1. GI for ISCEs Lorna Roden

2. What we’re covering… 0 History and examination 0 3 cases – differentials, investigations and management 0 Common ‘lists’ of differentials

3. Mrs Gladys Brown is a 69-year-old retired lawyer. She has been referred to your outpatient clinic complaining of tiredness and loss of energy. She initially thought this was due to looking after her grandchildren twice a week, but since stopping this the symptoms have persisted. She describes loose bowel motions for the last few months and has lost 12.5kg in weight

4. What questions should you ask? 0 Fatigue/ tiredness – duration of symptoms, relationship to work, preceding infection, intense exertion, stressful life events 0 Loose stool – colour, consistency, odour 0 Presence of blood mixed in with or separate to stool 0 Tenesmus (feeling of incomplete evacuation of stool) 0 Weight loss – intentional or unintentional 0 Abdo pain/discomfort – SOCRATES 0 Bloating, distension and excessive passing of flatus – malabsorption 0 Heartburn and reflux – upper GI 0 Systemic features – recurrent mouth ulcers, arthritis, rash 0 Medications – recent changes 0 Recent travel abroad – Giardia causes chronic diarrhoea 0 Smoking – negative impact in Crohn’s disease but affords protection in UC 0 Alcohol – pancreatic insufficiency as a result of misuse 0 Diet - intolerance 0 HIV-risk – health-compromising behaviours 0 Family history – inflammatory bowel or colorectal cancer

5. Describe these dermatological signs 0 Dermaitits herpetiformus – intensely itchy on the elbows/buttocks and associated with coeliac disease 0 Errythema nodosum – tender, palpable, erythematous nodules on the shins associated with inflammatory bowel disease

6. History Mrs Brown has been tired and lethargic for the last month She describes a 6 month history of watery loose stools, up to 3 times per day, associated with bloating and flatulence. There is no blood. She has had abdominal cramps intermittently for the last few years on most days. She has lost 12.5 kg in weight over 6 months unintentionally. She suffers from mouth ulcers every winter but not regularly. There have been no new rashes or additional symptoms. She takes aspirin, lisinopril and levothyroxine and beclometasone and salbutamol inhalers and is compliant with these. She is retired, drinks 2 units of alcohol per month and has never smoked. There is no recent travel history and no relevant family history.

7. Malabsorption and malnutrition Iron deficiency

8. Angular stomatitis Corneal Arcus Ileostomy Colostomy

9. Signs of chronic liver disease 0 Hepatomegaly 0 Jaundice 0 Ascites 0 Circulatory changes – spider telangiectasia, palmar errythema 0 Endocrine – loss of libido, hair loss, gyanecomastia, testicular atrophy, impotence, irregular menses, ammenorrhoea 0 Haemorrhagic tendency – bruises, purpura, epistaxis 0 Portal hypertension – splenomegaly, colateral vessels, variceal bleeding, fetor hepaticus 0 Hepatic encepahlopathy 0 Pigmentation, leukonychia

10. Causes of hepato-splenomegaly Hepatomegaly Splenomegaly 0 Parenchymal liver disease 0 Alcoholic liver disease 0 Autoimmune hepatitis 0 Viral hepatitis 0 Primary biliary cirrhosis 0 Malignancy 0 Primary HCC 0 Secondary metastatic cancer 0 Right heart failure 0 Haematological disorders 0 Lymphoma 0 Leukaemia 0 Myelofibrosis 0 Polycythaemia 0 Rare 0 Amyloidosis 0 Budd-chiari syndrome 0 Haematological 0 Lymphoma 0 Leukaemia (CML) 0 Myelofibrosis 0 Polycythaemia 0 Haemolytic anaemia 0 Portal hypertension 0 Infections 0 Glandular fever 0 Malaria 0 Brucellosis 0 Leishmaniasis 0 Subacute bacterial endocarditis 0 Rheumatological 0 RA (Felty’s Syndrome) 0 SLE 0 Rare 0 Sarcoidosis 0 Amyloidosis

11. Examination Examination reveals angular stomatitis and a few mouth ulcers. The abdominal examination was unremarkable with no palpable organomegaly or mass. The DRE was normal with good anal tone and no masses.

12. What is the differential diagnosis? 0 Coeliac disease 0 Chronic pancreatitis and pancreatic insufficiency 0 Thyrotoxicosis 0 Colorectal cancer 0 IBD 0 Microscopic colitis

13. Coeliac disease 0 Immune-mediated disorder resulting in small intestinal villous atrophy which resolves on gluten withdrawal from the diet 0 Main toxic component of gluten is α-gliadin 0 Causes a T-cell mediated inflammatory response 0 Anti-tissue tranglutaminase (anti-TTG) antibody, anti-gliadin antibody 0 Peaks in 3 rd decade Clinical features 0 Children: abdominal pain, anaemia, short stature, delayed puberty 0 Adults: abdominal bloating, lethargy, weakness, diarrhoea or constipation, iron-deficiency anaemia, malabsorption, oral ulcers 0 Associations 0 Dermatitis herpetiformus 0 Small bowel lymphoma

14. Investigations? AIMS: Confirm diagnosis, look for consequences, supportive factors 0 Confirm diagnosis 0 Duodenal biopsy - GOLD STANDARD – villous atrophy and crypt hyperplasia and intraepithelial lymphocytosis 0 IGA antibodies to tissue transglutaminase (TTG), endomysial and gliadin antigen – used to MONITOR treatment response 0 Consequences 0 FBC 0 Haematinics (low folate, B12, iron status) 0 Clotting screen (Vit K) 0 Bone investigation (low Ca2+, Vit D, albumin; osteopenia on DEXA scan) 0 BMI 0 Supportive factors 0 Liver enzymes (sometimes raised transamminases) 0 Intestinal permeability (increased) 0 Faecal fat (increased)

15. Management? 0 Life-long gluten-free diet 0 Correct deficiencies 0 Aggressive management of any bone disease 0 If patient remains refractory: 0 Check compliance with diet 0 Consider additional diagnosis (giardiasis, lactase deficiency) 0 Consider complications (small intestinal bacterial overgrowth, small intestine T-cell lymphoma)

16. CASE 3 Emma Ritchie is a 24 year old secretary. She has suffered with increased frequency of bowel opening, up to 5 times a day, abdominal pain and feeling generally unwell for the last 6 months.

17. Bowel habit? 0 How has it changed? 0 What is ‘normal’ for you? 0 Nature of the stool? 0 Unusual contents of stool (watery, blood-stained, mucous? 0 Colour change? 0 Odour change? 0 Urgency?

18. Poo! Pale, oily, malodorous and difficult to flush Watery and liquid; high frequency Black, tarry and malodorous Malabsorption of fat Bacterial overgrowth or microscopic colitis Upper GI bleeding

19. Differentials? 0 Crohn’s disease 0 Ulcerative colitis 0 Chronic parasitic infection i.e. giardiasis 0 Irritable bowel syndrome 0 Coeliac disease 0 Chronic pancreatitis Weight loss, anaemia and sustained ill health can rule this out Travel history Alcohol history and family history

20. Differentials for chronic diarrhoea and malabsorption? 0 Coeliac disease 0 Tropical sprue 0 Parasitic infections 0 Immunodeficiency syndromes 0 Crohn’s disease 0 Whipple’s disease 0 Irritable bowel syndrome 0 Inflammatory bowel disease 0 Microscopic colitis

21. Inflammatory bowel disease UCCrohns Area affectedColon onlyMouth to anus DistributionContinuousSkip lesions Histologic features Mucosa/submucosa, crypt abscesses, superficial ulcers Transmural granulomas, apthoid ulcer Macroscopic features Mucosal friability, pseudopolyps, loss of haustra (chronic) Cobblestoning, fistulas, fissures SymptomsRectal bleeding; Diarrhoea – often bloody, abdominal pain, weight loss Abdominal pain, diarrhoea, fever, weight loss, fistulas PresentationDiarrhoea + malaiseDiarrhoea, malaise + abdominal pain

22. Extra-intestinal features of inflammatory bowel disease 0 Most common: arthritis (10-35%) 0 Occur at roughly the same rates in Crohn’s and UC 0 These features are either related to disease activity or not What extra-intestinal features can you think of? Arthritis is more common in Crohn’s than in UC

23. Extra-intestinal features related to disease activity 0 Pauci-articular arthritis <5 joints Asymmetric Acute and self-limitting (weeks rather than months) 0 Errythema nodosum Tender, red or violet subcutaneous nodules 0 Apthous ulcers Painful, clearly defined round or ovoid, shallow ulcers of the smooth surfaces of the mouth and underside of the tongue 0 Episcleritis Red eye with injected sclera and conjunctiva, ± pain 0 Metabolic bone disease Osteo –penia/-porosis/-malacia Occurs in 30% 0 Thromboembolism and UC Hospitalisation, malnutrition and immobilisation contribute Platelets can also be high (acute phase reaction)

24. Extra-intestinal features not related to disease activity 0 Axial arthritis Sacroiliac and spine Pain in buttocks and back 0 Polyarticular arthritis Symmetrical Persistent Damaging to affected joints 0 Pyoderma gangrenosum Errythematous papules develop into deep ulcers containing sterile pus Occurs on the shins most commonly Sometimes where there has been previous trauma 0 Uveitis (irits) Bilateral, insidious onset Painful red eye, injected conjunctiva, blurred vision, photophobia, headaches REFER URGENTLY any patients with occular pain, redness and visual disturbance 0 Hepatobiliary conditions Primary sclerosing cholangitis (PSC), cholangitis, pericholangitis, steatosis, chronic hepatitis, cirrhosis, gallstones May be a complication or an adverse effect of drugs Present as incidental finding PBC is more common in UC 0 Rare: bronchiectasis, bronchitis, hyperhomocysteinaemia, pancreatitis, renal stones

25. Complications Crohn’s disease 0 Perforation 0 Abscess 0 Fistulae 0 Obstruction 0 Malabsorption 0 Low bile salt reabsorption 0 Malnutrition 0 Bacterial overgrowth Active small bowel disease/extensive small bowel resection Deficiencies? Iron, folate, B12, fat-soluble vitamins (ADEK) Complications? Osteoporosis, anaemia Predilection of Crohn’s for the ileum – bile salts spill into the colon and cause bile-salt induced diarrhoea Further disease/resection? Fat maldigestion and steatorrhoea This leads to predilection for renal calculi – calcium readily binds unabsorbed fatty acids, allowing oxalate to be taken up by the bowel in greater quantity Result from disease itself or the treatments given… From extensive resection UC 0 Colorectal cancer Risk factors? Duration, extent of disease, severity of inflammation, family history of CRC, concomittant PSC

26. Examination of the patient with IBD Now that you know the features, extra-colonic features and complications of the disease what would you examine in the ISCE station if you suspected IBD?

27. Investigation 0 Initial presentation – DIAGNOSIS is with history + histology + imaging 0 Bloods FBC – anaemia, raised platelets (surrogate sign of inflammation) WCC – infection Electrolytes – diarrhoea Liver chemistry – complications i.e. PSC (liver switches out of making albumin and makes inflammatory mediators like CRP) CRP – elevated in inflammatory conditions Haematinics – iron, folate, B12 Calcium, magnesium and zinc – malabsorption, important for wound healing Autoantibodies – gliadin peptides to rule out coeliac disease 0 Imaging Endoscopy (Crohn’s) – mucosal biopsy and balloon dilation Colonoscopy (UC) – to determine extent of disease CT and barium studies US – useful for detecting thickened bowel, abscess and fistulae 0 Special Examination of the stool - macroscopic, microscopic and culture (to exclude infective diarrhoea) 0 Chronic disease investigation 0 Assess disease activity – simple markers of inflammatory activity (CRP). ‘Activity Indices’ – Crohn’s Disease Activity Index 0 Complications – AXR, bloods, stool cultures 0 Severe colitis – recognize early

28. Management? 0 GOALS: 0 Relief of clinical symptoms 0 Medical therapy is a 3-pronged approach… 0 Remission from symptoms of active disease 0 Maintaining remission 0 Preventing complications 0 Also consider – RISK vs BENEFIT of toxic treatments For both UC and Crohn’s suggest an MDT approach Dietician Surgeons Physicians Psychological support

29. Management – Crohn’s 0 Pharmacological therapies 0 5-Aminosalicylates (5-ASA) – do not alter disease course, favourable ‘safety profile’, used more commonly for UC 0 Antibiotics – Ciprofloxacin and metronidazole, study data varies 0 Corticosteroids – achieve remission but don’t sustain it, PO Prednisolone for most, IV methylprednisolone for those with poor absorptive states, side-effect profile if used long term is poor, can cause non-healing fistulae 0 Thiopurines (azathioprine and 6-mercaptopurine) – purine analogues, immunosuppressive agents, achieve and maintain remission 0 Methotrexate – can achieve remission and maintain it, not for women of childbearing age 0 Anti-TNF agents (infliximab, adalimumab) – anti-TNF (pro- inflammatory cytokine important in Crohns) 0 Surgical management – 75% of patients will have surgery within 20 years of diagnosis 0 Needed to address: stricturing, penetrating or fistulating disease 0 Recurrence at anastomotic sites is common – surgery not recommended as a primary treatment Skin/soft tissue Cushingoid appearance Abdominal striae Acne Hirsutism Oedema Psychiatric Sleep disturbance/activation Mood disturbance Psychosis Neurologic Neuropathy Pseudomotor cerebri MSK Osteoporosis Asceptic necrosis of bone Myopathy Endocrine Diabetes mellitus Adrenal cortex suppression Immunologic Lymphocytopenia Immunosuppression False-negative skin test CV Hypertension Opthalmic Cataract Narrow-angle glaucoma Developmental Growth retardation Complications? Infection – especially TB (screen for this prior to administration), Hep B ↑ risk of lymphoma

30. Management - UC 0 Pharmacological therapies 0 5-ASA – mainstay of treatment, sulfazalazine is main drug in this class, SE’s: Nausea, vomitting, dyspepsia, headache, malaise, achieve and maintains remission, ask about adherence as 3-4 doses/day are required 0 Corticosteroids – achieve remission but do not maintain it, heavy SE profile 0 Thiopurines – not as good in UC as in Crohn’s 0 Infliximab 0 Cyclosporine – calcineurin inhibitor, last-line in hospitalised patients, induces short-term response 0 Surgical management 0 Offers a THERAPEUTIC option 0 Colectomy with ileo-anal pouch formation – removes diseased tissue and the need for further medical therapy 0 Indications: severe disease, disease refractory to medical therapy, complications of a severe attack (perforation, acute colonic dilation), colitis associated dysplasia/malignancy, impaired quality of life (unacceptable symptoms despite maximal therapy) 0 Surveillance of complications 0 Colorectal carcinoma → colonoscopies with biopsies every 2 years initially (every year if +PBC/long-standing disease) ACUTE COLITIS IV steroids Ciclosporin for disease not responding to steroids “random 4- quadrant biopsies every 10cm throughout the colon”

32. CASE 4 Betty Smith is a 45 year-old teacher who presents to her GP with itching for a few years that has gradually got worse. Her neighbour has also noticed a yellow tinge to her eyes. She has a past medical history of hypothyroidism. On examination the sclera are yellow and her chest and abdomen are mildly excoriated.

33. Differentials 0 Primary Biliary Cirrhosis 0 Autoimmune hepatitis 0 Iron deficiency 0 Hypothyroidism

34. PBC 0 Chronic 0 Progressive destruction of small bile ducts eventually leading to cirrhosis 0 Women (90%), 40-50 years old 0 Thought to be an immunological mechanism involved 0 Serum anti-mitochrondrial antibodies (AMA) present 0 E. Coli 0 Clinical features 0 Incidental finding - ↑ALP, AMA autoantibodies 0 Pruritis precedes jaundice by years 0 Fatigue 0 Hepatomegaly 0 Associations – autoimmune disorders occur with more frequency 0 Sjogrens 0 Scleroderma 0 Thyroid disease 0 Renal tubular acidosis, membranous glomerulonephritis, coeliac disease, interstitial pneumonitis 0 Chronic 0 Cholestatic liver disease characterised by fibrosing inflammatory destruction of both intra- and extra-hepatic bile ducts 0 Men (70%), 40 years old 0 Thought to be an immune-mediated 0 Serum pANCA in 60% 0 Clinical features 0 Incidental finding - ↑ALP 0 Fluctuating pruritis 0 Jaundice 0 Cholangitis 0 Associations – with ulcerative colitis in 75% of cases PSC

36. Investigations? 0 Bloods 0 Mitochondrial antibodies – measured by ELISA 0 Liver profile – ALP raised, no others 0 Serum cholesterol – raised 0 Imaging 0 US – diffuse alteration in liver architecture 0 MRCP 0 Biopsy – portal tract infiltrate, granulomas, loss of small bile ducts

37. Management? 0 Pharmacological 0 Ursodeoxycholic acid – improves bilirubin and aminotransferase levels, does not improve prognosis 0 Supplementation of fat-soluble vitamins (ADEK) 0 Cholestyramine – for pruritis 0 Complications – cirrhosis 0 PSC – the only proven treatment is liver transplantation