Winter 2018

DR RODERICK ROBERTS DR WILLIAM ROBINSON DR NEVILLE SANDFORD DR MICHAEL MIROS newsletter the insider DR HUGH SPALDING ur Mission at GastroIntestinal Endoscopy is to de O liver experienced and accessible endoscopy services with the highest quality of healthcare standards to improve the health outcomes of patients and the c ommunities we serve.

GIE operates an Open Access Endoscopy Service from four locations: • SUNNYBANK – Brisbane Endoscopy Services • EVERTON PARK – North West Private Hospital • CHERMSIDE – Chermside Day Hospital • AUCHENFLOWER – The Wesley Hospital

Diagnosis and management of Microscopic Dr Mostafa Seleem Summary There are two subtypes of microscopic colitis: of the subepithelial collagen plate. Microscopic colitis (MC) is a clinical • (LC): LC and CC have been suggested to syndrome of unknown aetiology, Lymphocytic colitis is characterized by represent different phases of a single characterized by chronic watery an intraepithelial lymphocytic infiltrate pathophysiologic process, with LC possibly in the absence of macroscopic changes (>20 per high power field). being a precursor or earlier phase of CC, in the large bowel. Its prevalence appears • (CC): however, this has not been proven. to be increasing, and it is included more Collagenous colitis is characterized by No definite aetiology has been determined often in the of colonic subepithelial collagen band for microscopic colitis. Certain drugs watery diarrhoea. Microscopic colitis >10 micrometers in thickness. may trigger or exacerbate diarrhea. The is diagnosed in up to 15% of patients high risk drugs include PPIs, nonsteroidal undergoing for chronic Epidemiology anti-inflammatory drugs (NSAIDs) diarrhoeai. The disease typically The general trend of MC diagnosis is and SSRIs. Cigarette smoking (past or occurs in middle aged patients with increasing. The estimated incidence of present) is associated with a significantly vi female preponderanceii. Currently, collagenous colitis and lymphocytic colitis increased risk of microscopic colitis . Also, is the only evidence-based are 1.1 to 5.2 and 3.1 to 5.5 per 100,000 autoimmune diseases including coeliac effective therapy. However, despite per year, respectivelyiii. The mean age disease, type 1 diabetes or autoimmune vii the progress of knowledge, still many at diagnosis of microscopic colitis is 65 thyroiditis, may be associated with MC . questions remain unsolved regarding the years. However, approximately 25 percent aetiology, pathophysiology, and optimal of patients with microscopic colitis are management of MC. diagnosed before the age of 45 years. Although microscopic colitis has been reported in children, it is rare. Microscopic colitis has a female preponderance, which appears to be more pronounced in 1 Microscopic collagenous (F:M :: 15:1) compared with Colitis lymphocytic colitis (F:M :: 3:1)iv. 3 Duodenal Pathophysiology and risk factors Intraepithelial The pathophysiology of MC is not fully Lymphocytosis understood. However, several studies have

IN THIS ISSUE 4 Recognizing suggested the involvement of an impaired GIE Staff or dysregulated immune response, possibly to a yet-to-be-identified luminal antigenv. The characteristic feature of LC is an infiltration by lymphocytes into the colonic PH: 1300 4 GASTRO . CC shares this feature but www.gastros.com.au additionally shows a distinctive thickening Continued on page 2

GASTROINTESTINAL ENDOSCOPY PTY LTD the insider PAGE 1 Continued from page 1 Diagnosis and management of Microscopic Colitis

Clinical presentation reducing to 3 mg daily for The clinical presentations of LC and CC are similar, and the diseases two weeks. Randomized cannot be distinguished on clinical grounds. Both disorders cause trials in patients chronic or recurrent watery diarrhea, often associated with urgency with collagenous (70%), nocturnal diarrhea (50%), (50%), and weight colitis suggest that loss. The diarrhea can be severe, causing faecal incontinence, budesonide is especially in the elderly. The onset of disease may be sudden, effective for short- mimicking an enteric infection. Severe complications are infrequent, term treatment and although a few cases of colonic perforations in CC have been can improve quality reported, either spontaneous or after colonoscopy. of life. No increased risk of has been reported in MC. The clinical symptoms may be misinterpreted as irritable bowel A meta-analysis of syndrome (IBS) and studies show that there is symptomatic overlap eight randomized trials between MC and IBS. Fatigue is reported in 50%–60% of patients. found that short-term clinical Concomitant bile-acid has been reported in 9%–60% response rates were significantly of patients with LC and in 27%–44% of patients with CC. higher with budesonide, compared with placeboxii. There is limited These findings are the basis for recommendations on treatment evidence from small case series that in patients with refractory with bile acid-binding therapy in MC. Extra-intestinal symptoms, microscopic colitis, anti-tumour necrosis factor (TNF) therapy (eg, viii such as arthralgia, , or uveitis, can rarely occur . infliximab adalimumab) or immunomodulators (6-mercaptopurine Diagnostic evaluation or azathioprine) can induce remission. Surgery has been used in xiii To establish the diagnosis of microscopic colitis, other causes of refractory cases that fail to respond to all medical therapy . diarrhoea should be initially excluded. Conclusion Laboratory studies Microscopic colitis is a common cause of chronic watery diarrhea, Stool studies should include stool Clostridium difficile toxin whose epidemiological impact has grown in recent years. Colonic and routine stool cultures (Salmonella, Shigella, Campylobacter, are required for the definitive diagnosis, and for the Yersinia). In addition, Coeliac serology and a full blood count, histological characterisation of the two subtypes of the disease (CC electrolytes, and albumin, as patients with microscopic colitis may and LC). A series of new pharmacological agents for the treatment have mild anaemia and, in rare cases, a protein-losing . of MC has been proposed. The role of oral budesonide is well Endoscopy and established. One of the issues in managing MC is the low attention As patients with MC usually have a macroscopically normal colon, paid to its diagnosis and treatment from the general community colonoscopy is important to exclude inflammatory bowel disease and all patients with chronic watery diarrhoea should be referred and also to take colonic biopsiesix. Sometimes nonspecific findings to gastroenterologists for further assessment and colonoscopy including slight oedema, erythema, and friability may be seen. for diagnosis. The disease concept is expanding to include Biopsies should be obtained from the right side of the colon as analogous diseases not only in the colon, but also in the stomach the severity of histologic changes declines from the proximal to or small intestinexiv. Thus, we should be aware that ‘‘microscopic’’ the distal colon. Collagenous colitis can be patchy, with normal may possibly appear in any part of the mucosa being found mainly in specimens from the rectosigmoid. . Rectosigmoid biopsies alone would miss the diagnosis of collagenous colitis in up to 40 percent of casesx. While colonoscopy References is generally safe in patients with microscopic colitis, perforations i Ianiro G et al. World J Gastroenterol 2012; vol 18(43). have been described in patients with significant collagen deposits ii Veress B et al. Department of Pathology 1995; vol 36(6). xi (“fractured colon”) . iii Bohr J et al. Gut 1995; vol 37(3). Treatment iv Bonderup O et al. Scand J Gastroenterol 2015; vol 50(4). v Ja ̈rnerot G et al. 1995; vol 109. A number of medical treatments have been attempted in patients with MC. Patients should be advised to avoid triggering factors vi Beaugerie L,et al. Aliment Pharmacol Ther 2005; vol 22. such as PPIs, nonsteroidal anti-inflammatory drugs (NSAIDs) and, vii Chande N et al. Scand J Gastroenterol 2005; vol 40. if possible, discontinue associated with microscopic viii Hjortswang H et al. Inflamm Bowel Dis 2009; vol 15. colitis. The use of traditional antidiarrheal agents (such as ix Ferna ́ndez-Ban ̃ares F et al. Aliment Pharmacol Ther 2016; vol 43. ) as first-line medical therapy can result in improvement x Carpenter H et al. Dig Dis Sci 1992; vol 37(12). in a third of patients. In patients with active disease (≥3 stools daily xi Allende D et al. Am J Gastroenterol 2008; vol 103(10). or ≥1 watery stool daily) or diarrhea that persists despite the use xii Stewart M et al. Clin Gastroenterol Hepatol 2011; vol 9(10). of antidiarrheals, it is recommended to add budesonide 9 mg daily xiii Esteve M et al. J Crohns Colitis 2011; vol 5. for four weeks followed by 6 mg daily for two weeks, and then xiv Miehlke S et al. Gastroenterology 2009; vol 136.

GASTROINTESTINAL ENDOSCOPY PTY LTD the insider PAGE 2 Duodenal Intraepithelial Lymphocytosis – what to do? Dr Hugh Spalding Intraepithelial lymphocytes (mostly Some have suggested that DIL be included • Microscopic colitis CD3 +ve T cells) are in the front line in the diagnoses of microscopic . • Crohn’s disease of immune defences, but finding >25 lymphocytes per 100 duodenal Reported associations include: Celiac disease and DIL epithelial cells is considered to be • Celiac disease In the absence of architectural abnormal. • Non-gluten food hypersensitivity abnormalities (crypt hyperplasia or villous Duodenal intraepithelial lymphocytosis (e.g. nuts, cow’s milk) atrophy) and only in patients with proven (DIL) in architecturally normal duodenal • Infection (viral enteritis, H. pylori, gluten sensitivity, DIL corresponds to epithelium occurs in about 2% of duodenal Giardia, Cryptosporidium) a Marsh Class 1 enteropathy. It is the biopsies, although some studies have • Small intestinal bacterial overgrowth earliest histological manifestation of celiac reported a significantly higher rate. The • disease and it can persist on a gluten mean age of patients is around 50 years, • Non-steroidal anti-inflammatory drugs free diet. Unfortunately there are no with a female preponderance (73%). including aspirin reliable histological features to distinguish Marsh 1 lesions from other causes of DIL The causes of DIL include reaction to • Proton pump inhibitors an ingested or endogenous antigen or and gastrointestinal symptoms are also • Angiotensin receptor blockers (“sartan autoimmune reactions, however up to one- similar. Around one-quarter to one-third enteropathy” particularly olmesartan) third or more of cases remain idiopathic. of patients with DIL who are initially • Azathioprine, mycophenolate, Duodenal intraepithelial lymphocytosis considered negative for celiac disease may methotrexate is a non-specific and relatively common subsequently have this diagnosis made, • Immunological disorders (immune finding which appears to be on the and the intensity of lymphocytosis appears thyroiditis, psoriasis, systemic increase; tripling in one American study to be predictive of the riskii, iii. over a 10 year periodi. The reasons for lupus erythematosus, graft vs host this increase are likely multifactorial, but disease, common variable immune References probably include increasing use of NSAIDs. deficiency, IgA deficiency, multiple i Schmidt E et al. Gastrointestinal Endoscopy Drug related enteropathy typically occurs sclerosis, rheumatoid arthritis, 2014; vol 80 (1). months to years after commencement of glomerulonephritis) ii Parihar V et al. Digestion 2017; vol 95 (4). the and discontinuation usually • Autoimmune enteropathy iii Losurdo G et al. World Journal of leads to resolution. • Gastroenterology 2015; vol 21 (24).

An approach to management of patients with Duodenal Intraepithelial Lymphocytosis Dr Hugh Spalding A reasonable approach to the incidental finding of DIL in an asymptomatic patient would be to take a guided history, exclude malabsorption (iron studies, B12, folate) and exclude H. pylori infection. Look for dermatitis herpetiformis and check celiac antibodies, which if positive essentially confirms the diagnosis of celiac disease. In the absence of symptoms, given the wide number of associated conditions, there is probably not enough known about the risk progression of drug associated isolated DIL into a more serious enteropathy to warrant modifying medications. However these patients should be more closely monitored given the potential for serious enteropathy and malabsorption even in the absence of villous atrophy. The presence of symptoms may highlight the need for further investigation (e.g. thyroid function, autoantibodies, celiac gene testing, stool culture and antigen testing, colonoscopy) and potentially withdrawal of drugs known to be associated with DIL. HLA testing is only useful if negative; >99% of patients with celiac disease will have HLA DQ 8 or DQ2, but only 1 in 30 people with these genotypes develop celiac disease. Repeat duodenal biopsy after 6 months of a normal (gluten- containing) diet is sensible. Most biopsies normalise, suggesting a viral cause. If DIL is still present then celiac disease becomes a strong possibility.

GASTROINTESTINAL ENDOSCOPY PTY LTD the insider PAGE 3 Recognising our staff Last month GastroIntestinal Endoscopy observed Administrative Professionals’ Day on the 4th of May, and International Nurses Day on the 12th of May. Our friendly and efficient reception, bookings and administrative staff are a vital part of GastroIntestinal Endoscopy, and are highly valued for the important support they give to our patients, gastroenterologists and nurses. Our team of experienced and professional registered nurses provide quality advice and specialized care to our patients and their families, at their prep appointment and on the day of the procedure. GastroIntestinal Endoscopy appreciate the hard work and dedication of our staff, and were pleased to acknowledge the contributions they Some of our wonderful administrative and nursing staff receiving their make on these days of recognition. gifts of appreciation.

If you require A5 referral pads, please contact one of o ur four locations below. l templates ca Electronic referra n be downloaded from our website www.gastros.com.au

Private practice locations and contact details GIE practice locations and contact details DR RODERICK ROBERTS MBBS FRACP AGAF For all appointments, call 1300 4 GASTRO (1300 4 427876) Main Rooms: Level 2, Suite 62, Ballow Chambers 121 Wickham Tce, Brisbane QLD 4000 Brisbane Endoscopy The Wesley Hospital Phone: 3831 2704 | Fax: 3835 1069 Services Endoscopy Unit, 451 Coronation Drive, DR WILLIAM ROBINSON MBBS FRACP Suites 16–18, Auchenflower QLD 4066 Open access endoscopy procedures only McCullough Centre, Phone: 07 3870 3799 Phone: 1300 442 787 259 McCullough Street, Fax: 07 3870 5069 DR NEVILLE SANDFORD Sunnybank QLD 4109 BSc (Med) MBBS (1st Class Hons) FRACP AGAF Phone: 07 3344 1844 North West Private Hospital Open access endoscopy procedures only Endoscopy Unit, 137 Flockton Street, Fax: 07 3344 2739 Phone: 1300 442 787 Everton Park QLD 4053 DR MICHAEL MIROS Phone: 07 3353 3322 MBBS (1st Class Hons Qld) FRACP Chermside Day Hospital Fax: 07 3353 9325 Main Rooms: 66 Bryants Rd, Level 1, Loganholme QLD 4129 Chermside Medical Complex, Phone: 3801 2233 | Fax: 3801 5212 Head Office 956 Gympie Road, Unit 6, 504 Lutwyche Rd, DR HUGH SPALDING MBBS FRACP BVSc PhD Chermside QLD 4032 Lutwyche QLD 4030 Main Rooms: 66 Bryants Road Loganholme QLD 4129 Phone: 07 3120 3407 Phone: (07) 3169 0146 Phone: 3801 2233 | Fax: 3801 5212 Fax: 07 3120 3443 Fax: (07) 3177 9965

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