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    Question Number: 1

    CaseA 70-year-old man with chronic obstructive pulmonary disease has a T8

    vertebral compression deformity noted on a lateral chest radiograph taken

    for evaluation of a chronic cough. The deformity was not present onradiographs taken 1 year ago. The patient does not have back pain and does

    not recall any injury to his back. He has not been taking corticosteroids.

    Laboratory data include:Serum testosterone: 205 ng/ml

    DEXA bone densitometry:

    lumbar spine T-score = -1.8

    Femoral neck T-score = -1.9Question

    Which of the following is the most appropriate therapeutic intervention at this

    time?

    A.Increase calcium intake to 1200 mg/day with vitamin D 800 IU/d

    B.Oral alendronate 70 mg once weekly in addition to supplemental calcium and vitamin D

    C.

    Transdermal testosterone 5 mg at night in addition to supplemental calcium and vitamin

    DD.

    Teriparatide 20 mcg SC daily in addition to supplemental calcium and vitamin D

    E.Intranasal calcitonin, 200 units once daily

    Correct Answer

    BAnswer RationaleThe presence of a vertebral compression fracture is sufficient to establish a

    diagnosis of osteoporosis, even though the bone mineral density T-scores are

    in the osteopenic range. If the bone mineral density in a man is evaluated

    using reference data from a healthy female population, then osteoporosis willbe 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 wouldbe a bisphosphonate (e.g. alendronate) or teriparatide. Given the expense

    and inconvenience of teriparatide, alendronate is the most appropriate first

    therapy for this patient. Intranasal calcitonin has not been shown to reducefracture risk in men with osteoporosis. This patient has a low normal

    testosterone level, most likely a consequence of an age-related decline in his

    gonadal function. The benefits of testosterone therapy for the prevention of

    osteoporotic fractures in hypogonadal men have not been established. There

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    is also uncertainty as to whether testosterone replacement improves bone mineral densityin older men with borderline low testosterone levels. Since androgen therapy has possible

    undesirable effects on other organ systems, particularly the prostate gland, testosteronetherapy would not be the first choice of therapy for this man.

    Question Number: 2

    Case

    An over-weight 14-year-old boy had been active at a soccer tournamentyesterday and complained of right knee pain when he returned home. Today

    the pain is still present and worsens with weight bearing. He has been

    previously diagnosed with mild hypothyroidism, and sometimes he forgets totake his replacement therapy.

    Physical examination shows no abnormalities of the knee, but internal

    rotation at the hips is limited.

    Radiograph of the hips is shown in figure below.

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    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 evaluationD.

    Use of crutches for two weeks and weight bearing as tolerated

    E.

    Physical therapy program to increase the range of movement of his hips

    Correct Answer

    CAnswer RationaleChildren often complain of knee pain when the hip is the source of the

    problem. SCFE is more common in obese adolescent boys and also in

    children with hypothyroidism. It is a surgical emergency; the child should bemade non-weight bearing immediately, additional radiographs (including

    frog-leg lateral view) should be obtained, and urgent orthopedic consultation

    should be ordered. Treatment is surgical pinning. There is increased risk ofslip on the other side, and some children develop aseptic necrosis orchondrolysis as a consequence of this condition.

    Question Number: 3

    CaseA 26-year-old man has had gradual onset of fixed proximal muscle weakness

    over the past 3 to 4 years. He had a healthy childhood but began

    experiencing exercise intolerance during his teen years. He often found that

    when he exercised, he would experience dyspnea and muscle pain shortlyafter beginning the activity. These symptoms would force him to stop what

    he was doing. However, after resting for 2 or 3 minutes, he could resume

    the activity without discomfort. On one occasion, he experienced severecramping and muscle tenderness after going fishing and carrying his catch in

    a bucket of water back to car, a distance of about a half mile. The cramps

    lasted more than an hour and the muscle tenderness resolved in 48 hours.

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    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 nervestimulation.

    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 subsarcolemmalvacuoles

    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

    McArdles disease is the most common glycogen storage disease. It maypresent 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 thegradual 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 toresume 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 whenasymptomatic and have myopathic changes on EMG. The finding of PAS

    positive vacuoles confirms the diagnosis of a glycogen storage disease.

    Perivascular infiltration of lymphocytes with perifasicular atrophy andcapillary plugging are classically seen in dermatomyositis.

    Many small triangular fibers and fiber type grouping would be seen in a

    neuropathic condition and imply denervation and reinervation.Some type II fiber atrophy and increase oil red O staining in type I fibers

    occurs with lipid storage diseases like carnitine deficiency of some

    mitochondrial myopathies.

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    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 weaknessover 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 whathe 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 nervestimulation.

    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

    vacuolesC.

    Many small triangular fibers and fiber type groupingD.

    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

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    Trichrome staining

    Correct Answer

    BAnswer RationaleMcArdles disease is the most common glycogen storage disease. It may

    present in childhood with exercise intolerance; in teen years with episodes of

    acute rhabdomyolysis associated with severe cramps, tenderness, andweakness that often occur after heavy exertion; or in adulthood with the

    gradual onset of fixed proximal muscle weakness. The fixed weakness is felt

    to be the result of recurrent rhabdomyolysis and an inability, after a time, toregenerate normal muscle. Many patients report a second wind

    phenomenon. They start to exercise but must stop, only then to be able to

    resume the activity after a brief rest. This is presumably the result of

    increased blood flow and delivery of nutrients that occur in response to theinitial exercise. Most of these patients have an elevated CK level even when

    asymptomatic and have myopathic changes on EMG. The finding of PAS

    positive vacuoles confirms the diagnosis of a glycogen storage disease.

    Perivascular infiltration of lymphocytes with perifasicular atrophy andcapillary plugging are classically seen in dermatomyositis.

    Many small triangular fibers and fiber type grouping would be seen in a

    neuropathic condition and imply denervation and reinervation.

    Some type II fiber atrophy and increase oil red O staining in type I fibersoccurs with lipid storage diseases like carnitine deficiency of some

    mitochondrial myopathies.

    Many fibers with central nuclei, occasional hypertrophic cell, and ragged redchange on Gamori Trichrome staining are indicative of a mitochondrial

    myopathy.

    Question Number: 5

    Case

    A 55-year-old woman has had an aching pain in her lower back for the past 2years.

    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)

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    1,25 hydroxyvitamin D: 40 pg/ml (normal 25-45 pg/ml)

    Parathormone: 108 pg/ml (normal 10-65 pg/ml)

    QuestionWhich of the following radiographic abnormalities is most likely in this

    patient?

    A.Increased bone mineral density

    B.

    Subperiosteal resorptionC.

    Loosers zones

    D.

    Erlenmeyer flask deformity of the distal femoraE.

    Mixed areas of lucency and sclerosis in the long bones

    Correct Answer

    CAnswer RationaleThis patient has osteomalacia as a result of vitamin D deficiency.

    Characteristically, both the serum calcium and the serum phosphorus levelsare decreased, while the serum alkaline phosphatase level is elevated. In

    vitamin D deficiency, parathormone levels rise, causing an increase in the

    metabolism of 25-hydroxyvitamin D to 1,25-hydroxyvitamin D. This in turn

    results in a greater deficiency of vitamin D but also a normal or elevated

    level of 1,25-hydroxyvitamin D.

    The characteristic radiographic feature of osteomalacia is Loosers zones orpseudofractures that appear as linear areas of rarefaction perpendicular to

    the cortical surface of the bone. Increased bone mineral density is a feature

    of osteopetrosis. Subperiosteal resorption occurs in primaryhyperparathyroidism. The Erlenmeyer flask deformity is a feature of

    Gauchers disease. Mixed areas of lucency and sclerosis in the long bones are

    a feature of Pagets disease.

    Question Number: 6

    Case

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    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-shapednegatively birefringent crystals are found under polarized light microscopy.

    Family history reveals that the patients 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 mgQuestion

    Which of the following findings is most likely in this patient?

    A.

    She is homozygous for phosphoribosylpyrophosphate (PRPP) synthase overactivityB.

    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 AnswerDAnswer Rationale

    Both PRPP synthase overactivity and partial HPRT deficiency cause

    hyperuicemia and gout, but both have X-linked inheritance and, therefore, donot 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 hyperuricemicnephropathy (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-stagerenal disease by mid-life.

    PNP deficient individuals have selective T-cell immunodeficiency.

    Question Number: 7

    Case

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    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 physicalexamination, 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 unchangedexcept 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 U/mlLFT: normal

    BUN: 23 mg/dlCreatinine: 1.0 mg/dl

    Albumin: 4.0 gm/dl

    Question

    Which of the following is the most likely cause of the patients weight loss?A.

    Active rheumatoid arthritis

    B.Methotrexate associated lymphoma

    C.

    Hyperthyroidism

    D.

    AnxietyE.

    Idiosyncratic effect of leflunomide

    Correct AnswerEAnswer Rationale

    Rheumatoid arthritis is a systemic inflammatory disease that affects the

    joints and extra-articular systems. Constitutional symptoms such as weightloss 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 heranxiety improved.

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    Leflunomide is a disease-modifying anti-rheumatic drug that works by

    inhibiting de novo pyrimidine biosynthesis. Actively dividing lymphocytes are

    inhibited by the drugs 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 drugs effect on

    oxidative phosphorylation within the mitochondria, rather than a secondaryeffect resulting from diarrhea or anorexia. Cessation of leflunomide may

    result in weight gain. The weight loss averaged between 19 and 53 pounds

    and occurred within weeks to months of beginning leflunomide. Recognitionof this side effect is important since unnecessary additional testing may be

    undertaken to investigate weight loss.

    Question Number: 8

    CaseA 49-year-old man has progressive swelling of the left foot. He had noted

    tingling and burning in the foot at night for the past year. The foot thenbecame 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 patients current medications are losartan,hydrochlorothiazide, metformin, glyburide, and simvastatin. He drinks one

    or two 12-ounce cans of beer on weekends. He is afebrile.

    Physical examination is notable for pain, swelling, and erythema of thedorsum of the left foot and ankle. The midfoot and ankle are tender. There

    is restricted range of motion of the ankle with pain. Deep tendon reflexes

    are absent at both ankles. There is diminished vibration sensation in bothfeet and decreased proprioception of the toes of both feet. No ulcers or rash

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    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 syndromeCorrect Answer

    CAnswer Rationale

    This patient has a long-standing history of diabetes mellitus type 2 andmonths of foot swelling. The radiograph shows hindfoot and midfoot joint

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    and osseous destruction, osteopenia, and reactive bone formation. No

    chondrocalcinosis is present making CPPD arthropathy unlikely. The

    radiographic changes are out of proportion to the pain the patientdescribes. This is unusual for reflex sympathetic dystrophy in which

    causalgic pain is usually prominent and allodynia typically

    present. Osteopenia and marked osseous destruction are not typical of

    osteoarthritis. This radiograph does not show typical features of gout

    including punched out, rounded defects marginally and erosions withoverhanging edges. Osteomyelitis may be present in diabetic patients with

    foot ulcers, but this patient has no preexisting foot ulcer. The patient alsohas no paronychia, cellulitic skin features nor constitutional symptomsincluding fever to suspect infection.

    Question Number: 9

    CaseAn 8-year-old boy has had hectic fevers for the past 5 days, a diffuse

    morbilliform rash on his trunk, swollen hands and feet, erythematous oral

    mucosa with no exudates, cracked lips, and red eyes. He has diffuselymphadenopathy and slight hepatomegaly. He is very irritable.

    Laboratory data include:

    ESR: 80 mm/hrRBC: mild anemia

    Hgb: 1.1 gm/dl

    WBC: 17,000/mm3

    Platelet count: 450,000/mm3Urinalysis: some WBCs but no bacteria or proteinuria

    Echocardiography: normal

    Spinal fluid analysis: a few lymphocytes but no organisms on gram stain

    QuestionWhich of the following is the most appropriate treatment?

    A.IVIG 2 gm/kg over 12 hours

    B.

    Aspirin 325 mg/dayC.

    Prednisone 2 mg/kg/day

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    D.

    Ibuprofen 40mg/kg /day

    E.Infliximab 5 mg/kg single dose

    Correct Answer

    AAnswer RationaleThe 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 antiplateletagent. Studies are ongoing to determine effectiveness of anti-TNF agents in

    Kawasaki disease; their effectiveness in treatment is not yet established.

    Question Number: 10Case

    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 andhamstrings 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 testingproduces the following results:

    Venous Blood

    lactate (mg/dL) NH3 (g/dL)

    At rest8

    20Two minutes after exercise 9

    90

    QuestionWhich of the following deficiencies is the most likely diagnosis?

    A.

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    Acid maltase

    B.

    Carnitine palmitoyltransferase IIC.

    Myoadenylate deaminase

    D.Myophosphorylase

    E.

    Phosphorylase b kinaseCorrect Answer

    DAnswer Rationale

    In phosphorylase b kinase deficiency there is a normal or only partially

    impaired rise in venous lactate with exercise. Ischemic forearm testingreveals a rise in blood lactate with impaired increase in ammonia levels in

    myoadenylate deaminase deficiency. In acid maltase deficiency the ischemic

    forearm muscle test is normal. CPT II deficiency usually begins in childhood

    with exercise-induced myalgia. The ischemic forearm test is normal in CPTII. McArdles disease, characterized by myophosphorylase deficiency, is the

    only choice associated with a flat venous lactate response to ischemic

    forearm exercise. Note that testing of muscle biopsy samples has in recent

    years become a precise diagnostic tool to confirm enzyme defects inmetabolic muscle disease.

    Question Number: 11

    CaseA 73-year-old woman who has had deforming rheumatoid arthritis for the

    past 20 years now has persistent neutropenia. She has been living in an

    assisted care facility for the past 3 years. Despite bilateral knee

    arthroplasties, her mobility and ability to live independently have beenprogressively 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, herWBC 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

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    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 granulesQuestion

    Which of the following studies is most likely to establish the diagnosis?

    A.Abdominal ultrasonography to measure spleen size

    B.

    Flow cytometry of peripheral blood

    C.Test for cyclic citrullinated peptide (CCP) antibodies

    D.

    Granulocyte antibody test

    E.Test for antinuclear antibodies (ANA)

    Correct AnswerBAnswer Rationale

    The leading diagnostic considerations for this patient are Feltys syndrome

    and large granular lymphocyte (LGL) syndrome. The LGL syndrome is a

    clonal disorder of cytotoxic T-lymphocytes and has been classified asleukemia, even though it usually has an indolent clinical course. About 25%

    of patients with LGL syndrome have rheumatoid arthritis. The demonstration

    of a clonal population of CD3+, CD8+, CD16+, CD57+ T cells with flowcytometry of the peripheral blood would serve to establish the diagnosis of

    LGL syndrome. Splenomegaly and granulocyte antibodies are common to both disorders.The histopathology of the bone marrow does not usually differentiate the two.

    Question Number: 12

    CaseA 44-year-old woman with a 20-year history of lupus undergoes follow-up

    evaluation. Initial manifestations included photosensitivity, small joint

    arthritis, fatigue with a positive ANA, dsDNA, and leukopenia. Her symptomsresponded to anti-inflammatory agents and hydroxychloroquine, which she

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    continues to take. She feels reasonably well but has noticed some difficulty

    climbing stairs. Findings on physical examination are normal. CPK and TSH

    levels are normal, and there is no evidence of lupus activity on serologicalstudies. She returns 1 month later, and proximal weakness affecting the hip

    flexors is noted.

    Laboratory data include:CBC: Normal

    ESR: 33 mm/hr

    CK: 250 U/LdsDNA: 26 IU

    TSH: 4.9 U/ml

    Electrolytes: Potassium 3.4 mmoles/L

    Mg: NormalCa: Normal

    Question

    Which of the following is the most likely cause of the patients proximal

    muscle weakness?A.

    Inclusion body myositisB.

    Lupus flare

    C.

    Hydroxychloroquine myopathyD.

    Hypothyroidism

    E.Hypokalemia

    Correct Answer

    C

    Answer Rationale

    Antimalarial therapy is commonly used in patients with lupus. Side effects of

    therapy include irreversible retinal toxicity, rash, and gastrointestinaldisturbance. A less common and under recognized complication of therapy is

    myopathy, which does not appear to correspond with the dose used. The

    pathogenesis of this myopathy is thought to be related to accumulation ofhydroxychloroquine in lysosomes, which then inhibit lysosomal enzymes. It is

    a reversible myopathy, and thus important to recognize. Inclusion body

    myositis is more common in men, and primarily affects the distalmuscles. There is nothing to suggest a lupus flare, and although the TSH

    level is at the high end of normal, hypothyroidism is unlikely to explain the

    weakness.

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    Question Number: 13Case

    An 86-year-old man was sent to the hospital from an Alzheimers unit 2 days

    ago because of a 2-day history of a swollen, red, warm, and tenderelbow. 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 ofcloudy fluid were obtained. Synovial fluid analysis showed cloudy fluid with a

    WBC of 95,000/mm3. Gram stain was negative, and the fluid was sent for

    culture. The patient was started on an intravenous antibiotic to cover gram-

    positive bacteria for presumed septic arthritis.He is now confused, but his mental status is reported to be his usual. His

    temperature is 99.6 degrees F (37.55 degrees C). His elbow is held in a

    flexed position and is slightly swollen in the area between the olecranon and

    lateral epicondyle. It is minimally erythematous, warm, and tender. Heresists any attempt to move the elbow. Findings on examination of the other

    joints are normal. CBC now has a WBC of 10,000/mm3. Radiograph of theelbow shows only soft tissue swelling. His synovial fluid and blood cultures

    have no growth. Sputum gram stain shows a few gram-positive cocci in pairs

    but grows out mixed flora.

    QuestionWhich of the following is the most appropriate next step in management?

    A.

    Surgical open drainage of the jointB.

    Continue present antibiotic regimen

    C.Aspirate the elbow and look for crystals

    D.

    Add another antibiotic to cover gram-negative organisms

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    Correct Answer

    CAnswer RationaleCPPD crystals can elicit an intense inflammatory response in a single jointthat may mimic septic arthritis. It is appropriate to start antibiotics in this

    clinical setting, but when cultures are negative, one should suspect a crystal-

    induced process. Open drainage is appropriate in septic arthritis, if the joint

    effusion cannot be controlled by percutaneous aspiration.

    Question Number: 14

    CaseA 4-year-old girl has recent onset of rash over her knuckles and knees.

    Nailfold capillaroscopy is shown in Figure 1 below.

    FigureQuestion

    The nailfold changes place this patient at highest risk for which of the

    following?

    A.

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    Calcinosis

    B.

    Pulmonary hemorrhage

    C.

    Retinal changes

    D.

    Gastrointestinal vasculitisE.

    Corticosteroid resistance

    Correct AnswerDAnswer 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 forgastrointestinal vasculitis, the most common vasculitic complication in

    juvenile dermatomyositis.Corticosteroid resistance or dependence does not correlate with nailfoldchanges.

    Educational Objective

    To recognize juvenile dermatomyositis and the association of gastrointestinal

    vasculitis in children with dermatomyositis and nailfold capillary changes.

    Question Number: 15

    CaseA 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 firstdiagnosed at age 58 years.

    Question

    Which of the following treatment regimens is most likely to be effective in

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    improving this patients bone mineral density over the next 3 years?

    A.

    Continue alendronate therapy aloneB.

    Continue alendronate and administer daily PTH (1-34) concurrently for the next 18

    months, afterwhich both drugs are discontinued

    C.

    Continue alendronate and administer daily PTH (1-34) concurrently for the next 18months, after

    which alendronate alone is continued

    D.

    Discontinue alendronate therapy and administer daily PTH (1-34) for the next 18 months

    Correct Answer

    CAnswer Rationale

    Cosman et al (2005) randomized 126 women who had been on alendronatefor at least 1 year to continue alendronate and to receive daily PTH (1-34),cyclic (3 month on/3 month off) PTH (1-34), or alendronate alone. Spine

    bone mineral density increased 6.1% in the daily PTH (1-34) and 5.4% in the

    cyclic PTH (1-34) groups, but remained unchanged in the alendronate alone

    group. In a study by Black et al (2005), patients originally randomized to 1year of treatment with PTH (1-84) were subsequently randomized to receive

    alendronate or placebo. Lumbar spine bone mineral density continued to

    increase in both groups in the first year following discontinuation of PTH (1-84), but continued to rise in the second year only in the alendronate-treated

    patients. In patients who have never been treated with alendronate, there is

    no clear evidence that the combination of PTH with alendronate provides asynergistic or additive effect on bone mineral density as compared to PTH

    alone (Black et al, 2003). These studies thus support the conclusion that this

    patient would have the greatest increase in bone mineral density at the end

    of 3 years if she receivs PTH in addition to alendronate for the first 18months, and then alendronate alone after the discontinuation of PTH.

    Question Number: 16

    CaseA 61-year-old man was recently admitted to the medical service for

    management of congestive heart failure. While hospitalized, he experiences

    acute and spontaneous onset of right knee pain and swelling.He has a longstanding history of seronegative nodular rheumatoid arthritis

    that has been refractory to disease-modifying anti-rheumatic drugs

    (DMARDs), including hydroxychloroquine and methotrexate, but responsive

    to brief courses of prednisone.

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    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, andwarm 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.

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    Perform arthrocentesis on the inflamed knee

    C.

    Start a nonsteroidal anti-inflammatory drug (NSAID)D.

    Start pulse corticosteroids

    Correct AnswerBAnswer Rationale

    Although the patient carries the diagnosis of nodular rheumatoid arthritis and is already

    being treated with disease-modifying agents, a patient with rheumatoid nodules would beexpected to be seropositive for rheumatoid factor. This merits a reassessment of his

    diagnosis and management.

    The most appropriate course of action is to perform arthrocentesis to assist

    in both reevaluating the underlying diagnosis and in determining why thisjoint is flaring out of proportion to the other joints in what is normally a

    symmetric polyarthritisrheumatoid arthritis.

    Radiography would be useful in ruling out a bony injury if there were a

    history of trauma. Instead, the patients symptoms developed spontaneouslyand only after admission. NSAIDs and/or pulse corticosteroids are effective

    interventions for the acute management of many inflammatory arthritides,but their salt- and fluid-retentive effects could be deleterious to the patient

    because he has congestive heart failure.

    Question Number: 17

    Case

    A 42-year-old woman with longstanding lupus treated with low-dosecorticosteroids and hydroxychloroquine has been doing well for many years.

    She presented at age 18 with severe Raynauds phenomenon and finger

    necrosis that was treated with IV cyclophosphamide. Other manifestations

    included chronic thrombocytopenia and pulmonary embolus secondary toanti-phospholipid antibodies. She has never had cardiac or kidney

    involvement. The patient would like to stop taking hydroxychloroquine

    because she has been doing so well and finds the yearly eye examinations

    onerous.Question

    Which of the following is most appropriate advice to the patient at this time?A.

    Stop the annual eye examinations

    B.Discontinue the hydroxychloroquine

    C.

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    Continue the hydroxychloroquine

    D.

    Discontinue visual field testing at her annual eye examinationsE.

    Increase the dose of corticosteroids

    Correct AnswerCAnswer Rationale

    Hydroxychloroquine is a useful treatment for the cutaneous and

    musculoskeletal manifestations of lupus. It has little effect upon nephritis orother 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. Thepermanent visual damage results from binding of the drug to melanin. The

    recommended dose is not greater than 6.5 mg/kg. Discontinuation of

    hydroxychloroquine has been associated with an increased risk of flares. Eye

    examinations should be continued while the patient takes antimalarialmedications, especially if the patient has been taking them for many

    years. A full visual field and color test is required to optimally track theretinal effects of hydroxychloroquine. Increasing steroids in lieu of taking

    hydroxychloroquine increases the likelihood of corticosteroid-related

    complications; corticosteroid use should be kept at a minimum.

    Question Number: 18Case

    A 66-year-old woman who has a history of corticosteroid-dependent chronic

    obstructive pulmonary disease and nondisplaced talus fracture 1 year ago now has

    burning, aching, and numbness of the sole of the right foot and toes. The discomfort is

    worse at night and improves with ambulation.Question

    Compression of which of the following nerves is the most likely cause of this

    patients discomfort?

    A.Anterior tibial nerve

    B.Deep peroneal nerve

    C.

    Posterior tibial nerveD.

    Superficial peroneal nerve

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    E.

    Common peroneal nerve

    Correct AnswerCAnswer Rationale

    This patient has tarsal tunnel syndrome marked by posterior tibial nerve

    compression. Foot trauma including talus or calcaneal fracture predisposesto the development of this condition. Deep peroneal nerve (or anterior tibial

    nerve) compression causes paresthesias and numbness of the dorsum of the

    foot. Note that the anterior tibial nerve is now more commonly called thedeep peroneal nerve. Superficial peroneal nerve compression causes

    paresthesias and numbness over the dorsolateral foot and worsens with

    exercise. Common peroneal nerve compression causes foot drop.

    Question Number: 19Case

    A 23-year-old man sustained multiple toe fractures while playing soccer four

    months ago. Since cast removal, he has had pain in the lower extremities

    and arthralgias. Past medical history reveals a clavicle fracture at age 3years, finger fractures while playing volleyball at age 9 years, and foot

    fractures at age 12 years when he kicked a can. Physical examination showsa thin man who is slightly nervous and sweating. His height is 5 feet 5

    inches and has normal dentition and no skeletal deformities. All MCP, ankle,

    and elbow joints go beyond the normal range of motion. Findings on

    examination of the skin and heart are normal. The sclerae are pale blue,which he says have always been like that, and there is no family history of

    this finding. He wears hearing aids.

    Laboratory data include:CBC: normal

    Alkaline phosphatase: 55 U/LVit 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 sequencingD.

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    Quantitative CT scans

    E.

    Histomorphometric analysis of boneCorrect Answer

    BAnswer Rationale

    This is a case of type I ostegenesis imperfecta (OI), a rare inheritedconnective tissue disorder with many phenotypic presentations. The cause of

    all cases of OI has not been definitely established. Although mutations in

    one or the other of two genes which code for proteins that combine to formtype I collagen (COL1A1 and COL1A2), account for many of the qualitative

    and quantitative defects in type I collagen seen in OI, its clinical

    manifestations vary substantially within families. One member may be quite

    affected clinically, whereas another member with the same mutation mayenjoy normal function. Skin biopsy for analysis if type I collagen genes

    and/or testing of genomic DNA for mutations in COL1A1 and COL1A2 may be

    a helpful in diagnosis especially in those with subtle clinical manifestations.

    However, normal results of these tests do not exclude thediagnosis. Identifying a mutation in a particular gene does not necessarily

    result in a clear clinical diagnosis for this reason the clinical diagnosis of OI isbased on the signs and symptoms as described in the above case. Mild (type

    I) OI, is the least severe form. Individuals with type I OI may have few or

    no fractures before puberty or numerous fractures throughout their

    lives. Deformity is minimal and stature is usually normal. Individuals withtype I OI usually do not begin to have fractures until they begin toddling or

    walking. The most frequently involved bones are the long bones of the arms

    and legs, ribs, and the small bones of the hands and feet. Clinicalmanifestations of OI include excess or atypical fractures (brittle bones), short

    stature, scoliosis, basilar skull deformities, which may cause nerve

    compression or other neurologic symptoms, blue sclerae, hearing loss,opalescent teeth that wear quickly (dentinogenesis imperfecta) increased

    laxity of the ligaments and skin with easy bruiseability. Measurement of

    BMD by dual-energy x-ray absorptiometry (DEXA) at any age discloses asignificant decrease in bone mass. This is the case for mild disease, in which

    BMD is reported to be 76 percent of that of an age-matched control in the

    spine and 71 percent of control in the femoral neck. T scores (i.e., standarddeviation from the young-adult mean BMD) are frequently in the range of

    -2.5 to -4.0 at the lumbar spine or proximal femur. Although bone biopsy is

    indicate when there is excessive skeletal fragility under unusualcircumstances and in this case he had a classic clinical picture of IO with

    multiple fractures at young age, blue sclerae, short stature, and hearing loss.

    Question Number: 20Case

    A 23-year-old woman has a 4-year history of polymyositis. At the onset of

    disease, she had a rash on her face and CK level was 35,000 U/L. EMG was

    consistent with inflammatory myopathy. A biopsy of the deltoid muscle wasconsistent with polymyositis. She was subsequently treated with numerous

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    drugs including high-dose prednisone, methotrexate, mycophenolate mofetil,

    and infliximab. She had an anaphylactic reaction to azathioprine. She has

    also received several courses of IVIG. None of these treatments have shownsignificant benefits although the CK levels are now lower, in the range of

    8,000-10,000 U/L.

    She now has significant difficulties with daily activities, requiring help fordressing and ambulation from her mother who lives with her. At times she

    uses a scooter. Social history is negative for use of illicit drugs, tobacco, and

    alcohol. Her family history is negative for autoimmune disease; she is anonly child. On examination, she is overweight, has cushingoid features, and

    is without rash or nail abnormalities. Muscle strength is 2-3/5 in all four

    extremities, worst in proximal muscles of both legs. An MRI scan using a

    STIR sequence shows increased signal intensity in muscles of the quadriceps,consistent with the presence of inflammation.

    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 leukocytesThe 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.

    PolymyositisE.

    Diabetic vasculopathy

    Correct AnswerCAnswer Rationale

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    The mean age of onset of limb girdle muscular dystrophy (LGMD) Type 2B, a

    dysferlinopathy, is 19 years of age. Proximal lower extremity weakness is a

    common initial finding, and unlike some types of juvenile dystrophies,hypertrophy of calf muscles usually does not occur. Truncal weakness can be

    marked, and this affects balance and gait making walking difficult. MRI STIR

    studies in LGMD can show increased signal intensity that is not readilydistinguished from the pattern seen in inflammatory myopathies. For these

    reasons, this disorder can be misdiagnosed as polymyositis. However, the

    muscle biopsy shows defective staining for dysferlin, a muscle membraneprotein, and this feature distinguishes the histologic changes from those seen

    with polymyositis.

    Another clue that this case may not be PM is the very high initial CK level,

    more than 100 times greater than the upper limit of normal, which isuncommon in the inflammatory myositis syndromes. Chronic juvenile DM is

    typically associated with more prominent cutaneous features than those

    described here and frequently also has vasculitic changes and prominent soft

    tissue calcifications, which are not present in this patient. Furthermore, thisyoung woman is not in the demographic category typical for IBM, which is

    generally observed in middle-aged or older men. Diabetes mellitus can alterblood flow in muscles and cause MRI changes, but this is usually associated

    with longstanding disease, which this patient does not have.

    Question Number: 21

    CaseA 46-year-old woman has had a 4-month history of recurring confluent

    erythematous macules over the sun-exposed areas of the forearms, anterior

    torso, face, and neck that are occasionally associated with superficial

    ulceration. She has not had associated mouth ulcers, sicca symptoms,

    xerostomia, or joint problems. Evaluation at the time her symptoms beganwas remarkable only for the rash and an otherwise very fair complexion;

    serology studies were notable for positive ANA at a titer of 1:640 (speckled

    pattern) and anti-SSA/Ro antibodies in a significant elevated titer. She was

    initially advised to use a high SPF sunscreen and was prescribedhydroxychloroquine 400 mg daily and prednisone 40 mg daily. The rash

    promptly responded to corticosteroids but has flared each time theprednisone 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?

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    A.

    Add pulse intravenous cyclophosphamide 750 mg/m2

    B.Add azathioprine 2 mg/kg/day

    C.

    Add dapsone 50 mg/dayD.

    Add quinacrine 100 mg/day

    E.Add thalidomide 50 mg/day

    Correct Answer

    DAnswer Rationale

    Cutaneous manifestations of lupus are quite variable, manifesting aserythematous macular or maculopapular rashes, discoid plaques, bullous

    lesions, or vasculitis manifest as nonblanching purpura, cutaneous ulcers, or

    urticarial lesions. While antimalarials are effective for suppressing many of

    the cutaneous manifestations of lupus and corticosteroids in sufficient dosewill usually effect resolution of cutaneous flares, other immunomodulating

    therapies are often required to suppress cutaneous manifestations of lupus toavoid the toxicity associated with long-term corticosteroid use.

    Intravenous pulse cyclophosphamide is effective in managing severe

    manifestations of SLE but is typically reserved for severe lupus nephritis,

    severe CNS manifestations, or refractory severe immune-mediatedcytopenias, with other less toxic options employed to manage active skin

    disease. Azathioprine is often effective as a corticosteroid-sparing therapy for

    a variety of lupus manifestations, including skin disease. However,concurrent leucopenia as is present in this patient may preclude use of

    azathioprine in doses sufficient to effectively manage skin disease. In the

    setting of leucopenia, mycophenolate mofetil might also be considered as an

    alternative to azathioprine as a corticosteroid-sparing therapy because it impactspredominantly lymphocyte proliferation with minimal impact on granulopoiesis, but the

    efficacy of mycophenolate in managing cutaneous manifestations of lupus is not well

    established.Other alternatives that do not impact granulopoiesis, such as dapsone,

    addition of a second antimalarial, or thalidomide, are often quite effective inmanaging cutaneous manifestations of lupus. Dapsone has been shown to beparticularly useful in managing cutaneous ulcers in SLE caused by small

    vessel vasculitis or bullous disease. Persistent mauclopapular eruptions that

    are not adequately suppressed with hydroxychloroquine often will respond toaddition of a second antimalarial such as quinacrine. If this option is used,

    combined use of these two antimalarials is more effective than either alone

    and is the concurrent use of both is recommended rather than discontinuing

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    hydroxychloroquine and adding quinacrine. Quinacrine is usually well

    tolerated although patients with a fair complexion may find it objectionable

    because of predictable yellow discoloration of the skin with prolonged use.Thalidomide is highly effective in managing mucocutaneous ulcers, as well as

    refractory erythematous rashes, including the eruption associated with

    subacute cutaneous lupus, a variant associated with elevated titers of anti-SSA/Ro antibodies.

    Question Number: 22

    CaseAn 18-year-old woman has 1-year history of progressive proximal muscle

    weakness. Four months ago, her CK level was 12,000 U/L, a short tau

    inversion recovery (STIR) MRI showed edema in her proximal thighs, and a

    muscle biopsy revealed fiber degeneration and regeneration with infiltrationof some lymphocytes and phagocytic cells. She was treated with high-dose

    corticosteroids, methotrexate, and monthly infusions of intravenous

    immunoglobulins for 3 months. Despite this treatment, muscle strength has

    continued to deteriorate and CK level is 16,000 U/L.Her family history reveals that similar symptoms developed 3 years ago in

    her 26-year-old brother.Question

    Testing of a repeat muscle biopsy specimen is most likely to show which of

    the following?

    A.Histochemistry revealing fiber type grouping

    B.

    Immunohistochemistry showing absence of dysferlinC.

    Trichrome staining revealing ragged red fibers

    D.

    Absence of carnitine palmitoyltransferase (CPT) activity

    Correct AnswerBAnswer 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 musculardystrophy. This condition is familial with the usual onset between 18 and 20

    years of age. CK levels may be 100 times the upper limit of normal. Muscle

    histology typically shows inflammation. Corticosteroid therapy is not helpfuland, in some cases, may make the condition worse.

    Fiber type grouping is characterisc of neuropathic processes that involve

    reinervation.Ragged red fibers are seen by Trichome staining of muscle in patients with

    some mitochondrial myopathies. Mitochondrial myopathies may be familial,

    can present with proximal weakness and elevated CK levels, and will not

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    respond to immunosuppressive therapy. Muscle tissue would not show

    regeneration or inflammatory cell infiltrate.

    This clinical course is not consistent with CPT deficiency. CPT deficiency causesepisodic rhabdomyolysis. Between episodes, strength and muscle enzymes are normal.

    Question Number: 23

    CaseA physician colleague asks for evaluation because he thinks he may have

    rheumatoid arthritis. He is 55 years old and enjoys excellent health; he is an

    avid bicyclist. Nine months ago, mild pain and swelling developed in the MCPjoint of his right thumb. Two months ago, similar symptoms developed in the

    PIP joint of the left ring finger. Both sets of symptoms developed without

    antecedent trauma. There is no morning stiffness. On physical examination,

    there is mild soft tissue swelling with minimal tenderness of the twosymptomatic joints. No other joint abnormalities are present.

    Laboratory data include:

    ESR: 1 mm/hr

    C-reactive protein: 100

    Question

    According to the available evidence from clinical trial data, which of thefollowing management approaches is most likely to retard progression of thispatients arthritis?

    A.

    Prednisone 10 mg po dailyB.

    Naproxen 500 mg po twice daily

    C.Sulfasalazine 1000 mg po bid

    D.

    Etanercept 25 mg subcutaneously twice weekly

    E.Methotrexate 15 mg po once weekly

    Correct Answer

    EAnswer RationaleThis patient does not meet the ACR criteria for rheumatoid arthritis and

    would thus be classified as having an undifferentiated arthritis. In contrast to

    early rheumatoid arthritis, there are few clinical trials that have examinedtherapy for patients with undifferentiated arthritis. The best such study was

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    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 wasincreased 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 Raynauds symptoms3 years ago and for the past year has had mild nonproductive cough with

    increasing exertional dyspnea. For the past 6 months, her fingers havebecome 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, andnormal 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 areotherwise 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/mm3Hct: 24% (MCV 76)

    Hgb: 7.4 mg/dl

    Platelet count: 720,000/mm3Creatinine: 1.6 mg/dl

    CK: 380 IU/ml (nl

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    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 wouldnot be indicated.

    Elevations in creatine kinase (CK) levels may occur in patients with systemic

    sclerosis, either because of concomitant hypothyroidism or inflammatorymyopathy. 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 inflammatorymyopathy 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. Treatmentoptions 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

    CaseA 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: positiveUrinalysis: normal

    Rheumatoid factor: 180 IU/ml

    Skin biopsy of the lower extremity rash reveals leukocytoclastic vasculitis.

    QuestionIn addition to prednisone, which of the following is the most appropriate

    treatment?

    A.

    Peg-Interferon RibavirinB.

    PlasmapheresisC.

    Cyclophosphamide

    D.Rituximab

    E.

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    Infliximab

    Correct Answer

    AAnswer RationaleMixed cryoglobulinemia is a systemic vasculitis associated with hepatitis C

    infection. The mixed cryoglobulinemia syndrome is associated with purpura,

    arthralgia, and asthenia. There may also be neurologic and renalinvolvement. Treatment of hepatitis C mixed cryoglobulinemia (HCV-MC)

    may target the viral load or the B-cell arm of autoimmunity. Peg-

    InterferonRibavirin is the first line therapy. For refractory HCV-associated cryoglobulinemia vasculitis or acute severe life-threatening organ

    involvement, plasmapheresis, corticosteroids in combination with cytotoxic

    agent, or Rituximab should be considered as treatment options.

    Question Number: 26

    Case

    A 56-year-old woman has a 4-month progression of 2nd and 4th bilateral DIPdeformity. Pruritic nodules on the left 4th DIP joint and right pinna also

    developed. She has a 2-month history of cough, dyspnea, weight loss, and

    malaise.Bilateral radiographs of the hands reveal extensive erosive changes in the

    bilateral 2nd and 4th DIP joints.

    Radiograph of the chest reveal hilar lymph nodes.CT Scan of the chest reveal nodular pleural thickening, pleural effusions, andmediastinal and hilar lymphadenopathy

    Biopsy of the 4th DIP nodule reveals villous, hypertrophic synovitis with

    plasma cells and multinucleated giant cellsQuestion

    Which of the following is the most likely diagnosis?

    A.Rheumatoid arthritis

    B.

    Relapsing polychondritis

    C.Seronegative spondyloarthropathy with peripheral joint involvement

    D.

    Multicentric reticulohistiocytosisE.

    Psoriatic arthritis

    Correct AnswerDAnswer Rationale

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    Multicentric reticulohistiocytosis is characterized by severe destructive

    arthritis and cutaneous papulonodular lesions. Histiologic analysis of the

    cutaneous nodules reveals infiltration of multinucleated giant cells andhistiocytes 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. Otherassociations 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, thebiopsy supports the diagnosis of multicentric reticulohistiocytosis

    Question Number: 27

    CaseA 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/hrCR-P: 0.9 URheumatoid factor: negative

    ANA: 1: 40

    AST: NormalALT: Normal

    CK: Normal

    Creatinine: NormalAlbumin: Normal

    TSH: 2.1 U

    Urinalysis: Normal

    Past medical history is notable for hypertension for which she takes atenolol50 mg daily.

    On physical examination now, pain restricts maximal abduction and rotation of the

    shoulders. Cervical spine range of motion is complete. No synovitis is detected. Motorstrength is normal in all extremities. There is no muscle tenderness. There is no cranial

    tenderness and temporal arteries are easily palpated with normal pulsations.

    QuestionWhich of the following is the most appropriate next step in management?

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    A.

    Begin prednisone 15 mg/day

    B.Begin amitriptyline 10 mg at bedtime

    C.

    Inject shoulders with intra-articular corticosteroidsD.

    Discontinue atenolol

    E.Begin pregabalin 75 mg/day

    Correct Answer

    AAnswer Rationale

    The clinical presentation of this patient is most consistent with polymyalgia

    rheumatica (PMR). The onset of bilateral, symmetric, shoulder and pelvic

    girdle stiffness and nocturnal symptoms in an older patient, with the absenceof peripheral joint swelling, is most consistent with this diagnosis. Though

    markers of inflammation such as ESR and C-RP are generally elevated, theycan be normal in about 20 percent of patients. These patients with PMR andnormal makers of inflammation have a similar clinical course to patients with

    elevated markers. Their response to low to moderate doses of corticosteroids

    is generally dramatic.

    MRI and ultrasound studies showed that patients who have PMR with normalor high ESRs have similar inflammatory shoulder lesions. These imaging

    studies may facilitate the proper diagnosis in patients with the typical

    proximal symptoms of PMR who also have normal ESRs.Intra-articular corticosteroids may provide short-term pain relief, but would

    not be recommended given the strong likelihood of symptom relapse.

    Increasing the dose of ibuprofen would likely provide little additional benefitand there is no evidence that NSAIDs are effective in managing patients with

    PMR.

    There are no clinical features to suggest fibromyalgia or another soft tissue pain

    syndrome, thus prescribing amitriptyline or pregabalin is not indicated. Beta-blockerssuch as atenolol do not cause these pain syndromes and so this medication should not be

    discontinued.

    Question Number: 28Case

    A 73-year-old woman who has had deforming rheumatoid arthritis for the

    past 20 years now has persistent neutropenia. She has been living in anassisted care facility for the past 3 years. Despite bilateral knee

    arthroplasties, her mobility and ability to live independently have been

    progressively impaired by arthritis of her ankles, feet, wrists, and hands. Pasttherapies have included parenteral gold, penicillamine, hydroxychloroquine,

    methotrexate, and etanercept. At the time of admission to the facility, her

    WBC was 3200/mm3 and her physician chose to maintain her on prednisone

    7.5 mg qAM alone for her rheumatoid arthritis. Her only infection was aurinary tract infection 3 months ago treated with oral ciprofloxacin. Other

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    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 cellsQuestion

    Which of the following is the most appropriate initial therapy for this patient?A.

    SplenectomyB.

    Increased dose of prednisone

    C.Infliximab

    D.

    MethotrexateE.

    Filgastrim

    Correct AnswerDAnswer RationaleThis 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 anindolent 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 bloodserved 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-

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    stimulating factors, such as filgastrim, may be used in severe neutropenia

    while a remission is being induced with immunosuppressive agents.Correct AnswerDAnswer 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: 35Case

    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

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    scan and venous Doppler studies would not be indicated in this clinicalsetting.Question Number: 36Case

    A 22-year-old college student has left knee swelling after playing soccer. He

    does not recall specific trauma to the affected joint. He denies sexual

    activity. Review of systems is notable for the lack of antecedent infectious

    symptoms, visual difficulties, oral ulcers, back pain, diarrhea, or rash. His

    home is in Connecticut, and deer frequent his back yard. On physical

    examination, the left knee is large and swollen.Analysis of aspirated joint fluid reveals WBC 11,000/mm3 with predominant

    neutrophils, no crystals, and negative bacterial cultures. Lyme titer is

    markedly positive with a confirmatory Western blot test showing 10 positive

    bands.

    He is treated with doxycycline for 30 days. The follow-up examination shows

    a persistent effusion and no abnormal neurological manifestations. The oral

    antibiotic is continued for another 30 days. Intravenous ceftriaxone is

    prescribed for 1 month after the extended course of oral doxycycline fails to

    eradicate the effusion. Synovial fluid aspiration now shows persistent

    inflammatory joint fluid with negative PCR for Borrelia burgdorferi.QuestionWhich of the following is most appropriate therapy at this time?A.

    EtanerceptB.

    Oral doxycycline for 30 daysC.

    IV ceftriaxone for 30 daysD.

    IV penicillin for 30 daysE.

    Hydroxychloroquine

    Correct AnswerEAnswer RationaleLyme arthritis is an inflammatory arthritis that primarily affects large joints,especially the knee, and is caused by infection with Borrelia burgdorferi,

    which is a spirochete transmitted by Ixodid ticks. In most patients,

    treatment with oral doxycycline for 30 to 60 days eradicates infection and the

    effusion. In a small percentage of patients, a persistent effusion occurs

    despite months of oral and intravenous antibiotic therapy. In these patients,

    the appropriate work-up should include PCR testing of the synovial fluid for

    Borrelia burgdorferi. If the PCR is positive, repeated courses of antibiotic

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    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: 37Case

    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/LUrinalysis: normal

    24-hr urinary calcium: 350 mg

    Chest (Image 1) and elbow (Image 2) radiographs are shown.

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    FigureFigure 1Figure 2QuestionWhich of the following is the most likely cause of these findings in thispatient?A.

    Hyperparathyroidism secondary to CKDB.

    Ectopic production of PTHC.

    Primary hyperparathyroidismD.

    Increased production of 1,25 Vit DE.

    Myositis ossificans

    Correct AnswerDAnswer Rationale

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    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