Inflammatory bowel disease affects more than 2 million people in Europe, with almost 20% of patients being diagnosed in pediatric age. Patients with inflammatory bowel disease are at increased risk ...of thromboembolic complications which may affect patients' morbidity and mortality. The risk of the most common thromboembolic events, such as deep venous thrombosis and pulmonary embolism, are estimated to be three-fold increased compared to controls, but many other districts can be affected. Moreover, patients with ulcerative colitis and Crohn's disease experience thromboembolic events at a younger age compared to general population. Many factors have been investigated as determinants of the pro-thrombotic tendency such as acquired risk factors or genetic and immune abnormalities, but a unique cause has not been found. Many efforts have been focused on the study of abnormalities in the coagulation cascade, its natural inhibitors and the fibrinolytic system components and both quantitative and qualitative alterations have been demonstrated. Recently the role of platelets and microvascular endothelium has been reviewed, as the possible link between the inflammatory and hemostatic process.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Background and aims The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than ...placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. Methods All patients with active disease treated with adalimumab were retrospectively reviewed. Co-primary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. Results Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twenty-two patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36–19.44; OR 2.63, 95% CI 2.32–14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, 95% CI 0.08–0.66) and with a higher rate of colectomy (HR 9.7, 95% CI 1.46–9.07). Conclusion In this large “real-life” experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Stevens–Johnson syndrome (SJS) is a severe mucocutaneous adverse drug reaction with a relatively high mortality rate. SJS is described during herpes simplex virus type 1 (HSV1) infection and, rarely, ...even during adalimumab therapy. We report the case of a patient with Crohn’s disease who developed SJS during an HSV1 infection and a contemporaneous anti-TNFα therapy with adalimumab. Remission was achieved with suspension of adalimumab and high doses of intravenous steroids and antivirals. Patients with HSV1 infection and on adalimumab therapy have a combined risk of SJS and should be monitored closely.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Azathioprine is a cornerstone of the therapy of Crohn’s disease. Unfortunately, infections and malignancies are relatively common adverse effects related to this drug; however, cirrhosis is ...exceptionally reported as a side effect. We report the case of a 49-year-old male patient with ileocolonic steno-penetrating Crohn’s disease who developed hepatic cirrhosis while treated with azathioprine. After taking azathioprine for 3 years with regular follow-up, he developed pancytopenia, and liver cirrhosis was diagnosed with ultrasound, abdomen computed tomography scan, transient elastography, and liver biopsy. As all other causes of liver damage were excluded, azathioprine was believed to be the cause of liver injury and therefore was interrupted.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Intracellular adhesion molecules and matrix metalloproteinases (MMPs) are up-regulated in intestinal mucosa of patients with inflammatory bowel diseases (IBD), i.e. ulcerative colitis (UC) ...or Crohn's disease (CD). Our aim was to verify whether the vitamin D analogue ZK 156979 (ZK) down-regulates adhesion molecules, and decreases MMPs production by PBMC of IBD patients. ICAM-1 and LFA-1 levels increase, when PBMC were incubated with PHA or LPS or TNF-α, and decrease when these substances were used in combination with ZK. MMPs activity increases incubating the cells with PHA or LPS or TNF-α. MMP-9 decreases when ZK was used in association, while MMP-2 decreases only when ZK was used in combination with anti-TNF-α. Our results suggest that the down-regulation of ICAM-1 and LFA-1 on PBMC and the inhibition of MMP-9 activity by ZK could provide a potential role of this low calcemic vitamin D derivative in future strategies in IBD therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective. Pathological evidence supports a potential role of the pro- and anti-inflammatory cytokine network in the pathogenesis of inflammatory bowel disease (IBD). Moreover, associated studies ...suggest a possible involvement of cytokine-related genes in IBD susceptibility. In this study, we evaluated the effect of the anti-inflammatory interleukin-10 (IL10) gene on ulcerative colitis (UC). Material and methods. Two functional single nucleotide polymorphisms (−1082 G/A, −819 T/C) in the IL10 promoter in 203 Italian sporadic UC patients and 391 controls were determined using high-resolution melting analysis. Results. The frequency of the −1082A allele was significantly higher in the UC patients than in controls (p=0.00003); −1082 genotype frequencies were also significantly different between UC patients and controls (p=0.0001). Allele and genotype frequencies of −819 T/C were not significantly associated with UC. Furthermore, the frequencies of haplotypes −1082A/−819C and −1082A/−819T, which have been reported to have a lower promoter activity, were significantly higher in UC patients than in controls (p=0.0004). After gender stratification, we found a significant difference in the −1082A allele (p=0.00004) and genotype (p=0.0002) frequencies only between female UC patients and controls; the same result was obtained for the −1082A/−819C and −1082A/−819T haplotypes (p=0.0006). Conclusions. A gender effect is observed, with women of AG/AA IL10 genotypes and AC/AT haplotypes having a higher risk of developing UC at a younger age. This finding could be related to the previously documented lower IL10 production associated with the −1082A allele and to the IL10 down-regulating effect of estrogens.
COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive ...therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.
This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).
Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.
Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.
Background/Aims: A recent alert from Spanish health authorities warned of a higher incidence of reported hypersensitivity reactions to hemodialysis membranes with polysulfone, in the 2017 review of ...acute reactions to dialyzers found only published reports in the 21st century on polysulfone and its derivatives. The aim is to assess/evaluate the current incidence and characteristics of hypersensitivity reactions in hemodialysis patients. Methods: A retrospective multicentre study in 9 Spanish hospitals evaluated patients in whom a hypersensitivity reaction required a change in dialyzer membrane. Results: A total of 37 patients out of 1561 (2.37%) had hypersensitivity reactions and clinical, epidemiological and analytical data were available for 33 patients (2.11%). The membranes involved were polysulfone (n=23), polynephron (n=8), polyethersulfone (n=1) and polyacrylonitrile (n=1). This distribution reflected the frequency of use of membranes in the participating dialysis units. The reactions were described as type A in 18 cases and type B in 15 cases. There were no significant differences between the two types in clinical symptoms, the composition of the membrane involved, the method of sterilization, the season, or the time during the session in which they occurred. The most frequent symptom was dyspnea/breathlessness (64% of reactions). Eosinophilia was common (74%). 54% of the reactions occurred within the first 30 minutes of hemodialysis, 64% occurred during the first year of dialysis, and 54% required discontinuation of dialysis session. Cellulose triacetate was used as an alternative dialyzer in 78% of the cases. Conclusion: The incidence of hypersensitivity reactions was in the range found in reports from 20 years ago and is observed associated with synthetic membranes, not just polysulfones. Cellulose triacetate appears to be a good alternative for these patients.
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