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Instructions for Authors
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Contents
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Treatment of inflammatory bowel diseases: To heal the wound or to heal the sick?
Inflammatory bowel diseases (IBDs), encompassing ulcerative colitis (UC) and Crohn's disease (CD) are chronic, progressive and relapsing pathologic conditions caused by a dysregulation of the immune system. IBDs are characterised by inflammation and ulceration of the intestinal mucosa. The main symptoms, such as abdominal pain, altered bowel functions and rectal bleeding, significantly alter a patient's quality of life (QOL). In the absence of any aetiological therapy, clinical improvement is the main treatment goal. Clinical improvement is typically associated with a gradual reduction in the severity of intestinal lesions; however, it is common for symptoms to recur. Mucosal healing (MH) offers a potential end point for IBDs treatment but until recently the aim of UC and CD treatment was to improve symptoms and prevent relapse episodes with no consideration of mucosal restitution. Improved disease prognosis is possible through the achievement of both clinical (resolution of symptoms) and endoscopic (healing of intestinal mucosa) remission, which represents the best case scenario for patients with IBDs, therefore efforts should be maximised to achieve these endpoints.
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Arthritis as a presenting symptom of subclinical Crohn's disease
Dear Sir, Crohn's disease (CD) is an immune-mediated, chronic inflammatory disease that can affect any part of the gastrointestinal tract from the mouth to the anus. Rheumatic, mucocutaneous, ophthalmologic or other extraintestinal findings may accompany such as around 40–50% during the course of the disease but rarely seen as the first sign. Several cases of rheumatological extraintestinal manifestations that appeared concomitantly with CD have been reported. Herein we describe a patient with monoarthritis that led to the diagnosis of asymptomatic CD.
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Spot diagnosis: Eruptive melanocytic naevi during azathioprine therapy in Crohn's disease
Long term use of thiopurines in the treatment of inflammatory bowel disease (IBD) is associated with the development of non-melanoma skin cancer. Here we present a patient who developed unusual skin abnormalities during azathioprine administration.
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Anti chimeric antibodies against chimeric monoclonal antibodies may result in Kounis hypersensitivity associated acute coronary syndrome
In the very important report published in this journal, a patient suffering from Crohn's disease with recurrent symptomatology and receiving repeated treatment with infliximab developed anaphylactic cardiac symptoms including precordial chest pain, severe dyspnoea, tachycardia and urticaria. The patient was treated with antihistamines and infliximab was replaced by adalimubad. However, adalimubad induced again urticaria symptoms. Measured IgE antibodies were negative but IgG antibodies were present in both instances. The authors characterized these events as acute anaphylactoid and delayed hypersensitivity reaction and commented that their precise mechanism is still not well known. Although cardiological work up was not described, it seems likely that cardiac symptoms induced by infliximab were due to Kounis hypersensitivity associated acute coronary syndrome. This syndrome is defined, today, as the concurrence of acute coronary syndromes with conditions associated with mast cell and basophil activation, involving interrelated and interacting inflammatory cells and including allergic, anaphylactic and anaphylactoid insults. Three variants of this syndrome have been described so far which include coronary artery spasm, plaque erosion and/or rupture manifesting as acute myocardial infarction and stent thrombosis.
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Autoimmune hepatitis following treatment with infliximab for inflammatory bowel disease
We read with interest the report of infliximab-induced hepatitis by Doyle et al. Infliximab-induced liver test abnormalities are quite common in clinical practice; however, the progression to clinical overt hepatitis is far less frequent.
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Treatment of Crohn's disease patients with infliximab is detrimental for the survival of Mycobacterium avium ssp. paratuberculosis within macrophages and shows a remarkable decrease in the immunogenicity of mycobacterial proteins
The association between Mycobacterium avium ssp. paratuberculosis (MAP) and Crohn's disease (CD) although debatable, is supported by several studies which have reported the detection or isolation of MAP from human tissues including serum, body fluids (breast milk), and high levels of TNF-α was found secreted by the gut mucosa in MAP-associated CD patients. Infliximab is a monoclonal antibody that specifically inhibits TNF-α and is used as a current therapy for CD.
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Chronic hepatitis C, inflammatory bowel disease and interferon therapy
Dear Sir, Interferon (IFN) alpha, in a combination with ribavirin, is currently the standard therapy for chronic viral hepatitis C (HCV). IFN-β1 alpha is also another kind of interferon which is commonly used in the treatment of multiple sclerosis. Both of these treatment modalities have been associated with various side effects, including the reactivation of autoimmune thyroid and liver diseases. Also, the exacerbation of preexisting inflammatory bowel disease (IBD) including, Crohn's disease and ulcerative colitis (UC) or the de novo induction of these entities, have been reported. Similarly, in February 2011 issue of Journal of Crohn's and Colitis, Tuna et al. reported a case of multiple sclerosis that developed UC during the course of IFN therapy. With this regard, we would like to present two cases, portraying the spectrum of the effects of INF during the treatment of HCV.
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Surgical management of gluteal metastatic cutaneous Crohn's disease
Abstract: Metastatic cutaneous Crohn's disease is a rare entity first described by McCallum et al. in 1976. It is diagnosed when histologically characteristic granulomata are seen at a site not contiguous with inflammatory disease in the gastrointestinal tract. We herein report presentation, diagnosis and management of a 28year old lady with disabling, symptomatic cutaneous Crohn's of the buttocks and natal cleft refractory to Infliximab therapy. To the best of our knowledge only four other adult cases have been reported in the literature of metastatic cutaneous Crohn's disease of the buttock area distant from a flexure or area of skin apposition. The differential diagnosis in this case was Hidradenitis Suppurativa. A good cosmetic result and excellent symptom control were achieved with extensive debridement, wide local excision, vacuum assisted closure and delayed skin grafting.
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Infliximab-induced psoriasis during therapy for Crohn's disease
Abstract: Although therapy with tumor necrosis factor-alpha inhibitors (anti-TNF) provides beneficial effects in different immune inflammatory disorders, paradoxical cases of anti-TNF-induced psoriasis have increasingly been reported, mostly in the setting of rheumatologic diseases. To date, less than 50 cases of infliximab-induced psoriasis in inflammatory bowel disease patients have been described. The present report was aimed at describing two new cases of infliximab-induced psoriasis during therapy for Crohn's disease and at carrying out a review on this intriguing phenomenon.
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Familial collagenous colitis involving a 6-year old child
Abstract: Collagenous colitis is a recognised cause of persistent, non-bloody, watery diarrhoea. There are few cases of collagenous colitis reported in children or occurring within families. To our knowledge, no familial cases under 14years of age have been reported previously; we describe a case of familial collagenous colitis affecting a 6-year old girl and her mother. The relevant published literature is reviewed and management is discussed. Colonic mucosal biopsies should be considered in both adults and children presenting with persistent watery diarrhoea even in the absence of any macroscopic abnormality at colonoscopy.
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Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: A single-center cohort study
Abstract: Background & Aims: The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use.Methods: In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments.Results: IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000pt/year vs 2.9/1000pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL,1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08–1.45; UC:HR 1.33;95%CI 1.15–1.55 for an increase by 5years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11–5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05–7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed).Conclusions: Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer.
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A functional polymorphism in UGT1A1 related to hyperbilirubinemia is associated with a decreased risk for Crohn's disease
Abstract: Background: An imbalance between the production of reactive oxygen species (ROS) and their capturing by antioxidants results in oxidative stress, this may play an important role in the pathogenesis of inflammatory bowel disease (IBD). Since bilirubin is an important endogenous antioxidant, increased levels of bilirubin may protect against IBD. UDP-glucuronosyltransferase 1A1 (UGT1A1) is the only enzyme involved in the conjugation of bilirubin and the common UGT1A1*28 allele in the UGT1A1 gene, which is strongly associated with Gilbert's syndrome in Caucasians, results in elevated plasma bilirubin levels.Aims: To test the hypothesis that the UGT1A1*28 allele is associated with lower disease susceptibility to, and disease behavior within, IBD. In addition, a possible altered risk for developing IBD-drug related side-effects was explored.Methodology: Genomic DNA of 751 patients with IBD (209 patients with ulcerative colitis and 542 patients with Crohn's disease) and 930 healthy controls was genotyped for the UGT1A1*28 promoter polymorphism, and genotype distribution was compared between patients and controls. Genotype phenotype interactions were also investigated.Results: Patients with Crohn's disease significantly less often bear the UGT1A1*28 homozygous genotype compared to the control group, with an odds ratio of 0.64, 95% CI: 0.42–0.98. The ulcerative colitis group showed no significant differences compared to controls.Conclusion: The homozygous state of the UGT1A1*28 polymorphism, associated with higher serum bilirubin levels, may be protective for the development of Crohn's disease, suggesting that the anti-oxidant capacity of bilirubin may play a part.
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Neuroimmune interactions in patients with inflammatory bowel diseases: Disease activity and clinical behavior based on Substance P serum levels
Abstract: Background and aim: The neuropeptide Substance P, plays a key role in modulating neuroimmune interactions in patients with inflammatory bowel diseases. We analyzed Substance P serum levels in patients with ulcerative colitis and Crohn's disease, to detail the involvement of the neuropeptide in the pathophysiology of these disorders.Methods: Serum samples were collected from 61 patients with ulcerative colitis (24 with active and 37 with inactive disease), 66 patients with Crohn's disease (29 with active and 37 with inactive disease) and 45 healthy subjects, enrolled into the study. Neuropetide serum levels were measured by means of an ELISA/EIA. Associations with disease activity and patients clinical features were also taken into account.Results: Compared to controls, Substance P serum levels were significantly increased in both patients with ulcerative colitis and Crohn's disease, (p<0.001). In patients with ulcerative colitis, levels paralleled disease activity (p=0.014), and the amount of the neuropeptide was considerably decreased during clinical and endoscopic remission of the disease, (p=0.025). Conversely, median Substance P levels did not differ between patients with active and inactive Crohn's disease. However, levels of the neuropeptide were more often elevated in patients with inactive and stricturing/fistulizing Crohn's disease, (p=0.002).Conclusions: Data underline that Substance P might exerts important immunomodulatory functions in inflammatory bowel disease. This study suggests a potential role for Substance P serum levels in monitoring intestinal inflammation in patients with inflammatory bowel disease.
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Internal fistula leakage due to a road traffic accident: A fortuitous diagnosis of Crohn's disease
Abstract: Background and aim: Fistulae are one of the most frequent complications of Crohn's disease (CD) and occur in 30–40% of patients. Conversely, free perforation is a rare complication and is one of the indications for emergency surgery of CD because of secondary peritonitis. We report a case of a spontaneous fistula rupture secondary to a road traffic accident.Methods: Case report.Results: A 22year-old man, with no personal significant medical history, was admitted in the emergency room after a road traffic accident. He underwent abdominal CT, which revealed pelvis fractures, abnormal bowel wall of the terminal ileum (wall thickening and mucosal enhancement), peritoneal effusion within the pelvis, mesenteric nodes and extra-luminal gas within an area of mesenteric inflammation: these features were suggestive of ileum perforation associated with inflammatory bowel disease, most likely CD. Laparoscopic assessment was decided and an ileocaecal resection with ileocolonic anastomosis was performed. Histological analysis revealed terminal ileitis with ulcers, non caseating granulomas and submucosal fibrosis, a transparietal fistula and a caecoappendicular inflammation, confirming CD. Post surgical outcome was uneventful and the patient was discharged at day 9.Conclusion: Our patient presented this rare complication revealing CD. The involvement of the terminal ileum and fistulae were characteristics of CD. Rupture of the fistula was favored by the trauma and responsible for the peritonitis. A resection with primary anastomosis was possible. To our knowledge, it is the first case described for the rupture of an ileal fistula secondary to traumatism in a patient with CD.
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Identification of areas of functioning and disability addressed in inflammatory bowel disease-specific patient reported outcome measures
Abstract: Background and aims: Patient-reported outcome measures (PROMs) make it possible to assess health-status problems from the perspective of persons suffering from a disease. The objective of the paper is to examine and compare the contents of PROMs related to IBD based on the World Health Organization's International Classification of Functioning, Disability and Health (ICF) as the frame of reference.Methods: A systematic literature review (1999–2009) in the databases Medline, EMBASE, PsycINFO, CINAHL and CENTRAL was performed to select IBD-specific PROMs. Abstracts and full-text articles were checked applying predefined eligibility criteria; IBD-specific PROMs were identified. The contents of the identified PROMs were examined by linking the items to ICF categories. The linked ICF categories of the PROMs were then compared.Results: The review resulted in the selection of eight IBD-specific PROMs (e.g., Cleveland Global Quality of Life, Inflammatory Bowel Disease Quality of Life Questionnaire, Inflammatory Bowel Disease Questionnaire-32, Rating Form of IBD Patient Concerns, Short Inflammatory Bowel Disease Questionnaire). In total, 129 items were identified, the majority of which (n=90; 69.8%) could be linked to specific ICF categories. None of the linked categories were contained in all PROMs. The most frequently identified categories were ‘b1300 Energy level’, ‘b5254 Flatulence’, ‘d910 Community life’ and ‘d920 Recreation and leisure’.Conclusion: The present study provides an overview of IBD-specific PROMs and their items. The results of the content comparison provide valuable information to facilitate and account for the selection of appropriate PROMs for different purposes of data collection in clinical and research settings.
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Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitis
Abstract: Aim: To evaluate the effect of infliximab induction therapy on calprotectin levels in patients with ulcerative colitis (UC).Patients and Methods: In this prospective study 53 patients with active UC from 17 centers were treated with infliximab therapy (5mg/kg) at baseline, week 2, and week 6. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10.Results: Median calprotectin levels decreased from 1260 (IQR 278.5- 3418 ) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p<0.001). After 10weeks, infliximab therapy induced endoscopic remission and a decrease in calprotectin to<50mg/kg or at least a 80% decrease from baseline level in 58% of patients.A significant and steep decrease of calprotectin levels was seen at week 2 for patients with an endoscopic remission at week 10 as compared to patients who did not show a remission. (p<0.001).At week 10 an excellent correlation was found between endoscopic remission and clinical Mayo score reflected by an AUC of ROC analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1)) : all patients with calprotectin levels <50mg/kg, and a normal clinical Mayo score (=0) were in endoscopic remission.Conclusions: Infliximab induces a fast and significant decrease of faecal calprotectin levels in anti-TNF naïve patients with ulcerative colitis predictive for remission of disease
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Thiopurine treatment in inflammatory bowel disease: Response predictors, safety, and withdrawal in follow-up
Abstract: Background and aims: Thiopurines represent the mainstay of immunosuppressive therapy in inflammatory bowel diseases. Since it is likely that response to therapy and adverse events depends on the genetic background of patients our study aimed to evaluate retrospectively response to therapy and safety in a mixed IBD population in Southern Europe.Methods: We evaluated demographic and clinical data of our patients treated with thiopurines. after 6months in responders and non-responders to therapy. Moreover the likelihood to remain in thiopurine monotherapy was evaluated in responders, whereas adverse events were investigated in all patients.Results: Among disease- and patient-related parameters a shorter disease duration, female gender and ileal disease in Crohn's patients were associated with better response. By ROC analysis, the best predictors of response were decreasing values of C-reactive protein and erythrocyte sedimentation rate. In the long-term more than half of IBD patients who responded at 6months remained on monotherapy at 42months. Flu-like syndrome represented the most frequent adverse event followed by abnormalities of liver function tests and myelotoxicity. Adverse events did occur at any time and were frequently impredictable.Conclusions: In this retrospective study, thiopurines showed a good clinical efficacy, especially in patients with short duration of disease. Normalization of markers of systemic inflammation represents the most useful tool to assess response. Careful monitoring of patients is required during the whole duration of treatment although it may not prevent all severe complications.
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Impact of budesonide on liver function tests and gut inflammation in patients with primary sclerosing cholangitis and ileal pouch anal anastomosis
Abstract: Background and aim: Budesonide has been studied in patients with primary sclerosing cholangitis (PSC). This study was designed to evaluate the efficacy of oral budesonide on liver function tests in patients with PSC and pouchitis associated with ileal pouch-anal anastomosis (IPAA).Materials and methods: The study group consisted of 18 pouch patients with underlying ulcerative colitis (UC) and PSC who were treated with 9mg daily of budesonide for their underlying pre-pouch ileitis and pouchitis for 1-3months followed by 3-6mg maintenance for another 9months. Demographic and clinical variables were analyzed.Results: The mean age was 39.4±12.4years (range, 21–59years). There was no significant change in aspartate aminotransferase (AST) [median (interquartile range) (IQR) 32 (25, 43.8) vs. 35.5 (25.5, 53), p=0.35], alanine aminotransferase (ALT) [37.5 (25.5, 49.5) vs. 40 (30, 84.3), p=0.29], alkaline phosphatase [142.5 (98.5, 264.5) vs. 126 (94.3, 189.5), p=0.35], serum bilirubin [0.7 (0.4, 1.3) vs., 0.6 (0.4, 1.6), p=0.13] or albumin levels [4.3 (3.9, 4.4) vs. 4.2 (3.8, 4.4), p=0.22] at the end of the treatment period (1year). The revised Mayo Risk Score did not change significantly and three patients required evaluation for liver transplantation during treatment. There was a significant improvement in the endoscopy subscores in the afferent limb and pouch after a year of budesonide treatment (p=0.001).Conclusions: Oral budesonide appears to have no impact on liver function tests in pouch patients with PSC. However it significantly improved afferent limb and pouch inflammation in IPAA patients.
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