pernicious anaemia

恶性贫血
  • 文章类型: Journal Article
    胃类癌是一种罕见的胃恶性肿瘤,约占所有胃肠神经内分泌肿瘤(NET)的7%。虽然大多数胃NETs(gNETs)通过上内窥镜直接可视化很容易看到,大约25%的胃类癌是不可见的,因为它们位于身体和眼底的胃粘膜下区域。位于粘膜内区域的gNETs可以通过胃标测来识别;这可以通过从胃窦进行随机胃活组织检查来完成,身体和眼底。我们报告了一例高分化的胃NET1型萎缩性胃炎,在上内镜和病理免疫组织化学染色中被诊断出。
    结论:该病例强调并非所有gNETs在直接内镜下可见。了解不同类型的gNET至关重要。了解gNETs的类型和大小都会影响治疗意义和预后。
    Gastric carcinoid is a rare type of gastric malignancy accounting for around 7% of all gastrointestinal neuroendocrine tumours (NETs). While most gastric NETs (gNETs) are readily visible through direct visualisation by upper endoscopy, around 25% of gastric carcinoids are invisible because they are located in the submucosal gastric regions of the body and fundus. gNETs located in the intra-mucosal areas can be identified by gastric mapping; this can be done by taking random gastric biopsies from the antrum, body and fundus. We report a case of a well-differentiated gastric NET type 1 with atrophic gastritis diagnosed on upper endoscopy and pathological immunohistochemistry staining.
    CONCLUSIONS: The case highlights that not all gNETs are visible under direct endoscopic visualisation.It is essential to understand the different types of gNETs.Understand that both type and size of gNETs impact therapeutic implications and prognosis.
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  • 文章类型: Case Reports
    色素沉着过度是维生素B12缺乏的公认标志,在补充维生素后可以解决。我们介绍了一名58岁的女性,患有神经精神症状,她的手脚逐渐变黑。诊断为恶性贫血继发的维生素B12缺乏症,补充维生素后,她的症状和色素沉着得以解决。临床医生应考虑维生素B12缺乏在掌底色素沉着的鉴别诊断,因为早期治疗可以避免这些患者的永久性残疾。
    Hyperpigmentation is a recognized sign of vitamin B12 deficiency that resolves after vitamin repletion. We present the case of a 58-year-old female with neuropsychiatric symptoms who developed progressive darkening of her hands and feet. A diagnosis of vitamin B12 deficiency secondary to pernicious anemia was made and her symptoms and hyperpigmentation resolved following vitamin repletion. Clinicians should consider vitamin B12 deficiency in the differential diagnosis of palmoplantar hyperpigmentation, as early treatment can avert permanent disability in these patients.
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  • 文章类型: Journal Article
    背景:维生素B12缺乏主要与恶性贫血有关,多发性神经病,和脊髓疾病,但是关于它与幻觉的关联的出版物正在增加。
    方法:我在PubMed中对这些幻觉进行了系统的文献检索,PsycINFO,和谷歌学者,直到2023年7月1日。
    结果:搜索产生了1960年至2023年之间发表的50个案例研究。其中描述的幻觉本质上主要是视觉和/或听觉的,20%被指定为复杂的,化合物,或全景。它们通常在维生素B12相关的神经精神疾病如痴呆的背景下被描述,谵妄,癫痫,精神病,分裂情感障碍,双相情感障碍,抑郁症,紧张症,或者强迫症.在这种疾病的背景下,它们往往首先出现,并且通常似乎是第一个消失的钴胺素治疗。平均2个月内,因此,75%的病例获得了全部改善,其余25%的病例获得了部分改善.值得注意的是,四分之一的病例涉及治疗抗性幻觉,在钴胺素单一疗法下完全消退,而维生素B12缺乏的其他神经精神表现在60%的治疗病例中消失。只有32%的病例涉及并发恶性贫血。这表明维生素B12缺乏的感知和血液学症状存在两个独立或不同的途径。
    结论:鉴于一般人群中维生素B12缺乏的高患病率,这里提出的发现应该非常谨慎地解释。尽管如此,它们为临床实践中的进一步研究和实验应用提供了线索。鉴于最近素食主义的普及和一氧化二氮(笑气)的娱乐性使用的增加,这可能尤其相关。都是维生素B12缺乏的危险因素。
    BACKGROUND: Vitamin B12 deficiency is primarily associated with pernicious anaemia, polyneuropathy, and spinal-cord disease, but publications on its association with hallucinations are on the rise.
    METHODS: I carried out a systematic literature search on these hallucinations in PubMed, PsycINFO, and Google Scholar, up until July 1, 2023.
    RESULTS: The search yielded 50 case studies published between 1960 and 2023. The hallucinations described therein are predominantly visual and/or auditory in nature, with 20% being specified as complex, compound, or panoramic. They are often described in the context of vitamin B12-related neuropsychiatric conditions such as dementia, delirium, epilepsy, psychotic disorder, schizoaffective disorder, bipolar disorder, depressive disorder, catatonia, or obsessive-compulsive disorder. In the context of such disorders, they tend to appear first and also often appear to be the first to disappear with cobalamin treatment. Within an average of 2 months, full amelioration was thus obtained in 75% of the cases and partial amelioration in the remaining 25%. Remarkably, a quarter of the cases involved therapy-resistant hallucinations that fully resolved under cobalamin monotherapy, while other neuropsychiatric manifestations of vitamin B12 deficiency disappeared in 60% of the treated cases. Only 32% of the cases involved comorbid pernicious anaemia. This suggests that two separate or diverging pathways exist for perceptual and haematological symptoms of vitamin B12 deficiency.
    CONCLUSIONS: In the light of the high prevalence rate of vitamin B12 deficiency in the general population, the findings here presented should be interpreted with great caution. Nonetheless, they offer cues for further research and experimental application in clinical practice. This may be especially relevant in light of the recent increase in the popularity of vegetarianism and the recreational use of nitrous oxide (laughing gas), which are both risk factors for vitamin B12 deficiency.
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  • 文章类型: Journal Article
    目的:我们的目的是评估患有一级抗体缺乏症(PAD)的人群的胃肠道癌症风险及其与自身免疫性和炎症性胃肠道疾病风险的关系。
    方法:调查2010年至2018年法国国家住院数据库,我们确定了12,748名PAD患者和38,244名对照非暴露者。我们使用条件逻辑回归进行了多个暴露-非暴露研究。
    结果:与未暴露的患者相比,PAD患者发生原位胃癌的风险增加(比值比(OR)=10.5[95%CI2.2;50.5]),胃恶性肿瘤(OR=3.2[95%CI2.2;4.4])和结直肠癌(OR=1.2[95%CI1;1.5])。PAD患者的恶性贫血风险也增加(OR=8|95%CI5.6;11.5),克罗恩病(OR=4.4[95%CI3.5;5.6]),溃疡性结肠炎(OR=2.9[95%CI2.4;3.6])和乳糜泻(OR=13.3[95%CI9.1;19.5])。在胃癌患者中,PAD患者发生恶性贫血的风险增加(OR=8.4[95%CI1.5;215];p=0.01),但与幽门螺杆菌感染无关.
    结论:PAD患者患胃癌的风险特别高,与恶性贫血相关的原位胃癌的风险显著。它支持对这些患者进行早期内镜筛查的指征。
    OBJECTIVE: We aimed to assess gastrointestinal cancers risks in a large cohort of individuals with primary antibody deficiency (PAD) and their association with risk of autoimmune and inflammatory gastrointestinal diseases.
    METHODS: Investigating a French national database of inpatient admissions between 2010 and 2018, we identified 12,748 patients with PAD and 38,244 control non-exposed individuals. We performed multiple exposed-non-exposed studies using conditional logistic regression.
    RESULTS: In comparison with non-exposed patients, PAD patients had increased risk of in situ gastric carcinoma (Odds Ratio (OR) =10.5 [95 % CI 2.2; 50.5]), malignant gastric tumor (OR=3.2 [95 % CI 2.2; 4.4]) and colorectal cancer (OR=1.2 [95 % CI 1; 1.5]). PAD patients had also increased risk of pernicious anaemia (OR=8 |95 % CI 5.6; 11.5]), Crohn\'s disease (OR= 4.4 [95 % CI 3.5; 5.6]), ulcerative colitis (OR=2.9 [95 % CI 2.4; 3.6]) and coeliac disease (OR=13.3 [95 % CI 9.1; 19.5]). Within patients with gastric cancer, those with PAD had increased risk of pernicious anaemia (OR=8.4 [95 % CI 1.5; 215]; p = 0.01) but not of H. pylori infection.
    CONCLUSIONS: Risk of gastric cancer is particularly high in PAD patients and notably risk of in situ gastric carcinoma in association with pernicious anaemia. It supports indication of early endoscopic screening in these patients.
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  • 文章类型: Case Reports
    背景:假血栓性微血管病(假血栓性微血管病(TMA))是B12缺乏的罕见表现。重叠特征,如LDH/总胆红素升高,血红蛋白/触珠蛋白/血小板低,可能暗示血栓性血小板减少性紫癜(TTP),导致可避免的程序/治疗。
    方法:一名患有甲状腺功能减退的36岁女性最初因疲劳而就诊,心悸,头昏眼花,和呼吸困难超过3个月的持续时间,被发现有5.7g/dL的血红蛋白。她在急诊室接受了两个打包的红细胞单位,随后出院,接受了门诊随访和经验性口服铁剂。在她的后续访问中,她被发现容易受伤,牙龈出血,和溶血性贫血引起的全身性虚弱(平均红细胞体积(MCV)90fL,触珠蛋白<8mg/dL,LDH>4,000U/L,CBC上的血吸虫增多)和血小板减少52K/uL。由于PLASMIC得分为6并怀疑TTP,她被转移到我们的设施,并接受了3个周期的血浆置换和泼尼松治疗,但当ADAMTS13水平恢复正常时,她停止治疗.虽然患者的B12水平正常,进一步检测显示固有因子抗体(IF-Ab)阳性,MMA水平升高1.56umol/L。用钴胺素替代导致实验室和症状正常化。
    结论:由于与TTP的几个重叠特征,包括正常B12和正常MCV,因此及时诊断假性TMA异常具有挑战性。由于IF-Ab干扰化学发光免疫测定,因此在恶性贫血中B12水平可能会出现正常。分裂细胞在自动细胞计数器中降低MCV。较低的网织红细胞指数(<2%),存在未成熟/大血小板和泪滴细胞,升高的MMA和较高的LDH(>2500)指示B12缺乏。
    BACKGROUND: Pseudo-thrombotic microangiopathy (pseudo- thrombotic microangiopathy (TMA)) is a rare presentation of B12 deficiency. Overlapping features like elevated LDH/total bilirubin with low haemoglobin/haptoglobin/platelets could deceivingly suggest thrombotic thrombocytopenic purpura (TTP) resulting in avoidable procedures/treatments.
    METHODS: A 36-year-old female with hypothyroidism initially presented to clinic with fatigue, palpitations, lightheadedness, and dyspnoea over a 3-month duration and was found to have a haemoglobin of 5.7 g/dL. She received two packed red blood cell units in the emergency room and subsequently discharged with outpatient follow-up and empiric oral iron. During her follow-up visit, she was found to have easy bruisability, gum bleeding, and generalized weakness from hemolytic anaemia (mean corpuscular volume (MCV) 90 fL, haptoglobin <8 mg/dL, LDH >4,000 U/L and schistocytosis on CBC) and thrombocytopenia of 52 K/uL. Due to PLASMIC score of 6 and suspicion for TTP, she was transferred to our facility and tr eated with three cycles of plasma exchange and prednisone but were discontinued when ADAMTS13 levels returned normal. While the patient had normal B12 levels, further testing revealed positive intrinsic factor antibodies (IF-Ab) and an elevated MMA level of 1.56 umol/L. Replacement with cobalamin led to normalization of labs and symptoms.
    CONCLUSIONS: Timely diagnosis of pseudo-TMA was exceptionally challenging due to several overlapping features with TTP including normal B12 and normal MCV. B12 levels may falsely appear normal in pernicious anemia due to IF-Ab interference with chemiluminescent immunoassay. Schistocytes lower the MCV in automated cell counters. Lower reticulocyte index (<2%), presence of immature/large platelets and teardrop cells, elevated MMA and a higher LDH (>2500) are indicative of B12 deficiency.
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  • 文章类型: Journal Article
    维生素B12水平的变化与整个生命周期中的一系列疾病有关,其因果关系仍然难以捉摸。我们的目的是询问基因预测的维生素B12状态与英国生物库提供的过多临床结果的关系。从丹麦和冰岛的45,576名个体中获得的全基因组关联研究(GWAS)汇总数据用于鉴定与维生素B12水平相关的8种遗传变异,在随后的分析中用作维生素B12状态的遗传工具。我们使用这8种遗传工具对来自英国生物库的439,738名个体中的945种不同表型的维生素B12状态进行了孟德尔随机化(MR)-表型全关联研究(PheWAS),以替代维生素B12状态的改变。我们使用外部GWAS汇总统计数据来复制重要的发现。使用5%错误发现率(FDR)阈值来考虑多次测试的校正。MR分析确定了较高的基因预测维生素B12状态与较低的维生素B缺乏风险(包括所有B族维生素缺乏)之间的关联。作为一个积极的控制结果。我们进一步确定了较高的遗传预测维生素B12状态与巨幼细胞性贫血(OR=0.35,95%CI:0.20-0.50)和恶性贫血(0.29,0.19-0.45)的风险降低之间的关联。在复制分析中支持。我们的研究强调,较高的基因预测维生素B12状态是潜在的保护与恶性贫血诊断相关的维生素B12缺乏的风险,并降低巨幼细胞性贫血的风险。基因预测的维生素B12状态在疾病诊断中的潜在用途,进展和管理还有待调查。
    Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20-0.50) and pernicious anaemia (0.29, 0.19-0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.
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  • 文章类型: Case Reports
    未经证实:恶性贫血是一种罕见的自身免疫性疾病,在0.1%的普通人群中普遍存在,其特征是钴胺素吸收减少。这种情况因其罕见而被忽视,非特异性症状的隐匿发作和临床无症状状态。血清内在因子抗体水平升高以及维生素B12水平降低证实了诊断。
    未确认:出现苍白和腹部压痛。血液学检查显示血小板计数升高,平均细胞体积升高,血红蛋白水平降低(11.4g/dl),降低维生素B12和高血清内在因子抗体水平。血清壁细胞抗体阳性。患者对肠胃外维生素B12反应良好。
    未经证实:在恶性贫血中,血清内在因子抗体和壁细胞抗体较高,是降低维生素B12吸收的原因。研究还表明,幽门螺杆菌与恶性贫血呈正相关。神经系统症状不太常见,但可能表现为感觉异常,由于周围神经病变引起的步态或痉挛的变化。它还与自身免疫性疾病相关。未经治疗的恶性贫血可导致神经和胃肠道并发症。
    未经证实:恶性贫血是一种被忽视的疾病,因为它隐匿地出现非特异性症状,临床无症状状态,罕见,因此及时诊断恶性贫血仍然是一个挑战。
    UNASSIGNED: Pernicious Anaemia is a rare autoimmune disorder prevalent among 0.1% of the general population and is characterised by decreased cobalamin absorption. This condition is overlooked because of its rarity, insidious onset of non-specific symptoms and clinically asymptomatic state. Elevated serum intrinsic factor antibody level along with reduced Vitamin B12 level confirms the diagnosis.
    UNASSIGNED: Pallor and abdominal tenderness was present. Haematological investigations showed elevated platelet count, elevated Mean Cell Volume reduced haemoglobin level(11.4 g/dl), reduced Vitamin B12 and high serum intrinsic factor antibody level. Serum parietal cell antibody was positive. The patient responded well to parenteral Vitamin B12.
    UNASSIGNED: In Pernicious anaemia, serum intrinsic factor antibody and parietal cell antibody are high which are responsible for reduced Vitamin B12 absorption. Studies have also shown positive correlation between H pylori and Pernicious Anaemia. Neurological symptoms are less common but may present as paraesthesia, changes in gait or spasticity due to peripheral neuropathy. It is also associated with autoimmune diseases. Untreated pernicious anaemia can lead to neurological and gastrointestinal complications.
    UNASSIGNED: Pernicious Anaemia is an overlooked condition because of its insidious onset of non-specific symptoms, clinically asymptomatic state, rarity and therefore timely diagnosis of Pernicious Anaemia still remains a challenge.
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  • 文章类型: Journal Article
    背景:自身免疫性萎缩性胃炎(AAG)很少与乳糜泻(CD)相关。
    目的:评估AAG-CD关联的频率,并比较临床,生物化学,和受两种疾病(病例)影响的成人的组织学特征与AAG对照。
    方法:本病例对照研究包括9例(F55%,中位年龄47岁,范围23-59岁)按年龄(±4岁)和性别与从我们的AAG队列(2009-2021)中随机选择的27名对照相匹配(1:3).AAG和CD诊断基于国际公认的标准。
    结果:在434名AAG患者中(中位年龄:62.5岁,范围18-92yrs,F:M比率=2.2:1),9具有伴随的CD诊断。在AAG/CD队列中,AAG-CD关联的发生率分别为2%和1.65%,分别。病例明显比AAG队列年轻(n=425,p=0.002)。在4/9案例中,通过主动筛查自身免疫性疾病来诊断AAG。5/9例存在自身免疫性甲状腺疾病。病例的正常细胞性贫血患病率明显高于对照组(p=0.004)。在临床和组织学特征方面,病例和对照组之间没有发现显着差异。
    结论:AAG-CD结合很少见。对于患有正常细胞性贫血和相关自身免疫性疾病的年轻人,建议进行胃和十二指肠活检,以及时诊断临床症状。
    Autoimmune atrophic gastritis (AAG) is rarely associated with coeliac disease (CD).
    To assess the frequency of AAG-CD association and to compare clinical, biochemical, and histological features of adults affected by both diseases (cases) with AAG controls.
    This case-control study included 9 cases (F55%, median age 47, range 23-59yrs) matched (1:3) by age (±4 yrs) and gender to 27 controls randomly selected from our AAG cohort (2009-2021). The AAG and CD diagnosis was based on internationally agreed criteria.
    Of 434 AAG patients (median age:62.5yrs, range18-92yrs, F:M ratio=2.2:1),9 had a concomitant diagnosis of CD. The occurrence of AAG-CD association was 2% and 1.65% among AAG/CD cohorts, respectively. Cases were significantly younger than AAG cohort (n = 425, p = 0.002). In 4/9cases, AAG was diagnosed by proactive screening for autoimmune disorders. Autoimmune thyroid disorders were present in 5/9 cases. Cases had a significant higher prevalence of normocytic anaemia than controls (p = 0.004). No significant differences were found between cases and controls concerning clinical and histological features.
    AAG-CD association is rare. Gastric and duodenal biopsies might be advisable in young people with normocytic anaemia and associated autoimmune disorders to timely diagnose clinically silent conditions.
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  • 文章类型: Case Reports
    恶性肿瘤和自身免疫之间的关联已经很好地确定。所提出的病理生理学和因果关系可以是双向的。例如,副肿瘤综合征可以由潜在的恶性肿瘤引发,反之亦然,其中受自身免疫影响的器官的慢性炎症可以诱导恶性转化,例如炎症性肠病和结直肠癌或原发性硬化性胆管炎和肝胆癌。本报告介绍了一个自身免疫现象的案例,即,自身免疫性溶血性贫血,恶性贫血,和与新诊断的乳腺癌相关的Graves病。我们还强调了假定的病理生理机制,以试图回答以下问题:我们患者中这些自身免疫现象的发生是否是简约定律的结果(奥卡姆剃刀),临床变量与病因相关,或者相反的论点,随机事件和疾病可以同时发生(希卡姆的格言)。
    The association between malignancies and autoimmunity had been well-established. The proposed pathophysiology and causality can be bidirectional. For example, a paraneoplastic syndrome can be triggered by an underlying malignancy or vice versa, where chronic inflammation of organs affected by autoimmunity can induce malignant transformation such as the case with inflammatory bowel disease and colorectal cancer or primary sclerosing cholangitis and hepatobiliary cancer. This report presents a case of autoimmune phenomena, namely, autoimmune hemolytic anemia, pernicious anemia, and Graves disease associated with newly diagnosed breast cancer. We also highlight the postulated pathophysiologic mechanisms in an attempt to answer the question of whether the occurrence of these autoimmune phenomena in our patient is a result of the law of parsimony (Occam\'s razor), where clinical variables are pathogenically related, or the counterargument, where random events and diseases can take place simultaneously (Hickam\'s dictum).
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  • 文章类型: Case Reports
    大红细胞增多症定义为平均红细胞体积大于100毫微微升(fL)。大细胞性贫血有几种原因,可分为巨幼细胞性贫血或非巨幼细胞性贫血。维生素B12缺乏是巨幼细胞性贫血的最常见原因之一。必须评估维生素B12缺乏的原因,包括恶性贫血的存在,因为它可能会改变治疗和随访。恶性贫血可能与构成多腺综合征的其他自身免疫性疾病有关。
    Macrocytosis is defined as a mean corpuscular volume greater than 100 femtolitres (fL). There are several causes for macrocytic anaemia, and they can be divided into megaloblastic or non-megaloblastic anaemia. Vitamin B12 deficiency is one of the most common causes of megaloblastic anaemia. The cause of vitamin B12 deficiency must be evaluated including the presence of pernicious anaemia as it could alter the treatment and follow-up. Pernicious anaemia can be associated with other autoimmune diseases constituting polyglandular syndromes.
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