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Musculoskeletal, Skin & Subcutaneous Tissue — Step 1 practice questions
188 questions in this area, with an explanation for every answer choice.
Three samples below, free and without an account.
How this shows up on Step 1
Dermatology is largely pattern recognition from a written description, so the vocabulary of lesion morphology has to be automatic. Rheumatology questions usually hinge on an antibody or a joint distribution. Muscle and bone questions draw on physiology and biochemistry more than the section title suggests.
Sample questions
Sample question 1
A patient with metastatic melanoma harboring a BRAF V600E mutation is considered for targeted therapy. Which of the following best describes the rationale for combining a BRAF inhibitor with a MEK inhibitor?
Explanations
A. MEK inhibitors act on an unrelated pathway with additive toxicity only
MEK lies immediately downstream of BRAF in the same pathway.
B. The combination eliminates the need for any monitoring
Monitoring for toxicity and resistance remains essential.
C. BRAF inhibition is only effective in melanomas lacking the V600E mutation
Efficacy requires the activating mutation.
D. Combined blockade at two points in the MAP kinase pathway improves response duration and reduces paradoxical pathway activation causing secondary squamous cell carcinomas · correct
BRAF V600E constitutively activates the MAP kinase pathway (RAS-RAF-MEK-ERK) driving proliferation in roughly half of cutaneous melanomas. BRAF inhibitors such as vemurafenib produce rapid responses but resistance emerges quickly, and paradoxical pathway activation in BRAF-wild-type cells causes secondary squamous cell carcinomas and keratoacanthomas. Adding a MEK inhibitor blocks the pathway downstream, improving response duration and REDUCING those secondary lesions. Checkpoint inhibitors are the other pillar of advanced melanoma treatment.
E. BRAF inhibitors are effective regardless of BRAF mutation status
BRAF inhibitors require the mutation and can be harmful without it.
Sample question 2
A 68-year-old man is found incidentally to have an isolated markedly elevated alkaline phosphatase with normal calcium, phosphate, and PTH. Which of the following is the most likely diagnosis?
Explanations
A. Paget disease of bone · correct
An isolated, markedly elevated alkaline phosphatase with otherwise normal calcium/phosphate/PTH is the classic laboratory signature of Paget disease of bone, reflecting high bone turnover.
B. Multiple myeloma
Multiple myeloma typically causes hypercalcemia and lytic lesions without primarily elevating alkaline phosphatase.
C. Osteomalacia
Osteomalacia shows low-normal calcium/phosphate with elevated PTH (secondary hyperparathyroidism), not normal calcium/phosphate.
D. Primary hyperparathyroidism
Primary hyperparathyroidism shows elevated calcium and PTH with low phosphate, not normal labs with isolated ALP elevation.
E. Osteoporosis
Osteoporosis shows entirely normal laboratory values (it is a bone quantity problem, not a laboratory-detectable metabolic disturbance).
Sample question 3
A patient beginning methotrexate for rheumatoid arthritis asks about safety. Which of the following is the most appropriate counseling?
Explanations
A. No laboratory monitoring is required
Regular laboratory monitoring is mandatory.
B. Daily dosing is standard for rheumatoid arthritis
Weekly dosing is standard; daily dosing causes severe toxicity.
C. Take folic acid supplementation to reduce adverse effects, avoid alcohol, use effective contraception given teratogenicity, and monitor blood counts, liver enzymes, and renal function · correct
Methotrexate inhibits dihydrofolate reductase, so FOLIC ACID supplementation reduces stomatitis, gastrointestinal upset, and cytopenias without compromising efficacy in rheumatoid arthritis. It is dosed WEEKLY — inadvertent daily dosing is a classic and potentially fatal medication error. It is TERATOGENIC and abortifacient, requiring effective contraception in both sexes, and causes hepatotoxicity (aggravated by alcohol), myelosuppression, and pneumonitis, so blood counts, transaminases, and creatinine are monitored regularly.
D. Folic acid must be avoided because it blocks efficacy
Folic acid reduces toxicity without diminishing efficacy in this setting.
E. Methotrexate is safe in pregnancy
Methotrexate is a potent teratogen and contraindicated in pregnancy.
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