Crohn's disease presenting as acute gastrointestinal hemorrhage

Severe gastrointestinal (GI) hemorrhage is a rare complication of Crohn’s disease (CD). Although several surgical and non-surgical approaches have been described over the last 2 decades this complication still poses significant diagnostic and therapeutic challenges. Given the relative infrequency of severe bleeding in CD, available medical literature on this topic is mostly in the form of retrospective case series and reports. In this article we review the risk factors, diagnostic modalities and treatment options for the management of CD presenting as GI hemorrhage.     

Effectiveness of infliximab after adalimumab failure in Crohn's disease

AIM: To evaluate the effectiveness of infliximab as a second-line therapy in Crohn’s disease patients after adalimumab failure.METHODS: A historical cohort study in a community-based gastroenterology practice evaluated Crohn’s disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA).RESULTS: We included 15 Crohn’s disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab.CONCLUSION: Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.     

Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn’s disease

AIM:To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn’s disease(CD).METHODS:The work was performed as a prospective study.All patients received infliximab combined withsurgery to treat perianal fistulizing CD,which was followed by an immunosuppressive agent as maintenance therapy.RESULTS:A total of 28 patients with perianal fistulizing CD were included.At week 30,89.3%(25/28)of the patients were clinically cured with an average healing time of 31.4 d.The CD activity index decreased to70.07±77.54 from 205.47±111.13(P0.01)after infliximab treatment.The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89(P0.01).C-reactive protein,erythrocyte sedimentation rate,platelets,and neutrophils all decreased significantly compared with the pretreatment levels(P0.01).Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up.After a median follow-up of 26.4 mo(range:14-41 mo),96.4%(27/28)of the patients had a clinical cure.CONCLUSION:Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD,and this treatment was associated with better longterm outcomes.     

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the pat...     

Enterolithiasis-associated ileus in Crohn's disease

Stasis of the flow of the intestinal contents, ingested material and unfavorable composition of the chylus can lead to the formation of enteroliths inside the bowel. Enterolithiasis represents a rare disorder of the gastrointestinal tract that can be associated with intermittent abdominal pain or more serious complications such as bleeding or obstruction. Enterolithiasis in Crohn’s disease represents an extremely rare condition and usually occurs only in patients with a long symptomatic history of Crohn’s disease. We report an unusual case of enterolithiasis-related intestinal obstruction in a young male patient with Crohn’s disease (A2L3B1 Montreal Classification for Crohn’s disease 2005) undergoing emergency laparotomy and ileocoecal resection. In addition, we present an overview of the relevant characteristics of enterolithiasis on the basis of the corresponding literature.     

Health care resource use and costs in Crohn's disease before and after infliximab therapy

BACKGROUND:

Infliximab therapy in patients with Crohn’s disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study.

METHODS:

A retrospective analysis of economic data one and two years before and after infliximab therapy was performed using patients who served as their own controls. Total health care resource use and direct health care costs were compared for patients with or without fistulae.

RESULTS:

Patients with one (n=66) and two (n=39) years of economic data before and after infliximab treatment had their resource use and direct health care costs estimated. In the year following initiation of infliximab therapy, there were significant decreases in health care use, reflected in total hospital days (495 to 155 [P<0.05]), inpatient colonoscopies (46 to 24 [P<0.05]), outpatient colonoscopies (58 to 33 [P<0.05]) and major surgeries (10 to 2 [P<0.05]). Direct health care costs of inpatient costs for luminal (−$1,747 [P<0.05]) and fistulizing disease (−$2,530 [P<0.05]), major surgeries (−$1240 [P<0.05]) and outpatient colonoscopies (−$184 [P<0.05]) were also significantly reduced before and after infliximab therapy. Total direct health care costs, including the drug cost of infliximab, increased ($21,416 [P<0.05]). In general, the trends in health care costs analyzed over four consecutive years paralleled the two consecutive-year analysis.

CONCLUSIONS:

Infliximab therapy in patients with Crohn’s disease resulted in a significant decrease in both resource use and health care costs, but an increase in total direct health care costs once the cost of infliximab was added.     

Effect of adalimumab on work productivity and indirect costs in moderate to severe Crohn's disease: a meta-analysis

OBJECTIVE:

To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn’s disease (CD) using a meta-analysis of clinical trials.

METHODS:

Study-level results were pooled from all clinical trials of adalimumab for moderate to severe CD in which work productivity outcomes were evaluated. Work Productivity and Activity Impairment Questionnaire outcomes (absenteeism, presenteeism and total work productivity impairment [TWPI]) were extracted from adalimumab trials. Meta-analyses were used to estimate pooled averages and 95% CIs of one-year accumulated reductions in work productivity impairment with adalimumab. Pooled averages were multiplied by the 2008 United States national average annual salary ($44,101) to estimate per-patient indirect cost savings during the year following adalimumab initiation.

RESULTS:

The four included trials (ACCESS, CARE, CHOICE and EXTEND) represented a total of 1202 employed adalimumab-treated patients at baseline. Each study followed patients for a minimum of 20 weeks. Pooled estimates (95% CIs) of one-year accumulated work productivity improvements were as follows: −9% (−10% to −7%) for absenteeism; −22% (−26% to −18%) for presenteeism; and −25% (−30% to −20%) for TWPI. Reductions in absenteeism and TWPI translated into per-patient indirect cost savings (95% CI) of $3,856 ($3,183 to $4,529) and $10,964 ($8,833 to $13,096), respectively.

CONCLUSION:

Adalimumab provided clinically meaningful improvements in work productivity among patients with moderate to severe CD, which may translate into substantial indirect cost savings from an employer’s perspective.     

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM: To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn’s disease in high-risk patients.METHODS: A multicenter, prospective, observational study was conducted from June 2009 until June 2010. We consecutively included high-risk Crohn’s disease patients who had undergone an ileal/ileocolonic resection. High-risk patients were defined as two or more criteria: smokers, penetrating pattern, one or more previous surgical resections or prior extensive resection. Subcutaneous adalimumab was administered 2 wk (± 5 d) after surgery at a dose of 40 mg eow, with an initial induction dose of 160/80 mg at weeks 0 and 2. Demographic data, previous and concomitant treatments (antibiotics, 5-aminosalicylates, corticosteroids, immunomodulators or biologic therapies), smoking status at the time of diagnosis and after the index operation and number of previous resections (type and reason for surgery) were all recorded. Biological status was assessed with C-reactive protein, erythrocyte sedimentation rate and fecal calprotectin. One year (± 3 mo) after surgery, an ileocolonoscopy and/or magnetic resonance enterography was performed. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. Morphological recurrence was based on magnetic resonance (MR) score ≥ MR1.RESULTS: Twenty-nine patients (55.2% males, 48.3% smokers at diagnosis and 13.8% after the index operation), mean age 42.3 years and mean duration of the disease 13.8 years were included in the study. A mean of 1.76 (range: 1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection. 51.7% had previously received infliximab. Immunomodulators were given concomitantly to 17.2% of patients. Four of the 29 (13.7%) developed clinical recurrence, 6/29 (20.7%) endoscopic recurrence and 7/19 (36.8%) morphological recurrence after 1-year. All patients with clinical recurrence showed endoscopic and morphological recurrence. A high degree of concordance was found between clinical-endoscopic recurrence (κ = 0.76, P < 0.001) and clinical-morphological recurrence (κ = 0.63, P = 0.003). Correlation between endoscopic and radiological findings was good (comparing the 5-point Rutgeerts score with the 4-point MR score, a score of i4 was classified as MR3, i3 as MR2, and i2-i1 as MR1) (P < 0.001, r_s = 0.825). During follow-up, five (17.2%) patients needed adalimumab dose intensification (40 mg/wk); Mean time to intensification after the introduction of adalimumab treatment was 8 mo (range: 5 to 11 mo). In three cases (10.3%), a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk. One patient suffered an adverse event.CONCLUSION: Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.     

Angioedema associated with Crohn's disease: Response to biologics

A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.     

Prognostic factors for recurrence of gastrointestinal bleeding due to Dieulafoy's lesion

AIM: To analyze the effectiveness of the endoscopic therapy and to identify prognostic factors for recurrent bleeding.METHODS: Retrospective study of patients with gastrointestinal bleeding secondary to Dieulafoy’s lesion (DL) from 2005 to 2011. We analyzed the demographic characteristics of the patients, risk factors for gastrointestinal bleeding, endoscopic findings, characteristics of the endoscopic treatment, and the recurrence of bleeding. We included cases in which endoscopy described a lesion compatible with Dieulafoy. We excluded patients who had potentially bleeding lesions such as angiodysplasia in other areas or had undergone other gastrointestinal endoscopic procedures.RESULTS: Twenty-nine patients with DL were identified. Most of them were men with an average age of 71.5 years. Fifty-five percent of the patients received antiaggregatory or anticoagulant therapy. The most common location for DL was the stomach (51.7%). The main type of bleeding was oozing in 65.5% of cases. In 27.6% of cases, there was arterial (spurting) bleeding, and 6.9% of the patients presented with an adherent clot. A single endoscopic treatment was applied to nine patients (31%); eight of them with adrenaline and one with argon, while 69% of the patients received combined treatment. Six patients (20.7%) presented with recurrent bleeding at a median of 4 d after endoscopy (interquartile range = 97.75). Within these six patients, the new endoscopic treatment obtained a therapeutic success of 100%. The presence of arterial bleeding at endoscopy was associated with a higher recurrence rate for bleeding (50% vs 33.3% for other type of bleeding) [P = 0.024, odds ratio (OR) = 8.5, 95% CI = 1.13-63.87]. The use of combined endoscopic treatment prevented the recurrence of bleeding (10% vs 44.4% of single treatment) (P = 0.034, OR = 0.14, 95% CI = 0.19-0.99).CONCLUSION: Endoscopic treatment of DL is safe and effective. Adrenaline monotherapy and arterial (spurting) bleeding are associated with a high rate of bleeding recurrence.     

Tracheobronchial nodules and pulmonary infiltrates in a patient with Crohn's disease

Crohn’s disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn’s disease is even more unusual, only a few cases have been reported to date. We herein report a rare case of tracheobronchial nodules and pulmonary infiltrates in both lungs as a complication of Crohn’s disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn’s disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheobronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn’s disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn’s disease is rare and responded well to steroids.     

Predicting, treating and preventing postoperative recurrence of Crohn's disease: the state of the field

The majority of patients diagnosed with Crohn's disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn's disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn's disease recurrence.     

Gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn＇s disease

We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the first report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.     

Mycobacterium avium paratuberculosis and the etiology of Crohn's disease: a review of the controversy from the clinician's perspective

Mycobacterium avium paratuberculosis (MAP) is an obligate intracellular organism that has frequently been associated with Crohn's disease (CD). Because CD is a chronic inflammatory condition, many researchers have speculated that an infectious agent must be the cause of CD. MAP has often been proposed to be one such agent; however, despite considerable research, the evidence remains inconclusive. Higher levels of MAP have been found in the tissues and blood of CD patients than in controls, forming the foundation for much of the research into the role of MAP in CD and the primary argument in support of a causative role for MAP in CD. MAP is a slow-growing and fastidious organism that is difficult to grow in culture and, therefore, challenging to detect in patients. As a result, there has been variability in the results of studies attempting to detect the presence of MAP in CD patients, and considerable controversy over whether this organism has a causative role in the etiology of CD. Two main hypotheses exist with respect to the role of MAP in CD. The first is that MAP is a principal cause of CD, while the second is that MAP is more prevalent because of the immune dysfunction seen in CD but does not play a causative role. Clinicians are often faced with questions regarding the role of this organism and the need to treat it. The present article attempts to provide an overview of the controversy including the nature of the mycobacterium, the difficulty in detecting it, the use of antimycobacterial agents to treat it and the effect of immunosuppressive agents - all from a clinician's perspective. Although the role of MAP in CD remains controversial and an area of considerable research, it is currently only of academic interest because there is no clinically useful test to identify the presence of the organism, and no evidence to support the use of antibiotics to eradicate it for the treatment of CD.     

Cost-effectiveness of Crohn's disease post-operative care

AIM: To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn's disease following intestinal resection.METHODS: In the "POCER" study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care(6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin(FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 mo.RESULTS: Sixty patients(active care n = 43, standardcare n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those inremission [ $ 26347( IQR 25045-27485) vs $2729(IQR 1182-5215), P 0.001]. FC to select patients for colonoscopy could reduce cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence prevented. CONCLUSION: Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated.     

An unusual presentation of fistulating Crohn's disease: Ascites

Whilst ascites is a common presenting complaint in patients with decompensated chronic liver disease and disseminated malignancy, in Crohn's disease however, it is exceptionally rare. We describe a patient with no prior history of inflammatory bowel or liver disease, presenting with rapid onset gross ascites and scrotal swelling. Further investigations revealed severe hypoalbuminemia and transudative ascitic fluid with normal other liver function tests and a negative liver screen. Computed tomography revealed widespread ascites and pleural effusions with no features of malignancy or portal hypertension, and a small bowel barium series showed features of fistulating small bowel Crohn's disease. An ileo-colonoscopy confirmed the presence of terminal ileal inflammatory stricture. The patient's clinical condition and serum albumin improved with a combination of diuretics, elemental diet, antibiotics and oral 5-aminosalicylic acid therapy.     

Time of infliximab therapy initiation and dose escalation in Crohn’s disease

AIM:To determine if early initiation of anti-tumor necrosis factor therapy affects the need for dose escalation.METHODS:This was a retrospective review of patients receiving infliximab therapy for Crohn’s disease(CD)at two outpatient gastroenterology clinics during July2009 to October 2010.All patients included in the study were biologic agent na?ve and had moderate to severe CD(Harvey Bradshaw index>8).Patients were divided into groups based on length of time between diagnosis to therapy initiation and concurrent immunosuppressant therapy.Kaplan-Meier survival analysis was used to compare the time to dose escalation for the four groups.RESULTS:There were 68 patients,51% female and 49% male,with an average age at diagnosis of 24.7±11.9 years.The average age at infliximab initiation was 34.8±14.8 years.Of the 68 patients,19%initiated inflixiamb within 2 years of diagnosis,and 51%had concurrent immunosuppressant therapy at the time of therapy initiation.Fifty percent of patients required dose escalation and the median time from therapy initiation to dose escalation was 10 mo(interquartile range:5.3-14.8).There was a statistically significant higher probability of requiring dose esclataion in patients who initiated biologic therapy within 2 years of diagnosis,without concurrent immunosuppressant therapy(P<0.01).CONCLUSION:Those who receive infliximab within 2years of CD diagnosis require more intense immunosuppressant therapy than those who received infliximab later.     

Fulminant legionellosis in two patients treated with infliximab for Crohn’s disease: Case series and literature review

Two cases of fulminant pulmonary legionellosis, complicated by prolonged intensive care unit stays and acute respiratory distress syndrome, and who were recently treated with infliximab for Crohn’s disease, are described. A review of the literature revealed three additional cases in patients with inflammatory bowel disease, and a total of 22 cases of Legionella pneumophila pneumonia in the context of treatment with antitumour necrosis (TNF)-alpha medications. The median age of the patients was 49 years, and men and women were affected equally. The case fatality rate was 14% (three of 22). Early recognition and treatment of this anti-TNF-alpha-related complication would likely result in reduced mortality and morbidity. Physicians prescribing anti-TNF-alpha drugs should be aware of this association.     

Accelerated infliximab infusions for inflammatory bowel disease improve effectiveness

AIM:To study the safety and effectiveness associated with accelerated infliximab infusion protocols in patients with inflammatory bowel disease(IBD).METHODS:Original protocols and infusion rates were developed for the administration of infliximab over 90-min and 60-min.Then the IBD patients on stable maintenance infliximab therapy were offered accelerated infusions.To be eligible for the study,patients needed a minimum of four prior infusions.An initial infusion of 90-min was given to each patient;those tolerating the accelerated infusion were transitioned to a 60-min infusion protocol at their next and all subsequent visits.Any patient having significant infusion reactions would be reverted to the standard 120-min protocol.A change in a patient’s dose mandated a single 120-min infusion before accelerated infusions could be administered again.RESULTS:The University of Virginia Medical Center’s Institutional Review Board approved this study.Fifty IBD patients treated with infliximab 5mg/kg,7.5mg/kg and 10mg/kg were offered accelerated infusions.Forty-six patients consented to participate in the study.Nineteen(41.3%) were female,five(10.9%) were African American and nine(19.6%) had ulcerative colitis.The mean age was 42.6 years old.Patients under age 18 were excluded.Ten patients used immunosuppressive drugs concurrently out of which six were taking azathioprine,three were taking 6-mercaptopurine and one was taking methotrexate.One of the 46 study patients used corticosteroid therapy for his IBD.Seventeen of the patients used prophylactic medications prior to receiving infusions;six patients received corticosteroids as pre-medication.Four patients had a history of distant transfusion reactions to infliximab.These reactions included shortness of breath,chest tightness,flushing,pruritus and urticaria.These patients all took prophylactic medications before receiving infusions.46 patients(27 males and 19 females) received a total of fifty 90-min infusions and ninety-three 60-min infusions.No infusion reactions were reported.There were no adverse events,including drug-related infections.None of the patients developed cancer of any type during the study timeframe.Total cost savings for administration of the both 90-min and 60-min accelerated infusions compared to standard 120-min infusions was estimated to be $53 632($116 965 vs $63 333,P=0.001).One hundred and eighteen hours were saved in the administration of the accelerated infusions(17 160 min vs 10 080 min,P=0.001).In the study population,overweight females [body mass index(BMI)>25.00kg/m2] were found to have statistically higher BMIs than overweight males(mean BMI 35.07±2.66kg/m2 vs 30.08±0.99kg/m2,P=0.05),finding which is of significance since obesity was described as being one of the risk factors for Crohn’s disease.CONCLUSION:We are the first US group to report substantial cost savings,increased safety and patient satisfaction associated with accelerated infliximab infusion.