Vous êtes sur la page 1sur 47

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 Answer
BAnswer 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 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 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 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 density
in older men with borderline low testosterone levels. Since androgen therapy has possible
undesirable effects on other organ systems, particularly the prostate gland, testosterone
therapy 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 tournament
yesterday 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 to
take his replacement therapy.
Physical examination shows no abnormalities of the knee, but internal
rotation at the hips is limited.
Radiograph of the hips is shown in figure below.
Figure
Question
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 evaluation
D.
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 Rationale
Children 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 be
made 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
Case
A 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 shortly
after 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 severe
cramping 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.
On examination, he has 4/5 strength in proximal muscles of the upper and lower
extremities. Findings on examination of the joints and the remainder of the neurologic
examination are normal.
Laboratory studies reveal CK of 900 U/L. EMG shows fibrillation potentials
and early recruitment of short-duration, low-amplitude motor unit action
potentials. A decremental response was observed to repetitive 20-Hz nerve
stimulation.
Question
Which of the following is the most likely finding on muscle biopsy?
A.
Perivascular infiltration of lymphocytes with perifasicular atrophy and capillary plugging
B.
Occasional degenerating and regenerating fiber with PAS positive subsarcolemmal
vacuoles
C.
Many small triangular fibers and fiber type grouping
D.
Some type II fiber atrophy and increased oil red O staining in type I fibers
E.
Many fibers with central nuclei, occasional hypertrophic cells, and ragged red changes on
Gamori
Trichrome staining
Correct Answer
BAnswer Rationale
McArdle’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, and
weakness 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, to
regenerate 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 the
initial 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 and
capillary 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 fibers
occurs with lipid storage diseases like carnitine deficiency of some
mitochondrial myopathies.
Many fibers with central nuclei, occasional hypertrophic cell, and ragged red
change on Gamori Trichrome staining are indicative of a mitochondrial
myopathy.

Question Number: 3
Case
A 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 shortly
after 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 severe
cramping 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.
On examination, he has 4/5 strength in proximal muscles of the upper and lower
extremities. Findings on examination of the joints and the remainder of the neurologic
examination are normal.
Laboratory studies reveal CK of 900 U/L. EMG shows fibrillation potentials
and early recruitment of short-duration, low-amplitude motor unit action
potentials. A decremental response was observed to repetitive 20-Hz nerve
stimulation.
Question
Which of the following is the most likely finding on muscle biopsy?
A.
Perivascular infiltration of lymphocytes with perifasicular atrophy and capillary plugging
B.
Occasional degenerating and regenerating fiber with PAS positive subsarcolemmal
vacuoles
C.
Many small triangular fibers and fiber type grouping
D.
Some type II fiber atrophy and increased oil red O staining in type I fibers
E.
Many fibers with central nuclei, occasional hypertrophic cells, and ragged red changes on
Gamori
Trichrome staining
Correct Answer
BAnswer Rationale
McArdle’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, and
weakness 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, to
regenerate 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 the
initial 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 and
capillary 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 fibers
occurs with lipid storage diseases like carnitine deficiency of some
mitochondrial myopathies.
Many fibers with central nuclei, occasional hypertrophic cell, and ragged red
change 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 2
years.
Laboratory data include:
Serum calcium: 8.2 mg/dl
Serum phosphorus: 2.3 mg/dl
Alkaline phosphatase: 175 U (normal 33-115 Units)
25-hydroxyvitamin D: 8 ng/ml (normal 20-100 ng/ml)
1,25 hydroxyvitamin D: 40 pg/ml (normal 25-45 pg/ml)
Parathormone: 108 pg/ml (normal 10-65 pg/ml)
Question
Which of the following radiographic abnormalities is most likely in this
patient?
A.
Increased bone mineral density
B.
Subperiosteal resorption
C.
Looser’s zones
D.
Erlenmeyer flask deformity of the distal femora
E.
Mixed areas of lucency and sclerosis in the long bones
Correct Answer
CAnswer Rationale
This patient has osteomalacia as a result of vitamin D deficiency.
Characteristically, both the serum calcium and the serum phosphorus levels
are 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 primary
hyperparathyroidism. The Erlenmeyer flask deformity is a feature of
Gaucher’s disease. Mixed areas of lucency and sclerosis in the long bones are
a feature of Paget’s disease.

Question Number: 6
Case
A 21-year-old white woman has sudden onset of swelling and pain in her
right knee associated with warmth and erythema. Synovial fluid analysis of
fluid obtained from the knee reveals 21,000 WBC/mm3, and needle-shaped
negatively birefringent crystals are found under polarized light microscopy.
Family history reveals that the patient’s father and brother have gout.
Laboratory data include:
Serum creatinine : 2.9 mg/dl
Serum urate: 10.5 mg/dl
24-Hour urinary uric acid: 350 mg
Question
Which of the following findings is most likely in this patient?
A.
She is homozygous for phosphoribosylpyrophosphate (PRPP) synthase overactivity
B.
She is heterozygous for hypoxanthine-guanine phosphoribosyltransferase (HPRT)
deficiency
C.
She homozygous for adenine phosphoribosyltransferase (APRT) deficiency
D.
She has a mutation in the uromodulin (UMOD) gene
E.
She is homozygous for purine nucleoside phosphoylase (PNP) deficiency
Correct Answer
DAnswer Rationale
Both PRPP synthase overactivity and partial HPRT deficiency cause
hyperuicemia and gout, but both have X-linked inheritance and, therefore, do
not occur in women.

A deficiency of APRT causes affected individuals to have kidney stones


composed of 2,8 dihydroxyadenine.
Mutations in UMOD gene are responsible for familial juvenile hyperuricemic
nephropathy (FJHN). FJNG is inherited as an autosomal dominant trait with a
high degree of penetrance and is usually associated with gout. Renal disease
usually develops in the second decade of life and progresses to end-stage
renal disease by mid-life.
PNP deficient individuals have selective T-cell immunodeficiency.

Question Number: 7
Case
A 52-year-old woman with seropositive erosive rheumatoid arthritis has
increasing joint pain, swelling, and stiffness and has been under stress at
work. She has been taking methotrexate for several months. On physical
examination, she is anxious and has synovitis. ESR is 74 mm/hr. She is
reluctant to take an anti-TNF blocker and agrees to start leflunomide in
addition to continuing methotrexate.
After several weeks, the joint pain and stiffness improve and follow-up
examination shows minimal synovitis; her mood is better. She returns for
evaluation two months later and findings on examination are unchanged
except she has lost 4 pounds. CBC and chemistries are normal and ESR is 30
mm/hr.
At her next visit 2 months later, she has lost an additional 6 pounds and feels
well. Examination shows no synovitis or adenopathy.
Laboratory data include:
CBC: normal
ESR: 26 mm/hr
TSH: 0.9 µU/ml
LFT: normal
BUN: 23 mg/dl
Creatinine: 1.0 mg/dl
Albumin: 4.0 gm/dl
Question
Which of the following is the most likely cause of the patient’s weight loss?
A.
Active rheumatoid arthritis
B.
Methotrexate associated lymphoma
C.
Hyperthyroidism

D.
Anxiety
E.
Idiosyncratic effect of leflunomide
Correct Answer
EAnswer Rationale
Rheumatoid arthritis is a systemic inflammatory disease that affects the
joints and extra-articular systems. Constitutional symptoms such as weight
loss are not uncommon with uncontrolled disease. Patients with rheumatoid
arthritis are at increased risk for lymphoma, and methotrexate is known to
cause reversible lymphomas, but there is no indication that this patient has
lymphoma. She does not appear to be clinically hyperthyroid, and her
anxiety improved.
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 secondary
effect 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. Recognition
of this side effect is important since unnecessary additional testing may be
undertaken to investigate weight loss.

Question Number: 8
Case
A 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 the
dorsum 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 both
feet and decreased proprioception of the toes of both feet. No ulcers or rash
are present. Hemoglobin level is 10.4 gm/dl.
A radiograph of the left foot is shown below:
Figure
Question
Which of the following is the most likely diagnosis?
A.
Calcium pyrophosphate dehydrate deposition disease
B.
Chronic gout
C.
Neuropathic osteoarthropathy
D.
Osteomyelitis
E.
Reflex sympathetic dystrophy syndrome
Correct Answer
CAnswer Rationale
This patient has a long-standing history of diabetes mellitus type 2 and
months of foot swelling. The radiograph shows hindfoot and midfoot joint
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 patient
describes. 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 with
overhanging edges. Osteomyelitis may be present in diabetic patients with
foot ulcers, but this patient has no preexisting foot ulcer. The patient also
has no paronychia, cellulitic skin features nor constitutional symptoms
including fever to suspect infection.

Question Number: 9
Case
An 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 diffuse
lymphadenopathy 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/mm3
Urinalysis: some WBCs but no bacteria or proteinuria
Echocardiography: normal
Spinal fluid analysis: a few lymphocytes but no organisms on gram stain
Question
Which of the following is the most appropriate treatment?
A.
IVIG 2 gm/kg over 12 hours
B.
Aspirin 325 mg/day
C.
Prednisone 2 mg/kg/day
D.
Ibuprofen 40mg/kg /day
E.
Infliximab 5 mg/kg single dose
Correct Answer
AAnswer Rationale
The clinical description is classic for Kawasaki disease. Although staph toxic
shock syndrome and EBV and CMV infections can sometimes present in a
similar way, echocardiographic changes are often later in the course.
When there is a clinical index of suspicion for Kawasaki disease, the
recommended treatment is high dose IVIG over 12 hours. This is most

effective early in the course, before periungual desquamation or


echocardiographic changes have occurred. Corticosteroids may be used if
IVIG has failed; aspirin (not ibuprofen) is recommended as an antiplatelet
agent. Studies are ongoing to determine effectiveness of anti-TNF agents in
Kawasaki disease; their effectiveness in treatment is not yet established.

Question Number: 10
Case
A 35-year-old man has had the gradual onset of pain and stiffness in his legs
when he jogs one-half mile on a treadmill. He has cramps in his calves and
hamstrings toward the end of the half-mile jog. The pain, stiffness, and
cramps resolve with rest. Physical examination shows 4/5 hip flexor muscle
strength. Serum creatine kinase level is 324 U/L. Electromyography reveals
low amplitude motor unit action potentials. Ischemic forearm muscle testing
produces the following results:
Venous Blood
lactate (mg/dL) NH3 (µg/dL)
At rest
8
20
Two minutes after exercise 9
90
Question
Which of the following deficiencies is the most likely diagnosis?
A.
Acid maltase
B.
Carnitine palmitoyltransferase II
C.
Myoadenylate deaminase
D.
Myophosphorylase
E.
Phosphorylase b kinase
Correct Answer
DAnswer Rationale
In phosphorylase b kinase deficiency there is a normal or only partially
impaired rise in venous lactate with exercise. Ischemic forearm testing
reveals 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 CPT
II. 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 in
metabolic muscle disease.

Question Number: 11
Case
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 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
than the 10-day course of ciprofloxacin, she has not been on any new
medications for the past 12 months.
WBC: 1800/mm3 (25% neutrophils, 65% lymphocytes)
Hgb: 10.3 gm/dl
Peripheral smear: paucity of neutrophils, occasional large lymphocyte with
pale blue cytoplasm and azurophilic granules
Question
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 as
leukemia, 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 flow
cytometry 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
Case
A 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 symptoms
responded 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 serological
studies. 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/L
dsDNA: 26 IU
TSH: 4.9 µU/ml
Electrolytes: Potassium 3.4 mmoles/L
Mg: Normal
Ca: Normal
Question
Which of the following is the most likely cause of the patient’s proximal
muscle weakness?
A.
Inclusion body myositis
B.
Lupus flare
C.
Hydroxychloroquine myopathy
D.
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 gastrointestinal
disturbance. 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 distal
muscles. 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
weakness.
Question Number: 13
Case
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. He
resists 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 the
elbow 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.
Question
Which of the following is the most appropriate next step in management?
A.
Surgical open drainage of the joint
B.
Continue present antibiotic regimen
C.
Aspirate the elbow and look for crystals
D.
Add another antibiotic to cover gram-negative organisms
Correct Answer
CAnswer Rationale
CPPD crystals can elicit an intense inflammatory response in a single joint
that 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
Case
A 4-year-old girl has recent onset of rash over her knuckles and knees.
Nailfold capillaroscopy is shown in Figure 1 below.
Figure
Question
The nailfold changes place this patient at highest risk for which of the
following?
A.
Calcinosis
B.
Pulmonary hemorrhage

C.
Retinal changes
D.
Gastrointestinal vasculitis
E.
Corticosteroid resistance
Correct Answer
DAnswer Rationale
Calcinosis occurs late in disease and mainly in patients who have had
prolonged disease activity.
Both pulmonary hemorrhage and retinal changes on the basis of vasculitis
are rare in dermatomyositis, but can occur as a part of the vasculitic picture.
However, nailfold capillary changes are a good predictor of risk for
gastrointestinal vasculitis, the most common vasculitic complication in
juvenile dermatomyositis.
Corticosteroid resistance or dependence does not correlate with nailfold
changes.
Educational Objective
To recognize juvenile dermatomyositis and the association of gastrointestinal
vasculitis in children with dermatomyositis and nailfold capillary changes.

Question Number: 15
Case
A 65-year-old woman with osteoporosis sustains her second thoracic
vertebral compression fracture within the past 12 months despite ongoing
therapy with alendronate for the past 3 years. She has routinely taken
calcium and vitamin D supplementation ever since osteoporosis was first
diagnosed at age 58 years.
Question
Which of the following treatment regimens is most likely to be effective in
improving this patient’s bone mineral density over the next 3 years?
A.
Continue alendronate therapy alone
B.
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 18
months, 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 alendronate
for 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 1
year 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 a
synergistic 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 18
months, and then alendronate alone after the discontinuation of PTH.

Question Number: 16
Case
A 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
to brief courses of prednisone.
On physical examination, his fingers are deformed with nodules at the
proximal but not distal IP joints (see figure below). He has bilateral, cool of
the olecranon bursa. His right knee is visibly swollen, erythematous, and
warm to the touch and has a ballotable effusion.

Figure
Question
Which of the following is the most appropriate course of action?
A.
Obtain a radiograph of the inflamed knee
B.
Perform arthrocentesis on the inflamed knee
C.
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 be
expected 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 spontaneously
and 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-dose
corticosteroids 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 to
anti-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.
Stop the annual eye examinations
B.
Discontinue the hydroxychloroquine
C.
Continue the hydroxychloroquine
D.
Discontinue visual field testing at her annual eye examinations
E.
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 antimalarial
medications, especially if the patient has been taking them for many
years. A full visual field and color test is required to optimally track the
retinal 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: 18
Case
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
patient’s discomfort?
A.
Anterior tibial nerve
B.
Deep peroneal nerve
C.
Posterior tibial nerve
D.
Superficial peroneal nerve
E.
Common peroneal nerve
Correct Answer
CAnswer Rationale
This patient has tarsal tunnel syndrome marked by posterior tibial nerve
compression. Foot trauma including talus or calcaneal fracture predisposes
to 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 the
deep 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: 19
Case
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 3
years, finger fractures while playing volleyball at age 9 years, and foot
fractures at age 12 years when he kicked a can. Physical examination shows
a 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 finding. He wears hearing aids.
Laboratory data include:
CBC: normal

Alkaline phosphatase: 55 U/L


Vit D: 23 ng/mL (range: 9.0-37.6 ng/mL)
Testosterone: normal
Question
Which of the following studies is the most appropriate next step?
A.
Skin fibroblast culture for collagen 1 alpha 1 mRNA production
B.
Bone densitometry
C.
COLA1 gene sequencing
D.
Quantitative CT scans
E.
Histomorphometric analysis of bone
Correct Answer
BAnswer Rationale
This is a case of type I ostegenesis imperfecta (OI), a rare inherited
connective 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 form
type 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 may
enjoy 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 the
diagnosis. 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 with
type 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. Clinical
manifestations 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 a
significant 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., standard
deviation 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 unusual
circumstances 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: 20
Case
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 was
consistent 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 shown
significant 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 an
only 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.
Laboratory data include:
CK: 8,000 U/L (normal range 40-150)
Creatinine: 0.6 mg/dL(0.6-1.5)
Blood glucose (fasting): 160 mg/dL (70-110)
Westergren ESR: 40 mm/hr (1-30)
Thyroid-stimulating hormone: 2 uU/ml (0.5-5.0)
ANA: negative
Jo-1 antibody: negative
Urinalysis: negative for protein, blood, and leukocytes
The decision is made to reevaluate her disease status and obtain another
muscle biopsy.

Question
Which of the following is the most likely finding on the repeat biopsy?
A.
Inclusion body myositis
B.
Dermatomyositis
C.
Limb girdle muscular dystrophy
D.
Polymyositis
E.
Diabetic vasculopathy
Correct Answer
CAnswer Rationale
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 readily
distinguished 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 is
uncommon 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, this
young 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
Case
A 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 began
was 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 prescribed
hydroxychloroquine 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?
A.
Add pulse intravenous cyclophosphamide 750 mg/m2
B.
Add azathioprine 2 mg/kg/day
C.
Add dapsone 50 mg/day
D.
Add quinacrine 100 mg/day
E.
Add thalidomide 50 mg/day
Correct Answer
DAnswer Rationale
Cutaneous manifestations of lupus are quite variable, manifesting as
erythematous 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 dose
will usually effect resolution of cutaneous flares, other immunomodulating
therapies are often required to suppress cutaneous manifestations of lupus to
avoid 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-mediated
cytopenias, 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 in
managing 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 to
addition 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
Case
An 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 infiltration
of 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 dysferlin
C.
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 helpful
and, 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 causes
episodic rhabdomyolysis. Between episodes, strength and muscle enzymes are normal.
Question Number: 23
Case
A 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 two
symptomatic joints. No other joint abnormalities are present.
Laboratory data include:
ESR: 1 mm/hr
C-reactive protein: <0.7 mg/dL
Rheumatoid factor: 256 IU/ml

CCP antibody level: >100


Question
According to the available evidence from clinical trial data, which of the
following management approaches is most likely to retard progression of this
patient’s arthritis?
A.
Prednisone 10 mg po daily
B.
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 Rationale
This 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 examined
therapy for patients with undifferentiated arthritis. The best such study was
the PROMPT trial in which 110 patients with undifferentiated arthritis (defined
by the 1958 ACR criteria for probable RA) were randomized to receive
methotrexate 15 mg weekly or placebo. The dose of methotrexate was
increased every 3 months if the Disease Activity Score (DAS) was >2.4. The
primary end-point was the fulfillment of the ACR criteria for RA.
Undifferentiated arthritis progressed to RA in 22 of the 55 methotrexate-
treated patients and in 29 of the 55 placebo-treated patients (p=NS). All of
the placebo-treated patients who eventually fulfilled ACR criteria did so within
one year, in contrast to only one-half of the methotrexate-treated patients
(p=0.04). At the end of 18 months, fewer methotrexate-treated patients
showed radiographic progression compared to the placebo-treated patients
(p=0.046). Methotrexate was effective in reducing the signs and symptoms
of undifferentiated arthritis.
Question Number: 24
Case
A 52-year-old woman is referred for further evaluation of progressive fatigue,
dyspnea, and stiffness in her hands. She began to have Raynaud’s symptoms
3 years ago and for the past year has had mild nonproductive cough with
increasing exertional dyspnea. For the past 6 months, her fingers have
become progressively stiff with impaired grip function. She has not had any
fever, rash, mouth ulcers, dysphagia, or changes in bowel function. Physical

examination shows blood pressure 120/86 mmHg, heart rate 100 bpm, and
normal respirations and temperature. Sclerodactyly without terminal digital
ulcers is present in the upper extremities with mild induration present on the
forearms and face. Ocular and oral membranes are notable for pallor but are
otherwise normal without evidence of ulceration or xerostomia. Bibasilar
crackles are present on chest auscultation but there is no audible pleural or
pericardial rub and the pulmonic second heart sound is not accentuated.
Other than limitation in extension of the wrists and IP joints of her hands,
findings on joint examination are normal. Muscle strength testing is normal.
Laboratory data include:
WBC: 6200/mm3
Hct: 24% (MCV 76)
Hgb: 7.4 mg/dl
Platelet count: 720,000/mm3
Creatinine: 1.6 mg/dl
CK: 380 IU/ml (nl<190)
AST: normal
ALT: normal
Urinalysis: negative protein, negative blood; 0-2 WBC/hpf, 0-2 RBC/hpf
Chest CT scan: bibasilar interstitial disease, no ground-glass opacities
Echocardiogram: normal LV, RV ejection fraction, mild pericardial effusion,
with estimated PA systolic pressure of 43 mmHg
Pulmonary function tests: mild restrictive impairment, DLCO 60% of
predicted; DLCO corrected for alveolar volume 86% of predicted.
Renal ultrasonography: normal size kidneys
Question
Which of the following procedures is most appropriate at this time?
A.
Esophagogastroduodenoscopy (EGD)
B.
Bone marrow aspiration and biopsy
C.
Open-lung biopsy
D.
Muscle biopsy
E.
Right heart catheterization
Correct Answer
AAnswer Rationale
Comprehensive management of systemic sclerosis requires attention to
complications that may occur in multiple visceral organs including the lungs,
heart, kidneys, and gastrointestinal tract. Significant anemia may occur in
patients with systemic sclerosis caused by iron deficiency or renal
dysfunction. Chronic gastrointestinal blood loss may occur because of
gastrointestinal arteriovenous ectasias (GAVE) that are prevalent in patients
with systemic sclerosis or erosive esophagitis arising from chronic reflux. GI
blood loss caused by GAVE should be considered in any patient with systemic
sclerosis and signs of iron deficiency anemia (microcytic indices,
thrombocytosis). Active bleeding can be managed with electrocautery or
laser treatment of lesions identified at endoscopy. Other clinicians advocate
use of estrogen if not otherwise contraindicated.
It is important to recognize that elevations in creatinine levels may herald impending
scleroderma renal crisis, even in the absence of elevated blood pressure, and should
prompt institution of treatment with an angiotensin- converting enzyme inhibitor. While
anemia resulting from chronic kidney disease may occur as a complication of systemic
sclerosis, treatment with erythropoietin preparations should not be instituted until other
treatable causes of anemia have been excluded.
Interstitial lung disease in systemic sclerosis causes significant morbidity and
is most commonly seen on radiographs as basilar interstitial markings.
Alveolitis is reliably detectable by high-resolution CT scan (without contrast).
In the absence of demonstrable alveolitis, there are at present no known
efficacious treatment interventions for scleroderma-associated ILD and
performance of a lung biopsy is seldom required for assessment and
management. In the absence of marked impairment of the DLCO corrected
for alveolar volume on pulmonary function testing or abnormalities on
echocardiography suggestive of pulmonary hypertension such as RV dilation
or elevated estimated PA systolic pressure, right heart catheterization would
not be indicated.
Elevations in creatine kinase (CK) levels may occur in patients with systemic
sclerosis, either because of concomitant hypothyroidism or inflammatory
myopathy. If there is no clinical weakness in association with moderate mild
to moderate CK elevations, it is not necessary to obtain a muscle biopsy. If
there is demonstrable weakness in a pattern consistent with inflammatory
myopathy and EMG findings are consistent with a myopathy (as opposed to a
primary neuropathic process), it may still be appropriate to proceed with
treatment for inflammatory myopathy without obtaining a confirmatory
muscle biopsy in patients with established systemic sclerosis. Treatment
options other than corticosteroids, such as weekly methotrexate,

azathioprine, or IVIG, should be considered due to the increased risk of renal


crisis associated with corticosteroids use in patients with systemic sclerosis.
Question Number: 25
Case
A 32-year-old woman has a 2-month history of lower extremity violaceous
macules, generalized arthralgias, and asthenia.
Laboratory data include:
HCV RNA: positive
C4: 10 mg/dl
Cryoglobulins: positive
Urinalysis: normal
Rheumatoid factor: 180 IU/ml
Skin biopsy of the lower extremity rash reveals leukocytoclastic vasculitis.
Question
In addition to prednisone, which of the following is the most appropriate
treatment?
A.
Peg-Interferon – Ribavirin
B.
Plasmapheresis
C.
Cyclophosphamide
D.
Rituximab
E.
Infliximab
Correct Answer
AAnswer Rationale
Mixed 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 renal
involvement. Treatment of hepatitis C mixed cryoglobulinemia (HCV-MC)
may target the viral load or the B-cell arm of autoimmunity. Peg-
Interferon&#9472;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 DIP
deformity. 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, and
mediastinal and hilar lymphadenopathy
Biopsy of the 4th DIP nodule reveals villous, hypertrophic synovitis with
plasma cells and multinucleated giant cells
Question
Which of the following is the most likely diagnosis?
A.
Rheumatoid arthritis
B.
Relapsing polychondritis
C.
Seronegative spondyloarthropathy with peripheral joint involvement
D.
Multicentric reticulohistiocytosis
E.
Psoriatic arthritis
Correct Answer
DAnswer Rationale
Multicentric reticulohistiocytosis is characterized by severe destructive
arthritis and cutaneous papulonodular lesions. Histiologic analysis of the
cutaneous nodules reveals infiltration of multinucleated giant cells and
histiocytes of monocyte/macrophage origin. An associated malignancy has
been identified in 15-28% of patients, particularly those with mesothelioma,
melanoma, lymphoma, sarcoma, ovarian cancer, and leukemia. Other
associations include hyperlipidemia, pregnancy, TB, and autoimmune
disease. This patient has an associated mesothelioma. Although the other
provided diagnoses could be considered in the differential diagnosis, the
biopsy supports the diagnosis of multicentric reticulohistiocytosis
Question Number: 27

Case
A 67-year-old woman has new-onset shoulder pain and stiffness. The
symptoms began insidiously 2 months ago. She describes pain and stiffness
around her shoulders and thighs, especially worse in the morning on arising.
She now has pain in these areas during the night which awakens her
routinely. Ibuprofen 400 mg qid provides only short-term relief. Four weeks
ago, she was examined by her internist who noted “normal findings.”
Laboratory data at that time included:
CBC: Normal
ESR: 29 mm/hr
CR-P: 0.9 U
Rheumatoid factor: negative
ANA: 1: 40
AST: Normal
ALT: Normal
CK: Normal
Creatinine: Normal
Albumin: Normal
TSH: 2.1 U
Urinalysis: Normal
Past medical history is notable for hypertension for which she takes atenolol
50 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.
Question
Which of the following is the most appropriate next step in management?
A.
Begin prednisone 15 mg/day
B.
Begin amitriptyline 10 mg at bedtime
C.
Inject shoulders with intra-articular corticosteroids
D.
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 absence
of peripheral joint swelling, is most consistent with this diagnosis. Though
markers of inflammation such as ESR and C-RP are generally elevated, they
can be normal in about 20 percent of patients. These patients with PMR and
normal 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 normal
or 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 benefit
and 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-blockers
such as atenolol do not cause these pain syndromes and so this medication should not be
discontinued.
Question Number: 28
Case
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 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
than the 10-day course of ciprofloxacin, she has not been on any new
medications for the past 12 months.
WBC: 1800/mm3 (25% neutrophils, 65% lymphocytes)
Hgb: 10.3 gm/dl
Peripheral smear: paucity of neutrophils, occasional large lymphocyte with
pale blue cytoplasm and azurophilic granules

Flow cytometry of peripheral blood demonstrates a clonal population of


CD3+, CD8+, CD16+, CD57+ T cells
Question
Which of the following is the most appropriate initial therapy for this patient?
A.
Splenectomy
B.
Increased dose of prednisone
C.
Infliximab
D.
Methotrexate
E.
Filgastrim
Correct Answer
DAnswer Rationale
This patient has large granular lymphocyte (LGL) syndrome resulting in an
autoimmune neutropenia. The LGL syndrome is a clonal disorder of cytotoxic
T-lymphocytes and has been classified as leukemia, even though it 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 flow cytometry of the peripheral blood
served to establish the diagnosis of LGL syndrome.
Methotrexate is considered first line therapy for patients with RA and LGL
syndrome. Cyclosporine A may also be of benefit in patients with LGL
syndrome. There are no data to indicate that glucocorticoids have lasting
benefit in the therapy for these diseases. While splenectomy may result in an
immediate improvement in the absolute neutrophil count, the clinical
response is usually not lasting. Given the morbidity of a splenectomy, it is
usually reserved for patients with active infections that are resistant to
treatment or patients with chronic refractory leg ulcers. Myeloid colony-
stimulating factors, such as filgastrim, may be used in severe neutropenia
while a remission is being induced with immunosuppressive agents.
Correct Answer
DAnswer Rationale
Intercurrent pregnancy in the context of active SLE poses significant
diagnostic and therapeutic challenges. Patients with a history of lupus
nephritis who become pregnant are at increased risk for hypertension and
the development of pre-eclampsia. The differentiation of pre-eclampsia from
lupus flare is often difficult diagnostically when edema, hypertension, and/or
azotemia develop during the late second or third trimester of pregnancy, but
the presence of active urine sediment and edema in the very early stages of
the pregnancy are more likely attributable to active lupus than to pre-
eclampsia.
The presence of active nephritis requires continued aggressive treatment
through the course of pregnancy, but the choice of needed
immunosuppressive therapy is limited to agents not known to cause
deleterious effects on the fetus. ACE inhibitors such as lisinopril are
teratogenic and must be discontinued in the context of pregnancy; labetalol
is an effective and safe alternative that can be supplemented with
vasodilators (such as hydralazine) as needed to manage blood pressure.
Mycophenolate has also been shown to be teratogenic and should be
discontinued at the onset of pregnancy. Corticosteroids may be continued
through the pregnancy in doses required to suppress disease activity, but
continued high doses may exacerbate edema and hypertension as well as
promote the development of gestational diabetes. Azathioprine has been
used through the course of pregnancy and has not been associated with fetal
malformation or birth defects. As such, corticosteroid-sparing therapy with
azathioprine to continue aggressive treatment of active SLE nephritis or
immune cytopenias is reasonable and may be necessary to manage SLE and
pregnancy. Antimalarials have not been shown to induce fetal abnormalities
and current recommendations are to continue antimalarial treatment in
patients with active SLE who become pregnant.
Question Number: 35
Case
A 35-year-old woman has had pain and swelling in her right foot for the past
3 weeks. Two months ago, she tore the medial meniscus and anterior
cruciate ligament in her right knee while skiing. These were repaired with
arthroscopic surgery. She was hospitalized on the third postoperative day for
severe pneumonia. Pulmonary function became compromised and she
required mechanical ventilation for 3 days. Total hospitalization was 11

days.
About 3 weeks ago, she began having swelling of her right foot. Over the
next few days, the foot became tender and she could not bare weight on
it. At first the pain was with use but soon became constant and more
severe. She describes the pain as both “lancinating and numb.” Now she is
afraid to let anyone or anything touch the foot because of the intense
increase in pain that occurs.
Physical examination shows global swelling of the right foot and ankle. The foot, up to the level of
the malleoli, is erythematous, warm, and extremely tender. Ankle and subtalar joint motion is
diminished. Homan’s sign is positive.
ESR and CBC are normal. Radiograph of the foot shows patchy osteopenia.
Question
Which of the following studies is most appropriate at this time?
A.
MRI of the foot and ankle
B.
DEXA scan of the foot and ankle
C.
Venous Doppler studies of the lower extremities
D.
Tecnitium triple-phase bone scan of the foot and ankle
Correct Answer
DAnswer Rationale
Complex regional pain syndrome (formerly known as reflex sympathetic
dystrophy) may occur spontaneously, but typically follows trauma, surgery,
or any incident that leads to immobilization of an extremity. The involved
part is typically distal and becomes swollen and tender, manifesting allodynia
(severe pain following a light touch) and hyperpathia (intense pain lasting
after the painful stimulus is removed). The extremity can appear red or blue
and feel warm or cool. Vasomotor changes may be noted as well. Patchy
osteopenia is observed on radiography, often within the first weeks of
symptoms.
Findings on triple-phase technitium bone scans are abnormal and consistent
with increased regional blood flow in the early phase and pooling and
increased bone uptake in the late phase.
MRI would confirm the regional bone loss but add no information. A DEXA
scan and venous Doppler studies would not be indicated in this clinical
setting.
Question Number: 36
Case
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.
Question
Which of the following is most appropriate therapy at this time?
A.
Etanercept
B.
Oral doxycycline for 30 days
C.
IV ceftriaxone for 30 days
D.
IV penicillin for 30 days
E.
Hydroxychloroquine
Correct Answer
EAnswer Rationale
Lyme 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
therapy should be considered. If the PCR is negative, antibiotics are not
recommended, and treatment with NSAIDs or hydroxychloroquine is
recommended. PCR testing is technically challenging and should thus be
performed in experienced laboratories.
Question Number: 37
Case
A 65-year-old woman has swelling in the right elbow. Four months ago, she
accidentally bumped it against a wall. She noted immediate pain that
resolved within few days but not the swelling. She has no pain, morning
stiffness, or limited function. She has a past medical history of hypertension
with stage II chronic kidney disease (CKD), takes Lisinopril 10 mg daily, is a
nonsmoker and nondrinker, and has not traveled outside the USA. The
patient is alert, oriented, and in no distress. Physical examination shows
normal vital signs. With the exception of a nontender firm nodular mass on
the right olecranon area, findings on the rest of the physical examination are
normal.
Laboratory data include:
Creatinine: 2.0 mg/dl (creatinine a year ago was 1.6 mg/dl)
CBC: Hgb 11 gm/dl; Hct 34% with normal indices
Calcium: 11 mg/dl
Phosphate: 3.5 mg/dl
Parathyroid hormone (PTH): 65 pg/ml
PTH rp: 1.1 pmol/L (normal < 1.5 pmol/L)
25 OH Vit D: 50 nmol/L
1,25 OH Vit D: 65 micromol/L
Angiotensin-converting enzyme: 80 U/L
Urinalysis: normal
24-hr urinary calcium: 350 mg
Chest (Image 1) and elbow (Image 2) radiographs are shown.
Figure
Figure 1
Figure 2
Question
Which of the following is the most likely cause of these findings in this
patient?
A.
Hyperparathyroidism secondary to CKD
B.
Ectopic production of PTH
C.
Primary hyperparathyroidism
D.
Increased production of 1,25 Vit D
E.
Myositis ossificans
Correct Answer
DAnswer Rationale
Mild to severe hypercalcemia and/or hypercalciuria occurs in 10% of patients
with sarcoidosis. The cause of this disordered regulation of calcium is due to
endogenous production of active metabolite of Vitamin D by macrophages in
the sarcoid granuloma. This extra renal synthesis of 1,25 OH Vit D is not
subject to the normal physiologic regulatory influences. This patient has CKD