Question Number: 1 Case A 70-year-old man with chronic obstructive pulmonary disease has a T8 vertebral compression deformity noted on a lateral chest radiograph taken for evaluation of a chronic cough. The deformity was not present on radiographs taken 1 year ago. The patient does not have back pain and does not recall any injury to his back. He has not been taking corticosteroids. Laboratory data include: Serum testosterone: 205 ng/ml DEXA bone densitometry: lumbar spine T-score = -1.8 Femoral neck T-score = -1.9 Question Which of the following is the most appropriate therapeutic intervention at this time? A. Increase calcium intake to 1200 mg/day with vitamin D 800 IU/d B. Oral alendronate 70 mg once weekly in addition to supplemental calcium and vitamin D C. Transdermal testosterone 5 mg at night in addition to supplemental calcium and vitamin D D. Teriparatide 20 mcg SC daily in addition to supplemental calcium and vitamin D E. Intranasal calcitonin, 200 units once daily Correct AnswerBAnswer Rationale The presence of a vertebral compression fracture is sufficient to establish a diagnosis of osteoporosis, even though the bone mineral density T-scores are in the osteopenic range. If the bone mineral density in a man is evaluated using reference data from a hea lthy female population, then osteoporosis will be significantly underdiagnosed. Given the presence of one vertebral fracture, this patient is at high risk of additional fractures and needs to receive drug therapy for his osteoporosis. The most effective therapies would be a bisphosphonate (e.g. alendronate) or teriparatide. Given the expense and inconvenience of teriparatide, alendronate is the most appropriate first therapy for this patient. Intranasal calcitonin has not been shown to reduce fracture risk in men with osteoporosis. This patient has a low normal testosterone level, most likely a consequence of an age-related decline in his gonadal function. The b enefits of testosterone therapy for the prevention ofosteoporotic fractures in hypogonadal men have not been established. There
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CaseA 70-year-old man with chronic obstructive pulmonary disease has a T8
vertebral compression deformity noted on a lateral chest radiograph taken
for evaluation of a chronic cough. The deformity was not present onradiographs taken 1 year ago. The patient does not have back pain and does
not recall any injury to his back. He has not been taking corticosteroids.
Laboratory data include:Serum testosterone: 205 ng/ml
DEXA bone densitometry:
lumbar spine T-score = -1.8
Femoral neck T-score = -1.9Question
Which of the following is the most appropriate therapeutic intervention at this
time?
A.Increase calcium intake to 1200 mg/day with vitamin D 800 IU/d
B.Oral alendronate 70 mg once weekly in addition to supplemental calcium and vitamin D
C.
Transdermal testosterone 5 mg at night in addition to supplemental calcium and vitamin
DD.
Teriparatide 20 mcg SC daily in addition to supplemental calcium and vitamin D
E.Intranasal calcitonin, 200 units once daily
Correct Answer
BAnswer RationaleThe presence of a vertebral compression fracture is sufficient to establish a
diagnosis of osteoporosis, even though the bone mineral density T-scores are
in the osteopenic range. If the bone mineral density in a man is evaluated
using reference data from a healthy female population, then osteoporosis will be significantly underdiagnosed. Given the presence of one vertebral
fracture, this patient is at high risk of additional fractures and needs to
receive drug therapy for his osteoporosis. The most effective therapies would be a bisphosphonate (e.g. alendronate) or teriparatide. Given the expense
and inconvenience of teriparatide, alendronate is the most appropriate first
therapy for this patient. Intranasal calcitonin has not been shown to reducefracture risk in men with osteoporosis. This patient has a low normal
testosterone level, most likely a consequence of an age-related decline in his
gonadal function. The benefits of testosterone therapy for the prevention of
osteoporotic fractures in hypogonadal men have not been established. There
is also uncertainty as to whether testosterone replacement improves bone mineral densityin older men with borderline low testosterone levels. Since androgen therapy has possible
undesirable effects on other organ systems, particularly the prostate gland, testosteronetherapy would not be the first choice of therapy for this man.
Question Number: 2
Case
An over-weight 14-year-old boy had been active at a soccer tournamentyesterday and complained of right knee pain when he returned home. Today
the pain is still present and worsens with weight bearing. He has been
previously diagnosed with mild hypothyroidism, and sometimes he forgets totake his replacement therapy.
Physical examination shows no abnormalities of the knee, but internal
Which of the following is the most appropriate next step in management?A.
Nonsteroidal anti-inflammatory drug
B.Antibiotics after aspiration for presumed septic hip
C.
Non-weight bearing and orthopedic evaluationD.
Use of crutches for two weeks and weight bearing as tolerated
E.
Physical therapy program to increase the range of movement of his hips
Correct Answer
CAnswer RationaleChildren often complain of knee pain when the hip is the source of the
problem. SCFE is more common in obese adolescent boys and also in
children with hypothyroidism. It is a surgical emergency; the child should bemade non-weight bearing immediately, additional radiographs (including
frog-leg lateral view) should be obtained, and urgent orthopedic consultation
should be ordered. Treatment is surgical pinning. There is increased risk of slip on the other side, and some children develop aseptic necrosis or chondrolysis as a consequence of this condition.
Question Number: 3
CaseA 26-year-old man has had gradual onset of fixed proximal muscle weakness
over the past 3 to 4 years. He had a healthy childhood but began
experiencing exercise intolerance during his teen years. He often found that
when he exercised, he would experience dyspnea and muscle pain shortlyafter beginning the activity. These symptoms would force him to stop what
he was doing. However, after resting for 2 or 3 minutes, he could resume
the activity without discomfort. On one occasion, he experienced severecramping and muscle tenderness after going fishing and carrying his catch in
a bucket of water back to car, a distance of about a half mile. The cramps
lasted more than an hour and the muscle tenderness resolved in 48 hours.
BAnswer RationaleMcArdle’s disease is the most common glycogen storage disease. It may
present in childhood with exercise intolerance; in teen years with episodes of
acute rhabdomyolysis associated with severe cramps, tenderness, andweakness that often occur after heavy exertion; or in adulthood with the
gradual onset of fixed proximal muscle weakness. The fixed weakness is felt
to be the result of recurrent rhabdomyolysis and an inability, after a time, toregenerate normal muscle. Many patients report a “second wind”
phenomenon. They start to exercise but must stop, only then to be able to
resume the activity after a brief rest. This is presumably the result of
increased blood flow and delivery of nutrients that occur in response to theinitial exercise. Most of these patients have an elevated CK level even when
asymptomatic and have myopathic changes on EMG. The finding of PAS
positive vacuoles confirms the diagnosis of a glycogen storage disease.
Perivascular infiltration of lymphocytes with perifasicular atrophy andcapillary plugging are classically seen in dermatomyositis.
Many small triangular fibers and fiber type grouping would be seen in a
neuropathic condition and imply denervation and reinervation.
Some type II fiber atrophy and increase oil red O staining in type I fibersoccurs with lipid storage diseases like carnitine deficiency of some
mitochondrial myopathies.
Many fibers with central nuclei, occasional hypertrophic cell, and ragged redchange on Gamori Trichrome staining are indicative of a mitochondrial
myopathy.
Question Number: 5
Case
A 55-year-old woman has had an aching pain in her lower back for the past 2years.
QuestionWhich of the following radiographic abnormalities is most likely in this
patient?
A.Increased bone mineral density
B.
Subperiosteal resorptionC.
Looser’s zones
D.
Erlenmeyer flask deformity of the distal femoraE.
Mixed areas of lucency and sclerosis in the long bones
Correct Answer
CAnswer RationaleThis patient has osteomalacia as a result of vitamin D deficiency.
Characteristically, both the serum calcium and the serum phosphorus levelsare decreased, while the serum alkaline phosphatase level is elevated. In
vitamin D deficiency, parathormone levels rise, causing an increase in the
metabolism of 25-hydroxyvitamin D to 1,25-hydroxyvitamin D. This in turn
results in a greater deficiency of vitamin D but also a normal or elevated
level of 1,25-hydroxyvitamin D.
The characteristic radiographic feature of osteomalacia is Looser’s zones or pseudofractures that appear as linear areas of rarefaction perpendicular to
the cortical surface of the bone. Increased bone mineral density is a feature
of osteopetrosis. Subperiosteal resorption occurs in primaryhyperparathyroidism. The Erlenmeyer flask deformity is a feature of
Gaucher’s disease. Mixed areas of lucency and sclerosis in the long bones are
Leflunomide is a disease-modifying anti-rheumatic drug that works by
inhibiting de novo pyrimidine biosynthesis. Actively dividing lymphocytes are
inhibited by the drug’s effect on the enzyme dihydroorotate dehydrogenase,which is directly involved in pyrimidine biosynthesis. Weight loss caused by
leflunomide is under recognized and may reflect the drug’s effect on
oxidative phosphorylation within the mitochondria, rather than a secondaryeffect resulting from diarrhea or anorexia. Cessation of leflunomide may
result in weight gain. The weight loss averaged between 19 and 53 pounds
and occurred within weeks to months of beginning leflunomide. Recognitionof this side effect is important since unnecessary additional testing may be
undertaken to investigate weight loss.
Question Number: 8
CaseA 49-year-old man has progressive swelling of the left foot. He had noted
tingling and burning in the foot at night for the past year. The foot then became swollen five months ago. One month ago, he began to note
discomfort in the foot with ambulation. He does not have pain in any other
joints. He has a 10-year history of diabetes mellitus type 2 and
hypertension. The patient’s current medications are losartan,hydrochlorothiazide, metformin, glyburide, and simvastatin. He drinks one
or two 12-ounce cans of beer on weekends. He is afebrile.
Physical examination is notable for pain, swelling, and erythema of thedorsum of the left foot and ankle. The midfoot and ankle are tender. There
is restricted range of motion of the ankle with pain. Deep tendon reflexes
are absent at both ankles. There is diminished vibration sensation in bothfeet and decreased proprioception of the toes of both feet. No ulcers or rash
and osseous destruction, osteopenia, and reactive bone formation. No
chondrocalcinosis is present making CPPD arthropathy unlikely. The
radiographic changes are out of proportion to the pain the patientdescribes. This is unusual for reflex sympathetic dystrophy in which
causalgic pain is usually prominent and allodynia typically
present. Osteopenia and marked osseous destruction are not typical of
osteoarthritis. This radiograph does not show typical features of gout
including “punched out,” rounded defects marginally and erosions withoverhanging edges. Osteomyelitis may be present in diabetic patients with
foot ulcers, but this patient has no preexisting foot ulcer. The patient alsohas no paronychia, cellulitic skin features nor constitutional symptomsincluding fever to suspect infection.
Question Number: 9
CaseAn 8-year-old boy has had hectic fevers for the past 5 days, a diffuse
morbilliform rash on his trunk, swollen hands and feet, erythematous oral
mucosa with no exudates, cracked lips, and red eyes. He has diffuselymphadenopathy and slight hepatomegaly. He is very irritable.
Laboratory data include:
ESR: 80 mm/hr RBC: mild anemia
Hgb: 1.1 gm/dl
WBC: 17,000/mm3
Platelet count: 450,000/mm3Urinalysis: some WBCs but no bacteria or proteinuria
Echocardiography: normal
Spinal fluid analysis: a few lymphocytes but no organisms on gram stain
QuestionWhich of the following is the most appropriate treatment?
In phosphorylase b kinase deficiency there is a normal or only partially
impaired rise in venous lactate with exercise. Ischemic forearm testingreveals a rise in blood lactate with impaired increase in ammonia levels in
myoadenylate deaminase deficiency. In acid maltase deficiency the ischemic
forearm muscle test is normal. CPT II deficiency usually begins in childhood
with exercise-induced myalgia. The ischemic forearm test is normal in CPTII. McArdle’s disease, characterized by myophosphorylase deficiency, is the
only choice associated with a flat venous lactate response to ischemic
forearm exercise. Note that testing of muscle biopsy samples has in recent
years become a precise diagnostic tool to confirm enzyme defects inmetabolic muscle disease.
Question Number: 11
CaseA 73-year-old woman who has had deforming rheumatoid arthritis for the
past 20 years now has persistent neutropenia. She has been living in an
assisted care facility for the past 3 years. Despite bilateral knee
arthroplasties, her mobility and ability to live independently have been progressively impaired by arthritis of her ankles, feet, wrists, and hands. Past
therapies have included parenteral gold, penicillamine, hydroxychloroquine,
methotrexate, and etanercept. At the time of admission to the facility, her WBC was 3200/mm3 and her physician chose to maintain her on prednisone
7.5 mg qAM alone for her rheumatoid arthritis. Her only infection was a
urinary tract infection 3 months ago treated with oral ciprofloxacin. Other
Peripheral smear: paucity of neutrophils, occasional large lymphocyte with
pale blue cytoplasm and azurophilic granulesQuestion
Which of the following studies is most likely to establish the diagnosis?
A.Abdominal ultrasonography to measure spleen size
B.
Flow cytometry of peripheral blood
C.Test for cyclic citrullinated peptide (CCP) antibodies
D.
Granulocyte antibody test
E.Test for antinuclear antibodies (ANA)
Correct Answer BAnswer Rationale
The leading diagnostic considerations for this patient are Felty’s syndrome
and large granular lymphocyte (LGL) syndrome. The LGL syndrome is a
clonal disorder of cytotoxic T-lymphocytes and has been classified asleukemia, even though it usually has an indolent clinical course. About 25%
of patients with LGL syndrome have rheumatoid arthritis. The demonstration
of a clonal population of CD3+, CD8+, CD16+, CD57+ T cells with flowcytometry of the peripheral blood would serve to establish the diagnosis of
LGL syndrome. Splenomegaly and granulocyte antibodies are common to both disorders.The histopathology of the bone marrow does not usually differentiate the two.
Question Number: 12
CaseA 44-year-old woman with a 20-year history of lupus undergoes follow-up
evaluation. Initial manifestations included photosensitivity, small joint
arthritis, fatigue with a positive ANA, dsDNA, and leukopenia. Her symptomsresponded to anti-inflammatory agents and hydroxychloroquine, which she
continues to take. She feels reasonably well but has noticed some difficulty
climbing stairs. Findings on physical examination are normal. CPK and TSH
levels are normal, and there is no evidence of lupus activity on serologicalstudies. She returns 1 month later, and proximal weakness affecting the hip
flexors is noted.
Laboratory data include:CBC: Normal
ESR: 33 mm/hr
CK: 250 U/LdsDNA: 26 IU
TSH: 4.9 µU/ml
Electrolytes: Potassium 3.4 mmoles/L
Mg: NormalCa: Normal
Question
Which of the following is the most likely cause of the patient’s proximal
muscle weakness?A.
Inclusion body myositisB.
Lupus flare
C.
Hydroxychloroquine myopathyD.
Hypothyroidism
E.Hypokalemia
Correct Answer
C
Answer Rationale
Antimalarial therapy is commonly used in patients with lupus. Side effects of
therapy include irreversible retinal toxicity, rash, and gastrointestinaldisturbance. A less common and under recognized complication of therapy is
myopathy, which does not appear to correspond with the dose used. The
pathogenesis of this myopathy is thought to be related to accumulation of hydroxychloroquine in lysosomes, which then inhibit lysosomal enzymes. It is
a reversible myopathy, and thus important to recognize. Inclusion body
myositis is more common in men, and primarily affects the distalmuscles. There is nothing to suggest a lupus flare, and although the TSH
level is at the high end of normal, hypothyroidism is unlikely to explain the
An 86-year-old man was sent to the hospital from an Alzheimer’s unit 2 days
ago because of a 2-day history of a swollen, red, warm, and tender elbow. He has a temperature of 100.9 degrees F (38.27 degrees C). On
admission, WBC was 12,500/mm3 with 60% PMN, and chest radiograph
showed mild right lower lobe atelectasis. His elbow was aspirated and 4 cc of cloudy fluid were obtained. Synovial fluid analysis showed cloudy fluid with a
WBC of 95,000/mm3. Gram stain was negative, and the fluid was sent for
culture. The patient was started on an intravenous antibiotic to cover gram-
positive bacteria for presumed septic arthritis.He is now confused, but his mental status is reported to be his usual. His
temperature is 99.6 degrees F (37.55 degrees C). His elbow is held in a
flexed position and is slightly swollen in the area between the olecranon and
lateral epicondyle. It is minimally erythematous, warm, and tender. Heresists any attempt to move the elbow. Findings on examination of the other
joints are normal. CBC now has a WBC of 10,000/mm3. Radiograph of theelbow shows only soft tissue swelling. His synovial fluid and blood cultures
have no growth. Sputum gram stain shows a few gram-positive cocci in pairs
but grows out mixed flora.
QuestionWhich of the following is the most appropriate next step in management?
A.
Surgical open drainage of the jointB.
Continue present antibiotic regimen
C.Aspirate the elbow and look for crystals
D.
Add another antibiotic to cover gram-negative organisms
CAnswer RationaleCPPD crystals can elicit an intense inflammatory response in a single jointthat may mimic septic arthritis. It is appropriate to start antibiotics in this
clinical setting, but when cultures are negative, one should suspect a crystal-
induced process. Open drainage is appropriate in septic arthritis, if the joint
effusion cannot be controlled by percutaneous aspiration.
Question Number: 14
CaseA 4-year-old girl has recent onset of rash over her knuckles and knees.
Nailfold capillaroscopy is shown in Figure 1 below.
FigureQuestion
The nailfold changes place this patient at highest risk for which of the
improving this patient’s bone mineral density over the next 3 years?
A.
Continue alendronate therapy aloneB.
Continue alendronate and administer daily PTH (1-34) concurrently for the next 18
months, after which both drugs are discontinued
C.
Continue alendronate and administer daily PTH (1-34) concurrently for the next 18months, after
which alendronate alone is continued
D.
Discontinue alendronate therapy and administer daily PTH (1-34) for the next 18 months
Correct Answer
CAnswer Rationale
Cosman et al (2005) randomized 126 women who had been on alendronatefor at least 1 year to continue alendronate and to receive daily PTH (1-34),cyclic (3 month on/3 month off) PTH (1-34), or alendronate alone. Spine
bone mineral density increased 6.1% in the daily PTH (1-34) and 5.4% in the
cyclic PTH (1-34) groups, but remained unchanged in the alendronate alone
group. In a study by Black et al (2005), patients originally randomized to 1year of treatment with PTH (1-84) were subsequently randomized to receive
alendronate or placebo. Lumbar spine bone mineral density continued to
increase in both groups in the first year following discontinuation of PTH (1-84), but continued to rise in the second year only in the alendronate-treated
patients. In patients who have never been treated with alendronate, there is
no clear evidence that the combination of PTH with alendronate provides asynergistic or additive effect on bone mineral density as compared to PTH
alone (Black et al, 2003). These studies thus support the conclusion that this
patient would have the greatest increase in bone mineral density at the end
of 3 years if she receivs PTH in addition to alendronate for the first 18months, and then alendronate alone after the discontinuation of PTH.
Question Number: 16
CaseA 61-year-old man was recently admitted to the medical service for
management of congestive heart failure. While hospitalized, he experiences
acute and spontaneous onset of right knee pain and swelling.He has a longstanding history of seronegative nodular rheumatoid arthritis
that has been refractory to disease-modifying anti-rheumatic drugs
(DMARDs), including hydroxychloroquine and methotrexate, but responsive
Start a nonsteroidal anti-inflammatory drug (NSAID)D.
Start “pulse” corticosteroids
Correct Answer BAnswer Rationale
Although the patient carries the diagnosis of “nodular rheumatoid arthritis” and is already
being treated with disease-modifying agents, a patient with rheumatoid nodules would beexpected to be seropositive for rheumatoid factor. This merits a reassessment of his
diagnosis and management.
The most appropriate course of action is to perform arthrocentesis to assist
in both reevaluating the underlying diagnosis and in determining why this joint is flaring out of proportion to the other joints in what is normally a
symmetric polyarthritis–rheumatoid arthritis.
Radiography would be useful in ruling out a bony injury if there were a
history of trauma. Instead, the patient’s symptoms developed spontaneouslyand only after admission. NSAIDs and/or pulse corticosteroids are effective
interventions for the acute management of many inflammatory arthritides, but their salt- and fluid-retentive effects could be deleterious to the patient
because he has congestive heart failure.
Question Number: 17
Case
A 42-year-old woman with longstanding lupus treated with low-dosecorticosteroids and hydroxychloroquine has been doing well for many years.
She presented at age 18 with severe Raynaud’s phenomenon and finger
necrosis that was treated with IV cyclophosphamide. Other manifestations
included chronic thrombocytopenia and pulmonary embolus secondary toanti-phospholipid antibodies. She has never had cardiac or kidney
involvement. The patient would like to stop taking hydroxychloroquine
because she has been doing so well and finds the yearly eye examinations
onerous.Question
Which of the following is most appropriate advice to the patient at this time?A.
Discontinue visual field testing at her annual eye examinationsE.
Increase the dose of corticosteroids
Correct Answer CAnswer Rationale
Hydroxychloroquine is a useful treatment for the cutaneous and
musculoskeletal manifestations of lupus. It has little effect upon nephritis or other major organ involvement. Assays are available to assess serum
concentrations of hydroxychloroquine, as low levels have been shown to be
associated with increased disease activity. Irreversible retinal toxicity is rare
but occurs with greater frequency the longer the drug is used. The permanent visual damage results from binding of the drug to melanin. The
recommended dose is not greater than 6.5 mg/kg. Discontinuation of
hydroxychloroquine has been associated with an increased risk of flares. Eye
examinations should be continued while the patient takes antimalarialmedications, especially if the patient has been taking them for many
years. A full visual field and color test is required to optimally track theretinal effects of hydroxychloroquine. Increasing steroids in lieu of taking
hydroxychloroquine increases the likelihood of corticosteroid-related
complications; corticosteroid use should be kept at a minimum.
Question Number: 18Case
A 66-year-old woman who has a history of corticosteroid-dependent chronic
obstructive pulmonary disease and nondisplaced talus fracture 1 year ago now has
burning, aching, and numbness of the sole of the right foot and toes. The discomfort is
worse at night and improves with ambulation.Question
Compression of which of the following nerves is the most likely cause of this
This patient has tarsal tunnel syndrome marked by posterior tibial nerve
compression. Foot trauma including talus or calcaneal fracture predisposesto the development of this condition. Deep peroneal nerve (or anterior tibial
nerve) compression causes paresthesias and numbness of the dorsum of the
foot. Note that the anterior tibial nerve is now more commonly called thedeep peroneal nerve. Superficial peroneal nerve compression causes
paresthesias and numbness over the dorsolateral foot and worsens with
exercise. Common peroneal nerve compression causes foot drop.
Question Number: 19Case
A 23-year-old man sustained multiple toe fractures while playing soccer four
months ago. Since cast removal, he has had pain in the lower extremities
and arthralgias. Past medical history reveals a clavicle fracture at age 3years, finger fractures while playing volleyball at age 9 years, and foot
fractures at age 12 years when he kicked a can. Physical examination showsa thin man who is slightly nervous and sweating. His height is 5 feet 5
inches and has normal dentition and no skeletal deformities. All MCP, ankle,
and elbow joints go beyond the normal range of motion. Findings on
examination of the skin and heart are normal. The sclerae are pale blue,which he says have always been like that, and there is no family history of
This is a case of type I ostegenesis imperfecta (OI), a rare inheritedconnective tissue disorder with many phenotypic presentations. The cause of
all cases of OI has not been definitely established. Although mutations in
one or the other of two genes which code for proteins that combine to formtype I collagen (COL1A1 and COL1A2), account for many of the qualitative
and quantitative defects in type I collagen seen in OI, its clinical
manifestations vary substantially within families. One member may be quite
affected clinically, whereas another member with the same mutation mayenjoy normal function. Skin biopsy for analysis if type I collagen genes
and/or testing of genomic DNA for mutations in COL1A1 and COL1A2 may be
a helpful in diagnosis especially in those with subtle clinical manifestations.
However, normal results of these tests do not exclude thediagnosis. Identifying a mutation in a particular gene does not necessarily
result in a clear clinical diagnosis for this reason the clinical diagnosis of OI is based on the signs and symptoms as described in the above case. Mild (type
I) OI, is the least severe form. Individuals with type I OI may have few or
no fractures before puberty or numerous fractures throughout their
lives. Deformity is minimal and stature is usually normal. Individuals withtype I OI usually do not begin to have fractures until they begin toddling or
walking. The most frequently involved bones are the long bones of the arms
and legs, ribs, and the small bones of the hands and feet. Clinicalmanifestations of OI include excess or atypical fractures (brittle bones), short
stature, scoliosis, basilar skull deformities, which may cause nerve
compression or other neurologic symptoms, blue sclerae, hearing loss,opalescent teeth that wear quickly (dentinogenesis imperfecta) increased
laxity of the ligaments and skin with easy bruiseability. Measurement of
BMD by dual-energy x-ray absorptiometry (DEXA) at any age discloses asignificant decrease in bone mass. This is the case for mild disease, in which
BMD is reported to be 76 percent of that of an age-matched control in the
spine and 71 percent of control in the femoral neck. T scores (i.e., standarddeviation from the young-adult mean BMD) are frequently in the range of
-2.5 to -4.0 at the lumbar spine or proximal femur. Although bone biopsy is
indicate when there is excessive skeletal fragility under unusualcircumstances and in this case he had a classic clinical picture of IO with
multiple fractures at young age, blue sclerae, short stature, and hearing loss.
Question Number: 20Case
A 23-year-old woman has a 4-year history of polymyositis. At the onset of
disease, she had a rash on her face and CK level was 35,000 U/L. EMG was
consistent with inflammatory myopathy. A biopsy of the deltoid muscle wasconsistent with polymyositis. She was subsequently treated with numerous
drugs including high-dose prednisone, methotrexate, mycophenolate mofetil,
and infliximab. She had an anaphylactic reaction to azathioprine. She has
also received several courses of IVIG. None of these treatments have shownsignificant benefits although the CK levels are now lower, in the range of
8,000-10,000 U/L.
She now has significant difficulties with daily activities, requiring help for dressing and ambulation from her mother who lives with her. At times she
uses a scooter. Social history is negative for use of illicit drugs, tobacco, and
alcohol. Her family history is negative for autoimmune disease; she is anonly child. On examination, she is overweight, has cushingoid features, and
is without rash or nail abnormalities. Muscle strength is 2-3/5 in all four
extremities, worst in proximal muscles of both legs. An MRI scan using a
STIR sequence shows increased signal intensity in muscles of the quadriceps,consistent with the presence of inflammation.
The mean age of onset of limb girdle muscular dystrophy (LGMD) Type 2B, a
dysferlinopathy, is 19 years of age. Proximal lower extremity weakness is a
common initial finding, and unlike some types of juvenile dystrophies,hypertrophy of calf muscles usually does not occur. Truncal weakness can be
marked, and this affects balance and gait making walking difficult. MRI STIR
studies in LGMD can show increased signal intensity that is not readilydistinguished from the pattern seen in inflammatory myopathies. For these
reasons, this disorder can be misdiagnosed as polymyositis. However, the
muscle biopsy shows defective staining for dysferlin, a muscle membrane protein, and this feature distinguishes the histologic changes from those seen
with polymyositis.
Another clue that this case may not be PM is the very high initial CK level,
more than 100 times greater than the upper limit of normal, which isuncommon in the inflammatory myositis syndromes. Chronic juvenile DM is
typically associated with more prominent cutaneous features than those
described here and frequently also has vasculitic changes and prominent soft
tissue calcifications, which are not present in this patient. Furthermore, thisyoung woman is not in the demographic category typical for IBM, which is
generally observed in middle-aged or older men. Diabetes mellitus can alter blood flow in muscles and cause MRI changes, but this is usually associated
with longstanding disease, which this patient does not have.
Question Number: 21
CaseA 46-year-old woman has had a 4-month history of recurring confluent
erythematous macules over the sun-exposed areas of the forearms, anterior
torso, face, and neck that are occasionally associated with superficial
ulceration. She has not had associated mouth ulcers, sicca symptoms,
xerostomia, or joint problems. Evaluation at the time her symptoms beganwas remarkable only for the rash and an otherwise very fair complexion;
serology studies were notable for positive ANA at a titer of 1:640 (speckled
pattern) and anti-SSA/Ro antibodies in a significant elevated titer. She was
initially advised to use a high SPF sunscreen and was prescribedhydroxychloroquine 400 mg daily and prednisone 40 mg daily. The rash
promptly responded to corticosteroids but has flared each time the prednisone is tapered below 20 mg/day. Other than persistent leucopenia
(WBC 2,200/mm3), other blood counts, chemistry profile, and urinalysis
have been repeatedly normal.Question
Which of the following is the most appropriate recommendation at this time?
Cutaneous manifestations of lupus are quite variable, manifesting aserythematous macular or maculopapular rashes, discoid plaques, bullous
lesions, or vasculitis manifest as nonblanching purpura, cutaneous ulcers, or
urticarial lesions. While antimalarials are effective for suppressing many of
the cutaneous manifestations of lupus and corticosteroids in sufficient dosewill usually effect resolution of cutaneous flares, other immunomodulating
therapies are often required to suppress cutaneous manifestations of lupus toavoid the toxicity associated with long-term corticosteroid use.
Intravenous pulse cyclophosphamide is effective in managing severe
manifestations of SLE but is typically reserved for severe lupus nephritis,
severe CNS manifestations, or refractory severe immune-mediatedcytopenias, with other less toxic options employed to manage active skin
disease. Azathioprine is often effective as a corticosteroid-sparing therapy for
a variety of lupus manifestations, including skin disease. However,concurrent leucopenia as is present in this patient may preclude use of
azathioprine in doses sufficient to effectively manage skin disease. In the
setting of leucopenia, mycophenolate mofetil might also be considered as an
alternative to azathioprine as a corticosteroid-sparing therapy because it impacts predominantly lymphocyte proliferation with minimal impact on granulopoiesis, but the
efficacy of mycophenolate in managing cutaneous manifestations of lupus is not well
established.Other alternatives that do not impact granulopoiesis, such as dapsone,
addition of a second antimalarial, or thalidomide, are often quite effective inmanaging cutaneous manifestations of lupus. Dapsone has been shown to be particularly useful in managing cutaneous ulcers in SLE caused by small
vessel vasculitis or bullous disease. Persistent mauclopapular eruptions that
are not adequately suppressed with hydroxychloroquine often will respond toaddition of a second antimalarial such as quinacrine. If this option is used,
combined use of these two antimalarials is more effective than either alone
and is the concurrent use of both is recommended rather than discontinuing
hydroxychloroquine and adding quinacrine. Quinacrine is usually well
tolerated although patients with a fair complexion may find it objectionable
because of predictable yellow discoloration of the skin with prolonged use.Thalidomide is highly effective in managing mucocutaneous ulcers, as well as
refractory erythematous rashes, including the eruption associated with
subacute cutaneous lupus, a variant associated with elevated titers of anti-SSA/Ro antibodies.
Question Number: 22
CaseAn 18-year-old woman has 1-year history of progressive proximal muscle
weakness. Four months ago, her CK level was 12,000 U/L, a short tau
inversion recovery (STIR) MRI showed edema in her proximal thighs, and a
muscle biopsy revealed fiber degeneration and regeneration with infiltrationof some lymphocytes and phagocytic cells. She was treated with high-dose
corticosteroids, methotrexate, and monthly infusions of intravenous
immunoglobulins for 3 months. Despite this treatment, muscle strength has
continued to deteriorate and CK level is 16,000 U/L.Her family history reveals that similar symptoms developed 3 years ago in
her 26-year-old brother.Question
Testing of a repeat muscle biopsy specimen is most likely to show which of
the following?
A.Histochemistry revealing fiber type grouping
B.
Immunohistochemistry showing absence of dysferlinC.
Trichrome staining revealing ragged red fibers
D.
Absence of carnitine palmitoyltransferase (CPT) activity
Correct Answer BAnswer Rationale
The idiopathic inflammatory myopathies can be confused with other
myopathies that may have an inflammatory component, such as muscular
dystrophies. Dysferlin deficiency causes limb-girdle muscular dystrophy. This condition is familial with the usual onset between 18 and 20
years of age. CK levels may be 100 times the upper limit of normal. Muscle
histology typically shows inflammation. Corticosteroid therapy is not helpfuland, in some cases, may make the condition worse.
Fiber type grouping is characterisc of neuropathic processes that involve
reinervation.Ragged red fibers are seen by Trichome staining of muscle in patients with
some mitochondrial myopathies. Mitochondrial myopathies may be familial,
can present with proximal weakness and elevated CK levels, and will not
respond to immunosuppressive therapy. Muscle tissue would not show
regeneration or inflammatory cell infiltrate.
This clinical course is not consistent with CPT deficiency. CPT deficiency causesepisodic rhabdomyolysis. Between episodes, strength and muscle enzymes are normal.
Question Number: 23
CaseA physician colleague asks for evaluation because he thinks he may have
rheumatoid arthritis. He is 55 years old and enjoys excellent health; he is an
avid bicyclist. Nine months ago, mild pain and swelling developed in the MCP joint of his right thumb. Two months ago, similar symptoms developed in the
PIP joint of the left ring finger. Both sets of symptoms developed without
antecedent trauma. There is no morning stiffness. On physical examination,
there is mild soft tissue swelling with minimal tenderness of the twosymptomatic joints. No other joint abnormalities are present.
According to the available evidence from clinical trial data, which of thefollowing management approaches is most likely to retard progression of this patient’s arthritis?
A.
Prednisone 10 mg po dailyB.
Naproxen 500 mg po twice daily
C.Sulfasalazine 1000 mg po bid
D.
Etanercept 25 mg subcutaneously twice weekly
E.Methotrexate 15 mg po once weekly
Correct Answer
EAnswer RationaleThis patient does not meet the ACR criteria for rheumatoid arthritis and
would thus be classified as having an undifferentiated arthritis. In contrast to
early rheumatoid arthritis, there are few clinical trials that have examinedtherapy for patients with undifferentiated arthritis. The best such study was
AAnswer RationaleMixed cryoglobulinemia is a systemic vasculitis associated with hepatitis C
infection. The mixed cryoglobulinemia syndrome is associated with purpura,
arthralgia, and asthenia. There may also be neurologic and renalinvolvement. Treatment of hepatitis C mixed cryoglobulinemia (HCV-MC)
may target the viral load or the B-cell arm of autoimmunity. Peg-
Interferon─Ribavirin is the first line therapy. For refractory HCV-associated cryoglobulinemia vasculitis or acute severe life-threatening organ
involvement, plasmapheresis, corticosteroids in combination with cytotoxic
agent, or Rituximab should be considered as treatment options.
Question Number: 26
Case
A 56-year-old woman has a 4-month progression of 2nd and 4th bilateral DIPdeformity. Pruritic nodules on the left 4th DIP joint and right pinna also
developed. She has a 2-month history of cough, dyspnea, weight loss, and
malaise.Bilateral radiographs of the hands reveal extensive erosive changes in the
bilateral 2nd and 4th DIP joints.
Radiograph of the chest reveal hilar lymph nodes.CT Scan of the chest reveal nodular pleural thickening, pleural effusions, andmediastinal and hilar lymphadenopathy
Biopsy of the 4th DIP nodule reveals villous, hypertrophic synovitis with
plasma cells and multinucleated giant cellsQuestion
Which of the following is the most likely diagnosis?
A.Rheumatoid arthritis
B.
Relapsing polychondritis
C.Seronegative spondyloarthropathy with peripheral joint involvement
Past medical history is notable for hypertension for which she takes atenolol50 mg daily.
On physical examination now, pain restricts maximal abduction and rotation of the
shoulders. Cervical spine range of motion is complete. No synovitis is detected. Motor strength is normal in all extremities. There is no muscle tenderness. There is no cranial
tenderness and temporal arteries are easily palpated with normal pulsations.
QuestionWhich of the following is the most appropriate next step in management?
Inject shoulders with intra-articular corticosteroidsD.
Discontinue atenolol
E.Begin pregabalin 75 mg/day
Correct Answer
AAnswer Rationale
The clinical presentation of this patient is most consistent with polymyalgia
rheumatica (PMR). The onset of bilateral, symmetric, shoulder and pelvic
girdle stiffness and nocturnal symptoms in an older patient, with the absenceof peripheral joint swelling, is most consistent with this diagnosis. Though
markers of inflammation such as ESR and C-RP are generally elevated, theycan be normal in about 20 percent of patients. These patients with PMR andnormal makers of inflammation have a similar clinical course to patients with
elevated markers. Their response to low to moderate doses of corticosteroids
is generally dramatic.
MRI and ultrasound studies showed that patients who have PMR with normalor high ESRs have similar inflammatory shoulder lesions. These imaging
studies may facilitate the proper diagnosis in patients with the typical
proximal symptoms of PMR who also have normal ESRs.Intra-articular corticosteroids may provide short-term pain relief, but would
not be recommended given the strong likelihood of symptom relapse.
Increasing the dose of ibuprofen would likely provide little additional benefitand there is no evidence that NSAIDs are effective in managing patients with
PMR.
There are no clinical features to suggest fibromyalgia or another soft tissue pain
syndrome, thus prescribing amitriptyline or pregabalin is not indicated. Beta-blockerssuch as atenolol do not cause these pain syndromes and so this medication should not be
discontinued.
Question Number: 28Case
A 73-year-old woman who has had deforming rheumatoid arthritis for the
past 20 years now has persistent neutropenia. She has been living in anassisted care facility for the past 3 years. Despite bilateral knee
arthroplasties, her mobility and ability to live independently have been
progressively impaired by arthritis of her ankles, feet, wrists, and hands. Pasttherapies have included parenteral gold, penicillamine, hydroxychloroquine,
methotrexate, and etanercept. At the time of admission to the facility, her
WBC was 3200/mm3 and her physician chose to maintain her on prednisone
7.5 mg qAM alone for her rheumatoid arthritis. Her only infection was aurinary tract infection 3 months ago treated with oral ciprofloxacin. Other
scan and venous Doppler studies would not be indicated in this clinicalsetting.Question Number: 36Case
A 22-year-old college student has left knee swelling after playing soccer. He
does not recall specific trauma to the affected joint. He denies sexual
activity. Review of systems is notable for the lack of antecedent infectious
symptoms, visual difficulties, oral ulcers, back pain, diarrhea, or rash. His
home is in Connecticut, and deer frequent his back yard. On physical
examination, the left knee is large and swollen.Analysis of aspirated joint fluid reveals WBC 11,000/mm3 with predominant
neutrophils, no crystals, and negative bacterial cultures. Lyme titer is
markedly positive with a confirmatory Western blot test showing 10 positive
bands.
He is treated with doxycycline for 30 days. The follow-up examination shows
a persistent effusion and no abnormal neurological manifestations. The oral
antibiotic is continued for another 30 days. Intravenous ceftriaxone is
prescribed for 1 month after the extended course of oral doxycycline fails to
eradicate the effusion. Synovial fluid aspiration now shows persistent
inflammatory joint fluid with negative PCR for Borrelia burgdorferi.QuestionWhich of the following is most appropriate therapy at this time?A.
EtanerceptB.
Oral doxycycline for 30 daysC.
IV ceftriaxone for 30 daysD.
IV penicillin for 30 daysE.
Hydroxychloroquine
Correct AnswerEAnswer RationaleLyme arthritis is an inflammatory arthritis that primarily affects large joints,especially the knee, and is caused by infection with Borrelia burgdorferi,
which is a spirochete transmitted by Ixodid ticks. In most patients,
treatment with oral doxycycline for 30 to 60 days eradicates infection and the
effusion. In a small percentage of patients, a persistent effusion occurs
despite months of oral and intravenous antibiotic therapy. In these patients,
the appropriate work-up should include PCR testing of the synovial fluid for
Borrelia burgdorferi. If the PCR is positive, repeated courses of antibiotic