Comparison of adenoma miss rate and adenoma detection rate between conventional colonoscopy and colonoscopy with second generation distal attachment cuff: a multicenter, randomized, back-to-back trial.

BACKGROUND AND AIMS: Endocuff VisionTM has been designed to enhance mucosal visualization thereby improving detection of (pre-)malignant colorectal lesions. This multicenter, international, back-to-back, randomized colonoscopy trial compared adenoma detection rate (ADR) and adenoma miss rate (AMR) between Endocuff Vision-assisted colonoscopy (EVC) and conventional colonoscopy (CC). METHODS: Patients aged 40-75 years referred for non-immunochemical fecal occult blood test-based screening, surveillance, or diagnostic colonoscopy were included at ten hospitals and randomized into four groups: Group 1; 2xCC, Group 2; CC followed by EVC, Group 3; EVC followed CC and Group 4; 2xEVC. Primary outcomes included ADR and AMR. RESULTS: A total of 717 patients were randomized of which 661 patients (92.2%) had one and 646 (90.1%) patients had two completed back-to-back colonoscopies. EVC did not significantly improve ADR compared to CC (41.1% [95%-CI;36.1-46.3] versus 35.5% [95%-CI;30.7-40.6], respectively, P=0.125), but EVC did reduced AMR by 11.7% (29.6% [95%-CI;23.6-36.5] versus 17.9% [95%-CI;12.5-23.5], respectively, P=0.049). AMR of 2xCC compared to 2xEVC was also not significantly different (25.9% [95%-CI;19.3-33.9] versus 18.8% [95%-CI;13.9-24.8], respectively, P=0.172). Only 3.7% of the polyps missed during the first procedures had advanced pathologic features. Factors affecting risk of missing adenomas were age (P=0.002), Boston Bowel Preparation Scale (P=0.008) and region where colonoscopy was performed (P<0.001). CONCLUSIONS: Our trial shows that EVC reduces the risk of missing adenomas but does not lead to a significant improved ADR. Remarkably, 25% of adenomas are still missed during conventional colonoscopies, which is not different from miss rates reported 25 years ago; reassuringly, advanced features were only found in 3.7% of these missed lesions. TRAIL REGISTRATION NUMBER: NCT03418948.

Predictors of Response to Vedolizumab in Patients with Ulcerative Colitis: Results from the Greek VEDO-IBD Cohort.

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

Endocuff-assisted colonoscopy is associated with a lower adenoma miss rate: a multicenter randomized tandem study.

Background and study aims The Endocuff (ARC Medical Design, Leeds, UK) is a device that, when mounted on the tip of an endoscope, may assist with inspection of a greater surface of the colonic mucosa by pulling backwards, flattening, and stretching the colonic folds as the endoscope is gradually withdrawn. We aimed to compare the adenoma miss rates of Endocuff-assisted colonoscopy with those of conventional colonoscopy. Patients and methods The included patients underwent same-day, back-to-back, (Endocuff-assisted colonoscopy as the index procedure followed by conventional colonoscopy or vice versa, randomly assigned 1:1) colonoscopies, performed by six endoscopists with documented adenoma detection rates > 35 %, in four tertiary endoscopy facilities. Results We randomized 200 patients (mean age 61.2 years [standard deviation 9.8]; 86.5 % colorectal cancer screening surveillance cases). Overall, there were seven incomplete examinations using Endocuff and one with conventional colonoscopy (P = 0.03). Times for endoscope insertion (5.0 minutes [0.8 - 21.0] vs. 5.0 minutes [1.0 - 16.0]; P = 0.49) and withdrawal (6.0 minutes [3.2 - 29.0] vs. 6.0 minutes [3.1 - 17.0]; P = 0.06) were similar for Endocuff-assisted and conventional colonoscopy. We detected one cancer and 195 adenomas; 84 in the proximal colon. Endocuff-assisted colonoscopy showed significantly lower overall and proximal colon adenoma miss rates compared with conventional colonoscopy (14.7 % [8.0 % - 21.0 %] vs. 38.4 % [28.1 % - 48.6 %] and 10.4 % [1.8 % - 19.1 %] vs. 38.9 % [23.0 % - 54.8 %], respectively). No difference between the two arms was shown regarding advanced adenoma miss rates, either overall or in the proximal colon. There were no serious adverse events related to the procedures. Conclusions In comparison with conventional colonoscopy, Endocuff-assisted colonoscopy has a significantly lower adenoma miss rate when performed by high-detector endoscopists. However, the incomplete colonoscopy rate with Endocuff is higher.ClinicalTrials.gov Identifier: NCT02340065.

Lower adenoma miss rate with FUSE vs. conventional colonoscopy with proximal retroflexion: a randomized back-to-back trial.

Background and study aims Full-spectrum colonoscopy (FSC) promises to increase adenoma detection by providing a wider field of view. The aim of this study was to compare adenoma miss rates of FSC with those of conventional colonoscopy complemented by right-colon re-examination using scope retroflexion (CC/R). Patients and methods At two tertiary endoscopy facilities, patients who were scheduled for colonoscopy for the assessment of symptoms or for colorectal cancer screening/surveillance were randomized (1:1) to undergo same-day, back-to-back colonoscopies (FSC or CC/R first), performed by one of five endoscopists who had documented adenoma detection rates > 35 %. Per-protocol data were analyzed. Results We randomized 220 patients. There were five FSC technical failures (three air pump and two left screen); therefore, 107 and 108 cases were analyzed in the FSC and CC/R index procedure arms, respectively. Withdrawal times were similar for FSC and CC/R (7.7 minutes vs. 7.6 minutes). Overall, we detected 3 cancers and 153 adenomas (FSC = 92; CC/R = 61); 81 were detected in the proximal colon, 3 of which were detected by retroflexed examination. By per-lesion analysis, FSC showed a significantly lower adenoma miss rate compared with CC/R overall (10.9 % [95 % confidence interval (CI) 3.8 to 18.1] vs. 33.7 % [95 %CI 23.4 to 44.1]) and in the proximal colon (13.9 % [95 %CI 2.6 to 25.2] vs. 42.2 % [95 %CI 27.8 to 56.7]). The advanced adenoma miss rate was lower with FSC overall (4.3 % [95 %CI - 4.0 to 12.7] vs. 25.9 % [95 %CI 9.4 to 42.5]). There were no adverse events. Conclusions FSC outperformed conventional colonoscopy with right-colon scope retroflexion in the detection of missed adenomas, both overall and in the proximal colon, even when performed by experienced endoscopists.Trial registered at ClinicalTrials.gov (NCT02117674).

Activation of NLRP3 Inflammasome in Inflammatory Bowel Disease: Differences Between Crohn's Disease and Ulcerative Colitis.

BACKGROUND: NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1ß to IL-1ß. AIMS: To investigate NLRP3 inflammasome activation in inflammatory bowel disease. METHODS: Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1ß, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1ß was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1ß production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1ß, TNFα, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping. RESULTS: NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (p = 0.042); no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (p = 0.008) with long-standing disease (>1.5 years). IL-1ß levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNFα, pro-IL-1ß and in the numbers IL-1ß, TNFα, NLRP3, and CASP1 transcripts among groups. IL-1ß production was similar between carriers of wild-type and of SNP alleles of the rs2241880. CONCLUSIONS: NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.

Increased levels of circulating platelet derived microparticles in Crohn's disease patients.

OBJECTIVE: Platelet activation is a consistent feature in inflammatory bowel disease. However, the role of circulating platelet derived microparticles (PDMPs) and the effects of disease activity and treatment on their levels has not been clarified yet in this disorder. MATERIAL AND METHODS: Using flow cytometry, we measured platelet derived microparticles and platelet derived microparticles expressing Annexin V in platelet rich plasma from 47 Crohn's disease and 43 ulcerative colitis patients and 24 healthy controls. RESULTS: Crohn's disease patients have greater PDMPs (0.31% ± 0.07% versus 0.14% ± 0.04%, p = 0.02) and PDMPs expressing Annexin V (27% ± 2.6% versus 14.6% ± 2.7%, p = 0.002) levels in comparison with healthy controls; however, both microparticles levels are not related with disease activity. Crohn's disease patients on 5-ASA therapy show lower levels of PDMPs in comparison with those on no 5-ASA (0.30% ± 0.07% versus 0.32% ± 0.09%, p = 0.048). Ulcerative colitis patients have similar PDMPs and PDMPs expressing Annexin V levels, compared to healthy controls (p = 0.06 and p = 0.2, respectively) and there is no correlation of both microparticles expression with disease activity. 5-ASA has no effect on both microparticles levels in ulcerative colitis patients. Anti-TNF-α treatment has no effect on study's microparticles expression in Crohn's and ulcerative colitis patients. CONCLUSIONS: Circulating levels of platelet derived microparticles are increased only in Crohn's patients, but they do not correlate with disease activity. 5-ASA treatment is associated with lower levels of PDMPs only in Crohn's, while anti-TNF-α treatment does not influence expression of microparticles in inflammatory bowel disease patients.

Evidence of Crohn's disease-related anti-glycoprotein 2 antibodies in patients with celiac disease.

BACKGROUND: Autoantibodies to exocrine-pancreatic glycoprotein 2 (anti-GP2) are Crohn's disease (CD) markers. However, CD-specific antibodies have also been found in celiac-disease (CeD) patients, in which type 1 diabetes-specific autoantibodies against endocrine pancreatic targets can be present. We investigated whether anti-GP2 are also present in CeD, a disease like CD which is also characterised by intestinal mucosal inflammation with barrier impairment. METHODS: Antibodies against GP2, tissue transglutaminase (tTG), deamidated gliadin (dGD), glutamic decarboxylase (GAD), and islet antigen-2 (IA2) were tested in sera from 73 CD patients, 90 blood donors (BD), and 79 (58 de novo) CeD patients (2 consecutive sera were available from 40 patients). RESULTS: IgA and/or IgG anti-GP2 were found in 15/79 (19.0%) CeD patients on at least one occasion, in 25/73 (34.2%) CD patients, and in 4/90 (4.4%) BD (CeD vs. CD, p=0.042; BD vs. CeD and CD, p<0.001, respectively). Amongst the 58 de novo CeD patients, anti-GP2 IgA and/or IgG were present in 11 (19.0%). Anti-GP2 IgA was significantly less prevalent in CeD compared with CD (p=0.004). Anti-GP2 IgA and IgG in CD patients demonstrated a significantly higher median level compared to patients with CeD (p<0.001, p=0.008, respectively). IgA anti-GP2 levels correlated significantly with IgA anti-tTG and anti-dGD levels in CeD Spearman's coefficient of rank correlation (ρ)=0.42, confidence interval (CI): 0.26-0.56, p<0.001; ρ=0.54, CI 0.39-0.65, p<0.001, respectively. CONCLUSIONS: The presence of anti-GP2 in CeD patients supports the notion that loss of tolerance to GP2 can probably be a manifestation of an autoinflammatory process in this intestinal disorder.

Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn's disease.

BACKGROUND: A link between measles virus and Crohn's disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry. METHODS: The BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins. Antibody responses to measles/human mimics were tested by an in-house ELISA using serum samples from 50 patients with CD, 50 with ulcerative colitis (UC), and 38 matched healthy controls (HCs). RESULTS: We identified 15 sets of significant (>70%) local amino acid homologies from two measles antigens, hemagglutinin-neuraminidase and fusion-glycoprotein, and ten human intestinal proteins. Reactivity to at least one measles 15-meric mimicking peptide was present in 27 out of 50 (54%) of patients with CD, 24 out of 50 (48%) with UC (CD versus UC, p = 0.68), and 13 out of 38 (34.2%) HCs (CD versus HC, p = 0.08). Double reactivity to at least one measles/human pair was present in four out of 50 (8%) patients with CD, three out of 50 (6%) with UC (p = 0.99), and in three out of 38 (7.9%) HCs (p >0.05 for all). Titration experiments yielded different extinction curves for anti-measles and anti-human intestinal double-reactive antibodies. Epitope prediction algorithms and three-dimensional modeling provided bioinformatic confirmation for the observed antigenicity of the main measles virus epitopic regions. CONCLUSIONS: Measles sequences mimicking intestinal proteins are frequent targets of antibody responses in patients with CD, but this reactivity lacks disease specificity and does not initiate cross-reactive responses to intestinal mimics. We conclude that there is no involvement of measles/human molecular mimicry in the etiopathogenesis of CD.

Partially hydrolyzed guar gum accelerates colonic transit time and improves symptoms in adults with chronic constipation.

BACKGROUND AND AIM: Partially hydrolyzed guar gum (PHGG) is a water-soluble, non-gelling dietary fiber with a wide range of uses in clinical nutrition. The aim of this prospective study was to investigate the effect of guar gum on colonic transit time (CTT) and symptoms of chronic constipation. METHODS: We enrolled patients fulfilling Rome III criteria for chronic constipation. CTT was measured before and at the end of treatment. After a 2-week run-in period, patients received 5 mg PHGG daily for 4 weeks. During study period, patients kept daily symptoms, stool and laxative usage diaries. They also recorded their symptom-related satisfaction weekly and treatment adverse events. RESULTS: Forty-nine patients received treatment; 39 (80 %) completed the study. Treatment significantly reduced colon transit time, from 57.28 ± 39.25 to 45.63 ± 37.27 h (p = 0.026), a reduction more prominent in slow transit patients (from 85.50 ± 27.75 to 63.65 ± 38.11 h, p = 0.016). Overall, the weekly number of complete spontaneous and spontaneous bowel movements increased significantly (p < 0.001); the latter correlated significantly with the acceleration of CTT in the overall population and in slow transit patients (B = 0.382; p = 0.016 and B = 0.483; p = 0.023, respectively). In addition, the number of bowel movements with straining decreased (p < 0.001) and stool form improved (p < 0.001), while days with laxative intake and days with abdominal pain decreased (p = 0.001 and p = 0.027, respectively). CONCLUSION: Four-week PHGG use accelerates colon transit time in patients with chronic constipation, especially in those with slow transit, and improves many of their symptoms including frequency of bowel movements.

Surgical Management of a Pancreaticopleural Fistula After Failed Endoscopic Therapy.

Inflammatory diseases of the pancreas or pancreatic trauma result in ductal cell disruption, which in turn may lead to leakage of pancreatic fluid, mostly in the retroperitoneal space. Pancreatopleural fistulas are uncommonly encountered following pancreatic injury; however, they often prove a difficult problem to manage. Herein, we present a rare case of a 68-year-old male suffering from a pancreaticopleural fistula (PF) between the pancreatic tail and the left pleural space one year following splenectomy for trauma. About three months after percutaneous drainage of a left pleural effusion and left upper quadrant abdominal collection and endoscopic pancreatic duct stent placement, surgical management was decided. Distal pancreatectomy and Roux-en-Y drainage of the pancreatic remnant were successfully performed.

Vedolizumab-induced acute interstitial lung injury in a 39-year-old male with ulcerative colitis.

Vedolizumab, an anti-integrin antibody, is effective for moderate to severe ulcerative colitis and Crohn's disease treatment with a good safety profile due to its gut selective mechanism of action. Upper respiratory tract vedolizumab adverse events are common; however, they are mild and do not require treatment withdrawal. Herein, we present a 39-year-old patient under vedolizumab treatment for ulcerative colitis who presented acute severe interstitial lung injury that necessitated vedolizumab withdrawal and systemic steroids administration.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Effect of sleep on excessive belching: a 24-hour impedance-pH study.

UNLABELLED: In patients with repetitive and troublesome belching an organic cause is seldom found, indicating the presence of an acquired abnormal behavior. The aim of our study was to investigate the incidence and pattern of belching during a 24-hour period. METHODS: Combined 24-hour pH and intraluminal impedance monitoring was performed in 14 patients (9 female; mean age: 43 y) with excessive belching and 10 patients (6 women, mean age 42 y; range 28 to 56) with noncardiac chest pain. Thereafter, we counted the number of belching events and differentiated the number of supragastric and gastric belches. RESULTS: During the 24-hour study, the hourly rate of belching was 38.7+/-6.0; rate of supragastric belches were significantly higher compared to gastric belches (37.7+/-6.0 vs 1.0+/-0.5, P<0.001). Patients with noncardiac chest pain showed a lower average hourly rate of belching (3.1+/-0.6, P<0.001). Dividing the recording into 2 periods (daily-upright and night-supine), there was a significant decrease in the hourly rate at night (37.8+/-6.1 vs. 0.9+/-0.5, respectively, P<0.001); mostly due to decrease in supragastric belches, where as the rate of gastric belches remained unchanged. None of the patients showed pathological acid reflux and none of the supragastric belches was associated with acid or nonacid reflux events. CONCLUSIONS: Supragastric belch is the prominent belching pattern in patients with excessive belching. Supragastric belches almost ceased at night suggesting the presence of a behavioral disorder. There were no diurnal changes in the rate of gastric belches.

Omeprazole maintenance therapy prevents recurrent ulcer bleeding after surgery for duodenal ulcer.

AIM: To evaluate the omeprazole maintenance therapy in patients with recurrent ulcer bleeding after surgery for duodenal ulcer. METHODS: We studied 15 consecutive patients with recurrent ulcer bleeding after surgery for duodenal ulcer. Omeprazole (20 mg/d) maintenance therapy was given after ulcer healing. In addition to clinical follow-up, ambulatory 24-h gastric pH assay was performed before and during omeprazole therapy in those patients and controls with previous duodenal ulcer surgery but no ulcer recurrence. RESULTS: All the 15 ulcers were healed after being treated with omeprazole (40 mg/d) for 2 mo. Eleven patients with two (1-9) episodes of recurrent ulcer bleeding completed the follow-up (43, 12-72 mo). None of them had a bleeding episode while on omeprazole. One patient discontinued the therapy and had recurrent bleeding. The median 24-h fraction time of gastric pH<4 in patients was 80, 46-95%, and was reduced to 32, 13-70% by omeprazole (P=0.002). CONCLUSION: Long-term maintenance therapy with omeprazole (20 mg/day) is effective in preventing recurrent ulcer bleeding.

Generalized Pyoderma Gangrenosum Associated with Ulcerative Colitis: Successful Treatment with Infliximab and Azathioprine.

Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, part of the spectrum of neutrophilic and auto-inflammatory dermatoses. Its pathogenesis is unknown, although immune pathways have been implicated. Lesion biopsies show a predominantly neutrophilic infiltrate. The incidence of PG is uncertain, but it is estimated to be 3-10 per million per year, occurring at any age but most commonly between 20 and 50 years with a possible slightly higher incidence in women. Approximately 50% of patients with PG also have another disease associated with PG. The most common is inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis (UC). Local treatment may be sufficient for mild cases, while for severe cases systemic immunosuppressants are the mainstay (1,2). We report the case of a patient with bullous PG and UC successfully treated with infliximab and azathioprine. A 32-year-old male Caucasian patient presented with painful violaceous vesicles and enlarging bullae of various sizes and with acute onset, located on the trunk and bilaterally on both the lower and the upper extremities. Lesions on the trunk were composed of hemorrhagic pustules with a surrounding erythematous overhanging border. Some of the lesions had undergone central necrosis and ulceration (Figure 1, a-d). The patient reported of the lesions had appeared one week ago, simultaneously with the exacerbation of a known inflammatory bowel disease with hemorrhagic mucoid diarrhea and fever of up to 38.5°C. The patient's medical history included UC affecting the whole colon (pancolitis), diagnosed 5 months prior to the onset of the epidermal lesions, for which the patient was receiving treatment with oral prednisolone 10 mg/day and mesalazine granules. Blood tests showed severe anemia, leukocytosis, and increased inflammatory markers (C-reactive protein, erythrocyte sedimentation rate). Antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA) andtibodies, antineutrophil cytoplasmic antibodies (cANCA), perinuclear neutrophil antibodies (p-ANCA), antiphospholipid antibodies, and tumor markers were within normal limits. The patient was negative for cryoglobulins, viral hepatitis (B, C) and human immunodeficiency virus (HIV). Blood cultures were negative. Microscopy and cultures for mycobacteria and fungi gave negative results. Stool samples tested negative for infections agents. The Mantoux skin test was negative. Colonoscopy showed severe pancolitis, and biopsies from the rectum and sigmoid colon were consistent with chronic ulcerative colitis. Abdominal ultrasound and chest and abdominal X-rays did not result in significant findings. Because of severe anemia, the patient received 2 blood transfusions. The histopathologic examination carried out on the erythematous border of a lesion on the lower leg showed a neutrophilic infiltrate, confined to the dermis. On the basis of clinical findings, the diagnosis of PG was established. Topical wound care consisted of local wound care and a topical corticosteroid. Systemic therapy was initiated with 40 mg/day methylprednisolone for 7 days, 30 mg/day for 7 days, then 25 mg/day, and then tapered down further. The patient received an infusion of infliximab 7.5 mg/kg at weeks 0, 2, and 6 and every 8 weeks thereafter. After week 2, oral azathioprine 2.5 mg/kg daily was added to the treatment. The patient also received mesalazine tablets (2 g ×2/day) and mesalazine enema (1-2/day). The patient showed good response to treatment, with clinical remission of skin lesions. Lesions healed with characteristic thin, atrophic scars (Figure 2, a-d). At 7-month follow-up the patient was continuing with infusions of infliximab 7.5 mg/kg and azathioprine 2.5 mg/kg and was still in remission. We reported our experience with a case of generalized bullous pyoderma gangrenosum associated with ulcerative colitis. Generalized pyoderma gangrenosum is very rare. Bullous or atypical PG was first described by Perry and Winklemann in 1972 (1). Brunsting et al. coined the term pyoderma gangrenosum (PG) to describe a series of patients with recurrent ulcerations (3). The incidence of this disease is uncertain. Its pathogenesis is unknown, but an immunological background has been suggested. In approximately 50% of patients, an underlying immunological disease is present, commonly inflammatory bowel disease (IBD) (4-6). In larger series of patients with PG, approximately 50% present with a primary disorder. Ulcerative colitis is found in 10-15% of cases. Crohn's disease is associated with PG closed than UC. Less than 3% of patients with Crohn's disease or UC develop PG (6). PG is characterized by cutaneous ulcerations with mucopurulent or hemorrhagic exudate. It begins as an inflammatory pustule with a surrounding halo that enlarges and begins to ulcerate. These very painful ulcers present with undermined bluish borders with surrounding erythema. The lesions of PG most commonly occur on the legs, but they may occur anywhere on the body. The clinical picture of PG is very characteristic. Therefore the diagnosis of PG is based firstly on clinical signs and on the patient's history of underlying diseases and then supported by biopsy. PG has four distinctive clinical and histological variants. Some have morphological and histological features that overlap with other reactive neutrophilic skin conditions. There are no diagnostic serologic features (6,7). There is no evidence that the efficacy of treatment strategies for PG differs between IBD and non-IBD patients. For patients with a diffuse disease or rapidly progressive process, systemic treatment is essential. Immunosuppression is the mainstay of treatment. Traditionally, the most commonly used drugs with the best clinical experience are systemic corticosteroids. Corticosteroids have been considered as first line treatment (6,8). As reported by the European Crohn's and Colitis Organisation (ECCO) in 2008, an evidence-based consensus on the management of special situations in patients with ulcerative colitis, systemic corticosteroids are recommended (9). Treatment with corticosteroids (e.g. prednisolone 1-2 mg per kg/day or pulse therapy with 1 g of methylprednisolone) aims to prevent progression and rapidly stop inflammation (6). Additional mesalamine and corticosteroids may be effective in patients with bowel disease (10). In recent years, tumor necrosis alpha (TNF-α) inhibitors, such as infliximab and adalimumab, were reported to be effective for PG associated with IBD. These drugs block the biological activity of TNF-α, which effects regulatory T cells, restoring their capacity to inhibit cytokine production. The TNF-α inhibitors thus suppress the inflammatory processes that is involved in the pathogenesis of PG (11). Infliximab, a chimeric monoclonal antibody, is given by infusion at weeks 0, 2, and 6 and then every 8 weeks, usually at a dosage of 5 mg/kg. UC of patients with frequent disease relapse or those that are resistant or dependent on corticosteroids is often treated with purine antimetabolites, such as azathioprine (AZA) (10). AZA, a purine antimetabolite (2.5 mg per kg/day) is administered for its steroid-sparing effects. The response occurs after 2 to 4 weeks (6, 10). Infliximab can be combined with AZA. Patients with UC treated with infliximab plus AZA were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy (10,12).

Prevalence and Characteristics of Extra-intestinal Manifestations in a Large Cohort of Greek Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Extraintestinal manifestations [EIMs] are common in inflammatory bowel disease [IBD]. Data on epidemiology and risk factors of EIMs in IBD patients are limited. The aim of this study was to investigate the prevalence of EIMs in a large cohort of Greek IBD patients and identify risk factors for their development. METHODS: The study population consisted of IBD patients, who were followed in eight tertiary Greek hospitals. Demographic and clinical characteristics of patients were analysed. The diagnosis of EIMs was based on standard criteria and on specialist consultation. RESULTS: In total, 1860 IBD patients (1001 with Crohn's disease [CD], 859 with ulcerative colitis [UC]) were registered. Among them 615 [33.1%] exhibited at least one EIM; 238 patients [38.6%] developed an EIM before IBD diagnosis. An association between active IBD and presence of an EIM was established in 61.1% of the patients. Arthritic [peripheral arthritis], mucocutaneous [erythema nodosum], and ocular [episcleritis] were the most common manifestations. EIMs were more prevalent in females, patients with CD, smokers [for all p <0.0001], patients with extensive UC [p = 0.007], and patients with a previous appendectomy [p < 0.0001] or a major IBD-related surgery [p = 0.012]. CONCLUSIONS: About one-third of Greek IBD patients developed at least one EIM. Of those, more than one-third had their EIM diagnosed before IBD, and in about two-thirds it was related to disease activity. EIMs were more frequently present in females and patients with extensive UC in multivariate analysis.