2023 Colitides - Non IBD PDF

COLITIDES – NON-IBD Dr Kar Yin Fok A/Prof Toufic El-khoury Words: 4997 INTRODUCTION There are many aetiologies of colitis that is not due to inflammatory bowel disease...

COLITIDES – NON-IBD Dr Kar Yin Fok A/Prof Toufic El-khoury Words: 4997 INTRODUCTION There are many aetiologies of colitis that is not due to inflammatory bowel disease (IBD). These are relevant as they may be encountered during investigation of symptomatic colitis, on endoscopy, and some may require surgery. They can be differentiated using a combination of clinical, endoscopic and histological features (1). This overview will provide a summary and updates on the topic. The initial approach is similar for these conditions, starting with supportive management. This includes analgesia, anti-emetics, and correction of fluid and electrolyte imbalance. Hospital admission may be needed if severe, and contact precautions if there is concern of infection. Stool cultures can detect an infectious cause, and radiological investigation with x-ray or CT may be performed looking for complications. Thereafter, treatment is directed to the underlying cause. If histopathological evaluation is required, it is recommended different segments of the ileocolonic tract be sampled. This includes two biopsies from five areas of colon: the right, transverse, left, sigmoid colon and rectum, as well as two biopsies from terminal ileum, and any endoscopically abnormal areas (1). In acute colitis endoscopy is usually only performed if there is a prolonged clinical course or lack of response to treatment, due to the risk of perforation. TYPES OF NON-IBD COLITIS 1. Infectious 2. Ischaemic 3. Diverticular/SCAD 4. Diversion 5. Microscopic 1|Page  6. Eosinophilic 7. Iatrogenic INFECTIOUS COLITIS The incidence of infectious colitis is increasing worldwide due to globalisation, business travel and tourism. Common causes are listed below, and important ones discussed (Table1). Causes of infectious colitis Bacteria Salmonella Shigella Campylobacter E. Coli C. Difficile Vibrio Cholera Virus Rotavirus Norovirus CMV Parasite Amoebiasis Schistosomiasis Protozoa Cryptosporidium Giardia Table 1: Common pathogens in infectious colitis Clostridium/Clostridioides Difficile Clostridium difficile (C. difficile), also known as clostridioides difficile since 2016, is a gram-positive, anaerobic, spore-forming, and toxin-producing bacterium (2). There are reports of increasing incidence, including since the COVID-19 pandemic. This is thought to be due to poor antibiotic stewardship and gut dysbiosis with COVID-19, which in combination with C. difficile is highly morbid (3). 2|Page In the community approximately 5% of adults and a majority of infants are colonised with C. difficile. In hospital and nursing home settings, up to 20-50% of adults are colonised, with higher rates seen in longer lengths of stay (4). The most important risk factor for C. difficile infection is antibiotic use, commonly broad-spectrum penicillins, cephalosporins, clindamycin and fluoroquinolones. However, almost all antibiotics have been implicated (4). Risk of C. difficile infection is up to 10-fold higher during antibiotic therapy and for the first month thereafter, and up to 3-fold higher for three months after antibiotics (2). Other risk factors are advanced age, hospitalisation, IBD and immunosuppression. Pathophysiology C. difficile is transmitted by spores resistant to heat and acid. Normal intestinal microflora is the main barrier to colonisation, which is altered by antibiotics. Additionally, a weakened immune system, reduced nutritional competition, and physical barrier breakdown, leads to colonisation (5) C. difficile then releases two exotoxins, toxin A and toxin B. Toxins are transported to the cell cytoplasm, where they inactivate the Rho family of GTPases, causing cell death, loss of intestinal barrier function and neutrophilic colitis (4). Clinical presentation Clinical presentation of infection can range from asymptomatic carrier state to life-threatening fulminant colitis. The majority experience watery diarrhoea that recovers after 5-10 days of antibiotic withdrawal. Other symptoms include abdominal pain, fever, and less commonly haematochezia. Mortality due to C. difficile is 5%, but up to 30% with a complication, such as toxic megacolon or perforation. Recurrence rates are up to 25% after one episode, and up to 65% after multiple infections (2). Diagnosis is based on detection of C. difficile toxin in stool, which can be done via enzyme immunoassay, with a sensitivity of 75-85% and specificity of 95-100%, or nucleic acid amplification using PCR, with sensitivity 80-100% and specificity of 87-99% (2). However, PCR detects the presence of the toxin producing gene, and not the toxin itself, therefore interpretation can be misleading. Endoscopy for visualisation and biopsy is reserved for cases of diagnostic uncertainty. Pseudomembranes comprising of dead colonocytes, neutrophils and fibrin appear on the mucosal surface, though this can also be seen in Bechet’s disease and IBD (2). 3|Page Treatment Initial treatment is supportive, with antibiotic withdrawal. Vancomycin has been found in recent meta-analyses to be superior to metronidazole, and Fidaxomicin has comparable efficacy to vancomycin, with reduced rates of recurrence in some groups (6). Since 2017, the Infectious Disease Society America stated vancomycin and fidaxomicin are the cornerstone of treatment, while newer agents continue to be developed (7). Available Australian guidelines still recommend oral metronidazole as first line in mild disease, followed by vancomycin. In severe disease, with leucocytosis, severe abdominal pain, elevated serum creatinine, lactaemia, hypoalbuminaemia, high fever, or organ dysfunction, vancomycin is first line, followed by additional metronidazole, or vancomycin retention enemas, especially if there is ileus. Faecal microbiota transplant (FMT) is preferred treatment for recurrent and refractory disease, recently approved by Therapeutic Goods Administration. As altered microbiota is considered key in development of C. difficile infection, antibiotic withdrawal with FMT has been found to have lowest rates of recurrent C. difficile infection (8). Prevention is by handwashing due to ubiquitous spores, and there is some evidence for prophylactic probiotics, however there was significant variation in the studies used in meta-analyses (2, 9). Other infectious causes Bacterial Salmonella Salmonella is a gram-negative rod, a common foodborne infection and cause of diarrhoea in the developed world. Salmonella typhi and paratyphi causes enteric or typhoid fever, with high fevers and abdominal pain. It can also cause hepatosplenomegaly or perforation due to ileocaecal lymphatic hyperplasia of Peyer’s patches. Chronic carriers pose an ongoing infection risk. Non- typhoidal salmonella causes a milder acute illness. Treatment is supportive; azithromycin or ceftriaxone may be required, or surgery if there has been perforation. Shigella Shigella is also a gram-negative rod, transmitted person to person by fecal-oral route, and invades intestinal epithelial cells. It causes fever and diarrhoea that can become bloody, especially Shigella dysenteriae which produces a shiga toxin. Rehydration is the mainstay of treatment, antibiotics if severe or immunocompromised, while complications such as toxic megacolon are uncommon. 4|Page Campylobacter Campylobacter jejuni and coli are gram negative bacteria, motile with flagella. They are often found in uncooked poultry, and causes a diarrhoea that can be watery or haemorrhagic. Detection is in stool cultures, and treatment is usually supportive as it is self-limiting, or, azithromycin orally if severe. The disease be complicated by reactive arthritis (20mg/dl, Hb250IU/L, sodium 15x109/L or colonic ulceration. Severe disease is more than three of the above, or, with peritonism, pneumatosis, gangrene on endoscopy or pancolitis (15). Majority of cases are self-limiting, with supportive management, fasting and intravenous fluids. Thereafter, treatment is directed at the underlying cause. Indications for acute surgery are signs of peritonism, haemorrhage, fulminant colitis with or without toxic megacolon, portal venous gas or pneumatosis coli on imaging, and ongoing clinical deterioration. The most common procedure is laparotomy with segmental resection, depending on the extent of affected bowel, however a small study has shown laparoscopic approach is also feasible (16). Prophylactic anticoagulation is 7|Page recommended, though not therapeutic, nor antiplatelet prophylaxis (17). Guidelines also suggest considering antibiotics in moderate and severe disease to combat translocation, though there is limited evidence on its efficacy and the choice of agent. Subacute indications for surgery include failure to respond to treatment in 2-3 weeks with continued symptoms or protein-losing colopathy, or apparent healing but recurrent sepsis. Chronic indications for surgery include symptomatic stricture (11). DIVERTICULAR COLITIS/SCAD Diverticular colitis, also known as segmental colitis associated with diverticulosis (SCAD), is the inflammation of colonic mucosa between, but not within, diverticula. It is an inflammatory disorder now recognised to be within the spectrum of inflammatory bowel disease (18). Epidemiology Epidemiological data is scarce and incidence estimated to be 4/100,000, affecting between 1-10% of those with diverticular disease (19). It is more common in males, and over the age of 60, coinciding with the second peak of IBD, and differentials for colitis in this age group are broad. Pathophysiology There is chronic inflammation of colon where there is diverticulosis, and as such most commonly affects sigmoid and left colon, sparing the rectum. The pathogenesis is poorly understood, but thought to be related to mucosal prolapse, faecal stasis, and localised ischaemia related to diverticula (18). There is macroscopic and microscopic inflammation of inter-diverticular mucosa, and histologically the inflammation is non-specific, non-granulomatous and localised. It was previously thought to be a complication of diverticulitis, however there is often a lack of leucocytosis, fever or peritonism associated with diverticulitis. There is also data to suggest SCAD may occur in individuals genetically susceptible to IBD, including some observational studies comparing IBD patients with and without diverticular disease (18, 20). Clinical presentation 8|Page Initial symptoms are usually diarrhoea and haematochezia, and less commonly abdominal pain. Work up includes ANCA and ASCA antibodies to help exclude IBD. The mainstay of diagnosis of SCAD is endoscopy, where there is visible colonic mucosal inflammation with sparing of diverticular orifices, and rectal biopsies negative for inflammation. SCAD has been classified into four types endoscopically. Type A, or ‘crescentic fold disease’, shows patchy acute inflammation confined to crescentic mucosal folds, histologically includes intraepithelial abscesses but no crypt architectural changes. Type B, also known as ‘mild to moderate ulcerative colitis (UC)-like’, has diffuse loss of vascular pattern, mucosal erosions and hyperaemia, but spares the rectum and diverticula unlike UC. Histologically, there is crypt architectural changes. Type C is ‘Crohn’s disease-like’, and resembles mild to moderate Crohn’s disease with aphthous ulcers. Histologically this type can be quite varied with transmucosal inflammation and micro-fissures. Type D is ‘severe UC-like’, with diffuse loss of vascular pattern, contact bleeding, mucosal oedema and ulceration, and there may be luminal narrowing. Histologically in type D there is crypt architectural changes, and there are crypt abscesses and goblet cell depletion (19, 21). Treatment Optimal treatment is not well defined. Traditionally, first line treatment has included antibiotics such as ciprofloxacin or metronidazole, with a salicylate such as mesalazine, in conjunction with a high fibre diet. Tursi et al showed that SCAD can be treated with oral mesalazine, or, a combination of beclomethasone dipropionate (BDP), which is a steroid with high first-pass metabolism, with probiotic VSL#3 (22). More recently a review has shown that most patients treated with mesalazine only, without antibiotics, or no drug therapy at all, recovered within 6 months (23). If needed, therapy can be escalated to prednisone, with consideration of biologicals such as infliximab based on case reports, given the similarity with UC in TNF-α expression (23). Now there is better recognition and treatment of not only SCAD but IBD, true failure of treatment of SCAD is thought to be rare. However, if this occurs with disease limited to sigmoid, anterior resection may be offered (18, 23). Most recently a prospective cohort of 2215 patients with diverticulosis found a rate of 1.99% of SCAD, with 44 patients, followed to 3 years (24). Type B and D had a worse clinical course, one developed UC, one required TNF-α treatment due to steroid dependency, and one underwent anterior resection for refractory disease (24). 9|Page Long term data after 5- to 7- year follow up suggests SCAD is a benign condition, drug responsive, though can recur, especially types B and D (22). There is overlap with features of IBD and there are even reports of COVID-19 contributing to such changes in the gastrointestinal tract, with a small study of COVID-19 patients undergoing colonoscopy finding SCAD most commonly, in 5 of 20 patients (25%), followed by colonic ischaemia in 4 patients, showing that there is more to be understood about its pathogenesis (25). DIVERSION COLITIS Diversion colitis is a nonspecific inflammatory disorder in bypassed colon and rectum, where the faecal stream has been surgically diverted. It was first described by Morson et al. in the 1970’s and the term coined by Glozer et al. in 1981 (26, 27). Epidemiology The true incidence is unknown, estimated at 70-100%, where almost all have histological evidence of colitis after diversion (28). There was no association with sex, age, or type of surgery performed. Pathophysiology The pathogenesis is hypothesised to involve: a decrease in short chain fatty acids (SCFA), increase in nitrate reducing bacteria, and altered mucosal immunity. SCFAs, predominantly acetate, propionate and n-butyrate are luminal nutrients from anaerobic bacterial metabolism of unabsorbed dietary carbohydrates. They are usually absorbed by colonocytes for energy, as well as has effects on electrolyte transport, colonic motility, mucosal blood flow and production of inflammatory cytokines. These are decreased in diverted colon and treatment with topical SCFA enemas can be beneficial, although inconsistent results suggest there are other mechanisms at play (29). There is also reduced anaerobic flora and an increase in nitrate reducing bacteria. This can result in higher levels of nitric oxide (NO), which is produced by these bacteria, and toxic to colonic tissue. IgA is the main antibody secreted into the intestinal lumen and helps defend against pathogens and maintain homeostasis. Intestinal IgA levels are increased in diversion colitis (29). Both these observations require more studies to demonstrate their role in pathogenesis. 10 | P a g e Clinical presentation The majority with diversion colitis are asymptomatic. In the 30% with symptoms, these are commonly tenesmus, urgency, bloody or mucus discharge, and pain, which can significantly affect quality of life (30). Bleeding requiring transfusion or sepsis from deep ulcerations are rare. In the longer term, strictures or mucus plugging may be seen. The risk of dysplasia or malignancy appears to be low in diversion colitis, without other risk factors of colorectal cancer or IBD (31). Endoscopic features can be non-specific, and include erythema, friability, oedema, and there may be ulcers, nodularity, mucus plugs or strictures. These generally do not correlate with severity of symptoms. Biopsies may be done to differentiate from other causes of colitis, though most findings are again non-specific. Prominent lymphoid hyperplasia with usually preserved crypt architecture on histology is suggestive of diversion colitis (31). Some features that mimic IBD such as architectural distortion in marked lymphoid hyperplasia can make differentiation difficult. At times a trial of medical therapy for either diversion colitis or IBD may assist diagnosis, prior to re-anastomosis. Treatment Restoring bowel continuity is the mainstay of treatment, with medical therapies reserved for those unable or unwilling to undergo restorative surgery. Anastomosis is associated with high rate of resolution of inflammation, with better symptom control if performed early (32). SCFA enemas are often used in medical therapy. Dosing in the literature varies from 10-60mL once or twice a day for 2 to 6 weeks. It usually includes sodium acetate, sodium propionate and sodium n- butyrate, made at a compounding chemist. It can be used to induce remission followed by a lower dose maintenance therapy. There is conflicting data on its efficacy despite initial reports (28, 33). Topical 5-aminosalycilates and steroids, usually in the form of enemas have also proven to be effective, to varying degrees (34). There are other reports of irrigation with fibre and autologous FMT as newer treatment modalities when other options above have failed. There is a lack of consensus for treatment of asymptomatic patients with endoscopic finding of diversion colitis, and any therapy or endoscopic surveillance is based on individual patient factors. 11 | P a g e MICROSCOPIC COLITIS Microscopic colitis encompasses 2 subtypes, collagenous and lymphocytic colitis, and can cause watery diarrhoea, predominantly in older people. The colon may appear macroscopically normal on colonoscopy, with eventual histological diagnosis (Figure 2). Epidemiology It is an inflammatory condition estimated at an incidence of 4 per 100 000 persons (35). Risk factors include increased age, female gender, autoimmune diseases, smoking, and medication such as PPI and NSAIDS (36). Pathophysiology Proposed mechanisms include an autoimmunity, due to association with conditions including hyper and hypothyroidism, Crohn’s disease, rheumatoid arthritis, type 1 diabetes, as well as a female predominance in the condition. It may involve immune response to a luminal antigen, which may be dietary, bile salts, or infectious agent, though none have been definitively proven to be causative. There is association with several medications such as PPIs and NSAIDs, however a more recent multicentre study suggests they may not cause microscopic colitis, only worsen diarrhoea and unmask the diagnosis, while discontinuation of these agents can still lead to symptom improvement (36, 37). Specifically at the cellular level, it is thought to be an immune mediated disorder involving the adaptive immune system and cytotoxic responses. An abnormal translocation of immune triggers from the gut lumen is believed to the initiating event. The presence of T-helper (Th)-1 and cytotoxic T-cell (Tc)1, or Th-17 and Tc-17 results in overexpression of TNF-α, IFN-γ, and interleukin, causing lymphocyte infiltration and proliferation and impairment of mucosal-barrier function, amongst other changes. Watery diarrhoea then results from sodium malabsorption. Abnormal collagen deposition or exaggerated response to chronic inflammation is also thought to a factor in collagenous colitis (38). Clinical presentation It commonly presents as chronic watery diarrhoea in older patients, with above risk factors. Differential diagnoses are broad, and work up often includes stool MCS and blood tests. 12 | P a g e Diagnosis requires colonoscopy and biopsy, usually taken randomly throughout the colon. The hallmark is intraepithelial lymphocytosis on histology, with lymphocytic and collagenous subtypes now considered to be part of the same spectrum. Lymphocytic colitis is defined by more than 20 intraepithelial lymphocytes per 100 surface epithelial cells, with acute and chronic inflammatory cells found in the lamina propria. Collagenous colitis is defined by the presence of a subepithelial collagen band typically greater than 7-10μm, and a chronic inflammatory cell infiltrate in the lamina propria (36). Treatment The initial step is modifying exacerbating factors, such as withdrawal of PPIs and NSAIDs, and smoking cessation, though the evidence base for these measures is low (39). For mild symptoms, antidiarrheals such as loperamide can be used. Most patients require medical therapy for clinical remission and improved quality of life, and studies suggest both subtypes respond similarly. Both American and European guidelines recommend oral budesonide as first line medical therapy, based on its effectiveness in randomised trials and meta-analyses (38, 39, 40, 41). It has potent anti- inflammatory effects and high first-pass metabolism, and does not need tapering for maintenance. There are reports of clinical remission in 70-91% of patients after 6-8 weeks, with normalisation of quality of life. However, recurrence rates can be as high as 80% with cessation of therapy, and maintenance budesonide 6mg daily is recommended (38). Other therapies include cholestyramine, a bile acid binding resin, due to the concurrent bile acid malabsorption that often occurs in microscopic colitis. Symptoms refractory to steroids can be escalated to biologicals such as anti-TNFα agents like infliximab, or immunotherapy like 6- mercaptopurine, based on limited evidence from small series. Surgery for medically refractory disease, with defunctioning ileostomy or colectomy, is rare (38). The natural history of microscopic colitis is a chronic intermittent course, with no increased risk of colorectal cancer (36). EOSINOPHILIC COLITIS 13 | P a g e Eosinophilic colitis is a rare condition within eosinophilic gastrointestinal disease, which also includes oesophagitis and enteritis (42). It remains poorly understood, with the term generally reserved for symptomatic disease, while primary colonic eosinophilia (PCE) describes incidentally discovered eosinophilia. Epidemiology It is estimated to have a prevalence of 2.3 per 100 000 adults, with a peak in neonates and early adulthood. It is more common in women. Pathophysiology Specific aetiology is unclear, however, it is thought to be due genetic and environmental factors, and associated with allergic conditions, such as asthma, eczema, and other atopic conditions. Primary eosinophilic colitis is a diagnosis of exclusion, as colonic eosinophilia can also occur secondary to parasitic infections, IBD and immunosuppression. Eosinophils reside in tissues and protect against pathogens such as parasites and bacteria, and regulate the intestinal microbiome. They can be activated by stimuli such as allergens and infections, and regulated by cytokines such as IL5, IL4, and TNF. Once activated, they result in degranulation and release of cytotoxic proteins, as well as cytokine and IgE production. Clinical presentation Symptoms are variable, and related to the depth of eosinophilic infiltration. Mucosal disease presents as diarrhoea, malabsorption and protein losing enteropathy. Transmural disease, less common, can have colonic wall thickening, and result in obstruction, intussusception and perforation. Serosal disease can present with ascites. Evaluation is often difficult, as endoscopic biopsies are mucosal only. There is a lack of consensus, but diagnosis is generally made on a combination of clinical and histological features, with attributable symptoms, and an excess of eosinophils in colonic biopsies, in the absence of other causes. Thresholds for excess eosinophil counts are >50/HPF in right colon, >35/HPF in transverse, and >25/HPF in left colon, though only used as guide based on case series (42). Natural history is also variable, adults with mucosal disease often have a chronic non-remitting illness, while transmural disease can be relapsing and remitting, while serosal disease often occurs once only. 14 | P a g e Treatment While affective in infants, an empiric elimination diet of main food allergens is rarely sufficient in adult with eosinophilic colitis. Corticosteroids in the form of oral prednisone is first line medical therapy, by inhibiting eosinophil growth factors. It has shown remission after a 2-week course and can be tapered, although some relapse and may require longer maintenance therapy. Mesalazine and immunomodulary agents such as azathioprine and infliximab have been used with some effect for steroid refractory or dependent disease, although data on their use is limited. One case of enterocolitis was successfully treated by FMT. Surgery, with segmental colonic resection, should be limited for severe complications such as obstruction, intussusception, perforation(42). IATROGENIC COLITIS Radiation Radiotherapy used in the treatment of various malignancies can affect all organs, including the colon, causing colitis. More commonly, pelvic radiotherapy can cause radiation proctitis. This may be acute, within 6 weeks of radiation, or chronic. Risk factors include external beam, as opposed to brachytherapy, and a dose greater than 45Gy. Acute inflammation it is caused by mucosal injury, while chronic radiation changes are due to obliterative endarteritis and chronic mucosal ischaemia. In colitis, patients may present acutely with abdominal pain and diarrhoea, which can be treated conservatively, with anti-diarrhoeals, and octreotide if refractory to these agents. Perforation is rare. Chronic colitis may also manifest as pain and diarrhoea, as well as other complications such as obstruction due to stricture, bleeding, fistula, malignancy, and treatment may require surgery. For proctitis, symptoms are non-specific and include diarrhoea, urgency, tenesmus, while endoscopy may show vascular ectasias. Acutely, butyrate enemas may help, while treatment is more selective for chronic proctitis. Sucralfate enemas may be effective for tenesmus symptoms, argon plasma coagulation can be used for bleeding and stool softeners and dilatation can be used for strictures (43). Drug-induced NSAIDs 15 | P a g e NSAIDs have been associated with colitis for some time, whether it be ulcerations, strictures, inflammatory changes due to non-specific colitis, or in conjunction with another form of colitis such as eosinophilic colitis, pseudomembranous colitis, or collagenous colitis. The dual inhibition of COX enzymes is the proposed mechanism of the drug-induced inflammatory colitis. While rare, it can cause significant symptoms, and withdrawal of the medication is recommended in the first instance (44, 45). Chemotherapy Many chemotherapy agents can cause diarrhoea, most commonly with fluoropyrimidines such as fluorouracil and capecitabine, irinotecan, and molecularly targeted agents such as tyrosine kinase inhibitors. They are due to a combination of mechanisms, including epithelial damage causing secretory diarrhoea, intraluminal substances causing osmotic diarrhoea, and altered motility. In some diarrhoea itself can be life-threatening due to dehydration and electrolyte disturbances, with or without colitis, and if severe, can result in perforation. Patients on chemotherapy are also develop other types of colitis, such as neutropenic enterocolitis, ischaemic colitis especially with docetaxel, and C. difficile colitis. Neutropenic enterocolitis is a life-threatening condition thought to arise from mucosal injury and impaired host defence to microorganisms in the immunosuppressed individual, resulting in transmural infection and necrosis. Treatment is supportive, with antibiotics, unless there is free perforation or other complication such as uncontrolled haemorrhage that may warrant surgical intervention (44, 46). Immunotherapy There has been an increase in immune check-point inhibitors (ICI) in cancer therapy, which are known to potentially cause an immune-mediated colitis. While those targeting PD-1/PD-L1 had an incidence of diarrhoea and colitis of 10% and 2% respectively, this was more prevalent with the anti- CT4 agent ipilimumab, with rates of 33-50% and 7-22% for diarrhoea and colitis respectively (47). Rates were also higher when ICI were used in combination, such as with a tyrosine kinase inhibitor. Histologically, it may appear as acute or chronic active inflammation, or microscopic-colitis-like. There is limited evidence on best therapy, initial supportive management and consideration of withholding ICI is used in mild grade 1 disease, whereas for grade 2 to 4, glucocorticoids are first line, with other options being biologics such as infliximab or vedolizumab, and consideration of FMT or surgery in severe, refractory disease(44). 16 | P a g e CONCLUSION Many types of colitis can be encountered in our practice, other than IBD. Some of these are relatively newly described entities and the data on their diagnosis and treatment are still emerging. There can be overlapping features clinically, endoscopically, and histologically, and while it may be difficult differentiating them, is important in order to successfully treat the underlying cause and improve patient symptoms. 17 | P a g e FIGURES Figure 1 Figure 1: a) & b) Ischaemic colitis on CT and endoscopy with dusky mucosa. c) Single stripe sign of ischaemic colitis. Figure 2 Figure 2: a) C. difficile superimposed on Crohn’s disease. b) Normal appearing colon in patient with chronic watery diarrhoea, ultimately biopsy proven to be microscopic collagenous colitis. c) Mild radiation proctitis. 18 | P a g e REFERENCES 1. Reggiani Bonetti L, Leoncini G, Daperno M, Principi MB, Baronchelli C, Manenti S, et al. Histopathology of non-IBD colitis practical recommendations from pathologists of IG-IBD Group. Dig Liver Dis. 2021;53(8):950-7. 2. Czepiel J, Dróżdż M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A, et al. Clostridium difficile infection: review. 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