Internal Medicine Correlations and Clinical Scenarios (CCS) USMLE Step 3

CASE 6: Inflammatory Bowel Disease

Setting: ED

CC: “I have blood in my stool.”

VS: BP:110/70 mm Hg; P: 84 beats/minute; T: 101.1°F; R: 12 breaths/minute

HPI: A 23 -year-old medical student arrives at the ED with blood and mucus in her stool that she says has been going on for several weeks to months. She also has low-grade fever and weight loss. The frequency of bowel movements has increased and that is why she has come today to the ED.

ROS: joint pain, diffusely

PMHX: none

Medications: Patient tried ciprofloxacin for diarrhea with no effect.

PE:

Image General: tired, weak, and angry appearing

Image Abdomen: soft, nontender

Image Skin: red-brown tender lesion below the knees

Initial Orders:

Image CBC

Image Stool studies: culture, ova/parasite examination

Image CHEM-20

Image IV NS

Image Orthostatic BP assessment

Which one of these is associated with blood?

a. Giardia

b. Entamoeba histolytica

c. Cryptosporidia

Answer b. Entamoeba histolytica

The only protozoan that gives blood in stool is Entamoeba. Infection of any kind is highly unlikely to be going on for “weeks to months.” It is very rare for any infection to last more than a few days. Infections are generally all self-limited and last for <1 week.

Forms of Diarrhea Never with Blood

• Viral

Staphylococcus aureus, Bacillus cereus

• Giardia

• Cryptosporidia

• Cholera

One hour later in the ED, the initial reports are ready:

Image CBC: hematocrit 32%; normal MCV; white blood cells (WBCs) 14,500/μL; platelets 535,000/μL

Image CHEM-20: potassium normal; albumin 2.7 g/dL (low); calcium 7.2 mg/dL (low)

Image Stool studies: results pending for the culture, ova/parasite examination

Image Orthostatic BP: not present

Platelet and WBC level can be elevated from any inflammatory stress.

Low Albumin Level = Low Total Calcium Level

Albumin down 1 g/dL = Calcium down 0.8 mg/dL

This is chronic diarrhea and it is nearly impossible to have an infection such as Campylobacter, Salmonella, or Shigella going on for weeks or months. There is evidence of malnutrition or malabsorption with the low albumin.

What test distinguishes between anemia of chronic disease and malabsorption with both iron and vitamin B12/folate deficiency?

a. Reticulocyte count

b. Red cell blood distribution width (RDW)

c. MCV

Answer b. Red blood cell distribution width (RDW)

RDW is a measure of how similar all the cells are in size. If all cells are the same size, the RDW is low, because there is no “distribution” of width, they are all the same. If some cells are small and some are large, the “mean” corpuscular volume or MCV will be normal, but the RDW will be increased. This is because some cells will be small and some large, with a normal average.

All nutritional deficiencies give a low reticulocyte count.

For chronic diarrhea cases, hydrate the patient and move the clock forward to get stool study results. Once you have excluded infections, order endoscopy and GI evaluation.

Reports:

Image Stool culture: no growth

Image RDW: Increased

Image Stool ova/parasites: negative

Several weeks of bloody diarrhea, mucus, fever, and weight loss are suggestive of inflammatory bowel disease (IBD) in general. There is no clear way to distinguish between Crohn disease (CD) of the colon and ulcerative colitis (UC) without endoscopy and sometimes biopsy.

What is the difference between UC and CD?

a. Joint pain

b. Iritis and uveitis

c. Sclerosing cholangitis

d. Skin symptoms: pyoderma gangrenosum and erythema nodosum

e. No difference

Answer e. No difference

The extraintestinal manifestations of both forms of IBD are identical. CD affects the large bowel in 40% of patients, and when this happens, CD can give sclerosing cholangitis. They can both give eye, skin, joint, and liver abnormalities.

Sigmoidoscopy reveals an inflamed mucosa consistent with IBD.

Orders:

Image Steroids IV

Image Iron studies, vitamin B12 level, methylmalonic acid level

Image Mesalamine

Mesalamine

• 5-ASA derivative

• Less adverse effects than sulfasalazine

Budesonide

• Oral steroid for IBD

• Extensive first-pass effect at liver

• Decreases systemic toxicity

Move the case forward 1 day. On the second hospital day, the frequency of diarrhea is reported as much decreased after the start of steroids and mesalamine.

Image Iron studies: low iron, high iron-binding capacity

Image Vitamin B12 level low, methylmalonic acid level high

• Iron is absorbed in the duodenum.

• Vitamin B12 is absorbed in the terminal ileum.

What is the greatest difference between CD and UC?

a. Response to mesalamine

b. Fistulae

c. Response to steroids

Answer b. Fistulae

CD causes fistulae, perirectal disease, and can affect any level in the bowel from mouth to anus. All IBD is treated with the 5-ASA medication mesalamine.

Transmural granuloma causes fistulae.

Which is consistent with CD?

a. Antineutrophil cytoplasmic autoantibody (ANCA) positive, Anti-Saccharomyces cerevisiae antibody (ASCA) negative

b. ANCA negative, ASCA antibody positive

Answer b. ANCA negative, ASCA positive

It can sometimes be difficult to distinguish between CD and UC especially when they both involve the large bowel. UC is ANCA positive/ASCA negative. The mechanism behind all of this is not clear.

By the third hospital day, the frequency of bowel movements and presence of blood is greatly decreased. Transfer the patient home. Every time you try to take the patient off steroids, her diarrhea, pain, bleeding, and mucus recur. Mesalamine is not enough to maintain them in remission.

Which therapy should you choose?

a. Azathioprine or 6-mercaptopurine

b. Methotrexate

c. Cyclophosphamide

d. Mycophenolate

Answer a. Azathioprine or 6-mercaptopurine

These agents are immunosuppressive agents that help wean a patient off steroids and prevent recurrence. Methotrexate is for rheumatoid arthritis, not IBD. Mycophenolate and cyclophosphamide are useful in lupus nephritis, but not IBD.

Perirectal Disease = Ciprofloxacin and Metronidazole

Rising Alkaline Phosphatase = Sclerosing Cholangitis

Magnetic Resonance Cholangiopancreatography (MRCP) = Best Test

Treat with cholestyramine or ursodeoxycholic acid.

• Cholestyramine binds bile in the bowel lumen.

• Ursodeoxycholic acid prevents bile formation.

Inflammatory bowel disease is a disorder that goes through intermittent periods of relative activity and inactivity. Several years later, the patient develops abdominal pain and a mass that is palpable. Despite mesalamine and steroids, a fistula develops between the bowel and the skin of the anterior abdominal wall.

What is the mechanism of the best therapy?

a. Interleukin inhibition

b. Inhibition of tumor necrosis factor (TNF)

c. Anti-CD20 antibody

d. Phospholipase inhibition

Answer b. Inhibition of tumor necrosis factor (TNF)

The anti-TNF medications are best used to close up fistulae in CD. Fistulae develop in the skin, vagina, and between bowel loops. Anti-TNF medications can reactivate tuberculosis (TB) and it is important to screen with a purified protein derivative (PPD) or interferon gamma release assay (IGRA) prior to using them. You do not have to complete all 9 months of therapy with isoniazid to safely use the anti-TNF drugs. These drugs are: infliximab, etanercept, and adalimumab.

What is the mechanism whereby TB is reactivated by anti-TNF medications?

a. They directly stimulate the growth of mycobacteria.

b. They suppress lymphocyte function.

c. TNF keeps granulomas intact.

d. No mechanism is known.

Answer c. TNF keeps granulomas intact.

TB is contained by the immune system and walled off in granulomas. TB can exist in a nonreplicative dormant state for many years inside a granuloma. TNF is the chemical signal the body uses to maintain the granuloma. When TNF is inhibited, the granuloma “unlocks” and TB starts to replicate again.

Starting the anti-TNF medication leads to resolution of the fistula over a few days. The medication also has an excellent effect on the primary disease, and the frequency of blood and diarrhea markedly improves.

Screening for Colon Cancer in IBD Patients

• Colonoscopy

• After 8 to 10 years of colon involvement

• CD patients also if the colon is involved

Features that do not change with disease activity:

• Sclerosing cholangitis

• Pyoderma gangrenosum

Move the clock forward 1 to 3 months at a time. Continue mesalamine chronically.

On CCS, it can be confusing if you think you have done everything, but the case does not end. Remember to do healthy maintenance such as vaccinations and tobacco cessation.



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