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.

Relative homogeneity of oral bacterial oral in Crohn's disease compared to ulcerative colitis and its connections with antioxidant defense - preliminary report.

INTRODUCTION: Interactions between oral microbiota and systemic diseases have been suggested. We aimed to examine the composition of oral microbiota with reference to antioxidative defense and its correlation with clinical state in Crohn's disease (CD) in comparison to ulcerative colitis (UC). MATERIALS AND METHODS: Smears were taken from the buccal and tongue mucosa of patients with CD, UC and controls, and cultured with classical microbiology methods. Bacterial colonies were identified using matrix-assisted laser desorption/ionization (MALDI) with a time-of-flight analyzer (TOF). Blood morphology and C-reactive protein (CRP) were analyzed in the hospital laboratory. Antioxidative defense potential (FRAP) was determined using spectrophotometry in saliva and serum. RESULTS: Oral microbiota in CD patients were characterized by lower diversity in terms of the isolated bacteria species compared to UC and this correlated with reduced FRAP in the oral cavity and intensified systemic inflammation. Oral microbiota composition in CD did not depend on the applied treatment. In CD patients, a negative correlation was observed between the FRAP value in saliva and serum and the CRP value in serum. Individual differences in the composition of oral microbiota suggest that different bacteria species may be involved in the induction of oxidative stress associated with a weakening of antioxidative defense in the oral cavity, manifested by ongoing systemic inflammation. CONCLUSIONS: Analysis of both the state of the microbiota and antioxidative defense of the oral cavity, as well as their referencing to systemic inflammation may potentially prove helpful in routine diagnostic applications and in aiding a better understanding of CD and UC pathogenesis associated with oral microbiota.

Oral mucosa lesions in patients with active Crohn's disease - a prospective study.

Introduction: Crohn's disease (CD) is a chronic inflammatory disease, which may involve any part of the gastrointestinal tract, including the oral cavity. Mucosal lesions in the oral cavity are described in various populations, but observations in active disease with severe clinical symptoms are quite rare. Objectives: To evaluate the prevalence and nature of oral mucosa lesions in adult patients with active CD and their correlation with clinical and laboratory indicators of disease activity. Material and Methods: Prospective study was performed in 62 patients (29 women, 33 men, age 18-49 years) admitted between December 2010 and February 2013 to the gastroenterology department with a confirmed diagnosis of CD and exacerbations of symptoms, and 40 sex- and gender-matched healthy volunteers. CD activity was classified according to clinical and blood parameters, and the CD activity index (CDAI). We examined: blood morphology, hemoglobin and CRP levels, BMI. Examination of the oral cavity included a detailed interview and physical examination, based on the WHO recommendations. Results: In patients with active CD we found: increased CDAI score (258.4±21.5), higher CRP levels (24.6±1.3 mg/l) and platelet count, anemia with significantly reduced RBC and hemoglobin level, and reduced BMI, in comparison to controls. The specific for CD symptoms were found in the mouth: indurated tag polypoid lesions on vestibular retromolar region in 12.9% of patients, cobblestoning of the mucosa in 9.7%, diffuse asymptomatic buccal swelling in 16.2%, mucogingivitis in 19.4% of patients. Oral nonspecific lesions were more frequent: angular cheilitis in 29.1%, atrophic glossitis in 14.5% of patients. Oral lesions correlated with hemoglobin and CRP concentrations (r=-0.431 and r=0.437; respectively; p<0.001), platelet count (r=0.45; p<0.003), CDAI (r=0.421; p<0.001) and BMI (r=0.307; p<0.006). No correlation has been found between specific or non-specific lesions and location of inflammatory changes in the gastrointestinal tract. Conclusions: Changes in the oral mucosa in adult patients with active CD are frequent. They should be correlated with other clinical symptoms of gastrointestinal tract and biochemical parameters in patients with CD. The nature of these changes may have an impact on the further therapeutic approach.

[Inflammatory changes of oral cavity proceeding appearance of clinical symptoms of Crohn's disease]. / Zmiany zapalne w jamie ustnej wyprzedzajace wystapienie objawów choroby Lesniowskiego-Crohna. Opis przypadku.

Crohn's disease belongs to the inflammatory bowel diseases. Inflammatory changes can be located in any part of the gastrointestinal tract including rarely oral cavity. We present a case of a 21 years old woman with unhealed by the local treatment, and verified by histological examination, inflammatory changes of oral cavity. These changes had proceed the diagnosis of typical changes in gastrointestinal tract for 6 months. Changes were located in terminal ileum and colon and were confirmed by colonoscopic, histologic and radiologic studies. Standard therapy of Crohn's disease with antiinflammatory and immunosuppressive drugs led to the healing of oral changes. We point out on the necessity of proper differential diagnosis of problematic unhealing changes, particularly with ulcerations of oral mucosa in young patients. Dental examination with histological confirmation of mucosal changes may be helpful in proper diagnosis of Crohn's disease in the young group of patients.

Markers of lipid peroxidation and antioxidant status in the serum and saliva of patients with active Crohn disease.

Introduction Increased oxidative stress has been implicated in the pathogenesis of Crohn disease (CD). Except for C­reactive protein (CRP), good biological markers of CD activity are lacking. Objectives We aimed to investigate the diagnostic usefulness of selected markers of oxidative stress in the serum and saliva of patients with active and inactive CD. Patients and methods A total of 58 patients with confirmed CD (32 with active CD, 26 with inactive CD, and 26 healthy controls) were prospectively enrolled to the study. The markers examined were malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), and catalase (CAT). Results MDA levels were higher in the serum and saliva of patients with active CD than in those with inactive CD and controls and were positively correlated with the Crohn's Disease Activity Index (r = 0.8, P <0.001) and CRP (P <0.001). Serum and saliva antioxidant indicators (FRAP and GSH) were decreased in both CD groups compared with controls and were negatively correlated with clinical activity and inflammation (FRAP, r = -0.5, P <0.001; GSH, r = -0.5, P <0.001; and CAT, r = -0.5, P <0.001). Conclusions The increased lipid peroxidation and decreased antioxidant activity in serum and saliva confirm that CD patients are under oxidative stress. The positive correlations of MDA with the clinical activity and inflammation, as well as the comparison of the receiver operating characteristic curves for MDA and CRP, suggest that MDA could be a good diagnostic marker of CD.

Proinflammatory cytokines in the saliva of patients with active and non-active Crohn's disease.

INTRODUCTION:  Crohn's disease (CD) involves the entire gastrointestinal tract, including the mouth. Numerous cytokines play a role in the regulation of inflammatory process in CD. OBJECTIVES:  The aim of the study was to examine the prevalence of oral lesions in adult patients with CD and to investigate whether salivary concentrations of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) are associated with the activity and oral manifestations of CD. PATIENTS AND METHODS:  A prospective study included 95 adult patients: 52 with active CD and 43 with inactive CD. The control group involved 45 subjects without CD. We performed blood tests, careful oral examination, and measurement of IL-1ß, IL-6, and TNF-α in unstimulated whole saliva by enzyme-linked immunosorbent assays. RESULTS:  IL-1ß, IL-6, and TNF-α were significantly elevated in patients with active CD. IL-1ß levels were 289.8 ±52.7 in patients with active CD vs. 196.7 ±42.9 pg/ml in patients with inactive CD (P <0.039), and 196.7 ±42.9 pg/ml (P <0.01) in controls. IL-6 levels were 13.8 ±4.2 vs. 7.2 ±3.1 pg/ml (P <0.041), respectively, and 6.3 ±1.4 pg/ml (P <0.001) in controls. TNF-α levels were 32.5 ±8.7 vs. 10.2 ±6.3 pg/ml (P <0.002), respectively, and 6.8 ±2.8 pg/ml (P <0.001) in controls. We observed CD-specific oral lesions: diffuse asymptomatic buccal swelling in 12 patients (23%) and cobblestoning in 5 patients (11.3%). CD-nonspecific lesions were observed in 17 patients (32.7%) with active CD, in 11 patients (25.6%) with inactive CD, and in 6 controls (13.3%). In active CD, higher salivary IL-6 and TNF-α and serum C-reactive protein levels correlated with specific oral lesions. CONCLUSIONS:  In patients with active CD, salivary IL-1ß, IL-6, and TNF-α levels are higher than in patients with inactive disease and controls. Elevated salivary IL-6 and TNF-α levels correlate with specific oral lesions. These cytokines may be used as markers of active CD, but the finding should be confirmed in a larger group of patients.

IL28B polymorphism as a predictor of antiviral response in chronic hepatitis C.

AIM: To evaluate the effect of single nucleotide polymorphisms of interleukin (IL)-28B, rs12979860 on progression and treatment response in chronic hepatitis C. METHODS: Patients (n = 64; 37 men, 27 women; mean age, 44 ± 12 years) with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was performed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, aminotransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured. RESULTS: A sustained virological response (SVR) was significantly associated with IL28B polymorphism (CC vs TT allele: odds ratio (OR), 25; CC vs CT allele: OR, 5.4), inflammation activity (G < 1 vs G > 1: OR, 3.9), fibrosis (F < 1 vs F > 1: OR, 5.9), platelet count (> 200 × 10(9)/L vs < 200 × 10(9)/L: OR, 4.7; OR in patients with genotype CT: 12.8), fatty liver (absence vs presence of steatosis: OR, 4.8), insulin resistance index (< 2.5 vs > 2.5: OR, 3.9), and baseline HCV viral load (< 10(6) IU/mL vs > 10(6) IU/mL: OR, 3.0). There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance (P = 0.064) of increased fibrosis in patients with the TT allele, and no differences in the insulin resistance index between groups of patients with CC, CT and TT alleles (P = 0.12). Spearman's rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively (P < 0.001). Significant differences were found in the insulin resistance index (P = 0.01) between patients with and without steatosis. Patients with the CT allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon (P = 0.07). CONCLUSION: IL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.

Efficacy of pegylated interferon alfa-2a or alfa-2b in combination with ribavirin in the treatment of chronic hepatitis caused by hepatitis C virus genotype 1b.

INTRODUCTION: Treatment of chronic hepatitis C (CHC) with pegylated interferon (Peg-IFN) and ribavirin leads to sustained virological response (SVR) in approximately 50% of the patients. SVR depends on hepatitis C virus (HCV) and host factors, including IL28B genotypes. OBJECTIVES: The aim of the study was to investigate the therapeutic efficacy of the difficult-to-treat HCV genotype 1b in patients from the south of Poland. PATIENTS AND METHODS: A total of 260 adult patients with CHC and HCV genotype 1b were treated with Peg-IFN alfa-2a or Peg-IFN alfa-2b with ribavirin for 48 weeks. Efficacy was assessed at 12 weeks (early virological response - EVR), 48 weeks (end-of-treatment response - ETR), and at 6 months (SVR). HCV-RNA, alanine transaminase (ALT), and other biochemical parameters were measured in serum at baseline and at 12, 48, and 72 weeks of therapy. RESULTS: HCV-RNA levels were 3.72 ±1.17 × 106 IU/ml at baseline and decreased significantly at 12 weeks (0.02 ±0.17 × 106 IU/ml); there were no differences between the group treated with Peg-INF alfa-2a and the group treated with Peg-INF alfa-2b. ALT was 94.1 ±7.6 IU/l at baseline and decreased significantly at 12 weeks (42.5 ±3.1 IU/l). The overall EVR, ETR, and SVR were achieved by 63.9%, 77.7%, and 48.1% of the patients, respectively. Tolerance of therapy was similar in both groups. CONCLUSIONS: Efficacy of Peg-IFN alfa-2a with ribavirin is not significantly different from that of Peg-IFN alfa-2b with ribavirin, and SVR was achieved in 48.3% and 44.3% of the patients, respectively. Our study confirms that the efficacy of treatment of patients with HCV genotype 1b from the southern region of Poland is similar to that observed in the overall Polish population.

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.