Marcin A. Kucharski

The impact of genetic factors on response to glucocorticoids therapy in IBD

ABSTRACT Glucocorticosteroids (GCs) are used for many years as first-line drugs for the achievement of remission in exacerbations of inflammatory bowel disease (IBD). However, close to 20% of patients are resistant to GCs, and 40% of patients become dependent on GCs. The challenge of today’s personalized medicine is the anticipation of the steroid therapy effects even before the initiation of treatment. As several studies show, individually variable response to GCs in population has a genetic background and may depend on gene variability encoding proteins involved in the function and metabolism of GCs. To those genes belong: NR3C1 – responsible for the synthesis of GC receptor (GR); Hsp90, HSP70, STIP1, FKB5 – genes of GR protein complex; ABCB1 and IPO13 coding glycoprotein p170; and importin 13 – involved in GCs transport; IL1A, IL1B, IL2, IL4, IL8, IL10, TNF, and MIF – genes of the epithelial pro-inflammatory factors synthesis, which excessive activation causes steroid resistance as well as CYP3A4 and CYP3A5 – encoding GCs biotransformation enzymes. This work systematizes and sums up the state of current knowledge in the field of pharmacogenetics as well as expectations for the future in the realm of individualized medicine in IBD patients treated with GC drugs.

Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn’s Disease

Background. Assessment of endoscopic activity of Crohns disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohns Disease (SES-CD).

Applicability of endoscopic indices in the determination of disease activity in patients with ulcerative colitis.

Objective The combination of clinical remission and mucosal healing represents a major goal of different treatment strategies for ulcerative colitis (UC). This study aimed to assess which of the endoscopic indices used to evaluate mucosal changes in UC are correlated with clinical indices currently used to determine disease activity, as well as which of the endoscopic indices are correlated with the Geboes Index used for histological evaluation. It also aimed to find correlations between the currently used clinical activity indices and the histological Geboes Index. Methods A group of 49 patients with a confirmed diagnosis of UC and a group of 52 individuals without a diagnosis of gastrointestinal disease, who constituted the control group, were investigated. All patients were evaluated by colonoscopy, and the severity of mucosal changes was scored in terms of nine different endoscopic indices commonly used in both pharmacological trials and clinical practice. Evaluation was also carried out using clinical and histological indices. Endoscopic indices used for UC were then correlated with different clinical and histological indices to find the strongest correlations. Results and conclusion A high correlation was demonstrated between three of the 11 evaluated clinical indices – Improvement Based on Individual Symptom Scores, Ulcerative Colitis Disease Activity Index, and Schroeder Index – and all nine endoscopic indices – Ulcerative Colitis Endoscopic Index of Severity, Baron Score, Schroeder Index, Feagan Index, Powell–Tuck Index, Rachmilewitz Index, Sutherland Index, Lofberg Index, and Lemman Index. Improvement Based on Individual Symptom Scores was the index with the highest correlation with all the endoscopic indices used for UC. The above indices are recommended for clinical evaluation of UC activity. The Ulcerative Colitis Endoscopic Index of Severity was moderately correlated with a histological index, and it is therefore recommended for routine endoscopic mucosal evaluation in patients with UC.

Prevalence of osteoporosis and osteopenia in a population of patients with inflammatory bowel diseases from the Wielkopolska Region

Introduction The incidence of osteoporosis in patients with inflammatory bowel disease (IBD) varies across different populations. Objectives The aim of this study was to evaluate the prevalence of osteoporosis in Polish patients with IBD, as well as the effect of the body mass index (BMI), disease duration, the number of hospital stays, and the use of glucocorticoids on bone mineral density (BMD). Patients and methods BMD of 208 patients with IBD (103 with Crohn disease [CD] and 105 with ulcerative colitis [UC]) and 41 healthy controls was measured using dual‑energy X‑ray absorptiometry. The association of BMD with the other parameters was analyzed using statistical methods. Results Osteoporosis of the lumbar (L2-L4) spine (T‑score) was observed in 11.7% of patients with CD and in 3.8% of those with UC, whereas that of the femoral neck (FN), in 5.8% and 2.9% of the patients with CD and UC, respectively. Osteopenia occurred in 35.9% (FN) and 36.9% (L2-L4) of CD patients, and in 25.7% (FN) and 29.5% (L2-L4) of UC patients. In CD patients, BMI was associated with lumbar and femoral BMD and with L2-L4 T‑score, whereas FN T‑score correlated with BMI. In UC patients, the cumulative glucocorticoid dose correlated with L2-L4 T‑score, FN BMD, FN T‑score, and FN Z‑score; the disease duration correlated with FN BMD, while the FN T‑score, with the number of hospital stays and FN BMD. Conclusions Osteoporosis and osteopenia are frequent in Polish patients with IBD. BMD correlated with BMI in all patients. In UC patients, BMD was associated with the cumulative glucocorticoid dose, disease duration, and number of hospital stays.

Influence of chlorinated water on the development of allergic diseases – An overview

Indoor swimming pools can be used all year round and serve for one of the most popular sport pursued for recreation. The positive effect of swimming arises in particular from the involvement of all the muscles of the body, decreasing the burden on the joints, as well as functional improvement of both the lungs and heart. Chlorine is typically used to disinfect swimming pool water and as a result the changes that take place lead to the formation of by-products, such as monochloramines (NH2Cl), dichloramines (NH2Cl2) i trichloramines (NH2Cl3), trihalogenometans (THM) or haloacetic acid (HAA). The highest concentration of these substances is just above the water surface and they may cause irritation of skin, eyes and mucosa of the respiratory tract. The toxic effect of high chlorine concentration and its side-products on the respiratory system is known, but the effect of low concentrations of these compounds is still not fully determined. Recent studies suggest that development of allergic diseases among swimmers may be increased by epithelial disorders driven by airway barrier dysfunction caused by chlorine irritation. Swimming in chlorinated water may be linked to symptoms of bronchial hyperreactivity, asthma and rhinitis especially in children, elite swimmers and employees of indoor swimming pools. Hypersensivity pneumonitis related to the use of swimming pools may manifest as a swimming pool or sauna user lung, most commonly caused by water polluting pathogens. The article summarizes recent data concerning the influence of chlorinated water on the development of allergic diseases.

Genotyping of CARD15/NOD2, ATG16L1 and IL23R Genes in Polish Crohn’s Disease (CD) Patients – Are They Related to the Localization of the Disease and Extra-Intestinal Symptoms?

Crohn’s Disease (CD), together with ulcerative colitis (UC) belongs to inflammatory bowel diseases (IBD). Among its typical symptoms are inflammation, abdominal pain, melaena, diarrhea, ulcers and even fistulas. So far the etiology of CD remains unclear, but what is certain, is that it is multifactorial. Causing chronic inflammation and starting an immunological response requires both genetic factors, as well as environmental ones. What is more, CD is multigenetic – various genes could be a potential cause of the disease; among them are e.g. CARD15/NOD2, ATG16L1 and IL23R (Barrett et al., 2008; Cukovic-Cavka 2006, Cho 2008, Lesage 2002).