免疫功能受损患者出现危及生命的胃肠道出血

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免疫功能受损患者出现危及生命的胃肠道出血

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获得性凝血因子（F）VIII抑制物较为罕见，但死亡率高达8%~22%。今天和大家分享的这篇病例，患者诊断为获得性FVIII抑制物，接受免疫抑制治疗后，出现巨细胞病毒（CMV）感染，随后发现CMV诱导形成假瘤伴大面积溃疡，患者最终因胃肠道和腹膜后广泛出血死亡。希望对您有所启发。

Life-Threatening Gastrointestinal Bleeding in an Immunocompromised Patient

免疫功能受损患者出现危及生命的胃肠道出血

Question

问题

A 79-year-old man presented to the hospital after several weeks of easy bruising and a syncopal episode. On admission he was noted to have a retroperitoneal hematoma requiring several transfusions. During initial evaluation his coagulation tests were noted to be abnormal, leading to the diagnosis of an acquired factor VIII inhibitor (FVIII; activity

患者，男性，79岁，就诊前几周总是容易发生瘀伤和晕厥。入院时，发现患者有一个腹膜后血肿，需要进行多次输血。但在对患者进行初步评估时，观察到患者的凝血试验结果异常，诊断为获得性凝血因子（F）VIII抑制物（FVIII；活性

He was admitted to our hospital several weeks later with a melena and fatigue. During this admission, he was noted to have new-onset pancytopenia (white blood cell count, 0.6K/μL; hemoglobin, 6.6 M/μL; platelets, 87K/μL). A broad workup for pancytopenia was initiated with normal vitamin B12, folate, and copper, and nondetectable hepatitis B and C virus, HIV, and Epstein–Barr virus. Cytomegalovirus (CMV) viral load was 213,508 IU/mL, for which he was started on IV ganciclovir.

几周后，患者因黑便和疲劳住院。住院期间，患者新发全血细胞减少症（白细胞计数，0.6K/μL；血红蛋白，6.6 M/μL；血小板，87K/μL）。对全血细胞减少症进行了全面检查，检查结果显示，维生素B12、叶酸和铜离子水平处于正常范围内，未检测到乙型肝炎和丙型肝炎病毒、人类免疫缺陷病毒（HIV）和EB病毒（又称人类疱疹病毒4型）。巨细胞病毒（CMV）载量为213,508 IU/mL，为此，患者开始了更昔洛韦静脉治疗。

Melena persisted and was associated with hemodynamic instability requiring transfer to the intensive care unit. Esophagogastroduodenoscopy and colonoscopy were performed. Esophagogastroduodenoscopy demonstrated 3 small nonbleeding duodenal ulcers with no high-risk stigmata. Colonoscopy demonstrated a 5- to 6-cm fungating, ulcerated, nonobstructing mass in the ascending colon with active bleeding (Figure A), which was firm on biopsy concerning for a malignancy.

患者的黑便症状一直存在，并与血流动力学不稳定相关，需要转至重症监护室。对患者进行了食管胃十二指肠镜检查及结肠镜检查。食管胃十二指肠镜检查显示存在3处小型非出血性十二指肠溃疡，无高危特征。结肠镜检查显示升结肠处有一个5~6 cm的蕈伞状、溃疡性、非梗阻性肿块伴活动性出血（图A），活检显示该肿块质地坚硬，考虑为恶性肿瘤。

Colonic mass histology demonstrated ulcer with many CMV viral inclusions but no definitive evidence of malignancy. The patient continued to have ongoing bleeding with accompanying hemodynamic instability despite correction of underlying coagulopathy and initiation of antiviral therapy. Given ongoing colonic bleeding, lack of therapeutic endoscopic options, and concern for possible underlying malignancy, the decision was made to proceeded with surgical resection of the colonic mass (Figure B).

该结肠肿块的组织学检查结果为溃疡和许多CMV病毒包涵体，但无明确证据证实为恶性肿瘤。虽然对基础性凝血病进行了治疗并开启抗病毒治疗，但患者仍存在持续性出血伴血流动力学不稳定。考虑到存在持续性结肠出血、缺乏内镜治疗选择以及对可能的潜在恶性肿瘤的担忧，决定接下来进行手术以切除结肠肿块（图B）。

What is most likely etiology of this colonic lesion?

这种结肠病变最可能的病因是什么？

Answer to: Image 3: CMV-Induced Pseudotumor

回答：图片3：CMV诱导形成的假瘤

The patient underwent an open hemicolectomy. The surgical specimen was negative for malignancy; however, it was consistent with a CMV-induced pseudotumor with extensive deep ulceration (Figure C) and CMV-infected cells in submucosal capillary endothelium (Figure D) involving the terminal ileum and cecum. Unfortunately, the patient eventually succumbed to his illness with the cause of death noted to be from extensive hemorrhage in his gastrointestinal tract and retroperitoneum on autopsy.

该患者接受了开放式半结肠切除术。手术切除的样本显示恶性肿瘤为阴性，但符合CMV诱导形成的假瘤伴大面积深度溃疡（图C）和涉及回肠末端和盲肠的黏膜下毛细血管内皮细胞的CMV感染（图D）。不幸的是，患者最终死亡，尸检发现死因为胃肠道和腹膜后广泛出血。

Although uncommon, CMV colitis can present with a large mass-like lesion in the colon. Reports of CMV-induced pseudotumor have be limited to cases reports, and predominantly occur in patients with AIDS or post-transplant patients on immunosuppressive therapy. The exact mechanism of pseudotumor formation is poorly understood; however, it is postulated that CMV invasion of vascular endothelial cells leads to vascular endothelial thickening with stromal and epithelial cell hypertrophy.

感染CMV的结肠炎虽然不是很常见，但可能会使患者结肠内出现大型肿块样病变。有关CMV诱导形成的假瘤仅出现在病例报告中，而且主要发生在艾滋病（AIDS）患者或接受免疫抑制治疗的移植后患者中。目前对于假瘤形成的确切机制尚不清楚，但是，可以推测，假瘤是因CMV侵入血管内皮细胞导致血管内皮增厚以及基质和上皮细胞肥大形成的。

CMV can affect the entire gastrointestinal tract from the esophagus to the rectum, although it seems to have an affinity for the right colon and the ileocecal valve, as was seen in our case. CMV-induced pseudotumors often respond to IV antiviral therapy and may even resolve completely. Surgery should be reserved for patients who fail to respond to medical therapy or those with colonic obstruction or refractory bleeding, which unfortunately was the case for our patient.

CMV可以影响从食管至直肠的整个胃肠道，但是似乎更容易感染右半结肠和回盲瓣，如本病例所示。CMV诱导形成的假瘤通常对抗病毒静脉治疗有反应，甚至有可能完全消失。而对药物治疗无反应或有结肠梗阻或难治性出血的患者，应进行外科手术治疗，本病例就是这种不幸的情况。

Acquired FVIII inhibitors are rare (1.3 cases per million people per year) and are associated with underlying illness in ≥50% of cases, namely connective tissues disorders, and less commonly solid and lymphoproliferative malignancies, which was a major factor in our decision to proceed with surgery. Patients often present with catastrophic bleeding episodes with a mortality as high as 8%–22% owing to a combination factors including delays in diagnosis and treatment, higher incidence in the elderly, and due to the severity of bleeding.

获得性FVIII抑制物较为罕见（1.3例/100万人/年），≥50%的病例与基础性疾病（即结缔组织疾病）有关，很少与实体瘤和淋巴细胞增生性恶性肿瘤有关，而本病例我们决定进行手术的一个主要因素就是怀疑恶性肿瘤。由于诊断和治疗上的延误、老年人中较高的发病率以及严重的出血等综合因素，患者常出现非常严重的出血事件，死亡率高达8%~22%。

Reference:

Berinstein JA, El-Dalati S, Chey WD. Life-Threatening Gastrointestinal Bleeding in an Immunocompromised Patient. Gastroenterology. 2021 Sep;161(3):e6-e7. doi: 10.1053/j.gastro.2021.01.227. Epub 2021 Feb 3. PMID: 33545144.

来源：柳叶新潮消化频道

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