IBD+IBS

Question 1

A 55-year-old man with a 25-year history of pan-ulcerative colitis in remission on mesalamine undergoes a surveillance colonoscopy. High-definition white light colonoscopy demonstrated that his colitis is in remission. There are rare pseudopolyps and patchy scarring of the mucosa. Multiple random biopsies are obtained throughout the colon. Biopsies reveal chronic inactive colitis. A single biopsy shows low-grade dysplasia. The finding is confirmed by a second pathologist. What is the next best step?

A. Send for colectomy and ileal pouch anal anastomosis (IPAA).

B. Refer the patient to a gastroenterologist to perform chromoendoscopy.

C. Repeat the colonoscopy in 1-2 years.

D. Add a biologic agent and repeat colonoscopy in 6 months.

Answer 1

• This patient has several risk factors for developing UC-related colorectal neoplasia including extensive and long-standing disease, mucosal scarring, pseudopolyps, male gender, and documented dysplasia. This patient is best served by referral to a gastroenterologist who can perform chromoendoscopy. Several studies have documented that chromoendoscopy can identify lesions detected on random biopsies taken during white light endoscopy. The finding of invisible low-grade dysplasia on random biopsies merits a repeat colonoscopic exam in 3-6 months. There are no data to suggest that adding a biologic agent when the patient is in remission will increase the detection of dysplasia. Although IPAA surgery is an option, most gastroenterologists would defer on recommending surgery until a chromoendoscopic exam is performed.

Question 2

A 52-year-old woman with a 10-year history of pan-ulcerative colitis on mesalamine was noted to have mild patchy inflammation in the colon as well as a 1.2-cm well-circumscribed polyp located in the descending colon at surveillance colonoscopy. The polyp was excised in its entirety. Which of the following treatment recommendations is most appropriate?

A. The patient should be advised to have a colectomy based on the high risk of developing cancer.

B. If the polyp has high-grade dysplasia, the patient should be advised to have a colectomy, but if it has low-grade dysplasia, continued surveillance is warranted.

C. If the polyp was fully excised with negative margins, the patient can be managed safely with continued surveillance.

D. Recommend colectomy if the degree of histologic inflammation is extensive and severe.

Answer 2

Patients with a polypoid dysplastic lesion that can be endoscopically resected do not require colectomy and can be managed by continued endoscopic surveillance. This is true regardless of whether the dysplastic lesion has low-grade or high-grade dysplasia. Severe inflammation elsewhere in the colon is associated with an increased risk of developing ulcerative colitis-related dysplasia but would not impact the decision to proceed with colectomy in this clinical scenario. Future exams should incorporate chromoendoscopy in her surveillance protocol.

Question 3

An 18-year-old high school student presents with a new diagnosis of ileocolonic Crohn’s disease. She had symptoms of diarrhea and abdominal pain for 2 months that were initially treated symptomatically. She subsequently underwent a colonoscopy that showed scattered aphthous ulcers in the ileum with no strictures. Biopsies confirmed chronic active inflammation with rare granulomas. She is in your office today to discuss various treatment options. She and her parents express significant concern with using pharmacologic therapy and request other options.

Laboratory test results reveal:
Hemoglobin 12.5 g/dL (normal: 12-16 g/dL)
Hematocrit 40% (normal: 36-47%)
Serum albumin 3.9 g/L (normal: 3.5-5.5 g/dL)
C-reactive protein 8.5 mg/dL

In this setting, the efficacy of which of the following treatment options are robustly supported by controlled clinical trial evidence?

A. Specific carbohydrate diet

B. Probiotic therapy with VSL#3 1 sachet twice daily

C. Curcumin 3 grams daily in combination with omega-3 fatty acid containing fish oil

D. Exclusive enteral nutrition

E. Low-fiber diet

Answer 3

• Of various nutritional and microbiome based therapies that have been studied in Crohn’s disease, efficacy of exclusive enteral nutrition alone is supported by high-quality randomized controlled trial data in the pediatric population.
• While case series have described clinical efficacy of the specific carbohydrate diet, this has not been demonstrated in controlled clinical trials.
• Probiotic therapy with VSL#3 and curcumin have demonstrated efficacy in inducing and maintaining remission in mild to moderate ulcerative colitis but have not been studied for Crohn’s disease.
• A low-fiber diet is frequently recommended for those with symptomatic strictures but is not a treatment of inflammatory Crohn’s disease.

Question 4

A 63-year-old man with a 25-year history of ulcerative colitis comes to see you for surveillance colonoscopy for dysplasia screening; his last colonoscopy was over 5 years ago. A 1-cm, nongranular superficially elevated lesion is noted in the ascending colon. Upon close inspection, there are areas of morphologic depression. What is the best next step in management?

A. Try to remove the lesion in piecemeal fashion.

B. Refer to a colorectal surgeon.

C. Refer to an advanced endoscopist.

D. Obtain CT enterography.

Answer 4

• Management of predysplastic and dysplastic lesions in patients with IBD has changed significantly over the years with the advancement of endoscopic techniques. While the areas of depression suggest advanced pathology such as mucosal or submucosal deep invasion, the lesion described still meets criteria for endoscopic removal.
• However, it should be correctly staged, marked, and referred to an advanced endoscopist who can perform a complete resection of the lesion. Note the location of the tattoo is dependent on the anticipated management of a lesion. For example, when marking a lesion for future endoscopic resection, then it is recommended that 2-3 separate injections at 3-5 cm distal (anal side) to the lesion should be performed.
• SCENIC guidelines also support the use of surveillance colonoscopy after complete resection over referral for colectomy, emphasizing the use of high-quality chromoendoscopy.
• CT enterography would not be required unless the lesion turns out be malignant and imaging is required for staging purposes.

Question 5

A 68-year-old woman presents with a 3-year history of ulcerative colitis. She was initiated on treatment with mesalamine 4.8 g/day but was not able to achieve durable steroid-free remission and remained dependent on budesonide 9 mg/day. Her past medical history is significant for a diagnosis of breast cancer when she was 55 years old that was treated by mastectomy with hormone therapy, and 2 basal cell cancers and 1 squamous cell skin cancer at age 60, 62, and 65, respectively. She also has known coronary artery disease and had an episode of congestive heart failure requiring hospitalization 2 years ago. Her family history is significant for a brother with multiple sclerosis. Which of the features in her history are of concern while considering initiation of azathioprine therapy?

A. Family history of multiple sclerosis

B. Her past history of breast cancer and use of hormone therapy

C. Her history of basal and squamous cell skin cancers

D. Prior decompensated heart failure

Answer 5

• Thiopurines are associated with an increased risk of primary as well as recurrent nonmelanomatous skin cancers (basal cell cancer and squamous cell cancers).
• Thus, they should be used with caution in those at elevated risk for such conditions or with a history of recurrent NMSC.
• In contrast, they have NOT been associated with an increased risk of primary or recurrent solid organ cancers or breast cancer.
• Anti-TNF biologics are contraindicated in patients with a personal history of demyelinating disease and decompensated heart failure, but these conditions do not contraindicate use of thiopurines.

Question 6

A 48-year-old man presents with a 10-year history of ulcerative colitis. He was initially treated with mesalamine 4.8 grams daily with durable remission for 5 years before experiencing loss of response requiring a course of systemic steroids. He developed pancreatitis with azathioprine and was then started on infliximab monotherapy. He lost response to infliximab after 2 years despite dose escalation to 10 mg/kg every 4 weeks. Adalimumab and golimumab were tried and were not effective, after which he achieved remission for 2 years on vedolizumab. He eventually experienced loss of response to this treatment and was initiated on tofacitinib 10 mg twice daily. He is at increased risk for which of the following adverse effects because of his use of tofacitinib?

A. Increase in serum triglycerides

B. Pancreatitis

C. Increase in serum LDL cholesterol

D. Interstitial nephritis

Answer 6

• Tofacitinib, a nonselective janus kinase inhibitor for treatment of ulcerative colitis, is associated with an increase in serum LDL and HDL cholesterol and creatine kinase.
• It is also associated with an increase in risk of herpes zoster infection.
• It is not associated with elevation in serum triglycerides. Pancreatitis can be seen in 1-3% of patients initiating thiopurine therapy but is not associated with tofacitinib use.
• Interstitial nephritis is a rare side effect (1: 1,000) of aminosalicylates and has not been associated with tofacitinib.

Question 7

A 35-year-old woman presents with a 1-year history of ileocolonic Crohn’s disease. After requiring prednisone at diagnosis, she was placed on treatment with azathioprine 150 mg daily (2.5 mg/kg body weight). She was in symptomatic remission for 6 months on azathioprine after tapering off the prednisone. However, she now begins to experience increasing diarrhea, abdominal cramping, and a weight loss of 5 lb. Stool testing is negative for enteric infections including Clostridium difficile.

Her laboratory tests results are as follows:
Hemoglobin 11.0 g/dL (normal: 12-16 g/dL)
Hematocrit 36% (normal: 36-47%)
White blood cell count 9.0 cells/mm3
MCV 85 fL (normal: 80-100 fL)
Albumin 3.8 g/L (normal: 3.5-5.5 g/dL)
ALT 65 U/L (normal: 0-35 U/L)
AST 55 U/L (normal: 0-35 U/L)
Alkaline phosphatase 101 U/L (normal: 36-92 U/L)
Bilirubin 0.4 mg/dL (normal: 0.3-1.2 mg/dL)

You obtain thiopurine metabolite testing that reveals a 6-thioguanine (6TGN) level of 150 pmol/8 x 108 RBCs and 6-methylmercaptopurine (6MMPN) level of 7,200 pmol/8 x 108 RBCs. You start her on budesonide 9 mg/day. Which of the following would be the best next step for this patient?

A. Assess for nonadherence and continue azathioprine at the same dose.

B. Increase azathioprine to 200 mg/day and add Pentasa® (mesalamine).

C. Reduce azathioprine to 50 mg/day.

D. Add allopurinol 100 mg/day and reduce azathioprine to 50 mg/day.

Answer 7

• The patient is experiencing a flare of her Crohn’s disease in the setting of subtherapeutic 6-TGN levels and shunting towards 6-MMPN production. Meta-analyses suggest that a 6-TGN level of 230-450 pmol/8 x 108 is associated with superior rates of response. Hence, continuing azathioprine at the same or lower dose here is not likely to be of durable benefit.
• Increasing the dose of azathioprine alone may not elevate 6TGN sufficiently into the therapeutic range and moreover, we are seeing evidence of hepatotoxicity mediated by elevated 6-MMPN levels. The addition of allopurinol will reverse this shunting and increase 6TGN levels into the therapeutic range. However, this should always be accompanied by a reduction in thiopurine dose by 50-75% to avoid significant increase in 6TGN levels and myelosuppression.

Question 8

Turmeric, a spice traditionally used in Indian and Chinese herbal medicine, originates from the root Curcuma longa and is a member of the ginger family. This complementary agent has recently been reported to be effective in the treatment of inflammatory bowel disease. Which of the following medications may adversely interact with turmeric based on its mechanism of action?

A. Hydrochlorathiazide

B. Clopidogrel

C. Citalopram

D. Metoprolol

Answer 8

Turmeric exhibits an inhibitory effect on platelet aggregation. Therefore, patients who are maintained on agents such as aspirin, clopidogrel, or ticlopidine should be closely monitored if prescribed this complementary therapy to avoid the possibility of a bleeding complication.

Question 9

A 27-year-old man with Crohn’s disease diagnosed 4 years ago is referred to your office after having an ileocolonic resection 6 months ago. He is recovering well with no postoperative infections or complications. He has an improved appetite and decreasing diarrhea; however, he has not been able to quit smoking despite his surgeon’s recommendation. He is currently not on any medications. His CT scan 2 months before the surgery revealed 2 segments of moderate terminal ileal wall thickening. His laboratory test results at this visit reveal Hgb 13.1 g/dL (normal: 14-17 g/dL) and MCV 79 fL (normal: 80-100 fL). His Quantiferon®-TB was negative, and he is hepatitis B immune. On exam, his abdominal scar is well healed. What is the next step in managing this patient?

A. Order CT scan of the abdomen and pelvis.

B. Schedule a colonoscopy.

C. Check fecal calprotectin.

D. Start infliximab.

E. Start budesonide.

Answer 9

Given the patient wasn’t already started on postoperative prophylaxis shortly after the surgery (the right time to think about infliximab or thiopurines), the recommendation is to check for disease recurrence at the neoterminal ileum at 6 months postoperatively. CT scan and fecal calprotectin, while indirectly suggestive of inflammation, do not allow for the grading of postoperative recurrence using Rutgeerts score. Budesonide is not accepted as a postoperative prophylaxis intervention.

Question 10

A 30-year-old man presents to the clinic for management of his newly diagnosed Crohn’s disease. For the past few months, he has been having diarrhea with 3-6 liquid stools per day. He denies abdominal pain, weight loss, or any extraintestinal symptoms. His primary doctor ordered blood and stool tests. Based on those test results, he was told he had Crohn’s disease. He has already had a colonoscopy with negative biopsies. He also underwent an MR enterography that was normal. You note that his stool calprotectin was elevated at 106 (normal: <50 µg/g). Physical exam findings are unremarkable except he has erythematous nodules over his elbows bilaterally. What is the next step in the management of this patient?

A. Start infliximab.

B. Order IgA tissue transglutaminase antibody.

C. Repeat colonoscopy.

D. Watchful waiting

Answer 10

The yield for repeating the colonoscopy would be low as it was recently normal and biopsies were normal. There is no tissue diagnosis of Crohn’s disease and the stool calprotectin is elevated but not very high, so answer A is incorrect. Recognizing that there are other etiologies for elevated calprotectin besides inflammatory bowel disease, this patient should be evaluated for celiac sprue, especially with the described rash, so an IgA tissue transglutaminase should be ordered. Watchful waiting is inappropriate in this scenario.

Question 11

developing a rash on his abdomen and hands for the last 2 months. It started out as “itchy redness” but now it is peeling and extremely itchy. Nonprescription 1% topical corticosteroid cream, prescribed by his primary care, has been ineffective. Six months ago, he was started on adalimumab with an induction regimen followed by 40 mg subcutaneously every other week for his moderately active Crohn’s disease. He has done very well on this regimen and has not required any steroids for the past 4 months.

On physical examination, vital signs are stable. Erythematous patches of desquamating skin are seen on both palms and on the extensor surfaces of the hands. Scattered patches of flaky, desquamating skin are also seen on the abdomen. Laboratory investigations including complete blood count, electrolytes and liver function tests and are within normal limits. Which of the following is the most appropriate management strategy for this patient?

A. Change adalimumab dose to every fourth week.

B. Discontinue adalimumab.

C. Increase adalimumab dose to once weekly.

D. Prescribe a short course of oral steroids and continue adalimumab

Answer 11

• Anti-tumor necrosis factor (TNF) therapy has been associated with the de novo development of psoriaform lesions in patients with inflammatory bowel disease. For mild cases, some physicians advocate treating the skin with topical steroids and continuing the anti-TNF agent.
• However, when a patient is significantly affected by the lesions, and their symptoms continue to worsen with exposure to continued anti-TNF administration, cessation is recommended until the lesions improve.
• Another anti-TNF may be tried, but re-induction with the same agent is not recommended. Dose escalation will cause the lesions to worsen. Decreasing the dosing interval will also not resolve the lesions, as continued exposure will perpetuate the condition.
• Treatment with steroids while continuing the offending agent has not been shown to be effective at eradicating the lesions completely.

Question 12

A 45-year-old patient with Crohn’s disease was started on infliximab nearly 20 years ago, and while he initially responded well to infliximab, he lost response after 8 years and was switched to adalimumab. He experienced only partial response to adalimumab and now weekly dosing is not controlling his disease. Which of the following is the most appropriate treatment?

A. Certolizumab pegol (anti TNF)

B. Tofacitinib (UC Only)

C. Golimumab (anti TNF)

D. Vedolizumab

Answer 12

This patient has lost response to 2 anti-TNF therapies. The chance of a third anti-TNF therapy (certolizumab pegol and golimumab) working is low and it would be preferable to choose a treatment with a different mechanism of action. Tofacitinib, a janus kinase inhibitor, is currently only approved for ulcerative colitis. Vedolizumab is FDA approved to treat active Crohn’s disease as well as ulcerative colitis and would be an appropriate option for this patient.

Question 13

A 50-year-old man with ulcerative colitis previously well on daily 5-ASA therapy develops worsening symptoms, and you are considering escalating his therapy to a biologic. He tells you that he is having some visual changes, and on physical exam, there is some weakness of his right leg and left arm. After a work-up by a neurologist, he is diagnosed with multiple sclerosis (MS). Which biologic would be most appropriate in this scenario?

A. Adalimumab

B. Golimumab

C. Ustekinumab

D. Vedolizumab

E. Infliximab

Answer 13

• Anti-TNF therapy is contraindicated in the setting of MS; therefore, adalimumab, golimumab, and infliximab should be avoided.
• Ustekinumab is also not an appropriate choice as it is not approved for ulcerative colitis.
• Vedolizumab is a gut specific anti-integrin monoclonal antibody and is safe in the setting of MS.

Question 14

Mechanism of action of

1. ustekinumab
2. vedolizumab

Answer 14

1. anti-IL12/23 - crohns
2. anti-integrin therapy - both

Question 15

A 27-year-old woman with ileocolonic Crohn’s disease with perianal involvement learns she is 8 weeks’ pregnant. Her disease has been well controlled on infliximab every 7-8 weeks. She experiences some mild drainage and discomfort from her perianal fistula if she receives her infusions more than 8 weeks apart. She tells you she wants to stay well through the pregnancy. What do you counsel her about infliximab infusions during pregnancy?

A. Stop infliximab now and resume after delivery.

B. Stop infliximab at 20 weeks’ gestation.

C. Stop infliximab around 30 weeks’ gestation.

D. Administer 1 dose of infliximab now at a dose of 10 mg/kg and then hold infliximab until after delivery.

Answer 15

This patient has perianal Crohn’s disease that is controlled on the current medical regimen, but she is not in deep remission. Infliximab crosses the placenta after week 20, which is why in patients who are in deep remission, it might be reasonable to hold future doses until after delivery. For someone who needs therapy to stay well, the last dose should be timed before the highest rate of placental transfer and when she could thereby hold off on any infusions until after delivery, which would be around week 30. Giving her a double dose now and holding has not been a strategy endorsed by any experts

Question 16

Epidemiologic and clinical studies indicate that UC patients at highest risk for poor outcomes are

Answer 16

• young, nonsmokers, anemic, hospitalized soon after diagnosis, have a high C-reactive protein or sedimentation rate, and have extensive colitis with deeper ulcerations.
• Family history increases the risk of ulcerative colitis, but there is no evidence to suggest a correlation with an aggressive disease course.
• Bowel frequency plays a limited role in defining disease severity and prognosis.
• Oral contraceptives have been implicated in the development of inflammatory bowel disease and possible exacerbation of Crohn’s disease, but not ulcerative colitis.

Question 17

A 32-year-old woman with Crohn’s colitis is in clinical remission on vedolizumab every 8 weeks with a therapeutic trough level (21 µg/mL) without anti-drug antibodies. Colonoscopy shows patchy areas of ulceration in the ascending, transverse, and descending colon. Fecal calprotectin is 680 mcg/gram (normal: <163 mcg/g). Hematocrit is 33%. What would you recommend?

A. Make no change as she is in clinical remission.

B. Have a discussion with the patient about switching to a different biologic agent.

C. Change the frequency of vedolizumab infusions to every 4 weeks.

D. Start mesalamine enemas.

Answer 17

In this patient, despite clinical remission, the presence of an elevated fecal calprotectin and persistent endoscopic inflammation confirms ongoing disease activity. The patient is at increased risk of developing a clinical recurrence. In the open label CALM study, patients initially treated with a course of prednisone were randomized to escalation of medical therapy (addition of adalimumab every 2 weeks, adalimumab every week and addition of azathioprine) based on clinical symptoms (CDAI) or laboratory parameters (CRP and fecal calprotectin). The results of the CALM study demonstrated that 45.9% of patients who received a treat to target approach with escalation of therapy met the primary endpoint of a Crohn’s disease Endoscopic Index of Severity Score of under <4 and absence of deep ulcers on colonoscopy compared with 30.3% in the clinical management group. Rates of secondary endpoints (deep remission and biologic remission) were also higher in the treat to target group. The decision to escalate therapy in a patient who is clinically well requires the use of the shared decision model with the patient to understand their goals of treatment. In a patient with therapeutic drug levels, changing the dose of vedolizumab is unlikely to increase the rate of endoscopic healing. As the patient’s disease in in the proximal colon, adding mesalamine enemas is unlikely to treat the endoscopic inflammation.

Question 18

A 57-year old man presents for further evaluation of dysphagia and noncardiac chest pain symptoms intermittently over the past 2 years. He has a past medical history notable for gastroesophageal reflux (GERD) on omeprazole, hypertension on amlodipine, chronic lower back pain on oxycodone, and he takes metoprolol and a daily aspirin for coronary artery disease. He undergoes an esophageal manometry evaluation with the following pattern on liquid swallows [FIGURE]. Which of his medications has been associated with this motility pattern?

A. Omeprazole

B. Amlodipine

C. Oxycodone

D. Metoprolol

E. Aspirin

Answer 18

This patient has a esophageal manometry pattern of esophagogastric junction outflow obstruction (EGJOO) with incomplete lower esophageal sphincter (LES) relaxation and high residual LES pressures with liquid swallows. In recent years, this pattern, as well as spastic (type III) achalasia has come to be recognized in association with chronic opiate use, in particular if opiates are taken within 24 hours of the manometry study. None of the other medications this patient is taking have any known association with this motility pattern. When identified, efforts to exclude structural disorders and pseudoachalasia via endoscopy and/or imaging should be undertaken, and where possible minimization or discontinuation of opioids is encouraged.

Question 19

A 21-year-old man presents to the emergency department with a 6-hour history of intractable nausea and vomiting. This started suddenly without warning the morning of presentation. He has had multiple episodes of vomiting and has been unable to tolerate any oral intake including fluids. These symptoms are associated with generalized abdominal pain. He has presented to the emergency department 8 times in the last 3 years for similar symptoms, and his symptoms are becoming more frequent. This is his second visit in the last 6 months. During those presentations, he was treated with IV hydration, IV ondansetron and IV diphenhydramine, which resolve his symptoms. The longest episode lasted 3 days before resolving. He states that he feels perfectly well in between episodes. He will have a mild headache after the vomiting begins but it is not severe. He has no neurologic symptoms with these episodes and his abdominal pain is never severe. He has no signs of gastrointestinal bleeding. His has not lost weight during the last 2 years. He has had to miss school when these symptoms occur. He is otherwise healthy and on no regular medications. His mother has a history of migraine headaches. He does not smoke cigarettes or drink alcohol. He has tried marijuana 3 times in the last year.

On examination, he appears pale and has vomited twice during the assessment. Blood pressure is 116/80 with a heart rate of 98 bpm. His abdomen is soft and nontender with no palpable masses. Laboratory data including complete blood count, comprehensive chemistry panel, and liver enzymes are normal. What is the most likely diagnosis in this patient?

A. Gastroparesis

B. Cyclic vomiting syndrome

C. Cannabis hyperemesis syndrome

D. Functional nausea and vomiting syndrome

Answer 19

This patient currently meets the Rome IV diagnostic criteria for cyclic vomiting syndrome. This is characterized by acute episodes of vomiting that last less than 1 week. There must be at least 3 episodes in the past year with at least 2 occuring in the last 6 months. There is a lack of symptoms in between the discrete episodes. The family history of migraine headaches in his mother is also suggestive. This is unlikely gastroparesis given that he is symptom-free in between these acute episodes. While he does have a history of some marijuana use, it is limited. Cannabis hyperemesis syndrome requires prolonged excessive use of marijuana. Chronic nausea and vomiting is diagnosed when the patient has at least 1 day per week of bothersome nausea and 1 day per week of vomiting with no evidence of systemic or organic disease.

Question 20

A 29-year-old woman presents to your clinic as a new patient for a third opinion for her GI problems. She complains of persistent nausea, early satiety, epigastric discomfort that is worse after eating, and postprandial fullness. She has had these symptoms for about 5 years. She has lost weight over the past 2 years. Multiple evaluations to date are as follows: normal EGD without ulcers, slightly delayed gastric emptying study, and negative biopsies for Helicobacter pylori. She had a cholecystectomy 5 years ago for pain. She did not have stones and this procedure did not change her symptoms. She has been given numerous trials of various proton pump inhibitors, antiemetics, sucralfate, metoclopromide, and combinations of these same medications without improvement of her symptoms.

Physical exam shows a thin female but otherwise normal. She has normal bowel sounds and no masses in the abdomen. You suspect she has functional dyspepsia and do not feel that further repeat testing is required. What empiric pharmacological treatment should be considered next?

A. Amitriptyline

B. Mirtazapine

C. Cyproheptadine

D. Pregabalin

Answer 20

• Treatment of functional dyspepsia remains challenging. In these treatment-refractory cases, the use of neuromodulating agents is often tried, and mirtazapine is one such option.
• There are anecdotal reports of benefit from cyproheptadine in cyclic vomiting syndrome, but the patient described does not meet the criteria for that diagnosis.
• Low-dose tricyclic antidepressants are commonly used to treat refractory functional disorders. In a randomized, placebo-controlled functional dyspepsia treatment trial, patients randomized to amitriptyline reported greater symptom improvement compared to either placebo or escitalopram, but the response was greater in those with ulcer like functional dyspepsia and those with normal gastric emptying. This patient has delayed gastric emptying, so amitriptyline is not a good option. There are no controlled trials of pregabalin in functional dyspepsia.

Question 21

A 39-year-old divorced executive presents with fullness after eating, inability to finish a normal-sized meal, and very mild recurrent dull epigastric pain for several years. The symptoms began after an acute episode of diarrhea and “upset stomach” attributed to food poisoning while on vacation in Las Vegas. The symptoms most often occur postprandially and trouble her regularly, although she has not lost weight. Occasionally, she may go symptom-free for a few days. She denies significant nausea and has had no vomiting. Mild heartburn occurs less than once a week, but she has no dysphagia, acid regurgitation, or weight loss. Her bowel habits are normal. Twice daily high-dose proton pump inhibitor therapy was of no help over a 6-month period. She does admit to being under stress at work and at home, but has no symptoms of depression. There is no family history of any malignancies.

Findings from the physical exam are normal and her BMI is 24. Esophagogastroduodenoscopy is completely normal; H. pylori testing, an abdominal ultrasound, and routine CBC and biochemistry are all negative. What is the next most appropriate step in management?

A. Refer for a gastric emptying study.

B. Reassure the patient, provide a diagnosis, and discuss treatment options.

C. Refer to a psychiatrist to rule out a psychiatric diagnosis.

D. Order esophageal manometry.

E. Arrange a colonoscopy.

Answer 21

• The patient presents with functional dyspepsia (FD) and a detailed work-up has excluded the likely known structural causes.
• Reassurance, an explanation of the diagnosis, and treatment options would be the appropriate next step.
• Gastroesophageal reflux disease (GERD) is unlikely – she has infrequent heartburn (less than once a week), no response to proton pump inhibitor (including high dose), and no evidence of esophagitis.
• A gastric emptying study is not immediately necessary.
• There are no indicators of a comorbid psychiatric illness.
• Esophageal manometry would add no diagnostic value here, just extra cost, as the patient denies dysphagia.
• A colonoscopy is not indicated as there are no colonic signs/symptoms. Empiric treatment with pro-motility agents is appropriate for symptoms consistent with FD-postprandial distress subtype.

Question 22

A 26-year-old woman presents in referral for further management of postprandial epigastric pain. She describes her symptoms as a “sharp pain” which she has experienced several days a week for the past 2 years. She also reports some early satiety, an exacerbation of her symptoms with meals, and bloating and fullness. Her pain is not associated with changes in her bowels, and she does not report any weight loss, nausea, vomiting, or overt gastrointestinal blood loss. Her symptoms do not awaken her from sleep at night. Her only past medical history is dysmenorrhea and migraines, and she takes ibuprofen as needed for these symptoms (usually 200 mg twice a day, no more than 5 days a month). She has been trialed on ranitidine 150 mg twice a day for 4 weeks, and subsequently omeprazole 40 mg once a day for 8 weeks. Neither approach led to symptom relief, however.

Her physical exam revealed moderate epigastric pain without guarding or rebound tenderness, and laboratory testing revealed a normal complete blood count and complete metabolic panel. She underwent upper endoscopic evaluation without findings of concern, and biopsies of the fundus and antrum of the stomach were normal, without evidence of H. pylori. A solid phase gastric emptying scan demonstrated gastric retention of 15% of the meal at 4 hours. Her epigastric pain is bothersome enough that she is missing work or social activities at least once a month. You consider starting her on amitriptyline to help control her symptoms. Which of the following is most likely to improve following amitriptyline therapy?

A. Epigastric pain

B. Bloating

C. Early satiety

D. Postprandial fullness

E. Abnormal gastric emptying

Answer 22

This patient has features of both the epigastric pain syndrome (EPS) variant of functional dyspepsia (FD), with pain centered in the upper abdomen as a predominant symptom, as well as the postprandial distress (PDS) variant, the latter manifesting with fullness and discomfort in association with meals. The Functional Dyspepsia Treatment Trial (FDTT) was undertaken as a multicenter study of antidepressants (amitriptyline or escitalopram) in the treatment of FD patients without depression. The study revealed antidepressants overall were superior to placebo in the treatment of FD. Further, amitriptyline was superior to escitalopram in treating FD, particularly in addressing the EPS-predominant pattern of symptoms. Postprandial symptoms (fullness, bloating, early satiety were much less responsive to antidepressant therapy). FDTT also revealed that antidepressant therapies were less effective in patients with abnormal gastric emptying, and moreover that these treatments had no effect on gastric emptying or meal-induced satiety. GI symptoms aside, both antidepressants improved patients’ overall quality of life in the study.

Question 23

A 47-year-old man complains of nausea and regurgitation, which have been worsening over 2 years. He reports passive regurgitation within 5-10 minutes of consuming solids or liquids. His symptoms started after he went through a difficult divorce. EGD, barium swallow, and CT scans of his abdomen and pelvis were normal. He was trialed on a twice daily PPI without symptom relief. A gastric emptying study was attempted, but the patient regurgitated the meal soon after ingestion, limiting the study interpretability. He denies weight loss and a laboratory analysis does not show electrolyte abnormalities. Which of the following is the most appropriate next step in this patient’s management?

A. Perform a gastric emptying study to establish the diagnosis.

B. Place a jejunostomy tube.

C. Place a gastric electrical stimulator.

D. Refer for relaxation and breathing techniques.

E. Prescribe antiemetics and benzodiazepine combination therapy.

Answer 23

• This patient has a history and work-up consistent with rumination syndrome, which is characterized by effortless regurgitation within minutes of liquid or oral consumption. This syndrome can be distinguished from gastroparesis based on timing of regurgitation.
• Vomiting due to gastroparesis can occur up to several hours after ingestion, while in rumination syndrome, it usually occurs within a few minutes and up to half an hour after meals.
• Antroduodenal manometry, available only in specialized centers, may show an “R-wave,” a simultaneous increase in pressure across all measurement levels from the jejunum to the stomach and esophagus as regurgitation develops. A work-up needs to be done on these patients to exclude other causes of regurgitation, including obstruction and motility disorders. Once these pathologies have been excluded, the diagnosis of rumination syndrome can be made.
• The treatment of rumination syndrome consists of relaxation and breathing technique. In addition, tricyclic antidepressants can be used as a pharmacologic adjunct to therapy.
• These patients have difficulty undergoing a gastric emptying study (GES) since they often regurgitate the ingested meal, and GES is not necessary to make the diagnosis. Jejunostomy tube placement is not necessary in this patient since he is not experiencing severe weight loss and is not having electrolyte abnormalities. Gastric electrical stimulator may have a role in some patients with refractory gastroparesis, but has not been studied in rumination syndrome. Although patients with rumination syndrome may require antiemetics for breakthrough symptoms, they are advised to avoid benzodiazepines due to concerns for potential dependence.

Question 24

A 36-year-old man presents with a 5-year history of recurrent lower abdominal pain on 2 days per week associated with formed to progressively loose, watery stools, as well as urgency and bloating. He has up to 4-5 bowel movements on days with pain and diarrhea. On other days, he either does not pass stool or has 1-2 formed bowel movements. His symptoms typically occur during the day and increase after ingestion of a meal. His symptoms have worsened over the last year after starting a new job. He does not have nocturnal diarrhea. He has no blood in his stool. When his symptoms started, he lost 5 lb but has since gained this back. He has never traveled outside of the United States and has never been camping. He has tried a lactose-free diet with no change in symptoms. He previously had a cholecystectomy at age 30 for symptomatic gallstones. He is otherwise healthy and on no regular medications. He has no relevant family history. He does not smoke, drink alcohol, or use illicit substances.

Findings from the physical examination are normal. Blood work including complete blood count, comprehensive chemistry panel, C-reactive protein, and celiac serologies were normal. A fecal calprotectin was <100 µg/g. He declined proceeding with a colonoscopy. Which of the following therapies is the best option for him at this time?

A. Amitriptyline

B. Budesonide

C. Eluxadoline

D. Alosetron

Answer 24

This patient meets the Rome IV diagnostic criteria for IBS with diarrhea (IBS-D). He does not have any alarm features such as blood in the stool, unintentional weight loss, or family history of colon cancer/inflammatory bowel disease. Negative celiac serologies, negative fecal calprotectin, and normal C-reactive protein are supportive of this diagnosis. From the choices given above, amitriptyline (a tricyclic antidepressant) is the best treatment option at this time. This has been shown in studies to reduce pain in patients with IBS. In addition, the anticholinergic properties of this medication may cause constipation which may be helpful in improving his stool form. Budesonide is not a treatment option for IBS-D. This is used to treat inflammatory bowel disease. While this is a diagnostic possibility, it is less likely given the duration of his symptoms, lack of alarm features, and normal investigations. Eluxadoline is a mu and kappa opioid receptor agonist and delta opioid receptor antagonist that is FDA approved for the treatment of IBS-D. However, due to the risk of pancreatitis seen as a side effect in randomized clinical trials, it is contraindicated for use in patients with a cholecystectomy. Alosetron is a 5-HT3 antagonist that is FDA approved for the management of severe IBS-D in females only. Furthermore, given the risk of ischemic colitis with this medication it is not considered first-line therapy.