Protein-losing enteropathy, deep venous thrombosis and pulmonary embolism in a patient with generalized inflammatory polyposis in remission stage of ulcerative colitis

We experienced a patient with severe protein-losing enteropathy and generalized inflammatory polyposis. In addition, this case was complicated by deep venous thrombosis and pulmonary embolism. Patients with inflammatory bowel disease are at increased risk for thromboembolic events, most commonly in the setting of active colitis. However, our patient was in the remission stage. We report the occurrence of deep venous thrombosis and pulmonary embolism as a complication of inflammatory polyposis and protein-losing enteropathy in the remission stage of ulcerative colitis.     

Obesity as a risk factor in venous thromboembolism

PURPOSE: Whether obesity is an independent risk factor for pulmonary embolism or deep venous thrombosis has not been fully determined. METHODS: We used the database of the National Hospital Discharge Survey to further investigate the potential risk of obesity in venous thromboembolic disease. RESULTS: The relative risk of deep venous thrombosis, comparing obese patients with non-obese patients, was 2.50 (95% confidence interval [CI] = 2.49-2.51). The relative risk of pulmonary embolism was 2.21 (95% CI = 2.20-2.23). Obese females had a greater relative risk for deep venous thrombosis than obese males, 2.75 (95% CI = 2.74-2.76) versus 2.02 (95% CI = 2.01-2.04). Obesity had the greatest impact on both men and women aged less than 40 years. CONCLUSION: The data indicate that obesity is a risk factor for venous thromboembolic disease in men as well as women.     

Venous thromboembolism in inflammatory bowel disease

Patients with inflammatory bowel disease(IBD) are at an increased risk for venous thromboembolism(VTE). VTE events carry significant morbidity and mortality, and have been associated with worse outcomes in patients with IBD.Studies have suggested that the hypercoagulable nature of the disease stems from a complex interplay of systems that include the coagulation cascade, natural coagulation inhibitors, fibrinolytic system, endothelium, immune system, and platelets. Additionally, clinical factors that increase the likelihood of a VTE event among IBD patients include older age(though some studies suggest younger patients have a higher relative risk of VTE, the incidence in this population is much lower as compared to the older IBD patient population), pregnancy, active disease, more extensive disease, hospitalization, the use of certain medications such as corticosteroids or tofacitinb, and IBD-related surgeries. Despite the increased risk of VTE among IBD patients and the safety of pharmacologic prophylaxis, adherence rates among hospitalized IBD patients appear to be low.Furthermore, recent data suggests that there is a population of high risk IBD patients who may benefit from post-discharge prophylaxis. This review will provide an overview of patient specific factors that affect VTE risk, elucidate reasons for lack of VTE prophylaxis among hospitalized IBD patients, and focus on recent data describing those at highest risk for recurrent VTE post-hospital discharge.     

The risk of venous thromboembolism is markedly elevated in patients with diabetes

Aims/hypothesis Diabetes mellitus is associated with several changes in coagulation and fibrinolysis that may lead to a thrombogenic propensity. However, it is not known whether these perturbations actually cause increased risk of venous thromboembolism.Methods In a retrospective population-based study we evaluated the medical records of all 302 adult patients who were admitted to the Umeå University Hospital with verified deep vein thrombosis or pulmonary embolism during the years 1997 to 1999. The patients were classified as diabetic (n=56) and non-diabetic (n=246) according to clinical information. The total number of diagnosed diabetic patients in different age groups in the catchment area was obtained from computerised registries in the primary health care centres and the Umeå University Hospital, and data on the background population were collected from the Swedish population registry.Results The annual incidence rate of venous thromboembolism among diabetic patients in the population was 432 per 100,000 individuals (95% CI 375–496). In non-diabetic individuals it was 78 (95% CI 68–88). The age-adjusted incidence rate among the diabetic population was 274 (95% CI 262–286). The annual incidence rate of venous thromboembolism was elevated in type 1 and type 2 diabetic patients and the incidence rates were 704 (95% CI 314–1,566) and 412 (95% CI 312–544) respectively. The overall standardised morbidity ratio was 2.27 (95% CI 1.75–2.95), i.e. diabetic patients were more prone to venous thromboembolism after adjustment for age differences.Conclusions/interpretation These results suggest that the age-adjusted risk for venous thromboembolism is more than two-fold higher among diabetic patients than in the non-diabetic background population.     

静脉血栓栓塞症治疗的研究进展

包括深静脉血栓形成（deep vein thrombosis,DVT）和肺栓塞（pulmonary embolism,PE）的静脉血栓栓塞症（venous thromboembolism,VTE）的年发病率为0.10％～0.27％[1].约2％的PE患者在诊断前或诊断后的第一天死亡,即使给予适当的治疗PE患者3个月内的死亡率仍高达11％.死亡多是由VTE的并发疾病所致[2].VTE的长期并发症包括高达40％的DVT患者患有血栓形成后综合征,1％～4％的PE患者发生慢性血栓栓塞性肺动脉高压[3,4].     

Cerebral venous thrombosis and heparin-induced thrombocytopenia in an 18-year old male with severe ulcerative colitis

The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. Furthermore, its treatment can be complex and is not without complications. We describe a case of an adolescent boy who developed a cerebral sinus venous thrombosis during a relapse of his ulcerative colitis and who, while on treatment with heparin, developed heparin-induced thrombocytopenia （HIT）. The treatment was then switched to fondaparinux, a synthetic and selective inhibitor of activated factor Ⅹ.     

Infliximab to treat severe ulcerative colitis

A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.     

Derivation and validation of a simple model to identify venous thromboembolism risk in medical patients

Background

Fewer than half of eligible hospitalized medical patients receive appropriate venous thromboembolism (VTE) prophylaxis. One reason for this low rate is the complexity of existing risk assessment models. A simple set of easily identifiable risk factors that are highly predictive of VTE among hospitalized medical patients may enhance appropriate thromboprophylaxis.

Methods

Electronic medical record interrogation was performed to identify medical admissions from January 1, 2000-December 31, 2007 (n = 143,000), and those patients with objectively confirmed VTE during hospitalization or within 90 days following discharge. Putative risk factors most predictive of VTE were identified, and a risk assessment model (RAM) was derived; 46,000 medicine admissions from January 1, 2008-December 31, 2009 served as a validation cohort to test the predictive ability of the RAM. The newly derived RAM was compared with a published VTE assessment tool (Kucher Score).

Results

Four risk factors: previous VTE; an order for bed rest; peripherally inserted central venous catheterization line; and a cancer diagnosis, were the minimal set most predictive of hospital-associated VTE (area under the receiver operating characteristic curve [AUC] = 0.874; 95% confidence interval [CI], 0.869-0.880). These risk factors upon validation in a separate population (validation cohort) retained an AUC = 0.843; 95% CI, 0.833-0.852. The ability of the 4-element RAM to identify patients at risk of developing VTE within 90 days was superior to the Kucher Score.

Conclusions

The 4-element RAM identified in this study may be used to identify patients at risk for VTE and improve rates of thromboprophylaxis. This simple and accurate RAM is an alternative to more complicated published VTE risk assessment tools that currently exist.     

Prolonged seated immobility at work is a common risk factor for venous thromboembolism leading to hospital admission

The role of seated immobility at work in the pathogenesis of venous thromboembolism (VTE) is uncertain. In this case series, 61 patients aged <65 years with a recent admission for deep venous thrombosis and/or pulmonary embolism completed an interviewer-administered questionnaire to obtain information regarding risk factors. Prolonged seated immobility at work in the 4 weeks before the VTE event was defined as being seated at least 8 h in a 24-h period and at least 3 h at a time without getting up, at least 10 h in a 24-h period and at least 2 h at a time without getting up or at least 12 h in a 24-h period and at least 1 h at a time without getting up. The most commonly identified risk factors were family history of VTE (21 of 61, 34%), seated immobility at work (21 of 61, 34%) and a thrombophilic state (19 of 61, 31%). We conclude that prolonged seated immobility at work may represent a common and important risk factor for VTE.     

Methotrexate in ulcerative colitis: A Spanish multicentric study on clinical use and efficacy

Background

Few data are available on the efficacy of methotrexate (MTX) in ulcerative colitis (UC).

Aim

To evaluate the efficacy and safety of MTX in UC patients.

Patients and methods

UC patients who had been treated with MTX were identified from the databases of 8 Spanish IBD referral hospitals. Patients were included in the study if they received MTX for steroid dependency or steroid refractoriness. Therapeutic success was defined as the absence of UC-related symptoms, complete steroid withdrawal and no requirement of rescue therapies within the first 6 months after starting MTX.

Results

Forty patients were included, 70% treated for steroid dependency and 27% for steroid refractoriness. Thiopurines had been previously attempted in 87.5% of patients. The median dose of MTX used for induction was 25 mg (IIQ 17.5–25) weekly given parenterally in 82.5% of cases. Eighty-five percent of patients were on steroids when MTX was started. Forty-five percent of patients met criteria for therapeutic success. Initial treatment failures were mainly due to inefficacy (50%) or intolerance (36%). After a median follow-up of 28 months (IQR 22–47), 38% of patients with initial therapeutic success required new steroid courses, 22% started biological therapy, and only 1 patient required colectomy. The cumulative probability of maintaining steroid-free clinical remission was 60%, 48%, and 35% at 6, 12, and 24 months after starting MTX, respectively. Eleven patients (27.5%) experienced adverse events, leading to MTX discontinuation in only 8 of them.

Conclusions

MTX appears to be effective to maintain clinical remission in UC, at least in the short-term, with an acceptable safety profile.     

Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease

AIM:To evaluate whether the effectiveness of Granulomonocyto apheresis(GMA),a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood,might vary according to the severity of ulcerative colitis(UC)in patients with mild to moderate-severe disease UC activity.METHODS:We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up.The demographics,clinical and laboratory data were extracted from the patients’charts and electronic records.The severity of UC was scored according to the Modified Truelove Witts Severity Index(MTWSI).A clinical response was defined as a decrease from baseline of≥2 points or a value of MTWSI≤2 points.RESULTS:A total of 41(24 males/17 females;meanage 47 years)patients were included in the study.After GMA cycle completion,21/28(75%)of mild UC patients showed a clinical response compared with 7/13(54%)of patients with moderate to severe disease(P=0.27).At 6-mo,14/28(50%)of the mild UC patients maintained a clinical response compared with 2/13(15%)of the patients with moderate to severe disease(P=0.04).After the GMA cycle completion and during the 6-mo follow up period,13/16(81%)and 9/16(56%)of mild UC patients with intolerance,resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6(33%)and 0/6(0%)of patients with moderate to severe disease activity with these characteristics(P=0.05and P=0.04,respectively).CONCLUSION:Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period.GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants,corticosteroids and/or biologics.     

Cerebral venous thrombosis associated with ulcerative colitis

Thromboembolic complications, such as deep venous thrombosis and pulmonary embolism, are well recognized in patients with inflammatory bowel disease (IBD). We describe three cases of cerebral venous thrombosis complicating ulcerative colitis. Cerebral venous thrombosis is a rare but potentially devastating complication of IBD, and the diagnosis needs to be considered in any patient with IBD presenting with neurological symptoms.     

Parameters of a severe disease course in ulcerative colitis

AIM: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT).METHODS: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy.RESULTS: In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can determine the need for an immunosuppressive drug therapy or if a “watch and wait” approach is reasonable already early in the treatment course of UC.CONCLUSION: Using six simple clinical parameters, we can estimate the patients individual risk of developing a progressive disease course.     

Refractory ulcerative colitis accompanied with cytomegalovirus colitis and multiple liver abscesses： A case report

Various hepato-biliary complications are an increased incidence in patients with inflammatory bowel disease, and portal bacteremia is well documented in patients with ulcerative colitis (DC). However, few reports mention UC in association with liver abscesses. Recently, there are several reports describing cytomegalovirus (CMV) infection in association with disease exacerbation and steroid refractoriness in patients with UC. Here we present a case of refractory UC accompanied with multiple liver abscesses and CMV colitis. The patient, a 72-year-old male, with a five-year history of repeated admissions to our hospital for UC, presented with an exacerbation of his UC. Sigmoidoscopy performed on admission suggested that his UC was exacerbated, then he was given prednisolone and mesalazine orally, and betamethasone enemas. However, he had exacerbated symptoms. Repeat Sigmoidoscopy revealed multiple longitudinal ulcers and pseudopolyps in the rectosigmoid colon. Although immunohistochemical staining of biopsy specimens and the serum testing for antigenemia were negative on admission and after the repeat Sigmoidoscopy, they became histologically positive for CMV. Nonetheless, the patient developed spiking fevers, soon after ganciclovir was administered. Laboratory studies revealed an increased white cell count with left shift, and Enterococcus fecalis grew in blood cultures. An abdominal computed tomography (CT) scan was obtained and the diagnosis of liver abscesses associated with UC was made, based on CT results. The hepatic abscesses were successfully treated with intravenous meropenem for 6 wk, without further percutaneous drainage. To our knowledge, this is the first reported case of multiple liver abscesses that develop during UC exacerbation complicated by CMV colitis.     

High-dose infliximab for treatment of pediatric ulcerative colitis: a survey of clinical practice

AIM:To assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis(UC).METHODS:A 19-item survey was distributed to subscribers of the pediatric gastroenterology(PEDSGI) listserv.Responses were submitted anonymously and results compiled in a secure website.RESULTS:A total of 113 subscribers(88% based in the United States) responded(101 pediatric gastroenterology attendings and 12 pediatric gastroenterology fellows).There were 46% in academic medical institutions and 39% in hospital-based practices.The majority(91%) were treating 10 patients with UC;13% were treating 100 patients with UC;91% had prescribed infliximab(IFX) 5 mg/kg for UC;72% had prescribed IFX 10 mg/kg for UC.Using a 5-point Likert scale,factors that influenced the decision not to increase IFX dosing in patients with UC included:"improvement on initial dose of IFX"(mean:3.88) and "decision to move to colectomy"(3.69).Lowest mean Likert scores were:"lack of guidelines or literature regarding increased IFX dosing"(1.96) and "insurance authorization or other insurance issues"(2.34)."Insurance authorization or other insurance issues" was identified by 39% as at least somewhat of a factor(Likert score ≥ 3) in their decision not to increase the IFX dose.IFX 10 mg/kg was more commonly used for the treatment of pediatric UC among responders based in the United States(75/100) compared to non-United States responders(6/13,P = 0.047).Induction of remission was reported by 78% of all responders and 81% reported maintenance of remission with IFX 10 mg/kg.One responder reported one death with IFX 10 mg/kg.CONCLUSION:IFX 10 mg/kg is more commonly used in the United States to treat pediatric UC.Efficacy and safety data are required to avoid insurance barriers for its use.     

Family history for venous thromboembolism and the risk for recurrence

Purpose

The relevance of a family history for venous thromboembolism with regard to the likelihood for recurrence is unknown.

Subjects and methods

We studied 826 patients for an average of 36 months after a first unprovoked venous thromboembolism and withdrawal of oral anticoagulation. Patients with cancer, lupus anticoagulant, or deficiency of antithrombin, protein C, or protein S were excluded. The study endpoint was objective evidence of recurrent symptomatic venous thromboembolism.

Results

Recurrence for venous thromboembolism was recorded in 23 of 190 patients (12.1%) with a family history (at least one affected first-degree family member) and in 79 of 636 patients (12.4%) without familial thrombosis (relative risk for recurrence 1.0; 95% confidence interval, 0.7-1.6; P = .9). At 5 years, the likelihood for recurrence was 20% among patients with a family history for venous thromboembolism and 18% among those without a family history for venous thromboembolism (P = .9). Risk determinants for venous thromboembolism including factor V Leiden, factor II G20210A, and high factor VIII were not statistically different between the 2 groups.

Conclusion

A family history for venous thromboembolism does not segregate patients into high- or low-risk categories and is not suitable to identify patients at increased risk for recurrent venous thromboembolism.     

A case of interstitial pneumonitis in a patient with ulcerative colitis treated with azathioprine

The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever, cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection, azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.     

Fecal calprotectin as an alternative to ulcerative colitis endoscopic index of severity to predict the response to corticosteroids of acute severe ulcerative colitis: A prospective observational study

BackgroundFecal calprotectin (FC) might be an alternative to ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to corticosteroids (CS) in acute severe colitis (ASC).MethodsOne hundred and seventeen ASC patients were prospectively enrolled. Demographic, clinical, laboratory and sigmoidoscopic data were documented. Multivariate and ROC analyses were performed to identify risk factors for non-response to CS, and the predictive accuracy of possible predictors was assessed.ResultsTotally, 39 (33.33%) patients failed intravenous CS therapy. CS responders among mild (UCEIS 3–4), moderate (UCEIS 5–6) and severe (UCEIS 7–8) groups were 40/44 (90.91%) vs. 36/55 (65.45%) vs. 2/18 (11.11%) (p < 0.001). UCEIS (OR = 5.08; 95% CI, 1.93–8.66; p < 0.001) and FC (OR = 2.56; 95% CI, 1.17–3.55; p = 0.022) were found to be independent risk factors for CS non-responders. Compared with C-reactive protein, platelet, hemoglobin and albumin, baseline FC had the strongest correlation with UCEIS (r = 0.701, p < 0.001). ROC analysis of UCEIS and baseline FC in predicting CS non-response showed an AUC of 0.85 and 0.76 respectively.ConclusionsBaseline FC levels correlated significantly with UCEIS in ASC, and both were useful in predicting short-term outcome of CS treatment. Baseline FC levels could be used as an alternative of UCEIS to guide the decision of early salvage therapy or colectomy and reduce the adverse effects of long-term futile CS usage.     

Recurrent myopericarditis with extensive ulcerative colitis

A 26-year-old man with ulcerative colitis was independently evaluated in different emergency rooms on two occasions, separated by six years, for episodes of severe chest pain consistent with myopericarditis. Cardiac enzyme and electrocardiographic changes were accompanied by extensive colonic inflammatory changes. Treatment with corticosteroids led to resolution. While his cardiac findings were initially believed to be caused by a previously reported drug hypersensitivity to mesalamine (5-aminosalicylate), sulphasalazine was tolerated. Recurrent myopericarditis with ulcerative colitis appears to be rare, but responsive to steroids. It may occur more often than is currently appreciated and may lead to fatal arrhythmias or cardiac failure.     

Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis

AIM:To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis(UC)patients.METHODS:This was a prospective,multicenter,observational study.Between May 2010 and August 2012,49 steroid-refractory UC patients(55 flare-ups)were consecutively enrolled.All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1mg/kg per day.The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/m L for the first 2 wk.Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index(CAI).RESULTS:The mean CAI was 12.6±3.6 at onset.Within the first 7 d,93.5%of patients maintained high trough levels(10-15 ng/m L).The CAI significantly decreased beginning 2 d after treatment initiation.At 2wk,73.1%of patients experienced clinical responses.After tacrolimus initiation,31.4%and 75.6%of patients achieved clinical remission at 2 and 4 wk,respectively.Treatment was well tolerated.CONCLUSION:Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation.Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.