Inflammation of axial and/or peripheral joints is one of the most frequent extra-intestinal manifestations complicating the clinical course and therapeutic approach in inflammatory bowel diseases ...（IBD）. The frequency of these complications seems to be similar for both diseases, Crohn＇s disease and ulcerative colitis. Arthritis associated with IBD belongs to the category of spondyloarthropathies. Axial involvement ranges from isolated inflammatory back pain to ankylosing spondylitis, whereas peripheral arthritis is noted in pauciarticular and in polyarticular disease. Asymptomatic radiological involvement of the sacroiliac joints is reported to occur in up to 50% of patients. Other musculoskeletal manifestations such as buttock pain, dactylitis, calcaneal enthesitis, and thoracic pain are frequently underdiagnosed and, consequently, are not treated appropriately. Several diagnostic approaches and criteria have been proposed over the past 40 years in an attempt to correctly classify and diagnose such manifestations. The correct recognition of spondylarthropathies needs an integrated multidisciplinary approach in order to identify common therapeutic strategies, especially in the era of the new biologic therapies.
Vitamin D deficiency has been recognized as an environmental risk factor for Crohn’s disease since the early 80s. Initially, this finding was correlated with metabolic bone disease. Low serum ...25-hydroxyvitamin D levels have been repeatedly reported in inflammatory bowel diseases together with a relationship between vitamin D status and disease activity. Subsequently, low serum vitamin D levels have been reported in various immune-related diseases pointing to an immunoregulatory role. Indeed, vitamin D and its receptor (VDR) are known to interact with different players of the immune homeostasis by controlling cell proliferation, antigen receptor signalling, and intestinal barrier function. Moreover, 1,25-dihydroxyvitamin D is implicated in NOD2-mediated expression of defensin-β2, the latter known to play a crucial role in the pathogenesis of Crohn’s disease (IBD1 gene), and several genetic variants of the vitamin D receptor have been identified as Crohn’s disease candidate susceptibility genes. From animal models we have learned that deletion of the VDR gene was associated with a more severe disease. There is a growing body of evidence concerning the therapeutic role of vitamin D/synthetic vitamin D receptor agonists in clinical and experimental models of inflammatory bowel disease far beyond the role of calcium homeostasis and bone metabolism.
Background:
Given the role of alexithymia—as the inability to identify, differentiate, and express emotions—in chronic and immune-mediated illness, this systematic review analyzed the prevalence of ...alexithymia in patients with inflammatory bowel diseases (IBDs), mainly represented by Crohn's disease (CD) and ulcerative colitis (UC).
Methods:
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed throughout this systematic review of the literature published between 2015 and 2020 in indexed sources from PubMed, PsycINFO, Scopus, and Web of Science databases. Search terms for eligible studies were: “Inflammatory bowel disease” AND “Alexithymia” Titles, Abstract, Keywords. Inclusion criteria were: articles written and published in English from 2015 and up to April 2020, reporting relevant and empirical data on alexithymia and IBD.
Results:
The initial search identified 34 indexed scientific publications. After screening, we found that five publications met the established scientific inclusion criteria. Overall, the mean value of alexithymia ranged from 39 to 53.2 Toronto Alexithymia Scale (TAS-20) score, thus mostly falling in non-clinical range for alexithymia (≤51). Comparisons of alexithymia between patients with UC and CD highlighted that patients with CD showed externally oriented thinking and difficulties identifying feelings to a greater extent. Regarding comparisons with other samples or pathologies, patients with IBD were more alexithymic than healthy controls and less alexithymic than patients with major depressive disorder, but no difference was found when compared with patients with irritable bowel syndrome (IBS). Then, regarding correlations with other variables, alexithymia was positively associated with anxiety and depression, as well as with psychopathological symptoms and somatic complaints.
Conclusion:
This systematic review suggests that patients with IBD cannot be generally considered alexithymic at a clinically relevant extent. However, their greater alexithymic levels and its associations with psychological variables and somatic distress may suggest a reactivity hypothesis, in which living with IBD may progressively lead to impaired emotion recognition over time. Specifically, the relationship between IBD and IBS should be further explored, paying deeper attention to the clinical psychological functioning of CD, as IBD requires more emotional challenges to patients.
Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis ...factor (TNF) inhibitors in these patients.
We collected data from patients with IBD treated with infliximab (n = 2475) and adalimumab (n = 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn's disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 years old or younger who were treated with both biologics and 190 patients older than 65 years who were treated with other drugs. The primary end points were severe infection, cancer, or death.
Among patients more than 65 years old who received infliximab and adalimumab, 11% developed severe infections, 3% developed neoplasms, and 10% died. No variable was associated with severe infection or death. Among control patients more than 65 years old, 0.5% developed severe infections, 2% developed cancer, and 2% died. Among control patients less than 65 years old, 2.6% developed severe infections, none developed tumors, and 1% died.
Patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age that did not receive these therapeutics. The effects of anti-TNF agents in older patients with IBD should be more thoroughly investigated, because these patients have higher mortality related to hospitalization than younger patients.
Inflammatory bowel diseases (IBD) are considered barrier diseases. After misleading initial results, the pathogenic importance of a disturbed mucosa is now widely accepted, largely because a certain ...percentage of first-degree relatives of patients with IBD do have permeability alterations, as assessed by oral markers. In the presence of a normal appearing gut mucosa, functional alterations of the highly dynamic inter-enterocyte tight junctions have to be considered to be responsible for the observed alterations. Indeed, various alterations of the transmembrane and intracytoplasmic proteins have been reported in IBD. An important therapeutic goal is to maintain disease remission by preservation of the correct organization of these complexes. Of the potential therapeutic approaches, the various anti-TNF agents are the best-studied agents, but other treatments may tighten the gut through as yet unknown mechanisms.
We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in ...patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA.
Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis.
Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23-2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03-1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00-2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76-2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24-1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44-1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD.
Oral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild-to-moderate UC with a similar safety profile.
The pathogenesis of ulcerative is still poorly understood. With the introduction of new culture-independent techniques the research on the intestinal microbiota has revealed an important reduction of ...Bacteroidetes and Firmicutes leading to a reduced biodiversity and dysbiosis in these patients. Going in depth, the intestinal barrier is covered under physiologic conditions by a mostly sterile mucus layer. Besides a reduction of mucus thickness or an alteration in mucus composition hypothesized for human ulcerative colitis, new evidence coming from mouse models has introduced a novel concept based on cellular stress due to misfolded mucus-associated proteins opening a new research area for the epithelial cell lining. A dysregulated immune response involving the innate (e.g. toll-like receptors, dendritic cells, etc) and the adaptive immune system (e.g. effector T-cells, regulatory T-cells, eosinophils, neutrophils, etc) may follow or precede the macroscopic lesions. The immune response in ulcerative colitis is represented principally by secretion of interleukin-5 and -13 being the latter responsible for the direct cytotoxicity against the epithelial cells. In latter stages the role of interleukin-17 producing cells, apparently differently regulated compared with Crohn's disease, remains to be elucidated. Finally, human ulcerative colitis is characterized by the presence of various types of autoantibodies including pANCA, antibodies against goblet cells and the isoforms 1 and 5 of human tropomyosin. The pathogenic potential of these antibodies is still debated. The present review focus on new achievements in the various scenarios converging to the clinical and histopathological feature of ulcerative colitis.
This issue presents a symposium held in Messina talking about inflammatory bowel disease (IBD) and associated spondyloarthropathies. The topic covers epidemiology and clinical manifestations of ...IBD-related arthropathies, common genetic and immunologic features, combined therapies for gut and joint inflammation, and future biologic therapies etc. I believe this series of articles will deeply facilitate understanding of and the approach to IBD and associated arthropathies.
Inflammatory bowel diseases (IBDs) are a public health issue with over 3.5 million patients in Europe, but the advent of several biologic agents has completely changed their management. ...Pharmacovigilance is needed to early detect expected/unexpected adverse events (AEs) to assess the safety of drugs in a real-world setting. Aim of this prospective pharmacovigilance study was to evaluate the occurrence of AEs in patients treated with biologic drugs in gastroenterology units in Southern Italy.
All consecutive patients treated with one biologic drug during a 2-years period (2017-2018) in six gastroenterology tertiary units and satisfying inclusion criteria were enrolled. Demographic and clinical characteristics of patients, type of treatment used, therapy discontinuation, failures, switch/swap to another biologic, and possible onset of AEs were collected. Adverse events have been compared to the number of AEs reported in the same centres in the two years before the protocol.
Overall, 623 patients (253 females) with Crohn's disease (352; 56.5%) or ulcerative colitis (271; 43.5%) have been included. Infliximab (IFX) was the most commonly used (308, 49.4%), followed by adalimumab (ADA; 215, 34.5%), vedolizumab (VED; 73, 11.7%), golimumab (GOL; 26, 4.2%) and ustekinumab (UST; 0.2%). Ninety-two patients have experienced AEs (14.8%) and 10 serious adverse events (SAEs) (1.6%) were recorded. Adverse events and SAEs have been reported with GOL (7/26; p = .88), IFX (51/308; p = .54), ADA (28/125; p = .40) and VED (6/73; p = .11), no AEs occurred with UST (0/1).
Overall, considering the low rate of AEs reported and discontinuation from therapy, our data seems to confirm the positive beneficial/risk ratio of biologic treatment for IBDs and provide useful data on biologic drugs in gastroenterology.
With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards ...different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years-old is steadily increasing, and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g., infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients, and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.
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