Journal of Crohn's and Colitis - Articles in Press

Corrigendum to “The second European evidence-based consensus on the diagnosis and management of Crohn's disease: Current Management” [J Crohn's & Colitis 4 (2010) 28–62] - Corrected Proof

Axel U. Dignass — 2010-07-16

The authors and publisher regret and apologise that, in the above article, the following mistake was inadvertently slipped: On page 38, first paragraph reads:

Cutaneous vasculitis in Crohn's disease - Corrected Proof

J.K. Limdi, H.M. Doran, J.R Crampton — 2010-07-15

Crohn's disease is associated with a variety of cutaneous manifestations many of which parallel disease activity. Associations such as erythema nodosum, pyoderma gangrenosum and apthous ulceration are well known and rarer associations such as Sweet's syndrome and metastatic Crohn's disease are recognised. Curiously, leucocytoclastic vasculitis as a cutaneous manifestation of Crohn's disease remains rare or under-recognised.

Rectal non-Hodgkin's lymphoma in an infliximab treated patient with ulcerative colitis and primary sclerosing cholangitis - Corrected Proof

2010-07-15

Abstract: A 20-year old man with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) was diagnosed with a rectal non-Hodgkin's lymphoma (NHL) at surveillance endoscopy while being in remission on infliximab therapy. Further staging identified a diffuse large B-cell NHL, EBV negative restricted to the rectal submucosa (stage IA). Until now, there has not been any evidence of an increased risk of NHL in patients with UC nor of an increased risk of lymphoproliferative disorders in IBD patients. Hence, the role of concomitant PSC in the pathogenesis of intestinal NHL is unclear. However, IBD patients treated with purine analogues and with anti-TNF are at risk of NHL, especially hepatosplenic T-cell lymphoma. The management of this particular young patient is further complicated by the possibility of a future colectomy due to intractable disease which compromises the use of radiotherapy for this localized disease.

A rare extraintestinal manifestation of ulcerative colitis: Tracheobronchitis associated with ulcerative colitis - Corrected Proof

2010-07-09

Abstract: We describe a 44year-old woman who presented with dyspnea and cough 5years after initial diagnosis of ulcerative colitis. The evaluation of patient showed findings of large airway inflammation with tracheal wall thickening and mucosal irregularities. The etiology was investigated and was diagnosed as tracheobronchitis that is a rare extraintestinal manifestation of ulcerative colitis. She was treated with systemic corticostreoids and rapid clinical improvement was detected.

Paneth's disease - Corrected Proof

Jan Wehkamp, Eduard F. Stange — 2010-07-06

Abstract: In about 70% of patients Crohn's disease (CD) affects the small intestine. This disease location is stable over time and associated with a genetic background different from isolated colonic disease. A characteristic feature of small intestinal host defense is the presence of Paneth cells at the bottom of the crypts of Lieberkühn. These cells produce different broad spectrum antimicrobial peptides (AMPs) most abundantly the α-defensins HD-5 and -6 (DEFA5 und DEFA6). In small intestinal Crohn's disease both these PC products are specifically reduced. As a functional consequence, ileal extracts from Crohn's disease patients are compromised in clearing bacteria and enteroadherent E. coli colonize the mucosa. Mechanisms for defective antimicrobial Paneth cell function are complex and include an association with a NOD2 loss of function mutation, a disturbance of the Wnt pathway transcription factor TCF7L2 (also known as TCF4), the autophagy factor ATG16L1, the endosomal stress protein XBP1, the toll-like receptor TLR9, the calcium mediated potassium chanel KCNN4 as well as mutations or inactivation of HD5. Thus we conclude that small intestinal Crohn's disease is most likely a complex disease of the Paneth cell: Paneth's disease.

A family report of Crohn's disease in three children immigrating from Albania to Greece and review of the literature - Corrected Proof

Konstantinos H. Katsanos, Vasileios Karetsos, Epameinondas V. Tsianos — 2010-07-05

Abstract: Cases of immigrant families affected by IBD have rarely been reported and seem to be of exceptional interest towards a better understanding of disease aetiopathogenesis.The first case of Crohn's disease in a family of immigrants from Albania to Greece with three offspring is described herein. A family with three children, one 22year-old male and two 18-year-old twin females immigrated from southern Albania to northwest Greece ten years ago. The whole family lived in the same house and had no previous history of bowel or other chronic diseases. Two years ago the boy complained of diarrhoea, perianal pain and loss of weight. Subsequent investigation revealed ileal and perianal Crohn's disease. One year after Crohn's disease was diagnosed in the boy, one of the twins was diagnosed with ileal Crohn's disease. Six months afterwards, the second twin underwent emergency appendectomy due to acute appendicitis; four months later she was diagnosed with ileal Crohn's disease.Genetically predisposed individuals seem to be vulnerable to a continuous pressure of a still unknown environmental factor(s). In addition, lifestyle modification seems to represent a predisposing factor toward inflammatory bowel disease in immigrants.

Adherence of gastroenterologists to European Crohn's and Colitis Organisation consensus on ulcerative colitis: A real-life survey in Spain - Corrected Proof

J.P. Gisbert, F. Gomollón, J. Hinojosa, A. López San Román — 2010-07-05

Abstract: Background & aims: A European consensus on the management of ulcerative colitis (UC) was recently published; however, there is no adequate evidence about adherence to such guidelines among gastroenterologists. This knowledge would allow the local evaluation of the situation and the adoption of actions to reduce the existent clinical variability.Methods: A cross-sectional survey was conducted in Spain to assess the adherence to the European Crohn's and Colitis Organisation (ECCO) guidelines on mild to moderate UC. We surveyed 700 gastroenterologists, and finally a total of 530 gastroenterologists specialised in inflammatory bowel disease (GSIBDs) and general gastroenterologists (GGs), responded to the survey (76%).Results: Agreement with the guidelines was high; discrepancies included that only 25% of the GGs used the combination of oral and topical 5-aminosalycilic acid (5-ASA) for treating extensive UC vs 45% of the GISBDs. In addition, topical rectal steroids were considered as effective as topical mesalazine by 48% of the GGs vs 31% of the GSIBDs, indefinite treatment with 5-ASA was prescribed by only 26% of the GGs vs 41% of the GSIBDs, and the once daily dosing of 5-ASA was generally used by 46% of the GGs vs 51% of the GSIBDs.Conclusions: The questionnaire showed a high degree of agreement between GGs and GSIBDs. Nevertheless, the GSIBD group showed closer agreement with the ECCO guidelines. Furthermore, some shortcomings were found in the GG group, in which increased maintenance treatment with 5-ASA, the use of a single daily dose of 5-ASA, and the use of combined oral and topical treatment for distal colitis should be advised.

Report of the ECCO workshop on anti-TNF therapy failures in inflammatory bowel diseases: Biological roles and effects of TNF and TNF antagonists - Corrected Proof

2010-07-01

Abstract: This second section of the first ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases addresses the biological roles of TNFα and the effects and mechanisms of action of TNFα antagonists. Mechanisms underlying their failure, including induction of TNF-independent inflammatory pathways and phenomena of paradoxical inflammation are discussed.

Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: Definitions, frequency and pharmacological aspects - Corrected Proof

2010-06-30

Abstract: The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts. This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists, including mechanisms of action of anti-TNF agents, and discuss hypothesis regarding their failures and phenomenon of paradoxical inflammation, including the potential role of TNF independent inflammatory pathways.

A case of orbital myositis preceding the intestinal symptoms of Crohn's disease - Corrected Proof

2010-06-28

Muscle involvement is a rare extraintestinal manifestation of Crohn's disease (CD). It can be related either to therapy or to disease related myositis or to a coexistent autoimmune disorder affecting the muscle. Colonic disease is more often associated with the myopathy than is small bowel involvement alone and precedes the development of myositis in most cases.

Hepatosplenic T-cell lymphoma and inflammatory bowel disease - Corrected Proof

Anne Thai, Thomas Prindiville — 2010-06-28

Abstract: Objective: This article reviews the current literature and knowledge about hepatosplenic T-cell lymphoma (HSTCL), providing an overview of the clinical features, a description of its pathology and immunophenotypic traits in relation to other lymphomas. In addition, we explore the history of reported cases of hepatosplenic T-cell lymphoma in relation to the possible existence of a causal relationship between infliximab use and HSTCL. The treatments for HSTCL will be briefly addressed.Methods: A comprehensive literature search using multiple databases was performed. Keyword search phrases including “lymphoma,” “hepatosplenic T-cell lymphoma,” “Inflammatory bowel disease,” “6-mercaptopurine,” and “infliximab” were used in various combinations. In addition references from published papers were reviewed as well.Results: There are over 200 reported cases of HSTCL. Only 22 cases of hepatosplenic T-cell lymphoma are associated with IBD treatment. Clinicians usually reserve immunomodulators and biologics for moderate to severe IBD cases. The ultimate goal of therapy is to control inflammation and therefore allow mucosal healing. IBD patients demonstrating mucosal healing are less likely to undergo surgery and experience complications related to their disease. We manipulate the immune system with corticosteroids, immunomodulators, and biologics, therefore causing bone marrow suppression. With bone marrow suppression, malignant degeneration may begin through selective uncontrolled cell proliferation, initiating HSTCL development in the genetically susceptible.Conclusion: Hepatosplenic T-cell lymphoma is a rare disease, often with a poor outcome. With the increasing number of reported cases of HSTCL linked to the use of infliximab, adalimumab, and AZA/6-MP, there appears to be an undeniable association of HSTCL development with the use of these agents. This risk is unquantifiable. When considering the rarity of cases and the multiple complications with uncontrolled disease, however, the benefit of treatment far outweighs the risk.

Nephrolithiasis as an extra-intestinal presentation of pediatric inflammatory bowel disease unclassified - Corrected Proof

2010-06-28

Abstract: Urolithiasis is quite rare in pediatric inflammatory bowel disease (IBD) compared with the incidence at 9–18% in adult cases. The diagnosis and treatment of pediatric IBD is challenging. Indeterminate colitis (IC), originally proposed as a subgroup of fulminant IBD, has also been used for patients when the diagnosis of either UC or CD cannot be made with certainty. Such patients should be diagnosed as having “IBD unclassified” based on evidence including mucosal biopsy samples. We report herewith a 9-year-old boy with isolated colitis that reached a diagnosis of IBD unclassified. Infliximab therapy led to a successful remission after the refractory course. However, urolithiases were impacted in the urethral valves and vesico-ureteral junction. Microhematuria was noticed from the onset of colitis. Renal calculi were detected on the X-ray films during the first line treatment. Transurethrally crushed stones consisted of calcium oxalate. Renal calculi are more closely associated with CD than ulcerative colitis in adult patients for the ileal involvement. The oxalate stones and treatment response indicated a CD-like pathophysiology. Nephrolithiasis might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Infliximab therapy could be an option in pediatric refractory colitis to change the critical steroid dependency.

Acute cryptosporidiosis as a cause of sudden recurrence of digestive symptoms in patients with Crohn's disease - Corrected Proof

2010-06-24

Abstract: Gastrointestinal symptoms occurring in patients with Crohn's disease (CD) can be related to disease activity or to intercurrent infection. Absence of appropriate stool work-up can lead to misdiagnosis and wrong treatment. We report here two cases of acute cryptosporidiosis in patients with CD. This microorganism can trigger IBD flare or cause severe infections in immunocompromised host. Adding specific search for oocysts of Cryptosporidium parvum using the Ziehl–Neelsen technique to the microbiologic work-up from stools in patients with Crohn's disease seeking medical intervention for sudden exacerbation of digestive symptoms seems to be recommended.

Paucity of mycobacteria in mucosal bowel biopsies from adults and children with early inflammatory bowel disease - Corrected Proof

2010-06-21

Abstract: Background: The presence of Mycobacterium avium subspecies paratuberculosis (MAP) has previously been inferred in the genesis of Crohn's disease (CD), and a higher incidence of MAP PCR positivity has been demonstrated in the gut and peripheral blood of CD patients than in healthy individuals. The objective of this prospective study was to assess the potential etiological role of MAP in the pathogenesis of CD.Methods: The presence of mycobacteria was assessed in bowel biopsies from newly diagnosed, treatment naïve Norwegian patients with IBD, including CD and ulcerative colitis (UC), as compared to a hospital-based cohort of CD and UC patients. Biopsies were collected from the small and large bowel in 354 individuals with suspected IBD. Detection of mycobacteria was performed by long-term cultivation in combination with direct detection by MAP IS900-specific PCR.Results: Among the specimens included from the patients with early IBD, samples from only two of the patients with CD (2.7%) and two of the non-IBD controls (1.5%) exhibited a positive growth signal. None of the CD patients and only one of the non-IBD controls was MAP PCR positive. Only the single PCR positive non-IBD control was also mycobacterial culture positive with Mycobacterium avium subsp. hominissuis. In the referral patients with long-term IBD, the prevalence of growth signal and MAP PCR positivity was higher (52 and 9%, respectively).Conclusions: These findings demonstrate the paucity of MAP in the gut of treatment naïve CD patients. This study does not provide evidence for a role of MAP in early IBD.

Suicide attempt in ulcerative colitis patient after 4months of infliximab therapy — A case report - Corrected Proof

E.J. Eshuis, K.M.M.Y. Magnin, P.C.F. Stokkers, W.A. Bemelman, J. Bartelsman — 2010-06-17

Abstract: In the summary of product characteristics of infliximab (IFX), psychiatric side effects are reported to be rare, and in literature only limited data exist. This report presents a case of a patient with ulcerative colitis who developed a depression with psychotic symptoms during IFX therapy and made a suicide attempt 4months after the initiation of therapy. Although the time between start of IFX therapy and onset of symptoms could suggest a correlation, this, of course, does not prove that IFX was the causative factor for his depression and suicide attempt.

Two cases of fatal Pneumocystis jirovecii pneumonia as a complication of tacrolimus therapy in ulcerative colitis — A need for prophylaxis - Corrected Proof

M. Escher, E.F. Stange, K.R. Herrlinger — 2010-06-16

Abstract: Here we report 2 cases of fatal Pneumocystis jirovecii pneumonia in patients with severe ulcerative colitis receiving combination immunosuppression including tacrolimus. We discuss the necessity of a P. jirovecii prophylaxis especially in elderly patients according to the European evidence-based consensus on the prevention and management of opportunistic infections in inflammatory bowel disease.

Filiform polyposis associated with sigmoid diverticulitis in a patient without inflammatory bowel disease - Corrected Proof

Hyun-Soo Kim, Kil Yeon Lee, Youn Wha Kim — 2010-06-16

Abstract: Filiform polyposis (FP) of the colon is an uncommon entity that is occasionally encountered in patients with inflammatory bowel disease (IBD). FP is morphologically characterized by multiple slender worm-like projections consisting of submucosal cores lined with normal mucosa. To date, only two cases of FP have been reported in patients with inflammatory conditions of the gastrointestinal tract other than ulcerative colitis or Crohn's disease. We report an additional case of FP occurring in an 83-year-old man with no history of IBD. The patient underwent anterior resection of the sigmoid colon for perforated diverticulitis. Around the diverticular orifice, localized FP involving a 13-cm colonic segment was observed. The filiform polyps consisted of submucosal fibrovascular cores lined with normal mucosa without epithelial dysplasia. To our knowledge, this is the first reported case of FP associated with colonic diverticulitis in a patient without IBD.

Eating the enemy in Crohn's disease: An old theory revisited - Corrected Proof

Renzo Caprilli, Pierre Lapaquette, Arlette Darfeuille-Michaud — 2010-06-15

Abstract: Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adherent-invasive E. coli (AIEC) colonizing the CD ileal mucosa and able to resist to macrophage killing. The role of impaired autophagy in Crohn's disease patients has been recently reinforced by the observation that the peptidoglycan receptor NOD2, in addition to sense intracellular bacteria, can induce autophagy by recruiting the critical autophagy protein ATG16L1 to the plasma membrane during bacterial internalization. Defects in autophagy might be the key element of the pathogenic pathway that lead to defective microbial killing, increased exposure to commensal and pathogenic intestinal bacteria and T cell activation. Defects in Paneth cells secreting lysozyme and antimicrobial peptides are observed in patients with ATG16L1 risk allele. Thus, the induction of autophagy or administration of preparations that mirrors the secretion of Paneth cells or both may be regarded as new therapeutic avenues for the treatment of Crohn's disease.

Increased fatigability of external anal sphincter in inflammatory bowel disease: Significance in fecal urgency and incontinence - Corrected Proof

2010-06-14

Abstract: Background and aims: Fatigability of external anal sphincter (EAS) has not been studied in inflammatory bowel disease (IBD) patients. We evaluated EAS fatigability in IBD patients with and without fecal incontinence (FI) and urgency, and correlated fatigability with demographic and clinical factors, and EAS endosonography.Methods: Fifty-eight consecutive IBD cases and 14 healthy volunteers completed Bristol stool form and a FI severity scale. Groups I, II and III included 27 patients with urgency including 13 with concomitant FI, 31 patients without FI or urgency, and 14 controls, respectively. We performed stationary pull-through manometry with an 8-channel water-perfused catheter. Fatigue rate (FR) was calculated by linear regression during a 20-s anal squeeze, and fatigue rate index (FRI) as the ratio of squeeze pressure increment to FR. EAS thickness and deficits were evaluated with an endoanal 10-MHz probe. Patients underwent sigmoidoscopy.Results: Group I demonstrated a higher Bristol score, more frequent defecations, and more EAS defects compared to group II. Resting, peak squeeze pressures and EAS thickness did not differ between groups. FR was increased in group I versus II, and in group II versus III; FRI was decreased in group I versus II and in group II versus III (p<0.001, adjusting for age and BMI). Gender, oral glucocorticoids, presence of proctitis, perianal disease and EAS defects did not interact with group membership on FR or FRI.Conclusions: IBD is associated with increased fatigue rate and decreased fatigue rate index. These differences were even more striking in patients with incontinence or urgency.

Case Report: Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's Disease - Corrected Proof

2010-06-09

Abstract: We present the case of a 28year old lady with refractory Crohn's Disease treated with infliximab throughout her pregnancy. Her baby was born healthy and received a Bacillus Calmette–Guérin (BCG) vaccine aged 3months. Soon after this the infant became unwell and died aged 4.5months. At post-mortem the cause of death was attributed to an unusual complication of the BCG vaccine, known as disseminated BCG.BCG vaccination is contraindicated in individuals who are receiving immunosuppressive drugs. We recommend physicians should exercise caution before such vaccines are used in infants born to mothers taking anti-TNF therapies or other potentially immunosuppressive IgG1 antibodies.

Ulcerative colitis in the county of Uppsala 1945–2007: Incidence and clinical characteristics - Corrected Proof

A. Rönnblom, S.-M. Samuelsson, A. Ekbom — 2010-06-07

Abstract: Objective: The incidence of ulcerative colitis has increased in many parts of the world during the second part of the twentieth century. In the county of Uppsala in the middle part of Sweden, the epidemiology of ulcerative colitis has been studied during two different time periods, 1945–1964 and 1965–1983. These figures have now been compared to the present day situation, 2005–2007.Method: The incidence figures in the two first studies were the results of retrospective studies but the figures from 2005 to 2007 were generated prospectively. The clinical characteristics during 1945–1964 were described according to the Montreal classification and a comparison between the first and third study periods could therefore be done.Results: During the study period, the population of the county increased from 146000 to 323270 inhabitants. The crude incidence of ulcerative colitis increased from 2 to 19.2 new cases per 100000 inhabitants/year. The age distribution was remarkably stable when the first 20years was compared with the last 3years (mean age 36 vs. 38.1 and range 2–84 vs. 3–84) except for those below 11years of age.Conclusion: Between 1945 and 2007 the incidence of UC in the County of Uppsala increased from 2 to 19.2 new cases/100000. The increase affected all age groups except those below 11years of age.

Usefulness of the measurement of azathioprine metabolites in the assessment of non-adherence - Corrected Proof

2010-06-07

Abstract: Azathioprine is a thiopurine immunosuppressive antimetabolite used to chronically treat inflammatory bowel disease and autoimmune hepatitis. Azathioprine treatment is a long-term therapy and therefore it is at risk for non-adherence, which is considered an important determinant of treatment inefficacy. Measurement of 6-thioguanine and 6-methylmercaptopurine nucleotides has been recently suggested as a screener for non-adherence detection.We describe four young patients in which non-adherence to azathioprine therapy was detected only through the measurement of drug metabolite concentrations, and the criterion for non-adherence was undetectable metabolite levels. After the identification of non-adherence, patients and their families were approached and the importance of a correct drug administration was thoroughly enlightened and discussed; this allowed obtaining a full remission in all subjects.Our observations support the use of undetectable metabolite levels as indicators of non-adherence to therapy in azathioprine treated patients. The additional level of medical supervision given by this assay allows getting a better adherence to medical treatment, which results in an improvement in the response to therapy; these benefits may justify the costs associated with the assay.

A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine - Corrected Proof

2010-05-31

Abstract: Background: 6-mercaptopurine (6-MP) is used for the induction and maintenance of remission of inflammatory bowel disease (IBD). 6-MP is converted into 6-methylmercaptopurine (6-MMP) or 6-thioguanine nucleotides (6-TGN) intracellularly. Treatment response in IBD patients correlates with 6-TGN levels. This study prospectively evaluated the effect of allopurinol on 6-MP metabolites in adult and pediatric IBD patients. Additionally, we quantified the prevalence of preferential metabolism towards 6-MMP through a retrospective analysis of IBD patients.Methods: Twenty patients (10 adult; 10 pediatric) with evidence of preferential metabolism towards 6-MMP, (6-TGN<250pmol/8×108RBCs and 6-MMP>5000pmol/8×108RBCs) were prospectively treated with allopurinol 100mg daily and up to 100mg of 6-MP. 6-MP dose was adjusted after a 3-week metabolite measurement.Results: The median dose of 6-MP for adults decreased from 100mg daily (range: 37.5–150mg) to 25mg daily (range: 12.5–50mg). The median dose of 6-MP for pediatric patients decreased from 50mg (range: 25–50mg) to 10.7mg (range: 10.7 to 21.4mg). Mean 6-TGN levels in all subjects increased from 197.4 (±59) to 284.8 (±107) pmol/8×108RBCs (p=0.0005). Mean 6-MMP levels in all subjects decreased from a mean of 7719.8 (±4716) to 404.8 (±332) pmol/8×108RBCs (p=0.0004). There were no complications associated with allopurinol therapy. Eighty-eight (30.9%) of 285 IBD patients had evidence of preferential metabolism towards 6-MMP. The proportion of preferential metabolism was equal in adults and pediatric patients.Conclusion: Our results indicate that the addition of allopurinol safely shifts metabolite production in both adult and pediatric IBD patients and that there is a high prevalence of preferential metabolism towards 6-MMP among IBD patients.

Long-term efficacy of adalimumab in Paediatric Crohn's disease patients naïve to other anti-TNF therapies - Corrected Proof

J. Martín-de-Carpi, N. Pociello, V. Varea — 2010-05-04

Abstract: Introduction: Adalimumab is a fully-humanized anti-TNF a antibody that has showed its efficacy in Crohn’s disease (CD) adult patients. Its less immunogenic composition seems to be an advantage compared to previous anti-TNF α, mainly infliximab. Good response to adalimumab has been reported in patients naïve to infliximab, in those in whom infliximab has shown no efficacy and in those intolerant or who have lost previous response to it. Adalimumab has shown also its efficacy as a second-line anti-TNF α in small series of paediatric CD but data regarding its use in children naïve to infliximab are scarce.Aim: To report our experience with adalimumab as first line anti-TNF α treatment in paediatric CD.Patients and methods: Four CD paediatric patients (2 boys) previously naïve to infliximab have received adalimumab. Mean age at diagnosis: 13years, 4months. Adalimumab was initiated in our patients soon after diagnosis (mean time from diagnosis: 8.5months, range: 1month 15days–14months) at decreasing loading doses (160mg and 80mg two weeks after) and then 40mg subsequently every two weeks.Results: The four patients entered in remission after the first dose of adalimumab (mean previous PCDAI: 35, mean PCDAI after first dose: 3.6). No adverse effects were registered. Azathioprine was stopped after 4months of combination therapy, without loss of efficacy or adverse reactions attributable to immunogenicity. All the 4 patients have remained in remission on adalimumab monotherapy for a mean follow-up of 17months (range 9–20months).Conclusion: Adalimumab has shown its efficacy in our paediatric CD patients naïve to other anti-TNF α drugs. Early introduction of anti-TNF α antibodies in these patients could help to a better control of the disease. Its less immunogenicity and the possibility of a home-based administration are advantages when compared to other parenteral anti-TNF treatments. Change to monotherapy after prior successful combination therapy with azathioprine and adalimumab is a safe strategy that can help to minimize possible risks of intensive immunomodulation.

Pulmonary manifestations of inflammatory bowel disease: Case presentations and review - Corrected Proof

Benjamin Basseri, Pedram Enayati, Alberto Marchevsky, Konstantinos A. Papadakis — 2010-05-03

Abstract: Inflammatory bowel disease (IBD) is associated with a number of extraintestinal manifestations that may involve most organ systems. Extraintestinal manifestations are more common in Crohn disease (CD) and may include rheumatologic, ocular, dermatologic, biliary and pulmonary manifestations. The most common pulmonary manifestations of IBD are drug-induced lung disease. Other manifestations include parenchymal disease, pleuritis and overlap syndromes. We present a case series of 7 patients with non-infectious pulmonary manifestations of IBD, which included cryptogenic organizing pneumonia, usual interstitial pneumonitis (UIP), Langerhan's granulomatosis, and eosinophilic pneumonia. Concurrent extraintestinal manifestations present in these patients included arthralgia, iritis, and pyoderma gangrenosum. In most patients the development of pulmonary disease parallels that of the intestinal disease activity, extraintestinal manifestations and concurrent use of 5-ASA medications.

Granulomas in Crohn's disease: Are newly discovered genetic variants involved? - Corrected Proof

2010-04-26

Abstract: Background: Non-caseating granulomas exist in a substantial portion of patients with Crohn's disease (CD). Several single nucleotide polymorphisms (SNPs) have been identified as a having strong association with CD, including SNPs within the autophagy related 4 homolog A (ATG4A) gene and the neutrophil cytosolic factor 4 (NCF4) gene. We hypothesized a possible association between the presence of granulomas in CD patients and variants in the ATG4A and NCF4 genes.Aims: To investigate whether variants in the NCF4 and ATG4A genes are associated with granuloma formation in a cohort of Israeli patients with CD, exploring demographic and clinical characteristics that differ between granuloma positive and granuloma negative patients.Methods: 307 Israeli patients with CD were studied. Patients with CD who underwent biopsy or resection of the intestine were classified according to presence or absence of granulomas. Using PCR-RFLP we determined the allele frequency in SNP rs4821544 (NCF4 gene) and SNP rs807185 (ATG4A gene) for all patients.Results: Granulomas were found in 85 out of 307 CD patients (27%). There were no significant differences between patients with or without granulomas in allele frequency in SNPs rs4821544 and rs807185. CD Patients with granuloma were younger at diagnosis than patients without granuloma (mean age 19 vs. 27, respectively, P<0.0001) and were more likely to undergo surgery (55.3% vs. 34.8%, respectively, P=0.002).Conclusions: No association was found between SNPs rs4821544 and rs807185 and the presence of granulomas in CD patients. Granuloma positive patients were more likely to be younger and to undergo surgery.

Kaposi's sarcoma: An opportunistic infection by human herpesvirus-8 in ulcerative colitis - Corrected Proof

2010-04-21

Abstract: Kaposi's sarcoma is a vascular tumor caused by human herpesvirus-8 infection. Iatrogenic Kaposi's sarcoma often occurs in patients receiving immunosuppressive therapy. To date, a few cases of colonic Kaposi's sarcoma have been reported in ulcerative colitis patients treated with immunomodulators. We describe a 65-year-old male diagnosed with left-sided ulcerative colitis who was treated with methotrexate and low-dose steroids for greater than 6years. He presented with several papular, violet lesions on both legs. Colonoscopy revealed the presence of multiple reddish, elevated lesions in the sigmoid colon and rectum. Histological evaluation of skin and colonic biopsies showed findings suggestive of Kaposi's sarcoma; immunohistochemistry for human herpesvirus-8 was positive in the colonic lesions. To avoid the need for further immunosuppressive treatment, the patient underwent a colectomy. Following immunomodulator discontinuation, the patient experienced spontaneous regression of his skin lesions. With the present case, we wish to stress the important interaction of immunosuppressive therapy (mainly corticosteroids) used in ulcerative colitis patients in relation to the development of colonic Kaposi's sarcoma. Human herpesvirus-8 infection should be recognized as a possible opportunistic infection in patients with inflammatory bowel disease.

Long-term outcome in patients with ulcerative colitis treated with intravenous cyclosporine A is determined by previous exposure to thiopurines - Corrected Proof

2010-04-20

Abstract: Background and aim: Rescue therapy with intravenous cyclosporine A (CsA) helps to avoid colectomy in a substantial proportion of patients with severe ulcerative colitis (UC) but the impact on long-term outcome remains unclear. Therefore, we aimed to define predictive factors for colectomy in patients treated with intravenous CsA for severely active UC.Methods: A retrospective, single-center study with a minimum follow-up of 18months was performed.Results: A total of 64 patients were evaluable (median age 33 years [range 17–80years], female 54.7%). Median intravenous CsA dose was 4mg/kg/day (range 2–5mg/kg/day). After a median follow-up of 65months (range 2–160months), 19 patients (29.7%) underwent colectomy, 15 within 18months. Of the various baseline parameters tested, only previous non-response to thiopurine treatment (p=0.006) was associated with an increased risk of colectomy. During 18months follow-up, thiopurine-naïve patients receiving thiopurine maintenance therapy after intravenous CsA (32/64, 50.0%) underwent colectomy in 12.5% of cases. The colectomy rate was 27.3% among 22 patients previously non-responsive to thiopurines who continued treatment after intravenous CsA, compared to 50.0% in the 10 patients who discontinued thiopurines prior to intravenous CsA or who never received thiopurines (p=0.037).Conclusions: The long-term colectomy rate after intravenous CsA in patients with severely active UC was relatively low in our series compared to the literature. Concomitant treatment with thiopurines was the only predictor for a reduced risk of colectomy.

Dermatofibroma in a patient with Crohn's disease: A novel clinical manifestation - Corrected Proof

2010-04-20

Crohn's disease (CD) is an inflammatory disease of the digestive tract, which could affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It is often associated with extra-intestinal manifestations, complications, and other autoimmune disorders. Although dermatofibromas (DF) are benign dermal nodules mostly affecting the extremities, shoulders, and buttocks of young adults it has not been reported among the skin manifestations of CD. Reported herein is the first case of a newly diagnosed CD with dermatofibroma.

A case of Crohn's disease complicated by Adult Onset Still's Disease - Corrected Proof

M.N. Rajabally, G.A. Watermeyer, D.A. Levin — 2010-04-16

Abstract: Arthritis and arthralgia are the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD), occurring in up to a third of patients. These may affect the peripheral or axial skeletal system and may or may not reflect disease activity. As a result, it is challenging to identify an alternative diagnosis to account for joint manifestations in the setting of IBD.We describe a case of a 30year old woman with quiescent Crohn's colitis who presented with 2weeks of fever, flitting arthralgia, a sore throat and a nocturnal rash on her thighs. She denied any gastrointestinal symptoms to suggest a flare up of IBD. Investigations revealed a neutrophilia and a markedly elevated serum ferritin. The patient met all four major and several minor Yamaguchi criteria for Adult Onset Still's Disease (AOSD). She was treated with corticosteroids and analgesia with resolution of her symptoms and normalisation of her biochemical markers.While joint manifestations are the most common extra-intestinal symptoms of Inflammatory Bowel Disease, atypical presentations should raise the concern of an additional diagnosis. This case represents a rare presentation of Crohn's disease complicated by AOSD.

Non-invasive diagnosis and grading of postsurgical endoscopic recurrence in Crohn's disease: Usefulness of abdominal ultrasonography and 99mTc-hexamethylpropylene amineoxime-labelled leucocyte scintigraphy - Corrected Proof

2010-04-12

Abstract: Non-invasive techniques aim to be an alternative to endoscopy in the assessment of postsurgical recurrence of Crohn's disease (CD). The object of this study was to evaluate the accuracy of abdominal ultrasonography (AUS) and 99mTc-hexamethylpropylene amineoxime (99mTc-HMPAO)-labelled leucocyte scintigraphy (LLS) compared with endoscopy in the diagnosis and grading of postsurgical recurrence of CD.Between January 2006 and May 2007, all patients with CD and resection with ileocolic anastomosis were included prospectively. Within three days they underwent an ileocolonoscopy, AUS with evaluation of bowel wall thickness and the presence of Doppler flow, and LLS.Forty patients who met the study conditions were included; 5 patients did not agree to have the ileocolonoscopy and it was not possible to assess the anastomosis in 2 patients. Endoscopic recurrence was detected in 26 patients (78.8%), in 15 of whom it was moderate-severe. For the diagnosis of recurrence, both AUS and LLS showed acceptable sensitivity and positive predictive value, with an accuracy of 72.7% and 78.1%, respectively. The results of the AUS and LLS for diagnosing moderate-severe recurrence were better, with an accuracy of 78.8% and 81.3%, respectively. The best assessment of the severity of the recurrence was obtained with the combination of both techniques (sensitivity, specificity, positive and negative predictive values, accuracy and kappa index were, respectively: 93.3%, 72.2%, 73.7%, 92.9%, 81.8% and 0.64). The variables evaluated, both sonographic and scintigraphic, had areas under the curve that were similar and significantly different from 0.5.Conclusion: Abdominal ultrasonography and 99mTc-HMPAO-labelled leucocyte scintigraphy are two useful non-invasive techniques for the assessment of postsurgical recurrence of Crohn's disease.

Revisiting the past: Intra-arterial vasopressin for severe gastrointestinal bleeding in Crohn's disease - Corrected Proof

2010-03-29

Abstract: Technological advances in the last couple of decades have led to a tremendous improvement in the safety and efficacy of embolization making it the therapeutic intervention of choice in angiogram positive lower gastrointestinal bleeding. Vasopressin has thus been forgotten and it is hardly ever used by the current generation of interventionists. However, coil embolization is technically challenging and requires greater expertise. Difficulty in super-selective catheterization and lack of adequate collateralization can also prevent successful delivery of coils. In this article we present the successful use of intra-arterial vasopressin in a patient with Crohn's disease with severe lower gastrointestinal bleeding. Despite not being the first choice, vasopressin can be safely and effectively used in selected patients who are not candidates for embolotherapy. The purpose of this article is to discuss the relative merits and demerits of vasopressin vis-à-vis embolization and to identify the role of vasopressin in the current era of super-selective embolization. Successful control of massive lower gastrointestinal bleeding by intra-arterial vasopressin infusion has previously been reported only once before in Crohn's disease. We suggest that this technique may be used in an attempt to avoid surgery in these patients.

A role for B12 in inflammatory bowel disease patients with suppurative dermatoses? An experience with high dose vitamin B12 therapy - Corrected Proof

Marianne Mortimore, Timothy H.J. Florin — 2010-03-23

Abstract: Background: Inflammatory dermatoses in conjunction with inflammatory bowel disease (IBD) comprise a diverse range of disorders. Some but not all of these respond to conventional treatments for the underlying IBD, such as immunomodulating or antibiotic treatments. We describe our experience with high dose vitamin B12, where conventional therapies have failed.Case reports: The first case had pouchitis complicated by perianal abscesses and a recto-vaginal fistula. The second case had biopsy proven hidradenitis suppurativa affecting the perianal, inguinal and pubic skin. High dose vitamin B12 appeared to be the major factor in preventing the recurrence of suppuration in both patients. Neither patient had vitamin B12 deficiency. Open label experience: high dose vitamin B12 treatment of a further 10 consecutive IBD patients with dermatoses was thought to provide benefit to six of them, but did not appear useful in four patients with perianal Crohn's disease with fistulae as the only manifestation of cutaneous disease.Conclusions: There appears to be a subset of IBD patients with perianal and more distant inflammatory dermatoses, who benefit from high dose vitamin B12 treatment. Clinical trials in IBD patients with biopsy-characterised suppurative dermatoses will be required in order to properly define the role of this safe and economical therapy.

Combination of thiopurines and allopurinol: Adverse events and clinical benefit in IBD - Corrected Proof

Shail M. Govani, Peter D.R. Higgins — 2010-03-23

Abstract: Background and aims: Allopurinol has been presented as a safe and effective adjunct to thiopurine therapy in inflammatory bowel disease (IBD). We aimed to determine the rate of infectious complications and clinical successes with a combination of thiopurine/allopurinol in IBD, and to identify which variables predict 6-thioguanine, 6-methylmercaptopurine, and white blood cell levels. Additionally we aimed to identify which variables predict complications.Methods: A retrospective database search identified patients with inflammatory bowel disease on both thiopurines and allopurinol. Regression modeling was used to identify which variables predicted metabolite levels, white blood cell levels, and complications.Results: Twenty-seven subjects were found, with 20 treated intentionally and 7 inadvertently after a concurrent gout diagnosis. Thirteen of 20 patients had a major clinical improvement and 7 of 16 stopped steroids. Five infectious complications occurred. These included 2 cases of shingles, and one each of PCP, EBV, and viral meningitis. Significant predictors of metabolite levels included the dose of thiopurine and allopurinol, age, and BMI. Low white blood cell count levels were associated with increased doses, high BMI, and older age. Despite having only 5 events, there was a difference in absolute lymphocyte count between patients with and without infection (median 200 per mm3 vs 850 per mm3 respectively, p=0.0503).Conclusions: Adjunctive allopurinol therapy in shunting patients produced major clinical improvement in 48% of patients. However, a surprising number of opportunistic infections have occurred. Low absolute lymphocyte count may be a previously unrecognized indicator of risk of opportunistic infections.

Inflammatory bowel disease and hepatitis B and C in Western Balkans: A referral centre study and review of the literature - Corrected Proof

2010-03-23

Abstract: Background and aims: There is limited data on IBD patients diagnosed with viral hepatitis B and C. The aim of the study was to assess the prevalence of chronic HBV or HCV infection in IBD patients followed by our centre and to describe and review the course of bowel and liver disease during therapy.Methods: Single centre retrospective study on 482 consecutive IBD patients. Laboratory investigation for HBV and HCV was performed with routine methods. Treatment protocols for HBV included IFNa and nucleot(s)ide administration and for HCV combined IFNa and ribavirin.Results: We diagnosed 15 patients (15/482, 3.1%) with HBV or HCV. Of these, 11 were HBV (11/482, 2.3%) and 4 were HCV (4/482, 0.8%). Nine of eleven HBV patients received antiviral therapy (8 lamivudine, 1 IFNa). Five lamivudine patients were switched to tenofovir and in another one adefovir dipivoxil were added. Bowel disease was in remission in ten of the eleven HBV patients. One patient was diagnosed with carcinoid tumor. Two HCV patients received IFNa that was well tolerated. One HCV patient denied therapy and one died from hepatocellular cancer. Of the seven patients on azathioprine only one achieved sustained response. Four patients on Infliximab achieved bowel disease remission but experienced biochemical or virological flare.Conclusions: This study demonstrates that prevalence of HBV and HCV infection in a large IBD cohort from Western Balkans is compared to that of the background population. IBD patients under immunosuppressants may apparently be treated with safety if preventive antiviral treatment is administered.

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease - Corrected Proof

2010-03-19

Abstract: Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti‐TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.

Pulmonary diseases associated with inflammatory bowel diseases - Corrected Proof

2010-03-18

Abstract: Among the extra-intestinal manifestations of inflammatory bowel diseases, those involving the lung are relatively rare. However, there is a wide array of such manifestations, spanning from drug-related pathologies to airway disease, fistulas, granulomatous diseases, autoimmune and thromboembolic disorders. Although infrequent, people dealing with inflammatory bowel diseases must be aware of these conditions, sometimes life-threatening, to avoid further impairment of the health status of the patients and to alleviate their symptoms by prompt recognition and treatment.

Anterior ischemic optic neuropathy in a patient with Crohn's disease and aberrant MTHFR and GPIIIa gene variants - Corrected Proof

2010-03-17

Abstract: Large spectrums of ophthalmic manifestations from the anterior to the posterior segment have been so far reported in patients with inflammatory bowel disease.Anterior ischemic optic neuropathy is caused by acute ischemic infarction of the optic nerve head and is distinguished in two different types, non-arteritic anterior ischemic optic neuroparhy (NAION) which is the most frequent type and arteritic anterior ischemic optic neuropathy. Non-arteritic anterior ischemic optic neuroparhy may result in severe visual field loss.We present the case of a 69year-old man with known history of Crohn's disease that was referred to the Department of Ophthalmology after noticing sudden blurred vision of his left eye. Ophthalmologic examination revealed a corrected visual acuity of 8/10 OS and 10/10 OD. Pupil examination showed a relative afferent pupillary defect of the left pupil and fluoroangiography revealed hyperfluorescence of the left optic disc, indicating edema and NAION attack on his left eye.Genetic analysis showed that the patient was homozygous for MTHFR C677T genetic polymorphism and A1/A2 heterozygous for GPIIIa polymorphism.

Transient menorrhagia without adalimumab discontinuation in a patient with Crohn's disease - Corrected Proof

Konstantinos H. Katsanos, Vasileios E. Tsianos, Epameinondas V. Tsianos — 2010-03-15

Menstrual disorders are listed as possible rare side effects during infliximab or adalimumab administration but very few case reports regarding the management of such menstrual side effects exist.

Fistulating Crohn's disease in a patient with rheumatoid arthritis - Corrected Proof

Philip Stather, Helen Cheshire — 2010-03-02

With recent advances in the treatment of autoimmune conditions this can make the diagnosis in many patients with multiple autoimmune pathologies more difficult. Patients with inflammatory bowel disease have a high incidence of peripheral arthropathy, 0.4–34.6%. However, due to the crossover of treatments between rheumatoid arthritis and Crohn's it can be difficult to detect the latter condition.

Endoscopic vs ultrasonographic findings related to Crohn's Disease recurrence: A prospective longitudinal study at 3years - Corrected Proof

2010-02-22

Abstract: Background and aims: Ileocolonoscopy (IC) is the gold standard for assessing Crohn's Disease (CD) recurrence after ileo-colonic resection. In a prospective longitudinal study we compared findings related to CD recurrence when using techniques visualizing either the luminal or the extraluminal surface (IC and small bowel follow through, SBFT vs Small Intestine Contrast Ultrasonography, SICUS).Methods: From 2003 to 2008, 25 CD patients undergoing ileo-colonic resection were enrolled. Clinical assessment (CDAI) was performed at 1, 2 and 3years. IC was performed at 1 (n=25) and 3years (n=15), SBFT at 2years (n=21) and SICUS at 1 (n=25), 2 (n=21) and 3years (n=15). Recurrence was assessed by SBFT and SICUS (bowel wall thickness, BWT) when using IC as gold standard.Results: At 1year, all patients were inactive and recurrence was detected by IC in 24/25 (96%) and by SICUS in 25/25 patients. At 2years, 6/21 patients (29%) were active and recurrence was detected by SBFT in 12/21 (57%) and by SICUS in 21/21 patients. At 3years, 5/15 patients (33%) were active, IC showed recurrence in 14/15 (93%), and SICUS in 15/15 patients. The endoscopic score at 1year was higher in patients developing relapse at 2years (n=5) than in patients maintaining remission (n=10) (median: 4, range 3–4 vs 2, range 0–3; p=0.003). The same finding was not observed by using SICUS (median BWT at 1year: 5, range 4–7 vs 3.7, range 3.5–6; p=0.19).Conclusions: Although IC and SICUS provide a different view of the bowel wall, in experienced hands SICUS provides findings compatible with endoscopic recurrence after ileo-colonic resection for CD. Discrepant findings may be observed in a low proportion of patients with minor lesions related to CD recurrence.

A United Kingdom inflammatory bowel disease database: Making the effort worthwhile - Corrected Proof

2010-02-22

Abstract: Background: Inflammatory bowel disease (IBD), a paradigm of chronic illness, requires for its safe clinical management ready access to complete information, not always possible using paper records.Aim: To develop an IBD database (DB) for both individual patient management and collating information across centres.Methods: Access® based, with a minimum dataset.Results: Prospectively collected data for 11,432 patients from 21 centres.Profile Diagnosis: Ulcerative colitis (UC) 56%, Crohn's disease (CD) 40%, indeterminate colitis 4%. M:F ratio: UC 1.08:1, CD 0.72:1. Median age at diagnosis: UC 39, CD 30years. Operated: UC 16%, CD 47%. Thiopurine use: UC 16%, CD 29%. IBD related mortality: 0.74%.Discussion: A snapshot of this large IBD cohort shows the disease profile across the UK is similar to other large series. Unexpected gaps, sometimes large emerged (e.g. data on smoking and immunosuppression) highlighting the need for clear definition, consistency and completeness of data collection. Clinical management is made easier by the ‘at a glance’ summary, automated clinic letters, and facility for monitoring and audit, but the time required limited its ‘real-time’ use.Conclusion: Our experience shows it is possible to collect data from centres across the country which truly reflects clinical practice. We have learned as much from the process itself as from the data, principally, information needs to be well defined, validated at entry, and updated at every visit, a time consuming sequence which we had underestimated. Our lessons learned may help inform the development of a national database, and support national IBD standards and audit.

5-Aminosalicyclic acid induced multisystem disorders in the course of Crohn' s disease - Corrected Proof

Erdem Akbal, Seyfettin Köklü, Erdem Koçak, Başak Çakal, Fatma Kılıç — 2010-02-22

5-Aminosalicyclic acid (5-ASA) is extensively prescribed drug for the treatment of inflammatory bowel disease but has a wide range of described adverse effects. The most common side effects of 5-ASA include hematological (20%), gastrointestinal (16%) and skin reactions (14%). 5-ASA has rarely been implicated as a cause of serious blood disorders. Liver toxicity due to 5-ASA is uncommon. Renal impairment (including interstitial nephritis and nephrotic syndrome) is also rare and idiosyncratic. We present here a patient with Crohn's disease who manifested with pancytopenia, renal failure and hepatotoxicity while receiving oral 5-ASA treatment.

The pattern and outcome of acute severe colitis - Corrected Proof

2010-02-22

Abstract: Background: The prognosis of acute severe ulcerative colitis (ASC) influences therapeutic decisions, but data on prevalence or long-term outcome are few.Methods: A systematic review of all patients with UC diagnosed in Oxford was performed to assess the prevalence of ASC defined by Truelove and Witts' (TW) criteria and determine whether outcome is related to disease activity on admission, likelihood of recurrence and long-term prognosis.Results: 750 patients (median follow up 12.7yr, range 0–648mo) met inclusion criteria out of a total cohort of 1853 patients. 24.8% (186/750) had at least one admission for ASC (294 admissions in 186 patients). Overall, 12% (93/750) had a colectomy, compared to 39.8% (74/186) of patients with one or more episodes of ASC (p<0.0001) and 3.4% (19/564) in those with no admission. The colectomy rate on first admission (37/186, 19.9%) was lower than on the second or subsequent admissions (OR 2.35, 95% CI 1.33–4.14, p=0.003), being 29.0%, 36.6%, 38.2% after two, three, or subsequent episodes respectively. It was 8.5% (11/129) if patients had one TW criterion in addition to ≥6 bloody bowel motions/day, compared to 31% (29/94) if two additional criteria were present and 48% (34/71) if three or more additional criteria were present (p=1.4×10−5; OR 4.35, 95% CI 2.20–8.56 one criterion vs two or more).Conclusions: A quarter of all patients with ulcerative colitis experience at least one episode of ASC; 20% come to colectomy on first admission, but 40% after two admissions. The likelihood of colectomy is related to biological severity on admission.

The health care cost of intravenous iron treatment in IBD patients depends on the economic evaluation perspective - Corrected Proof

Palle Bager, Jens F. Dahlerup — 2010-02-18

Abstract: Background and aim: Anemia is common in IBD patients and intravenous iron treatment is preferred. The drug cost of intravenous iron carboxymaltose is approximately twice the cost of intravenous iron sucrose. The aim was to evaluate the health care costs of intravenous iron sucrose (Venofer®, Vifor) and intravenous iron carboxymaltose (Ferinject®, Vifor) treatment to IBD patients in an outpatient setting.Methods: Based on data from111 IBD patients treated with intravenous iron in an outpatient setting health care costs were evaluated by means of Budget Impact Analysis, Cost Effective Analysis and Cost Benefit Analysis.Results: The Cost Effective Analysis showed that iron carboxymaltose was more cost-effective than iron sucrose, due to fewer outpatient setting visits. Even a sensitivity analysis using a reduced patient income (50%) in the Cost Effective Analysis showed iron carboxymaltose to be the most cost effective treatment. The Budget Impact Analysis from a hospital perspective showed that iron carboxymaltose was more expensive than iron sucrose regardless of the dose given. In contrast the Cost Benefit Analysis showed that the average patients' ‘willingness to pay’ for a total of iron dose of 1400mg was €233 in order to reduce the number of infusions from 7 to 2 by using iron carboxymaltose rather than iron sucrose.Conclusion: Both the Cost Effective Analysis and the Cost Benefit Analysis showed clearly that iron carboxymaltose is a more cost effective way of giving intravenous iron than iron sucrose in IBD patients. Only the Budget Impact Analysis showed that intravenous iron sucrose was the cheapest choice if only direct cost was included in the analysis.

The burden of inpatient costs in inflammatory bowel disease and opportunities to optimize care: A single metropolitan Australian center experience - Corrected Proof

Daniel R. van Langenberg, Stephen B. Simon, Gerald J. Holtmann, Jane M. Andrews — 2010-02-15

Abstract: Background and aims: Inflammatory bowel disease (IBD) causes significant morbidity, frequently resulting in hospital admission and resection surgery. However, little is known about: 1. how IBD patients' inpatient healthcare utilisation compares to other inpatients and 2. whether there are potentially modifiable factors which may influence this.Methods: Over five months a cohort of admitted IBD patients were acquired and each assigned five admitted, age and gender matched controls at a single tertiary center. Data compared over 15months included: total cumulative length of stay (TLoS), number of admissions (index and subsequent re-admissions), inpatient costs, care complexity (defined by relative stay index [RSI]), and disease-specific factors amongst the IBD cohort. Data were confirmed by case notes review.Results: There were 102 IBD patients and 510 controls (median age 44years, 57% female). IBD patients had more re-admissions (mean 1.72 vs 1.55, p=0.002) and longer TLoS (median 6.8 vs 3.4days, p<0.0001) than controls. Both median cumulative cost of inpatient healthcare and RSI were also higher in IBD compared to controls ($7052 vs $5470 and RSI 362% vs 293%, each p<0.008). IBD patients seen by a gastroenterologist prior to their index admission had fewer re-admissions (mean 1.37 vs 2.02, p=0.016,) and tended to have lower total cumulative inpatient costs than those without prior Gastroenterologist review (median $6439 vs $9479, p=0.069).Conclusions: IBD patients have significantly greater inpatient healthcare utilization, complexity and costs than age and gender matched, hospitalized controls. Prior gastroenterologist care in IBD may reduce subsequent admission rates, and inpatient-related costs.

Factors that modify therapy adherence in patients with inflammatory bowel disease - Corrected Proof

2010-02-15

Abstract: Objectives: Inflammatory bowel disease is associated with a high risk of deficient adherence to therapy. Our study was designed to analyze the adherence to treatment in a specialized inflammatory bowel disease clinic, and to study which factors could influence it.Methods: 107 consecutive patients (64% Crohn's disease, 36% ulcerative colitis) filled up an anonymous survey with data on demography, disease, therapy and a self-applied adherence declaration.Results: A 69% (95%CI: 60–77%) showed some type of non-adherence. A 66% (95CI%: 57–75%) acknowledged some involuntary non-adherence: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (95CI%: 9–22%) showed some voluntary non-adherence: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% forgot at least a dose a week in the last 12months. Multivariate analysis identified as risk factors for a lower adherence the dosing in three or more takes a day (OR 3; 95%CI: 1.1–8.4; p=0.03) and feeling little informed about their disease (OR 4.9; 95%CI: 1.1–23.8; p=0.04). Immunomodulator therapy predicted better adherence (OR 0.29; 95%CI: 0.11–0.74; p=0.01).Conclusions: Adherence to therapy in inflammatory bowel disease patients is not satisfactory, and worse in patients treated with mesalazine. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adherence.

On the updated ECCO consensus guidelines for medical management of Crohn's disease - Corrected Proof

Dirk Esser, Freddy Cornillie, Robert H. Diamond, Robert J. Spiegel — 2010-02-15

During the 2009 annual meeting of the European Crohn's and Colitis Organisation (ECCO), the updated consensus guidelines for medical management of Crohn's disease (CD) were presented. ECCO deserves recognition for using a rigorous, evidence-based approach in developing these guidelines. However, whilst we acknowledge our own interests as marketing authorisation holder and distributor of Remicade, we would like to respectfully point out our objections to an assumption of a class effect between anti-TNF agents, as the updated guidelines and in particular section 5I suggest:“All currently available anti-TNF therapies appear to have similar efficacy and adverse-event profiles, so the choice depends on availability, route of delivery, patient preference, cost and national guidance [EL5, RG D].”

Assessment of activity of Crohn's disease by Doppler sonography of superior mesenteric artery flow - Corrected Proof

2010-01-21

Abstract: Background: Evaluation of activity of Crohn's disease is based on CDAI. Several other tools have been studied to assess disease activity with more accuracy.Aims: To assess the correlation between Doppler parameters of superior mesenteric artery and disease activity and to assess the accuracy of these parameters in discriminating between active and quiescent Crohn's disease.Material and methods: We perform a prospective study including non-operated and non-complicated Crohn's disease patients involving terminal ileum and/or right colon and sex and age-matched controls. Doppler sonography of superior mesenteric artery was performed in all subjects.Results: We studied 41 patients and 15 controls. There was no statistical difference between patients and controls according to the studied US parameters. The difference in resistance index between the three groups using analysis of variance is not significant (p=0.064). Resistance index was significantly lower in patients with active disease compared to inactive disease patients (0.82+/−0.04 vs 0.85+/−0.03; p=0.01). Pulsatility index was also lower in patients with active disease compared to inactive disease patients (1.37+/−0.21 vs 1.53+/−0.15; p=0.01). A value of resistance index less than 0.79 predicted active disease with a sensitivity of 35.3% and specificity of 95.7%. A value of pulsatility index less than 1.56 predicted active disease with a sensitivity of 94.1% and specificity of 43.5%. In case of resistance index less than 0.79 and pulsatility index less than 1.56 in the same patient, the probability of active disease was 86%. However, in case of resistance index over than 0.79 and pulsatility index over than 1.56, this probability was only 9%. In Crohn's disease patients, correlation study showed that resistance index value was significantly correlated with CDAI (r=−0.46; p=0.003). Pulsatility index value was also correlated with CDAI (r=−0.39; p=0.01).Conclusion: Doppler sonographic parameters of superior mesenteric artery are significantly correlated with disease activity in non-operated and non-complicated Crohn's disease.

Regional variations in the use of complementary and alternative medicines (CAM) for inflammatory bowel disease patients in Italy: An IG-IBD study - Corrected Proof

2010-01-18

Abstract: Background and aim: Complementary and alternative medicines (CAM) are being used increasingly by patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and usage of CAM in different geographical areas of Italy and possible predictors of their use.Methods and materials: A structured questionnaire, administered to outpatients, attending 8 general hospitals and 9 tertiary referral centres, was completed by 2011 patients (909 CD, 1087 UC and 15 indeterminate colitis). 583 patients lived in the North, 659 in Central Italy and 769 in the South.Results: CAM users were 475 (23.6%) with no regional differences in their distribution. Usage correlated significantly with female gender (p=0.030), higher education (p=0.021), hospitalization rates (p=0.000), extra-intestinal complications (p=0.000), non-adherence to conventional treatments (p=0.054), adverse reactions to conventional treatments (p=0.000), and active disease (p=0.007); 5-ASA usage was associated with a more limited use of CAM (p=0.005). Dietary changes or supplements and prayer were significantly more frequently reported in South, while Northern Italian patients more frequently used homeopathy, herbal medicines and physical exercises. Patients in Central Italy adopted an intermediate behavior. CAM use ameliorated the patient's general well-being according to two thirds of the users. Costs were higher for Northern patients than in Central or Southern Italy.Conclusion: One in four IBD patients in Italy use CAM. More money is spent on CAM in Northern Italy. Regional differences emerged as regards the type of CAM but not in terms of disease features, frequency of and reasons for CAM use, or perceived effects.