Aleksandra Szymczak

Is faecal calprotectin equally useful in all Crohn's disease locations? A prospective, comparative study.

Introduction There are data suggesting that the diagnostic usefulness of faecal calprotectin (FC) may vary depending on the Crohns disease (CD) location. The aim of the study was to compare the diagnostic usefulness of FC in CD patients with different disease locations. Material and methods We prospectively enrolled 120 CD patients in the study. Disease activity was assessed by using Crohns Disease Activity Index (CDAI), biochemical markers, and endoscopic and radiographic methods. Faecal calprotectin concentration was assessed in single stool samples by using the ELISA method. Results Among all patients, 54 (45%) had ileocolonic CD location, 44 (36.5%) had isolated small bowel location, and 22 (18.5%) had colonic CD location. FC correlated significantly with C-reactive protein concentration and endoscopic and radiographic activity among patients with isolated small bowel CD (p = 0.03, r = 0.32; p < 0.0001, r = 0.78; p = 0.03, r = 0.35; respectively) and with C-reactive protein and endoscopic activity in isolated colonic CD (p = 0.0009, r = 0.7; p = 0.0002, r = 0.78; respectively). CDAI and inflammatory biochemical markers did not correlate with endoscopic and radiographic assessment in small bowel CD. In patients with ileocolonic CD, FC correlated significantly with endoscopy (p = 0.006, r = 0.5), radiographic assessment (p = 0.04, r = 0.3), CDAI (p = 0.0006, r = 0.5) and the majority of biochemical markers. Conclusions Faecal calprotectin is a useful diagnostic marker in all CD patients. Although its usefulness in small bowel CD seems to be the lowest, it should be utilized particularly in this disease location because of the lack of other reliable, non-invasive diagnostic methods.

Osteoporosis in Gastrointestinal Diseases.

Secondary osteoporosis occurs as an isolated pathology or co-exists with types I and II osteoporosis. The gastroenterologist may come across osteoporosis or osteopenia in a patient with a gastrointestinal disease. This is often a young patient in whom investigations should be carried out and appropriate treatment initiated, aimed at preventing bone fractures and the formation of the best peak bone mass. Osteoporosis occurs in patients with the following conditions: Crohns disease, ulcerative colitis, celiac disease, post gastrectomy patients, patients with short bowel syndrome, chronic hepatitis and cirrhosis, treated with steroids (steroid-induced osteoporosis) and patients using proton pump inhibitors chronically (state of achlorhydria). It is therefore necessary to approve a list of risk factors of secondary osteoporosis, the presence of which would be an indication for screening for osteoporosis, including a DXA study and the development of a separate algorithm for the therapeutic management of secondary osteoporosis accompanying gastrointestinal diseases, especially in premenopausal young women and young men, because there are currently no registered drugs with proven antifracture activity for this group of patients.

Magnetic resonance enterographic predictors of one-year outcome in ileal and ileocolonic Crohn’s disease treated with anti-tumor necrosis factor antibodies

The aim of the study was to assess the role of magnetic resonance enterography (MRE) in predicting one-year efficacy of anti-tumor necrosis factor antibodies - infliximab (IFX), adalimumab (ADA) in Crohn’s disease (CD) patients primarily responding to therapy. We performed retrospective analysis among 61 CD patients who had undergone a successful IFX/ADA induction therapy and were treated with maintenance doses. All patients underwent MRE at week 0. We assessed which MRE features were predictive for steroid-free remission at week 52, and which were associated with a secondary loss of response. 44 patients were in steroid-free remission at week 52, 17 - were secondary non-responders. The ROC curve showed that bowel thickening with contrast enhancement analyzed together at week 0 were associated with steroid-free remission at week 52 (p = 0.01; AUC 0.67). Bowel stenosis with or without prestenotic dilatation [OR 5.8 (95% CI 1.4 – 25) and 2.4 (95% CI 1.2 – 5) respectively; p = 0.01] and the presence of intra-abdominal fistulas [OR 1.4 (95% CI 1.1 – 2); p = 0.004] were related to secondary non-response. A high baseline inflammatory activity detected by MRE predicts one-year response in CD after IFX/ADA. In case of bowel stenosis, intra-abdominal fistulas, other therapeutic options should be considered.

Intestinal healing after anti-TNF induction therapy predicts long-term response to one-year treatment in patients with ileocolonic Crohn’s disease naive to anti-TNF agents

Introduction Objective assessment of Crohn’s disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD. Aim To assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment. Material and methods Twenty-six patients with ileocolonic CD were enrolled into the study. In this group a parallel assessment of disease activity was estimated before and after induction doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate scores. Subsequently the patients were treated until 12 months and then followed-up. The associations between intestinal healing (assessed in MRE and endoscopy), and mucosal and transmural healing with long-term results of 1-year anti-TNF therapy were analysed statistically. Results The median time of follow-up was 29 months (interquartile range – IQR: 14–46). Intestinal healing was significantly associated with favourable therapeutic outcomes (p = 0.02) and had 75% (IQR: 35–97%) sensitivity and 72% (IQR: 46–90%) specificity in predicting long-term remission. Other parameters were not useful (transmural healing) or their usefulness was of borderline significance (mucosal healing). Conclusions Dynamic assessment of intestinal healing is an accurate method in predicting long-term outcomes in CD patients responding to 1-year anti-TNF therapy.

The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases.

Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D.

The diagnostic usefulness of fecal lactoferrin in the assessment of Crohn's disease activity

BACKGROUND Diagnosis and monitoring of Crohns disease (CD) is difficult and time-consuming. In recent years, diagnostic usefulness of fecal calprotectin has been proven. However, data on the utility of other fecal markers are scarce. AIMS To evaluate the usefulness of fecal lactoferrin (FL) in the assessment of CD activity. METHODS The group consisted of 101 CD patients (median age: 30 years, IQR: 24-37). FL was measured in a single stool sample by using the immunoenzymatic methods. The clinical activity of the disease was evaluated by using the Crohns Disease Activity Index (CDAI). Depending on the location of the disease, either a colonoscopy or magnetic resonance enterography was performed or both in order to evaluate the disease activity by using appropriate endoscopic and enterographic scores. RESULTS Median FL concentration was 84.14 (IQR: 36.4-302.9) μg/ml and it correlated with C-reactive protein concentration (p=0.0000001, r=0.5), CDAI (p=0.002, r=0.3) and colonic Simple Endoscopic Score for Crohns Disease (SES-CD) (p=0.000004, r=0.5). Assuming endoscopic remission in the large intestine with colonic SES-CD≤3 points, a ROC curve showed that FL concentration of 145.82 μg/ml had 84.6% sensitivity and 60.5% specificity in discriminating CD patients with endoscopically active and inactive disease [AUC: 0.676 (95% CI: 0.531-0.8), (p=0.0347)]. The positive predictive value for this concentration was 42% and negative predictive value -92%. CONCLUSIONS FL is a sensitive marker of CD activity and it reliably reflects the mucosal inflammatory lesions in large intestine. Thus, it can be helpful in diagnostics and monitoring of CD.

Diagnostic importance of faecal markers in long-term monitoring of anti-TNF- therapy in primary responders with Crohn’s disease

Introduction Monitoring the response to biological treatment in Crohn’s disease (CD) is a very important element of the therapeutic optimisation. Aim To evaluate the usefulness of measuring calprotectin, lactoferrin, and myeloperoxidase in stool as markers of long-term clinical and endoscopic response to anti-tumour necrosis factor α (anti-TNF) treatment in CD. Material and methods The studied group consisted of 35 CD patients treated with anti-TNF-α antibodies. Clinical activity was evaluated using Crohn’s Disease Activity Index (CDAI), and the exacerbation of endoscopic changes was evaluated using a Simple Endoscopic Score for Crohn’s Disease (SES-CD). The concentration of calprotectin, lactoferrin, and myeloperoxidase was measured using the ELISA method. All measurements were performed three times – before, after 3 months, and after a year of therapy. Results During anti-TNF treatment the concentrations of all measured faecal markers decreased significantly in relation to baseline values. We observed a significant correlation at all time-points: before the therapy, after 3 months, and 12 months after starting the therapy, between the concentration of calprotectin and SES-CD, calprotectin and CDAI, as well as between lactoferrin and SES-CD, and lactoferrin and CDAI. Myeloperoxidase correlated with both SES-CD and CDAI only after 1 year of treatment. Conclusions Faecal calprotectin and lactoferrin are valuable markers of clinical and endoscopic activity of CD in patients treated with anti-TNF antibodies. They are useful in monitoring the response to treatment. The usefulness of myeloperoxidase in this respect remains controversial.

Osteoprotegerin, s-RANKL, and selected interleukins in the pathology of bone metabolism in patients with Crohn’s disease

Introduction Crohns disease (CD) promotes the development of osteopaenia/osteoporosis, the cytokine background of which is not fully known. Aim Evaluation of bone mineral density (BMD), the prevalence of osteopaenia and osteoporosis, and the determination of the levels of selected interleukins (IL), osteoprotegerin (OPG), and s-RANKL proteins in patients with CD in relation to a control group and assessment of the relationship between the tested cytokines, OPG, s-RANKL, and BMD. Material and methods Thirty-seven CD patients and 37 healthy volunteers (control group) were enrolled into the study. Densitometry of the lumbar spine (L2–L4) and of the femoral neck using the DXA technique was carried out. Serum levels of: IL-13, IL-4, IL-17, IL-1β, OPG, and s-RANKL were determined using the ELISA method. Progression-of-disease questionnaires were collected. Results The prevalence of osteoporosis and osteopaenia in the CD group was: 18.92% and 32.43% in L2–L4; 13.51% and 35.13% in the neck, respectively. The IL-13 and IL-1β concentrations were significantly higher and OPG was significantly lower in CD patients when compared to controls. In the case of all subjects: IL-13 correlated negatively with the BMD of the neck, IL-17 correlated negatively with the Z-score of L2–L4, and OPG correlated negatively with the IL-13. In the case of CD patients, IL-4 correlated negatively with the BMD of L2–L4. Conclusions The incidence of osteopaenia and osteoporosis in Polish CD patients is high. IL-13, IL-1β, and IL-4 seem to be connected with the pathology of decreased BMD in CD. It can be hypothesised that IL-13 may lower BMD by modulating OPG.