INFLAMMATORY BOWEL DISEASE ULCERATIVE COLITIS

Editor's Notes

1. Taken together, the incidence of UC in Hindus was about twice as high as that in Muslims; the higher frequency of smoking among Muslims was used to explain the observed difference.
2. There is some support for "genetic anticipation," which refers to the development of earlier onset and more severe disease in offspring of affected parents in subsequent generations [15,22,23]. In one study, for example, 48 of 57 children with CD born of parents with CD developed symptoms a median of 16 years earlier than the onset of disease in their parents [22]. Rather than reflecting genetic anticipation, the preceding observations may in part be explained by ascertainment bias because children of parents with IBD may be subjected to earlier diagnostic evaluation [17,24]. In addition, apparent genetic anticipation may be explained in part by bias secondary to the lack of adjustment for different observation times among subjects [25]. Since children of affected parents are typically followed for a much shorter time span than their parents (up to a lower average age), the average age of disease onset in children may be lower than would be found if this group were followed for a longer time. However, this cannot be the entire explanation since the parents may be first diagnosed after the child (12 of 49 cases in one series) 
3. IRGM:IMMUNITY RELATED GTPase FAMILY M GENE
4. In addition, we could also demonstrate decreased concentrations of faecal SCFAs, especially of n-butyrate, iso-butyrate, and acetate, in the faecal sam- ples of the UC patients.
5. Genetic and environmental factors induce impaired barrier function in the intestinal mucosa. Initiating triggers may involve infections in some patients. Altered barrier function subsequently induces the translocation of commensal bacteria and microbial products from the gut lumen into the bowel wall, which leads to immune cell activation and cytokine production. If acute mucosal inflammation cannot be resolved by anti-inflammatory mechanisms and the suppression of pro-inflammatory immune responses, chronic intestinal inflammation develops. In turn, chronic inflammation may cause complications of the disease and also tissue destruction, which are both drivenby mucosal cytokine responses. DC, dendritic cell; IBD, inflammatory bowel disease; NSAIDs, non-steroidal anti-inflammatory drugs; TReg cell, regulatory T cell
6. In patients with inflammatory bowel disease (IBD) and in experimental mouse models of colitis, pro-inflammatory and anti-inflammatory cytokines produced by various cells of the mucosal immune system in response to environmental triggers, such as commensal microorganisms. In particular, dendritic cells (DCs), neutrophils, macrophages, natural killer (NK) cells, intestinal epithelial cells (IECs), innate lymphoid cells (ILCs), mucosal effector T cells (T helper 1 (TH1), TH2 and TH17) and regulatory T (TReg) cells produce cytokines in the inflamed mucosa. The key transcription factors and cytokines produced by T helper cell subsets in IBD-affected mucosa are shown. The balance between pro-inflammatory and anti-inflammatory cytokines in the mucosa regulates the development and potential perpetuation of mucosal inflammation in patients with IBD. The dashed arrow indicates that ILCs, which produce cytokines that are involved in intestinal inflammation, may respond to IL-18. GATA3, GATA-binding protein 3; IL, interleukin; RORγt, retinoic acid receptor-related orphan receptor-γt; TGFβ, transforming growth factor-β; TNF tumour necrosis factor.
7. IN IBD increased amounts of soluble and membrane-bound tumour necrosis factor (TNF) are produced by various immune and stromal cell populations, such as macrophages, dendritic cells s , effector T cells, adipocytes and fibroblasts TnF has been shown to exert various pro-inflammatory functions in the inflamed mucosa in IBD. In particular, TNF induces hypervasculariation and angiogenesis, augments pro-inflammatory cytokine production by macrophages and T cells, causes barrier alterations and promotes cell death of intestinal epithelial cells (IECs) and Paneth cells. TNF also promotes tissue destruction by increasing the production of matrix metalloproteinases by myofibroblasts and drives T cell resistance to apoptosis via the induction of TNF receptor-associated factor 2 (TRAF2) and the activation of nuclear factor-κB (NF-κB). TNF-specific antibodies may alleviate disease by simultaneously suppressing several pro-inflammatory pathways in patients with IBD. IL, interleukin; MLCK, myosin light chain kinase; RIPK, receptor-interacting protein kinase; TIMP1, tissue inhibitor of matrix metalloproteinases 1.
8. Intestinal epithelial cells (IECs) are exposed to numerous pro-inflammatory and anti-inflammatory cytokines during chronic intestinal inflammation in inflammatory bowel disease (IBD). These cytokines are produced by cells in the local microenvironment and by IECs themselves. Local cytokine responses have major effects on mucosal healing and cancer development in patients with IBD. The cellular sources of key cytokines and their signalling cascades that regulate IEC survival, cell death and proliferation are shown. In the context of mucosal healing in ulcers (left), green boxes indicate beneficial effects of cytokines, whereas red boxes highlight pathogenic effects of cytokines. In colitis-associated cancer (right), blue boxes indicate pro-tumour effects of cytokines. DC, dendritic cell; IFN, interferon; IL, interleukin; ILC, innate lymphoid cell; TH cell, T helper cell; TNF, tumour necrosis factor.
9. Cytokine signalling pathways and intracellular Janus kinase(JAK)–signal transducer and activator of transcription (STAT) signalling cascades in mucosal immune cells are shown. In IBD, the activation of certain STATs in mucosal T cells results in augmented cytokine production Several pro-inflammatory cytokines have been implicated in IBD pathogenesis and are potential targets for therapy. Antibodies targeting soluble tumour necrosis factor (TNF) and membrane-bound TNF (such as infliximab, adalimumab, certolizumab pegol and golimumab) are routinely used in the clinic. In addition, cytokine blockers (for example, tocilizumab, which targets interleukin-6 (IL-6) and ustekinumab, which targets the p40 subunit of IL-12 and IL-23) have been recently tested in clinical studies. In addition, inhibitors of JAK and STAT signalling (for example, the JAK3 and JAK1 inhibitor tofacitinib, which blocks IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 signalling) have yielded promising results in clinical trials. Future therapy of IBD may also use bispecific tetravalent dual variable domain IgG (DVD-Ig) antibodies. Finally, the identification of specific cytokines and cytokine expression patterns that are unique to certain subsets of patients with IBD may open new avenues for future personalized medicine for these disorders. βc, cytokine receptor common subunit-β; γc, cytokine receptor common subunit-γ; gp130, IL-6R subunit-β; LIFR, leukaemia inhibitory factor receptor; OSMR, oncostatin-M-specific receptor subunit-β; TRAF2, TNFR-associated factor 2; TYK2, tyrosine kinase 2.
10. For instance, topical therapy in the form of suppositories (for proctitis) or enemas (for left-sided colitis) is often the first line choice, but oral therapy - often combined with topical therapy is appropriate for extensive colitis [EL1b, RG B].
11. The appearance of erythema nodosum usually parallels intestinal disease activity, and treatment directed at the underlying IBD usually results in resolution of the lesions.  
12. Pyoderma gangrenosum lesions usually do not parallel IBD activity [12]. In patients with active IBD and pyoderma gangrenosum, therapy with systemic steroids usually results in healing.
13. Evaluation of small bowel if Macroscopic and Histological rectal sparing Presence of a caecal patch in newly diagnosed colitis
14. and this challenges the pathogenic theory that backwash ileitis is caused simply by reflux of caecal contents into the ileum.
15. The diagnostic value of neutrophils in UC, however, is limited because they are also present in infective colitis and other forms of colitis.
16. To avoid diagnostic error, the criteria of diffuse transmucosal inflammation for diagnosing ulcerative colitis should be avoided in biopsies from early onset disease in children,159 or after treatment and when disease is resolving or quiescent. In these circumstances the biopsy may be normal or show focal changes.
17. However these lesions may occur in infections and other types of colitis. Lamina propria and intraepithelial neutrophils are absent in inactive or quiescent disease.