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Question Number: 38

Case
A 52-year-old woman has a history of progressive ulnar deviation and PIP
enlargement. She also has lumbosacral spine and hip, knee, and shoulder
joint involvement. Two years ago, she required right knee
replacement. Eight years ago, she had nephrolithiasis with several recurrent
episodes. The kidney stones have not been analyzed. She notes that there
are dark stains on her undergarments. She has a long history of
rosacea. One week ago, she began treatment for rosacea with minocycline.

Physical examination shows bilateral bluish-gray sclerae, mild ulnar deviation


of the fingers, bilateral 2nd, 3rd, and 4th PIP enlargement, and a modified
Schober test of 10 cm to 13 cm. Examination of the face shows erythema,
papules, and dilated blood vessels.

Radiographs of the lumbar sacral spine reveal loss of disc height, disc
calcification, very thick syndesmophytes, and “bamboo spine” (see figure
below).

Figure

Question
Which of the following is the most likely diagnosis?
A. Rheumatoid arthritis
B. Minocycline-induced hyperpigmentation

C. Alkaptonuria

D. Hyperuricemia and gout

E. Ankylosing Spondylitis

Correct Answer
C

Answer Rationale
Alkaptonuria is an autosomal recessive inborn error of metabolism. The
enzyme homogentisic acid oxidase is deficient resulting in large volume
excretion of
homogentisic acid (HGA) in the urine and sweat. Urine that contains HGA
will turn dark as the acid is oxidized to melanin-like product. This may result
in dark stains on clothing and undergarments. HGA may also accumulate on
cartilage, tendons, sclerae, skin, and intima of large vessels. Nephrolithiasis
is a manifestation of the disease. Alkaptonuria resembles ankylosing
spondylitis involving the spine and large joints, however, it differs in that the
sacroiliac joints (SI joints) are spared. Minocycline has been associated with
hyperpigmentation resembling alkaptonuria, however, urine has normal HGA
measurement.

Question Number: 39

Case
A 56-year-old man has a maculopapular rash over the lower extremities that
comes and goes. He notes some edema when he has the rash. He has
fatigue and some joint pain but no paresthesias. He has been losing weight.
Review of other systems is unremarkable. He takes no medications.
Examination shows a normotensive man with palpable purpura and no
abnormal neurological or musculoskeletal features. Findings on the
remainder of the general examination are normal.

Laboratory data include:

CBC: Normochromic anemia


BUN: 32 mg/dl
Creatinine: 1.9 mg/dl
AST: 86 U/L
ALT: 94 U/L
Alkaline phosphatase: 110 U/L
Total bilirubin: 0.8 mg/dl

ESR: 98 mm/hr
ANA: 1:40 speckled
dsDNA: negative
ANCA: negative
RF: 450
Anti-CCP antibody: negative
Total protein: 8.8 gm/dl
Urinalysis: 1+ protein, 2+ blood, no casts

Findings on chest radiograph are normal.

Question
Based on the information above, which of the following is the most likely
cause of the patient’s elevated rheumatoid factor?
A. Rheumatoid arthritis

B. Sjögren’s syndrome

C. Lupus

D. Hepatitis-associated cryoglobulinemia

E. Wegener’s granulomatosis

Correct Answer
D

Answer Rationale
The patient is a middle-aged man with palpable purpura, which is highly
suggestive of vasculitis. There is little in the history to suggest infection as a
trigger, and there are no symptoms referable to the upper respiratory tract,
which are present in about 80% of patients with Wegener’s
granulomatosis. He is not taking any medications that might trigger a
hypersensitivity vasculitis. The examination is unrevealing other than
showing purpura, and the laboratory studies show renal insufficiency, an
active urinary sediment, hepatitis, a low titer ANA with negative anti-dsDNA
antibodies, and markedly elevated rheumatoid factor. The anti-CCP antibody
is negative, arguing against RA, especially in light of the absence of joint
inflammation.

Causes of very high levels of rheumatoid factor include rheumatoid arthritis,


Sjögren’s syndrome, and cryoglobulinemia. Cryoglobulinemia can be caused
by autoimmune diseases, chronic infections, and lymphoproliferative
disorders. Type I cryoglobulins are comprised of monoclonal
immunoglobulins, and are associated with lymphoproliferative disorders.
Type II cryoglobulins contain a monoclonal and polyclonal component, and
can be seen with autoimmune diseases and infectious disease like hepatitis
C. Hepatitis C infection, as well as other infectious diseases, produce “mixed”
cryoglobulins, composed entirely of polyclonal immunoglobulins.

Rheumatoid arthritis is not likely, given the absence of joint findings and
negative anti-CCP antibody. Sjögren’s syndrome is in the differential
diagnosis, but there is little in the clinical history to suggest its presence.
Results of SSA and SSB antibodies are not given. Wegener’s granulomatosis
is not likely given the absence of symptoms referable to the upper
respiratory tract and the negative ANCA, which are seen in the majority of
patients with Wegener’s granulomatosis. Lupus is also a possibility but the
patient does not appear to fulfill sufficient criteria to support the diagnosis.

Question Number: 40

Case
A 30-year-old man has gradually increasing right knee pain for the past 21
days. He is a long-distance runner who averages 30 miles a week. He says
the pain began after a “speed work out.” The pain is on the lateral aspect of
the knee. It resolves with rest to some degree, but any running causes it to
return and causes him to limp for a day or 2. He can also bring on pain by
standing on his right leg and flexing his knee. The knee does not lock.

Physical examination shows tenderness over the lateral knee and lateral tibial
condyle. There is a creaking over the tender area with knee flexion and
extension. The knee is stable and there is no effusion.

Question
Which of the following is the best course of action at this time?
A. Prescribe NSAID and avoid running

B. Inject the right knee with a depot-corticosteroid preparation

C. Inject the bursa with anserine

D. Apply an elastic bandage (ACE wrap) and have the patient use crutches for 4-6 weeks

Correct Answer
A

Answer Rationale
Iliotibial band syndrome is a common injury in long-distance runners that
usually develops with over-training and after vigorous running or hiking. The
treatment involves avoiding running and NSAID therapy. In severe cases,
physical therapy and local corticosteroid injection may be helpful.
There is no role for intra-articular injection or avoiding weight bearing in this
condition.

An MRI would be done if one expects a meniscal tear or ligament


injury. These conditions are unlikely because the joint is stable and there is
no effusion, locking, or joint-line tenderness.

A bone scan would be indicated if one suspects a stress fracture.

Surgery is not indicated for this condition unless it is chronic and refractory
to all other therapies.

Question Number: 41

Case
A 6-year-old girl with polyarticular juvenile idiopathic arthritis has a negative
rheumatoid factor and positive ANA.

Question
How often should she undergo slit-lamp examination to screen for chronic
iritis?
A. Every three to four months for four years then every six months

B. Every six months for four years then every year

C. Every year for four years then every two years

D. When her eyes hurt

E. When she is moved to the front of the class because of difficulty seeing the blackboard

Correct Answer
A

Answer Rationale
Iritis in children is usually chronic and asymptomatic until extensive scarring
has occurred. Those at highest risk of developing iritis are children with
young onset oligoarticular disease and who are ANA positive. However,
polyarticular ANA positive disease also carries a significant risk of iritis,
although lower than the oligaorticular group, and should be screened at the
same intervals.

Question Number: 42

Case
A 38-year-old woman is undergoing evaluation of new-onset polyarthritis
involving the small joints of her hands. She also has had a recurrent
urticarial eruption over her shins (see figure below) for the past 3-4
days. Both symptoms developed over the past 6 months.

Review of systems is notable for the recent need to switch from contact
lenses to traditional lenses because of persistent corneal irritation. Although
her previous dental health was excellent, she has recently developed three
new caries. She takes no medications.

Physical examination shows mildly injected conjunctivae. Having just taken a


drink of water, her oral mucosa is moist, but there is no salivary pool. There
are 3 recently restored dental caries, two at the gingival margin.There is no
palpable lymphadenopathy. Findings on pulmonary, cardiac, and abdominal
examinations are normal. Peripheral articular examination shows symmetric
synovitis affecting the wrists and MCP and PIP joints.

Laboratory data include:

C3: 123 mg/dl


C4: 32 mg/dl

Figure

Question
Which of the following additional findings is most likely in this patient?
A. Hilar adenopathy

B. Cryoglobulins

C. Anti-SSA/Ro antibody

D. Anti-thyroglobulin antibody

E. Anti-neutrophil cytoplasmic antibody

Correct Answer
C
Answer Rationale
The patient has secondary Sjögren syndrome in the setting of what is most
likely rheumatoid arthritis, given the symmetrical involvement of the small
joints of her hands. Sjögren syndrome may have a variety of cutaneous
manifestations, including urticarial eruptions. Sjögren syndrome patients with
anti-SSA/Ro antibody are more likely to have such extraglandular
manifestations of their disease. Dental caries at the gingival margin, as seen
in this patient, are characteristic in patients with oral sicca symptoms,
autoimmune or otherwise.

Hilar adenopathy is seen in the Löfgren syndrome, a female-predominant


presentation of sarcoidosis that is also marked by inflammatory polyarthritis
and erythema nodosum. Sarcoidosis may also present with sicca symptoms.
The knees and ankles are the most commonly affected joints. However,
erythema nodosum is characterized by erythematous, tender – but
nonpruritic - subcutaneous nodules over the shins. Cryoglobulins may be
seen in rheumatoid vasculitis, but the cutaneous eruption is typically more
acral in distribution and is not typically pruritic. Anti-thyroglobulin antibody is
associated with autoimmune thyroid disease, but not rheumatoid arthritis or
Sjögren syndrome. Anti-neutrophil cytoplasmic antibodies are associated
with necrotizing vasculitis, including Wegener granulomatosis and Churg-
Strauss syndrome, but not rheumatoid arthritis or Sjögren syndrome.

Question Number: 43

Case
A 38-year-old man has polyarticular arthritis. Despite his relative youth and
absence of any history of joint trauma, he has widespread arthritis affecting
his axial skeleton, shoulders, and hips. He reports no visible articular swelling
or erythema or palpable heat. He has otherwise been in excellent health and
has no family history of early-onset arthritis, either inflammatory or
mechanical.

Physical examination shows blue-black pigmentation of both sclerae (see


Figure 1).

Radiographs of his spine (see Figure 2) reveal calcification of the


intervertebral discs and disc space narrowing.
Figure

Figure 1 Figure 2

Question
Which of the following tests is most likely to confirm the diagnosis?
A. COMP haplotype analysis

B. FRZB 2-marker single-nucleotide polymorphism (SNP) haplotype analysis

C. Targeted type II collagen polymorphism analysis

D. Plasma homogentisic acid assay

Correct Answer
D

Answer Rationale
The patient has alkaptonuria, an inborn error of metabolism resulting in
inability to metabolize homogentisic acid. Homogentisic acid is deposited in
the soft tissues and cartilage causing ochronosis, darkening of the sclerae,
pinnae, and other soft tissues, as well as premature osteoarthritis. The urine
will also darken if exposed to air.

The COMP haplotype, FRZB 2-marker SNP haplotype, and type II collagen
polymorphisms have all been associated with premature osteoarthritis, an
effect that varies with the gender and ethnicity of the patient and the specific
joint studied, but will not cause the pigmentary changes seen in ochronosis.

Question Number: 44

Case
A 55-year-old woman has noted a sensation of grit in her eyes for the past 2
years. She has been using artificial tears 2 or 3 times a day, particularly
while watching TV or working at a computer. Within the past year, she has
also noted dryness of her mouth. She keeps a bottle of water at her bedside
and must drink water frequently to aid in swallowing dry food. She has not
noted any recent increase in dental caries. She does not have a rash, joint
pain, or fatigue. She does not have clinical evidence of systemic lupus
erythematosus, rheumatoid arthritis, or scleroderma.

Laboratory data include:

WBC: 5600/mm3
Hgb: 13.2 gm/dl
Platelet count: 253,000/ mm3
ANA testing (multiplex assay): negative antinuclear antibodies, negative SS-
A and SS-B antibodies

Question
Which of the following additional findings is an absolute requirement for
establishing the diagnosis of primary Sjögren’s syndrome in this patient?
A. Schirmer’s I test with wetting of 7 mm in the right eye and 4 mm in the left eye.

B. Unstimulated salivary flow of 0.1 ml/min

C. Labial salivary gland focus score of 1

D. Absent salivary pool

E. Parotid sialography showing extensive sialectasis

Correct Answer
C

Answer Rationale
Although there have been several sets of diagnostic criteria for Sjögren’s
syndrome over the past 40 years, the set that is currently accepted was
derived by an international consensus group in 2002. According to the 2002
International Consensus Criteria for Sjögren’s Syndrome, the diagnosis of
primary Sjögren’s syndrome requires sicca signs/symptoms in the presence
of either Sjögren’s antibodies (SS-A and/or SS-B) or a positive labial gland
biopsy, defined by the presence of a focus score of 1 or more. With the
exception of the absent salivary pool, the other tests (abnormal Schirmer’s,
unstimulated salivary flow, or parotid sialography) would provide objective
evidence of the ocular or oral component of the disease and at least one
would be required to establish a diagnosis of Sjögren’s syndrome in concert
with the abnormal labial gland biopsy.

Question Number: 45

Case
A 34-year-old woman with a 1-year history of scleroderma is seen in your
practice as a new patient after moving from another city. She has had
Raynaud’s phenomenon in her hands as well as skin tightening on the hands
and face. She is currently taking lisinopril, 20 mg/day and ASA 325
mg/day. She is a nonsmoker and has no family history of autoimmune
disease. Recently, she has developed a persistent dry cough and she
becomes short of breath after walking one block.

Blood pressure is 135/70 mmHg. She has tightening of the skin on the face
and fingers with digital pitting but no cyanosis. Velcro crackles are present
at both lung bases and she has borderline tachycardia at 105 bpm. Lower
extremities are without edema. Findings on chest radiograph are
normal. Echocardiogram shows a normal ejection fraction and an estimated
PA pressure of 25 mmHg. She is referred to a pulmonary specialist who does
bronchoaveolar lavage, and the fluid from this procedure shows 4%
neutrophils. Cultures and stains on the fluid are negative for infectious
agents.

Question
Which of the following medications should be initiated at this time?
A. Prednisone 60 mg/day

B. Cyclophosphamide 1-2 mg/kg po daily

C. Mycophenolate Mofetil 1000 mg twice daily

D. Rituximab 750 mg/m2 x 2 doses

E. Infliximab 3 mg/kg

Correct Answer
B

Answer Rationale
The use of cyclophosphamide in scleroderma lung disease is based on results
from the Scleroderma Lung Study that compared in a blinded fashion oral
cyclophosphamide to placebo. Data from this 1-year study showed a
statistically significant improvement in lung function parameters in patients
treated with cyclophosphamide. Improvements were also observed in
dyspnea and in quality of life indices, and these improvements persisted in
the year following cessation of cyclophosphamide treatment. The patient in
this case has neutrophilia on BAL consistent with the presence of
alveolitis. Prednisone in high doses is relatively contraindicated in
scleroderma because of the risk of precipitating renal crisis. The use of
mycophenolate mofetil has been assessed only in limited retrospective
studies and data regarding utility of rituximab and infliximab are largely
limited to case reports. There have been some reports suggesting that TNF
blockade might induce a scleroderma-like syndrome.

Question Number: 47

Case
A 30-year-old man was given the diagnosis with of rheumatoid arthritis 2
years ago after he was evaluated for intermittent episodes of migratory
painful polyarthritis involving the knees, ankles, and elbows. The initial
episode lasted two weeks and on recurrence, synovitis of both elbows and
tenderness in the wrists and hands was noted. At that time, rheumatoid
factor was positive and anti-citrullinated peptide antibodies were
negative. Therapy was initiated with methotrexate up to 20 mg orally every
week without improvement. Between episodes he has polyarthralgias. His
father died at age 36 years from a myocardial infarction. Findings on
physical examination are normal with the exception of small nodules on the
Achilles, olecranon, and tibial tubercle. His hands and foot films are normal.

Question
Which of the following tests is the most appropriate next step to establish the
diagnosis?
A. Anti-citrullinated peptide antibody titer

B. Rapid plasma reagent test

C. Anti-endomysial tissue transglutaminase antibody titer

D. Fasting serum lipid profile

E. Anti-nuclear antibody titer

Correct Answer
D

Answer Rationale
Lipoprotein disorders result from defect in either the synthesis or catabolism
of lipoprotein. Familial hypercholesterolemia is an autosomal dominant
disorder caused by mutation in the gene encoding for low density lipoprotein
(LDL) receptor. Deficiency results in high concentration of LDL in connective
tissues and arterial beds causing xanthomas and atherosclerosis. In patients
with the heterozygous from of familial hypercholesterolemia, tendinous
xanthomas usually occur in the second decade of life and coronary artery
disease events after the third decade. Tendon xanthomas are typically seen
within the extensor tendons of the hands, Achilles tendon, and tibial
tubercle. Arthritis (seen in 40%-50% of patients) most commonly involves
the knees and ankles. Patients can develop intermittent episodes of either
migratory, pauciarticular, or polyarticular arthritis lasting for several
days. Assay for IgA antibodies to endomysium are sensitive and specific for
celiac disease and although peripheral and/or axial arthritis may be present,
most patients have other autoimmune and/or intestinal manifestations not
present in this patient. There is no indication for ANA, Anti-CCP, or PRP as
the probability of an autoimmune systemic disorder, RA, or disseminated GC
presenting with two years of migratory arthritis is very low and given low
pretest probability these tests are not the diagnostic studies of choice in this
case.

Question Number: 48

Case
A 50-year-old woman with a 17-year history of rheumatoid arthritis is
undergoing routine follow-up evaluation. She has no new symptoms except
the presence of a new skin lesion on the nailfold of the right little finger (5th
digit) (see Figure). She does not recall any trauma to the area and she says
that it is not painful. There is no discharge from the lesion and she does not
have any similar lesions anywhere else on her body. She describes a
sensation of numbness and tingling and a perception of weakness in both
hands and both feet.

She has no other illnesses. Her current medications are methotrexate 15 mg


po weekly and folate 1 mg daily.

Findings on physical examination include the skin lesion shown in the figure.
Examination of the joints shows mild swelling over the MCP joints 2-3-4 of
both hands and minimal swelling of both wrists. There are rheumatoid
nodules over both olecranon surfaces, each measuring about 1.5 cm in
diameter, unchanged in size since the last visit.

There is intact diminished sensation to light touch and pinprick in both hands
and feet in a stocking and glove distribution.

Laboratory data include:

CBC: normal
ESR: 33 mm/hr
C-RP: 5.1 mg/dL
C3: Low
C4: Low
Rheumatoid factor: 298 U
CCP: < 10 U

Figure

Question
Which of the following is the most appropriate next step in management?
A. Add an anti-TNF agent

B. Increase methotrexate dose

C. Add anti- B cell therapy

D. Begin cyclophosphamide

E. Add aspirin

Correct Answer
D

Answer Rationale
This patient has a nailfold infarction and sensory symptoms. This should raise
concern about the possibility of the development of rheumatoid vasculitis
(RV). RV refers specifically to a protean, destructive inflammatory process
that is centered on the blood vessel wall itself and associated with substantial
morbidity. It may affect a wide range of blood vessel types, from medium
muscular arteries to somewhat smaller arterioles to postcapillary venules.
Within a given patient, clinical features of both medium- and small-vessel
disease may be found. RV leads to necrosis, blood vessel occlusion, and
tissue ischemia in a manner that resembles other forms of systemic
vasculitis, particularly polyarteritis nodosa.

RV typically occurs in patients with long-standing, joint-destructive RA. In


one study, the mean duration between the diagnosis of RA and the onset of
vasculitic symptoms was 13.6 years. Presentations of RV within 5 years of
the RA diagnosis are very unusual. Patients with RV nearly always have
rheumatoid nodules and are typically strongly positive for rheumatoid
factor. RV usually develops at a time when the inflammatory arthritis is
"burned out," ie, when the erosive process that led to joint destruction has
become less active.

The areas of the body involved most commonly by RV are the skin, digits,
peripheral nerves, eyes, and heart. The most devastating form of RV is
characterized by a medium-sized vasculitis reminiscent of (and histologically
identical to) polyarteritis nodosa. Many of the clinical manifestations of RV
reflect this predilection for medium-sized vessels, even though purpura,
petechiae, and papules (manifestations of small-vessel involvement) may
also occur.

In one study of 32 patients with rheumatoid vasculitis, the presence of


cutaneous vasculitis, multifocal neuropathy,and depressed C4 levels were the
3 independent variables that best predicted mortality. This patient had all
three of these variables that suggests that the use of cyclophosphamide
would be appropriate for this patient.

Question Number: 49

Case
A 66-year-old man with a history of ongoing chronic alcohol abuse, comes to
the emergency department because of bilateral knee pain. Physical
examination shows a thin man with stigmata of liver disease, poor hygiene,
several nonblanching ecchymoses on both upper and lower extremities (see
picture) and bilateral knee effusions. There are no skin abrasions or
ulcers. He is able to flex his knees to 95 degrees with discomfort; both
knees are warm to touch. Arthrocentesis of the right knee is performed and
shows a hemorrhagic effusion. A nontraumatic tap of the left knee reveals a
hemorrhagic effusion also. (Image 1)

Laboratory data include:

CBC: WBC 5,000/mm3, hgb11.6 gm/dl; platelet count 95,000/mm3


PT: 10.7 seconds
PTT: 36 seconds
BUN: 24 mg/dl
Creatinine: 1.4 mg/dl
AST: 96 U/L
ALT: 45 U/L

Figure

Question
Which of the following is the most likely cause of the hemarthrosis?
A. Thrombocytopenia

B. Pigmented villonodular synovitis

C. Decreased ascorbic acid

D. Circulating anticoagulant

Correct Answer
C

Answer Rationale
Vascular fragility due to vitamin C deficiency may lead to hemarthrosis and
subperiosteal bleeding. Scurvy is a clinical syndrome seen with ascorbic acid
deficiency largely due to impaired collagen synthesis with disordered
connective tissue. Symptoms (occurring as early as three months after
deficient intake) include ecchymoses, bleeding gums, petechiae,
hyperkeratosis, Sjögren-like syndrome, arthralgias, and impaired wound
healing. Generalized systemic symptoms are weakness, malaise, joint
swelling, arthralgias, edema, coiled hair, depression, neuropathy, and
vasomotor instability. In the United States, ascorbic acid deficiency occurs
mostly in severely malnourished individuals, drug and alcohol abusers, or
those living in poverty. Although as many as 80 percent of hospitalized
alcoholics have mild thrombocytopenia, in most the platelet function remains
normal. Decreased production of coagulation factors occurs in hepatic failure
but this patient’s PT and PTT are normal, which also eliminates the possibility
of a circulating anticoagulant as the cause of the hemarthrosis. Pigmented
villonodular synovitis or diffuse tenosynovial giant cell tumor is a benign
neoplasm that typically presents as an intra-articular tumor expanding along
the synovial surface into the soft tissue. Clinical presentation of PVNS
usually involves the knee with pain, swelling, and dysfunction. Bloody
effusions are common. These tumors present at a younger age with most
patients younger than 40, monoarticular, and without systemic
manifestations.

Question Number: 50

Case
A 36-year-old man has a 14- month history of intermittent pain and stiffness
in the hands and feet. One year ago, he was evaluated for the persistent
symptoms in his hands and feet. He had Achilles tendon pain. Occasionally
he would have lumbar spine pain; however, activity helped improve the
symptoms.

Physical examination one year ago showed swelling of the right 2nd and 4th
toes and the left 3rd finger. A modified Schober test was 10 cm to 15 cm.

Laboratory data one year ago include:

ESR: 25 mm/hr

Treatment with indomethacin provided incomplete resolution of the


symptoms; however, he was able to resume some of his daily activities.
Indomethacin was continued for two months and then discontinued.
Methotrexate was then prescribed for treatment.

He now has had progressive low back pain and stiffness for the past 4
months. He describes morning stiffness that lasts for 2 hours. Two months
ago, he had iritis that was treated with topical corticosteroids.

Physical examination today shows modified Schober test of 10 cm to 13


cm. The 2nd and 4th toes are swollen, but there is no tenderness.

Radiograph of the sacroiliac joint (SI joints) reveals erosive changes on the
iliac sides.

Laboratory data now include:

ESR: 25 mm/hr

Question
Which of the following is the best treatment option at this time?
A. Leflunomide

B. Cyclosporine
C. Methotrexate

D. Azathioprine

E. TNF alpha antagonist

Correct Answer
E

Answer Rationale
Ankylosing spondylitis affects mainly the axial skeleton. The majority of
patients will have sacroiliac joint involvement. If a patient has peripheral
joint arthritis then sulfasalazine, cyclosporine, methotrexate or Arava may be
effective. However, axial involvement is best treated with TNF alpha
antagonist. Concomitant use of methotrexate with TNF alpha antagonist has
not been found to be superior to TNF alpha antagonist monotherapy for
treatment of axial manifestations.

Question Number: 51

Case
A 19-year-old African-American man has joint pain and a positive ANA (1:80
dilution). Approximately 3 years ago, he started having intermittent
episodes of severe bilateral knee, ankle, and hip pain. During these episodes
he has difficulty getting around. They occur 2 to 3 times a year, last for 2 to
3 days, and resolve spontaneously. He has not had any associated
symptoms, such as fever, rash, swollen joints, or cardiopulmonary
problems. NSAIDs, oxycodone, and morphine did not provide any
benefit. He is a smoker, nondrinker, and denies any illicit drug use. He
plays golf but has no other physical activities. He has not traveled outside
the USA. His mother has systemic lupus erythematosus. Findings on
physical examination are normal.

Laboratory data include:

Hgb: 11 gm/dl
Hct: 36%
ENA: negative
Chemistry profile: normal
Urinalysis: normal
Plain radiographs of chest and knees: normal
MRI of the right knee: Infarct of the medial femoral condyle, small infarct of
the anterior distal femoral metaphysis and multiple small areas of edema.

Question
Which of the following studies is most likely to establish the diagnosis?
A. Bone marrow biopsy
B. Bone scan

C. Hemoglobin electrophoresis

D. Anti-native DNA antibodies

E. Antiphospholipid antibodies

Correct Answer
C

Answer Rationale
The clinical diagnosis of osteonecrosis is appropriately made in a
symptomatic patient when imaging findings are compatible with this disease
and other causes of pain and bony abnormalities are either unlikely or have
been excluded by appropriate testing as in this case. Although there are
many conditions that lead to avascular necrosis, the most likely cause in this
case is hemoglobinopathy. Clues to this are young age of onset, the painful
crisis, his ethnicity, and lack of systemic symptoms. Hemoglobin
electrophoresis will help to determine the cause of the painful crisis
associated with bone infarct. Long-bone infarct occurs most commonly with
HgBSS (sickle cell disease) but also with HbSC, HbS alpha thal, and least
commonly in sickle cell trait.

Bone marrow biopsy would be indicated if there were clinical findings


suggestive of Gaucher’s disease. Gaucher’s disease is a hereditary
(autosomal recessive) disorder of glucocerebroside metabolism that results in
the accumulation of cerebroside-filled cells within the bone marrow. This
process may lead to compression of the vasculature and subsequent
osteonecrosis (60% of cases). Patients with Gaucher’s disease usually have
hepatosplenomegaly, thrombocytopenia, and bleeding, which are not present
in the above case. Bone scan will help to confirm osteonecrosis and identify
other asymptomatic areas but would not provide the cause. Patients with
classic antiphospholipid antibody syndrome present with venous and/or
arterial thrombosis and not with isolated osteonecrosis. A native-DNA
antibody is not indicated as nothing in this patient’s history or examination
points to a systemic autoimmune process.

Question Number: 52

Case
A 58-year-old man has a 3-year history of progressive muscle weakness
involving his shoulder and pelvic girdles. He had some difficulty swallowing
liquids. He has been treated for 3 months with prednisone 60 mg/day with
no benefit.
Physical examination shows 4/5 strength in shoulder abduction and hip
flexion.

Previously, he has had CK levels that were 3 to 4 times the upper range of
normal. Electrophysiologic studies revealed increased insertional activity,
fibrillation, and positive waves. Motor units were of low amplitude and short
duration. A muscle biopsy showed some atrophic and triangular fibers with
a few lymphocytes in and around muscle fibers. Centralized nuclei were seen
but no necrosis or regenerating cells were present. Vacuoles were seen in
some fibers. Trichrome staining revealed rare ragged red change.
Histochemistry with ATPase staining revealed fiber type grouping, and Congo
red staining was positive in fibers with vacuoles.

Question
In addition to physical therapy for muscle strengthening, which of the
following management options is most appropriate at this time?
A. Taper the prednisone

B. Sart azathioprine after checking thiopurine methyltransferase (TPMT) activity and slowly taper
prednisone
C. Start methotrexate and azathioprine after checking thiopurine methyltransferase (TPMT) activity
and slowly taper prednisone
D. Add IVIg

E. Add methotrexate

Correct Answer
A

Answer Rationale
Muscle histology in patients with inclusion body myositis may look identical to
that from patients with polymyositis; that is, degenerating and regenerating
muscle fibers with lymphocytes infiltrating the muscle and inside muscle
fibers. Over time, these inflammatory changes tend to resolve. In addition,
Trichrome staining may show ragged red change within some fibers. This
change is indicative of mitochondrial abnormalities and would suggest a
mitochondrial myopathy. However, ragged red fibers are reported with aging
and a mitochondrial myopathy would not be associated with the
inflammatory changes seen in this patient. In addition, patients with
inclusion body myositis may have neuropathic abnormalities. On physical
examination, these may manifest as distal or asymmetric muscle
weakness. In muscle tissue, these are indicated by finding triangular cells
and fiber type grouping. Amyloid, as demonstrated with Congo red staining,
is present in IBM muscle fibers and in some vacuoles.

Although it is appropriate to give a trial of immunosuppressive therapy to


patients with presumed inclusion body myositis, these agents should be
discontinued when it is clear that the patient is not responding because
inclusion body myositis is refractory to these medications.

Question Number: 53

Case
A 46-year-old man has had hypertension and diabetes mellitus for 20 years
and has now developed chronic kidney disease. Ten years ago, he had what
appears to have been his first attack of gout. Synovial fluid aspirated from
his right knee at the time of a second attack contained monosodium urate
crystals. Over the next few years, he had multiple attacks of gout and visible
tophi developed on his elbows.

Two years ago, when his serum creatinine level was 2.0 mg/dl, he was
prescribed allopurinol 100 mg. This treatment led to a drop in his serum
urate level from 11.0 mg/dl to 9.0 mg/dl. One year ago, the dose of
allopurinol was increased to 300 mg and colchicine 0.5 mg every other day
was added.

The diabetes mellitus is managed with insulin, he is taking


hydrochlorothiazide 12.5 mg/day and losartan 25 mg for blood pressure
control, and he takes ASA 81 mg daily for cardioprotection.

He has not had a gout flare in the past 9 months but the tophi remain
unchanged. Currently blood pressure is 165/100 mmHg, creatinine level is
2.3 mg/dl, and serum urate is 6.9 mg/dl (normal urate level in men is listed
as 3.6-8.5 mg/dl).

Question
Which of the following interventions is most appropriate at this time?
A. Discontinue colchicne

B. Switch losartan to lisinopril

C. Discontinue the ASA

D. Add probenecid 1 g BID

E. Increase allopurinol to 400 mg/day

Correct Answer
E

Answer Rationale
Although many laboratories list the upper limit of normal for serum urate
levels above 6.8 mg/dl, the true physiochemical upper limit of normal of
serum urate is 6.8 mg dl. Above this concentration, body fluids are
supersaturated with urate and crystals can form and deposit. When levels
above 6.8 mg/dl are listed as normal, they are based on statistical norms for
a population and are misleading regarding the pathophysiology of the
gout. To eliminate attacks and shrink tophi, serum urate levels must be
maintained below 6.8 mg/dl and preferably below a target value of 6.0
mg/dl.

Renal dysfunction increases the effectiveness of a given dose of allopurinol


because it delays the excretion of its active metabolite from the
body. Accordingly, the dose of allopurinol that is effective is usually lower
than that required for patients with normal renal function. Regardless, the
appropriate management of hyperuricemia in gout patients is to use the
lowest dose of whatever urate-lowering agent is used to maintain the serum
urate below 6.0 mg/dl.

Cochicine-induced axonal neuromyopathy most commonly occurs when renal


dysfunction is present, but it is reversible not permanent.

Losartan is an ideal antihypertensive agent for gout patients because it has


modest uricosuric effects. Hypertension in diabetic patients should be
managed with both an ACE inhibitor (such as lisinopril) and an ARB (such as
losartan). Increasing the dose of hydrochlorothiazide would not improve
blood pressure control but would induce a diuresis and have a hyperuricemic
effect.

Probenecid is not an effective agent in patients with renal dysfunction.

Question Number: 54

Case
A 52-year-old woman has recently received the new diagnosis of
osteoarthritis in the knees, which was made by her primary care
physician. She is otherwise generally healthy. She was a very active runner
for many years and participated in 5K races until about 2 years ago. Now
she just jogs recreationally because she is somewhat limited by pain in her
knees. She does not recall that anyone in her family had arthritis, and she
wants to know if there is anything she can do to improve her prognosis.

She had a hysterectomy 3 years ago. Her current medications include an


estrogen patch and calcium supplements. She does not have diabetes
mellitus or hypertension. She has smoked about a pack of cigarettes daily
for many years.

On examination, blood pressure is 135/72 mmHg and heart rate is 72/min.


She weighs 145 pounds and her height is 5 feet 5 inches; her calculated BMI
is 24.1. She has crepitance in both knees, but the joints have full range of
motion. There are no effusions in the knees. She has normal quadriceps
mass and strength bilaterally.

Radiograph of the knee is shown in figure below.

Figure

Question
Which of the following has most likely contributed to cartilage loss in this
patient?
A. BMI of 24.1

B. Jogging

C. Use of cigarettes

D. Use of the estrogen patch

Correct Answer
C

Answer Rationale
While weight can impact osteoarthritis of the knee, this woman has a normal
BMI, so loss of weight is not likely to have significant benefit. Several
studies have now discounted the role of jogging or distance running in
accelerating the progression of knee OA. Furthermore, strength of the
quadriceps muscles that can be developed by this kind of exercise appears to
be an important factor in protection of the knee joint. Recent data suggest
that smoking is a modifiable risk factor for cartilage loss, so quitting cigarette
use is something that she can do to improve her joint health. Estrogen
supplements may slow rather than accelerate cartilage loss, so discontinuing
the patch probably will not help her joints.
Question Number: 55

Case
A 28-year-old woman with a history of systemic lupus erythematosus,
manifesting in the past as pleurisy, arthralgia, malar rash, and prior second
trimester fetal loss, now has a positive pregnancy test. Her last menstrual
period was eight weeks ago. She feels fatigued but has no other
symptoms. She takes hydroxychloroquine 400 mg once daily and a prenatal
multivitamin. On physical examination, blood pressure is 110/70 mmHg and
pulse rate is 88 bpm. No rashes are present.

Laboratory data include:

ANA: 1:1280; homogeneous pattern


Urinalysis: trace protein; no RBC or WBC casts or cells/hpf
Serum creatinine: 0.9 mg/dl
Hgb: 11.3 mg/dl
WBC: 3400/mm3
Platelet count: 122,000/mm3
APTT: 56 sec
Anticardiolipin antibodies: IgG 58 GPL units; IgM 11 MPL units

Question
Which of the following is the most appropriate additional treatment for this
patient at this time?
A. Aspirin 81 mg per day

B. Aspirin 325 mg per day

C. Heparin 10,000 IU sq bid and prednisone 60 mg orally daily

D. Heparin 10,000 IU sq bid and aspirin 81 mg per day

E. Prednisone 60 mg orally daily

Correct Answer
D

Answer Rationale
This patient is in her first trimester of pregnancy and has a history of
antiphospholipid syndrome with moderate titer anticardiolipin IgG antibody
positivity and prior fetal loss. Her risk for miscarriage is increased. Studies
comparing heparin and aspirin versus aspirin alone show superiority of
combination therapy. Prednisone use poses greater risk for corticosteroid
complications without improvement in outcome.

Question Number: 56
Case
A 72-year-old woman has had a 3-month history of an erythematous rash
over her face, forearms, and upper torso. Serologic testing revealed the
presence of ANA (1:640, speckled pattern) and hydroxychloroquine 400
mg/day was prescribed. She has had no joint swelling or muscle weakness
but has had some mild dysphagia for liquids. Physical examination shows
normal blood pressure; there is a confluent erythematous papular rash over
the upper torso and sun-exposed areas of her arms extending onto the
dorsal aspect of the hands with periungual erythema and mild scale
formation over the dorsal PIP and MCP joints. Erythema is also present over
the sun-exposed areas of the face and eyelids. Oral and ocular membranes
are normal and lungs are clear without audible rub or crackles. Joints are
normal without limitation or synovitis. Strength in the upper and lower
extremity muscle groups is normal.

Laboratory data include:

CBC: normal
Chemistry profile: normal
Urinalysis: normal
CK: normal
Aldolase: normal

Barium swallow radiograph: no mass, abnormal peristalsis in upper


esophagus
Chest, abdominal and pelvic CT scans: normal

Question
Which of the following studies is most appropriate at this time?
A. Biopsy of affected dermis

B. EMG-directed muscle biopsy of an extremity muscle

C. MRI of the shoulder and pelvic girdle muscles

D. Vaginal ultrasonography and Ca-125 antigen study

E. Serologic tests for anti-dsDNA and anti-SSA

Correct Answer
D

Answer Rationale
Erythematous rash occurring on the face, eyelids, neck, and upper torso
along with papular lesions on the dorsum of the hands with periungual
erythema are very characteristic of dermatomyositis. The presence of orbital
violaceous erythema (heliotrope rash) and erythematous papules over the
dorsum of the hands is sufficient to establish the diagnosis of
dermatomyositis. Skin biopsy frequently reveals interface dermatitis similar
to that seen in lupus and, for patients with these classic cutaneous
manifestations, adds little information to guide management. For patients
with demonstrable muscle weakness or CK elevation in the context of these
characteristic skin lesions, muscle biopsy is also not required to establish the
diagnosis.

The myopathy of dermatomyositis may be quite indolent or not clinically


manifest (dermatomyositis cine myositis). Moreover, it is important to
recognize that significant motor weakness may occur in the absence of
demonstrable elevations in creatine kinase or aldolase levels. Dysphagia due
to inflammatory myopathy of the pharyngeal muscles and/or striated portion
of the upper esophagus may be the initial presenting symptom of motor
weakness in patients with dermatomyositis.

The development of dermatomyositis, particularly in elderly patients,


requires consideration of possible associated malignancy. As such, in patients
such as the one presented, appropriate studies to determine the presence of
underlying lung, gastrointestinal/abdominal, or pelvic malignancies should be
performed. The prevalence of ovarian cancers in female patients with
dermatomyositis is particularly increased relative to the expected occurrence
and ovarian tumors in the early stages may be difficult to detect on routine
CT scanning. Serum studies for ovarian tumor antigens (Ca125) and vaginal
ultrasonography should, therefore, be performed to look for ovarian tumors
in female patients with dermatomyositis who have not undergone
oopherectomy.

Initial treatment of dermatomyositis occurring in the context of malignancy is


directed toward treatment of the neoplasm. In the absence of malignancy (or
in patients with persistent dermatomyositis manifestations despite removal
or treatment of the tumor), the inflammatory myopathy usually responds
favorably to corticosteroids, methotrexate, or other immunosuppressive
medications such as azathioprine. The cutaneous manifestations of
dermatomyositis are not uncommonly refractory to treatment with
corticosteroids and conventional immunosuppressive therapies. Skin disease
as well as the myopathy (when refractory to corticosteroids, methotrexate,
and/or other immunosuppressives) often responds favorably to a course of
IVIG, usually at a dose of 2 gm/kg administered in divided doses over 2-4
days. Preparations stabilized with sugars such as sucrose carry a higher risk
for renal toxicity and are best administered slowly, not exceeding 0.5
gm/kg/day.
Question Number: 57

Case
A 42-year-old man has had bilateral hand pain for the past 2 years. The
symptoms are variously characterized as paresthesias and numbness. A
nerve conduction study revealed an axonal neuropathy with conduction delay
at his wrists. Nocturnal wrist splints failed to lead to improvement in his
symptoms, and he underwent bilateral carpal tunnel release. However, his
symptoms became progressively worse.

Physical examination shows a slightly-built and finely-featured man weighing


142 pounds. There is no synovitis affecting his wrists, no muscle atrophy of
the thenar eminence, and Tinel and Phalen signs are normal. Light touch and
vibratory sensation are diminished in his feet.

Laboratory data include:

Fasting glucose: 72 mg/dl


Hct: 38%
MCV: 99 cubic micrometers

Question
Which of the following laboratory studies is most likely to determine the
cause of the patient’s progressive symptoms?
A. Hemoglobin A1c

B. Red blood cell folic acid

C. Vitamin B12

D. Insulin-like growth factor I

Correct Answer
C

Answer Rationale
Clinically, the patient had carpal tunnel syndrome at his initial presentation.
While rheumatologists frequently encounter this in the setting of wrist
synovitis, peripheral neuropathy resembling carpal tunnel syndrome may
also result from other metabolic and systemic processes, including
acromegaly, amyloidosis, diabetes mellitus, hypothyroidism,
hyperparathyroidism, pregnancy, and vitamin B12 deficiency.

This patient has vitamin B12 deficiency as noted by the abnormal sensory
examination in his lower extremities, as well as mild anemia and marginally
elevated mean corpuscular volume.
Diabetes mellitus is a much less likely cause of underlying peripheral
neuropathy, given the low-normal fasting glucose level. There is no
association between folic acid deficiency and carpal tunnel syndrome.
Acromegaly, diagnosed by the detection of an elevated insulin-like growth
factor I level, is also unlikely to be the cause of the worsening peripheral
neuropathic symptoms given his slight build and fine features, as opposed to
the more coarse features and broad hands expected in an individual with the
onset of acromegaly after puberty.

Question Number: 58

Case
A 55-year-old woman with diabetic glomerulosclerosis started hemodialysis 3
years ago. One year ago, swelling of her feet, lower legs, and hands
developed. Within a few weeks, this swelling progressed to a woody
induration, leading to flexion contractures of her fingers. There was also
progression of the induration to the forearms, upper legs, and thighs.
Currently the affected skin has a brawny induration with areas of a peau
d’orange appearance as well as deep furrowing and loss of skin appendages.
Skin biopsy shows diffuse dermal fibroplasia with spindle cells extending into
the subcutaneous tissues. There are thick collagen bundles separated by
large clefts in the dermis. Increased mucin is present.

Question
Which of the following additional findings is most likely in this patient?
A. Monoclonal gammopathy

B. Peripheral eosinophilia

C. Normal sedimentation rate and C-reactive protein

D. Raynaud’s phenomenon

E. Myocardial fibrosis

Correct Answer
E

Answer Rationale
Nephrogenic systemic fibrosis (NSF), formerly known as nephrogenic
fibrosing dermopathy, has been observed exclusively in patients with renal
insufficiency, most but not all of whom have undergone dialysis for renal
failure. The disease was initially thought to be confined to the skin. However,
recent reports have documented involvement of the liver, myocardium,
lungs, diaphragm, and skeletal muscle. Increased ESR and C-reactive protein
level are commonly present. Paraprotein is a feature of scleromyxedema but
is not seen in NSF. The disease has been linked recently to the use of
gadolinium-based contrast agents for magnetic resonance imaging.

Question Number: 59

Case
A 72-year-old woman has had right knee pain and stiffness for the past six
months when arising from sitting. The knee pain worsens when she climbs
stairs. She has had no trauma. She has a history of gastroesophageal reflux
disease and hypertension for which she takes omeprazole and enalapril. On
physical examination, her weight is 110 pounds. Blood pressure is 130/80
mmHg. Right knee crepitus, medial joint tenderness, and a fluid wave are
present. Radiograph of the right knee shows mild joint space
narrowing. She is treated with three weekly intra-articular injections of hylan
G-F 20.

Three days after her last injection, she has severe worsening of pain and
swelling of the right knee. Arthrocentesis of the right knee is performed and
reveals 55 cc of cloudy yellow fluid.

Synovial fluid analysis is performed and reveals the following results:

WBC: 74,000/ mm3, differential 85% neutrophils,15% lymphocytes


RBC: 100/mm3
Crystal analysis: no crystals observed
Gram stain: negative
Culture: pending

Question
Which of the following is the most likely diagnosis?
A. Osteonecrosis

B. Pseudogout

C. Pseudoseptic reaction

D. Rheumatoid arthritis

E. Septic joint

Correct Answer
C

Answer Rationale
This patient has a pseudoseptic reaction to injection with a hyaluronate. This
type of reaction may occur in 11% of injections with hyaluronate and is most
commonly noted with hylan G-F 20. This reaction usually occurs in the first
week after the injection. Nucleated cell counts may exceed 100,000/mm3
and are predominantly neutrophils. Iatrogenic septic joint after intra-
articular injection has been estimated to occur once in 2,000 to once in
15,000 injections. Some cases of crystal-proven pseudogout have been
reported to occur after injection of hylan G-F 20. However, this patient’s
synovial fluid did not contain any crystals. Osteonecrosis is not a
complication of hyaluronate injection and is not associated with highly
inflammatory synovial fluid. This patient does not meet criteria for a
diagnosis of RA.

Question Number: 60

Case
A 14-year-old girl has a 6-week history of unexplained low-grade fever,
fatigue, and joint pain. Family history reveals that her 4-year-old brother
has a history of perirectal abcesses, two hospitalizations for staphylococcal
pneumonia, and a chronic cervical lymphadenitis for which culture grew
Serratia species.

Question
Which of the following is the most likely diagnosis in the sister?
A. Inflammatory bowel disease

B. Common variable immune deficiency

C. Endocardial elastosis

D. Systemic lupus erythematosus

E. Chronic EBV syndrome

Correct Answer
D

Answer Rationale
The x-linked form of CGD usually presents with perirectal abcess and
difficulties in clearing staph infection and infection caused by other catylase-
positive organisms. Having a brother with these symptoms should raise the
index of suspicion of SLE. More commonly, this is discoid lupus, but it can
also be systemic. In the absence of that diagnosis, IBD and CVID could also
cause similar symptoms and appropriate evaluation should be undertaken.

Inflammatory bowel disease may present with fever, fatigue, and arthralgia,
but the family history points more toward SLE. Common variable immune
deficiency (CVID) may also have similar features, but the age of onset and
types of infections in the brother are not those usually found with CVID. The
carriers of CGD are also at higher risk for endocardial fibroelastosis, but the
symptoms would more likely be shortness of breath and cardiac failure. The
patient had no adenopathy or rash suggestive of EVB, and duration is too
long for this to be likely.