A 22-year-old man comes to the office due to 3 months of progressive back pain.  He has also had intermittent subjective fever.  The patient emigrated from Nepal for a master’s program 6 months ago.  He has no other medical conditions, takes no medication, and does not use tobacco, alcohol, or illicit drugs.  Temperature is 38.3 C (100.9 F), blood pressure is 122/78 mm Hg, and pulse is 84/min.  BMI is 19 kg/m².  Tenderness is noted over the lumbar spine; flexion, extension, and rotation of the spine are limited due to pain and muscle spasm.  MRI of the lower spine reveals partial destruction of the anterior portion of the L1-L3 vertebral bodies and a fluid collection beneath the anterior longitudinal ligament.  Which of the following is the most likely diagnosis?

A 70-year-old woman is brought to the emergency department due to acute right hip pain after a fall.  She was walking in her house when she tripped on a floor rug and fell, landing on her hip.  The patient has been unable to bear weight on the right leg since the fall and had to call for emergency transport to the hospital.  She has no significant medical history and does not use tobacco, alcohol, or illicit drugs.  The patient’s only medication is an over-the-counter multivitamin.  Family history is notable for a hip fracture in her mother.  Blood pressure is 150/90 mm Hg and pulse is 112/min.  The patient is in moderate pain and her right leg appears shortened and externally rotated.  There is tenderness and swelling of the right hip.  Radiographs reveal a right femoral neck fracture.  Which of the following changes in bone structure is most likely responsible for this patient’s condition?

A 57-year-old man comes to the emergency department due to a 1-day history of pain and swelling in his right knee.  The pain is severe, and he has had difficulty bearing weight on the right leg.  He previously felt well.  Past medical history is notable for hypertension and seasonal allergies.  The patient does not use tobacco and drinks 1 or 2 alcoholic beverages a week.  On examination, the right knee is red and swollen.  He has pain with passive range of motion at the knee.  The knee ligaments show no significant laxity.  Synovial fluid obtained from the involved joint shows a white blood cell count of 25,000/mm³, with a neutrophilic predominance, and numerous crystals (shown below).

These crystals are most likely composed of which of the following substances?

A 29-year-old woman is evaluated for severe left hip pain after twisting her leg.  She has bony deformities of the lower extremities, and her mobility is limited at baseline.  The patient has a history of hyperthyroidism, which was managed with radioiodine therapy.  Menarche was at age 7, and she has regular 30-day cycles.  Physical examination shows large, hyperpigmented macules with irregular borders located on the left shoulder, left side of the neck, and left buttock.  X-ray findings are shown in the image below.

Which of the following is the most likely diagnosis?

A 34-year-old man comes to the office due to progressive low back pain for several years.  The patient reports that the stiffness and pain are worse in the morning but gradually improve during the day.  Lately, he has been taking over-the-counter ibuprofen, which provides some relief.  Laboratory evaluation shows a positive HLA-B27 antigen.  X-ray imaging reveals fusion of the sacroiliac joints.  Periodic measurement of which of the following is most helpful to monitor disease progression in this patient?

A 70-year-old man comes to the clinic due to intermittent leg pain and difficulty walking.  He describes the pain as mild-to-moderate, deep, and lasting throughout the day.  The patient has a history of osteoarthritis in his hands for which he takes over-the-counter nonsteroidal anti-inflammatory drugs, but says that he never has had problems with his knees.  Physical examination shows point tenderness over the right tibia.  Laboratory studies show elevated serum alkaline phosphatase.  Bone biopsy shows haphazardly oriented segments of lamellar bone with prominent cement lines.  The initial phase of this patient’s disorder involves increased activity of which of the following cell types?

A 47-year-old woman comes to the physician with progressive joint pain and swelling in her hands for the past several months.  She also has easy fatigability that has gradually worsened over the same period.  Morning activities are especially difficult due to stiffness lasting 1 to 2 hours after waking.  Examination shows warmth, swelling, and tenderness involving the proximal interphalangeal joints, metacarpophalangeal joints, and wrists bilaterally.  A blood sample is obtained for laboratory analysis.  Autoantibodies against which of the following components are most specific for this patient’s condition?

A 45-year-old woman comes to the clinic with a 3-month history of persistent shoulder and back pain and easy fatigability.  She also has pain and stiffness in all her muscles that worsens in the morning and evening.  She does not participate in any regular exercise because her pain is exacerbated with activity.  She works as a computer programmer and reports some difficulty concentrating on her job.  Past medical history is significant for depression and gastroesophageal reflux disease, but she is not currently taking any medications.  Physical examination shows normal range of motion and 5/5 muscle strength in both upper and lower extremities.  Soft tissue tenderness is present at several locations bilaterally above and below the waist.  Which of the following is the most likely diagnosis?

A 62-year-old woman comes to the office due to a 3-month history of painful, swollen wrists and knees.  She also has joint stiffness, which is worse upon wakening and limits her daily activities.  Review of systems is positive for fatigue.  The patient’s only other medical condition is hypothyroidism for which she takes levothyroxine.  She smoked a pack of cigarettes daily for 20 years and quit 15 years ago.  Vitals signs are within normal limits.  Physical examination shows symmetric, moderate swelling of the wrists and knees.  The joints are tender and warm.  Range of motion is intact but painful.  Plain radiographs of the symptomatic joints show joint space narrowing and marginal erosions.  Which of the following cytokines are primarily involved in the pathogenesis of this patient’s joint destruction?

A 34-year-old woman comes to the office with several months of vision problems, difficulty chewing, and trouble speaking.  The symptoms fluctuate, but the patient has noticed that they are worse after a long day.  She works as a telemarketer and has been putting in increasingly long hours to meet her quotas.  Regarding her symptoms, she says, “It’s probably just exhaustion; an ice pack to my face seems to help.”  During physical examination, the patient is asked to keep her eyes focused on a spot on the ceiling, and after 2 minutes, her vision becomes blurry.  The remainder of the examination is normal.  Further evaluation shows that the patient’s symptoms are reversible on administration of an acetylcholinesterase inhibitor.  The pathogenesis of this patient’s disease is most similar to which of the following conditions?

A 64-year-old man comes to the emergency department due to acute knee pain.  He developed redness, swelling, and severe pain affecting the right knee the day before his arrival.  The patient has had 3 similar episodes in the past year that resolved quickly with over-the-counter analgesics.  He has a history of polycythemia vera but has been noncompliant with phlebotomy treatments.  Vital signs and cardiopulmonary examinations are normal.  The right knee is red and warm.  There is severe pain with movement at the joint; the other joints are grossly normal.  Needle aspiration of the joint is performed.  Which of the following is the most likely finding on analysis of this patient’s synovial fluid?

A 43-year-old man comes to the office with muscle weakness.  His symptoms began 6 weeks ago and are worst in the hips and shoulders.  The weakness has had a progressive course so that he is now having difficulty rising from chairs and combing his hair.  The patient has had to reduce his regular exercise regimen due to weakness and has requested a modified work schedule for his job as a building maintenance manager.  He has no history of spinal injury and no neck pain.  Past medical history is insignificant, and the patient takes no medications.  Muscle biopsy reveals major histocompatibility complex class I molecule overexpression on the sarcolemma with CD8⁺ lymphocyte infiltration.  Which of the following is the most likely cause of this patient’s condition?

A 35-year-old man comes to the clinic with acute right knee pain and swelling.  His symptoms have been present for a week and have moderately worsened over this period.  The patient is able to bear weight but has significant pain when climbing stairs or walking for extended distances.  He attempted treatment with ibuprofen, which provided prompt but only temporary relief.  Past medical history is unremarkable, though the patient was seen by his primary care provider for a diarrheal illness 2 weeks before onset of the current symptoms.  Examination shows a moderate-sized effusion at the right knee.  Cultures of a joint aspirate reveal no bacteria.  Which of the following is most likely associated with this patient’s joint symptoms?

A 54-year-old man is admitted to the hospital following a high-speed motor vehicle accident.  He is found to have right leg long bone fractures requiring open reduction/internal fixation.  After the patient is stabilized, he is transferred to a skilled nursing facility for an extended rehabilitation period.  During his stay at the facility, his right leg is immobilized for several weeks.  The patient’s management is complicated by decreased nutritional intake due to side effects from opioid pain medications.  Measurement of his thigh following removal of casting materials finds a 2-centimeter decrease in diameter during the time of immobilization.  This change in body measurement is due to a pathologic process similar to that seen in which of the following?

A 24-year-old woman comes to the office at 12 weeks gestation for prenatal counseling.  She is 120 cm (3 ft 11 in) tall with short upper and lower extremities but normal torso length.  Physical examination is also significant for depression of the nasal bridge and a bulging forehead.  Her husband is phenotypically normal and has no medical problems.  The patient knows that there is a 50% chance of passing on her condition to the fetus.  An abnormality involving which of the following cells is most likely responsible for this patient’s features?

A 48-year-old previously healthy woman comes to the office due to progressively worsening muscle weakness for the past 2 months.  The patient has difficulty with activities such as climbing stairs, getting up from chairs, and placing dishes in overhead cabinets.  She also reports a 4.5-kg (10-lb) unintentional weight loss and occasional abdominal discomfort over the same interval.  Physical examination shows weakness of the shoulder and hip girdle muscles.  Other examination findings are shown in the image below.

Further evaluation of this patient is most likely to reveal which of

the following underlying conditions?

A 55-year-old man comes to the office for evaluation of chronic muscle weakness.  Over the past several months, he has had increasing difficulty walking up stairs and lately has had trouble removing objects out of the overhead cabinets in his kitchen.  Temperature is 36.7 C (98 F), blood pressure is 125/80 mm Hg, and pulse is 78/min.  On examination, the patient has symmetric proximal muscle weakness and mild muscle tenderness.  There is no rash.  Muscle biopsy reveals an endomysial mononuclear infiltrate and patchy muscle fiber necrosis.  An autoantibody directed against which of the following antigens is most likely to be seen in this patient?

An 18-year-old man is evaluated due to 3 months of lower extremity pain.  The pain is persistent and present both day and night.  He has no fever, chills, or history of leg trauma.  Imaging shows an expansile lesion of the distal femur.  Surgical resection is performed, and the specimen is shown below.

Mutations involving which of the following genes are most likely present in this patient?

A 15-year-old boy is brought to the emergency department due to hemoptysis.  He has a history of amputation of the right lower extremity due to bone cancer.  Chest imaging reveals a lung mass.  Excisional biopsy of the mass shows sheets of uniform, round, small cells slightly larger than lymphocytes with scant, clear cytoplasm.  The cellular deposits are interrupted by vascular fibrous septa, with areas of hemorrhage and an abrupt transition from viable to necrotic cells.  A representative sample is shown in the image below.

Which of the following is the most likely diagnosis?

A 68-year-old woman is brought to the emergency department with severe right hip pain after a fall.  She tripped on a rug and fell against a wall and then to the floor, landing on her right hip.  The patient has a history of depression and polymyalgia rheumatica.  Medications include sertraline and low-dose prednisone.  She also has a 40-pack-year smoking history.  Blood pressure is 145/85 mm Hg and pulse is 96/min.  The patient appears to be in significant pain.  She is unable to move the right hip, and the right leg appears shorter than the left.  A pelvic x-ray is shown in the image below:

Injury involving which of the following arteries is most likely to lead to osteonecrosis in this patient?

A 92-year-old woman is being evaluated due to the presence of skin blisters for the past week.  The patient is bed-bound and fatigued.  Vital signs are within normal limits.  She has no blisters or erosions in the mouth.  Skin findings are shown in the image below:

Serologic studies are most likely to show an autoantibody directed against which of the following components?

A 41-year-old man comes to the office for evaluation of right hip and groin pain.  He is an avid bicyclist and has been unable to ride for the past 3 months due to increasing pain exacerbated by cycling or walking.  The patient does not recall any recent trauma; ibuprofen has not relieved the pain.  Medical history is notable for systemic lupus erythematosus.  Temperature is 36.7 C (98 F).  On physical examination, the patient has a noticeable limp.  There is decreased rotation of the right hip, and both active and passive range of motion are limited due to pain.  An x-ray of the hip is inconclusive.  MRI of the pelvis is shown in the image below.

Which of the following is the most likely cause of the patient’s pain?

A 45-year-old man participates in a research study.  He undergoes percutaneous skeletal muscle biopsy.  Microscopic analysis shows his type I and type II muscle fibers are clustered in groups in contrast to a normal intermixed pattern as shown below.

Which of the following is the most likely cause of the changes observed in this patient’s skeletal muscle?