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. C. D. E.

Minocycline-induced hyperpigmentation Alkaptonuria Hyperuricemia and gout 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. B. C. D. E. Rheumatoid arthritis Sjögren’s syndrome Lupus Hepatitis-associated cryoglobulinemia 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. B. C. D. Prescribe NSAID and avoid running Inject the right knee with a depot-corticosteroid preparation Inject the bursa with anserine 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. B. C. D. E. Every three to four months for four years then every six months Every six months for four years then every year Every year for four years then every two years When her eyes hurt 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. B. C. D. E. Hilar adenopathy Cryoglobulins Anti-SSA/Ro antibody Anti-thyroglobulin antibody 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 ChurgStrauss 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. B. C. D. COMP haplotype analysis FRZB 2-marker single-nucleotide polymorphism (SNP) haplotype analysis Targeted type II collagen polymorphism analysis 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 SSA 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. B. C. D. E. Schirmer’s I test with wetting of 7 mm in the right eye and 4 mm in the left eye. Unstimulated salivary flow of 0.1 ml/min Labial salivary gland focus score of 1 Absent salivary pool 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. B. C. D. E. Prednisone 60 mg/day Cyclophosphamide 1-2 mg/kg po daily Mycophenolate Mofetil 1000 mg twice daily Rituximab 750 mg/m2 x 2 doses 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. B. C. D. E. Anti-citrullinated peptide antibody titer Rapid plasma reagent test Anti-endomysial tissue transglutaminase antibody titer Fasting serum lipid profile 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. B. C. D. E. Add an anti-TNF agent Increase methotrexate dose Add anti- B cell therapy Begin cyclophosphamide 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. B. C. D. Thrombocytopenia Pigmented villonodular synovitis Decreased ascorbic acid 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. B. Leflunomide Cyclosporine

C. D. E.

Methotrexate Azathioprine 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. C. D. E.

Bone scan Hemoglobin electrophoresis Anti-native DNA antibodies 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. B. C. D. E. Taper the prednisone Sart azathioprine after checking thiopurine methyltransferase (TPMT) activity and slowly taper prednisone Start methotrexate and azathioprine after checking thiopurine methyltransferase (TPMT) activity and slowly taper prednisone Add IVIg 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. B. C. D. E. Discontinue colchicne Switch losartan to lisinopril Discontinue the ASA Add probenecid 1 g BID 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. B. C. D. BMI of 24.1 Jogging Use of cigarettes 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. B. C. D. E. Aspirin 81 mg per day Aspirin 325 mg per day Heparin 10,000 IU sq bid and prednisone 60 mg orally daily Heparin 10,000 IU sq bid and aspirin 81 mg per day 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. B. C. D. E. Biopsy of affected dermis EMG-directed muscle biopsy of an extremity muscle MRI of the shoulder and pelvic girdle muscles Vaginal ultrasonography and Ca-125 antigen study 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. B. C. D. Hemoglobin A1c Red blood cell folic acid Vitamin B12 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. B. C. D. E. Monoclonal gammopathy Peripheral eosinophilia Normal sedimentation rate and C-reactive protein Raynaud’s phenomenon 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. B. C. D. E. Osteonecrosis Pseudogout Pseudoseptic reaction Rheumatoid arthritis 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 intraarticular 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. B. C. D. E. Inflammatory bowel disease Common variable immune deficiency Endocardial elastosis Systemic lupus erythematosus 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 catylasepositive 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.