Oral non-specific lesions in patient with Crohn's disease - a case report.

Crohn's disease (CD) is a chronic and granulomatous inflammatory disease of the entire gastrointestinal tract. The etiopathogenesis is not fully elucidated. The most common symptoms in the active phase of the disease include abdominal pain, prolonged diarrhea, fever, fatigue, malaise and weight loss. Oral manifestations of CD are classified into specific for CD with granulomatous changes and non-specific ones. This rare extraintestinal manifestation of CD in adults may precede gastrointestinal tract involvement, occur together or appear after years of its duration. Oral lesions can be initiated by malnourishment, poor absorption of nutrients or side-effect of medications. A CASE REPORT: We describe a 28-year-old female with a 9-years CD history, who presented in the active disease with oral lesions. They were classified as non-specific ones, and included oral candidiasis, irregular erythematous patches on the cheek mucosa, exfoliative lip inflammation, and angular cheilitis. The patient was treated with azathioprine, and since the last exacerbation of symptoms, induction therapy with adalimumab, (anti-TNF-alpha), has been prescribed. Nystatin was applied to treat the oral lesions, based on the microbiological assessment of the Candida albicans susceptibility, and symptomatic treatment. After a two-week treatment the oral mucosa was healed and angular cheilitis showed marked improvement compared to the initial presentation. CONCLUSIONS: The young female with active CD presented the nonspecific lesions in the oral cavity. The lesions coexisted with the active inflammatory process in the intestinal tract with characteristic clinical symptoms, and were associated with sideropenic anemia. The implementation of the local therapy, systemic CD treatment and supplementation of micronutrient deficiencies have led to a healing of the oral lesions. We emphasize a personalized approach to treatment and close cooperation between the dentist and the gastroenterologist.

Effect of long-term proton pump inhibitor therapy on complete blood count parameters and selected trace elements: a pilot study.

INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed for several gastrointestinal conditions, often as long­term therapy. The effects of term PPI use have not been fully elucidated. OBJECTIVES: We aimed to determine the association between long­term PPI use and complete blood count parameters, particularly red blood cell (RBC) count, white blood cell (WBC) count, and hemoglobin concentrations, as well as serum levels of selected micronutrients such as selenium (Se), iron (Fe), copper (Cu), and zinc (Zn). PATIENTS AND METHODS: We enrolled 37 patients on long­ term PPI therapy (mean [SD] age, 57.1 [15.4] years) and 30 healthy controls (mean [SD] age, 39.3 [11.8] years). In each group, complete blood count, and serum Fe levels were performed, and serum Cu, Zn, and Se levels were measured using atomic absorption spectrometry. RESULTS: Red blood cell and WBC counts were lower in the PPI group compared with controls (mean [SD], 4.24 [0.55] ×106/µl vs 4.7 [0.4] ×106/µl; P <0.001 and 6.13 [1.44] ×103/µl vs 7.3 [1.28] ×103/µl; P <0.001, respectively). Hemoglobin and serum Fe concentrations were also lower in the PPI group (mean [SD], 12.5 [1.8] g /dl vs 14.3 [0.8] g /dl; P <0.001 and 16.3 [5.4] µmol/l vs 23.4 [2.7] µmol/l; P <0.001, respectively). Serum Zn and Cu concentrations were higher in PPI users than in controls. CONCLUSIONS: Long­term PPI therapy may reduce RBC and WBC counts as well as hemoglobin levels, leading to iron deficiency. It may also aff ect concentrations of some micronutrients, although the underlying mechanism of this association is not fully clear.

Diet and nutritional factors in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) development is affected by complex interactions between environmental factors, changes in intestinal flora, various predisposing genetic properties and changes in the immune system. Dietary factors seem to play an underestimated role in the etiopathogenesis and course of the disease. However, research about food and IBD is conflicting. An excessive consumption of sugar, animal fat and linoleic acid is considered a risk factor for IBD development, whereas a high fiber diet and citrus fruit consumption may play a protective role. Also, appropriate nutrition in particular periods of the disease may facilitate achieving or prolonging remissions and most of all, improve the quality of life for patients. During disease exacerbation, a low fiber diet is recommended for most patients. In the remission time, an excessive consumption of alcohol and sulfur products may have a negative effect on the disease course. Attempts are also made at employing diets composed in detail in order to supplement IBD therapy. A diet with a modified carbohydrate composition, a semi-vegetarian diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols are under investigation. Due to chronic inflammation as well as side effects of chronically used medications, patients with IBD are also at increased risk of nutritional factor deficiencies, including iron, calcium, vitamin D, vitamin B12, folic acid, zinc, magnesium and vitamin A. It should also be remembered that there is no single common diet suitable for all IBD patients; each of them is unique and dietary recommendations must be individually developed for each patient, depending on the course of the disease, past surgical procedures and type of pharmacotherapy.

Homocysteine in patients with inflammatory bowel diseases.

BACKGROUND: Hyperhomocysteinemia seems to be a common phenomenon in both patients with ulcerative colitis and Crohn's disease. Many factors including deficiencies of cobalamin, folate and pyridoxine, smoking habits, alcohol and coffee intake, some medications and age may predispose subjects to hyperhomocysteinemia. The study aimed to evaluate homocysteine levels in an inflammatory bowel disease cohort as dependent of life style and disease activity. METHODS: 85 consecutive patients with inflammatory bowel disease (38 with Crohn's disease and 47 with ulcerative colitis) and 65 control subjects were included in the prospective study. The following parameters were analyzed: disease activity, duration of the disease, location of pathological changes, presence of complications, current medications, past surgical procedures, smoking history, concomitant diseases, biochemical parameters and plasma homocysteine levels. RESULTS: Mild hyperhomocysteinemia was found in 16 patients with Crohn's disease (42%), 19 patients with ulcerative colitis (40%) and 19 patients in the control group (29%) (p = 0.59). There was not any significant correlation between homocysteine level and disease activity. Only folic acid supplementation and gender affected homocysteine level. Folic acid intake led to reduction of homocysteine levels in all groups of patients (11.8 micromol/l vs. 8.33 miccromol/l, p = 0.0065 in Crohn's disease patients and 10.94 micromol/l vs. 7.78 micromol/l, p = 0.0069 in ulcerative colitis patients). CONCLUSION: Homocysteine level in patients with inflammatory bowel disease is mostly normal or slightly elevated. Disease activity does not have an impact on homocysteine level. Folic acid is the most important factor having an influence on homocysteine level in patients with inflammatory bowel disease.

Intrahepatic expression of genes related to metabotropic receptors in chronic hepatitis.

AIM: To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis. METHODS: Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C. For this purpose, a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used. Evaluation of gene expression was performed in relation to transcript level, correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment. Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase, γ-glutamyltranspeptidase, alkaline phosphatase and cholinesterase activity, levels of iron ions, total cholesterol, triglycerides, albumin, glucose, hemoglobin, platelets, histological analysis of inflammatory and necrotic status, fibrosis according to METAVIR score, steatosis, as well as anthropometric body mass index, waist/hip index, percentage of adipose tissue and liver size in ultrasound examination. Gender, age, concomitant diseases and drugs were also taken into account. Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways, such as the α subunit of G-coupled protein, phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, transcription factor early growth response protein 1 and lysophosphatidic acid receptor, were characterized by the lowest expression (0.002 < P < 0.046), while the factor potentially triggering hepatic cancer, transcription factor JUN-B, had a 20-fold higher expression. The correlation between expression of genes of protein kinases PDPK1, phosphoinositide 3-kinase and protein kinase A (Spearman's coefficient range: 0.762-0.769) confirmed a functional link between these enzymes. Gender (P = 0.0046) and inflammation severity, measured by alanine aminotransferase activity (P = 0.035), were characterized by diverse metabotropic receptor gene expression patterns. The Pearson's coefficient ranging from -0.35 to 0.99 from the results of qRT-PCR and microarray indicated that qRT-PCR had certain limitations as a validation tool for oligonucleotide microarray studies. CONCLUSION: A microarray-based analysis of hepatocyte metabotropic G-protein-related gene expression can reveal the molecular basis of chronic hepatitis.

Biological therapy of inflammatory bowel disease.

Ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis are defined as inflammatory bowel diseases (IBD). Those diseases involve disorders of numerous immunological mechanisms associated with cellular and humoral immune response. In CD cellular response is considered to be of crucial importance, and dominant cytokines include: tumor necrosis factor alpha (TNF-alpha), interferon gamma (INF-gamma) and interleukins 1beta (IL-1beta), IL-2, IL-6, IL-8, IL-12. In UC, increased expression of Th2 (responsible for humoral response) is observed. It is connected with increased production of interleukins: 4 (IL-4), IL-5, IL-6, IL-10 and TNF-alpha. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is of vital importance in pathogenesis of IBD. Conventional therapy of CD and UC quite commonly fails to bring satisfactory results, therefore an interest in new therapeutic options, that is, biological therapy, gene therapy, hematopoietic stem cell transplantation, and leucapheresis, has aroused recently. Biological therapy is focused on different stages of the inflammatory process. The fundamentals of biological strategy involve neutralization of pro-inflammatory cytokines, use of anti-inflammatory cytokines and inhibition of neutrophil adhesion. Biological therapy is a promising option because it enables to withdraw corticosteroids and immunosuppressive agents or to reduce their dose. Moreover, it shortens the hospital stay, allows to avoid surgical procedures, extends the remission period and improves patients' quality of life. Currently, 2 agents, infliximab and adalimumab, are registered for the biological therapy of CD in Poland.