Treatment of acute severe ulcerative colitis using accelerated infliximab regimen based on infliximab trough level: A case report

BACKGROUNDAcute severe ulcerative colitis (ASUC) is a complication of ulcerative colitis associated with high levels of circulating tumor necrosis factor alpha, due to the intense inflammation and faster stool clearance of anti-tumor necrosis factor drugs. Dose-intensified infliximab treatment can be beneficial and is associated with lower rates of colectomy. The aim of the study was to present a case of a patient with ASUC and megacolon, treated with hydrocortisone and accelerated scheme of infliximab that was monitored by drug trough level.CASE SUMMARYA 22-year-old female patient diagnosed with ulcerative colitis, presented with diarrhea, rectal bleeding, abdominal pain, vomiting, and distended abdomen. During investigation, a positive toxin for Clostridium difficile and colonic dilatation of 7 cm consistent with megacolon were observed. She was treated with oral vancomycin for pseudomembranous colitis and intravenous hydrocortisone for severe colitis, which led to the resolution of megacolon. Due to the persistent severe colitis symptoms, infliximab 5 mg/kg was prescribed, monitored by drug trough level (8.8 μg/mL) and fecal calprotectin of 921 μg/g (< 30 μg/g). Based on the low infliximab trough level after one week from the first infliximab dose, the patient received a second infusion at week 1, consistent with the accelerated regimen (infusions at weeks 0, 1, 2 and 6). We achieved a positive clinical and endoscopic response after 6 mo of therapy, without the need for a colectomy.CONCLUSIONInfliximab accelerated infusions can be beneficial in ASUC unresponsive to the treatment with intravenous corticosteroids. Longitudinal studies are necessary to define the best therapeutic drug monitoring and treatment regimen for these patients.     

Myocarditis as an extraintestinal manifestation of ulcerative colitis: A case report and review of the literature

BACKGROUNDAlthough extraintestinal manifestations of inflammatory bowel disease (IBD) are well documented, myocarditis has only rarely been reported as an extraintestinal manifestation, and it can be fatal. The various clinical presentations and causes of myocarditis in IBD patients complicate making a correct and timely diagnosis.CASE SUMMARYHere we report a 15-year-old boy who presented with myocarditis as the initial presentation of a relapse of ulcerative colitis. In reviewing the literature for cases of myocarditis complicating IBD, we found 21 other cases, allowing us to expand our understanding of the clinical presentation, diagnosis, management, and outcomes of this rare condition. The most frequent diagnostic clues for myocarditis in IBD patients are dyspnea, chest pain, tachycardia, raised cardiac biomarkers, and abnormalities on trans-thoracic echocardiography. Additionally, we discuss the etiology of myocarditis in IBD patients, which include an extraintestinal manifestation, the adverse effects of mesalamine and infliximab, selenium deficiency, and infection, to help provide a framework for diagnosis and management.CONCLUSIONMyocarditis as an extraintestinal manifestation of IBD can be life-threatening. Trans-thoracic echocardiogram and cardiac magnetic resonance may assist its diagnosis.     

Spontaneous remission of autoimmune pancreatitis: Four case reports

BACKGROUNDAutoimmune pancreatitis (AIP) is a particular type of chronic pancreatitis, and steroid treatment of AIP is effective. Spontaneous remission (SR) of AIP without steroids is relatively rare. The international consensus for the treatment of autoimmune pancreatitis suggests that patients with AIP with obstructive jaundice, abdominal pain, and back pain related to the pancreas or the bile duct should be treated with steroids; most asymptomatic patients with AIP may improve without steroids. However, in our clinical work, we found that the clinical characteristics of AIP patients with SR vary. Four of these cases are described here. In addition, to our knowledge, there is no previously published report of dynamic imaging before and after SR of AIP at present.CASE SUMMARYWe present the cases of four patients with AIP (two females and two males) in which the AIP improved spontaneously without steroid treatment. Two patients were asymptomatic, one patient had abdominal pain with obstructive jaundice, and one patient had intermittent right upper abdominal pain. Three patients presented with localized pancreatic enlargement and one with diffuse pancreatic enlargement. In addition to the pancreatic lesions, bile duct involvement was seen in two patients, and no extra-pancreatic organ involvement was found in the other two patients. The serum IgG4 level of all patients was more than twice the normal level. After SR in the four patients, the affected pancreases exhibited three types of image features: Return to normal, progressive fibrosis, and atrophy and calcification.CONCLUSIONThe clinical features of SR in our four patients with AIP differ, but the imaging findings share some characteristics. After SR, in some cases the affected pancreas could return to normal, although some patients suffer from progressive fibrosis and atrophy as well as calcification.     

Gallium-67-citrate scintigraphy in ulcerative colitis

Gallium-67-citrate scanning was performed in 9 patients with ulcerative colitis. In all patients there was good correlation between the regional uptake of gallium and the extent and activity of disease. In 2 patients the scans were positive during an acute exacerbation and reverted to normal or near normal during clinical remission. In one patient in whom the colon was resected because of toxic dilatation, good correlation was found between pathologic and scintigraphic examinations. During the acute attack of ulcerative colitis, when colonoscopy or barium enema may be contraindicated, gallium scanning may be a noninvasive means of assessing the extent of colonic involvement. It may also be an alternative means of following the clinical course of the disease.     

E-钙粘附蛋白在溃疡性结肠炎发病中的作用

通过研究Ｅ－钙粘附蛋白（Ｅ－ＣＤ）在溃疡性结肠炎（ＵＣ）中的表达,探讨Ｅ－ＣＤ在ＵＣ发病中的作用。方法应用免疫组织化学方法,研究正常结肠和ＵＣ标本中的Ｅ－ＣＤ表达。结果正常组和ＵＣ组中Ｅ－ＣＤ水平无显著性差异（Ｐ＞０．０５）：ＵＣ组中Ｅ－ＣＤ表达与病情程度不相关（Ｐ＞０．０５）。结论Ｅ－ＣＤ在ＵＣ进展阶段不起主要作用,Ｅ－ＣＤ在ＵＣ触发阶段的作用尚须进一步研究。     

The 17-year single-center experience with the use of azathioprine to maintain remission in ulcerative colitis

Despite the accumulation of positive data, the role of azathioprine (AZA) in the maintenance of remission of ulcerative colitis is still controversial. We looked at the follow-up of the ulcerative colitis patients who, after responding to either steroids or cyclosporin (CsA), received AZA at our referral center for over a decade. The 39 patients (29 m/10f) were treated between 1991 and 2007. Twenty-five of them had responded to CsA, the remaining 14 to corticosteroids. AZA was usually overlapped with either of the two agents at the initial dose of 2 mg/kg/day. The definitions of remission, relapse, and AZA toxicity followed commonly agreed criteria. The median duration of the AZA treatment was 14 months (<1–201). Fifty-two percent and 14%, respectively, of the CsA and the steroid responders needed surgery (overall rate = 38%). The figures were 32 and 15 at the first year. The majority of the patients had 1–2 relapses often in connection with withdrawal of AZA; only 3 of these relapsers needed hospitalization. AZA caused toxicity in 16/39 (41%) patients, requiring withdrawal in 23% of the cases; leukopenia (17%) and hepatitis/cholestasis (10%) ranked first and second for frequency. All of the patients in whom AZA was stopped (or reduced) relapsed. In conclusion, the 1-year colectomy rates compare favorably with the figures reported by the literature. By contrast, the toxicity rates were higher than expected. Failure to genotype or to use escalating AZA doses can only be hypothesized as causes.     

Tofacitinib for the treatment of ulcerative colitis: A review of the literature

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory condition affecting the colon. Recently, tofacitinib, an oral small molecule that is an inhibitor of the Janus kinase signal transduction pathway, was proven efficacious for inducing and maintaining remission in adult patients with moderate to severe UC in three global Phase III studies. The purpose of this review is to summarize existing data on the efficacy, safety, and quality of life issues related to use tofacitinib as well as highlight recent real-world experience with this drug among patients with UC.     

溃疡性结肠炎合并结肠多发性锯齿状息肉的临床病理分析

目的 探讨溃疡性结肠炎(UC)合并结肠多发性锯齿状息肉的临床病理特点及免疫组化表型. 方法报告2例分别有10年和8年溃疡性结肠炎病史、合并多发性结肠锯齿状息肉病的临床、内窥镜及病理组织学改变.行AE1/AE3、CK7、CK20、CEA、CD34、SMA、p53和Ki-67免疫组化染色,并结合文献进行复习讨论. 结果 2名患者均为中年女性,间断腹泻10年和8年,分别多次行内窥镜检查发现结直肠黏膜多处糜烂、浅表溃疡.例1,降、乙状结肠可见密集分布、大小不等的息肉,最大直径3cm;例2,全结肠可见10余枚息肉.镜检:结直肠溃疡糜烂处符合溃疡性结肠炎病变;息肉处腺体大部分呈锯齿状扩张增生,部分细胞核增生呈复层,可见异型增生.免疫组化:息肉部腺体CEA(+),Ki-67阳性细胞位于锯齿状隐窝基底及中1/3;例2局部p53(+).结论 UC相关锯齿状息肉/腺瘤病具有肿瘤性病变特征,UC合并锯齿状息肉或腺瘤可能更易癌变.     

Zingiber officinale and oxidative stress in patients with ulcerative colitis: A randomized,placebo-controlled,clinical trial

ObjectivesOxidative stress plays an essential role in ulcerative colitis (UC) initiation and severity. We aimed to investigate the effect of ginger as a well-known antioxidant agent on the quality of life, disease activity index and oxidative stress in patients with UC.MethodsForty six patients with active mild to moderate UC randomly assigned to consume 2000 mg/day dried ginger powder in 4 capsules or similar placebo capsules for 12 weeks. Disease activity index, quality of life and some oxidative stress factors were measured before, at the middle and at the end of the intervention through valid and reliable questionnaires and blood sampling.ResultsGinger reduced Malondialdehyde (MDA) significantly after 6 weeks (p = 0.003) and 12 weeks (p < 0.001) of intervention, whereas it did not affect serum total anti-oxidant capacity (TAC). The scores of severity of disease activity at 12th week was significantly improved in ginger group in comparison to placebo (p = 0.017). Moreover, ginger increased patients quality of life significantly at 12^th week (p = 0.039).ConclusionOur data indicate that ginger supplementation can improve treatment of patients with UC. Further clinical trials with different dosages and duration of ginger or its standard extract supplementation are needed to obtain firm conclusion.     

Anti-MADCAM therapy for ulcerative colitis

ABSTRACT

Introduction: The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) plays a key role in the endothelial adhesion and migration of lymphocytes to sites of inflammation in inflammatory bowel disease. Therapies that target this pathway appear to be a promising therapeutic approach in the management of ulcerative colitis (UC).

Areas covered: This review provides a summary of the preclinical and available clinical data on the safety and efficacy of ontamalimab (SHP647), a fully human monoclonal antibody that binds and inhibits the action of MAdCAM-1.

Expert opinion: Intestinal immune cell trafficking is emerging as an important component in the pathogenesis of UC. Ontamalimab (SHP647) inhibits this process by preventing the binding of integrins found on the surface of lymphocytes and the endothelial ligand adhesion molecule MAdCAM-1. This monoclonal antibody has already demonstrated safety and efficacy in phase II clinical trials. Its targeted mechanism of action suggests a superior safety profile as compared with the current systemic immunosuppressive therapies. Results from the phase III trials are awaited to establish ontamalimab (SHP647) as a therapeutic option in the management of UC.