1、IgG4相关性疾病的影像改变福建医科大学附属第一医院 影像科 胡建平.IgG4相关性疾病的历史及概念相关性疾病的历史及概念o 1961年 Sarles 首次报道有自身免疫特征的胰腺慢性炎症硬化。o 1995 年 Yoshida 正式提出AIP概念。o 2001年 Hamano 指出IgG4水平升高对AIP有重要诊断及鉴别诊断意义。o 2003年Kamisawa发现AIP患者胰腺外器官或组织(如胆道、腹膜后、唾液腺等)内亦见相同的病理表现，引入了IgG4相关自身免疫性疾病概念。o 2010年日本专家达成共识：将此类疾病定义为IgG4相关性疾病。IgG4相关性疾病o 累及多器官或组织的慢性进行性自
2、身免疫性疾病。o 该疾病以血清IgG4升高及IgG4+浆细胞广泛浸润多器官或组织为特征，其临床谱广泛。o 血清IgG4细胞水平显著增高(1350mgL),IgG4阳性淋巴细胞在组织中浸润(IgG4阳性淋巴细胞占淋巴细胞的50以上)。IgG4相关性疾病o 特征性病理改变为组织及多个器官中广泛的IgG4阳性淋巴细胞浸润，进而导致硬化和纤维化；o 一个或多个器官或组织肿胀增大，似肿瘤性；o 对糖皮质激素治疗反应良好。IgG4相关性疾病o 中老年男性好发，临床表现取决受累器官或组织。 胰腺(自身免疫性胰腺炎) 胆道（IgG4相关性硬化性胆管炎） 肾(间质性肾炎) 肺(间质性肺炎) 头颈部(唾液腺和泪腺
3、/垂体/眼眶/脑膜) 其他器官(心血管系统/胃肠道/腹膜后间隙)自身免疫性胰腺炎（autoimmune pancreatitis，AIP)o IgG4相关性疾病在胰腺的局部表现，受累器官见大量淋巴、浆细胞及IgG4阳性细胞浸润。o 以胰腺淋巴细胞及浆细胞浸润并发生纤维化、影像学表现胰腺肿大和胰管不规则狭窄、血清IgG4水平升高、类固醇激素疗效显著为特征。o 国外报道AIP病例数约占同期CP的2%-10%，我国报道比例3.6%-9.7%。男女比例约2:1，多见于老年人，大部分患者初次发病年龄超过50岁，但也可于青少年期发病。o 易被误诊为胰腺癌，因疑诊胰腺癌而行手术切除最常见的良性病变，约占所有
4、胰十二指肠切除术的2.5左右。自身免疫性胰腺炎（autoimmune pancreatitis，AIP)自身免疫性胰腺炎（autoimmune pancreatitis，AIP)o 早期临床症状轻微而无特异性，故早期诊断比较困难。o 可有轻微腹痛、周身不适、四肢乏力、恶心、厌食等症状，部分患者有阻塞性黄疸(多由于胰腺头部炎症肿胀压迫远端胆管导致狭窄所致)。影像学表现o 形态学改变 弥漫型：弥漫肿大呈腊肠样，小叶轮廓消失，边界清楚，胰周炎症或纤维化表现为环形影或“晕征”。局灶型：局灶性肿块。胰头常见，边界清晰，部分见环形或“晕征”。多灶型；多发的肿块样表现。 o CT上表为低密度，MRIT1WI
5、低信号， T2WI信号轻度增高，早期强化不明显，均匀或不均匀延迟强化；胰周环形影呈低密度，T1WI及T2WI低信号。o 胰管弥漫性、不规则狭窄，狭窄胰管无梗阻或轻度扩张胰腺段胆总管可见不规则狭窄。Different patterns of autoimmune pancreatitisVlachou et al， RadioGraphics 2011; 31:13791402 Vlachou et al， RadioGraphics 2011; 31:13791402 Diffuse autoimmune pancreatitis in a 75-year-old manFollow-up C
6、T image obtained 8 months later, after steroid treatment.F-43，间断上腹部疼痛，肝酶升高，胰管扩张；实验室检查：，间断上腹部疼痛，肝酶升高，胰管扩张；实验室检查：IG4/IG2升升高，脂肪酶升高；高，脂肪酶升高；CEA,CA199正常正常M-75，上腹部疼痛，上腹部疼痛.focal autoimmune pancreatitis Kawamoto et al RadioGraphics 2008; 28:157170诊断标准o 2002年 日本胰腺学会首次提出AIP诊断标准。o 2006年 日本、韩国、美国 发布AIP诊断标准。o 2
7、010年年 国际胰腺协会国际胰腺协会 AlP诊断标准国际诊断标准国际共识。共识。o 2012年年 我国自身免疫性胰腺炎共识意见。我国自身免疫性胰腺炎共识意见。2010年 AlP诊断标准国际共识o 诊断依据包括影像学(细分为胰腺实质影像学和胰管影像学)、血清学、胰腺外器官受累、组织病理学和诊断性激素治疗等5个方面。o 特点：强调胰腺实质影像学检查特点：强调胰腺实质影像学检查(CT/MRI)在在AlP诊断中的首要地位。诊断中的首要地位。o 实验室检查指标仅有IgG4一项。o 评价诊断性激素治疗效果的指标主要依靠影像评价诊断性激素治疗效果的指标主要依靠影像学，实验室检查指标不再作为监测指标。学，实验
8、室检查指标不再作为监测指标。 患者有典型影像学征患者有典型影像学征象，且有实验室检查或胰象，且有实验室检查或胰腺外受累证据，即可诊断腺外受累证据，即可诊断AIP，可行激素治疗。，可行激素治疗。 如影像学不典型，需如影像学不典型，需除外胰腺癌，再结合实验除外胰腺癌，再结合实验室检查、组织病理学证据室检查、组织病理学证据做出诊断。做出诊断。 如行诊断性激素治疗，如行诊断性激素治疗，必须除外胰腺癌，疗程不必须除外胰腺癌，疗程不长于长于2周；复查影像学提周；复查影像学提示胰腺或胰腺外病变明显示胰腺或胰腺外病变明显好转者支持好转者支持AIP诊断。诊断。IgG4相关性硬化性胆管炎o 最常累及的部位为胰腺段
9、胆总管；o 临床表现主要为梗阻性黄疸、体质量减轻及腹部不适等，并常合并AIP ；o 与原发性硬化性胆管炎在临床及影像表现方面均有重叠，故两者鉴别困难。IgG4相关性硬化性胆管炎o 影像学所见 典型表现为长且连续性的胆道狭窄，狭窄前胆道常可见扩张； 胆道壁呈对称性的环周增厚增厚的胆道壁增强扫描可见强化； 胆囊受累时表现为胆囊壁弥漫性增厚，增强延迟强化。Follow-up MRCP image obtained 2 years later, after steroid therapy。A 61-year-old man with biopsy proven IgG4-related scleros
10、ingcholangitis mimicking cholangiocarcinoma.diagnosis of IgG4-related disease following cholecystectomyA 56-year-old man with intrahepatic IgG4-related sclerosing cholangitisIgG4相关性肾病o 肾脏是IgG4相关性疾病另一常见累及的器官，临床表现主要为蛋白尿、血尿及肾功能异常等。o 病理特征是间质性肾炎、纤维化伴间质内多发斑片或弥漫的淋巴浆细胞浸润。其极少累及肾小球o 常合并AIP，如无合并AIP，与其他类型间质性肾炎鉴
11、别困难。o 临床表现随糖皮质激素治疗而好转。IgG4相关性肾病的影像学表现o 4种表现类型： 圆形或楔形的肾皮质结节 肾外周皮质病变 肿瘤样病变 肾盂受累o 肾皮质病变常多发并双肾受累，单发病灶少见。o 单发肿瘤样表现与肾肿瘤鉴别困难。o 肾盂受累表现肾盂壁弥漫性增厚，腔内表面光滑。IgG4相关性肾病的影像学表现o CT平扫病灶常为低密度，部分可无明显异常表现，增强扫描早期与肾实质相比呈低密度，延迟扫描见轻度强化。o 经治疗后，部分小病灶会消失但大部分病灶会形成疤痕残留于皮质。Vlachou et al， RadioGraphics 2011; 31:13791402 M. Kawano Cl
12、in Exp Nephrol (2011) 15:615626Takahashi et al Radiology: Volume 242: Number 3March 2007Takahashi et al Radiology: Volume 242: Number 3March 2007M. Kawano Clin Exp Nephrol (2011) 15:615626Sunchan Kim, Korean J Urol 2013;54:209-211M. Kawano Clin Exp Nephrol (2011) 15:615626男，男，58岁岁,外院检外院检查发现右肾占位。查发现右
13、肾占位。2013年年1月月CT2013年年7月月CT女女 43岁；岁；纳差、恶心、皮肤巩膜黄染2个月。IgG4相关间质性肺疾病o 多数患者为中老年男性。o 多数肺IgG4相关性肺疾病伴有或继发自身免疫性胰腺炎，但也有单独累及肺部的报道。IgG4相关间质性肺疾病o IgG4相关性肺疾病的影像学模式： 肺泡间质型，伴有蜂窝样变、支气管扩张和弥漫性磨玻璃影的改变； 支气管血管束和小叶间间隔增厚型； 实性结节或团块样损害型； 以多发的圆形磨玻璃影为特征的圆形磨玻璃影型。Inoue et al Radiology: Volume 251: Number 1April 2009；13个caseSchema
14、tic of four types of IgG4-related lung disease: (a) solid nodular, (b) round-shaped GGO,(c) alveolar interstitial, and (d) bronchovascularInoue et al Radiology: Volume 251: Number 1April 2009(a, b) Thin-section CT scans of left lung in a 76-year-old woman (case 3) with IgG4-related lung disease demo
15、nstrate a solid nodule in the left upper lobe (black arrow). This nodule is accompanied by perinodularspiculation. DiffuseGGOis also shown in the left upper lobe separated by a solid nodule (white arrows).(a d) Thin-section CT scans in a 43-year-old man (case 6) with IgG4-related lung disease.Multip
16、le GGOs are shown in both lungs. Each lesion is well defined and round shaped (arrow).(a, b) Thin-section CT scans in a 59-year-old man (case 7) with IgG4-related lung disease show honeycombing in both lower lobes (black arrows). Bronchiectasis is also observed in both lower lobes (white arrows). Di
17、ffuse GGOs are found in both middle and lower lobes.(a, b) Thin-section CT scans in a 59-year-old man (case 9) with IgG4-related disease demonstrate thickening of bronchovascular bundles of the right lung (white arrows). Mild thickening of the interlobular septa is also noted (black arrows).(a, b) T
18、hin-section CT scans in a 59-year-old woman (case 11) with IgG4-related lung disease reveal multiple small nodules in both lungs (white arrows). These nodules distribute in the centrilobular areas. Mild interlobular septal thickening is also identified (black arrows).IgG4相关性疾病头颈部改变o IgG4相关性桥本甲状腺炎o 唾
19、液腺和泪腺(米库利兹病)o 眼眶(炎性假瘤)o 垂体(垂体机能减退综合症)o 脑膜(硬脑膜炎)IgG4-related disease in a 58-year-old woman. (a) Coronal contrast-enhanced CT scan shows diffuse symmetric swelling of the submandibular glands (arrows). Low-attenuation lesions (arrowheads) are incidentally noted in the thyroid gland. (b, c) Axial unen
20、hanced (b) and contrast-enhanced (c) CT scans demonstrate diffuse low attenuation of the thyroid gland with poor enhancement (arrowheads), findings that are suggestive of IgG4-related disease.IgG4-related disease (hypophysitis) in a 56-year-old man. (a) Coronal T2-weighted MR image demonstrates bila
21、teral swelling of the parotid glands with low-signal-intensity infiltration (arrows). (b) Coronal contrast-enhanced fat-suppressed T1-weighted MR image shows the lesions with homogeneous enhancement (arrows). (c) On a sagittal contrast-enhanced T1-weighted MR image, thickening of the pituitary stalk
22、 (arrowhead) is incidentally noted.Mikulicz disease in a 67-year-old man. Biopsy revealed IgG4-related sclerosing disease.Dacryoadenitis in a 68-year-old woman. Unilateral dacryoadenitis can be difficult to differentiate from a lacrimal tumor with imaging alone; however, IgG4- related dacryoadenitis
23、 was confirmed at surgical resection. A 42-year-old man with Mikuliczs disease. Contrast-enhanced coronal (left, centre) and axial (right) CT images show diffuse enlargement of the homogeneously enhancing lacrimal (black arrows), parotid, and submandibular glands, respectively (black asterisks). The
24、 same patient had biopsy-proven IgG4-related sclerosing cholangitis.Biopsy of a left lower eyelid mass (not shown) and elevated serum levels of IgG4 were used to establish the diagnosis. Histopathological diagnosis of IgG4-related disease was made following biopsy of the periorbital masses.A 37-year
25、-old man with IgG4-related pituitary infundibulo-hypophysitis and hypertrophic pachymeningitis (same patient as in the top image of Fig 11). Contrast-enhanced axial T1-weighted MRI images reveal (top) enlargement of the enhancing pituitary stalk (white arrow) and (bottom) focal dural thickening with
26、in the floor of the middle cranial fossa on the left side (white arrow).其它器官受累o IgG4相关性疾病累及腹膜后组织多导致腹膜后纤维化；o IgG4相关性疾病累及血管时表现多样，可包括主动脉炎、主动脉周围炎、炎性主动脉瘤等；o IgG4相关性疾病与炎症性肠病之间的相关性目前尚不明确。有研究发现，IBD在AlP病人中的发病率为6一17 ，是普通人群发病率的1215倍Sclerosing mesenteritis in a 73-year-old man.Follow-up CT image, obtained 3 mon
27、ths later after high-dose oral steroid therapyParavertebral mass and periaortitis in a 55-year-old man.Histopathological diagnosis of IgG4-related disease was made following imaging guided biopsy of the paravertebral soft tissue.A 52-year-old man with coronary artery involvement in IgG4-related dise
28、aseContrast-enhanced CT scans (early phase) of IgG4-related perivascular lesion in 55-year-old man .) A paravertebral mass (arrow) was also diagnosed; at needle biopsy, it was diagnosed as IgG4-related disease.(a, b) Contrast-enhanced CT scans (early phase) of IgG4-related perivascular lesion in79-y
29、ear-old-man (case 14) and (c, d) histologic features. Contrast-enhanced CT scans(early phase) of IgG4-related perivascular lesion in 70-year-old manAn 18-year-old man with IgG4-related autoimmune pancreatitis. Contrast-enhanced axial (top) and coronal (bottom) CT images demonstrate diffuse mild colonic wall thickening (white arrows).Colonoscopy confirmed the presence of a pancolitis总结o IgG4相关性疾病是最近才被认识的累及多器官或组织的慢性进行性自身免疫性疾病；o 累及器官组织广泛，临床表现无特征性，主要特征血清IgG4 水平增高；组织病理学特征为病变组织弥漫性淋巴浆细胞浸润、纤维化以及大量IgG4 阳性的浆细胞；o 糖皮质激素治疗反应良好。早期正确诊断及治疗可以避免一些不必要的有创治疗；o 某些器官组织受累时会出现一些相对特征的影像学表现。谢谢.
