Increased anal resting pressure and rectal sensitivity in crohn’s disease

Anal pathology occurs in 20 to 80 percent of patients with Crohn’s disease in which abscesses, fistulas, and fissures account for considerable morbidity. The etiology is not clearly defined, but altered anorectal pressures may play a role. This study was designed to investigate anorectal physiologic conditions in patients with Crohn’s disease compared with healthy controls. METHODS: Twenty patients with Crohn’s disease located in the ileum (n = 9) or the colon (n = 11) without macroscopic proctitis or perianal disease were included. All were subjected to rectal examination, anorectal manometry, manovolumetry, and rectoscopy. Comparison was made with a reference group of 173 healthy controls of whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both examinations. RESULTS: Maximum resting pressure and resting pressure area were higher in patients than in controls (P = 0.017 and P = 0.011, respectively), whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal sensitivity was increased in patients expressed as lower values both for volume and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum tolerable pressure (P = 0.025). CONCLUSIONS: This study demonstrates how patients with Crohn’s disease without macroscopic proctitis have increased anal pressures in conjunction with increased rectal sensitivity. This may contribute to later development of anal pathology, because increased intra-anal pressures may compromise anal circulation, causing fissures, and also discharging of fecal matter into the perirectal tracts, which may have a role in infection and fistula development.     

Acute coronary syndrome after infliximab therapy in a patient with Crohn’s disease

INTRODUCTION Serious adverse events (infections, malignancies, serum sickness, lupus syndrome) that need hospitalization have been reported with a divergent frequency of 6%-18.9% for patients with inflammatory bowel disease (IBD) treated with infliximab[1…     

Surgical management of crohn’s disease in children

Opinion statement One of the most common beliefs in the management of Crohn’s disease is that surgery should be considered only as a last resort. Surgery is often considered by patients and gastroenterologists to represent a "failure." However, the role of surgery in the care of patients with Crohn’s disease has increasingly become a collaborative effort, with surgeons involved in many aspects of the management of these patients. This is particularly true in pediatric patients, as issues of growth and development may involve surgical intervention at earlier stages than might be required in older patients. In fact, surgical interventions may be indicated at any stage of the disease process. For example, early examination under anesthesia with abscess drainage and delineation of fistula tracts has proven very useful in patients with complex perineal disease. Surgery may contribute to the medical management of the disease by way of providing chronic enteral or parenteral access for nutritional interventions such as elemental feedings and total parenteral nutrition. Finally, surgical treatment of intraabdominal complications including fistulas, phlegmon, and bowel strictures may have a dramatic impact on patient symptoms and side effects. Although bowel resection carries the long-term risk of short bowel syndrome should future resections be required, the improvements in medical therapy continue to reduce the risk of recurrent disease, making surgical resection more palatable. Surgical treatment of complicated disease offers significant potential to limit toxic medical therapy and improve quality of life. In addition, application of minimally invasive techniques can minimize the impact of insults to body image in this vulnerable patient population as well as speed recovery. Future interventions may be facilitated by reducing adhesion formation through the use of minimally invasive techniques. The dynamic nature of growth and development in the pediatric population presents unique complications from medical therapies that are different from those seen in adults. Criteria for surgical intervention must be interpreted in light of the specific challenges facing the pediatric population as frequently pointed out in the oft-quoted maxim, "children are not small adults!"     

Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn’s disease with anal endosonographic monitoring: a single-centre experience

During infliximab treatment of perianal Crohn's disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10+/-2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4+/-8.8 months (range 3-28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25+/-5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.     

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.     

Fistula-associated anal carcinoma in Crohn’s disease

Introduction: Fistula-associated anal carcinoma in patients with Crohn’s disease (CD) is a rare condition. More recently, this entity has been increasingly reported likely due to increased recognition, and the incidence may be greater than once appreciated. There remains a paucity of data regarding the incidence, diagnosis, treatment, and outcome of fistula-associated anal carcinoma.

Area covered: This review evaluates the clinical features, pathology, treatment, and prognosis of fistula-associated anal carcinoma in patients with CD. A strategy for surveillance of this carcinoma is proposed by the authors based on the evidence obtained from this review.

Expert commentary: Clinicians caring for patients with CD and perianal involvement need to be aware of the rare yet extremely important association of long-standing perianal disease and fistula-associated carcinoma. Only through awareness, a high level of suspicion will be diagnosed in a timely manner. This involves a thorough history, a proper, and complete anorectal examination, along with early imaging and examination under anesthesia. Through this approach, it is hoped that early diagnose can be achieved in at-risk patients and change the significant morbidity and mortality associated with this diagnosis.     

Efficacy of early treatment with infliximab in pediatric Crohn’s disease

AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and mainte...     

Acute coronary syndrome after infliximab therapy in a patient with Crohn＇s disease

Infliximab is a potent anti-TNF antibody, which is used with great success in Crohn's disease patients. Since its release in clinical practice, several adverse reactions have been observed. The interest in possible consequences of its administration is still high because of the recent introduction of the drug for the long-term maintenance therapy of refractory luminal and fistulizing Crohn's disease. We present a case of acute coronary syndrome (non-STEMI) in a patient with corticoid resistant Crohn's disease after his first dose of infliximab. By reviewing the scant articles that exist in the literature on this topic we made an effort to delineate the possible mechanisms of this phenomenon.     

Evolving medical therapies for crohn’s disease

Medical therapy for Crohn’s disease has changed dramatically over the past few years. Physicians have become increasingly willing to use traditional immunosuppressive agents such as azathioprine/6-mercaptopurine (6-MP) and methotrexate as well as new biologic therapies such as infliximab. Azathioprine, 6-MP, and methotrexate have demonstrated efficacy in induction and maintenance of remission in Crohn’s disease. 6-MP has also demonstrated efficacy in the pediatric population and possibly as first-line therapy. As use of the purine metabolites grows, therapeutic drug monitoring for efficacy and toxicity will become an emerging area of interest. With respect to the biologic therapies, infliximab is increasingly used to treat patients with difficult disease; however, knowledge is still evolving regarding optimal dosing schedules and the significance of immune reactions to the compound. A humanized anti-tumor necrosis factor antibody, CDP571, may be less immunogenic. Interleukin-10 did not consistently demonstrate benefit in Crohn’s disease. Similarly, antisense to intracellular adhesion molecule 1 (ISIS 2302) was not efficacious when administered either subcutaneously or intravenously. Finally, growth hormone has shown promising results in a small trial.     

6-Mercaptopurine for children newly diagnosed with crohn’s disease

Conclusions Addition of 6-MP to a regimen of corticosteroids significantly lessened the need for prednisone and improved maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe Crohn’s disease.     

Crohn’s disease complicated by adult-onset Still’s disease

A 31-year-old man with Crohns disease developed arthritis, spiking fever, and skin rash indistinguishable from that of adult-onset Stills disease. He was admitted to our hospital because of a periumbilical intestinal skin fistula. Crohns disease had been diagnosed in 1991, and had required intestinal resection twice, and schizophrenia had been diagnosed in 1993. He developed polyarthritis and spiking fever, accompanied by a macular skin rash on both forearms. Marked hepatosplenomegaly and bilateral pleural effusion were detected on computed tomography examination. These findings are indistinguishable from those of adult-onset Stills disease. Because his mental status had deteriorated following high-dose prednisolone on a previous admission, he was treated with an immunosuppressive agent on this occasion, with the treatment being successful. This is the first report of adult-onset Stills disease complicating Crohns disease. In patients with Crohns disease, polyarthritis and skin rash can easily be misdiagnosed as enteropathic arthritis with erythema nodosum associated with the Crohns disease. Although adult-onset Stills disease may not be fatal, early diagnosis is important because it can, in rare cases, result in life-threatening complications.     

Long-term efficacy of infliximab maintenance therapy for perianal Crohn’s disease

AIM:To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease(CD). METHODS:Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s database.The activities of the perianal lesions were evaluated using the modified perianal CD activity index(mPDAI)score.The primary endpoint was a clinical response at 12-15 wk after su...     

Long-term response rates to infliximab therapy for Crohn’s disease in an outpatient cohort

BACKGROUND:

Infliximab’s efficacy in the induction and maintenance of remission in luminal Crohn’s disease has been confirmed by randomized, controlled trials. Less clearly described are long-term outcomes in the clinical practice setting since the establishment of regularly scheduled, every eight-week maintenance infliximab infusions. Existing reports describing clinical practice outcomes are limited by short durations of follow-up or by the use of episodic dosing, or focus on safety data rather than clinical outcomes.

OBJECTIVE:

To examine induction and maintenance responses to infliximab in an outpatient inflammatory bowel disease clinic.

METHODS:

A retrospective chart review was performed. Clinical outcomes were infliximab induction and maintenance responses, defined as the ability to stop and remain off corticosteroids while not requiring additional therapy for active disease.

RESULTS:

One hundred thirty-three patients were identified with records sufficiently detailed to be analyzed. Of these, 117 patients (88%) demonstrated a clinical response to induction; 104 of 117 (89%) were on concomitant immunosuppressive therapy; 80 of 104 on azathioprine/6-mercaptopurine (77%); and 24 of 104 on methotrexate (23%). The mean duration of clinical response was 94 weeks (95% CI 78.8 to 109.2). The proportion of patients who maintained response at 30 weeks was 83.2%, at 54 weeks was 63.6% and at 108 weeks was 44.9%. Adverse events occurred for 15 of 117 patients (12.8%), consisting of nine infusion reactions, four serum sickness-like reactions, one rash and one infection.

CONCLUSION:

Patients treated with infliximab therapy for luminal Crohn’s disease in our outpatient clinic achieved excellent induction and maintenance of response rates, confirming the real-life efficacy of maintenance infliximab established in clinical trials.     

Advances in therapeutic approaches to ulcerative colitis and crohn’s disease

Advances (from 2004 to 2006) in the use of conventional agents include the molecular mechanisms of action, which have implications for monitoring (azathioprine and thioguanosine triphosphate) and chemoprevention (mesalamine and peroxisome proliferator activated receptor [PPAR]γ). Advances in biotherapy include new data on monoclonal antibodies (infliximab in ulcerative colitis, adalimumab, certolizumab pegol, fontolizumab, selective anti-adhesion molecules, and others), antisense oligonucleotides, the development of small molecules, and cell-gene therapy (including helminth ova, leukocytapheresis, stem cell transplantation, and probiotic intestinal mucosal delivery systems). However, management of inflammatory bowel disease is about more than drug therapy, dose, and timing. The goals remain induction of remission, limitation of side effects, modification of the pattern of disease, and avoidance of complications. With the cost and complexity of biotherapy, inflammatory bowel disease is emerging as a specific subspecialty.     

Liver test abnormalities predict complicated disease behaviour in patients with newly diagnosed Crohn’s disease

Backgrounds

In coeliac disease, the prevalence of liver test abnormalities (LTAs) is higher in patients with more severe mucosal inflammation. In Crohn’s disease, prognosis is related to the severity of mucosal inflammation.

Aim

The aim of this study was to investigate whether the presence of LTA predicts the occurrence of complicated disease behaviour in newly diagnosed Crohn’s disease.

Methods

A retrospective cohort study was performed in patients newly diagnosed with Crohn’s disease between 2002 and 2011. The complicated disease was defined as the occurrence of stricturing and/or perforating disease. LTAs were defined as a value of any of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) over the upper limit of normal.

Results

Three hundred eighty-three patients were included, of whom 34.1% had LTA. LTAs were mostly mild (less than two times the upper limit of normal). During the 5-year follow-up, 33.1% of patients in the group with LTA developed complicated disease behaviour compared to 14.6% in patients without LTA (p < 0.001). The presence of LTA was identified as a risk factor for complicated disease behaviour (HR 2.6, 95% confidence interval (CI) 1.5–4.2, p < 0.0001).

Conclusions

In newly diagnosed Crohn’s disease, the presence of LTA was an independent risk factor for the development of complicated disease behaviour.

     

Optimizing biological therapy in Crohn’s disease

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn’s disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn’s disease and identify strategies to optimize biological treatment.     

Successful treatment of life-threatening intestinal ulcer in Behçet’s disease with infliximab: rapid healing of Behçet’s ulcer with infliximab

Behçet’s disease is a chronic, relapsing, multisystem inflammatory disorder characterized predominantly by recurrent orogenital ulcers, skin involvement, and uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases, but ocular, gastrointestinal, and central nervous system involvement may occur in severe cases. We report in this study the successful treatment with infliximab of severe life-threatening GI bleeding caused by an ileal ulcer in a patient with Behçet’s disease. Antitumor necrosis factor (TNF) therapy could be an emergency therapeutic option in patients with massively bleeding Behçet’s disease and unstable patients or those with acute bleeding with other TNF-α-mediated autoimmune diseases. Another option for anti-TNF therapy could be as bridging management between conservative and surgical treatment.