Osteonecrosis of both knees in a woman with Crohn's disease

Osteonecrosis is a very rare complication of Crohn's disease(CD).It is not clear if it is related to corticosteroid therapy or if it occurs as an extraintestinal manifestation of inflammatory bowel disease.We present the case of a patient with CD who presented with osteonecrosis of both knees.A 22 years old woman was diagnosed with CD in April 2012(Montreal Classification A2L1 + L4B3p).She was started on prednisolone(40 mg/d),azathioprine(100 mg/d) and messalazine(3 g/d).In July 2012,due to active perianal disease,infliximab therapy was initiated.In September 2012,she had a pelvic abscess complicated by peritonitis and an ileal segmental resection and right hemicolectomy were performed.In December 2012 she was diagnosed with bilateral septic arthritis of both knees with walking impairment.She was treated with amoxicillin-clavulanic acid,started a physical rehabilitation program and progressively improved.However,then,bilateral knee pain exacerbated by movement developed.Magnetic resonance imaging showed multiple osseous medullary infarcts in the distal extremity of the femurs,proximal extremity of the tibiae and patellas and no signs of subchondral collapse,which is consistent with osteonecrosis.The patient recovered completely and maintains therapy with azathioprine and messalazine.A review of the literature is also done.

Current role of capsule endoscopy in Crohn's disease

Capsule endoscopy(CE) currently plays an important role in Crohn's disease(CD). It is a noninvasive technique that has led to a breakthrough in the endoscopic diagnosis of diseases of the small intestine. Its superior diagnostic performance and excellent safety profile lead to its considerable acceptance on the part of the patient. This paper reviews current indications of CE in three stages of clinical practice: Suspected CD, unclassified colitis and its extensive role in diagnosed CD. The diagnostic and therapeutic impact of the results of CE on the monitoring of this disease is also reviewed. Knowledge of its applications, the interpretation of its results in an appropriate context and the existence of a validated endoscopic activity index could change the way in which these patients are managed. The definition of mucosal healing and postoperative recurrence by means of endoscopic scoring systems will endow CE with new applications in the management of CD in the near future.

Influence of environmental factors in the development of inflammatory bowel diseases

Idiopathic inflammatory bowel diseases(IBD), Crohn's disease(CD) and ulcerative colitis(UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miR NAS could explain the connection between genes and environmental factors in triggering the development of IBD.

Sieving characteristics of cytokine-and peroxide-induced epithelial barrier leak:Inhibition by berberine

AIM:To study whether the inflammatory bowel disease(IBD)colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak.METHODS:We examined the effects of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-1-β(IL1β)and hydrogen peroxide(H_2O_2)-singly and in combinations-on barrier function of CACO-2 cell layers.Our focus was on the type(not simply the magnitude)of transepithelial leak generated by these agents as measured by transepithelial electrical resistance(TER)and transepithelial flux of ^(14)C-D-mannitol,3H-Lactulose and ^(14)C-Polyethylene glycol as radiolabeled probe molecules.The isoquinoline alkaloid,berberine,was then examined for its ability to reduce specific types of transepithelial leak.RESULTS:Exposure to TNF-α alone(200 ng/mL;48 h)induced a 50% decrease in TER,i.e.,increased leak of Na^+ and Cl--with only a marginal but statistically significant increase in transepithelial leak of ^(14)C-mannitol(Jm).Exposure to TNF-α + IFN-γ(200 ng/mL;48 h)+ IL1β(50 ng/mL;48 h)did not increase the TER change(from TNF-α alone),but there was now a 100% increase in J_m.There however was no increase in transepithelial leak of two larger probe molecules,~3H-lactulose and ^(14)C-polyethylene glycol(PEG).However,exposure to TNF-α + IFN-γ + IL1β followed by a 5 h exposure to2 mmol/L H_2O_2 resulted in a 500% increase in ^(14)C-PEG leak as well as leak to the luminal mitogen,epidermal growth factor.CONCLUSION:This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances.

Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease

There is currently no gold standard test for the diagnosis of inflammatory bowel disease(IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis(UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Noninvasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.

Diagnosis and management of functional symptoms in inflammatory bowel disease in remission

Inflammatory bowel disease(IBD) patients in remission may suffer from gastrointestinal symptoms that resemble irritable bowel syndrome(IBS). Knowledge on this issue has increased considerably in the last decade, and it is our intention to review and summarize it in the present work. We describe a problematic that comprises physiopathological uncertainties, diagnostic difficulties, as IBS-like symptoms are very similar to those produced by an inflammatory flare, and the necessity of appropriate management of these patients, who, although in remission, have impaired quality of life. Ultimately, from almost a philosophical point of view, the presence of IBS-like symptoms in IBD patients in remission supposes a challenge to the traditional functional-organic dichotomy, suggesting the need for a change of paradigm.

Endoscopic evaluation in diagnosis and management of inflammatory bowel disease

Endoscopy is a keystone in the management of patients with inflammatory bowel disease(IBD).It is the fundamental diagnostic tool for IBD,and can help discern between ulcerative colitis and Crohn's disease.Endoscopic assessment provides an objective end point in clinical trials,and identifies patients in clinical practice who may benefit from treatment escalation and may assist risk stratification in patients seeking to discontinue therapy.Recent advances in endoscopic assessment of patients with IBD include video capsule endoscopy,and chromoendoscopy.Technological advances enable improved visualization and focused biopsy sampling.Endoscopic resection and close surveillance of dysplastic lesions where feasible is recommended instead of prophylactic colectomy.

Elderly patients and inflammatory bowel disease

The incidence and prevalence of inflammatory bowel disease(IBD) is increasing globally. Coupled with an ageing population, the number of older patients with IBD is set to increase. The clinical features and therapeutic options in young and elderly patients are comparable but there are some significant differences. The wide differential diagnosis of IBD in elderly patients may result in a delay in diagnosis. The relative dearth of data specific to elderly IBD patients often resulting from their exclusion from pivotal clinical trials and the lack of consensus guidelines have made clinical decisions somewhat challenging. In addition, age specific concerns such as co-morbidity; locomotor and cognitive function, poly-pharmacy and its consequences need to be taken into account. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this vulnerable group and set appropriate boundaries maximising benefit and minimising harm. Meanwhile, clinicians need to make personalised decisions but as evidence based as possible in the holistic, considered and optimal management of IBD in elderly patients. In this review we will cover the clinical features and therapeutic options of IBD in the elderly; as well as addressing common questions and challenges posed by its management.

Video capsule endoscopy in inflammatory bowel disease

Video capsule endoscopy(VCE) has evolved to become an important tool for the non-invasive examination of the small bowel, which hitherto had been relatively inaccessible to direct visualisation. VCE has beenshown to play a role in monitoring the activity of small bowel Crohn's disease and can be used to assess the response to anti-inflammatory treatment in Crohn's disease. For those patients with Crohn's disease who have undergone an intestinal resection, VCE has been assessed as a tool to detect post-operative recurrence. VCE may also aid in the reclassification of patients with a diagnosis of Inflammatory Bowel Disease Unclassified to Crohn's disease. The evolution of colon capsule endoscopy(CCE) has expanded the application of this technology further. The use of CCE to assess the activity of ulcerative colitis has been described. This advance in capsule technology has also fuelled interest in its potential role as a minimally invasive tool to assess the whole of GI tract opening the possibility of its use for the panenteric assessment of Crohn's disease. VCE is a safe procedure. However, the risk of a retained capsule is higher in patients with suspected or confirmed Crohn's disease compared with patients having VCE examination for other indications. A retained video capsule is rare after successful passage of a patency capsule which may be utilised to pre-screen patients undergoing VCE. This paper describes the use of VCE in the assessment of inflammatory bowel disease.

Faecal incontinence and health related quality of life in inflammatory bowel disease patients: Findings from a tertiary care center in South Asia

AIM: To analyze the frequency and severity of faecal incontinence(FI) and its effect on the quality of life(QOL) in inflammatory bowel disease(IBD) patients. METHODS: All patients who attended surgical and medical gastroenterology outpatient clinics in a tertiary care center with an established diagnosis of either ulcerative colitis(UC) or Crohn's disease(CD) over a period of 10 mo were included in this study. Before enrollment into the study, the patients were explained about the study and informed consent was obtained. The patients with unidentified colitis were excluded. The data on demographics, disease characteristics, FI(Vaizey score), and quality of life(IBD-Q) were collected. Data were analyzed using SPSS version 21.RESULTS: There were 184 patients(women = 101, 54.9%; UC = 153, 83.2%) with a female preponderance for UC(male/female ratio = 1:1.5) and a male preponderance for CD(male/female = 2:1). Forty-eight(26%) patients reported symptoms of FI. Among the patients with FI, 70.8% were women(n = 34) and 29.2% were men(n = 14) with an average age of 52.7 years(range, 20-78 years). Average age of onset of FI was 48.6(range, 22-74) years. Ten percent(n = 5) reported regular FI. Incontinence to flatus was seen in 33.3%(n = 16), to liquid faeces in 56.2%(n = 27), to solid faeces in 6.2%(n = 3) and to all three in 4.1%(n = 2). Twenty-one percent(n = 10) complained of disruption of their physical and social activity. There was no association between FI and type of IBD. Significant associations were found between FI and age(P = 0.005) and gender(P < 0.001). QOL in our cohort of patients was significantly affected by FI.CONCLUSION: In our study, nearly a quarter of patients reported FI. There was a significant correlation between FI and QOL. Therefore, enquiring about FI in IBD patients can lead to identification of this debilitating condition. This will enable early referral for continence care in this group of patients.

Infertility in men with inflammatory bowel disease

Inflammatory bowel disease(IBD) predominantly affects young adults. Fertility-related issues are therefore im-portant in the m-anagem-ent of patients with IBD. However, relatively m-odest attention has been paid to reproductive issues faced by m-en with IBD. To investigate the effects of IBD and its treatm-ent on m-ale fertility, we reviewed the current literature using a system-atic search for published studies. A PubM ed search were perform-ed using the m-ain search term-s "IBD AND m-ale infertility", "Crohn's disease AND m-ale infertility", "ulcerative colitis AND m-ale infertility". References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, sm-oking, m-edications, and surgery m-ay cause infertility in m-en with IBD. In surgery such as proctocolectom-y with ileal pouch-anal anastom-osis, rectal incision seem-s to be associated with sexual dysfunction. Of the m-edications used for IBD, sulfasalazine reversibly reduces m-ale fertility. No other m-edications appear to affect m-ale fertility significantly, although sm-all studies suggested som-e adverse effects. There are lim-ited data on the effects of drugs for IBD on m-ale fertility and pregnancy outcom-es; however, patients should be inform-ed of the possible effects of paternal drug exposure. This review provides inform-ation on fertility-related issues in m-en with IBD and discusses treatm-ent options.

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

Inflammatory bowel diseases(IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease(CD) and ulcerative colitis(UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria(microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroidfree long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered(oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease(CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems(Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8^+ T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.

Pancreatic disorders in inflammatory bowel disease

An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been rec-orded in patients with inflammatory bowel disease(IBD) compared to the general population.Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced,in some cases pancreatitis were defined as idiopathic,suggesting a direct pancreatic damage in IBD.Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis.This review will discuss the most common pancreatic diseases seen in patients with IBD.

Minimally invasive surgery for inflammatory bowel disease: Current perspectives

The surgical management of complicated and recurrent inflammatory bowel disease(IBD),has remained a challenge.Minimally invasive surgery(MIS),in the form of laparoscopic resections,single port approach and robotic-assisted dissections in the management of IBD,have been examined in several prospective studies.All of them have shown advantages over open surgeryin terms of reduction of physical trauma of surgery,recovery time,better cosmetic outcomes and shorter hospitalization.However,it is important to appreciate that not all patients with IBD are suitable for MIS,so a combination of both open and MIS should be adopted to achieve optimum outcomes.A review on this subject performed by Neumann et al in this issue of World Journal of Gastrointestinal Pharmacology and Therapeutics have provided evidence in support of the contemporary practice of MIS in the management of IBD and the accompanying commentary further critically evaluates their application in clinical practice.