Serological Screening for Celiac Disease in Adult Chinese Patients With Diarrhea Predominant Irritable Bowel Syndrome.

Celiac disease (CD) is common in Caucasians, but thought to be rare in Asians. Our aim was to determine the prevalence of CD in Chinese patients with chronic diarrhea predominant irritable bowel syndrome (IBS-D).From July 2010 to August 2012, 395 adult patients with IBS-D and 363 age and sex-matched healthy controls were recruited in Zhongnan Hospital of Wuhan University and Xiaogan Central Hospital in Hubei province, central China. Patients with IBS-D were diagnosed according to the Rome III criteria. Serum Immunoglobulin (IgA/IgG) anti-human tissue transglutaminase (anti-htTG)-deamidated gliadin peptide (DGP) antibodies were measured in a single ELISA (QUANTA Lite h-tTG/DGP Screen). Upper endoscopy with duodenal biopsies and HLA-DQA1 and HLA-DQB1 genotyping were performed in seropositive subjects and a gluten-free diet was prescribed.Seven IBS-D patients (7/395, 1.77%) and 2 healthy controls (2/363, 0.55%), were positive for anti-htTG/DGP antibodies. Of these 9 cases, 1 was lost to follow-up, 3 were suspected to have CD and 5 were eventually diagnosed as CD with intestinal histological lesions classified as Marsh Type II in 2 and Type III in 3. Of these 5 diagnosed CD patients, 4 (4/395, 1.01%) were from the IBS-D group and 1 (1/363, 0.28%) from the healthy control had asymptomatic CD. Two Type III CD patients with relatively high titers in the serologic assay were homozygous and heterozygous for haplotype HLA-DQA1*03-DQB1*03:03 (HLA-DQ9.3), respectively.In the present study, CD was present in 1.01% of patients with IBS-D and in 0.28% of the control group. We like to suggest that the haplotype HLA-DQA1*03-DQB1*03:03 (HLA-DQ9.3), which is common in Chinese, is a new susceptibility factor for CD in China. Larger screening and genetic studies are needed in the Chinese population of different regions.

Microscopic enteritis: Bucharest consensus.

Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

Relevance of IL7R genotype and mRNA expression in Dutch patients with multiple sclerosis.

BACKGROUND: The interleukin 7 receptor (IL7R) has been recognized as a susceptibility gene for Multiple Sclerosis (MS). Analysis of rs6897932 (the most strongly MS-associated single nucleotide polymorphism (SNP)), showed effects of genotype on the relative expression of membrane-bound to total amount of IL7R mRNA. OBJECTIVE: We assessed the relevance of IL7R on MS phenotype (including clinical and magnetic resonance imaging (MRI) parameters) at DNA and mRNA level in Dutch patients with MS. METHODS: The genotype of rs6897932 was analyzed in 697 patients with MS and 174 healthy controls. The relevance of genotype and carriership of the C allele on MS phenotype (disease activity and severity, using clinical and MRI parameters) was assessed. In addition, relative gene expression of membrane-bound to total IL7R mRNA was analyzed with respect to disease phenotype in a subgroup of 95 patients with early relapsing MS. RESULTS: In particular, homozygosity for the risk allele is a risk factor for MS in our population (OR(CC vs CT and TT) = 1.65 (95% CI: 1.18-2.30), two-sided p = 0.004). However, no effect of genotype or the relative expression of membrane-bound IL7R (presence of exon 6-7) to total amount of IL7R mRNA (presence of exon 4-5) was found on MS phenotype. DISCUSSION: Homozygosity for the IL7R exon 6 rs6897932 C allele is associated with a higher risk for MS in our Dutch population. No effect was found of genotype or mRNA expression on disease phenotype.

Association of FcgR2a, but not FcgR3a, with inflammatory bowel diseases across three Caucasian populations.

BACKGROUND: The Fc receptors II and III (FcgR2a, and FcgR3a) play a crucial role in the regulation of the immune response. The FcgR2a*519GG and FcgR3a*559CC genotypes have been associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, nephritis, and possibly to type I diabetes, and celiac disease. In a large multicenter, two-stage study of 6570 people, we tested whether the FcgR2a and FcgR3a genes were also involved in inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We genotyped the FcgR2a*A519G and FcgR3a*A559C functional variants in 4205 IBD patients in six well-phenotyped Caucasian IBD cohorts and 2365 ethnically matched controls recruited from the Netherlands, Spain, and New Zealand. RESULTS: In the initial Dutch study we found a significant association of FcgR2a genotypes with IBD (P-genotype = 0.02); while the FcgR2a*519GG was more common in controls (23%) than in IBD patients (18%; odds ratio [OR] = 0.75; 95% confidence interval [CI] 0.61-0.92; P = 0.004). This association was corroborated by a combined analysis across all the study populations (Mantel-Haenszel [MH] OR = 0.84; 0.74-0.95; P = 0.005) in the next stage. The Fcgr2a*GG genotype was associated with both UC (MH-OR = 0.84; 0.72-0.97; P = 0.01) and CD (MH-OR = 0.84; 0.73-0.97; P = 0.01), suggesting that this genotype confers a protective effect against IBD. There was no association of FcgR3a*A559C genotypes with IBD, CD, or UC in any of the three studied populations. CONCLUSIONS: The FcgR2a*519G functional variant was associated with IBD and reduced susceptibility to UC and to CD in Caucasians. There was no association between FcgR3a*5A559C and IBD, CD or UC.

Analysis of multiple candidate genes in association with phenotypes of multiple sclerosis.

Multiple sclerosis is a heterogeneous neurological disease with varying degrees of severity. The common hypothesis is that susceptibility to multiple sclerosis and its phenotype are caused by a combination of environmental and genetic factors. The genetic part exerts its effect through several genes, each having modest effects. We evaluated whether disease severity could be predicted by a model based on clinical data and data from a DNA chip. The DNA chip was designed containing several single nucleotide polymorphisms in 44 genes, previously described to be associated with multiple sclerosis. A total of 605 patients with multiple sclerosis were included in this analysis, using gender, onset type and age at onset as clinical covariates. We correlated 80 single nucleotide polymorphisms to the degree of disease severity using the following three outcome measures: linear Multiple Sclerosis Severity Score, dichotomous Multiple Sclerosis Severity Score (using a cut-off point of 2.5) and time to reach Expanded Disability Status Scale score 6. Sixty-nine single nucleotide polymorphisms were included in the analysis. No individual single nucleotide polymorphism showed a significant association; however, a combination of single nucleotide polymorphisms significantly improved the prediction of disease severity in addition to the clinical variables. In all three models the Interleukin 2 gene was included, confirming a previously reported modest effect on disease severity. The highest power was obtained using the dichotomized Multiple Sclerosis Severity Score as outcome. Several single nucleotide polymorphisms showed their added predictive value over the clinical data in the predictive models. These results support our hypothesis that disease severity is determined by clinical variables and genetic influences (through several genes with small effects) in concert.

HLA-DRB1*1501 and spinal cord magnetic resonance imaging lesions in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a heterogeneous neurologic disease with extensive variation with respect to the most affected central nervous system region (brain vs spinal cord). OBJECTIVE: To test the hypothesis that this variation in lesion location (brain vs spinal cord) might be (partially) genetically determined. DESIGN: Candidate gene study. SETTING: Academic research. PATIENTS: Patients were selected for the availability of DNA material, clinical variables, and brain and spinal cord magnetic resonance images (evaluating T2-weighted lesion load in the brain and the number of spinal cord lesions). MAIN OUTCOME MEASURES: For genotyping, we used a DNA chip containing a set of genes mentioned in previous publications noting their relation to different phenotypes of MS. We assessed the association between brain and spinal cord abnormalities and the genotypes of the patients. RESULTS: One hundred fifty patients were included in the analysis. Five single-nucleotide polymorphisms within the major histocompatibility complex region were associated with the number of focal abnormalities in the spinal cord. The most significant was rs3135388 (surrogate marker for the HLA-DRB1*1501 allele). Carriers of HLA-DRB1*1501 had a median of 4 spinal cord lesions compared with 2 lesions for noncarriers (P < .001). No significant association was noted between the single-nucleotide polymorphisms and T2-weighted lesion load in the brain. CONCLUSIONS: Carriership of HLA-DRB1*1501 (via rs3135388) was associated with the extent of focal abnormalities in the spinal cord. Spinal cord lesions might be an explanation for increased MS disease severity in patients carrying HLA-DRB1*1501.

Decreased circulating iNKT cell numbers in refractory coeliac disease.

INTRODUCTION: A small proportion of coeliac disease (CD) patients become refractory (RCD) to a gluten-free diet (GFD) showing uncontrolled immune-mediated enteropathy. Some of these patients exhibit a high risk to develop enteropathy-associated T-cell lymphoma (EATL). AIM: The aim of the study was to find whether a lack of circulating homeostatic T cells, such as Treg, Tgammadelta(+) or iNKT cells would be associated with the development of RCD or EATL. PATIENTS AND METHODS: We investigated in a total of 137 CD patients [28 untreated, 80 responsive to GFD and 29 RCD (14 type I and 15 type II)] and 73 age-matched healthy volunteers the frequency of Treg, Tgammadelta(+) and iNKT lymphocytes by flow cytometric analysis of peripheral blood. RESULTS: Circulating Tgammadelta(+) cell and Treg frequencies in RCD were comparable to those in healthy controls. However, RCD patients had significantly reduced numbers of circulating iNKT cells, as compared to age-matched patients responding to a GFD. This reduction was similar in RCD patients with and without aberrant intraepithelial lymphocytes and in patients with EATL. Circulating iNKT cell numbers were not reduced in untreated coeliac patients. GFD treated patients had a significantly increased proportion of CD4(+) iNKT cells. CONCLUSION: Follow-up studies are necessary to determine whether CD4(+) iNKT cells control the immune response against gluten and their absence contributes to the progression to RCD and EATL.

Increasing prevalence of advanced colonic polyps in young patients undergoing colonoscopy in a referral academic hospital in Hong Kong.

AIM: To investigate the distribution and frequency of advanced polyps over eight years. METHODS: 6424 colonoscopies were reviewed during the study period 1998 to 2005. The study period was subdivided into period I: 1998 to 2001 and period II: 2002-2005. RESULTS: 1856 polyps (33% advanced polyps) and 328 CRCs were detected. The mean ages of the patients with advanced polyps and cancer were 69.2 +/- 12.0 and 71.6 +/- 13.8 years, respectively. Advanced polyps were mainly left sided (59.5%). Advanced polyps were found in patients 0.05). CONCLUSION: Advanced polyps increased significantly in the younger male group in the most recent period and there seems to be a shift towards a proximal location.

IL-1RN gene polymorphism is associated with peri-implantitis.

OBJECTIVES: Interleukin (IL)-1alpha, IL-1beta and their natural specific inhibitor IL-1 receptor antagonist (IL-1ra) play a key role in the regulation of the inflammatory response in periodontal tissues. Polymorphisms in the IL-1 gene cluster have been associated with severe adult periodontitis. We aimed to investigate the IL-1 gene cluster polymorphisms in patients with peri-implantitis. MATERIAL AND METHODS: The study included 120 North Caucasian individuals. A total of 71 patients (mean age 68 years, 76% smokers) demonstrating peri-implantitis at one or more implants as evidenced by bleeding and/or pus on probing and bone loss amounting to >3 threads on Brånemark implants and 49 controls (mean age 66 years, 45% smokers) with clinical healthy mucosa and no bone loss around the implants were recruited for the study. The titanium implants, ad modum Brånemark, had been in function for at least 2 years. Mouthwash samples were collected and used for genotyping of the bi-allelic polymorphisms IL-1A(-889), IL-1B(+3953), IL-1B(-511) and a variable number of tandem repeat IL-1RN gene polymorphisms using PCR technique. RESULTS: Significant differences were found in the carriage rate of allele 2 in the IL-1RN gene between peri-implantitis patients and controls (56.5% vs. 33.3%, respectively; odds ratios (OR) 2.6; 95% confidence interval (CI) 1.2-5.6; P=0.015). Logistic regression analysis taking smoking, gender and age into account confirmed the association between the IL-1RN allele 2 carriers and peri-implantitis (OR 3; 95% CI 1.2-7.6; P=0.02). CONCLUSIONS: Our results provide evidence that IL-1RN gene polymorphism is associated with peri-implantitis and may represent a risk factor for this disease.

Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?

BACKGROUND: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Variations, like single nucleotide polymorphisms (SNPs), in immunologically important host genes are assumed to play a role in the course and outcome of a C. trachomatis infection. We studied whether genetic traits (carrying multiple SNPs in different genes) in the bacterial sensing system are associated with an aberrant immune response and subsequently with tubal pathology following a C. trachomatis infection. The genes studied all encode for pattern recognition receptors (PRRs) involved in sensing bacterial components. METHODS: Of 227 subfertile women, serum was available for C. trachomatis IgG antibody testing and genotyping (common versus rare allele) of the PRR genes TLR9, TLR4, CD14 and CARD15/NOD2. In all women, a laparoscopy was performed to assess the grade of tubal pathology. Tubal pathology was defined as extensive peri-adnexal adhesions and/or distal occlusion of at least one tube. RESULTS: Following a C. trachomatis infection (i.e. C. trachomatis IgG positive), subfertile women carrying two or more SNPs in C. trachomatis PRR genes were at increased risk of tubal pathology compared to women carrying less than two SNPs (73% vs 33% risk). The differences were not statistically significant (P = 0.15), but a trend was observed. CONCLUSION: Carrying multiple SNPs in C. trachomatis PRR genes tends to result in an aberrant immune response and a higher risk of tubal pathology following a C. trachomatis infection. Larger studies are needed to confirm our preliminary findings.

TNF-857 polymorphism in Israeli Jewish patients with inflammatory bowel disease.

Tumour necrosis factor (TNF)-alpha is an important pro-inflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The promoter TNF-857 C-->T single nucleotide polymorphism (SNP) is functional through the binding to the transcription factor octamer transcription factor-1 (OCT-1). In order to investigate the frequency of this SNP in Israeli Jewish IBD patients, we analysed a cohort of well-characterized patients, 153 with Crohn's disease (CD) and 78 with ulcerative colitis (UC) and 188 healthy controls individually matched for age, sex and ethnicity. Forty-one per cent of the patients were of Ashkenazi and 48% were of non-Ashkenazi background. The remaining 11% were of mixed Ashkenazi-non-Ashkenazi background. Patients and controls were genotyped for the TNF-857 SNP by Taqman technology. Stratification for the CARD15 Arg702Trp, Gly908Arg and Leu1007fsinsC mutations took place in 136 CD patients. Carrier frequency of TNF-857T between CD and controls (36% vs. 40%; P = 0.556; OR: 1.18, 95% CI 0.74-1.88), or between UC and controls (41% vs. 37%; P = 0.743; OR: 0.85, 95% CI 0.45-1.62) did not differ significantly. Neither did stratifying for the presence of at least one of the common CARD15 mutations result in a significant difference between CD and controls. No associations were found between TNF-857T and CD phenotype as defined by the Vienna classification, perianal disease or extra-intestinal disease irrespective of CARD15 carrier status. In conclusion, it appears that TNF-857 SNP does not contribute to susceptibility of IBD, neither does it define the phenotype of CD in Israeli Jewish IBD patients.

Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma.

BACKGROUND & AIMS: Celiac disease (CD) is a common gluten-sensitive enteropathy associated with human leukocyte antigen (HLA)-DQ2 and HLA-DQ8. The aim of this study was to determine if a particular HLA-DQ subtype predisposes to complications such as refractory CD with (RCD II) or without aberrant T cells (RCD I), and enteropathy-associated T-cell lymphomas (EATL). METHODS: Molecular HLA-DQ typing was performed on 43 RCD I, 43 RCD II, and 30 EATL patients, and compared with age-matched groups of 121 patients with histologically defined uncomplicated CD and 183 healthy controls. All individuals were Dutch Caucasians and were at least 21 years of age. RESULTS: HLA-DQ2 was present in 79% of RCD I, 97.7% of RCD II, and 96.6% of EATL patients. The differences were significant when compared with 28.9% in controls but not with 91.7% in uncomplicated CD. Homozygosity for HLA-DQ2 was observed in 25.5% of RCD I, 44.1% of RCD II, and 53.3% of EATL patients vs 20.7% of uncomplicated CD patients and 2.1% of controls. HLA-DQ8 was present in 10.7% of CD, 16.2% of RCD I, 9.3% of RCD II, and 6.6% of EATL patients vs 20.2% of controls. CONCLUSIONS: Homozygosity for HLA-DQ2 is associated with RCD II and EATL. Early identification of HLA-DQ2 homozygous CD patients may help to recognize CD patients at risk for developing these severe complications.

Slow epidemic of lymphogranuloma venereum L2b strain.

We traced the Chlamydia trachomatis L2b variant in Amsterdam and San Francisco. All recent lymphogranuloma venereum cases in Amsterdam were caused by the L2b variant. This variant was also present in the 1980s in San Francisco. Thus, the current "outbreak" is most likely a slowly evolving epidemic.

The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology.

BACKGROUND: The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women. METHODS: The different CD14 -260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology status and the tubal status at laparoscopy. RESULTS: In the control cohort the CC, CT and TT genotype distribution was: 28.2%, 48.2%, and 23.5% respectively. No differences were found in the overall prevalence of CD14 -260 genotypes (28.1%, 50.7%, and 21.2%) in cohort 1 when compared to the control cohort. Also no differences were observed in women with or without CT-DNA, with or without serological CT responses, with or without symptoms, or in combinations of these three variables. In subfertile women with tubal pathology (cohort 2, n = 50) the genotype distribution was 28.0%, 48.0%, and 24.0% and in subfertile women without tubal pathology (n = 203), 27.6%, 49.3% and 23.2%. The genotype distribution was unchanged when CT IgG status was introduced in the analyses. CONCLUSION: The CD14 -260 C>T genotype distributions were identical in all three cohorts, showing that this polymorphism is not involved in the susceptibility to or severity of sequelae of C. trachomatis infection.

Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease.

AIM: Prostaglandin G/H synthase 2 (PTGS2 or COX2) is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases (IBD). In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS: We have genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTGS2 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5' exonuclease assay (TaqMan). New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS: Allele 5209G was weakly associated with Crohn's disease (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.03-2.57), and allele 8473T with ulcerative colitis (OR 1.50, 95%CI 1.00-2.27). The haplotype including both alleles showed a strong association with IBD (OR 13.15, 95%CI 3.17-116.15). This haplotype, while rare (-0.3%) in the general population, is found more frequently in the patients (3.5%). CONCLUSION: Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.

Acquired homotypic and heterotypic immunity against oculogenital Chlamydia trachomatis serovars following female genital tract infection in mice.

BACKGROUND: Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen causing female genital tract infection throughout the world. Reinfection with the same serovar, as well as multiple infections with different serovars, occurs in humans. Using a murine model of female C. trachomatis genital tract infection, we determined if homotypic and/or heterotypic protection against reinfection was induced following infection with human oculogenital strains of C. trachomatis belonging to two serovars (D and H) that have been shown to vary significantly in the course of infection in the murine model. METHODS: Groups of outbred CF-1 mice were reinfected intravaginally with a strain of either serovar D or H, two months after initial infection with these strains. Cellular immune and serologic status, both quantitative and qualitative, was assessed following initial infection, and the course of infection was monitored by culturing vaginal samples collected every 2-7 days following reinfection. RESULTS: Serovar D was both more virulent (longer duration of infection) and immunogenic (higher level of circulating and vaginal IgG and higher incidence of IgA in vaginal secretions) in the mouse genital tract. Although both serovars induced cross-reacting antibodies during the course of primary infection, prior infection with serovar H resulted in only a slight reduction in the median duration of infection against homotypic reinfection (p approximately 0.10), while prior infection with serovar D resulted in significant reduction in the median duration of infection against both homotypic (p < 0.01) and heterotypic reinfection (p < 0.01) when compared to primary infection in age and conditions matched controls. CONCLUSION: Serovar D infection resulted in significant homotypic and heterotypic protection against reinfection, while primary infection with serovar H resulted in only slight homotypic protection. In addition to being the first demonstration of acquired heterotypic immunity between human oculogenital serovars, the differences in the level and extent of this immunity could in part explain the stable difference in serovar prevalence among human isolates.

Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology.

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Probiotics (VSL#3) in arthralgia in patients with ulcerative colitis and Crohn's disease: a pilot study.

Arthralgia is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Alterations of the immunologic regulation in the gut may contribute to the pathogenesis of arthralgia. Probiotics (VSL#3) have proven effective in the treatment of pouchitis in patients with ileal pouch anal anastomosis after panproctocolectomy for ulcerative colitis both in maintaining remission and in preventing a flare-up without side effects. The aim of this study was to determine the safety and efficacy of VSL#3 in patients with quiescent IBD who suffered from arthralgia for more than two weeks. An open-label trial was conducted using VSL#3. Pre- and post-treatment joint pain intensity were measured on the Ritchie Articular Index and visual analog scale. Disease activity of the bowel was assessed by the Truelove-Witts and the Harvey-Bradshaw scores. Sixteen of 29 patients completed the trial; in 10 of the 16 patients a statistically significant improvement was documented by the Ritchie Articular Index. No one of the patients had a relapse of intestinal disease while on probiotics. These preliminary results suggest that the probiotic mixture VSL#3 may be an alternative treatment for arthralgia in patients with IBD without inducing exacerbation of the disease. Because probiotics may be effective in the treatment of IBD as well, our results suggest that patients with active disease and arthralgia may also derive benefit from this treatment. Proper randomized controlled studies are indicated.