case is described herein of IRPF associated with subclinical pancreatitis that was most probably AIP in a 70-year-old man. Biopsy specimens of the retroperitoneal pseudotumor revealed a marked lymphoplasmacytic infiltration with dense fibrosis. Infiltrating plasma cells were immunoreactive for anti-IgG4 antibodies. Subsequent systemic examinations showed an extremely elevated serum IgG4 level and pancreatitis concordant with AIP. Following oral steroid administration, the serum IgG4 level normalized, although the appearance of the pseudotumor did not alter. Some AIP cases have been associated with idiopathic fibrosclerosing disorders including IRPF, but histological evidence of IgG4-related IRPF has rarely been provided.     

Inflammatory abdominal aortic aneurysm: close relationship to IgG4-related periaortitis

Inflammatory abdominal aortic aneurysm (AAA) is a member of a family of disorders referred to as "chronic periaortitis" together with retroperitoneal fibrosis. Retroperitoneal fibrosis is included in IgG4-related disease, which is characterized by numerous infiltrating IgG4-positive plasma cells and high serum IgG4 concentrations. However, the relationship between IgG4-related disease and inflammatory AAA has not been documented. In this study, we examined the clinicopathologic characteristics of inflammatory (10 cases) and atherosclerotic (22 cases) AAAs, based on the hypothesis that inflammatory AAA might be related to IgG4-related disease. Cases of inflammatory AAA could be classified into 2 groups based on immunostaining of IgG4. Four patients showed diffuse infiltration of abundant IgG4-positive plasma cells (IgG4-related cases), whereas the remaining 6 cases of inflammatory AAA and all cases of atherosclerotic AAA had only a few IgG4-positive plasma cells (non-IgG4-related cases). IgG4-related inflammatory AAA was pathologically characterized by the frequent infiltration of eosinophils, lymph follicle formation, perineural inflammatory extension, and inconspicuous infiltration of neutrophils compared with non-IgG4-related inflammatory AAA. Obliterative phlebitis, which is venous occlusion with inflammatory cell infiltration, is observed in all IgG4-related cases. In addition, serum IgG4 concentrations were significantly higher in IgG4-related inflammatory AAA (109 to 559 mg/dL, normal range: 4 to 110 mg/dL) than non-IgG4-related inflammatory AAA (32 to 59 mg/dL) and all atherosclerotic AAA (12 to 83 mg/dL). In conclusion, inflammatory AAAs might be classified into 2 groups: IgG4-related or nonrelated. The former might be one of the IgG4-related diseases, and could be included in IgG4-related periaortitis together with retroperitoneal fibrosis.     

Current approach to diagnosis and management of retroperitoneal fibrosis

Retroperitoneal fibrosis is characterized by fibrotic lesions around the abdominal aorta and common ileac artery causing ureteral obstruction. Secondary retroperitoneal fibrosis is associated with malignant disease, drugs, exposure to radiation and surgery. In contrast, the majority of retroperitoneal fibrosis is classified into idiopathic retroperitoneal fibrosis, for which immunological etiology has been suggested. Recently, idiopathic retroperitoneal fibrosis has been considered to be a spectrum of immunoglobulin G4-related disease, a systemic inflammatory disease, the concept of which has been developed during the past decade. In the management of retroperitoneal fibrosis, assessment of systemic lesions associated with immunoglobulin G4-related disease and the exclusion of secondary retroperitoneal fibrosis is mandatory. Histological examination of retroperitoneal lesions is desired for accurate diagnosis and management. Laparoscopic or open biopsy is often beneficial, although it is more invasive than needle biopsy. Treatment for idiopathic retroperitoneal fibrosis consists of meticulous glucocorticoid therapy based on that for immunoglobulin G4-related disease, which is expected to be highly effective. Ureteral obstruction is usually managed with conservative procedures, such as ureteral stenting or percutaneous nephrostomy. The goal of treatment for retroperitoneal fibrosis should be freedom from the stent/nephrostomy with withdrawal of the glucocorticoid in addition to salvage of renal function; however, conservative management does not always provide favorable outcomes. In contrast, aggressive surgical treatment, such as ureterolysis, can achieve the goal; however, the procedure is associated with high morbidity. Establishment of a consensus about treatment for idiopathic retroperitoneal fibrosis, including the optimal indications for the invasive surgical procedure and conservative management, is desired.     

Behandlungsergebnisse der primären und sekundären retroperitonealen Fibrose

Retroperitoneal fibrosis (RPF) is an uncommon inflammatory disease of the retroperitoneum leading to extensive fibrosis with consecutive obstruction of adjacent organs, namely the ureters. Since no consensus on the standard therapy exists, aim of the current study was to evaluate the outcome of 39 patients with RPF. Between 1986 and 1997 39 cases of RPF were diagnosed: 21 cases had primary RPF and 18 patients had secondary RPF after aortofemoral graft (n = 13), radiation (n = 2), or prior retroperitoneal surgery (n = 2). 21 patients demonstrated unilateral and 16 cases had bilateral hydronephrosis, in 2 patients no dilatation was observed. In 28 cases (n = 12 primary RPF, n = 16 secondary RPF) initial management consisted of DJ-stent placement, whereas in 11 cases (n = 9 primary RPF, n = 2 secondary RPF) percutaneous nephrostomy had to be placed. All patients received oral immunosuppressive agents (prednisolone 1 mg/kg, azathioprine 1 mg/kg/day) for 3 months before reevaluation was performed. In case of complete remission, immunosuppressive medication was continued for another 3 months, in case of stable disease or progression surgery was performed. In 26 cases (n = 15 primary RPF, n = 11 secondary RPF) ureterolysis with intraperitoneal displacement and omental wrapping was performed. 3 patients demonstrated complete remission after oral prednisolone/azathioprine; in 2 cases RPF presented as pelvic mass and was resected followed by immunosuppressive therapy, in another 2 cases bilateral ileal replacement of the ureters had to be performed and 4 cases remained on DJ-stents and nephrostomy, resp. Postoperatively, all patients with primary RPF were continued on immunsuppressive medication for another 3 months. After a follow-up of 6 to 120 months only 3 patients developed a retroperitoneal recurrence and were treated by unilateral nephrectomy or DJ stent placement (n = 2). Our data suggest that the combination of both immunosuppressive medication and surgical management results in an excellent longterm outcome in idiopathic retroperitoneal fibrosis with a recurrence rate of only 8%. Combination therapy should be considered as therapeutic option early in the course of the disease. Primary reconstructive surgery appears to be the most promising approach in secondary retroperitoneal fibrosis with a recurrence rate of only 5%; short external compression of the ureter might be managed by endoluminal balloon dilatation.