USMLE PRACTICE QUESTION #91
TOPIC: Multisystemic Processes
Today’s question will test your understanding of a commonly tested multisystemic process.
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A 12-year-old girl presents to the clinic with a 3-day history of migratory polyarthritis involving her knees, elbows, and ankles. She also reports a fever and fatigue. Two weeks ago, she had a sore throat, which resolved on its own without any medical intervention. On examination, you note a new-onset heart murmur and a slightly raised, erythematous rash with well-defined borders on her trunk. Laboratory results reveal an elevated erythrocyte sedimentation rate, C-reactive protein, and anti-streptolysin O titer. Which of the following is the most likely underlying mechanism behind this patient's condition?
A) Direct invasion of the joints by a bacterial pathogen
B) Binding of a bacterial exotoxin to host cell receptors, leading to tissue damage
C) Molecular mimicry resulting in a cross-reactive immune response against host tissues
D) Activation of the complement system by immune complexes deposited in tissues
E) Viral-induced cytopathic effect on host cells leading to tissue injury
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
The MENTAL MODEL used to answer this question comes from our detailed test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following is the most likely underlying mechanism behind this patient's condition?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Diagnose the problem, and 2nd: Identify the underlying mechanism.
Step 3: Read the vignette carefully and ask yourself: “Knowing that the diagnosis is _____________, I also know that the underlying mechanism is ___________.”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
The 12-year-old girl presents with migratory polyarthritis, fever, fatigue, a new-onset heart murmur, and a raised erythematous rash (likely erythema marginatum). She also has a history of a sore throat two weeks prior, which resolved without treatment. In addition to these findings, her laboratory results are highly suggestive of acute rheumatic fever—a complication of untreated or inadequately treated group A strep pharyngitis.
ANSWER CHOICES:
CHOICE A: Direct invasion of the joints by a bacterial pathogen
Explanation: This mechanism would describe septic arthritis, where bacteria directly infect the joints. The arthritis in ARF is due to immune-mediated inflammation rather than bacterial infection.
CHOICE B: Binding of a bacterial exotoxin to host cell receptors, leading to tissue damage
Explanation: This mechanism would describe diseases like toxic shock syndrome or scarlet fever, where bacterial exotoxins cause systemic effects.
CHOICE C: Molecular mimicry resulting in a cross-reactive immune response against host tissues
Explanation: The pathogenesis of ARF involves molecular mimicry, where the immune system produces antibodies against GAS antigens that cross-react with host tissues, particularly the joints, heart, skin, and brain. The streptococcal M protein shares structural similarities with human proteins such as cardiac myosin and other tissues. This leads to the production of cross-reactive antibodies that attack these host tissues, causing the characteristic manifestations of ARF, including polyarthritis, carditis, erythema marginatum, and Sydenham chorea.
CHOICE D: Activation of the complement system by immune complexes deposited in tissues
Explanation: This mechanism is seen in conditions like post-streptococcal glomerulonephritis (PSGN), where immune complexes deposit in the kidneys.
CHOICE E: Viral-induced cytopathic effect on host cells leading to tissue injury
Explanation: This describes viral infections where viruses directly damage host cells.
FINAL VERDICT…
The most likely underlying mechanism behind this patient's condition is molecular mimicry resulting in a cross-reactive immune response against host tissues, which is characteristic of acute rheumatic fever following group A streptococcal infection.
CORRECT ANSWER: C) Molecular mimicry resulting in a cross-reactive immune response against host tissues.
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That’s it for question 91!
See ya tomorrow 👋