USMLE Step 1 Question (MSK)
Recognizing the pathophysiology of MSK conditions.
HEADS-UP EVERYONE… There’s very little feedback on these posts despite a lot of you reading, listening, etc. I need to see more positive or negative feedback throughout the week (like buttons or comments), or I’ll assume this isn’t a valuable use of my time. So, if you want me to keep making content, please let me know by liking the posts - thanks!
The following is a high-yield USMLE Step 1 MSK question.
It is followed by a deep dive into each answer choice—the answer can be found at the bottom of the post.
If you need more help with your USMLE Step 1 exam prep, click HERE.
Good luck!
QUESTION:
A 32-year-old female presents to the clinic with complaints of fatigue, joint pain, and a malar rash. She also reports sensitivity to sunlight and episodes of mouth ulcers. Her vital signs are within normal limits. Laboratory studies show positive antinuclear antibodies (ANA), positive anti-double-stranded DNA (anti-dsDNA) antibodies, and low complement levels. Which of the following is most likely responsible for her condition?
A. Overactivation of the classical complement pathway leading to immune complex deposition
B. Autoantibodies against the enzyme that catalyzes the conversion of xanthine to uric acid
C. Defective production of collagen due to a mutation in the genes encoding type I procollagen
D. Autoantibodies against the enzyme responsible for the synthesis of myelin in the central nervous system
E. Autoantibodies against the nicotinic acetylcholine receptors at the neuromuscular junction
F. Increased activity of tissue transglutaminase leading to deposition of gluten-derived peptides
G. Deficiency of alpha-1 antitrypsin causing uninhibited neutrophil elastase activity
To see the answer, scroll to the bottom of the page. If you’re unsure or want to learn more about the answer choices, see the DEEP DIVE below.
DEEP-DIVE:
The Mental Model for answering this question is as follows:
Step 1. Identify the key features of the patient's presentation and laboratory findings (fatigue, joint pain, malar rash, photosensitivity, mouth ulcers, ANA & anti-dsDNA antibodies, low complement).
Step 2. Based on the given information, make a diagnosis. (The most likely diagnosis is SLE.)
Step 3. Identify the pathophysiology underlying your diagnosis and find it in the answer choices. (this one’s up to you).
A. Overactivation of the classical complement pathway leading to immune complex deposition
In SLE, autoantibodies form immune complexes with self-antigens, which can activate the classical complement pathway. This leads to complement consumption (explaining the low complement levels) and immune complex deposition in various tissues, causing inflammation and damage.
B. Autoantibodies against the enzyme that catalyzes the conversion of xanthine to uric acid
This describes the pathophysiology of gout, where deficiency or inhibition of xanthine oxidase leads to hyperuricemia and uric acid crystal deposition in joints. While joint pain is present in this patient, the other features are inconsistent with gout.
C. Defective production of collagen due to a mutation in the genes encoding type I procollagen
This describes the pathophysiology of osteogenesis imperfecta, a genetic disorder characterized by fragile bones and other connective tissue abnormalities. The patient's presentation is not consistent with this condition.
D. Autoantibodies against the enzyme responsible for the synthesis of myelin in the central nervous system
This describes the pathophysiology of multiple sclerosis, an autoimmune disorder targeting the myelin sheaths in the central nervous system. While fatigue is a common symptom in multiple sclerosis, the other features and laboratory findings are more consistent with SLE.
E. Autoantibodies against the nicotinic acetylcholine receptors at the neuromuscular junction
This describes the pathophysiology of myasthenia gravis, an autoimmune disorder affecting neuromuscular transmission. The patient's presentation does not include muscle weakness - the hallmark of myasthenia gravis.
F. Increased activity of tissue transglutaminase leading to deposition of gluten-derived peptides
This describes the pathophysiology of celiac disease, an autoimmune disorder triggered by gluten ingestion. While mouth ulcers can occur in celiac disease, the other features and laboratory findings are inconsistent with this condition.
G. Deficiency of alpha-1 antitrypsin causing uninhibited neutrophil elastase activity
This describes the pathophysiology of alpha-1 antitrypsin deficiency, a genetic disorder that primarily affects the lungs and liver. The patient's presentation is not consistent with this condition.
VERDICT: The vignette describes the signs, symptoms, and lab findings consistent with SLE.
FINAL ANSWER: A. Overactivation of the classical complement pathway leading to immune complex deposition
