A 61-year-old man is evaluated in the emergency department for a 4-day history of severe d… — USMLE Step 3

A $61$ -year-old man is evaluated in the emergency department for a $4$ -day history of severe diarrhea and abdominal cramping. He reports having $8$ to $9$ large, watery bowel movements daily, compared to a baseline of $1$ formed stool per day. The patient has a history of metastatic non-small cell lung cancer, for which he has been receiving pembrolizumab therapy for the past $6$ months. He has not traveled recently, and he has not taken any recent antibiotics. Temperature is $37.7^\circ\text{C}$ ( $99.9^\circ\text{F}$ ), blood pressure is $108/66 \text{ mm Hg}$ , and pulse is $108/\text{min}$ . The abdomen is non-distended but diffusely tender to palpation without rebound or guarding. Laboratory evaluation shows:

Hemoglobin: $12.4 \text{ g/dL}$
Leukocyte count: $8,500/\text{mm}^3$
Potassium: $3.1 \text{ mEq/L}$
Creatinine: $1.3 \text{ mg/dL}$ (baseline $0.9 \text{ mg/dL}$ )

Stool studies for bacterial pathogens and *Clostridioides difficile* have been sent. Which of the following is the most appropriate next step in the management of this patient's symptoms?

Hold pembrolizumab and initiate intravenous methylprednisoloneCevap
B
Continue pembrolizumab and prescribe oral loperamide
C
Permanently discontinue pembrolizumab and administer intravenous infliximab
D
Withhold pembrolizumab and observe with intravenous fluids until stool testing results are finalized
E
Continue pembrolizumab and initiate empiric oral vancomycin

Cevap

Hold pembrolizumab and initiate intravenous methylprednisolone

The patient is presenting with Grade 3 immune-related colitis secondary to pembrolizumab (a PD-1 inhibitor). According to the Common Terminology Criteria for Adverse Events (CTCAE), Grade 3 diarrhea is defined by an increase of

\geq 7

stools per day over baseline, incontinence, or severe limitations in activities of daily living. The standard of care for Grade 3 immune-related adverse events (irAEs) is to immediately withhold the offending immune checkpoint inhibitor and initiate high-dose systemic corticosteroids (e.g., intravenous methylprednisolone at

1

2 \text{ mg/kg/day}

). Delaying treatment for pending diagnostic studies significantly increases the risk of severe complications, including bowel perforation and toxic megacolon.

Adım Adım Çözüm

Calculate the increase in bowel movements above baseline to grade the toxicity.

The patient has

8

9

stools daily with a baseline of

1

, resulting in an increase of

7

8

stools per day.

Grading immune-related adverse events (irAEs) dictates the management algorithm.

Correlate the stool frequency with the Common Terminology Criteria for Adverse Events (CTCAE) for colitis.

An increase of

\geq 7

stools per day over baseline defines Grade 3 diarrhea/colitis.

Grade 1 and 2 toxicities may allow for continued therapy or oral steroids, whereas Grade 3 and 4 require aggressive intervention.

Determine the appropriate pharmacologic intervention for Grade 3 immune-related colitis.

Hold the checkpoint inhibitor (pembrolizumab) and start high-dose intravenous corticosteroids (e.g., methylprednisolone

1

2 \text{ mg/kg/day}

Prompt immunosuppression is required to halt the autoimmune destruction of the colonic mucosa, preventing severe complications like perforation.

Anahtar Kavram

Management of Grade 3 Immune-Related Colitis

Soru

Cevap

Adım Adım Çözüm

Anahtar Kavram

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