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Background and Aim Pneumocystis jirovecii pneumonia [PJP] is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease [IBD]. Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP. Methods PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organisation. Clinical data were provided through a case report form. Results In all, 18 PJP episodes were reported in 17 IBD patients [10 ulcerative colitis and seven Crohn's disease]. The median age at PJP diagnosis was 55 years (interquartile range [IQR], 40–68 years]. Two PJP [11.1%] occurred in patients on triple immunosuppression, 10 patients [55.6%] had double immunosuppressive treatment, four patients [22.2%] had monotherapy and two PJP occurred in absence of immunosuppressive treatment [one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation]. Immunosuppressive therapies included steroids [ n  = 12], thiopurines [ n  = 10], infliximab [ n  = 4], ciclosporin [ n  = 2], methotrexate [ n  = 1], and tacrolimus [ n  = 1]. None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulphamethoxazole or atovaquone and an intensive care unit [ICU] stay was required in seven cases. Two patients [aged 71 and 32 years] died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others. Conclusion This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Primary varicella zoster virus [VZV] infection results in varicella [chickenpox] and its reactivation results in herpes zoster [HZ; shingles]. Patients with inflammatory bowel disease [IBD] are susceptible to complications of primary VZV infection and have an increased risk of HZ. Concerns of VZV and HZ infection in the IBD population have been highlighted by the emergence of JAK inhibitors and their safety profile in this patient population, as with tofacitinib for the treatment of ulcerative colitis [UC]. The current pipeline of emerging therapies includes novel molecules targeting multiple pathways, including JAK/signal transducer and cytokine signalling pathways, such as JAK/STAT. Hence VZV and HZ will be increasingly relevant for gastroenterologists treating IBD patients in light of these emerging therapies. This review will focus on the epidemiology, disease course, prevention, and management of these two distinct infections in patients with IBD. [ABSTRACT FROM AUTHOR]

Background and Aims Crohn's disease [CD] can involve any part of the gastrointestinal tract. We aimed to characterize the clinical, endoscopic and histological features and treatment outcomes of CD patients with oesophageal involvement. Methods We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. Results A total of 40 patients were reported (22 males, mean [±SD, range] age at oesophageal CD diagnosis: 25 [±13.3, 10–71] years and mean time of follow-up: 67 [±68.1, 3–240] months). Oesophageal involvement was established at CD diagnosis in 26 patients [65%] and during follow-up in 14. CD was exclusively located in the oesophagus in two patients. Thirteen patients [32.2%] were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in five patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors [PPIs] were administered in 37 patients [92.5%]. Three patients underwent endoscopic dilatation for symptomatic strictures but none underwent oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients [82.5%] after a mean time of 7 [±5.6, 1–18] months. Follow-up endoscopy was performed in 29/40 patients and 26/29 [89.7%] achieved mucosal healing. Conclusion In this case series the endoscopic and histological characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing inflammatory bowel disease-related therapy occurring in two-thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients. [ABSTRACT FROM AUTHOR]

Background Interstitial lung [ILD] disease and granulomatous lung disease [GLD] are rare respiratory disorders that have been associated with inflammatory bowel disease [IBD]. Clinical presentation is polymorphic and aetiology is unclear. Methods This was an ECCO-CONFER project. Cases of concomitant ILD or GLD and IBD, or drug-induced ILD/GLD, were collected. The criteria for diagnosing ILD and GLD were based on definitions from the American Thoracic Society and the European Respiratory Society and on the discretion of reporting clinician. Results We identified 31 patients with ILD. The majority had ulcerative colitis [UC] [ n = 22]. Drug-related ILD was found in 64% of these patients, 25 patients [80.6%] required hospitalisation, and one required non-invasive ventilation. The causative drug was stopped in all drug-related ILD, and 87% of patients received systemic steroids. At follow-up, 16% of patients had no respiratory symptoms, 16% had partial improvement, 55% had ongoing symptoms, and there were no data in 13%. One patient was referred for lung transplantation, and one death from lung fibrosis was reported. We also identified 22 GLD patients: most had Crohn's disease [CD] [ n = 17]. Drug-related GLD was found in 36% of patients and 10 patients [45.4%] required hospitalisation. The causative drug was stopped in all drug-related GLD, and 81% of patients received systemic steroids. Remission of both conditions was achieved in almost all patients. Conclusions ILD and GLD, although rare, can cause significant morbidity. In our series, over half of cases were drug-related and therefore focused pharmacovigilance is needed to identify and manage these cases. [ABSTRACT FROM AUTHOR]

Background and Aims The optimal timing of treatment escalation in Crohn's disease [CD] remains a challenging issue, and very little is known about its long-term development following early versus late administration of anti-TNF antibodies. The long-term outcome of Swiss CD patients was comparatively assessed in an up to 10-year follow-up, using patients participating in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. Methods Prospectively collected SIBDCS patient data, including disease history, baseline characteristics at enrolment, and course of disease, were analysed in patients with early versus late [<24 versus ≥24 months after diagnosis] and no anti-TNF treatment. Results A reduced risk of developing bowel stenosis was found in patients who received early anti-TNF treatment. This association was seen in patients overall and also in the subgroups of CD patients without pre-existing complications [Log-rank test: p < 0.001]. Furthermore, osteoporosis and anaemia were observed significantly less frequently in patients who received early anti-TNF treatment, compared with either patients who received treatment late [ p < 0.001 and p = 0.046, respectively] or were never [ p < 0.001 for both] treated with anti-TNF antibodies. Patients with early anti-TNF administration sought medical consultations significantly less often, including gastroenterologists in private practice [ p = 0.017], ambulatory [outpatient] hospital visits [ p = 0.038], and a composite of any medical visits [ p = 0.001]. The percentage of patients unable to work was lowest for early-anti-TNF–treated patients, in comparison with patients who were treated late or never [3.6% vs 8.8% vs 3.7%, p = 0.016]. Conclusions In CD patients within the SIBDCS, early anti-TNF administration was found to be associated with several indicators of a more favourable long-term outcome. [ABSTRACT FROM AUTHOR]

Objectives: Previous population-based studies in patients with ulcerative colitis [UC] revealed variable colectomy rates and colectomy-associated risk factors. Over the past two decades, a decrease in colectomy rates was observed. We assessed risk factors and colectomy rates over time in UC in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. Methods: Prospectively collected SIBDCS data, including disease history, baseline characteristics at enrolment, and course of disease, were retrospectively analysed. Cumulative and adjusted annual colectomy rates were calculated. Results: Among 1245 UC patients analysed [54.6% male], 114 [9.2%] underwent colectomy. We observed 5-, 10-, 15-, and 20-year cumulative colectomy rates after diagnosis of 4.1%, 6.4%, 10.4%, and 14.4% of patients, respectively. Male sex (odds ratio [OR] 1.54; p = 0.035), pancolitis at diagnosis [OR = 2.16; p = 0.005], younger age at diagnosis [OR 0.89 per 5 years of age; p = 0.006] and presence of extraintestinal manifestations [EIM] [OR 2.30; p < 0.001] were risk factors for undergoing colectomy. We did not observe a significant protective effect of smoking on colectomy risk [OR 0.64; p = 0.106]. The majority of colectomies were performed within first 10 years of disease onset, with a rapidly decreasing colectomy rate after 15 years. In patients diagnosed after 2003, colectomy was performed much earlier during and individual's disease course. Nevertheless, we found a significantly decreasing trend in yearly colectomy rates over time after 2005. Conclusions: Crude and adjusted colectomy rates in Swiss UC patients were lower than those reported previously in the literature, and decreased over time. [ABSTRACT FROM AUTHOR]

Background: Pathogenesis of cutaneous extraintestinal manifestations [EIM] in inflammatory bowel disease [IBD] remains elusive. Efficacy of anti-TNF agents suggests TNFdependent mechanisms. The role of other biologics, such as anti-integrins or JAK-inhibitors, is not yet clear. Methods: We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, and Hsp-27/70 on 240 intestinal [55 controls, 185 IBD] and 64 skin biopsies [11 controls, 18 erythema nodosum [EN], 13 pyoderma gangenosum [PG], 22 psoriasis]. A semiquantitative score [0-100%] was used for evaluation. Results: TNFα was upregulated in intestinal biopsies from active Crohn's disease [CD] vs controls [36.2 vs 12.1, p < 0.001], but not ulcerative colitis [UC: 17.9]. NFκB, however, was upregulated in intestinal biopsies from both active CD and UC [43.2 and 34.5 vs 21.8, p < 0.001 and p = 0.017, respectively]. TNFα and NFκB were overexpressed in skin biopsies from EN, PG, and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, whereas it was upregulated in active UC vs controls [57.5 vs 35.4, p = 0.003]. STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, and a similar upregulation was seen in skin biopsies from EN [84.7 vs 22.3, p < 0.001] and PG [60.5 vs 22.3, p = 0.011], but not in psoriasis. Caspase 3 and CD68 overexpression in skin biopsies distinguished EN/PG from psoriasis and controls. Conclusions: Upregulation of TNFα/NFκB in EN and PG is compatible with the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not MAdCAM1, support a rationale for JAK-inhibitors in EN and PG, while questioning the role of vedolizumab. [ABSTRACT FROM AUTHOR]

Background and Aims: An imbalance between cellular antioxidant defence system[s] and reactive oxygen species [ROS]-driven oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease. Peroxiredoxin [PRDX] 6 contributes to an appropriate redox balance by clearing ROS and reducing peroxidized membrane phospholipids. We here studied the role of PRDX6 in acute and chronic dextran sodium sulphate [DSS]-induced colitis. Methods: To investigate the impact of PRDX6 on intestinal inflammation, we used wild type [WT], Prdx6 knock-out mice [Prdx6-/-] and transgenic mice [Prdx6tg/tg], overexpressing Prdx6. Acute and chronic colitis was induced by DSS in WT, Prdx6-/- and Prdx6tg/tg mice. Colitis was evaluated by endoscopy, colon length, histopathological assessment and myeloperoxidase [MPO] activity. Changes in mRNA and protein expression of pro-inflammatory cytokines and antioxidant enzymes were evaluated by real-time quantitative polymerase chain reaction [RT-qPCR] and western blot. Total glutathione [GSH] levels in colon samples were determined. Results: Prdx6-/- mice exposed to acute and chronic DSS showed a significant decrease in the clinical parameters and in colonic expression of pro-inflammatory cytokines compared with WT mice. mRNA expression of antioxidant enzymes in colon samples was significantly increased in Prdx6-/- compared with WT mice exposed to acute and chronic DSS. In addition, total GSH levels were increased in Prdx6-/- mice treated with DSS in comparison with WT. Overexpression of Prdx6 did not significantly influence acute and chronic colitis. Conclusions: Our data indicate that a lack of the antioxidant enzyme PRDX6 protects against the development of acute and chronic experimental colitis and is associated with increased expression and function of other antioxidant enzymes, suggesting effective compensatory mechanisms. [ABSTRACT FROM AUTHOR]

This paper is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al. JCC 2016]. [ABSTRACT FROM AUTHOR]

Background: Cogan's syndrome (CSy) is a very rare autoimmune disorder, mainly affecting the inner ear and the eye, and is associated with inflammatory bowel disease (IBD). Methods: This was a European Crohn's and Colitis Organisation (ECCO) retrospective observational study, performed as part of the CONFER project. A call to all ECCO members was made to report concomitant CSy and inflammatory bowel disease (IBD) cases. Clinical data were recorded in a standardized questionnaire. Results: This international case series reports on 22 concomitant CSy-IBD cases from 14 large medical centres. Mean duration of IBD until diagnosis of CSy was 8.7 years (range 0.0-38.0) and mean age at CSy diagnosis was 44.6 years (range 9.0-67.0). Six patients had underlying ulcerative colitis (UC) and 16 had Crohn's disease. Eleven patients (50%) had active disease at CSy diagnosis. Sixteen patients were under IBD treatment at the time of CSy diagnosis, of whom 6 (37.5%) were on anti-tumour necrosis factor (TNF). Seven out of 10 patients, who were treated for CSy with immunomodulators (mostly with corticosteroids), demonstrated at least partial response. Conclusion: This is the largest CSy-IBD case series so far. Although CSy is considered to be an autoimmune disease and is associated with IBD, immunomodulatory IBD maintenance treatment and even anti-TNF therapy do not seem to prevent disease onset. Moreover, IBD disease activity does not seem to trigger CSy. However, vigilance may prompt early diagnosis and directed intervention with corticosteroids at inception may potentially hinder audiovestibular deterioration. Finally, vigilance and awareness may also offer a better setting to study the pathophysiological mechanisms of this rare but debilitating phenomenon. [ABSTRACT FROM AUTHOR]

Background and aims: Smoking is a crucial environmental factor in inflammatory bowel disease [IBD]. However, knowledge on patient characteristics associated with smoking, time trends of smoking rates, gender differences and supportive measures to cease smoking provided by physicians is scarce. We aimed to address these questions in Swiss IBD patients. Methods: Prospectively obtained data from patients participating in the Swiss IBD Cohort Study was analysed and compared with the general Swiss population [GSP] matched by age, sex and year. Results: Among a total of 1770 IBD patients analysed [49.1% male], 29% are current smokers. More than twice as many patients with Crohn's disease [CD] are active smokers compared with ulcerative colitis [UC] [UC, 39.6% vs CD 15.3%, p < 0.001]. In striking contrast to the GSP, significantly more women than men with CD smoke [42.8% vs 35.8%, p = 0.025], with also an overall significantly increased smoking rate compared with the GSP in women but not men. The vast majority of smoking IBD patients [90.5%] claim to never have received any support to achieve smoking cessation, significantly more in UC compared with CD. We identify a significantly negative association of smoking and primary sclerosing cholangitis, indicative of a protective effect. Psychological distress in CD is significantly higher in smokers compared with non-smokers, but does not differ in UC. Conclusions: Despite well-established detrimental effects, smoking rates in CD are alarmingly high with persistent and stagnating elevations compared with the GSP, especially in female patients. Importantly, there appears to be an unacceptable underuse of supportive measures to achieve smoking cessation. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Hypoxia can induce inflammation in the gastrointestinal tract. However, the impact of hypoxia on the course of inflammatory bowel disease (IBD) is poorly understood. We aimed to evaluate whether flights and/or journeys to regions lying at an altitude of >2000m above the sea level are associated with flare-ups within 4weeks of the trip. Methods: IBD patients with at least one flare-up during a 12-month observation period were compared to a group of patients in remission. Both groups completed a questionnaire. Results: A total of 103 IBD patients were included (43 with Crohn's disease (CD): mean age 39.3±14.6years; 60 with ulcerative colitis (UC): mean age 40.4±15.1years). Fifty-two patients with flare-ups were matched to 51 patients in remission. IBD patients experiencing flare-ups had more frequently undertaken flights and/or journeys to regions >2000m above sea level within four weeks of the flare-up when compared to patients in remission (21/52 [40.4%] vs. 8/51 [15.7%], p=0.005). Conclusions: Journeys to high altitude regions and/or flights are a risk factor for IBD flare-ups occurring within 4weeks of travel. [Copyright &y& Elsevier]

Abstract: Background and aims: A significant fraction of patients with ulcerative colitis (UC) is not sufficiently controlled with conventional therapy or suffers from therapy related side effects. Anthocyanins, highly abundant in bilberries (Vaccinium myrtillus), were shown to have antioxidative and anti-inflammatory effects. We aimed to explore the therapeutic potential of bilberries in active UC. Methods: In an open pilot trial with a total follow-up of 9weeks the effect of a daily standardized anthocyanin-rich bilberry preparation was tested in 13 patients with mild to moderate UC. Clinical, biochemical, endoscopic and histologic parameters were assessed. Results: At the end of the 6week treatment interval 63.4% of patients achieved remission, the primary endpoint, while 90.9% of patients showed a response. In all patients a decrease in total Mayo score was detected (mean: 6.5 and 3.6 at screening and week 7, respectively; p<0.001). Fecal calprotectin levels significantly decreased during the treatment phase (baseline: mean 778μg/g, range 192–1790μg/g; end of treatment: mean 305μg/g, range <30–1586μg/g; p=0.049), including 4 patients achieving undetectable levels at end of treatment. A decrease in endoscopic Mayo score and histologic Riley index confirmed the beneficial effect. However, an increase of calprotectin levels and disease activity was observed after cessation of bilberry intake. No serious adverse events were observed. Conclusions: This is the first report on the promising therapeutic potential of a standardized anthocyanin-rich bilberry preparation in UC in humans. These results clearly indicate a therapeutic potential of bilberries in UC. Further studies on mechanisms and randomized clinical trials are warranted. [Copyright &y& Elsevier]

Abstract: Background and Aims: Cogan''s syndrome (CS) is a rare autoimmune disease with less than 250 cases reported. It mainly affects the audiovestibular system and the eyes frequently resulting in deafness. Inflammatory bowel disease (IBD) consists of two subtypes, Crohn''s disease (CD) and ulcerative colitis (UC), and represents a common form of chronic intestinal inflammation. Here, we report an association between CS and IBD in four patients. Methods: Patient data were collected using a questionnaire that was sent to one of our outpatients and three of the 13 members of the German CS self-help group. Results: In all Cogan patients with IBD (3 female with UC, 1 male with CD), intestinal disease was diagnosed years before the onset of CS. After suffering from a complicated IBD disease course, they suddenly developed CS-related symptoms, such as hearing loss, tinnitus or eye inflammation. Three of them went deaf within a few years after diagnosis. Although all of them had been on immunosuppressive IBD therapy, these treatment regimens did not prevent the onset of CS. Conclusions: Our data suggest a strong association of IBD and CS. Since CS rapidly leads to bilateral deafness, it seems to be a rare, but nevertheless important disease that can occur in association with IBD. However, neither an early diagnosis nor an immunosuppressive therapy seems to efficaciously prevent disease progression. [Copyright &y& Elsevier]

Abstract: Background: Anaemia represents a common complication of inflammatory bowel disease (IBD). Most studies on anaemia in IBD patients have been performed in tertiary referral centres (RC) and data from gastroenterologic practices (GP) are lacking. We investigated the frequency and severity of anaemia in IBD patients from tertiary referral centres and gastroenterologic practices compared to the general population. Methods: Data were acquired from patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by CDAI and modified Truelove and Witts severity index (MTWSI). Anaemia was defined as haemoglobin ≤120g/L in women and ≤130g/L in men. Results: 125 patients from RC (66 with Crohn''s disease (CD) and 59 with ulcerative colitis (UC)) and 116 patients from GP (71 CD and 45 UC) were included and compared to 6074 blood donors. Anaemia was found in 21.2% (51/241) of the IBD patients and more frequently in patients from RC as compared to GP and healthy controls (28.8% vs. 12.9% vs. 3.4%; P <0.01). IBD patients from RC suffered more frequently from active disease compared to IBD patients in GP (36% vs. 23%, P =0.032). Supplementation therapy (iron, vitamine B12, folic acid) was performed in 40% of anaemic IBD patients in GP as compared to 43% in RC. Conclusions: Anaemia is a common complication in patients with IBD and significantly more prevalent in patients from referral centres as compared to patients from gastroenterologic practices. Physicians treating IBD patients should pay attention to the presence of anaemia and ensure sufficient supplementation therapy. [Copyright &y& Elsevier]

Patients with inflammatory bowel disease [IBD] increasingly use alternative and complementary therapies, for which appropriate evidence is often lacking. It is estimated that up to half of all patients with IBD use various forms of complementary and alternative medicine during some point in their disease course. Considering the frequent use of such therapies, it is crucial that physicians and patients are informed about their efficacy and safety in order to provide guidance and evidence-based advice. Additionally, increasing evidence suggests that some psychotherapies and mind–body interventions may be beneficial in the management of IBD, but their best use remains a matter of research. Herein, we provide a comprehensive review of some of the most commonly used complementary, alternative and psychotherapy interventions in IBD. [ABSTRACT FROM AUTHOR]