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Melasma is an acquired dysfunction of melanogenesis, that poses a major therapeutic challenge and tends to recur after therapy. Several combination therapies are being tested nowadays for the treatment of melasma, with promising results. Metformin, an anti-diabetic medication, seems to inhibit melanogenesis by different mechanisms. In addition, there has been a long-term improvement in melasma after microneedle therapy. To evaluate the potential therapeutic role of topical metformin combined with micro-needling for the treatment of melasma. Eighteen patients with melasma received treatment in split-face manner, right side with micro-needling and topical metformin, while the left side was treated with micro-needling and topical placebo for four sessions at 2-week intervals. Hemi-mMASI score was used for the final evaluation of results. The variability pattern in Hemi-mMASI score between both sides revealed significant reduction in the right side (micro-needling + metformin), as compared to the left side (micro-needling + placebo) (2.39 ± 1.42 vs 4.72 ± 1.27, p = 0.001). The effectiveness of topical metformin in the management of melasma could be significantly improved by pretreatment with micro-needling as a combined therapy, without any apparent side effects.

Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues. Demographics and clinical data were recorded from newly diagnosed UC patients. Blood, urine and faecal samples were collected at three time points over one year. Bacterial content was analysed by 16S rRNA sequencing. Bile acid profiles and polar molecules in three biofluids were measured using liquid-chromatography mass spectrometry (HILIC) and nuclear magnetic resonance spectroscopy. We studied 42 patients with a new diagnosis of UC (27 South Asians; 15 Caucasians) with 261 biosamples. There were significant differences in relative abundance of bacteria at the phylum, genus and species level. Relative concentrations of urinary metabolites in South Asians were significantly lower for hippurate (positive correlation for ) and 4-cresol sulfate ( ) ( <0.001) with higher concentrations of lactate (negative correlation for ). Faecal conjugated and primary conjugated bile acids concentrations were significantly higher in South Asians ( =0.02 and =0.03 respectively). Results were unaffected by diet, phenotype, disease severity and ongoing therapy. Comparison of time points at diagnosis and at 1 year did not reveal changes in microbial and metabolic profile. Ethnic-related microbial metabolite associations were observed in South Asians with UC. This suggests a predisposition to UC may be influenced by environmental factors reflected in a distinct gene-environment interaction. The variations may serve as markers to identify risk factors for UC and modified to enhance therapeutic response.

Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory adipokine, functions via leptin receptors, signaling via the long isoform of receptor, LepRb. Leptin promotes DC maturation and increases CCR7 expression on blood DC. Increased mesenteric fat and leptin occur early in Crohn's disease (CD), suggesting leptin-mediated change in intestinal CCR7 expression on DC as a pro-inflammatory mechanism. We have demonstrated CCR7 expression and capacity to migrate to its ligand macrophage inflammatory protein 3β in normal human ileal DC but not colonic or blood DC. In CD, functional CCR7 was expressed on DC from all sites. Only DC populations containing CCR7-expressing cells produced LepRb; in vitro exposure to leptin also increased expression of functional CCR7 in intestinal DC in a dose-dependent manner. In conclusion, leptin may regulate DC migration from gut, in homeostatic and inflammatory conditions, providing a link between mesenteric obesity and inflammation.

Introduction Immunomodulators (IM) and biological agents are now used more often and earlier in Inflammatory Bowel Disease (IBD), leading to an increase in opportunistic infections (OI). The RR of OI is reported as OR of 2.9 with one IM, increasing to OR of 14.5 with ≥2 concomitant IMs. Age (>50 years) is also an independent risk factor for OI. These vaccinations are recommended by the European Crohn's and Colitis Organisation (ECCO) to minimise OI in immunocompromised IBD patients; Varicella Zoster Virus (VZV) (if no history of chickenpox/shingles and serology is negative), Human Papilloma Virus (HPV), annual Influenza (inactivated vaccine), Pneumococcal and Hepatitis B (if HBV seronegative). Following the Influenza A outbreak (H1N1) in 2009, Swine Flu vaccination was also recommended. The authors aimed to investigate the vaccination status of IBD patients on one or more IM. Methods The authors identified a cohort of 200 patients on IM or biological therapy from outpatients attendance between September 2009 and June 2010. Questionnaires were posted to the General Practitioners (GP) to obtain vaccination status for Flu (within 1 year), Pneumococcal (within last 5 years), VZV, HPV and Swine Flu. T test was used to examine for differences in higher risk groups. Results The response rate was 51.5% (103/200). Median age was 42 years (range 16–74); 54 were female (52.4%). 82 were tertiary referrals (79.6%). 75.7% had Crohn's disease (n=78). IMs included Azathioprine (35.9%, n=37), 6-Mercaptopurine (9.7%, n=10), corticosteroids (5.8%, n=6), Methotrexate (3.8%, n=4) and Tacrolimus (1.9%, n=2). Biological agents included Infliximab (36.9%, n=38) and Adalimumab (25.2%, n=26). Table 1 PTH-063 Administered vaccinations Not administered (n (%)) Vaccine Administered (n (%) Not invited Patient refused Unknown status (n (%)) Not eligible (n (%)) Flu 38 (36.9) 56 (54.4) 9 (8.7) 0 (0) 0 (0) H1N1 33 (32.0) 60 (58.3) 9 (8.7) 0 (0) 1 (0.9)* Pneumococcal 7 (6.8) 91 (88.3) 4 (3.4) 1 (0.9) 0 (0) HPV 0 (0) 14 (13.6) 0 (0) 1 (0.9) 88 (85.4) VZV 0 (0) 72 (70.0) 0 (0) 7 (6.7) 24 (23.3)* *Patient previously contracted illness, not eligible for vaccination. 21 patients were ≥50 years old; 47.6% (10/21) had received the Influenza and/or Swine Flu vaccination compared to 40.2% (33/82) in the younger age group (p=0.6). Of the 10 patients receiving dual IM and biological therapy, 9 (90%) received both annual Influenza and Swine Flu vaccinations (p<0.001). Conclusion Majority of patients at risk of OI in this cohort are on biological therapy. Very few received the recommended vaccinations. Patients on dual immunosuppression had significantly higher vaccine uptake. These findings may be due to lack of awareness of the risks associated with immunosuppression. Information leaflets on the ECCO-recommended vaccines directed at GPs and patients may improve compliance.

Objective The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists. Design A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. Results 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Introduction Gut dendritic cells (DCs) are crucial in bacterial recognition, T cell signalling and inflammatory regulation. DC TLR expression is altered in CD: increased on myeloid DC (MDC) in colonic CD and reduced on plasmacytoid DCs (PDC) in postoperative CD (POCD) ileum. In active CD, peripheral CD4 and CD8 T cells showed increased intestinal homing with high CCR9 levels. In Crohn's colonic tissues, CCR7, a homing marker crucial for DC trafficking to mesenteric lymph nodes, was elevated compared with controls. Additionally CCR7 expression on MDC is higher in ileal compared with colonic tissue in CD. CCR7 and CCR9 expression on DC in POCD is unknown. After ileo-caecal resection the neo-terminal ileum is exposed to the bacteria rich contents of the colon. The authors hypothesise that alteration in gut microflora after surgery may modulate expression of homing markers on DC from POCD patients. The authors aimed to examine homing marker expression on MDC and PDC from the ileum and the colon in healthy controls (HC) and POCD patients. Methods HC and POCD patients were identified at colonoscopy. Intestinal lamina propria mononuclear cells were collected using collagenase digestion and labelled with directly conjugated monoclonal antibodies to CCR7 and 9. PDC and MDC were characterised as CD11c+ve and –ve respectively and expression of CCR7 and 9 by multicolour flow cytometry measured. Statistical analysis was via unpaired t tests. In experiments with paired colonic and ileal samples paired t tests were performed. Results In paired samples, HC ileal CCR9+ve PDC concentrations were lower than colonic PDC (26.46±10.43/ml SEM vs 53.76±20.16/ml SEM, p<0.05). However, POCD ileal CCR9+ve PDC did not differ from colonic concentrations (108.0±33.24/ml SEM vs 93.1±43.01/ml SEM, p=NS). There were significantly higher concentrations of CCR9+ve and CCR7+ve PDCs within ileal POCD compared with ileum normal controls (103.8±22.64/ml vs 37.68±7.434/ml, p=0.039 and 117.4±26.97/ml SEM vs 40.47±3.97/ml SEM, p=0.03). No differences in MDC concentrations of both homing markers in all types of tissue existed. Conclusion POCD neo-terminal ileum showed higher CCR7+ve and CCR9+ve PDC than normal ileum. This novel finding indicates a potential role for PDC in CD pathogenesis. The loss of the ileocaecal valve in POCD may alter microbiota flora exposure in the ileum with an adaptive response of CCR9+ve DC to a level seen in normal colonic tissue. Additionally, this may induce migration of PDC by upregulation of CCR7 expression. Further studies to examine the changes with disease progression may unravel the function of PDC in ileal POCD tissues.

Introduction Previous epidemiological studies suggest a higher rate of pan-colonic disease in South Asians (SA) compared with Caucasians. There is limited data on disease severity across ethnic groups. Refractory disease and development of dysplasia indicate aggressive disease and are both indications for colectomy. The aim of the study was to compare the risk of colectomy for ulcerative colitis (UC) in SA migrants to Caucasians. Method Patients with UC were identified from a national administrative dataset (Hospital Episode Statistics - HES) between 1997-2012 according to ICD-10 diagnosis code K51 for UC. From the cases coded for ethnicity, colectomy cases were identified according to the Office of Population Censuses and Surveys (OPCS) codes. The colectomy rate for each ethnic group was calculated as the proportion of patients who underwent colectomy from the total UC cases for that group. The median age at time of colectomy was calculated for each ethnic group. Chi-squared testing was used to determine significant differences in colectomy rate and Kruskal-Wallis test to ascertain differences in age at colectomy between ethnic groups. Results Of 212,430 UC cases, 74,988 (35.3%) were coded for ethnicity. Of these cases most were White Europeans (Caucasians) 69,208/74,988 (92.3%). The SA group consisted of: 1,954/74,988 (2.6%) Indian, 832/74,988 (1.1%) Pakistani and 129/74,988 (0.2%) Bangladeshi ( Table 1 ). Indians had a significantly higher colectomy rate than White Europeans (10.8% vs 7.4%, p < 0.001). In contrast Pakistanis had a similar (7.0%) and Bangladeshis a significantly lower (4.7%) colectomy rate than the White European group. (7.4%, p < 0.001). SAs undergoing colectomy were significantly younger than White Europeans for each ethnic group (median age; Bangladeshis - 29 years, Pakistanis - 37 years and Indians - 41 years, compared with White Europeans - 49 years, p < 0.001). Abstract PTH-063 Table 1 Colectomy rate in UC patients by ethnicity Ethnicity --- White Europeans Indian Pakistani Bangladeshi --- No. of colectomies 5150 211 58 6 Total no. of UC cases 69208 1954 832 129 Colectomy rate (%) 7.4 10.8 7.0 4.7 Conclusion The colectomy rate is higher in Indians compared to White Europeans. Across SA ethnic groups there are differences in colectomy rate. All SA groups required a colectomy for UC at a younger age than White Europeans. These findings suggest a more aggressive phenotype in SAs and should be validated with a prospectively recruited ethnic cohort. This will also allow examination of contributing factors. Disclosure of interest None Declared.

Introduction Previous studies suggest changing incidence and prevalence of Inflammatory Bowel Disease (IBD) in migrant groups, particularly South Asians. Most of these studies were retrospective and within local hospital settings. They also suggest a different phenotype: pan-colonic ulcerative colitis (UC) was commoner in migrants from India compared with Caucasians. One study in East London reported on differing phenotype of Crohn's disease (CD) in Bangladeshis; they developed perianal complications, received anti-TNFs earlier and underwent surgery later than Caucasians. We examined the ethnic diversity of patients with IBD attending hospitals in England. Method We identified patients from a national hospital episodes statistics (HES) database between 1997-2012. The database captures all hospital episodes between these dates. Patients were identified according to ICD-10 diagnosis code; K51 for UC and K52 for CD. Only patients with a documented ethnicity code were included. Results Patients with an ethnicity code and a diagnosis of UC and CD are shown in Table 1 . Only 35.3% of cases had an ethnicity code. The majority of patients were of White European (Caucasian) descent. In Bangladeshis, CD was commoner than UC in contrast to Indian and Pakistani ethnic groups where UC was commoner than CD. Abstract PTH-064 Table 1 Number of patients with UC and CD by ethnicity Ethnicity Crohn's disease Ulcerative colitis Total with IBD --- n= % n= % n= % --- White European 52,142 93.7 69208 92.30 121,350 92.9 Indian 778 1.4 1954 2.60 2,732 2.1 Pakistani 476 0.9 832 1.10 1,308 1.0 Bangladeshi 156 0.3 129 0.20 285 0.2 Other 2102 3.8 2865 3.90 4967 3.7 Total 55,654 100.0 74988 100.0 130,642 100.0 Conclusion Bangladeshis are more likely to have CD compared with Indians and Pakistanis and require more hospital interventions for CD than UC. This may represent a more aggressive phenotype consistent with previous literature. This data is limited by the nature of the HES database: retrospective, hospital episodes and incomplete coding for ethnicity. Prospective studies are needed to validate these findings and explore underlying reasons for the difference. Disclosure of interest None Declared.

This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab.MethodsRetrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered at an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5–10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis).ResultsTwelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35–203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects.ConclusionOral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted.