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Flashcards in QUESTIONS Deck (38):
1

A 29-year-old man is evaluated for a 1-day history of left shoulder pain. He was throwing a football when the pain began. The pain is located over the left lateral deltoid muscle and is associated with weakness with arm abduction. The patient has no previous history of shoulder problems and no history of trauma. He has been taking ibuprofen as needed for pain. On physical examination, temperature is normal, blood pressure is 126/80 mm Hg, and pulse rate is 96/min. There is pain in the left shoulder with active abduction beginning at approximately 60 degrees, and he has difficulty actively abducting the left arm beyond 60 degrees. The patient is unable to slowly lower his left arm to his waist (positive drop-arm test). Strength, other than during abduction, is intact. Which of the following is the most appropriate next step in management?

This patient most likely has a complete left supraspinatus rotator cuff tear and should undergo MRI of the left shoulder to confirm the diagnosis. The diagnosis is suggested by his difficulty abducting the left arm and the positive drop-arm test. The drop-arm test can be performed by the examiner passively abducting the patient's arm and then having the patient slowly lower the arm to the waist. When a complete supraspinatus tear is present, the patient's arm often drops to the waist. Although imaging is not necessary in most patients with uncomplicated shoulder pain, because of this patient's high likelihood of having a complete supraspinatus tear based on history and examination findings, it is appropriate to obtain an MRI to confirm the diagnosis. MRI has a high sensitivity (98%) and specificity (79%) in the diagnosis of rotator cuff tears. Shoulder ultrasonography is another diagnostic option for rotator cuff tears in centers where it is available. Not all rotator cuff tears require surgical intervention and many respond to conservative therapy; however, establishing the diagnosis and obtaining more detailed anatomic information are necessary in deciding whether surgery is indicated. Medication with an a nonsteroidal anti-inflammatory drug may be part of the initial treatment plan, but a confirmed diagnosis is necessary to make definitive treatment decisions. Although referral to physical therapy is appropriate for patients with suspected or confirmed incomplete rotator cuff tears, it would not be the appropriate first step for this patient with a suspected complete tear who is young and has no medical comorbidities. A subacromial glucocorticoid injection is not the most appropriate option in this patient with a suspected complete supraspinatus rotator cuff tear. Subacromial glucocorticoid injections have been shown to provide pain relief that lasts up to 9 months in patients with rotator cuff tendinitis or an impingement syndrome, but a significant tear may require surgical intervention, and this should be determined as an initial step in management.

2

A 42-year-old man is evaluated for a 1-month history of a painful, swollen right finger and a swollen left toe. He has no other symptoms and generally feels well. He has not noticed a skin rash. Medical history is unremarkable, and his only medication is as-needed ibuprofen for his joint pain. On physical examination, vital signs are normal. The right third distal interphalangeal joint is swollen, with localized tenderness to palpation and pain with active and passive range of motion. The appearance of the nails is shown :. Examination of the left second toe shows fusiform swelling and mild diffuse tenderness with decreased active and passive range of motion. There is onycholysis of several toenails, including the left second toenail. The remainder of the examination is normal. Which of the following is the most likely diagnosis?

This patient has psoriatic arthritis, a systemic chronic inflammatory arthritis associated with numerous clinical manifestations. Typically, psoriasis predates the arthritis by years, whereas arthritis develops before skin disease in 15% of patients. Although there is a poor correlation between the severity of skin and joint disease, there is a good correlation between the severity of nail disease and the severity of both skin and joint disease. Psoriatic findings may also be limited to nail pitting and onycholysis. There are five patterns of joint involvement in psoriatic arthritis: involvement of the distal interphalangeal joints; asymmetric oligoarthritis; symmetric polyarthritis (similar to that of rheumatoid arthritis); arthritis mutilans (extensive osteolysis of the digits with striking deformity); and spondylitis. Characteristic features of psoriatic arthritis include enthesitis (inflammation of sites where tendons or ligaments insert into bone), dactylitis (inflammation of an entire digit), and tenosynovitis (inflammation of the synovial sheath surrounding a tendon). This patient has findings characteristic of psoriatic arthritis, including inflammation of a distal interphalangeal joint and dactylitis of a toe. He also has nail changes, including pitting and onycholysis. Lyme arthritis typically involves medium- or large-sized joints rather than distal interphalangeal joints and does not typically cause tenosynovitis. Furthermore, this disorder does not cause nail changes, as seen in this patient. Osteoarthritis can involve the distal interphalangeal joints but does not cause dactylitis or nail changes. Rheumatoid arthritis can initially present with an asymmetric pattern, although it classically takes on a symmetric distribution with time. In contrast to this patient, patients with rheumatoid arthritis typically have sparing of the distal interphalangeal joints and preferential involvement of the proximal interphalangeal joints and metacarpophalangeal joints. In addition, rheumatoid arthritis also does not cause nail changes.

3

A 26-year-old man is hospitalized for a 2-month history of daily spiking fever, diffuse joint pain, myalgia, intermittent rash, and a 9-kg (20-lb) weight loss.

On physical examination, temperature is 38.4°C (101.2°F), blood pressure is 126/68 mm Hg, pulse rate is 92/min, and respiration rate is 16/min. There are enlarged cervical lymph nodes. A salmon-colored rash is noted on the trunk and proximal extremities. Abdominal examination discloses hepatomegaly. Musculoskeletal examination reveals tenderness of the wrists, knees, and ankles without swelling; there is decreased range of motion of the wrists.

Laboratory studies:

Hemoglobin

9.8 g/dL (98 g/L)

Leukocyte count

21,000/µL (21 × 109/L)

Platelet count

560,000/µL (560 × 109/L)

Erythrocyte sedimentation rate

102 mm/h

Aspartate aminotransferase

56 U/L (0.94 µkat/L)

Alanine aminotransferase

63 U/L (1.05 µkat/L)

Ferritin

5250 ng/mL (5250 µg/L)

Computed tomography of the chest, abdomen, and pelvis reveals diffuse lymphadenopathy. Bone marrow biopsy results are normal. Blood cultures are negative.

Which of the following is the most likely diagnosis?

This patient most likely has adult-onset Still disease (AOSD), a systemic inflammatory disorder characterized by quotidian (daily) fever, evanescent rash, arthritis, and multisystem involvement. Diagnosis is based on the typical clinical presentation and exclusion of infection and malignancy, particularly leukemia and lymphoma. Laboratory abnormalities in patients with AOSD include leukocytosis, anemia, thrombocytosis, elevated erythrocyte sedimentation rate, elevated serum ferritin level (≥1000 ng/mL [1000 µg/L]), and abnormal liver chemistry tests; antinuclear antibody titer and rheumatoid factor typically are negative.

Lymphadenopathy and fever may suggest lymphoma; however, the constellation of other signs and symptoms in this patient, as well as the negative bone marrow biopsy results, suggests AOSD. Furthermore, elevated serum ferritin levels are not associated with lymphoma or leukemia.

Patients with parvovirus B19 infection have arthritis and rash lasting days to weeks, often after a flu-like illness. Spiking fevers, lymphadenopathy, and an elevated leukocyte count and serum ferritin level are not associated findings.

Fever, arthritis, and lymphadenopathy occur in patients with systemic lupus erythematosus (SLE), but the presence of elevated (rather than decreased) leukocyte and platelet counts and the markedly elevated serum ferritin level point toward a diagnosis of AOSD. An evanescent, salmon-colored rash also is not associated with SLE.

4

A 31-year-old woman is evaluated for a 4-week history of left anterior knee pain. The pain developed insidiously and has progressively worsened, especially with prolonged sitting and walking up and down stairs. There is no morning stiffness. The patient has no history of trauma. She is taking acetaminophen as needed for the pain.

On physical examination, vital signs are normal. The pain is reproduced by applying pressure to the surface of the patella with the knee in extension and moving the patella both laterally and medially. There is no effusion, swelling, or warmth. Range of motion of the knee is normal, without crepitus or pain.

Which of the following is the most likely diagnosis?

This patient most likely has patellofemoral pain syndrome, the most common cause of knee pain in patients younger than age 45 years. Patellofemoral pain syndrome is a clinical diagnosis, and additional diagnostic testing such as radiography is not necessary. Patellofemoral pain syndrome is more common in women and is characterized by anterior knee pain that is made worse with prolonged sitting and with going up and down stairs. The pain is reproduced by applying pressure to the patella with the knee in extension and moving the patella both medially and laterally (patellofemoral compression test).

According to the American College of Rheumatology's clinical criteria, osteoarthritis of the knee can be diagnosed if knee pain is accompanied by at least three of the following features: age greater than 50 years, morning stiffness lasting less than 30 minutes, crepitus, bone tenderness, bone enlargement, and no palpable warmth. These criteria are 95% sensitive and 69% specific for a diagnosis of osteoarthritis but have not been validated for use in clinical practice. Crepitus of the knee is common in patients with osteoarthritis between the patella and the femur. Passive range of motion of the knee often elicits pain at the extremes of flexion and extension. Palpation of the knee discloses only mild tenderness. This patient has no clinical evidence of knee osteoarthritis.

Pes anserine bursitis characteristically produces pain that is located near the anteromedial aspect of the proximal tibia. On examination, tenderness is elicited at the level of the tibial tuberosity (approximately 3.8 cm [1.5 in] below the level of the medial joint line). Swelling may be present at the insertion of the medial hamstring muscles. This patient's presentation is not consistent with pes anserine bursitis.

Prepatellar bursitis is often caused by recurrent trauma, such as repeated kneeling (“housemaid's knee”) but can also be caused by infection or gout. Although the pain is located anteriorly, examination reveals swelling, tenderness to palpation (usually localized near the lower pole of the patella), and erythema, all of which are lacking in this patient.

5

A 35-year-old woman is evaluated for a 1-week history of right knee pain that began when she jumped from a 4-foot height and twisted her knee. At the time she felt a popping sensation; her knee became swollen over the next several hours. She has continued to have moderate pain, particularly when walking up or down stairs. There is no locking or “giving way” of the knee. She reports no previous knee injury.

On physical examination, vital signs are normal. The right knee has a minimal effusion. There is full range of motion. The medial aspect of the joint line is tender to palpation. Maximally flexing the hip and knee and applying abduction (valgus) force to the knee while externally rotating the foot and passively extending the knee (McMurray test) results in a palpable snap.

Which of the following is the most likely diagnosis?

The patient's history is suspicious for a meniscal tear. Patients typically describe a twisting injury with the foot in a weight-bearing position, in which a popping or tearing sensation is often felt, followed by severe pain. Swelling occurs over several hours, in contrast to ligamentous injuries, in which swelling is immediate. Patients with meniscal tears may report a clicking or locking of the knee secondary to loose cartilage in the knee but often have pain only on walking, particularly going up or down stairs. Although no clinical maneuver is able to definitively diagnose or exclude a meniscal tear, pain along the joint line is 76% sensitive for a meniscal tear, and an audible pop or snap on the McMurray test is 97% specific for such a tear.

Anserine bursitis is characterized by pain and tenderness over the anteromedial aspect of the lower leg below the joint line of the knee. The location of this patient's pain and her abnormal physical examination findings do not support the diagnosis of anserine bursitis.

Ligamentous damage, such as an anterior cruciate ligament tear, usually occurs as a result of forceful stress or direct blows to the knee while the extremity is bearing weight. Excessive medial rotation with a planted foot stresses the anterior cruciate ligament. A popping or tearing sensation is frequently reported in patients with ligamentous damage. This patient's physical examination findings, particularly the result of the McMurray test, support a diagnosis of a meniscal, rather than a ligamentous, injury.

Patellofemoral pain syndrome is the most common cause of chronic knee pain in active adults, particularly women, younger than age 45 years. The exacerbation of the pain by going down steps and the development of knee stiffness and pain at rest when the knee is flexed for an extended period of time are clues to the diagnosis. Reproducing the pain by firmly moving the patella along the femur confirms the diagnosis. This patient's history and physical examination findings are consistent with acute injury to the meniscus rather than the patellofemoral pain syndrome.

6

A 38-year-old woman is evaluated for left knee pain that has been present for the past 3 weeks. Before onset, she had been preparing for a 5-kilometer race by running approximately 2 miles each day, 6 days each week, for the past 6 months. Walking up stairs makes the pain worse; she also notes pain at night. She has never had this pain before.

On physical examination, vital signs are normal. There is tenderness to palpation located near the anteromedial aspect of the proximal tibia. A small amount of swelling is present at the insertion of the medial hamstring muscle. There is no medial or lateral joint line tenderness.

Which of the following is the most likely diagnosis?

This patient most likely has pes anserine bursitis. Although pes anserine bursitis most commonly occurs in patients with medial compartment osteoarthritis, it also occurs in the setting of overuse, as in this patient. The pain is typically located along the anteromedial aspect of the proximal tibia distal to the joint line of the knee. Pain is worse with climbing stairs and frequently worsens at night.

Iliotibial band syndrome is a common cause of knife-like lateral knee pain that occurs with vigorous flexion-extension activities of the knee, such as running. It is treated conservatively with rest and stretching exercises. This patient's presentation is not consistent with iliotibial band syndrome, as her pain is located medially. Also, the pain with iliotibial band syndrome is characteristically worsened with walking both up and down stairs, which this patient does not report.

The most common cause of knee pain in persons younger than age 45 years, especially in women, is the patellofemoral pain syndrome. The pain is peripatellar and exacerbated by overuse (such as running), descending stairs, or prolonged sitting. On examination, pain can often be elicited by applying pressure on the patella (the patellofemoral compression test).

Patients with prepatellar bursitis present with pain in the anterior aspect of the knee. On examination, swelling and tenderness to palpation are frequently present near the lower pole of the patella.

7

A 42-year-old woman is evaluated for a 10-day history of posterior and superior right shoulder pain that becomes worse with overhead activities. The patient recently painted her basement ceiling but reports no history of trauma. She has no arm weakness or paresthesia. She has been taking ibuprofen as needed for pain relief.

On physical examination, vital signs are normal. There is no shoulder asymmetry and no tenderness to palpation of bony structures or soft-tissue structures. There is full range of motion (other than with internal rotation, which is limited by pain), and strength is 5/5 throughout the right arm, with sensation intact. She is able to slowly lower her extended arm from over her head to her side (negative drop-arm test). Pain occurs with abduction of the right arm between 60 and 120 degrees.

Which of the following is the most likely diagnosis?

This patient most likely has rotator cuff impingement syndrome caused by underlying tendinitis. She presents with pain in her shoulder that began after performing the repetitive overhead motion of painting, and her pain is most pronounced with abduction of her arm. On examination, her pain occurs between 60 and 120 degrees of abduction, which supports the diagnosis of rotator cuff tendinitis. Rotator cuff tendonitis is often caused by an impingement syndrome in which the greater tuberosity of the humerus pushes against the coraco-humeral ligament, trapping the intervening structures and causing inflammation. This syndrome may be identified by the Hawkins test in which the patient is examined with the arm at 90° and the elbow flexed to 90°, supported by the examiner to ensure maximal relaxation. The examiner then stabilizes the elbow with their outside hand and with the other holds the patient's arm just proximal to the wrist. The arm is then quickly internally rotated. This test has a sensitivity for detecting impingement of >90%, although it has a significantly lower specificity. Treatment is typically with physical therapy and specific exercises.

Acromioclavicular joint degeneration is typically associated with trauma (in younger patients) or osteoarthritis (in older patients). Palpable osteophytes may be present, and radiographs, if obtained, may show degenerative changes. Acromioclavicular joint degeneration characteristically presents with pain that occurs with shoulder adduction and abduction above 120 degrees. This diagnosis is unlikely in this patient given that she has no history of trauma and that there is no acromioclavicular joint tenderness on examination.

Adhesive capsulitis is caused by thickening of the capsule surrounding the glenohumeral joint. Adhesive capsulitis is characterized by loss of both passive and active range of motion in multiple planes and patient-reported stiffness, which are not present in this patient. Also, pain is typically slow in onset and is located near the insertion of the deltoid muscle.

Rotator cuff tears are usually accompanied by weakness and loss of function. Examination findings include supraspinatus muscle weakness, weakness with external rotation, and a positive drop-arm test. The absence of weakness and the negative drop-arm test argue against the presence of a rotator cuff tear in this patient.

8

A 29-year-old man is evaluated for a 1-day history of left shoulder pain. He was throwing a football when the pain began. The pain is located over the left lateral deltoid muscle and is associated with weakness with arm abduction. The patient has no previous history of shoulder problems and no history of trauma. He has been taking ibuprofen as needed for pain.

On physical examination, temperature is normal, blood pressure is 126/80 mm Hg, and pulse rate is 96/min. There is pain in the left shoulder with active abduction beginning at approximately 60 degrees, and he has difficulty actively abducting the left arm beyond 60 degrees. The patient is unable to slowly lower his left arm to his waist (positive drop-arm test). Strength, other than during abduction, is intact.

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

This patient most likely has a complete left supraspinatus rotator cuff tear and should undergo MRI of the left shoulder to confirm the diagnosis. The diagnosis is suggested by his difficulty abducting the left arm and the positive drop-arm test. The drop-arm test can be performed by the examiner passively abducting the patient's arm and then having the patient slowly lower the arm to the waist. When a complete supraspinatus tear is present, the patient's arm often drops to the waist. Although imaging is not necessary in most patients with uncomplicated shoulder pain, because of this patient's high likelihood of having a complete supraspinatus tear based on history and examination findings, it is appropriate to obtain an MRI to confirm the diagnosis. MRI has a high sensitivity (98%) and specificity (79%) in the diagnosis of rotator cuff tears. Shoulder ultrasonography is another diagnostic option for rotator cuff tears in centers where it is available. Not all rotator cuff tears require surgical intervention and many respond to conservative therapy; however, establishing the diagnosis and obtaining more detailed anatomic information are necessary in deciding whether surgery is indicated.

Medication with an a nonsteroidal anti-inflammatory drug may be part of the initial treatment plan, but a confirmed diagnosis is necessary to make definitive treatment decisions.

Although referral to physical therapy is appropriate for patients with suspected or confirmed incomplete rotator cuff tears, it would not be the appropriate first step for this patient with a suspected complete tear who is young and has no medical comorbidities.

A subacromial glucocorticoid injection is not the most appropriate option in this patient with a suspected complete supraspinatus rotator cuff tear. Subacromial glucocorticoid injections have been shown to provide pain relief that lasts up to 9 months in patients with rotator cuff tendinitis or an impingement syndrome, but a significant tear may require surgical intervention, and this should be determined as an initial step in management.

9

An 83-year-old man is evaluated for poorly controlled pain from osteoarthritis of the left knee. Osteoarthritis was diagnosed 15 years ago, and his pain had been controlled until recently with regular doses of acetaminophen. Over the past 8 weeks, acetaminophen has no longer provided relief. There is no history of trauma, and he does not have fever or chills. Medical history is significant for hypertension, chronic kidney disease, and a healed peptic ulcer. Medications are amlodipine and metoprolol.

On physical examination, vital signs are normal. Body mass index is 26. The left knee has a moderate-sized, ballottable effusion without overlying erythema or warmth. There is crepitus with knee flexion and extension. The remainder of the examination is unremarkable.

Which of the following is the most appropriate treatment?

The most appropriate treatment at this time is to perform arthrocentesis followed by an intra-articular glucocorticoid injection. In patients with osteoarthritis in whom a single joint or several joints cause pain that is disproportionate to pain in other joints and limits function, intra-articular glucocorticoids may be effective in providing pain relief and improving function. The degree and duration of pain relief vary by patient; furthermore, there is no good method for identifying who might respond well to this therapy. Successful injections provide pain relief for an average of 3 months. Risks of injection, including pain, bleeding, and infection, should be discussed with the patient before the injection. Potential long-term risks from repeated injections may occur, including atrophy of the cartilage. Therefore, the general recommendation calls for no more than three injections per year in a single joint. Rare adverse effects include fat atrophy and depigmentation of the skin. Intra-articular injection may be particularly useful in patients who obtain no relief from acetaminophen and have contraindications to the use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as this patient who has chronic kidney disease, hypertension and a history of peptic ulcer disease.

Diclofenac is an NSAID and should be avoided in this patient for multiple reasons, including his history of advanced chronic kidney disease, hypertension and distant history of peptic ulcer disease. In younger patients without these comorbidities, NSAIDs are reasonable second-line treatment if acetaminophen has failed to provide relief.

Celecoxib is a cyclooxygenase-2–specific inhibitor. Although celecoxib may decrease the risk of gastrointestinal side effects, it has similar effects on the kidney and blood pressure as nonselective NSAIDs and should therefore be avoided in this patient.

A 2010 meta-analysis of the effects of glucosamine sulfate, chondroitin, and the combination of glucosamine sulfate and chondroitin concluded that these drugs alone or in combination were no more effective than placebo in controlling knee or hip pain due to osteoarthritis.

10

A 69-year-old woman is evaluated for pain in her thumbs for the past 3 months, with the right being worse than the left. She describes the pain as a dull ache at the base of her thumbs. The pain is most pronounced early in the morning, improves after she has been up and active for about 20 minutes, and recurs with repetitive use of her hands later in the day. She does not have swelling, fever, chills, or any other symptoms.

On physical examination, vital signs are normal. There is tenderness at the base of both thumbs to palpation. Her left thumb is shown :.

Which of the following is the most likely diagnosis?

Q image thumb

The most likely diagnosis is osteoarthritis. Osteoarthritis is the most common form of arthritis, and the incidence increases with age. Common sites of osteoarthritis in the hand include the first carpometacarpal joint (base of the thumb), as well as the distal and proximal interphalangeal joints. Involvement of the carpometacarpal joint leads to “squaring” of the contour of the joint, as seen in the image. Systemic symptoms are generally absent in patients with osteoarthritis. Typically, these patients have morning joint stiffness that persists for less than 30 minutes, whereas patients with inflammatory arthritis generally have a longer duration of morning stiffness.

de Quervain tenosynovitis is caused by inflammation of the abductor pollicis longus and extensor pollicis brevis tendons in the thumb. It is usually associated with repetitive use of the thumb but can also be associated with other conditions, including pregnancy, rheumatoid arthritis, and calcium apatite deposition disease. The typical presentation is of pain on the radial aspect of the wrist that occurs when the thumb is used to pinch or grasp. Examination findings include localized tenderness over the distal portion of the radial styloid process and pain with resisted thumb abduction and extension. The patient's findings are not consistent with de Quervain tenosynovitis.

Ganglion cysts, swellings that overlie either joints or tendons most typically on the dorsal surface, develop as a result of chronic irritation of the wrist. If the cyst is not painful, no intervention is required. A ganglion cyst would not explain this patient's symptoms at the base of the thumb or the squaring of the first carpometacarpal joint.

Rheumatoid arthritis is an inflammatory arthritis that typically causes a symmetric, inflammatory arthritis often involving the proximal interphalangeal joints and the metacarpophalangeal joints. Although rheumatoid arthritis is more common in women than in men, patients tend to have a younger age of presentation than the patient described here and should have a longer duration of morning stiffness, as well as objective signs of inflammation (synovitis, swollen joints), findings that are absent in this patient. Squaring of the first carpometacarpal joint is not characteristic of rheumatoid arthritis.

11

A 52-year-old man is evaluated for a 5-year history of gradually progressive left knee pain. The patient has 20 minutes of morning stiffness that recurs after prolonged inactivity. He has minimal to no pain at rest and no clicking or locking of the knee. Over the past several months, the pain has limited ambulation so that he can only walk a few blocks.

On physical examination, vital signs are normal. Body mass index is 25. The left knee has a small effusion without erythema or warmth. Range of motion of the knee elicits crepitus. There is medial joint line tenderness to palpation, bony hypertrophy, and a moderate varus deformity. There is no evidence of joint instability on stress testing.

Radiographs of the knee reveal bone-on-bone joint-space loss and numerous osteophytes.

Which of the following diagnostic studies should be done next?

No additional diagnostic testing is indicated for this patient who has osteoarthritis, which is a clinical diagnosis. According to the American College of Rheumatology's clinical criteria, knee osteoarthritis can be diagnosed if knee pain is accompanied by at least three of the following features: age greater than 50 years, stiffness lasting less than 30 minutes, crepitus, bone tenderness, bone enlargement, and no palpable warmth. These criteria are 95% sensitive and 69% specific for diagnosis. Additional diagnostic testing is not appropriate because it has no impact on the management of advanced disease.

Computed tomography (CT) of the knee is very sensitive for detecting pathologic findings in bone and can be used to look for evidence of an occult fracture, osteomyelitis, or bone erosions. However, none of these are suspected in this patient.

Small- to moderate-sized effusions can occur in patients with osteoarthritis, and the fluid is typically noninflammatory. Joint aspiration in this patient without evidence of joint inflammation and evident osteoarthritis is not useful diagnostically but is often done in the context of intra-articular glucocorticoid injections.

Magnetic resonance imaging (MRI) is useful to evaluate soft-tissue structures in the knee such as meniscal tears. Patients with meniscal tears may report a clicking or locking of the knee secondary to loose cartilage but often have pain only on walking, particularly going up or down stairs. Patients with degenerative arthritis often have MRI findings that indicate meniscal tears. These tears are part of the degenerative process but do not impact management; arthroscopic knee surgery for patients with osteoarthritis provides no clinical benefit. The one exception may be in patients with meniscal tears that result in a free flap or loose body, producing painful locking of the joint. These findings are not present in this patient.

12

A 76-year-old woman is evaluated for a 3-month history of moderate left knee pain that worsens with ambulation. She reports minimal pain at rest and no nocturnal pain. There are no clicking or locking symptoms. She has tried naproxen and ibuprofen but developed dyspepsia; acetaminophen provides mild to moderate pain relief. Medical history is significant for hypertension. Medications are lisinopril and as-needed acetaminophen.

On physical examination, vital signs are normal. Body mass index is 32. Range of motion of the left knee elicits crepitus. There is a small effusion without erythema or warmth. Tenderness to palpation is present along the medial joint line. Testing for meniscal or ligamentous injury is negative.

Radiographs of the knee reveal medial tibiofemoral compartment joint-space narrowing and sclerosis; small medial osteophytes are present.

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

Weight loss and exercise are indicated for this patient with knee osteoarthritis. Her knee pain, which is worse with weight bearing, is suggestive of tibiofemoral osteoarthritis, a diagnosis supported by the presence of medial joint line tenderness and radiographic findings of medial tibiofemoral compartment joint-space narrowing. The strongest risk factors for osteoarthritis are advancing age, obesity, female sex, joint injury (caused by occupation, repetitive use, or actual trauma), and genetic factors. Obesity, in particular, is the most important modifiable risk factor for knee osteoarthritis. Several trials have demonstrated that weight loss and/or exercise programs can provide relief of pain and improved function comparable to the benefits of nonsteroidal anti-inflammatory drug (NSAID) use. In long-term studies, sustained weight loss of approximately 6.8 kg (15 lb) has resulted in symptomatic relief.

Celecoxib, a cyclooxygenase-2 (COX-2)–specific inhibitor, has a lower risk of causing gastrointestinal ulcers than nonselective NSAIDs but can still cause dyspepsia, which occurred in this patient after taking naproxen and ibuprofen. COX-2 inhibitors are not more effective than nonselective NSAIDs, are significantly more expensive, and are associated with an increased risk for adverse cardiovascular events. Therefore, celecoxib would not be a preferred treatment for this patient.

Although glucosamine sulfate is commonly used in the management of osteoarthritis, multiple studies have failed to document its effectiveness in reducing pain or affecting the course of the disease.

Magnetic resonance imaging of the knee is indicated to evaluate possible meniscal or other ligamentous injuries, none of which is suggested by this patient's history (no knee locking or “giving way”) or examination findings (negative examination for tendinous or ligamentous injury).

13

A 38-year-old man is evaluated during a follow-up examination. An abnormal serum uric acid level of 7.9 mg/dL (0.47 mmol/L) was obtained at a health screening performed at his place of employment. All other measures from the comprehensive metabolic profile were normal. He drinks two alcoholic beverages each weekend and eats meat several times weekly. Medical history is otherwise unremarkable, and he takes no medications. Family history is notable for his father who has gout.

On physical examination, vital signs are normal. Body mass index is 24. The remainder of the examination is normal.

Which of the following is the most appropriate treatment at this time?

No treatment is required for this patient with asymptomatic hyperuricemia. This condition is characterized by a moderately elevated serum uric acid level without evidence of symptoms of gout. Patients with asymptomatic hyperuricemia have an increased risk for gout over the long term but a low likelihood of a gout attack in the short term; thus, a pharmacologic intervention at this time is not indicated. Although studies suggest that hyperuricemia may contribute to several comorbidities (hypertension, kidney disease, cardiovascular disease), there is not yet consensus that these risks are sufficient to independently warrant chronic urate-lowering therapy. In patients with asymptomatic hyperuricemia, dietary and lifestyle considerations are always worth reviewing. Decreasing consumption of high-purine foods (particularly meat and seafood), alcohol, and high-fructose foods may lower serum uric acid concentrations. An increase in dairy consumption, as well as weight loss (if indicated), may also help lower serum uric acid concentrations. In making recommendations for lifestyle changes, the ability of the patient to comply should always be taken into account.

Allopurinol is an effective urate-lowering agent used to treat symptomatic hyperuricemia. Colchicine is an anti-inflammatory agent that can treat or prevent gout attacks. Probenecid is a uricosuric drug that is also used to treat symptomatic hyperuricemia. All of these agents may be helpful in treating patients with gout; however, based on this patient's findings, none of these treatment options is warranted at this time.

The diuretic hydrochlorothiazide is used to treat hypertension and promotes increases in serum uric acid concentration by inhibiting kidney urate excretion; this patient does not have hypertension, and such a strategy would increase his risk of future gout attacks while providing no specific benefit. In patients who are taking thiazide diuretics and require urate lowering, switching to an alternative antihypertensive agent that does not raise the serum uric acid concentration is a reasonable intervention.

14

A 59-year-old man is evaluated for a 10-year history of gout. He is currently asymptomatic but has had four to five attacks per year over the past 3 years. The patient's only medication is ibuprofen as needed for gout attacks.

On physical examination, vital signs are normal. The general physical examination is normal. The joint examination is unremarkable, and no tophi are seen.

Results of laboratory studies, including complete blood count, metabolic profile, and liver chemistry tests, are normal; the erythrocyte sedimentation rate is 16 mm/h, and the serum uric acid level is 9.2 mg/dL (0.54 mmol/L).

Radiographs of the hands and feet are normal.

Which of the following is the most appropriate treatment to prevent further gout flares in this patient?

This patient should be started on allopurinol and colchicine. He has frequent, symptomatic gout attacks, and treatment with urate-lowering therapy such as allopurinol is indicated. Gout manifests as acute, intermittent attacks of severe pain, redness, and swelling of a joint accompanied by intracellular urate crystals seen on polarized light microscopy of the synovial fluid. For acute gout attacks, nonsteroidal anti-inflammatory drugs, glucocorticoids, and colchicine are appropriate management strategies; choice of treatment is based on relative efficacy and, most importantly, the side-effect profiles of the agents and the risk of toxicity in the individual patient.

Because gout is associated with hyperuricemia, patients with recurrent episodes (≥2 attacks in 1 year) usually benefit from urate-lowering therapy to prevent both future attacks and occult urate deposition. However, the addition of urate-lowering therapy transiently increases the risk for acute gout attacks for at least 3 to 6 months; accordingly, prophylaxis with an anti-inflammatory agent such as colchicine, at least during that period, is indicated concurrent with urate-lowering therapy.

Along with this treatment regimen, management of risk factors can help to lower serum uric acid concentrations, including reducing dietary purine and fructose and increasing dairy intake (within the limits of individual tolerance), weight loss if indicated, and reducing alcohol consumption. Medications that raise serum uric acid levels, including thiazide diuretics and low-dose salicylates, should be discontinued if alternative therapy is appropriate.

Use of either allopurinol or febuxostat would be appropriate but only in the setting of concurrent prophylaxis. The dose of both febuxostat and allopurinol should be adjusted to achieve a serum uric acid level ≤6.0 mg/dL (0.35 mmol/L), rather than a fixed dose. The relative effectiveness of these two agents is not well established; febuxostat is more potent on a per-mole basis but is also more expensive than allopurinol.

Treatment with colchicine alone might lower the risk of gout attacks in this patient but would not address the underlying problem of urate deposition, which would likely worsen progressively over time.

15

A 74-year-old woman is evaluated for a 2-year history of progressive pain of the fingers and knees, along with morning stiffness lasting 20 minutes. She has no other pertinent personal or family medical history. Her only medication is acetaminophen as needed for pain.

On physical examination, vital signs are normal. Musculoskeletal examination reveals tenderness, erythema, some soft-tissue swelling, and bony hypertrophy of the second and third metacarpophalangeal joints bilaterally. Bony hypertrophy and fluctuance of the knees are noted bilaterally.

Results of laboratory studies, including erythrocyte sedimentation rate, serum ferritin and serum iron levels, and transferrin saturation, are normal. Rheumatoid factor and anti–cyclic citrullinated peptide antibody assay are negative.

Radiographs of the hands reveal joint-space narrowing, particularly of the second and third metacarpophalangeal joints; osteophytes; subchondral sclerosis; and linear calcification of the cartilage. Radiographs of the knees show diffuse joint-space narrowing with osteophytes and cartilaginous calcification.

Which of the following is the most likely diagnosis?

This patient has chronic calcium pyrophosphate dihydrate (CPPD) deposition disease, sometimes referred to as calcium pyrophosphate arthropathy. CPPD deposition disease is a clinical diagnosis made by observing typical osteoarthritis features along with radiographic evidence of calcium deposition in the cartilage (chondrocalcinosis) in locations atypical for osteoarthritis, such as the metacarpophalangeal joints. A chronic inflammatory condition may result, leading to progressive joint destruction. This patient has polyarthritis with radiologic findings that resemble osteoarthritis (subchondral sclerosis and osteophytes); however, involvement includes the second and third metacarpophalangeal joints, which are not typically involved in osteoarthritis. There also is evidence of calcium deposition in the cartilage of the affected joints. This constellation of findings is pathognomonic for CPPD deposition disease. Although this patient has not had acute gout-like attacks, termed pseudogout, an acute inflammatory arthritis may be caused by calcium pyrophosphate crystals in the joints.

Hemochromatosis may overlap with CPPD deposition disease and can cause osteoarthritis-like arthritis in atypical joints. However, this patient has no evidence of iron overload (normal serum ferritin, iron, and transferrin saturation values) that is characteristic of hemochromatosis.

Although this patient has radiographic findings consistent with osteoarthritis, the involvement of metacarpophalangeal joints and the presence of chondrocalcinosis are not typical for this disorder.

This patient's findings, including involvement of only the second and third metacarpophalangeal joints; limited morning stiffness and soft-tissue swelling; negative rheumatoid factor and anti–cyclic citrullinated peptide antibody assay results; and no marginal erosions or periarticular osteopenia, do not support a diagnosis of rheumatoid arthritis.

16

A 30-year-old woman is evaluated in the emergency department for a 2-day history of fever and progressive swelling and pain of the right knee. The patient fell 2 weeks ago and abraded both knees. She later developed cellulitis over the left knee and was treated with a first-generation cephalosporin for 7 days with resolution of the infection. She is otherwise healthy and takes no medications.

On physical examination, temperature is 38.1°C (100.5°F); other vital signs are normal. Healing abrasions are noted on the anterior surfaces of both knees; there are no rashes or other skin lesions. The right knee is swollen, erythematous, warm, and exquisitely tender with markedly diminished range of motion but no instability.

Radiographs of the right knee reveal soft-tissue swelling and a large effusion but no bony changes.

Which of the following is the most likely diagnosis?

This patient has Staphylococcus aureus infection. Gram-positive microorganisms are the most frequent causes of infectious arthritis, with S. aureus being the most common. These infections typically are monoarticular, affect the large joints (particularly the knee), and have a rapid onset (hours or 1 to 2 days). This otherwise healthy patient has an acute arthritis following a skin break with cellulitis over the knee, consistent with hematogenous spread of a skin-derived infection. The presence of fever, along with a markedly swollen and inflamed joint, is consistent with S. aureus infection.

Acute gouty arthritis typically is monoarticular and frequently involves the knee; however, gout is exceedingly rare in healthy premenopausal women.

Anterior cruciate ligament tear can cause acute swelling, but the joint is usually less inflamed, and this condition is not associated with fever. This patient's knee was not injured after her fall, making this diagnosis unlikely. In addition, an anterior cruciate ligament tear causes anterior instability (assessed using the anterior drawer and Lachman tests), whereas this patient's knee remained stable.

Although chronic Lyme arthritis can manifest as monoarticular arthritis of the lower extremity, the onset is typically gradual, rather than acute, and is not associated with fever.

17

A 77-year-old woman is evaluated in follow-up for a prosthetic joint infection. Three years ago, she underwent right total knee replacement to treat osteoarthritis. Three days ago she developed right knee pain and swelling around the knee, and a low-grade fever. A synovial fluid aspirate was obtained and sent for culture, and empiric intravenous vancomycin was started. Her culture grew methicillin-sensitive Staphylococcus aureus.

On physical examination today, temperature is 38.0°C (100.4°F); other vital signs are normal. There is a well-healed surgical scar overlying the right knee. The knee is slightly warm with pain on passive range of motion.

Laboratory studies are significant for a leukocyte count of 13,000/µL (13 × 109/L), with 88% neutrophils, and an erythrocyte sedimentation rate of 88 mm/h.

Radiographs of the right knee show prosthetic loosening and periprosthetic lucency of the femur.

In addition to switching to intravenous nafcillin, which of the following is the most appropriate next step in management?

This patient has a prosthetic knee joint infection caused by methicillin-sensitive Staphylococcus aureus and requires surgical removal of the prosthesis. This patient's findings, including joint pain and elevated leukocyte count, elevated erythrocyte sedimentation rate (ESR), along with positive synovial fluid cultures, prosthetic loosening, and periprosthetic bone erosion, are consistent with prosthetic joint infection.

Prosthetic joints may become infected late after implantation (>3 months to years) via hematogenous spread of microorganisms or a delayed response to low-intensity pathogens. The joint may be swollen and inflamed or only painful. Leukocyte counts may be only modestly elevated; inflammatory markers such as the ESR or C-reactive protein (CRP) are usually elevated. Radiographs may reveal erosion or loosening around the implantation site. Diagnosis requires synovial fluid aspiration or open debridement, along with Gram stain and cultures. Treatment of prosthetic joint infection typically involves removal of the infected prosthesis, and is required for late infection or with infection-related dysfunction of the prosthesis, such as loosening. After removal, an antibiotic spacer is often inserted, and long-term (weeks to months) antibiotic therapy is initiated. Reimplantation can only be considered after complete resolution of the infection.

Surgical debridement alone with a prolonged course of antibiotics may be curative in some selected cases of early prosthetic joint infection. However, dysfunction of the prosthesis and late presentation, both features in this patient, make this approach inappropriate.

Some evidence suggests that adding rifampin to treatment with sensitive antibiotics may improve outcomes in patients with methicillin-sensitive S. aureus prosthetic joint infection who undergo early extensive surgical debridement in an attempt to preserve the prosthesis. However, this patient is not a candidate for this approach, and rifampin is therefore not indicated.

Intravenous vancomycin is useful for treating infection with methicillin-resistant S. aureus and was a reasonable initial choice for antibiotic therapy pending culture results. However, this patient has methicillin-sensitive S. aueus infection, which should respond to nafcillin or oxacillin along with joint removal, and no additional benefit from vancomycin would be expected. Additionally, except in specific cases, there is no evidence that dual antibiotic therapy is more effective than treatment with a single antibiotic agent to which the infecting organism is sensitive.

18

A 24-year-old woman is evaluated in the emergency department for a 5-day history of fever and right knee pain. Over the past 2 days, the left ankle and right wrist have also become painful and swollen. The patient was previously well and has no history of trauma. Her only medication is an oral contraceptive.

On physical examination, temperature is 38.4°C (101.2°F); other vital signs are normal. The right wrist is swollen, erythematous, warm, and painful. The dorsum of the right hand is swollen, erythematous, and warm with tenderness to direct palpation and minimal ability to move the fingers. The right knee is tender to palpation with a moderate effusion. The left ankle is tender, and the dorsum of the foot is swollen and tender. Findings on examination of the skin are shown :.

Arthrocentesis of the knee shows a synovial fluid leukocyte count of 14,400/µL (14.4 × 109/L), with 85% neutrophils. The synovial fluid is negative for crystals, and Gram stain and cultures are negative.

Which of the following is the most likely diagnosis?

Q image thumb

This patient has disseminated gonococcal infection with associated gonococcal arthritis. This form of infectious arthritis most commonly occurs in young, sexually active adults, particularly women. Disseminated gonococcemia is characterized by a prodrome of tenosynovitis, migratory or additive polyarthralgia, and cutaneous lesions that progress from papules or macules to pustules. Fever and rigors are common. As in this patient, subsequent frank arthritis can develop, affecting large and medium-sized joints and accompanied by tendinitis and papulopustular skin lesions. The leukocyte count is typically less than that of other types of bacterial arthritis, and Gram stain and culture results are usually negative.

Gout also may be highly inflammatory and polyarticular; however, it rarely occurs in premenopausal women, who typically have lower serum uric acid levels. Furthermore, the first attack of gout is rarely polyarticular, does not typically affect the wrists, usually involves the first metatarsophalangeal joint, and is not associated with papulopustular skin lesions.

Rheumatoid arthritis also is a systemic polyarticular disease. However, onset is typically more gradual; arthritic changes characteristically involve the proximal small joints of the hands; tendinitis is not present; and papulopustular skin lesions do not occur. Fever is not a common feature of rheumatoid arthritis.

Staphylococcal arthritis is the most common form of infectious arthritis and can damage joints rapidly. It is more common in children, older patients, and those with previously damaged joints, unlike this 24-year-old patient with no history of, or risk factors for, staphylococcal infection. Staphylococcal arthritis is usually monoarticular, does not cause tenosynovitis, and is not accompanied by systemic skin findings such as the classic papulopustular skin lesions of disseminated gonococcal infection.

19

A 49-year-old woman is evaluated for a 3-month history of progressive joint pain. She has bilateral hand, knee, and foot pain associated with 90 minutes of morning stiffness. Over the last 6 weeks, she has noted swelling in her hands. She now has functional limitations due to her disease. She cannot turn a door knob or open jars or walk more than 2 blocks because of pain. Ibuprofen provides minimal relief. She otherwise is well and takes no additional medications.

On physical examination, vital signs are normal. Musculoskeletal examination reveals tenderness and swelling of the first and second metacarpophalangeal and proximal interphalangeal joints and tenderness and swelling of the metatarsophalangeal joints and ankles. Her knees are noticeably swollen but without a clear effusion, and tender to palpation. The remainder of the examination is unremarkable.

Laboratory studies:

Erythrocyte sedimentation rate

58 mm/h

Rheumatoid factor

48 U/mL (40 kU/L)

Anti–cyclic citrullinated peptide antibodies

Positive

Parvovirus B19 IgM antibody

Negative

Hand radiographs show soft-tissue swelling without bone erosions or periarticular osteopenia.

Which of the following is the most appropriate therapy?

Methotrexate is indicated for this patient with early rheumatoid arthritis. She has synovitis; symmetric distribution of arthritis involving small joints of hands, feet, and ankles; an elevated erythrocyte sedimentation rate; and positive rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP) antibodies, which support the diagnosis of rheumatoid arthritis. Experts recommend that patients begin disease-modifying antirheumatic drugs (DMARDs) within 3 months of the onset of rheumatoid arthritis. The earlier that DMARDs are instituted, the more likely that damage from this condition will be limited. The initial choice of a DMARD is based on the severity of the inflammatory disease, the rate of disease progression, whether erosive disease is seen on radiographs, and whether a patient has anti-CCP antibody positivity. Use of methotrexate may benefit patients with early mild to moderate rheumatoid arthritis, but its use is imperative in patients with rapid disease progression or functional limitations. In the absence of contraindications, methotrexate should be instituted immediately in patients with erosive disease documented at disease onset. This agent can be used a monotherapy in patients with early disease, as it is highly effective, is well tolerated, is associated with high rates of adherence, and has a relatively low cost compared with other DMARDs.

Monotherapy with hydroxychloroquine or sulfasalazine or combination therapy with these agents is indicated to treat early, mild, and nonerosive disease. Hydroxychloroquine alone has not been shown to retard radiographic progression of rheumatoid arthritis and therefore should be used only in patients whose disease has remained nonerosive for several years. Sulfasalazine is an aspirin-like agent that is often used in combination with methotrexate or another nonbiologic DMARD when there is an inadequate response to therapy. Sulfasalazine is not indicated initially in this patient who has not had a trial of methotrexate therapy alone.

Infliximab is a tumor necrosis factor α inhibitor that is often used when patients do not respond to methotrexate or if they have advanced disease and a poor prognosis, such as early erosive disease.

20

A 65-year-old woman is evaluated for a 7-month history of hand, wrist, and knee pain. The joint pain is associated with morning stiffness that improves after 2 hours of activity. Naproxen provides some relief. The patient has had no recent illnesses, has no other medical problems, and takes no additional medications.

On physical examination, vital signs are normal. Bogginess is noted when palpating the metacarpophalangeal and proximal interphalangeal joints of the second through fifth digits of each hand. There is tenderness to palpation over the wrists. A right knee effusion with mild overlying erythema is present. A smaller knee effusion is present on the left. The patient has pain with range of motion in her fingers, wrists, right knee, and left shoulder. She has full range of motion of her back without any midline tenderness on palpation.

Aspiration of the right knee reveals a synovial fluid leukocyte count of 10,500/µL (10.5 × 109/L).

Which of the following is the most likely diagnosis?

The most likely diagnosis is rheumatoid arthritis. Morning stiffness lasting more than 60 minutes and a synovial fluid leukocyte count greater than 5000/µL (5 × 109/L) are typical of an inflammatory arthritis. Most patients with rheumatoid arthritis have a symmetric polyarthritis involving small, medium, and large joints. The wrists, the metacarpophalangeal and proximal interphalangeal joints of the hands, and the metatarsophalangeal joints of the feet are almost always affected. Early in the disease course, the oligoarthritis may be asymmetric in some joints but becomes symmetric as the disease progresses. Typically, the distal interphalangeal joints and lumbar spine are spared.

Ankylosing spondylitis is a spondyloarthritis that begins in the sacroiliac joints and lumbar spine and progresses cranially over time. There is a male predominance, and patients are typically between 20 and 30 years of age at presentation. Patients with inflammatory back pain and synovitis of peripheral joints should be evaluated for spondyloarthropathy.

Acute gout typically develops over hours and often starts at night. Early in the disease course, acute gouty attacks occur in single joints, typically the first metatarsophalangeal joint of the foot. Gouty attacks can occur in any joint and are associated with erythema, swelling, and pain of the affected joint. Patients may experience a low-grade fever. Patients with gout whose high serum uric acid levels go unmanaged are at risk for developing tophi, which are urate crystal deposits that are often surrounded by local inflammation. Patients with long-standing gout and established tophaceous disease typically have increased frequency of acute gouty attacks and may experience smoldering chronic arthritis. This patient has no characteristics of acute, tophaceous, or chronic gouty arthritis.

Osteoarthritis often affects the first metacarpophalangeal joint and the proximal and distal interphalangeal joints, knees, lumbar and cervical spine, and hips. Joint involvement tends to be asymmetric. Morning stiffness associated with noninflammatory osteoarthritis typically lasts less than 30 minutes. This patient's morning stiffness exceeds 60 minutes.

21

A 29-year-old woman is evaluated during a routine examination. She seeks advice about reducing her risk of developing rheumatoid arthritis because her mother was recently diagnosed with this disorder. The patient is asymptomatic. She has a 10-pack-year history of smoking and consumes six alcoholic beverages per week, usually on weekends. She is sedentary and overweight. Her only medication is an oral contraceptive.

On physical examination, vital signs are normal. Body mass index is 29. There is no synovitis or bony abnormalities. The remainder of the examination is normal.

Which of the following lifestyle modifications is most likely to reduce this patient's risk of developing rheumatoid arthritis?

Smoking is associated with an increased risk of developing rheumatoid arthritis, and cessation is therefore recommended for this and other health reasons. Hereditary factors convey susceptibility for developing rheumatoid arthritis, and changes in environmental factors seem to modify this risk. The duration and intensity of smoking correlate with the risk of developing rheumatoid arthritis. Users of smokeless tobacco do not have an increased risk of developing this disorder, suggesting that it is not simply an effect of nicotine. Smoking cessation is associated with a decline in the risk of developing rheumatoid arthritis, although this benefit is not immediate.

Alcohol use is not associated with an increased risk of rheumatoid arthritis. This patient may be advised to moderate her consumption of alcohol, but it will not alter her risk of developing this disorder.

Hormonal factors may play a role in developing rheumatoid arthritis. The risk is higher in women, but is not as high in women who have had children. Breastfeeding is associated with a decreased risk of developing rheumatoid arthritis and may account for some or all of the protective effect of parity. The risk of rheumatoid arthritis is inversely associated with duration of lifetime breastfeeding. Use of oral contraceptives may also be protective. In one study, use of oral contraceptives for 7 or more years was associated with a decreased risk of rheumatoid arthritis. Discontinuing oral contraceptives in this patient may be associated with increased risk or no change in her risk but not with a decreased risk of rheumatoid arthritis.

Obesity and sedentary lifestyle are associated with a number of health risks but have not been clearly linked to the development of rheumatoid arthritis. In patients with rheumatoid arthritis, range-of-motion exercises help preserve joint motion; in patients with osteoarthritis, aerobic exercise helps maintain muscle strength, joint stability, and physical performance, and weight reduction reduces stress on weight-bearing joints.

22

A 52-year-old man is evaluated for an 8-week history of bilateral hand pain. He also has 2 hours of morning stiffness of the hands that improves with activity. The patient has no pertinent personal or family medical history. He takes no medications.

On physical examination, vital signs are normal. Synovitis is noted at the metacarpophalangeal joints of the second through fifth digits bilaterally with swelling, tenderness, and pain on range of motion. The remainder of the examination is normal.

Laboratory studies are significant for a mild normochromic, normocytic anemia and erythrocyte sedimentation rate of 100 mm/h; rheumatoid factor is negative, and liver chemistry tests are normal.

Radiographs of the hands are normal.

Which of the following antibody assays would be most helpful in establishing this patient's diagnosis?

An anti–cyclic citrullinated peptide (anti-CCP) antibody assay is warranted for this patient in whom rheumatoid arthritis is suspected. Anti-CCP antibodies are present in approximately 40% to 60% of patients with early rheumatoid arthritis, including some patients with a negative rheumatoid factor. These antibodies are 95% specific for rheumatoid arthritis. The presence of higher titers of either rheumatoid factor or anti-CCP antibodies or the presence of both increases the likelihood of disease. Although this patient's rheumatoid factor is negative, rheumatoid arthritis remains a significant concern because he has synovitis of eight small joints and morning stiffness lasting more than 1 hour, common symptoms of rheumatoid arthritis. Additionally, he has evidence of systemic inflammation with an elevated erythrocyte sedimentation rate and mild anemia. Therefore, an anti-CCP antibody assay is appropriate to determine whether this patient's symptoms are caused by rheumatoid arthritis.

Antimitochondrial antibodies are present in patients with autoimmune hepatitis. Patients with this disease can develop arthralgia and arthritis similar to findings in this patient; however, he does not have liver chemistry test abnormalities that are characteristic of autoimmune hepatitis.

Antineutrophil cytoplasmic antibodies are typically associated with vasculitis such as granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), microscopic polyangiitis, Churg-Strauss syndrome, anti–glomerular basement membrane antibody disease, and drug-induced vasculitis. Arthritis and arthralgia can be associated with these syndromes; however, the presence of these vascular inflammatory disorders would be unusual in the absence of other systemic involvement.

Assay for antinuclear antibodies (ANA) can be clinically useful when there is clinical suspicion for autoimmune conditions associated with these antibodies, such as systemic lupus erythematosus (SLE). Patients with SLE may present with arthritis, but SLE is less likely than rheumatoid arthritis in the patient described here. SLE typically occurs in women of childbearing age and is associated with additional clinical and/or laboratory abnormalities rather than with isolated arthritis. ANA are present in some patients with rheumatoid arthritis but are not specific for this disorder.

23

A 33-year-old woman is evaluated during a follow-up examination. Rheumatoid arthritis was diagnosed 3 months ago, and methotrexate was begun at that time. The patient also takes ibuprofen and acetaminophen. Despite this treatment, she still has 2 to 3 hours of morning stiffness daily and wakes frequently during the night with pain and stiffness.

On physical examination, vital signs are normal. The neck and shoulders are stiff but have full range of motion. The wrists and metacarpophalangeal and metatarsophalangeal joints are tender bilaterally, and there is synovitis of the wrists. The left knee has a small effusion.

Laboratory studies show a hemoglobin level of 12.2 g/dL (122 g/L), platelet count of 460,000/µL (460 × 109/L), and erythrocyte sedimentation rate of 45 mm/h.

Radiographs of the hands show periarticular osteopenia and erosion of the right ulnar styloid.

Which of the following is the most appropriate next step in this patient's treatment?

This patient has early, aggressive rheumatoid arthritis, and the addition of etanercept is indicated. Methotrexate is the most commonly used and safest among the more effective disease-modifying antirheumatic drugs (DMARDs), has the greatest potential for modifying disease compared with hydroxychloroquine and sulfasalazine, and is central to most treatments for rheumatoid arthritis. Despite treatment with methotrexate, this patient has persistent morning stiffness, numerous tender and swollen joints, and an elevated erythrocyte sedimentation rate.

When adequate disease control is not achieved with one or more oral DMARDs, biologic therapy is indicated. The preferred initial biologic agent is a tumor necrosis factor α (TNF-α) inhibitor such as etanercept, which is usually added to baseline methotrexate therapy. Use of a TNF-α inhibitor in addition to methotrexate is significantly more effective in controlling joint damage and improving function compared with single-agent therapy with either medication alone. Screening for tuberculosis is indicated before beginning therapy with any biologic agent, and patients who test positive for latent tuberculosis should be treated with isoniazid before beginning this therapy.

Hydroxychloroquine is an effective agent in the treatment of early, mild, and nonerosive rheumatoid arthritis but most likely would not be beneficial in a patient with aggressive disease, functional limitations, and radiographic evidence of joint erosion. Even the addition of hydroxychloroquine to methotrexate is unlikely to be as helpful for treating erosive rheumatoid arthritis as is the combination of methotrexate and a TNF-α inhibitor.

Cyclophosphamide is not indicated for the treatment of active rheumatoid arthritis except in patients with rheumatoid vasculitis in whom major organ function is compromised. This patient does not have manifestations consistent with rheumatoid vasculitis, such as cutaneous ulcers and mononeuritis multiplex.

Sulfasalazine is often administered in combination with methotrexate and/or hydroxychloroquine in the treatment of early rheumatoid arthritis. Single-agent therapy with sulfasalazine also may be used when there are contraindications to the use of methotrexate. However, sulfasalazine is less effective than methotrexate in the treatment of rheumatoid arthritis and is not likely to benefit this patient if substituted for methotrexate.

24

A 52-year-old woman is evaluated for a 3-month history of fatigue, a photosensitive rash on her face, and hand pain accompanied by morning stiffness. She has no other pertinent personal or family medical history and takes no medications.

On physical examination, vital signs are normal. There is a 5-mm shallow ulcer on the hard palate. There is an erythematous rash across the cheeks and bridge of the nose. Tenderness of the metacarpophalangeal and proximal interphalangeal joints is noted; there is no swelling. The remainder of the examination is normal.

Initial laboratory studies, including complete blood count, erythrocyte sedimentation rate, and urinalysis, are normal. Antinuclear antibody assay results are positive with a titer of 1:160.

Which of the following tests is most specific for confirming this patient's diagnosis?

An anti–double-stranded DNA (anti-dsDNA) antibody assay has the greatest specificity for confirming a diagnosis in this patient, who has manifestations of systemic lupus erythematosus (SLE). She meets criteria for SLE because of the presence of positive antinuclear antibodies (ANA), along with arthritis, an oral ulcer, and photosensitive rash. Patients with a high pretest probability of SLE and positive ANA assay (usually a titer ≥1:160) should undergo confirmatory testing using a more specific autoantibody study with either an anti-dsDNA antibody assay or an anti-Smith antibody assay. Anti-dsDNA antibodies are present in approximately 50% to 70% of patients with SLE and generally are not found in those with other autoimmune diseases. The presence of anti-dsDNA antibodies is correlated with kidney disease in patients with SLE, and rising titers may precede disease flare. Anti-Smith antibodies, which are present in approximately 30% of patients with SLE, are also very specific for the disease. Patients with a new diagnosis of SLE should also undergo screening for anticardiolipin antibodies and the lupus anticoagulant.

Anti-Ro/SSA and anti-La/SSB antibodies are present in 10% to 60% of patients with SLE; however, these antibodies are less specific than anti-dsDNA antibodies because they can also be present in patients with rheumatoid arthritis, systemic sclerosis, and Sjögren syndrome.

Anti-U1-ribonucleoprotein (RNP) antibodies are found in patients with mixed connective tissue disease, which is characterized by features of systemic sclerosis, polymyositis, and SLE. The diagnosis requires the presence of high-titer RNP antibodies, generally in the absence of other autoantibodies. Positive RNP antibodies are also found in 30% to 40% of patients with SLE, but the test is less sensitive and specific than anti-dsDNA antibody testing. The presence of antiproteinase-3 antibodies, which produces a c-ANCA pattern on immunofluorescence testing, is suggestive of granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), a necrotizing vasculitis that typically affects the respiratory tract and kidneys. This test is not indicated, because this patient does not have findings consistent with granulomatosis with polyangiitis.

25

A 25-year-old woman is evaluated during a follow-up examination. The patient was first seen 3 months ago because of fatigue, a malar rash, and arthralgia. After laboratory confirmation of systemic lupus erythematosus, she was treated with hydroxychloroquine and a 1-month course of low-dose prednisone. She reports some improvement, although fatigue and joint pain continue.

On physical examination, temperature is 36.4°C (97.6°F), blood pressure is 148/95 mm Hg, pulse rate is 84/min, and respiration rate is 18/min. The facial rash has resolved, the joint examination is normal, and there is trace bipedal edema. The remainder of the examination is unremarkable.

Laboratory studies are significant for a serum creatinine level of 1.0 mg/dL (88.4 µmol/L) and a urinalysis showing 2+ protein; 3+ blood; 5-10 leukocytes/high-power field (hpf), 15-20 erythrocytes/hpf, and 1 erythrocyte cast/hpf. Serum complement levels (C3 and C4) are decreased.

Which of the following is the most appropriate next step in this patient's treatment?

This patient should be treated with high-dose glucocorticoid therapy such as prednisone. Her hypertension, ankle edema, hematuria, proteinuria, and erythrocyte casts on urinalysis are highly suggestive of lupus nephritis despite the absence of kidney insufficiency. To prevent irreversible kidney damage, early treatment with a high-dose glucocorticoid is indicated for patients whose condition raises strong suspicion for lupus nephritis. Whether kidney biopsy is necessary in order to establish a diagnosis remains uncertain, and treatment with high-dose glucocorticoids would not significantly alter subsequent biopsy results if a decision is made to pursue biopsy.

Ibuprofen may help to control this patient's arthralgia. However, nonsteroidal anti-inflammatory drugs can significantly worsen kidney function in patients with lupus nephritis and are therefore contraindicated in this patient population.

Initiation of antihypertensive therapy, such as lisinopril, would benefit this patient but is not the most appropriate next step in the management of her condition; treatment of her nephritis takes precedence and may itself help to control her hypertension. Angiotensin-converting enzyme inhibitors such as lisinopril are the antihypertensive drugs of choice in patients with lupus nephritis because these agents help to control proteinuria.

Low-dose prednisone may help to alleviate this patient's arthralgia and rash but would not treat her lupus nephritis.

26

A 20-year-old man is evaluated for a 6-month history of low back pain accompanied by prolonged morning stiffness. His symptoms improve over the course of the day, but he is now unable to play recreational soccer. Rest and physical therapy have not improved his symptoms. Use of acetaminophen or ibuprofen provides only partial relief. He has no other pertinent medical history and takes no additional medications.

On physical examination, vital signs are normal. There is loss of normal lumbar lordosis, and flexion of the lumbar spine is decreased. The low back and pelvis are tender to palpation. Pain increases when the patient crosses his legs. Reflexes and muscle strength are intact.

Radiographs of the lumbar spine and sacroiliac joints are normal.

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

This patient most likely has ankylosing spondylitis, and magnetic resonance imaging (MRI) of the sacroiliac joints is most likely to establish the diagnosis. Radiographic evidence of sacroiliitis is required for definitive diagnosis and is the most consistent finding associated with this condition. Onset of ankylosing spondylitis usually occurs in the teenage years or 20s and manifests as persistent pain and morning stiffness involving the low back that is alleviated with activity. This condition also may be associated with tenderness of the pelvis.

Typically, the earliest radiographic changes involve the sacroiliac joints, but these changes may not be visible during the first few years from onset; therefore, this patient's normal radiographs of the sacroiliac joints do not exclude sacroiliitis. MRI findings of the sacroiliac joints can include bone marrow edema, synovitis, and erosions. Bone marrow edema is the earliest finding and can precede the development of erosions. MRI, especially with gadolinium enhancement, is considered a sensitive method for detecting early erosive inflammatory changes in the sacroiliac joints and spine and can assess sites of active disease and response to effective therapy.

A bone scan can demonstrate increased radionuclide uptake of the sacroiliac joints in patients with ankylosing spondylitis but is less sensitive and specific than MRI for establishing the diagnosis.

Computed tomography is the most sensitive modality available to demonstrate bone changes such as erosions; however, it cannot detect early changes such as bone marrow edema that precede erosive change in patients with ankylosing spondylitis.

Sacroiliac joint MRI is more sensitive than lumbar spine MRI in diagnosing early ankylosing spondylitis. Although changes in the lumbar spine can be detected on MRI, they are usually preceded by changes in the sacroiliac joints. Therefore, if imaging of the lumbar spine is negative, subsequent imaging of the sacroiliac joints would still be necessary to exclude ankylosing spondylitis.

27

A 24-year-old woman is evaluated for a 3-week history of pain and swelling of the right knee and left ankle. The patient also reports mild burning with urination. She has no history of tick exposure, skin rash, diarrhea, or abdominal pain. She has not been sexually active in the past month. She takes no medications.

On physical examination, vital signs are normal. Musculoskeletal examination shows swelling, tenderness, warmth, pain on range of motion, and an effusion of the right knee; the left ankle is also swollen and tender.

Serologic studies for Lyme disease are negative. Urinalysis reveals 18 leukocytes/high-power field and 2+ leukocyte esterase but is otherwise normal.

Aspiration of the right knee shows a synovial fluid leukocyte count of 7500/µL (7.5 × 109/L) and negative Gram stain. Synovial fluid culture results are pending.

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

This patient should have urine nucleic acid amplification testing for Chlamydia trachomatis infection. She has acute arthritis of the right knee, enthesitis of the left ankle, and urethritis, all of which can occur with disseminated gonorrheal infection. However, in the absence of any recent history of sexual activity, these findings are more suggestive of reactive arthritis that can develop after C. trachomatis infection. Reactive arthritis occurs in both men and women, and enthesitis and oligoarthritis are common. The classic triad of arthritis, urethritis, and conjunctivitis occurs in only about one third of patients. Symptoms typically develop 2 to 4 weeks after an infection.

Classic pathogens associated with reactive arthritis include C. trachomatis as well as several enteric pathogens. C. trachomatis infection may be asymptomatic, and examination of a urine sample can establish the diagnosis. If infection is present, antibiotic treatment is warranted, and sexual partners should also be counseled and treated. However, nonsteroidal anti-inflammatory drugs are first-line therapy for musculoskeletal symptoms, as antibiotics do not effectively treat the reactive arthritis.

Antinuclear antibody testing can be helpful in the diagnosis of systemic lupus erythematosus (SLE). Although arthritis and pyuria can occur in SLE, the pyuria typically results from glomerulonephritis and is therefore not associated with the lower urinary tract symptoms of frequency and urgency. The patient does not have any other symptoms or signs of SLE.

Rheumatoid factor is present in approximately 70% of patients with rheumatoid arthritis. This disorder typically presents with a symmetric, small joint polyarthritis and does not explain this patient's urinary symptoms and pyuria.

This patient's negative Lyme disease serology results indicate that she does not have Lyme arthritis, and testing the synovial fluid for Borrelia burgdorferi infection is not needed. In patients with Lyme arthritis, testing by polymerase chain reaction (PCR) can detect B. burgdorferi DNA in synovial fluid. However, synovial fluid PCR testing has not been validated for wide use.

28

A 24-year-old man is evaluated for worsening low back pain of 6 months' duration. He notes severe back stiffness on awakening in the morning or after prolonged sitting that seems to improve with activity. He otherwise feels well and has no other symptoms. Medical history is significant for Crohn disease diagnosed 4 years ago that has been well controlled with daily mesalamine.

On physical examination, vital signs, including temperature, are normal. Cutaneous examination, including the nails and oral mucosa, is normal. There is no evidence of conjunctivitis or iritis. Musculoskeletal examination reveals moderate tenderness to palpation over the low back, with decreased ability to flex at the waist. The remainder of the examination is unremarkable.

Laboratory studies include a normal hemoglobin level and leukocyte count and negative rheumatoid factor.

Which of the following is the most likely diagnosis?

This patient most likely has Crohn disease–related arthritis, which is a form of enteropathic arthritis (arthritic conditions associated with gastrointestinal disease). Up to 20% of patients with Crohn disease or ulcerative colitis develop inflammatory joint disease. Polyarthritis that resembles seronegative rheumatoid arthritis develops in 20% of these patients, whereas 10% to 15% of these patients develop spondylitis and sacroiliitis. The risk for inflammatory joint disease associated with Crohn disease or ulcerative colitis increases in patients with more advanced colonic conditions and additional concomitant extraintestinal manifestations, including abscesses, erythema nodosum, uveitis, and pyoderma gangrenosum. Peripheral arthritis associated with inflammatory bowel disease (IBD) is often classified as one of two types. In type I arthropathy, the peripheral arthritis tends to be acute, affects only a few joints, tends to occur early in the course of IBD, may worsen with flares of IBD, and is often self-limited. In type II arthropathy, more joints tend to be involved and symptoms may be migratory. Joint pain is usually not related to IBD activity, and symptoms may wax and wane over years. In patients with arthritis sensitive to flares of IBD, treating the underlying gastrointestinal disease is indicated. Additional treatment for sacroiliitis and peripheral joint disease is otherwise symptomatic.

Psoriatic arthritis is a systemic chronic inflammatory arthritis associated with numerous clinical manifestations, including joint pain that appears similar to rheumatoid arthritis. Cutaneous involvement may be limited to nail pitting and commonly precedes joint inflammation, although 15% of patients develop joint inflammation first. This patient's lack of cutaneous findings makes psoriatic arthritis unlikely.

Reactive arthritis is characterized by the presence of inflammatory arthritis that manifests within 2 months of an episode of bacterial gastroenteritis or nongonococcal urethritis or cervicitis in a genetically predisposed patient. Reactive arthritis was previously called Reiter syndrome, which referred to the coincidence of arthritis, conjunctivitis, and urethritis (or cervicitis). However, only about one third of patients have all three symptoms. Reactive arthritis usually affects the peripheral joints, often in the lower extremities, although inflammatory back pain also may be present. This patient has no history of a previous infection or findings typical of reactive arthritis.

Rheumatoid arthritis is a symmetric polyarthritis that involves the small joints of the hands and feet as well as other joints throughout the body and is a consideration in the differential diagnosis of this patient. However, rheumatoid arthritis does not have an association with IBD, and this patient's symptoms in the context of his Crohn disease make enteropathic arthritis a much more likely diagnosis.

29

A 42-year-old man is evaluated for a 1-month history of a painful, swollen right finger and a swollen left toe. He has no other symptoms and generally feels well. He has not noticed a skin rash. Medical history is unremarkable, and his only medication is as-needed ibuprofen for his joint pain.

On physical examination, vital signs are normal. The right third distal interphalangeal joint is swollen, with localized tenderness to palpation and pain with active and passive range of motion. The appearance of the nails is shown :. Examination of the left second toe shows fusiform swelling and mild diffuse tenderness with decreased active and passive range of motion. There is onycholysis of several toenails, including the left second toenail. The remainder of the examination is normal.

Which of the following is the most likely diagnosis?

Q image thumb

This patient has psoriatic arthritis, a systemic chronic inflammatory arthritis associated with numerous clinical manifestations. Typically, psoriasis predates the arthritis by years, whereas arthritis develops before skin disease in 15% of patients. Although there is a poor correlation between the severity of skin and joint disease, there is a good correlation between the severity of nail disease and the severity of both skin and joint disease. Psoriatic findings may also be limited to nail pitting and onycholysis. There are five patterns of joint involvement in psoriatic arthritis: involvement of the distal interphalangeal joints; asymmetric oligoarthritis; symmetric polyarthritis (similar to that of rheumatoid arthritis); arthritis mutilans (extensive osteolysis of the digits with striking deformity); and spondylitis. Characteristic features of psoriatic arthritis include enthesitis (inflammation of sites where tendons or ligaments insert into bone), dactylitis (inflammation of an entire digit), and tenosynovitis (inflammation of the synovial sheath surrounding a tendon). This patient has findings characteristic of psoriatic arthritis, including inflammation of a distal interphalangeal joint and dactylitis of a toe. He also has nail changes, including pitting and onycholysis.

Lyme arthritis typically involves medium- or large-sized joints rather than distal interphalangeal joints and does not typically cause tenosynovitis. Furthermore, this disorder does not cause nail changes, as seen in this patient.

Osteoarthritis can involve the distal interphalangeal joints but does not cause dactylitis or nail changes.

Rheumatoid arthritis can initially present with an asymmetric pattern, although it classically takes on a symmetric distribution with time. In contrast to this patient, patients with rheumatoid arthritis typically have sparing of the distal interphalangeal joints and preferential involvement of the proximal interphalangeal joints and metacarpophalangeal joints. In addition, rheumatoid arthritis also does not cause nail changes.

30

A 46-year-old woman is evaluated for pain and color changes in her fingers and hands. She has had these symptoms for several years, but they have worsened since her diagnosis of limited systemic sclerosis 1 year ago. She notes that her symptoms occur mostly with exposure to cold (such as taking items out of a freezer or when not wearing gloves outside in the winter). She also believes that stress may make her symptoms worse. During an episode, her fingers turn white and become very painful, then blue, and over 15 to 20 minutes become red with eventual resolution of her pain. Her episodes are worsening despite her efforts to avoid cold exposure and minimize stress. Medical history is significant only for gastroesophageal reflux disease and her only medication is omeprazole.

On physical examination, she is afebrile, blood pressure is 122/68 mm Hg, and pulse rate is 82/min. Examination of the hands shows sclerodactyly but with evidence of normal perfusion. The radial and ulnar pulses are normal bilaterally. The remainder of her examination is unremarkable.

Which of the following is the most appropriate additional treatment for this patient?

This patient has Raynaud phenomenon, which is present in more than 95% of patients with systemic sclerosis and is particularly likely to develop in patients with limited cutaneous disease. The most appropriate treatment for this patient is a long-acting dihydropyridine calcium channel blocker such as amlodipine.

Systemic sclerosis is classified according to the degree of skin involvement. Systemic sclerosis with limited cutaneous involvement, or CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia), manifests as skin thickening distal to the elbows and knees. Conversely, systemic sclerosis with diffuse cutaneous involvement is associated with skin thickening proximal to the elbows and knees. Diffuse and limited cutaneous systemic sclerosis may affect the face.

Raynaud phenomenon is an abnormal vascular response to cold exposure or stress and usually involves the extremities. Although Raynaud phenomenon may occur in the absence of another disorder (primary Raynaud phenomenon), it frequently accompanies connective tissue diseases in which there are believed to be microvascular changes that alter normal vasoconstrictor activity. Episodes commonly involve an initial onset of vasoconstriction lasting for 15 to 20 minutes with ischemia (white phase) or cyanosis (blue phase), with erythema (red phase) developing with reperfusion.

In patients with Raynaud phenomenon, cigarette smoking is contraindicated and avoidance of cold is recommended; pharmacologic therapy is warranted for patients in whom these interventions do not provide sufficient relief. Dihydropyridine calcium channel blockers such as amlodipine have been shown to reduce the frequency and severity of attacks in patients with both primary and secondary Raynaud phenomenon, and these agents are frequently used as first-line treatment in this condition. Antiplatelet agents, such as aspirin and dipyridamole, also are used. The phosphodiesterase type 5 inhibitor sildenafil reduces the development of digital ulcers. Surgical revascularization, sympathetic nerve blockade or sympathectomy, prostacyclin analogues, or endothelin antagonists may be indicated in severe, refractory cases.

Topical nitrates applied to the finger webs are often used in the treatment of Raynaud phenomenon but are usually used as second-line therapy. Oral therapy with nitroglycerin is less effective and less well tolerated than amlodipine and is not indicated as a first-line drug for this condition.

Raynaud phenomenon is caused by microvascular involvement in patients with systemic sclerosis and is characterized by intimal proliferation and progressive luminal obliteration, as well as digital spasm. This process does not respond to anti-inflammatory agents; therefore, prednisone is not indicated in the treatment of Raynaud phenomenon.

β-Blockers such as metoprolol are not indicated in the treatment of Raynaud phenomenon and may actually worsen symptoms by preventing β-adrenergic–mediated vasodilation.

31

A 60-year-old man is evaluated for an 8-month history of progressive, generalized weakness and difficulty rising from a chair. He reports occasional fever and muscle aches. Medical history is otherwise unremarkable. He does not smoke and drinks 1 to 2 alcoholic beverages daily. He takes no medications.

On physical examination, temperature is 37.4°C (99.3°F), blood pressure is 128/76 mm Hg, pulse rate is 72/min, and respiration rate is 18/min. No rash is present. Bilateral proximal upper and lower extremity weakness is noted with mild tenderness of the large muscle groups to palpation. Distal muscle strength is normal.

Laboratory studies reveal an erythrocyte sedimentation rate of 56 mm/h and a serum creatine kinase level of 1100 U/L.

Electromyogram shows muscle irritability without evidence of neuropathy. A proximal thigh muscle biopsy reveals pronounced lymphocytic infiltration of the muscle fascicles; there is no evidence of perivascular infiltration or filamentous particles in the sarcoplasm.

Which of the following is the most likely diagnosis?

This patient most likely has polymyositis, a disorder characterized by acute or subacute onset of proximal muscle weakness without rash or distal muscle involvement. Electromyography (EMG) cannot reliably distinguish polymyositis from other forms of inflammatory myopathy. Muscle biopsy is the gold standard for diagnosing the idiopathic inflammatory myopathies. The muscle biopsy is usually not obtained on the same side as the EMG because the EMG can disrupt muscle architecture, cause local inflammation, and affect biopsy results. Biopsy characterization of the infiltration pattern and cell markers allows for the diagnosis of polymyositis, dermatomyositis, or inclusion body myositis. Muscle biopsy results from a patient with polymyositis characteristically show CD8-positive T-cell infiltration within the muscle fascicles, often with invasion of intact major histocompatibility complex–expressing muscle fibers. This pattern is seen in this patient and is often accompanied by evidence of muscle fiber necrosis and regeneration.

Patients with chronic alcohol-related myopathy may present with diffuse, often proximal muscle weakness that develops over weeks or months. However, this disorder tends to occur in patients with very high levels of chronic alcohol use, involves only a mild elevation of muscle enzymes, and is not associated with evidence of inflammation on muscle biopsy, as seen in this patient. Dermatomyositis is characterized by myopathic symptoms similar to those in polymyositis but is also associated with a typical rash (heliotrope rash on the upper eyelids and periorbital area, photosensitive rashes involving the shoulders, neck, and anterior chest) and Gottron papules (hyperkeratotic red papules and plaques over bony prominences). Biopsy results differ from those in polymyositis and are notable for CD4-positive T cells around the muscle fascicles and in the perimysial areas.

Inclusion body myositis usually affects older persons, has an insidious course, and is characterized by proximal and distal muscle weakness. Typical biopsy results are similar to those of polymyositis but also include characteristic filamentous particles in the sarcoplasm, termed inclusion bodies, which are not present in this patient.

32

A 38-year-old woman is evaluated for a gritty, burning sensation in her eyes that worsens over the course of the day. Her eyes are often dry, especially on windy days. She also reports a dry mouth with difficulty salivating at times. She has no other symptoms.

On physical examination, vital signs are normal. The conjunctivae are irritated. Visual acuity and funduscopic examination are normal. Decreased tear production is documented with the Schirmer test. The remainder of the examination is normal.

Laboratory studies are significant for a positive antinuclear antibody assay, rheumatoid factor, and anti-Ro/SSA and anti-La/SSB titers.

Which of the following is the most likely diagnosis?

This patient has primary Sjögren syndrome. Sjögren syndrome is characterized by sicca syndrome, which causes xerophthalmia (dry eyes), and xerostomia (dry mouth). The absence of oral mucosal moisture often causes difficulty with mastication and swallowing and increases the risk for dental caries and periodontal disease. Vaginal dryness and parotid gland enlargement are frequently present, and mild fatigue and arthralgia are common. Abnormal findings on the Schirmer test, which measures moisture under the lower eyelids, are consistent with Sjögren syndrome. Approximately 50% of patients with this syndrome are antinuclear antibody positive and 60% to 75% of patients with primary Sjögren syndrome are anti-Ro/SSA antibody positive, and approximately 40% of these patients are anti-La/SSB antibody positive. In addition, 60% to 80% of patients with this condition have rheumatoid factor positivity. The presence of xerophthalmia and xerostomia accompanied by anti-Ro/SSA and anti-La/SSB antibody positivity and abnormal findings on the Schirmer test have a 94% sensitivity and specificity for diagnosing primary Sjögren syndrome. Other systemic features of Sjögren syndrome are uncommon but may include an inflammatory polyarthritis, cutaneous vasculitis, peripheral neuropathy, interstitial nephritis, and interstitial lung disease.

Lacrimal gland dysfunction is a common cause of dry eyes that may be age-related or due to obstruction of the lacrimal gland. However, given this patient's age and the presence of a dry mouth and anti-Ro/SSA and anti-La/SSB positivity, lacrimal gland dysfunction would not be adequate to explain her clinical picture.

Both rheumatoid arthritis and systemic lupus erythematosus (SLE) can be associated with Sjögren syndrome, in which case multiple systemic symptoms and findings such as joint involvement, pleuritis, cerebritis, lung dysfunction, and skin changes may all occur. Despite this patient's positive antinuclear antibody and rheumatoid factor test results, her lack of systemic symptoms and normal physical examination findings (except for xerophthalmia and xerostomia) argue against rheumatoid arthritis or SLE as a cause of secondary Sjögren syndrome.

33

A 34-year-old woman is evaluated during a follow-up examination. Fibromyalgia was diagnosed 1 year ago. At that time, she received intensive education about her condition, and an aerobic exercise program was prescribed. Pregabalin was also initiated but was discontinued when she developed hives. She continues to have fatigue, widespread pain, and difficulty sleeping. She currently takes an over-the-counter nonsteroidal anti-inflammatory drug intermittently without relief of pain.

On physical examination, vital signs are normal. Musculoskeletal examination reveals multiple tender points but no synovitis or muscle weakness. Screening for mood disorders is negative. The remainder of the examination is normal.

Repeat laboratory studies since her initial diagnosis, including erythrocyte sedimentation rate and serum thyroid-stimulating hormone level, are normal.

Which of the following is the most appropriate class of pharmacologic treatment for this patient?

Treatment with a serotonin-norepinephrine reuptake inhibitor (SNRI) is appropriate for this patient with fibromyalgia. Fibromyalgia is characterized by widespread pain and tenderness of at least 3 months' duration. Other manifestations include fatigue, sleep disturbance, mood disorder, and cognitive dysfunction. Nonpharmacologic therapy is the cornerstone of fibromyalgia treatment and should be initiated in all patients. Regular aerobic exercise has been shown to be effective in this setting. Although high-impact aerobic exercises frequently are poorly tolerated, walking and/or water aerobics are often better accepted. Cognitive behavioral therapy has been shown to be beneficial but may not be as readily available to some patients. This patient has a 1-year history of widespread pain and tenderness along with fatigue and difficulty sleeping, features consistent with fibromyalgia. She tried pregabalin, which was discontinued because of an allergic reaction; therefore, treatment with an SNRI is warranted. Duloxetine and milnacipran are SNRIs approved by the Food and Drug Administration (FDA) to treat fibromyalgia with or without mood disorder and are as effective as pregabalin.

Fibromyalgia is not an inflammatory condition and therefore does not respond well to either glucocorticoids or nonsteroidal anti-inflammatory drugs (NSAIDs). Use of anti-inflammatory medications is not only ineffective, but in the case of glucocorticoids, exposes the patient to possible serious side effects. NSAIDs can help control pain caused by conditions such as osteoarthritis but are not effective as monotherapy for fibromyalgia symptoms; however, NSAIDs can be useful when combined with centrally acting drugs such as duloxetine or milnacipran in patients with resistant symptoms. This patient does not have evidence of another source of pain that requires treatment with NSAIDs and has not yet had a trial of a centrally acting medication.

Opioid medications have not been shown to be effective in treating fibromyalgia and also carry the significant risk of side effects and dependency. They should therefore not be used in treating patients with this disorder.

Data on the use of selective serotonin reuptake inhibitors in patients with fibromyalgia are conflicting, and none of these agents is currently FDA approved for this condition. Neurotransmitters other than serotonin may be important in fibromyalgia.

34

A 58-year-old man is evaluated for a 6-week history of pain and stiffness of the shoulders and hips. His symptoms are worse in the morning, and he notes significant discomfort when putting on his clothes. Over the past 2 weeks, he has developed fever, a 2.2-kg (5-lb) weight loss, and headache. The patient is otherwise well and takes no medications.

On physical examination, temperature is 38.6°C (101.5°F), blood pressure is 140/70 mm Hg, pulse rate is 100/min and regular, and respiration rate is 16/min. There is mild tenderness of the scalp to palpation. Musculoskeletal examination reveals mild pain and limitation at the extremes of shoulder and hip rotation bilaterally. Neurologic examination is unremarkable.

Laboratory studies are significant for a hematocrit of 32%, an erythrocyte sedimentation rate of 103 mm/h, and normal kidney function tests and urinalysis.

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

This patient, who has symptoms and signs of both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), should undergo a temporal artery biopsy. PMR is a condition closely related to GCA that presents with hip and shoulder girdle stiffness and pain and elevated inflammatory markers. Although PMR may occur independently from GCA and is not considered a vasculitis, it shares many features with GCA, including the same inflammatory cytokines and associations with age, ethnicity, and HLA class II alleles. GCA may be present in 15% to 30% of patients with PMR. Patients with only PMR do not have the classic findings of GCA such as temporal artery tenderness, headache, jaw pain, vision loss, or noncranial ischemia (such as arm claudication). In the absence of symptoms or clinical findings consistent with GCA, a trial of glucocorticoid therapy is indicated, as PMR typically responds dramatically to this therapy. However, this patient has headache and scalp tenderness in addition to PMR symptoms, suggesting the possibility of GCA. Therefore, a temporal artery biopsy is indicated.

Visual manifestations such as amaurosis fugax and anterior ischemic optic neuropathy due to vascular occlusion are the most feared complications of GCA. However, a dilated ophthalmologic examination may be normal in patients with GCA and would not provide adequate diagnostic information to guide therapy.

Although patients with suspected GCA may have headache and scalp tenderness, standard magnetic resonance imaging (MRI) brain imaging is not able to detect the vascular lesions associated with vasculitis and would not provide adequate diagnostic information. Magnetic resonance angiography may be abnormal in patients with GCA, but also does not provide enough information to establish the diagnosis and guide therapy.

MRI of the shoulder and hip joints may show evidence of inflammation of the periarticular structures in patients with PMR, but these findings are not required for diagnosis of this condition.

35

A 58-year-old woman is evaluated for a 3-month history of a nonproductive cough and hoarseness and a 3-week history of worsening shortness of breath. She is otherwise well and takes no medications.

On physical examination, temperature is 37.7°C (99.8°F), blood pressure is 160/105 mm Hg, pulse rate is 100/min, and respiration rate is 18/min. Oral mucous membranes are normal. There is scattered lymphadenopathy and mild tenderness to palpation over the anterior aspect of the neck. Diffuse crackles are auscultated. The remainder of the examination is unremarkable.

Laboratory studies are significant for a hematocrit of 32% and serum creatinine level of 1.6 mg/dL (141.4 µmol/L). A urinalysis shows 2+ protein, 10-15 erythrocytes/high-power field (hpf), 0-5 leukocytes/hpf, and erythrocyte casts.

A chest radiograph reveals right upper and lower lobe pulmonary infiltrates with several cavitary lesions.

Which of the following is the most likely diagnosis?

This patient most likely has granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), a systemic necrotizing vasculitis that predominantly affects the upper and lower respiratory tract and kidneys. More than 70% of patients have upper airway manifestations such as sinusitis. Orbital, nasal, inner ear, and laryngotracheal inflammation may also occur. Pulmonary manifestations include cough, hemoptysis, and pleurisy. Characteristic radiographic findings include multifocal pulmonary infiltrates or nodules, some of which may cavitate. Pauci-immune glomerulonephritis occurs in up to 80% of patients. Although glomerulonephritis may be the presenting manifestation, it is most often preceded by respiratory tract manifestations.

Sarcoidosis may cause inflammatory lesions of the orbits and trachea as well as nodular pulmonary infiltrates (necrotizing sarcoid granulomatosis) and an interstitial nephritis but is not associated with significant glomerular disease.

Patients with Sjögren syndrome may have salivary gland enlargement and pulmonary infiltrates; however, significant tracheal inflammation and nodular or cavitary lung lesions are rare. Sjögren syndrome may cause an interstitial nephritis but is not associated with significant glomerular disease.

Tuberculosis may cause cavitary pulmonary lesions, but would not account for the glomerulopathy in this patient.

36

A 62-year-old man is evaluated for a 2-week history of purpuric lesions on the lower extremities. He is otherwise well and takes no medications.

On physical examination, temperature is 37.2°C (99.0°F), blood pressure is 160/100 mm Hg, pulse rate is 88/min, and respiration rate is 12/min. The mucous membranes are normal. Tender, nonblanching, purpuric papules are present on the feet and distal lower extremities. There is 1+ bilateral tibial and pedal edema. No joint swelling is noted.

Laboratory studies:

Hematocrit

28%

Leukocyte count

9500/µL (9.5 × 109/L) with a normal differential

Creatinine

1.9 mg/dL (168 µmol/L)

Urinalysis

2+ protein, 15-20 erythrocytes/high-power field (hpf), 0-5 leukocytes/hpf

A skin biopsy shows a leukocytoclastic vasculitis with deposits of IgA.

Which of the following is the most likely diagnosis?

This patient has clinical features most consistent with Henoch-Schönlein purpura (HSP), a syndrome that most commonly occurs in children but can affect adults with greater severity. Characteristic features are a purpuric rash predominantly affecting the distal lower extremities, arthritis, abdominal pain, and hematuria. Skin biopsy specimens reveal the presence of leukocytoclastic vasculitis with deposits of IgA. Kidney biopsies obtained in patients with persistent hematuria and proteinuria or kidney disease following an attack of HSP reveal glomerulonephritis with IgA deposition consistent with lesions seen in IgA nephropathy. Kidney disease may be aggressive in some patients, with transition to diffuse proliferative glomerulonephritis. In men over the age of 50 years, HSP has been reported to occur in association with solid tumors or the myelodysplastic syndrome.

Churg-Strauss syndrome is a vasculitis that typically occurs in patients with a history of asthma. Common associated laboratory findings include peripheral eosinophilia and the presence of perinuclear antineutrophil cytoplasmic antibody (pANCA).

Microscopic polyangiitis typically involves small arterioles and may be associated with glomerulonephritis and purpuric skin lesions; however, immune deposits in the skin are not characteristic of this disorder, and most patients have a positive p-ANCA titer.

Polyarteritis nodosa is a small- to medium-vessel vasculitis that may be associated with renal artery involvement and hypertension. Purpura with skin biopsy findings of immune deposits is not a characteristic cutaneous feature.

37

A 47-year-old man is evaluated for a 3-week history of paresthesia of the left leg and a 6-month history of a nonproductive cough. He also has allergic rhinitis and a history of asthma. Medications are fluticasone and inhaled albuterol as needed.

On physical examination, temperature is 37.1°C (98.8°F), blood pressure is 150/100 mm Hg, pulse rate is 100/min, and respiration rate is 18/min. There is no rash, and ocular, nasal, and oral mucous membranes are normal. Examination of the lungs reveals scattered expiratory rhonchi. There is weakness of eversion of the left foot.

Laboratory studies:

Leukocyte count

12,500/µL (12.5 × 109/L) with 44% neutrophils, 32% eosinophils, 15 lymphocytes, and 9% monocytes

Creatinine

1.8 mg/dL (159.1 µmol/L)

Perinuclear antineutrophil cytoplasmic antibody

Positive

Urinalysis

1+ protein, 5-10 erythrocytes/high-power field (hpf), 0-5 leukocytes/hpf

A chest radiograph reveals scattered bilateral nodular pulmonary infiltrates.

Which of the following is the most likely diagnosis?

This patient most likely has Churg-Strauss syndrome, a form of systemic vasculitis that most often occurs in the setting of antecedent asthma, allergic rhinitis, or sinusitis. Patients typically have eosinophilia, migratory pulmonary infiltrates, purpuric skin rash, and mononeuritis multiplex; fever, arthralgia, and myalgia also are common presenting features. Up to 40% of patients have perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positivity with specificity for antimyeloperoxidase antibodies. Patients with p-ANCA positivity are more likely to have glomerulonephritis, alveolar hemorrhage, mononeuritis multiplex, and purpura.

Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) is a necrotizing vasculitis that typically affects the respiratory tract and kidneys. Radiographs show pulmonary infiltrates or nodules that are often cavitary, as well as pulmonary hemorrhage.

Microscopic polyangiitis is a necrotizing vasculitis that typically involves the kidneys and lungs. Patients frequently present with rapidly progressive glomerulonephritis; 50% of patients have pulmonary involvement that usually manifests as pulmonary hemorrhage. Fever, arthralgia, purpura, and mononeuritis multiplex can also occur.

Microscopic polyangiitis or granulomatosis with polyangiitis could account for the lung and kidney lesions in this patient; however, his findings of profound eosinophilia and antecedent allergic rhinitis, as well as his history of reactive airways disease, are more suggestive of Churg-Strauss syndrome.

Patients with polyarteritis nodosa typically present with fever, abdominal pain, arthralgia, and weight loss that develop over days to months. Two thirds of these patients have mononeuritis multiplex, and one third have hypertension and cutaneous involvement, including nodules, ulcers, purpura, and livedo reticularis (testicular pain also occurs in about one third of male patients). However, lung involvement is uncommon and ANCA test results typically are negative.

38

A 75-year-old woman is evaluated for a sudden loss of vision in the left eye that began 30 minutes ago. She has a 2-week history of fatigue, malaise, and pain in the shoulders, neck, hips, and lower back. She also has a 5-day history of mild bitemporal headache.

On physical examination, temperature is 37.3 °C (99.1 °F), blood pressure is 140/85 mm Hg, pulse rate is 72/min, and respiration rate is 16/min. BMI is 31. The left temporal artery is tender. Funduscopic examination reveals a pale, swollen optic disc. Range of motion of the shoulders and hips elicits moderate pain. The remainder of the examination is unremarkable.

Laboratory studies are significant for a hemoglobin of 9.9 g/dL (99 g/L), leukocyte count of 7300/µL (7.3 × 109/L), platelet count of 456,000/µL (456 × 109/L), and erythrocyte sedimentation rate of 116 mm/h.

Which of the following is the most appropriate next step in this patient's management?

Immediate high-dose intravenous methylprednisolone is indicated for this patient. The patient's headache, temporal artery tenderness, fever, and mild anemia are strongly suggestive of giant cell arteritis (GCA), and her pain in the shoulder and hip girdle accompanied by a significant elevation in the erythrocyte sedimentation rate is consistent with polymyalgia rheumatica, which is present in approximately a third of patients with GCA. Patients with GCA are usually treated with high-dose glucocorticoids, such as 1 mg/kg/d of prednisone. In some patients with GCA, however, anterior ischemic optic neuropathy may cause acute and complete visual loss with funduscopic examination revealing a pale, swollen optic nerve. Rarely, patients with GCA regain vision if treated immediately with high dose (“pulse”) intravenous glucocorticoid such as methylprednisolone (1 g/d or 100 mg every 8 hours for 3 days) followed by oral prednisone (1 to 2 mg/kg/d). More importantly, this aggressive regimen helps to prevent blindness in the contralateral eye. Therefore, although temporal artery biopsy is the gold standard for diagnosing GCA, diagnostic testing should not precede treatment in patients whose clinical presentation is suspicious for this condition.

Low-dose oral prednisone is appropriate therapy for isolated polymyalgia rheumatic but does not sufficiently treat GCA. It would therefore not be appropriate treatment for a patient with suspected giant cell arteritis with visual loss.

A process in the brain is unlikely to cause monocular visual loss, and patients with GCA typically have normal findings on brain MRI. Therefore, this study would most likely be unhelpful in this patient.

In patients whose condition raises a strong suspicion of GCA, temporal artery biopsy should be performed after corticosteroid therapy is begun. Corticosteroid therapy will not affect the results of temporal artery biopsy as long as biopsy is performed within 4 weeks of initiating this therapy; positive biopsy results have been seen as late as 6 weeks after institution of high-dose glucocorticoid therapy, but the yield of biopsy is higher when this study is performed sooner.