A 33-year-old woman with Crohn’s disease colitis presents to her physician after 2 days of photophobia and blurred vision. She has had no similar episodes in the past. She has no abdominal pain or diarrhea and takes mesalazine, azathioprine, and prednisone as maintenance therapy. Her vital signs are within normal range. Examination of the eyes shows conjunctival injection. The physical examination is otherwise normal. Slit-lamp examination by an ophthalmologist shows evidence of inflammation in the anterior chamber. Which of the following is the most appropriate modification to this patient’s medication at this time?

No modification of therapy at this time

Decreasing dose of azathioprine

A 25-year-old man presents with abdominal pain and bloody diarrhea. His symptoms have been recurrent for the past few months, and, currently, he says he is having on average four bowel movements daily, often bloody. He describes the pain as cramping and localized to the left side of his abdomen. He also says that he has lost around 4.5 kg (10 lb) over the past 3 months. There is no other significant past medical history and the patient is not on current medications. His temperature is 37.7° C (100.0° F), pulse rate is 100/min, respiratory rate is 18/min, and blood pressure is 123/85 mm Hg. On physical examination, there is mild tenderness to palpation in the lower left quadrant of the abdomen with no rebound or guarding. Laboratory studies show anemia and thrombocytosis. Colonoscopy is performed, which confirms the diagnosis of ulcerative colitis (UC). What is the mechanism of action of the recommended first-line medication for the treatment of this patient’s condition?

Inhibition of leukotriene synthesis and lipoxygenase

Suppression of cellular and humoral immunity

Inhibition of enzyme phospholipase A2

A 28-year-old male presents to his primary care physician with complaints of intermittent abdominal pain and alternating bouts of constipation and diarrhea. His medical chart is not significant for any past medical problems or prior surgeries. He is not prescribed any current medications. Which of the following questions would be the most useful next question in eliciting further history from this patient?

"Can you tell me more about the symptoms you have been experiencing?"

"Does the diarrhea typically precede the constipation, or vice-versa?"

"Is the diarrhea foul-smelling?"

"Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"

"Are the symptoms worse in the morning or at night?"

A 25-year-old man presents to the emergency department for severe abdominal pain. The patient states that for the past week he has felt fatigued and had a fever. He states that he has had crampy lower abdominal pain and has experienced several bouts of diarrhea. The patient states that his pain is somewhat relieved by defecation. The patient returned from a camping trip 2 weeks ago in the Rocky Mountains. He is concerned that consuming undercooked meats on his trip may have caused this. He admits to consuming beef and chicken cooked over a fire pit. The patient is started on IV fluids and morphine. His temperature is 99.5°F (37.5°C), blood pressure is 130/77 mmHg, pulse is 90/min, respirations are 12/min, and oxygen saturation is 98% on room air. Laboratory studies are ordered and are seen below. Hemoglobin: 10 g/dL Hematocrit: 28% Leukocyte count: 11,500 cells/mm^3 with normal differential Platelet count: 445,000/mm^3 Serum: Na+: 140 mEq/L Cl-: 102 mEq/L K+: 4.1 mEq/L HCO3-: 24 mEq/L BUN: 24 mg/dL Glucose: 145 mg/dL Creatinine: 1.4 mg/dL Ca2+: 9.6 mg/dL Erythrocyte sedimentation rate (ESR): 75 mm/hour Physical exam is notable for a patient who appears to be uncomfortable. Gastrointestinal (GI) exam is notable for abdominal pain upon palpation. Ear, nose, and throat exam is notable for multiple painful shallow ulcers in the patient's mouth. Inspection of the patient's lower extremities reveals a pruritic ring-like lesion. Cardiac and pulmonary exams are within normal limits. Which of the following best describes this patient's underlying condition?

Transmural granulomas in the bowel

p-ANCA positive autoimmune bowel disease

Gram-negative microaerophilic organism

A 22-year-old man presents to the emergency department with abdominal pain. The patient states that he has had right lower quadrant abdominal pain for "a while now". The pain comes and goes, and today it is particularly painful. The patient is a college student studying philosophy. He drinks alcohol occasionally and is currently sexually active. He states that sometimes he feels anxious about school. The patient's father died of colon cancer at the age of 55, and his mother died of breast cancer when she was 57. The patient has a past medical history of anxiety and depression which is not currently treated. Review of systems is positive for bloody diarrhea. His temperature is 99.5°F (37.5°C), blood pressure is 100/58 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Cardiopulmonary exam is within normal limits. Abdominal exam reveals diffuse tenderness. A fecal occult blood test is positive. Which of the following is the most likely diagnosis?

Inflammatory bowel disease (IBD)

A 44-year-old woman comes to the physician with increasingly yellow sclera and pruritus over the past 3 months. She has intermittent right-upper-quadrant pain and discomfort. She has no history of any serious illnesses and takes no medications. Her vital signs are within normal limits. Her sclera are icteric. Skin examination shows linear scratch marks on the trunk and limbs. The remainder of the physical examination is unremarkable. Laboratory studies show: Complete blood count Hemoglobin 15 g/dL Mean corpuscular volume 95 μm3 Leukocyte count 6,000/mm3 with a normal differential Serum Alkaline phosphatase 470 U/L Aspartate aminotransferase (AST, GOT) 38 U/L Alanine aminotransferase (ALT, GPT) 45 U/L γ-Glutamyltransferase (GGT) 83 U/L (N=5–50 U/L) Bilirubin, total 2.7 mg/dL Bilirubin, direct 1.4 mg/dL Magnetic resonance cholangiopancreatography (MRCP) shows a multifocal and diffuse beaded appearance of the intrahepatic and extrahepatic biliary ducts. Which of the following is the most appropriate diagnostic study at this time?

No further testing is indicated

Endoscopic retrograde cholangiopancreatography (ERCP)

Medical management of Crohn's disease for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Treatment Goals - The Game Plan

Primary Goal: Induce and maintain remission.
Clinical Remission: Symptom control (e.g., Crohn's Disease Activity Index [CDAI] < 150).
Endoscopic Remission: Mucosal healing seen on endoscopy. This is the key therapeutic target to alter the natural history of the disease.

⭐ Mucosal healing is a better predictor of long-term, complication-free survival (e.g., ↓ hospitalizations, ↓ surgeries) than clinical remission alone.

Mild-to-Moderate CD - Starting Easy

Primary goal is inducing remission. Treatment choice depends on disease location and severity.

Corticosteroids (Induction)
- Budesonide (controlled-release): Preferred for ileal/right-sided colonic disease due to fewer systemic side effects.
- Prednisone: For patients who don't respond to budesonide or have more diffuse disease.
Other Agents
- 5-ASA (Mesalamine): Limited efficacy in inducing remission for Crohn's disease; more effective in UC.
- Antibiotics: Reserved for infectious complications like abscesses or fistulas, not for uncomplicated luminal disease.

⭐ Budesonide undergoes extensive first-pass metabolism in the liver, minimizing systemic corticosteroid exposure and side effects compared to prednisone.

Moderate-to-Severe CD - Bringing in Biologics

Induction of Remission: Systemic corticosteroids (e.g., prednisone 40-60 mg/day) are used for initial control of flares, followed by a taper.
Maintenance & Steroid-Sparing: Early introduction of a biologic agent is crucial for maintaining remission and avoiding long-term steroid toxicity. They can be used with or without an immunomodulator (e.g., azathioprine).

Biologic Mechanisms in Crohn's Disease

Drug Class	Examples (Generic/Brand)	MOA	Key Side Effects & Warnings	Pre-Screening
Anti-TNF	Infliximab (Remicade), Adalimumab (Humira)	Binds TNF-α, a key pro-inflammatory cytokine	↑ Infection risk, infusion reactions, demyelination, worsening HF	TB, Viral Hepatitis (HBV)
Anti-integrin	Vedolizumab (Entyvio)	Gut-selective; blocks α4β7 integrin, preventing leukocyte migration into gut tissue	Nasopharyngitis, headache. ⚠️ PML risk (rare)	Baseline labs, PML risk factors
Anti-IL-12/23	Ustekinumab (Stelara)	Inhibits pro-inflammatory cytokines IL-12 and IL-23	Upper respiratory infections, headache, fatigue	TB

Maintenance Therapy - Keeping the Peace

Goal: Achieve and maintain steroid-free remission.

Thiopurines:
- Azathioprine (AZA) & 6-Mercaptopurine (6-MP).
- ⚠️ Monitoring is key: Check TPMT activity before starting. Monitor CBC for leukopenia and LFTs.
Methotrexate:
- Used weekly (IM or SC).
- Effective for maintaining remission, especially if used for induction.
Biologics (Monoclonal Antibodies):
- Anti-TNF agents: Infliximab, Adalimumab, Certolizumab.
  - 📌 Mnemonic (Anti-TNF): Certolizumab, Infliximab, Adalimumab (CIA).
- Anti-integrin: Vedolizumab.
- Anti-IL-12/23: Ustekinumab.

⭐ High-Yield: Patients on thiopurines require regular monitoring for myelosuppression, a potentially fatal complication. TPMT enzyme testing helps identify patients at high risk for toxicity.

High-Yield Points - ⚡ Biggest Takeaways

For mild-to-moderate ileocolonic Crohn's, budesonide is first-line; 5-ASA compounds show minimal efficacy.

Moderate-to-severe disease requires anti-TNF agents (e.g., infliximab) or other biologics like ustekinumab.

Immunomodulators (azathioprine, methotrexate) are key steroid-sparing agents for maintenance.

For fistulizing disease, anti-TNF therapy is the primary treatment, often with antibiotics.

Smoking cessation is a critical intervention that improves disease course.

Surgery is not curative (unlike in UC) and is reserved for complications like strictures or abscesses.

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