Inflammatory Bowel Disease Flashcards
Crohn’s Disease - Mx
Crohn’s disease is a form of inflammatory bowel disease. It commonly affects the terminal ileum and colon but may be seen anywhere from the mouth to anus. NICE published guidelines on the management of Crohn’s disease in 2012.
General points
patients should be strongly advised to stop smoking
some studies suggest an increased risk of relapse secondary to NSAIDs and the combined oral contraceptive pill but the evidence is patchy
Crohn’s Disease - Inducing Remission
Inducing remission
Glucocorticoids (oral, topical or intravenous) are generally used to induce remission. Budesonide is an alternative in a subgroup of patients
Enteral feeding with an elemental diet may be used in addition to or instead of other measures to induce remission, particularly if there is concern regarding the side-effects of steroids (for example in young children)
5-ASA drugs (e.g. mesalazine) are used second-line to glucocorticoids but are not as effective
Once remission is obtained then a thiopurine such as azathioprine or mercaptopurine is first line treatment to maintain remission. Methotrexate is an alternative agent but tends to be less well tolerated than thiopurines.
Azathioprine or mercaptopurine* may be used as an add-on medication to induce remission but is not used as monotherapy. Methotrexate is an alternative to azathioprine
Infliximab is useful in refractory disease and fistulating Crohn’s. Patients typically continue on azathioprine or methotrexate
Metronidazole is often used for isolated peri-anal disease
*assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine
Crohn’s Disease - Maintaining Remission
Maintaining remission
as above, stopping smoking is a priority (remember: smoking makes Crohn’s worse, but may help ulcerative colitis)
azathioprine or mercaptopurine is used first-line to maintain remission
methotrexate is used second-line
5-ASA drugs (e.g. mesalazine) should be considered if a patient has had previous surgery
Crohn’s Disease - Surgery
Surgery
around 80% of patients with Crohn’s disease will eventually have surgery
Surgical interventions in Crohn’s disease
The commonest disease pattern in Crohn’s is stricturing terminal ileal disease and this often culminates in an ileocaecal resection. Other procedures performed include segmental small bowel resections and stricturoplasty. Colonic involvement in patients with Crohn’s is not common and, where found, distribution is often segmental. However, despite this distribution segmental resections of the colon in patients with Crohn’s disease are generally not advocated because the recurrence rate in the remaining colon is extremely high, as a result, the standard options of colonic surgery in Crohn’s patients are generally; sub total colectomy, panproctocolectomy and staged sub total colectomy and proctectomy. Restorative procedures such as ileoanal pouch have no role in therapy.
Crohn’s disease is notorious for the developmental of intestinal fistulae; these may form between the rectum and skin (perianal) or the small bowel and skin. Fistulation between loops of bowel may also occur and result in bacterial overgrowth and malabsorption. Management of enterocutaneous fistulae involves controlling sepsis, optimising nutrition, imaging the disease and planning definitive surgical management.
*assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine
Aminosalicylate Drugs
Aminosalicylate drugs
5-aminosalicyclic acid (5-ASA) is released in the colon and is not absorbed. It acts locally as an anti-inflammatory. The mechanism of action is not fully understood but 5-ASA may inhibit prostaglandin synthesis
Sulphasalazine
a combination of sulphapyridine (a sulphonamide) and 5-ASA
many side-effects are due to the sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia
other side-effects are common to 5-ASA drugs (see mesalazine)
Mesalazine
a delayed release form of 5-ASA
sulphapyridine side-effects seen in patients taking sulphasalazine are avoided
mesalazine is still however associated with side-effects such as GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis
Olsalazine
two molecules of 5-ASA linked by a diazo bond, which is broken by colonic bacteria
*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine
Mesalazine and Acute Pancreatitis - Example Question
A 25-year-old with recently diagnosed ulcerative colitis is started on mesalazine after a recent tapering of high dose steroids. Two weeks later, he develops severe pain in his epigastrium and right upper quadrant. What is the most likely diagnosis?
Hepatitis > Acute pancreatitis Duodenal ulceration Flare in ulcerative colitis Primary sclerosing cholangitis
Gastric side-effects are not uncommon with oral aminosalicylates, including diarrhoea, nausea, vomiting and exacerbation of colitis. In occasional cases, it can cause acute pancreatitis. Pancreatitis is significantly more common as a side-effect with mesalazine than sulfasalazine.
UC and Colorectal Ca
Ulcerative colitis: colorectal cancer
Overview
risk of colorectal cancer is significantly higher than that of the general population although studies report widely varying rates
the increased risk is mainly related to chronic inflammation
worse prognosis than patients without ulcerative colitis (partly due to delayed diagnosis)
lesions may be multifocal
UC - Factors increasing risk of Cancer
Factors increasing risk of cancer disease duration > 10 years patients with pancolitis onset before 15 years old unremitting disease poor compliance to treatment
UC and Colorectal Ca - Colonoscopy Surveillance
Colonoscopy surveillance in inflammatory bowel disease patients should be decided following risk stratification.
In the UK, surveillance colonoscopy is recommended for all patients (excluding those with isolated proctitis alone) starting 10 years after diagnosis.
Lower risk
5 year follow up colonoscopy
Extensive colitis with no active endoscopic/histological inflammation
OR left sided colitis
OR Crohn’s colitis of <50% colon
Intermediate risk
3 year colonoscopy
Extensive colitis with mild active endoscopy/histological inflammation
OR Pancolitis
OR post-inflammatory polyps
OR family history of colorectal cancer in a first degree relative aged 50 or over
Higher risk
1 year follow up colonoscopy
Extensive colitis with moderate/severe active endoscopic/histological inflammation
OR stricture in past 5 years
OR dysplasia in past 5 years declining surgery
OR primary sclerosing cholangitis / transplant for primary sclerosing cholangitis
OR family history of colorectal cancer in first degree relatives aged <50 years
UC and Risk of Colorectal Ca - Example Question
A 25-year-old gentleman presents with bloody diarrhoea, fevers and lower abdominal pain. An initial colonoscopy shows extensive ulceration in his distal colon withs one mild active inflammation. His dad developed colorectal cancer at the age of 52. His gastroenterologist discusses the necessity of colonic surveillance. What is the risk that he will develop colorectal cancer?
Low risk (offer colonoscopy at 5 years) High risk (offer colonoscopy at 1 year) > Intermediate risk (offer colonoscopy at 3 years) Too early to ascertain No risk
In anyone with inflammatory bowel disease, be it Crohn’s or ulcerative colitis, a baseline colonoscopy with chromoscopy and target biopsy is necessary to determine the risk of developing colorectal cancer.
According to NICE guidance on the colonoscopic surveillance of colorectal cancer, this patient fulfils intermediate risk: extensive ulcerative or Crohn’s colitis with mild active inflammation (confirmed endoscopically or histologically) or post-inflammatory polyps or family history of colorectal cancer in a first-degree relative aged 50 or over.
Crohns Surgical Cx - Example Question
A 48-year-old female with a history of Crohn’s disease is admitted to hospital with abdominal pain and distension. This has been getting progressively worse over the past 24 hours.
Her Crohn’s disease is now well controlled with azathioprine. In the past she has had a number of abdominal operations to treat complications including an ileal resection.
An abdominal film is requested:
SEE AXR Caecal Volvulus
What is the most likely diagnosis?
Toxic megacolon Vesicocolonic fistula Faecal loading Intussusception > Caecal volvulus
The x-ray shows a large dilated loop of bowel centrally consistent with caecal volvulus. Adhesions secondary to Crohn’s and previous surgery are a risk factor for caecal volvulus.
Toxic megacolon is seen in ulcerative colitis.
Crohn’s Disease
Crohn’s disease
Crohn’s disease is a form of inflammatory bowel disease. It commonly affects the terminal ileum and colon but may be seen anywhere from the mouth to anus.
Pathology
cause is unknown but there is a strong genetic susceptibility
inflammation occurs in all layers, down to the serosa. This is why patients with Crohn’s are prone to strictures, fistulas and adhesions
Crohn’s Disease - Features
Crohn’s disease typically presents in late adolescence or early adulthood. Features include:
presentation may be non-specific symptoms such as weight loss and lethargy
diarrhoea: the most prominent symptom in adults. Crohn’s colitis may cause bloody diarrhoea
abdominal pain: the most prominent symptom in children
perianal disease: e.g. Skin tags or ulcers
extra-intestinal features are more common in patients with colitis or perianal disease
Extra-intestinal Features of IBD
Questions regarding the ‘extra-intestinal’ features of inflammatory bowel disease are common:
Common to both Crohn’s disease (CD) and Ulcerative colitis (UC)!
Related to disease activity:
Arthritis: pauciarticular (oligoarticular), asymmetric
Erythema nodosum
Episcleritis
Osteoporosis
- Arthritis is the most common extra-intestinal feature in both CD and UC
- Episcleritis is more common in CD
Unrelated to disease activity: Arthritis: polyarticular, symmetric Uveitis Pyoderma gangrenosum Clubbing Primary sclerosing cholangitis - Primary sclerosing cholangitis is much more common in UC - Uveitis is more common in UC
Note that whilst some features are present in both, some are much more common in one of the conditions, for example colorectal cancer in ulcerative colitis
IBD Autoantibodies
Anti-Saccharomyces cerevisiae antibodies are more likely to be positive in Crohn’s disease. Ulcerative colitis patients are more likely to be pANCA positive.
IBD Example Question
A 26-year-old man comes to the outpatient clinic. He describes a 2-month history of weight loss, cramping lower abdominal pain with increasing stool frequency. His stools often have blood and mucus in them and occasionally he passes pure blood with no faeces. He is normally fit and well and takes no regular medications. On examination, he has a low-grade fever at 37.5 and pale. His abdomen is soft but tender across the lower half. His bloods checked by the GP earlier in the week are as follows:
Hb 110 g/l
Platelets 400 * 109/l
WBC 12.0 * 109/l
Neuts 9.0 * 109/l
Na+ 139 mmol/l K+ 4.5 mmol/l Urea 4.0 mmol/l Creatinine 89 µmol/l CRP 60 mg/L (<10)
Bilirubin 8 µmol/l
ALP 78 u/l
ALT 34 u/l
Albumin 36 g/l
Stool cultures sent by the GP are negative.
He is admitted the same day for a flexible sigmoidoscopy which shows mild colitis extending to the mid-descending colon. Biopsies are taken which are show mild colitis but of indeterminate cause.
He is transferred to the ward and started on IV hydrocortisone 100mg QDS and he clinically improves and is started on regular mesalazine. He is found to be positive for anti-Saccharomyces cerevisiae antibodies but negative for pANCA. What is the likely cause of his colitis?
Ulcerative colitis Microscopic colitis C.difficile infection Behcet's disease > Crohn's disease
This patient has Crohn’s disease. Anti-Saccharomyces cerevisiae antibodies are more likely to be positive in Crohn’s disease. Ulcerative colitis patients are more likely to be pANCA positive. The patient has microscopic colitis on flexible sigmoidoscopy excluding microscopic colitis. Behcet’s usually present in Middle Eastern men with oral and genital ulcers, conjunctivitis and colitis.
Mesalazine Monitoring
A 25-year-old man who is normally fit and well presents with a 2-week history of crampy abdominal pain and bloody diarrhoea. A colonoscopy shows erythema and oedema in the distal colon and evidence of proctitis. He is started on mesalazine. What blood test(s) must be done prior to its commencement?
> Renal function and full blood count Thiopurine methyltransferase activity Amylase Hepatitis screen Liver function test and full blood count
Renal function should be monitored before starting an oral aminosalicylate, at 3 months and then annually thereafter. This should be done more often in the presence of renal impairment. Blood disorders can also occur with mesalazine, and patients should be asked to look out for bruising, bleeding, purpura, fever and sore throat.
TPMT levels should only be needed on commencement of mercaptopurine or azathioprine.
Amylase, hepatitis screen and liver function tests are not required in aminosalicylate therapy monitoring.
Reference: British National Formulary
UC - Mx
Ulcerative colitis: management
Treatment can be divided into inducing and maintaining remission. NICE released guidelines on the management of ulcerative colitis in 2013.
The severity of UC is usually classified as being mild, moderate or severe:
mild: < 4 stools/day, only a small amount of blood
moderate: 4-6 stools/day, varying amounts of blood, no systemic upset
severe: >6 bloody stools per day + features of systemic upset (pyrexia, tachycardia, anaemia, raised inflammatory markers)
UC - Inducing Remission
Inducing remission
treatment depends on the extent and severity of disease
rectal (topical) aminosalicylates or steroids: for distal colitis rectal mesalazine has been shown to be superior to rectal steroids and oral aminosalicylates
oral aminosalicylates
oral prednisolone is usually used second-line for patients who fail to respond to aminosalicylates. NICE recommend waiting around 4 weeks before deciding if first-line treatment has failed
severe colitis should be treated in hospital. Intravenous steroids are usually given first-line
UC - Maintaining Remission
Maintaining remission
oral aminosalicylates e.g. mesalazine
azathioprine and mercaptopurine
methotrexate is not recommended for the management of UC (in contrast to Crohn’s disease)
there is some evidence that probiotics may prevent relapse in patients with mild to moderate disease
UC and Infliximab: Example Question
A 19-year-old man presented to the Emergency Department with frequent, bloody diarrhoea. He reported increasing stool frequency over the past two weeks and at presentation was opening his bowels 20 times per day including nocturnal episodes. He also reported feeling increasingly tired and lethargy with some cramping abdominal pains. The patient had no previous past medical history and took no regular medications Past medical history was unremarkable and the patient took no regular medications. He worked as a trainee plumber, drank alcohol moderately and did not smoke.
Examination demonstrated some diffuse lower abdominal tenderness but with no signs of peritonism. Blood tests at presentation demonstrated anaemia (Hb 105 g / dL) and raised inflammatory markers (ESR 85 mm / h). Initial impression was of an acute severe colitis and treatment with intravenous hydrocortisone and oral 5-aminosalicylates was initiated. A limited flexible sigmoidoscopy demonstrated severe proctitis with inflammation extending beyond the limits of the study at the mid-sigmoid colon. Plain film imaging of chest and abdomen was unremarkable.
A summary of the patients observations and investigations at day 4 from presentation is given below.
Stool chart: 12 large volume bloody type 7 stools over previous 24 hours
Blood pressure: 105 / 67 mmHg
Heart rate: 98 beats / min
Respiratory rate: 19 breaths / min
Temperature: 36.5ºC
Haemoglobin 99 g / dL White cell count 15 * 109/l Neutrophils 13.2 * 109/l Platelets 421 * 109/l Urea 6.8 mmol / L Creatinine 87 micromol / L Erythrocyte sedimentation rate 67 mm / h
What is the next step in management?
> Infliximab Azathioprine Colectomy Add topical 5-aminosalicylates Rituximab
The patient is suffering from an acute severe colitis as assessed using the Truelove-Witt criteria with > 5 bloody stools per day, tachycardia, raised ESR and anaemia. Appropriate initial treatment is IV glucocorticoids. Response to glucocorticoid therapy should be assessed after 3-5 days with consideration of rescue therapy with Infliximab (or Ciclosporin) if disease remains severely active.
Meta-analysis has shown a significant effect of infliximab over placebo in moderate-severe disease with a relative risk of remission not being achieved of 0.72 (0.57-0.91).
If Infliximab has not given adequate response at 5-7 days post-treatment then colectomy must be considered. Azathioprine has a role as maintenance therapy in ulcerative colitis once remission has been achieved. Topical 5-aminosalicylates have a key role in the management of mild disease but are unlikely to achieve remission in severe flares. Rituximab is not used as a treatment for ulcerative colitis.
UC and Risk of Colorectal Ca: Example Question
A 36-year-old man was diagnosed with ulcerative colitis 10 years previously. At his initial presentation a course of intravenous hydrocortisone was required to achieve remission. Subsequently, the patients disease has been fairly well controlled with azathioprine, although occasion courses of oral steroids had been required to treat minor flares. The patient had experienced no extra-gastrointestinal manifestations of his disease and had no other past-medical history. Family history included the patients father being diagnosed with sigmoid adenocarcinoma at the age of 67 years.
The patient was referred for routine screening colonoscopy. This demonstrated extensive colitis extending to the hepatic flexure but no active endoscopic inflammation or post-inflammatory polyps. Mapping biopsies were taken with no evidence of histological inflammation.
Prior to the procedure the patient stated his concern regarding his future risk of colorectal cancer due to his ulcerative colitis and expressed his willingness to undergo surveillance colonoscopy at the recommended time interval.
In what time interval should the patient undergo his next surveillance colonoscopy?
1 year 2 years > 3 years 5 years 10 years
A meta-analysis of population-based studies found that patients with ulcerative colitis have approximately double the incidence of colorectal cancer than individuals without the disease. In the UK, surveillance colonoscopy is recommended for all patients (excluding those with isolated proctitis alone) starting 10 years after diagnosis.
The interval of subsequent surveillance colonoscopy depends on risk stratification of the patient. Factors to be considered include the extent of colitis, the presence of endoscopic or histological inflammation, the presence of pseudo-polyps, a history of primary sclerosing cholangitis and family history of colorectal cancer. Patient preference is also a factor to be included in decisions around surveillance.
In this case, the patient has a family history of colorectal cancer in a first-degree relative diagnosed at an age greater than 50 years placing him in the intermediate risk category. A further colonoscopy in three years is therefore appropriate. Those in lower risk and higher risk groups are recommended to have colonoscopies every 5 years and 1 year respectively.
Crohn’s PSC and the risk of Colorectal Ca
Patients with Crohns disease have an increased risk of small bowel and colorectal malignancy (standard incident ratios 40.6 and 1.9 respectively). Surveillance usually begins 10 years after the diagnosis of inflammatory bowel disease with risk stratification to determine frequency of surveillance. The concurrence of Crohns disease and primary sclerosing cholangitis confers greatly increased risk of malignancy with recommendations calling for annual surveillance after diagnosis.
Example Question:
A 45-year-old man with long-standing Crohns disease is reviewed in gastroenterology clinic. Initial diagnosis was 12 years previously when he presented as an emergency due to a perianal fistula and associated abscess. This had necessitated emergency surgery and treatment with intravenous corticosteroids. Once remission had been obtained through use of corticosteroids, azathioprine had been used as an immunomodulating agent to maintain remission. Subsequently, the patients disease had been fairly well controlled with disease flares on average less than every 2 years. When flares occurred they tended to cause the patient severe bouts of bloody diarrhoea. Large bowel endoscopies performed following disease exacerbation tended to show colonic inflammation with multiple biopsies consistent with the original histological diagnosis of Crohns disease.
Two months previously, the patients routine monitoring bloods had demonstrated derangement of liver function tests prompting further investigations (details given below). Following conclusion of these investigations, the patient had been initiated on cholestyramine and vitamin supplementation.
Alanine aminotransferase 45 U / L Alkaline phosphatase 356 U / L Bilirubin 105 micromol / L Albumin 30 g / L ANCA (PR3) Negative ANCA (MPO) Positive Anti-smooth muscle antibody Positive
Endoscopic retrograde cholangio-pancreatogram: multiple intrahepatic bile duct strictures and beading
Following discussion with the patient about his new diagnosis he raised his concerns about his future risk of bowel cancer and whether he would require regular endoscopic surveillance.
What is the appropriate frequency of surveillance colonoscopy for this patient?
Not indicated > Every 1 year Every 3 years Every 5 years Every 10 years
The patients investigation results point to a new diagnosis of primary sclerosing cholangitis, known to be associated with Crohns disease and ulcerative colitis.
Crohn’s Disease and Infliximab: Example Question
A 25-year-old woman is reviewed in gastroenterology clinic six weeks after a recent hospital admission with abdominal symptoms. During the initial admission, the patient had presented with a 6 week history of very frequent bloody diarrhoea, a 10 kg weight loss and intermittent severe abdominal pain. Endoscopy had demonstrated a pan-colitis with histological features consistent with Crohn’s disease. In addition, a CT scan of the abdomen had revealed a localised abscess associated with the proximal colon that had required percutaneous drainage and a course of IV antibiotics.
In addition to the above, the patient had been treated with IV hydrocortisone followed by a reducing course of prednisolone (initially 40 mg daily, tapered over 8 weeks). Steroid treatment had initially given a good response with the patients symptoms markedly improving during her hospital stay. Azathioprine treatment had been initiated prior to discharge in an attempt to maintain remission during wean of oral steroids.
In clinic, the patient reported being concordant with azathioprine therapy. However, she found that when she had reduced her prednisolone dose below 15 mg daily, she had recurrent abdominal pains and frequent bloody diarrhoea (although less severe than at presentation). She had also noted some pain to the left side of her anus when defecating.
Examination of the patients abdomen revealed some lower abdominal tenderness but without features of peritonitis. External examination showed an area of ulceration one centimetre lateral to the anus.
Haemoglobin 95 g / dL Mean cell volume 98 fL White cell count 16.9 x 10>3 / microlitre Neutrophils 12.6 x 10>3 / microlitre Platelets 451 x 10>3 / microlitre Urea 8.0 mmol / L Creatinine 97 micromol / L Sodium 143 mmol / L Potassium 3.9 mmol / L CRP 125 mg / L
What is the appropriate next line treatment to induce remission in this patient?
Colectomy Methotrexate Metronidazole > Infliximab Budesonide
This patient has multiple risk factors for a severe phenotype of Crohn’s disease. In particular, her young age (< 40 years), female sex, the need for steroids to control her first exacerbation, the presence of an intra-abdominal abscess and likely perianal disease are all associated with an aggressive disease course. Another feature of concern not present in this patient is lesions of the upper GI tract.
While having given some improvement, the appropriate initial steroid treatment has failed to induce full remission. In cases with features of a severe phenotype, a rapid step-up to biological therapy is indicated. Infliximab is effective at inducing remission in moderate-to-severe Crohn’s disease compared to placebo (remission rate at four weeks 81 % vs 17 %) and is also an effective treatment of peri-anal disease.
Budesonide is indicated to induce remission in mild-moderate disease confined to the small bowel or proximal colon and is associated with fewer side effects compared to other corticosteroids. Like azathioprine, methotrexate is effective in maintaining but not inducing remission from Crohn’s disease.
Surgery in Crohn’s disease is reserved to treat the consequences of failure of medical therapy only (for example, fistulas, abscesses or strictures). Ileocaecal resection can be first line treatment for discrete terminal ill disease, although anastomotic recurrence remains common. Metronidazole has a role in treating peri-anal Crohn’s disease although would not be sufficient to induce remission in this patient.
Crohn’s - Maintaining Remission: Example Question
A 42-year-old woman attends the gastroenterology clinic for outpatient review approximately one month following a recent admission to hospital. She had presented with a 6 week history of frequent bloody diarrhoea and cramping abdominal pain. In addition, she reported a long-standing tendency to suffer from multiple mouth ulcers. She had lost approximately, 8 kilograms of weight between the onset of diarrhoea and presentation to hospital.
The results of investigations performed during the hospital admission are given below. Following investigation, a short course of intravenous steroids had been given followed by oral prednisolone (initial dose 40 mg daily, slowly tapered over 8 weeks).
The patient reported near complete resolution of her previous symptoms and welcome relief from her oral ulceration. She had regained some of the weight she had previously lost and reported her appetite to be good. A discussion was had with the patient about future therapy and she indicated that she would prefer to consider the initiation of further medication to attempt to maintain her symptom remission.
Stool microscopy: no organisms seen
Stool culture: no organisms grown
Colonoscopy: patchy inflammation with ‘cobblestone’ appearance affecting ascending and transverse colon and terminal ileum
Colonic histology: multiple samples demonstrating signs of chronic transmural inflammation, crypt abscesses and submucosal fibrosis
CT abdomen: no evidence of intra-abdominal collection, structuring or abnormal fistulation
What is the most appropriate medication to maintain disease remission in this patient?
Methotrexate Infliximab Budesonide > Azathioprine Metronidazole
The patients presentation and investigation results are consistent with a new diagnosis of Crohns disease. She appears to have had a good response to initial treatment with corticosteroids, however introduction of an immunomodulating agent to maintain remission and limit steroid exposure is appropriate, especially given the patients risk factors for a severe Crohns disease phenotype (female sex; need for steroids to treat first flare).
Once remission is obtained then a thiopurine such as azathioprine or mercaptopurine is first line treatment to maintain remission. Methotrexate is an alternative agent but tends to be less well tolerated than thiopurines.
Biological therapies such as infliximab are considered to maintain remission only after failure of treatment with the immunomodulating agents above. Budesonide is an oral corticosteroid and is therefore not an appropriate choice for maintenance of remission. Metronidazole has efficacy in perianal Crohns disease only.
IBD and CMV Colitis - Example Question
A 38-year-old man is referred in by his GP with increasing frequency of diarrhoea over the last 4 days. He is a known ulcerative colitis patient who is well managed on azathioprine 200mg OD and mesalazine 2.4mg BD. He last had a flare 2 years ago and has been well in the interim. He is passing up to 10 watery motions a day and is suffering from faecal urgency and nocturnal episodes. He describes cramping left iliac fossa pain. There is no blood or mucus in the stools. On examination, he is febrile at 38.2 degrees celsius. His blood pressure is 120/75 mmHg and his heart rate is 100/min. On examination, he is underweight with a BMI of 18.5 and dehydrated. His abdomen is soft but he is tender in the left iliac fossa. He refuses a PR examination. Respiratory and cardiovascular examinations are normal.
His blood tests show:
Hb 110 g/l Platelets 189 * 109/l WBC 3.8 * 109/l Neutrophils 0.89 * 109/l INR 1.1 (0.9-1.2)
Na+ 136 mmol/l K+ 4.9 mmol/l Urea 8.0 mmol/l Creatinine 100 µmol/l Mag nesium 0.79 mmol/L (0.7-1.0) Calcium 2.4 mmol/L (2.1-2.58) CRP 78 mg/l
Bilirubin 5 µmol/l
ALP 78 u/l
ALT 28 u/l
Albumin 33 g/l
He is started on IV hydrocortisone 100mg QDS and IV fluids. Stool specimens are sent and are reported as negative for C. difficile toxin. He has a flexible sigmoidoscopy the next day which shows widespread left sided colitis. The biopsy results show the presence of inclusion bodies in the colonic mucosa. What is the appropriate treatment to start for this gentleman?
Infliximab > Ganciclovir Metronidazole Fluconazole Tazocin
This patient has CMV colitis. It can be a consequence of immunosuppressive agents such as azathioprine. It can present with fever and diarrhoea +/- blood. It can also present as an exacerbation of IBD patients in those on immunosuppressants. Inclusion bodies are characteristic at biopsy. It will respond well to an antiviral agent and ganciclovir is the treatment necessary here. Tazocin, metronidazole and fluconazole will not treat appropriately and infliximab would only be indicated if a colitis flare was not due to an infective cause.
Crohn’s - Investigation
Crohn’s disease: investigation
Crohn’s disease is a form of inflammatory bowel disease. It commonly affects the terminal ileum and colon but may be seen anywhere from the mouth to anus
Bloods
C-reactive protein correlates well with disease activity
Endoscopy
colonoscopy is the investigation of choice
features suggest of Crohn’s include deep ulcers, skip lesions
Histology
inflammation in all layers from mucosa to serosa
goblet cells
granulomas
Small bowel enema high sensitivity and specificity for examination of the terminal ileum strictures: 'Kantor's string sign' proximal bowel dilation 'rose thorn' ulcers fistulae
UC and Cancer Screening: Example Question
A 29 year old man with ulcerative colitis presents to clinic. His colitis has been relatively well controlled since his diagnosis at 18 years old, with two flare-ups requiring steroids in the last 3 years. He has never needed hospital admission. He is currently in full time employment as an engineer.
He has been taking Pentasa (mesalazine) for two years, which is very well tolerated. On examination, his height is 180cm, and weight 58kg (body mass index 18 kg/m²). His abdomen is soft and non-tender. His last colonoscopy 8 months ago showed no active inflammation and no suspicious areas.
He is anxious as his father died from colorectal cancer in his 60’s. There is no other family history of gastrointestinal disease. How regularly should he have a surveillance colonoscopy?
Yearly > 3 years 2 years 4 years 5 years
Since this patient has a first degree relative with a history of bowel cancer over 50 years old, he would fall into the ‘intermediate category’, and thus require a 3 yearly colonoscopy.
Guidelines: BSG Guidelines for the management of inflammatory bowel disease
Crohns and Smoking - Example Question
A 38-year-old woman comes to the follow up clinic some 6 weeks after a small bowel resection for Crohn’s disease. She is currently prescribed azathioprine and a tapering dose of corticosteroids. She smokes 10 cigarettes per day and endeavours to eat a normal diet.On examination her blood pressure is 115/78 mmHg, pulse is 70 beats per minute and regular. Cardiac and respiratory systems are unremarkable, abdomen is soft and non tender, with a midline scar consistent with the recent laparotomy. Her body mass index is 22 kg/m². Routine bloods are unremarkable.
Which of the following is most important with respect to reducing risk of future exacerbations?
Anti-TNF biological therapy Gluten free diet Lactose free diet Oral mesalazine > Smoking cessation
A prospective study suggests that continued smoking raises the risk of Crohn’s exacerbation by approximately 50%.The study examined 573 Crohn’s disease patients for a follow up period of 4 years. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval : 1.102.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers.
http://www.nature.com/ajg/journal/v111/n3/full/ajg2015401a.html
Mesalazine in Crohn’s disease has debatable efficacy. A meta-analysis conducted in 2004 revealed a statistically significant but probably clinically insignificant effect on disease progression. Anti-TNF agents are effective in maintaining remission in fistulating Crohn’s disease, but must be continued, as relapse rates are high, and come with not insignificant risks from immunosuppression. These interventions contrast with smoking cessation, which has a positive effect independent of background therapy.
Gluten free diet impacts on the clinical course of coeliac disease, and a lactose free diet often improves recovery after gastroenteritis.
Severity of UC Flare - Classification
The severity of a flare of ulcerative colitis can be categorised used the Truelove and Witt criteria:
SEVERITY OF FLARE:
1) MILD Bowel movements per day = fewer than 4 Blood in stools > Small amounts Pyrexia (temp >37.8ºC) No Pulse >90 bpm No Anaemia No ESR (mm/hr) 30 or below
2) MODERATE Bowel movements per day = 4-6 Blood in stools > Between Mild and Severe Pyrexia (temp >37.8ºC) No Pulse >90 bpm No Anaemia No ESR (mm/hr) 30 or below
3) SEVERE Bowel movements per day = > 6 and features of systemic upset Blood in stools > Visible blood Pyrexia (temp >37.8ºC) Yes Pulse > 90 Yes Anaemia > Yes ESR (mm/hr) Above 30
UC Flare and VTE Prophylaxis - Example Question
A 31-year-old gentleman, with known ulcerative colitis, presents with a three-day history of profuse bloody diarrhoea. He reports opening his bowels up to 12 times each day and describes passing both bloody stool and frank blood.
On examination he is pale. His heart rate is 95 beats per minute, respiratory rate 16 breaths per minute, blood pressure 128/78 mmHg. His chest is clear to auscultation and his abdomen is soft but diffusely tender. The patient is ambulant and despite his diarrhoea appears relatively well.
The patient is diagnosed with a flare of his ulcerative colitis. Intravenous access is obtained and fluids and intravenous steroids given.
Admission bloods show:
Hb 102 g/l
Platelets 556 * 109/l
WBC 17.5 * 109/l
ESR 78 mm/h
Regarding his venous thromboembolism prophylaxis, what should happen during this admission?
Compression stockings only No prophylaxis due to active bleeding Intermittent pneumatic compression devices > Prophylactic dose low molecular weight heparin and compression stockings Treatment dose low molecular weight heparin and compression stockings
This patient can be defined as suffering an acute severe flare of ulcerative colitis which is a medical emergency. Intensive treatment with intravenous steroids and early surgical intervention has reduced the mortality from acute severe ulcerative colitis to 2.9% however the colectomy rate of 30% in acute flares has not changed for 40 years.
Whilst this patient is complaining of passing blood per rectum an acute flare of ulcerative colitis is an extremely prothrombotic state and as a result, the British Society of Gastroenterology recommends that all patients should receive subcutaneous heparin to reduce the risk of thromboembolism. Intermittent pneumatic compression devices are a form of venous thromboembolism prevention that has evidence in acute stroke so is not the correct answer here. Whilst the patient is in a prothrombotic state, there is no indication for treatment dose low molecular weight heparin and this would increase the patient’s risk of excessive blood loss.
The full guideline from the British Society of Gastroenterology can be found here:
http://www.bsg.org.uk/images/stories/docs/clinical/guidelines/ibd/ibd2011.pdf
Crohn’s - Inducing Remission 2nd Line Mx: Example Question
A 21-year-old female presents for the first time with crampy right iliac fossa pain and diarrhoea. Colonoscopy shows patchy erythema in what appears to be a cobblestone appearance in her caecum and terminal ileum. She refuses to take prednisolone as her mother had taken it previously and had some particularly ‘nasty’ side-effects.
What is the next best agent to offer?
Mercaptopurine > Budesonide Azathioprine Methotrexate Infliximab
Patient choice and involvement are particularly important in inflammatory bowel disease. Although you as a professional may feel prednisolone is the best option for her, you have to respect her decision to decline.
In patients who present for the first time and a corticosteroid is declined, contraindicated or cannot be tolerated, consider budesonide. Budesonide is not as effective in inducing remission but does have fewer side-effects.
UC Mx - Example Question
A 25-year-old man with a history of ulcerative colitis is seen in the Emergency Department with severe abdominal pain and diarrhoea. He is passing stool 8 times a day with blood.
On admission his temperature is 38.2 ºC. His heart rate is 110/min and his blood pressure is 100/62 mmHg. His abdomen is soft but very tender in the the left lower quadrant with normal bowel sounds.
He is started on intravenous fluids, methylprednisolone and antibiotics.
His initial abdominal x-ray shows mural thickening of the descending colon.
His blood and stool culture results show no growth and antibiotics are stopped
After three days his stool frequency is 6 per day with visible blood and he continues to be tachycardic.
The gastroenterology team decide to escalate his therapy by adding in ciclosporin. Which of the following factors would prompt a decision to use infliximab instead?
> Chronic kidney disease Megacolon on abdominal x-ray Previous hepatitis B Previous renal transplant Previous tuberculosis
This man has severe ulcerative colitis which is steroid refractory at 72 hours and therefore warrants additional therapy.
The first choice for this is generally ciclosporin. However, in patients with pre-existing chronic kidney disease, ciclosporin is contraindicated.
Previous hepatitis B and previous tuberculosis are both contraindications to infliximab due to risk of reactivation and should be checked prior to starting this.
Megacolon on x-ray would be an indication for urgent surgical review and intervention.
Previous renal transplant patients may already be on immunosuppression and careful multidisciplinary management would be indicated. However, ciclosporin is used as immunosuppression for patients with renal transplant and so this is not a contraindication to its use.
Reference:
National Institute for Health and Care Excellence. Ulcerative colitis: management
NICE guidelines [CG166] 2013 .
UC and AXR Features - Example Question
A 42-year-old man presents with a three week history of abdominal pain and diarrhoea to the Emergency Department. Over the past 48 hours the pain has become quite severe and is scored at 8/10 in terms of severity. The pain is worse in the left lower quadrant and has no obvious aggravating features. He is now passing around 8 loose stools per day. He has a history of irritable bowel syndrome and depression. He also completed a course of flucloxacillin for a skin abscess around 6 weeks ago.
On examination he is diffusely tender across the lower abdomen but there is no guarding. The heart rate is 102/min, blood pressure 104/66 mmHg and temperature 37.2ºC.
Bloods show the following:
Hb 13.4 g/dl Na+ 144 mmol/l Platelets 421 * 109/l K+ 4.3 mmol/l WBC 9.6 * 109/l Urea 6.8 mmol/l Creatinine 72 µmol/l CRP 62 mg/l
An abdominal film is requested:
PASSMED AXR UC Features
What is the most likely diagnosis?
Crohn's disease Acute diverticulitis > Ulcerative colitis Clostridium difficile colitis Coeliac disease
The abdominal film shows a featureless transverse colon and distal descending colon and proximal sigmoid consistent with the lead pipe sign of chronic ulcerative colitis (red arrows). Additionally chronic sacroiliitis with ankylosis on the left and partial ankylosis on the right (yellow arrows). Asymmetric left hip joint arthropathy is also seen.
Ulcerative Colitis
Ulcerative colitis
Ulcerative colitis (UC) is a form of inflammatory bowel disease. Inflammation always starts at rectum (hence it is the most common site for UC), never spreads beyond ileocaecal valve and is continuous. The peak incidence of ulcerative colitis is in people aged 15-25 years and in those aged 55-65 years.
The initial presentation is usually following insidious and intermittent symptoms. Features include:
bloody diarrhoea
urgency
tenesmus
abdominal pain, particularly in the left lower quadrant
extra-intestinal features (arthritis, erythema nodosum, episcleritis, osteoporosis, PSC, clubbing, pyoderma gangrenosum)
Pathology
red, raw mucosa, bleeds easily
no inflammation beyond submucosa (unless fulminant disease)
widespread ulceration with preservation of adjacent mucosa which has the appearance of polyps (‘pseudopolyps’)
inflammatory cell infiltrate in lamina propria
neutrophils migrate through the walls of glands to form crypt abscesses
depletion of goblet cells and mucin from gland epithelium
granulomas are infrequent
Barium enema
loss of haustrations
superficial ulceration, ‘pseudopolyps’
long standing disease: colon is narrow and short -‘drainpipe colon’
Cx of Total Colectomy in UC - Example Question
A 35-year-old man attends Gastroenterology clinic with some new and troubling symptoms. Seven years previously he had undergone total colectomy after presenting with an acute severe episode of ulcerative colitis that had failed to respond to intravenous glucocorticoids and biological therapy. Seven months after colectomy, the patient underwent restorative proctocolectomy with ileal pouch-anal anastomosis. The patient had made a good recovery from his surgeries and had experienced minimal gastrointestinal problems in the following years. Medical history was otherwise unremarkable and the patient took no regular medications.
However, over the past two months the patient had noticed an increase in stool frequency (up to 7 times per day), increasing urgency of defecation and on several occasions some seepage of stool over night. He denied any history of fevers, weight loss or bloody stool. The patient denied having contact with any individuals with gastrointestinal illnesses and had no recent travel history.
Abdominal examination demonstrated a soft and non-tender abdomen with active bowel sounds. Basic investigations arranged by the patients General Practitioner are listed below.
Stool microscopy, culture and sensitivity: no organisms seen; no growth
Clostridium difficile toxin: not detected
Haemoglobin 138 g / dL White cell count 9.9 * 109/l Neutrophils 7.8 * 109/l Platelets 336 * 109/l Urea 5.6 mmol / L Creatinine 87 micromol / L Sodium 140 mmol / L Potassium 5.0 mmol / L Erythrocyte sedimentation rate 40 ml / h
What is the appropriate first line management for the patients condition?
> Metronidazole Vancomycin Prednisolone Infliximab Pouch excision with permanent ileostomy
Up to 30 % of patients develop pouchitis following ileal pouch-anal anastomosis after total colectomy in ulcerative colitis. This presents with increased stool frequency, urgency, incontinence and nocturnal seepage.
First line treatment is with antibiotics such as metronidazole or ciprofloxacin. Probiotics are used in some cases. In 5 % of cases, pouchitis can become chronic, ultimately leading to pouch failure and requiring pouch excision.
Prednisolone and infliximab are important treatments of ulcerative colitis but are not used in the treatment of pouchitis.
UC - Inducing Remission - Example Question
You review a 30-year old male who was seen in the gastroenterology department with a first presentation of ulcerative colitis symptoms He was having diarrhoea 5 times a day with small amount of blood in his stool. He had been systemically well and haemodynamically stable and thus did not require hospital admission. He was started on daily Pentasa.
Today, he reports his symptoms have not improved despite treatment. He is still opening his bowels 5 times per day and is concern about it.
He is mildly dehydrated clinically, but haemodynamically stable, with a blood pressure of 120/76 mmHg and a heart rate of 70 beats per minute. His abdomen is soft and not distended.
What is the most appropriate management?
Stop 5 ASA and start infliximab > Add prednisolone oral therapy Topical 5 ASA Oral ciclosporin Oral mercaptopurine
This gentleman has symptoms of moderate ulcerative colitis which was not managed with oral 5 ASA. He is not on topical therapy following initial assessment which gives you the clue that his disease is not isolated to proctitis.
His symptoms are still that of moderate ulcerative colitis and given his failure to respond to treatment he should now be started on oral prednisolone with a follow up in 2 weeks for re review of symptoms.
Mild to moderate ulcerative colitis ( up to 6 motions per day with mild bleed. ESR <30) should be managed using a step wise approach.
Proctitis: Induce remission with a topical 5-ASA (aminosalicylic acid). If no response, or cant tolerate, 5-ASA the next step would be to add topical steroids. Oral should be considered if remission not achieved or patient presents with left sided extensive ulcerative colitis.
Left sided extensive disease should be managed using oral 5-ASA initially with or without topical 5-ASA. If no improvement within 4 weeks oral prednisolone therapy should be added. If no response to oral prednisolone, tacrolimus should be started to induce remission.
For full guidelines refer to:
http://pathways.nice.org.uk/pathways/ulcerative-colitis
UC - Flares
Ulcerative colitis: flares
Flares of ulcerative colitis are usually classified as either mild, moderate or severe:
Mild:
Fewer than four stools daily, with or without blood
No systemic disturbance
Normal erythrocyte sedimentation rate and C-reactive protein values
Moderate:
Four to six stools a day, with minimal systemic disturbance
Severe: More than six stools a day, containing blood Evidence of systemic disturbance, e.g. - fever - tachycardia - abdominal tenderness, distension or reduced bowel sounds - anaemia - hypoalbuminaemia
NB: Patients with evidence of severe disease should be admitted to hospital.
Crohns - Mx: Example Question
A 40 year-old man is referred by his GP with a two-day history of severe abdominal pain located in the lower left and lower right quadrants. Other symptoms involve diarrhoea, malaise and weight loss. His past medical history includes Crohn’s disease, for which he has recently been treated with mycophenolate mofetil for the past 4 months, however this is starting to lose its effect. Other treatments for the Crohn’s disease include steroid therapy, 6-mercaptopurine and a course of azathioprine, although all have failed to control his disease. Surgical history includes an ileocaecal resection 7 years ago.
Blood test results reveal:
Hb 9.8 g/L Platelets 190 * 109/l WBC 14.9 * 109/l Na+ 135 mmol/l K+ 3.8 mmol/l Urea 6.8 mmol/l Creatinine 90 µmol/l CRP 58 mg/l ESR 64 mm/hr
This episode is diagnosed as a severe flare-up of his Crohn’s disease.
What is most appropriate next management?
Oral ciclosporin > Intravenous infliximab Beta-interferon therapy Oral Sulfasalazine Intravenous cyclophosphamide
Infliximab should be considered (and is licensed) for corticosteroid or immunomodulator refractory disease or intolerance to the above drugs. It works as a monoclonal antibody to the cytokine tumour necrosis factor (TNF) alpha.
The National Institute for Health and Clinical Excellence (NICE) recommends infliximab for severe active or active fistulising Crohn’s disease until treatment failure (including surgery) or for 12 months, whichever is the shorter. Treatment should only be continued after that if there is evidence of active disease. Adalimumab can be used as an alternative.
UC Screening: Example Question
A 55-year-old man attends outpatient clinic for review. He was diagnosed with ulcerative pancolitis 13 years ago, and is currently treated with Asacol (mesalazine). He had a colonoscopy last month that showed mild active inflammation throughout the colon, and no polyps. He has no relevant family history. What should be the time interval until his next surveillance colonoscopy?
2 years > 3 years 5 years 7 years 1 year
Patients with inflammatory bowel disease are 6 times more likely to develop colorectal cancer compared to the general population. Because of this, it is recommended that regular colonoscopies are performed for surveillance. These are only initiated 10 years after diagnosis, and their frequency depends on previous endoscopic findings, distribution of inflammation, family history of colorectal cancer and other factors in the patient’s past medical history (e.g. PSC).
This patient falls into the intermediate risk category as he has a pancolitis (inflammation throughout the colon), with mild inflammation on previous endoscopy. This means the time interval is 3 years between surveillance investigations.
Faecal Calprotectin in IBD - Example Question
A 23-year-old man presents with four months of abdominal bloating and diarrhoea. He is opening his bowel 2-3 times a day. He also gets recurrent aphthous ulcers, but denies weight loss and has never passed mucus or blood in his stools. He has not travelled anywhere in the last year and there is no family history of inflammatory bowel disease.
On examination, his abdomen was soft with no organomegaly.
Coeliac serology is negative.
What is the next appropriate test?
> Faecal calprotectin H. Pylori serology Faecal elastase Sigmoidoscopy Small bowel capsule endoscopy
Faecal calprotectin is increased in inflammatory conditions of the bowel including crohns disease, ulcerative colitis, infectious colitis and malignancy. The faecal calprotectin level is normal in irritable bowel syndrome the most likely diagnosis in this case. If normal, the patient would not require further investigation such as a sigmoidoscopy or colonoscopy.
Faecal elastase is used to assess pancreatic exocrine function in pancreatic insufficiency.
Sigmoidoscopy would be an alternative, more invasive approach to investigate this gentlemans diarrhoea. However, if negative would not rule out inflammatory bowel disease as it only visualises the sigmoid.
A large proportion (around 20%) of the general population suffers from aphthous ulcers.
H.pylori serology would indicate whether the patient has been previously exposed to Helicobacter pylori; however it is associated with upper gastrointestinal symptoms.
Small bowel capsule endoscopy is used to visualize areas of the bowel unreachable by conventional endoscopy. This would not be used without initially performing a colonoscopy to rule out large bowel pathology.
Further reading:
NICE diagnostics guidance [DG11]: Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel.
https://www.nice.org.uk/guidance/dg11
Risk of Combination Immunomodulator and Biological Therapy - Example Question
A 35-year-old woman with known Crohns disease is reviewed in gastroenterology clinic. Following her initial diagnosis 2 years previously she has been treated with azathioprine as a immunomodulating agent. This medication has been well tolerated and the patient reported no significant side effects. However, the patients disease had not been well controlled over the previous 6 months with frequent exacerbations of bloody diarrhoea and abdominal pain. Each flare had been treated with a tapered course of corticosteroids, however the patient had been unable to fully wean herself off steroids due to recurrent symptoms.
A severe recent exacerbation had involved the patient suffering significant nausea and vomiting necessitating admission to hospital. The report from a gastroscopy performed at this time is given below.
Following discussion with the patient it was agreed that additional therapy was needed in order to maintain disease remission. The patient felt that the azathioprine she had been taking was effective and was keen to continue this medication in conjunction with infliximab.
Gastroscopy: normal oesophagus and lower oesophageal sphincter; small areas of patchy inflammation affecting antrum; further multiple areas of inflammation throughout first part of duodenum
What additional risk of combination immunomodulator and biological therapy compared to biological therapy alone is it necessary to discuss with the patient?
Reactivation of latent tuberculosis Aplastic anaemia > Increased risk of non-melanoma skin cancer Congestive cardiac failure Hypersensitivity reaction
Anti-tumour necrosis factor agents used in combination with immunomodulating agents are more effective at maintaining steroid-free clinical remission than when used as mono-therapy (56.8 % vs 30 % P < 0.001).
However, compared with mono-therapy, combination therapy carries an increased risk of non-melanoma skin cancer (standardised incidence ratio 3.46) and other cancers (standardised incidence ratio 2.82). Of particular concern are cases of hepatosplenic T-cell lymphoma reported in adolescent and young adult patients with Crohns disease treated with infliximab and azathioprine or mercaptopurine.
The other answers are all risks factors of infliximab treatment with or without concomitant immunomodulator therapy.
Crohn’s Immunosuppression and Pregnancy: Example Question
A 25-year-old woman with a long history of Crohns’ disease comes to the clinic for review. She is 12 weeks pregnant. Current medication for Crohns’ includes 100mg BD of azathioprine and her disease is currently stable. She is opening her bowels 2-3 times per day with a normal, formed motion. Clinical examination is unremarkable, abdomen is soft and non tender, with no palpable masses, bowel sounds are normal.
Hb 110 g/l Na+ 139 mmol/l Platelets 180 * 109/l K+ 4.0 mmol/l WBC 6.7 * 109/l Urea 7 mmol/l Neuts 3.2 * 109/l Creatinine 80 µmol/l Lymphs 1.4 * 109/l CRP 10 mg/l Eosin 0.7 * 109/l
Which of the following is the most appropriate way to manage her Crohn’s?
Stop all immunosuppressives Add prednisolone > Continue azathioprine Switch to methotrexate Switch to prednisolone
Considerable data has now accumulated on use of azathioprine in women during pregnancy who have an underlying diagnosis of inflammatory bowel disease, arthritis or skin disease. Although this is registry data, and hence not as robust as a randomised controlled trial, it does not suggest a significant increase in risk of teratogenicity associated with azathioprine use. For this reason guidance from the BGS supports it’s continued use.
Methotrexate is teratogenic and therefore cannot be recommended for use in pregnancy. Given adverse effects of prednisolone use such as weight gain and reduced bone mineral density, long term use of corticosteroids in pregnancy isn’t recommended, although they would still be used to manage an exacerbation whilst on azathioprine. Stopping all immunosuppressives risks worsening Crohns’ and is clearly not advisable.
Cholestyramine
Cholestyramine
Cholestyramine is a bile acid sequestrant used in the management of hyperlipidaemia. It decreases bile acid reabsorption in the small intestine, therefore upregulating the amount of cholesterol that is converted to bile acid. The main effect it has on the lipid profile is to reduce LDL cholesterol. It is also occasionally used in Crohn’s disease for treatment resistant diarrhoea.
Adverse effects abdominal cramps and constipation decreases absorption of fat-soluble vitamins cholesterol gallstones may raise level of triglycerides
Crohn’s Resistant Diarrhoea - Example Question
You see a 45-year-old patient with Crohn’s disease in clinic. They had an extensive terminal ileal and small bowel resection in 2011 for active disease with strictures after the failure of medical therapy. Since then he has been well controlled on 8 weekly Infliximab infusions and mesalazine. They come to see you with increasing stool frequency, up to 10 times per day. It is watery and loose and he has been having some nocturnal episodes as well. His observations are within normal limits and his BMI is 21. On examination, his abdomen is soft and non-tender. Rectal examination is unremarkable.
Blood tests are as follows;
Hb 125 g/l
Platelets 298 * 109/l
WBC 8.3 * 109/l
Na+ 141 mmol/l
K+ 4.4 mmol/l
Urea 4.1 mmol/l
Creatinine 95 µmol/l
Bilirubin 7 µmol/l ALP 74 u/l ALT 23 u/l Albumin 37 g/l CRP 7 mg/l
Faecal calprotectin 13 µg/g (normal < 50)
Faecal MC&S NAD
He goes on to have a colonoscopy which is macroscopically normal and the biopsies show no active disease.
He has a SeHCAT (selenium homocholic acid taurine) scan which shows <5% Selenium retention at 7 days. He is diagnosed as having bile acid malabsorption secondary to terminal ileal resection.
What is the most appropriate treatment to start him on?
Loperamide Codeine phosphate Octreotide > Cholestyramine Increase infliximab frequency
This patient has bile acid malabsorption following extensive terminal ileal and small bowel resection for his Crohn’s disease. A complication of extensive terminal ileal resection is bile acid diarrhoea which presents with watery loose stools including nocturnal episodes. The diagnostic test is the SeHCAT scan (nuclear medicine) which used radiolabelled selenium and measures the retention of the labelled molecule. BAD is diagnosed by a <15% retention of SeHCAT at 7 days.
The treatment is with bile acid sequestrants including cholestyramine (Questran). This is the correct answer here, the patient does not have an acute flare so Infliximab frequency does not need altering. Loperamide and codeine will not treat the underlying cause and octreotide can be used to treat diarrhoea in VIPomas.
UC Flare - Example Question
A 26 year old woman presents with a flare up of her ulcerative collitis. Since admission she has been treated on intravenous steroids and ciclosporin. You are asked to review her for discharge on day 4 of her admission. On examination she has a temperature of 37.7 °C, pulse is 91/min, She has opened her bowels 9 times today (>10 times a day on admission), has been eating and drinking and says she feels ready to go home. Her abdomen is mildly tender in the left flank, but is otherwise soft with active bowel sounds present. Current blood tests are as follows:
Hb 101 g/l Platelets 200 * 109/l WBC 9.5 * 109/l ESR 35 mm/h CRP 98 mg/l
What is the next step in this patient’s management?
Start infliximab 5mg/kg Commence daily steroid enemas Discharge home with reducing course of oral steroids > Request an urgent abdominal radiograph and surgical review Consider oral loperamide for her diarrhoea
The Truelove and Witts criteria helps to guide physicians in the management of ulcerative collitis:
Mild: Bowel movements <4/day, temp <37.8 °C, pulse <90/min, ESR<30mm/hour, No anaemia, no or small amounts of blood in stool,
Moderate: Bowel movements 4-6, the remainder of the parameters are the same for mild.
Severe; Bowel movements 6 or more plus one or more of the systemic features such as: temp >37.8°C, Pulse > 90/min, ESR >30mm/hour, visible blood in stool and anaemia.
In this scenario, the patient has a severe exacerbation of her disease despite medical treatment. As a result, early involvement of the surgeons is paramount as it is likely that she will need surgical intervention.
Nice state that:
‘Assess and document on admission, and then daily, the likelihood of needing surgery for people admitted to hospital with acute severe ulcerative colitis.’
‘Be aware that there may be an increased likelihood of needing surgery for people with any of the following:’
stool frequency more than 8 per day
pyrexia
tachycardia
an abdominal X-ray showing colonic dilatation
low albumin, low haemoglobin, high platelet count or C-reactive protein (CRP) above 45 mg/litre (bear in mind that normal values may be different in pregnant women).
For further information, please take time to revisit : https://www.nice.org.uk/guidance/cg166/chapter/recommendations#assessing-likelihood-of-needing-surgery-2
Use of Methotrexate in Crohns - Example Question
A 21-year-old female presents for the first time with crampy right iliac fossa pain and diarrhoea. Colonoscopy shows moderate ileocaecal disease, with the appearance of linear ulcerations and patchy erythema. She responds well to oral prednisolone and is discharged home with follow-up. On tapering the steroid dose, she feels that her abdominal pain gets worse and the frequency of diarrhoea increases. Her gastroenterologist performs a blood test showing:
Thiopurine methyltransferase (TPMT) <10Mu/L Normal range 68 - 150mu/L
What is the next best agent to offer?
> Methotrexate Azathioprine Mercaptopurine Infliximab Increase prednisolone
This patient presents with Crohn’s disease. The initial monotherapy of prednisolone is effective at high dose but symptoms return on tapering its dose. An add-on treatment is therefore needed. The next agent to think about is azathioprine or mercaptopurine, in accordance with NICE guidance. Before either is commenced, a TPMT level must be done. If it is deficient, very low or absent, neither azathioprine or mercaptopurine should be offered.
Methotrexate is the next most suitable agent to add if the patient cannot tolerate mercaptopurine or azathioprine.
Infliximab is used only when patients have failed conventional therapy, including immunosuppressives and corticosteroids.
Toxic Megacolon - Example Question
A 50-year-old man is admitted to hospital with a 5 day history of worsening abdominal pain. Over the past 24 hours the pain has become very severe. On examination his pulse is 110/min, blood pressure 110/62 mmHg and temperature 37.7ºC. Bloods show the following:
Hb 10.5 g/l
Platelets 452 * 109/l
WBC 16.3 * 109/l
CRP 263 mg/l
The abdominal film is shown below:
SEE AXR TOXIC MEGACOLON
What is the most likely underlying disorder?
Perforated diverticulum Sigmoid volvulus > Ulcerative colitis Spontaneous bacterial peritonitis Crohn's disease
This patient had toxic megacolon secondary to underlying ulcerative colitis - note the dilated transverse colon. The abdomen demonstrates a markedly dilated transverse colon (9 cm) with impression of slight dilatation of the descending colon with some ‘thumb printing’ in the wall. No free subphrenic gas is seen.
They went on to have a subtotal colectomy.
Severe UC Flare Mx - Example Question
A 24-year-old female is admitted to the gastroenterology ward with a one-week history of profuse bloody diarrhoea and abdominal cramps. On the second day of her admission, she undergoes a flexible sigmoidoscopy, at which a diagnosis of ulcerative colitis is made. She is commenced on an appropriate regime of intravenous steroids and mesalazine enemas. She is given intravenous fluid and electrolyte replacement and is started on low molecular weight heparin and venous thromboembolism prophylaxis. A pregnancy test is performed on admission which is negative. She is reviewed daily by the gastroenterology team.
After three days of therapy, the patient is still opening her bowels at least 10 times a day. Examination on day three reveals a soft but diffusely tender abdomen. Bloods show:
Hb 92 g/l
Platelets 220 * 109/l
WBC 15.2 * 109/l
Na+ 145 mmol/l K+ 3.4 mmol/l Urea 9 mmol/l Creatinine 150 µmol/l CRP 121 mg/L
What is the next most appropriate management step?
Urgent surgical review, further two days of intravenous steroids then re-evaluate Urgent surgical review to request colectomy > Urgent surgical review, intravenous ciclosporin 2mg/kg/day Urgent surgical review, intravenous tacrolimus 200mcg/kg/day Application for urgent anti-TNF (tumour necrosis factor) therapy
This patient is suffering a severe acute flare of ulcerative colitis. It would appear that so far he has been managed appropriately. The British Society of Gastroenterology recommend the following basic measures during an acute flare:
- ) Intravenous fluid and electrolyte replacement
- ) Blood transfusion if required to maintain a haemoglobin >10g/dL
- ) Intravenous antibiotics ONLY if infection is considered or prior to surgery
- ) Subcutaneous heparin to reduce the risk of thromboembolism
- ) Intravenous corticosteroids (either hydrocortisone 100mg four times a day or methylprednisolone 60mg/day)
- ) Flexible sigmoidoscopy and biopsy within 72 hours to confirm diagnosis and exclude cytomegalovirus infection
- ) Daily monitoring with physical examination, recording of vital signs, stool chart, bloods (full blood count, c-reactive protein, serum electrolytes, serum albumin, liver function tests and glucose) and consider the need for daily abdominal X-ray.
Intravenous steroids are given for five days with no additional benefit seen beyond seven days.
At day three a c-reactive protein >45 mg/l or a stool frequency of >8/day predicts the need for surgery in 85% of cases.
The National Institute for Clinical Excellence (NICE) recommends that if no improvement is seen after 72 hours of intravenous steroid treatment or if the patient deteriorates at any time despite corticosteroid treatment then an urgent surgical review is required ciclosporin (2mg/kg/day) should be added. NICE recommends that in this acute setting infliximab reserved for patients in whom ciclosporin is contraindicated or clinically inappropriate.
The NICE guideline is available here:
www.nice.org.uk/guidance/cg166/chapter/1-Recommendations#inducing-remission-in-people-with-ulcerative-colitis
Severe UC Flare Mx - Example Question
A 25-year-old man presents with bloody diarrhoea and fevers. His blood tests are as follows:
Hb 12 g/dl
Platelets 350 * 109/l
WBC 11.5 * 109/l
CRP 75 mg/L
He has known ulcerative colitis and presents with his second flare-up in the last few months. The option of surgery was offered to him last time but he declined and wants to exhaust all pharmacological therapies first. During this admission, he is started on IV hydrocortisone. After 3 days, he still has bloody stools up to 7 times a day. What is the next most suitable agent?
IV infliximab > IV ciclosporin Continue IV hydrocortisone for up to 7 days Oral tacrolimus Mesalazine
This patient has acute severe ulcerative colitis and shows little improvement with step 1 therapy of IV hydrocortisone. According to NICE guidance, intravenous ciclosporin should be added in people with little improvement to 72 hours of intravenous steroids. Surgery is an option but from his strong wishes last time of his preferences, it is more appropriate to trial him further medical management.
Intravenous infliximab is an option only after ciclosporin is contraindicated or clinically inappropriate.
Oral tacrolimus and mesalazine have no role in inducing remission in an acute, severe exacerbation of ulcerative colitis. There is little evidence that continuing intravenous steroids, after a trial of 3 days, would show any improvement.
Crohns and Azathioprine - Example Question
A 54-year-old man presents to Gastroenterology outpatient clinic, for review of his Crohn’s disease which was diagnosed 3 years ago. His other past medical history includes ischaemic heart disease, hypercholesterolaemia and gout. He has been suffering from a few months of increased diarrhoea and abdominal pain, and you feel he would benefit from starting azathioprine. Which medication is it important to ensure he is not taking before commencing azathioprine?
Ramipril > Allopurinol Losartan Aspirin Simvastatin
Allopurinol inhibits the enzyme xanthine oxidase (XO). This enzyme is also required to inactive 6-mercaptopurine (the active agent from azathioprine). When XO is inhibited, this causes an increase in 6-mercaptopurine levels, which are then shunted down a different metabolic pathway, leading to higher levels of 6-thioguanine metabolites. There are incorporated into the DNA of white blood cells, leading to reduced activation and reduced replication potential.
Coadministration of azathioprine and allopurinol requires dose reductions and extra monitoring for life threatening agranulocytosis. The other medications listed do not interact with azathioprine and require no extra monitoring
Azathioprine
Azathioprine
Azathioprine is metabolised to the active compound mercaptopurine, a purine analogue that inhibits purine synthesis. A thiopurine methyltransferase (TPMT) test may be needed to look for individuals prone to azathioprine toxicity.
Adverse effects include
bone marrow depression
nausea/vomiting
pancreatitis
A significant interaction may occur with allopurinol and hence lower doses of azathioprine should be used.
Fistulating Crohn’s - Example Question
A 31-year-old lady presents with a two-week history of cramping abdominal discomfort associated with troublesome diarrhoea. She explains to you that she can barely leave the house due to the constant need to use the toilet. She has a background of Crohn’s disease diagnosed 6 years previously. This is her second flare of Crohn’s disease in the past six months and she has lost approximately 2 stone (12 kg) in weight. Initially, she was started on azathioprine but could not tolerate the side effects. She was switched onto mercaptopurine six months ago which she is still taking.
Her admission bloods are summarised below:
Hb 98 g/l Na+ 140mmol/l Platelets 350 * 109/l K+ 3.2 mmol/l WBC 6 * 109/l Urea 10 mmol/l Neuts 3 * 109/l Creatinine 50 µmol/l Lymphs 2 * 109/l CRP 210 mg/l
The gastroenterologist in charge of her care requested MR enterography. The result of this has confirmed the presence of fistulating disease. What next step of treatment should be considered in her case?
Low residue diet > Infliximab Intravenous corticosteroids Methotrexate Urgent surgical opinion
Infliximab, within its licensed indication, is recommended as a treatment option for people with active fistulating Crohn’s disease whose disease has not responded to conventional therapy (including antibiotics, drainage and immunosuppressive treatments), or who are intolerant of or have contraindications to conventional therapy.
IBD - Diagnosis and Ix: Example Question
A 21-year-old woman presents to gastroenterology clinic with a 6 months history of abdominal bloating and diarrhoea. She is a university student and finds that her symptoms are exacerbated by periods of stress. She does not take any regular medications and has no drug allergies. Her uncle was diagnosed with ulcerative colitis at the age of 30 and is currently on biologic therapy for it.
On examination, her temperature is 36.7ºC, blood pressure is 100/50 mmHg and heart rate is 90 beats per minute. Her body mass index is 20.5 kg/m². There were no abnormalities to find on an examination of her cardiovascular, respiratory or abdominal systems.
Her GP had organised some blood tests prior to referring her to clinic:
Hb 130 g/l Na+ 135 mmol/l Bilirubin 12 µmol/l Platelets 280 * 109/l K+ 4.6 mmol/l ALP 85 u/l WBC 6.5 * 109/l Urea 3.5 mmol/l ALT 40 u/l Neuts 4.0 * 109/l Creatinine 50 µmol/l γGT 35 u/l CRP <1 mg/l Albumin 40 g/l
Which is the next most appropriate investigation for this patient?
Faecal elastase Colonoscopy Flexible sigmoidoscopy > Faecal calprotectin CT abdomen
This young patient has features of diarrhoea-predominant IBS. Patients with IBS often find that their symptoms are exacerbated by stress. Although there is some evidence patients with IBD may have a genetic predisposition, it does not follow a mendelian pattern of inheritance. Despite her family history of IBD, the nature of her symptoms and normal blood tests make the diagnosis of IBD unlikely and it would not be appropriate to proceed with a lower GI endoscopy or CT scan at this stage.
Faecal calprotectin is a test for intestinal inflammation and has been recommended by NICE as a screening tool for IBD for GPs. It can also be used to monitor the response to treatment in IBD patients.
IBD Histology: Crohns vs UC
Ulcerative Colitis:
- Inflammation in MUCOSA and SUBMUCOSA only
- Widespread ulceration with preservation of adjacent mucosa - appearance of POLYPS (Pseudopolyps)
- Inflammatory cell infiltrate in lamina propria
- Crypt abscesses
- Depletion of goblet cells and mucin from gland epithelium
- Granulomas are infrequent
Crohns:
- Inflammation occurs in ALL layers, down to the serosa > predisposes to strictures, fistulas and adhesions
- Oedema of mucosa and submucosa combined with deep fissured ulcers (ROSE-THORN) leads to a COBBLESTONE pattern
- Lymphoid aggregates
- Non-Caseating granulomas
Crohns Disease
= a form of IBD
Commonly affects the terminal ileum and colon but may be seen anywhere from mouth to anus
Pathology:
- cause is unknown but there is a strong genetic susceptibility
- inflammation occurs in all areas down to serosa
Siblings are 30x more likely to develop Crohns than gen pop
Smoking is BAD for Crohns - makes flares more likely but not thought to be a cause
Inflammation occurring in all layers = why patients are prone to strictures, fistulas, adhesions
- Crohn’s typically presents in late adolescence - early adulthood
- Presentation may be non-specific Sx e.g. weight loss and lethargy
- Diarrhoea - most prominent Sx in adults - Crohns colitis can potentially be bloody
- Abdo pain is most prominent Sx in children
- Perianal disease - skin tags, ulcers
- Extra-intestinal Fx more common in patients with colitis or perianal disease
Mx of Severe UC Flare
Acute severe colitis as assessed using the Truelove-Witt criteria with > 5 bloody stools per day, tachycardia, raised ESR and anaemia:
- Appropriate initial treatment is IV glucocorticoids + Oral 5-ASA aminosalicylates. Response to glucocorticoid therapy should be assessed after 3-5 days with consideration of rescue therapy with
- Infliximab (or Ciclosporin) if disease remains severely active.
Meta-analysis has shown a significant effect of infliximab over placebo in moderate-severe disease with a relative risk of remission not being achieved of 0.72 (0.57-0.91).
If Infliximab has not given adequate response at 5-7 days post-treatment then colectomy must be considered.
Azathioprine has a role as maintenance therapy in ulcerative colitis once remission has been achieved.
Topical 5-aminosalicylates have a key role in the management of mild disease but are unlikely to achieve remission in severe flares.
Severe Crohn’s
Risk Factors indicating severe phenotype of Crohn’s disease:
- young age (< 40 years)
- female sex
- need for steroids to control first exacerbation
- presence of an intra-abdominal abscess
- perianal disease
- lesions of upper GI tract
All of above are associated with an aggressive disease course.
If appropriate initial steroid treatment has failed to induce full remission, in cases with features of a severe phenotype, a rapid step-up to biological therapy is indicated. Infliximab is effective at inducing remission in moderate-to-severe Crohn’s disease compared to placebo (remission rate at four weeks 81 % vs 17 %) and is also an effective treatment of peri-anal disease.
The National Institute for Health and Clinical Excellence (NICE) recommends infliximab for severe active or active fistulising Crohn’s disease until treatment failure (including surgery) or for 12 months, whichever is the shorter. Treatment should only be continued after that if there is evidence of active disease. Adalimumab can be used as an alternative.
CMV Colitis in IBD
CMV colitis can be a consequence of immunosuppressive agents such as azathioprine.
It can present with fever and diarrhoea +/- blood. It can also present as an exacerbation of IBD patients in those on immunosuppressants.
Inclusion bodies are characteristic at biopsy.
It will respond well to an antiviral agent e.g. Ganciclovir
Crohn’s Disease and Smoking
A prospective study suggests that continued smoking raises the risk of Crohn’s exacerbation by approximately 50%.The study examined 573 Crohn’s disease patients for a follow up period of 4 years. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval : 1.102.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers.
Alternative to Steroids for Inducing Remission in Crohns
In patients who present for the first time and a corticosteroid is declined, contraindicated or cannot be tolerated, consider budesonide. Budesonide is not as effective in inducing remission but does have fewer side-effects.
Severe UC Flare = PROTHROMBOTIC state
Although the patient may be complaining of passing blood per rectum, an acute flare of ulcerative colitis is an extremely prothrombotic state and as a result, the British Society of Gastroenterology recommends that all patients should receive subcutaneous heparin to reduce the risk of thromboembolism
Contraindications to Ciclosporin and Infliximab in IBD
Contraindication to Ciclosporin:
- Pre-existing chronic kidney disease,
Contraindication to Infliximab:
- Previous hepatitis B
- Previous tuberculosis
= due to risk of reactivation and should be checked prior to starting this.
Pouchitis
Up to 30 % of patients develop pouchitis following ileal pouch-anal anastomosis after total colectomy in ulcerative colitis. This presents with increased stool frequency, urgency, incontinence and nocturnal seepage.
First line treatment is with antibiotics such as metronidazole or ciprofloxacin. Probiotics are used in some cases. In 5 % of cases, pouchitis can become chronic, ultimately leading to pouch failure and requiring pouch excision.
Mild-moderate UC - Inducing Remission
Mild to moderate ulcerative colitis ( up to 6 motions per day with mild bleed. ESR <30) should be managed using a step wise approach.
Proctitis: Induce remission with a topical 5-ASA (aminosalicylic acid). If no response, or cant tolerate, 5-ASA the next step would be to add topical steroids. Oral should be considered if remission not achieved or patient presents with left sided extensive ulcerative colitis.
Left sided extensive disease should be managed using oral 5-ASA initially with or without topical 5-ASA. If no improvement within 4 weeks oral prednisolone therapy should be added. If no response to oral prednisolone, tacrolimus should be started to induce remission.
Faecal Calprotectin
Faecal calprotectin is increased in inflammatory conditions of the bowel including crohns disease, ulcerative colitis, infectious colitis and malignancy. The faecal calprotectin level is normal in irritable bowel syndrome the most likely diagnosis in this case. If normal, the patient would not require further investigation such as a sigmoidoscopy or colonoscopy.
Faecal calprotectin is a test for intestinal inflammation and has been recommended by NICE as a screening tool for IBD for GPs. It can also be used to monitor the response to treatment in IBD patients.
Combination Anti-Tumour Necrosis Factor Biological Agents with Immunomodulating agents
Eg Infliximab and Azathioprine in IBD
Anti-tumour necrosis factor agents used in combination with immunomodulating agents are more effective at maintaining steroid-free clinical remission than when used as mono-therapy (56.8 % vs 30 % P < 0.001).
However, compared with mono-therapy, combination therapy carries an increased risk of non-melanoma skin cancer (standardised incidence ratio 3.46) and other cancers (standardised incidence ratio 2.82). Of particular concern are cases of hepatosplenic T-cell lymphoma reported in adolescent and young adult patients with Crohns disease treated with infliximab and azathioprine or mercaptopurine.
Risks of Infliximab treatment alone
Reactivation of latent tuberculosis
Aplastic anaemia
Congestive cardiac failure
Hypersensitivity reaction
Complication of Extensive Terminal Ileal Resection in Crohns
A complication of extensive terminal ileal resection is bile acid diarrhoea (BAD) which presents with watery loose stools including nocturnal episodes.
The diagnostic test is the SeHCAT scan (nuclear medicine) which used radiolabelled selenium and measures the retention of the labelled molecule. BAD is diagnosed by a <15% retention of SeHCAT at 7 days.
The treatment is with bile acid sequestrants including cholestyramine (Questran).
Management of Acute UC Flare in Hospital
The British Society of Gastroenterology recommend the following basic measures during an acute flare:
- ) Intravenous fluid and electrolyte replacement
- ) Blood transfusion if required to maintain a haemoglobin >10g/dL
- ) Intravenous antibiotics ONLY if infection is considered or prior to surgery
- ) Subcutaneous heparin to reduce the risk of thromboembolism
- ) Intravenous corticosteroids (either hydrocortisone 100mg four times a day or methylprednisolone 60mg/day) + 5-ASA
- ) Flexible sigmoidoscopy and biopsy within 72 hours to confirm diagnosis and exclude cytomegalovirus infection
- ) Daily monitoring with physical examination, recording of vital signs, stool chart, bloods (full blood count, c-reactive protein, serum electrolytes, serum albumin, liver function tests and glucose) and consider the need for daily abdominal X-ray.
Intravenous steroids are given for five days with no additional benefit seen beyond seven days.
At day three a c-reactive protein >45 mg/l or a stool frequency of >8/day predicts the need for surgery in 85% of cases.
The National Institute for Clinical Excellence (NICE) recommends that if no improvement is seen after 72 hours of intravenous steroid treatment or if the patient deteriorates at any time despite corticosteroid treatment then an urgent surgical review is required ciclosporin (2mg/kg/day) should be added. NICE recommends that in this acute setting infliximab reserved for patients in whom ciclosporin is contraindicated or clinically inappropriate.
According to NICE guidance, intravenous ciclosporin should be added in people with little improvement to 72 hours of intravenous steroids.
Intravenous infliximab is an option only after ciclosporin is contraindicated or clinically inappropriate.
Oral tacrolimus and mesalazine have no role in inducing remission in an acute, severe exacerbation of ulcerative colitis. There is little evidence that continuing intravenous steroids, after a trial of 3 days, would show any improvement.
Azathioprine and Allopurinol
Allopurinol inhibits the enzyme xanthine oxidase (XO). This enzyme is also required to inactive 6-mercaptopurine (the active agent from azathioprine). When XO is inhibited, this causes an increase in 6-mercaptopurine levels, which are then shunted down a different metabolic pathway, leading to higher levels of 6-thioguanine metabolites. There are incorporated into the DNA of white blood cells, leading to reduced activation and reduced replication potential.
Crohn’s Example Question
A 26-year-old man comes to the outpatient clinic. He describes a 2-month history of weight loss, cramping lower abdominal pain with increasing stool frequency. His stools often have blood and mucus in them and occasionally he passes pure blood with no faeces. He is normally fit and well and takes no regular medications. On examination, he has a low-grade fever at 37.5 and pale. His abdomen is soft but tender across the lower half. His bloods checked by the GP earlier in the week are as follows:
Hb 110 g/l
Platelets 400 * 109/l
WBC 12.0 * 109/l
Neuts 9.0 * 109/l
Na+ 139 mmol/l K+ 4.5 mmol/l Urea 4.0 mmol/l Creatinine 89 µmol/l CRP 60 mg/L (<10)
Bilirubin 8 µmol/l
ALP 78 u/l
ALT 34 u/l
Albumin 36 g/l
Stool cultures sent by the GP are negative.
He is admitted the same day for a flexible sigmoidoscopy which shows mild colitis extending to the mid-descending colon. Biopsies are taken which are show mild colitis but of indeterminate cause.
He is transferred to the ward and started on IV hydrocortisone 100mg QDS and he clinically improves and is started on regular mesalazine. He is found to be positive for anti-Saccharomyces cerevisiae antibodies but negative for pANCA. What is the likely cause of his colitis?
Ulcerative colitis Microscopic colitis C.difficile infection Behcet's disease > Crohn's disease
This patient has Crohn’s disease. Anti-Saccharomyces cerevisiae antibodies are more likely to be positive in Crohn’s disease. Ulcerative colitis patients are more likely to be pANCA positive. The patient has microscopic colitis on flexible sigmoidoscopy excluding microscopic colitis. Behcet’s usually present in Middle Eastern men with oral and genital ulcers, conjunctivitis and colitis.
