TABLE IV-114 Risk Factors for Active Tuberculosis Among Persons Who Have Been Infected With Tubercle Bacilli 28 page

IX-58. The answer is A. (Chap. 331) Rotator cuff tendinitis or tear is a common cause of shoulder pain. The rotator cuff is formed by the tendons of four muscles that attach to the humerus. These muscles are responsible for stabilizing the humerus within the glenohumeral joint and are important in lifting and rotating the arm, especially in abduction. The muscles that comprise the rotator cuff are the supraspinatus, infraspinatus, teres minor, and subscapularis muscles. In young individuals, it is uncommon to have a complete tear of the rotator cuff unless there is trauma. In most cases, rotator cuff tendinitis is the more common cause of pain due to rotator cuff injuries. Rotator cuff tendinitis is demonstrated by pain with active, but not passive, abduction of the arm. Other symptoms of rotator cuff tendinitis include pain over the lateral deltoid muscle, night pain, and the impingement sign. The impingement sign is positive if pain is elicited with forward flexion of the arm at less than 180°. However, individuals who engage in activities that cause repetitive stress to the rotator cuff can develop tears in the tendons that would require surgery. Examples of such activities include baseball, rowing, and tennis. To evaluate for a tear of the rotator cuff, the arm is passively abducted and the individual is asked to maintain the arm in abduction. The test is positive if the individual is not able to maintain the arm at 90° of abduction. Pain with palpation over the bicipital groove is a sign of bicipital tendinitis. Pain with palpation anteriorly when the arm is rotated internally and externally is a sign of problems within the glenohumeral joint.

IX-59. The answer is B. (Chap. 331) This patient has degenerative arthritis. His obesity predisposes him

to degenerative joint disease that will be worse in the large weight-bearing joints. The physical examination findings of decreased range of motion, crepitus, and varus deformity that is exacerbated on weight bearing are consistent with this diagnosis. The radiogram of the knee demonstrates narrowing of the joint space with osteophyte formation. Occasional effusions may be seen, especially after overuse injuries. The joint fluid analysis in patients with degenerative disease reveals a clear, viscous fluid with a white blood cell count less than 2000/μL. Positively birefringent crystals on polarizing light microscopy will be seen in pseudogout that most commonly affects the knee, whereas negatively birefringent crystals are characteristic of gout. Joint fluid in these inflammatory conditions would generally have a white blood cell count of less than 50,000/μL and is yellow and turbid in character. Septic arthritis presents with fevers and a very warm and tender joint. The joint fluid can have the appearance of frank pus and is opaque. The white blood cell count is usually higher than 50,000/μL and can have a positive Gram stain for organisms.

IX-60. The answer is A. (Chap. 332) Osteoarthritis (OA) is one of the most common causes of disability among older adults and is more common among women than men. OA characteristically affects some joints but spares others. The joints in the hands most commonly affected by OA are the distal and proximal interphalangeal joints and the base of the thumb. It is uncommon for OA to affect the wrist. In addition, OA also is more common in the hips, knees, and cervical and lumbosacral spine. The pain that occurs in OA occurs during or just after joint use, gradually resolving with rest. Thus, the pain of OA in the hands would be expected to be worse while preparing meals (option C) or sewing. The stiffness of OA is not prominent in the mornings as is common in inflammatory arthritis. Rather, stiffness in OA is most marked following brief periods of rest. It can also be associated with the gel phenomenon in which a joint can lock following brief rest periods. On physical examination of the hands of an individual with OA, one may note the presence of bony swellings of the distal and proximal interphalangeal joints. These are known as Heberden’s and Bouchard’s nodes, respectively. No blood tests are routinely required for the evaluation of OA when the history and physical examination are consistent with the diagnosis. If radiographs are performed, one would expect joint space narrowing due to loss of cartilage. In addition, osteophytes and bony enlargement can be seen. Findings of joint swelling, warmth, and erythema are more common in inflammatory causes of arthritis, and furthermore, it would be unlikely for OA to affect only the wrists.

IX-61. The answer is A. (Chap. 332) Osteoarthritis (OA) represents joint failure in which pathologic changes have occurred in all structures of the affected joint. The central pathology in OA is articular cartilage loss. The components leading to the development of OA can be separated into those that contribute to joint loading and those that increase joint vulnerability. The most potent risk factor for OA is aging, which affects joint vulnerability. Radiographic evidence of OA is rare in individuals younger than 40; however, more than 50% of individuals older than 70 will have changes of OA. A young joint has in place protective mechanisms that allow it to tolerate excessive loading without lasting damage. Specifically, the cartilage of younger joints is more responsive to dynamic loading, whereas older cartilage fails to respond, leading to breakdown of the cartilage matrix. Women are more susceptible to OA than men, especially after the sixth decade, but the relationship is not as strong as with aging and OA. Joint injury is a strong predictor of the future development of osteoarthritis. Obesity is a well-recognized risk factor in hip and knee arthritis likely due to increased loading forces. Obesity appears to play a role in OA of the hand as well, suggesting that obesity has both a mechanical and metabolic mechanism of action. The genetics of OA are not well understood. Inherited polymorphisms appear to

play a role in hand and hip OA but not as much in other joints.

IX-62. The answer is E.(Chap. 332) This patient presents with symptoms suggestive of OA. OA is primarily a disease that is mechanically driven, and nonpharmacologic therapy should be a first-line treatment for disease that is mild or intermittent. Avoiding activities that cause pain and overload the joint, strengthening and conditioning the adjacent muscle groups, and supporting or unloading the joint with a brace or crutch are all examples of fundamental treatments aimed at reversing the pathophysiology of OA. In this patient, weight loss should be the primary goal of therapy. Each pound of weight increases loading across a weight-bearing joint three- to six-fold. This patient would benefit from a daily minimal-weight-bearing exercise regimen combined with nutritional goals aimed at slow, consistent weight loss. Avoidance of walking is impractical; a cane or supportive device to lessen the joint load can be offered. Steroids and narcotics are not indicated in this case.

IX-63. The answer is C.(Chap. 333) This individual has had three recent acute gout attacks and has risk factors for recurrence including chronic kidney disease and the need for diuretic therapy. In this setting, he demonstrates elevation of his uric acid levels. When considering initiation of hypouricemic therapy, one should consider the number of attacks, the serum uric acid levels outside of an acute attack, and the patient's willingness to commit to lifelong therapy. In addition, individuals with uric acid stones or tophaceous gout should also receive hypouricemic therapy. Current agents that are commonly used to treat hyper-uricemia include uricosuric agents and xanthine oxidase inhibitors. Probenecid is the most commonly used uricosuric agent. It is started at a dose of 250 mg twice daily, but can be titrated as high as 3 g daily. However, it is generally not effective when the serum creatinine is greater than 2.0 mg/dL. Benzbromarone is a uricosuric agent that is more effective in individuals with renal failure, but it is not available in the United States. The medication most commonly prescribed in individuals with recurrent gout is allopurinol. This xanthine oxidase inhibitor lowers serum uric acid levels in overproducers, but has multiple associated toxicities including toxic epidermal necrolysis, bone marrow suppression, and renal failure. The initial starting dose is typically 300 mg daily and can be increased to as high as 800 mg daily. However, caution must be taken in individuals with renal failure. Febuxostat is a newer chemically unrelated xanthine oxidase inhibitor. It has been demonstrated to lower uric acid levels as effectively as allopurinol. The initial dose of febuxostat is 40-80 mg daily, and dose adjustment is not required in mild to moderate renal failure. Colchicine is a microtubule stabilizer that decreases inflammation in acute gout attacks. It does not affect levels of uric acid. However, it is commonly used as adjunctive therapy in individuals to prevent gout flares that occur as uric acid levels decline. Indomethacin is a nonsteroidal anti-inflammatory agent that is commonly used in acute gout flares. It does not have a role in the treatment of hyperuricemia or outside of the acute gout attack. Caution should be taken in using nonsteroidal anti-inflammatory drugs in individuals with renal insufficiency.

IX-64. The answer is C.(Chap. 333) Acute gouty arthritis is frequently seen in individuals on diuretic therapy. Diuretics result in hyperuricemia through enhanced urate reabsorption in the proximal tubule of the kidney in the setting of volume depletion. Hyperuricemia remains asymptomatic in many individuals but may manifest as acute gout. Acute gout is an intensely inflammatory arthritis that frequently begins at night. While any joint may be affected, the initial presentation of gout is often in the great toe at the metatarsophalangeal joint. There is associated joint swelling, effusion, erythema, and exquisite tenderness. A typical patient will complain that the pain is so great that he or she is unable to wear socks or allow sheets or blankets to cover the toes. Arthrocentesis will reveal an inflammatory cloudy-

appearing fluid. The diagnosis of gout is confirmed by the demonstration of monosodium urate crystals seen both extracellularly and intracellularly within neutrophils. Monosodium urate crystals appear strongly negatively birefringent under polarized light microscopy and have a typical needle- and rod-shaped appearance. The WBC count is usually below 50,000/uL with values above 100,000/uL being more likely to be associated with a septic arthritis. Likewise, very low glucose levels and a positive Gram stain are not manifestations of acute gout but are common in septic arthritis. Calcium pyrophosphate dihydrate crystals appear as weakly positively birefringent rhomboidal crystals and are seen in pseudogout.

IX-65. The answer is A.(Chap. 334) This patient presents with a history consistent with a true septic arthritis due to gonococcal infection. Although gonococcal infection has generally declined in incidence in the past several decades, Neisseria gonorrhoeae is responsible for about 70% of acute infectious arthritis in individuals younger than 40 years. Women are two to three times more likely to develop disseminated gonococcal infection than men, likely related to the fact that asymptomatic cervical infection is more common in women. Women appear to be at greatest risk for disseminated gonococcal infection during menses or pregnancy. Disseminated gonococcal infection presents with fevers, chills, migratory arthritis and tenosynovitis, and a papular rash on the trunk and the extensor surfaces of the distal extremities. The rash can progress to hemorrhagic pustules. The joint symptoms and rash are thought to represent immune-complex deposition. In disseminated gonococcal infection, the synovial fluid from inflamed joints usually contains only 10,000-20,000 leukocytes/uL. In this setting, synovial cultures are negative and blood cultures are positive less than 45% of the time.

In this patient, there is evidence of a true septic arthritis with involvement of a single joint and a high leukocyte count (>50,000/uL). Septic arthritis due to N. gonorrhoeae is less common than disseminated gonococcal infection but always follows this syndrome. In the clinical scenario presented, the symptoms of fevers, chills, migratory arthralgias, and rash occurred 3 weeks prior to presentation with monoarticular septic arthritis. Blood cultures are almost always negative, and synovial fluid cultures are positive less than 40% of the time. The diagnostic procedure of choice is a culture of a potentially infected mucosal site, including the cervix, urethra, or pharynx.

Individuals with Lyme disease who are untreated frequently develop joint symptoms. Most commonly, this presents as waxing and waning episodes of mono- or oligoarthritis. Ten percent of individuals can develop an inflammatory erosive arthritis that leads to destructive disease of the joint if untreated. This patient's symptoms are not consistent with Lyme arthritis and testing for Borrelia burgdorferi is not indicated. Likewise, this patient presents with findings of monoarticular arthritis, which is not consistent with rheumatoid arthritis, and a rheumatoid factor is not indicated.

IX-66. The answer is B.(Chap. 334) Although the crystals suggest that the patient may have active pseudogout, the more important acute medical problem is septic arthritis. This is highly probable based on the joint leukocyte count above 100,000/uL, high percentage of PMNs, and positive Gram stain. Crystal-induced, rheumatoid, and other noninfectious causes of arthritis typically have WBC counts in the 30,000-50,000/uL range. WBC counts in indolent infections such as fungal or mycobacterial arthritis are commonly in the 10,000-30,000/uL range. The bacteria of septic arthritis usually enter the joint via hematogenous spread through synovial capillaries. Patients with rheumatoid arthritis are at high risk of a septic arthritis due to Staphylococcus aureus because of chronic inflammation and glucocorticoid therapy. The concurrent presence of pseudo-gout does not preclude the diagnosis of septic arthritis. In adults, the most common bacterial pathogens are Neisseria gonorrhoeae and S.

aureus. Antibiotics, prompt surgical evaluation for drainage, and blood cultures to rule out bacteremia are all indicated. Prompt local and systemic treatment of infection can prevent the destruction of cartilage, joint instability, or deformity. Direct instillation of antibiotics into the joint fluid is not necessary. If the smear shows no organisms, a third-generation cephalosporin is reasonable empirical therapy. In the presence of gram-positive cocci in clusters, antistaphylococcal therapy should be instituted based on the community prevalence of methicillin resistance or recent hospitalization (which would favor empirical vancomycin). Typically, acute flairs of pseudogout can be addressed with glucocorticoids. However, this could portend a higher risk in the context of infection. Nonsteroidal anti-inflammatory agents might be a possibility depending on the patient's renal function and gastrointestinal history.

IX-67. The answer is C.(Chap. 335) This patient presents with a characteristic history for fibromyalgia, a diffuse pain syndrome associated with increased sensitivity to evoked pain. The underlying pathophysiology of pain in fibromyalgia is felt to be related to altered pain processing in the central nervous system. Epidemiologically, women are affected nine times more frequently than men. The worldwide prevalence of fibromyalgia is 2-3%, but in primary care practices it is as high as 5-10%. The disorder is even more common in patients with degenerative or inflammatory rheumatic disorders, with a prevalence of 20% or higher. The most common presenting complaint is diffuse pain that is difficult to localize. Pain is both above and below the waist and affects the extremities as well as the axial skeleton. However, it does not localize to a specific joint. The pain is noted to be severe in intensity, difficult to ignore, and interferes with daily functioning. While this patient demonstrates pain at several tender points, the American College of Rheumatology no longer includes tender point assessment in the diagnostic criteria for fibromyalgia. Rather, the new criteria focus on clinical symptoms of widespread pain and neuropsychological symptoms that have been present for at least 3 months. Some of the neuropsychological conditions that are frequently observed in fibromyalgia include sleep disturbance, impaired cognitive functioning, fatigue, stiffness, anxiety, and depression. The lifetime prevalence of mood disorders in patients with fibromyalgia is 80%. Sleep disturbances can include difficulty falling asleep, difficulty staying asleep, and nonrestorative sleep, among others.

IX-68. The answer is D.(Chap. 335) Fibromyalgia is a common disorder affecting 2-5% of the population. It presents as a diffuse pain syndrome with associated neuropsycho-logical symptoms including depression, anxiety, fatigue, cognitive dysfunction, and disturbed sleep. Treatment for fibromyalgia should include a combination of non-pharmacologic and pharmacologic approaches. Patient education regarding the disease is important to provide a framework for understanding symptoms. The focus of treatment should not be on eliminating pain, but rather improving function and quality of life. Physical conditioning is an important part of improving function and should include a multifaceted exercise program with aerobic exercise, strength training, and exercises that incorporate relaxation techniques such as yoga or Tai Chi. Cognitive behavioral therapy can be useful in improving sleep disturbance and also in decreasing illness behaviors.

Pharmacologic therapy in fibromyalgia is targeted at the afferent and efferent pain pathways. The two most common categories of medications for fibromyalgia are antidepressants and anticonvulsants. Amitriptyline, duloxetine, and milnacipran have all been used with some efficacy in fibromyalgia. Duloxetine and milnacipran have been approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia. The anticonvulsants that are predominantly used in fibromyalgia are those that are ligands of the a-2-5 subunit of voltage-gated calcium channels. These include gabapentin and

pregabalin, which are also FDA approved for treatment of fibromyalgia.

Anti-inflammatory medications and glucocorticoids are not effective in fibromyalgia. However, if there is a comorbid triggering condition such as rheumatoid arthritis, appropriate therapy directed at the underlying disorder is critical to controlling symptoms of fibromyalgia as well. Opioid analgesics such as oxycodone should be avoided. They have no efficacy in treating fibromyalgia and may induce hyperalgesia that can worsen both pain and function.

IX-69. The answer is A.(Chap. 335) Fibromyalgia is characterized by chronic widespread musculoskeletal pain, stiffness, paresthesia, disturbed sleep, and easy fatigability. It occurs in a 9:1 female-to-male ratio. It is not confined to any particular region, ethnicity, or climate. While the pathogenesis is not clear, there are associations with disturbed sleep and abnormal pain perception. Fibromyalgia is diagnosed by the presence of widespread pain, a history of widespread musculoskeletal pain that has been present for more than 3 months, and the presence of neuropsychological dysfunction (fatigue, waking unrefreshed, or cognitive symptoms). In the prior diagnostic criteria, it was required to demonstrate pain on palpation at 11 of 18 tender point sites. However, this was abandoned in the updated criteria because it was felt that strict application of a threshold of pain could lead to under-diagnosis of the disorder. Besides pain on palpation, the neurologic and musculoskeletal examinations are normal in patients with fibromyalgia. Psychiatric illnesses, particularly depression and anxiety disorders, are common comorbidities in these patients but do not help satisfy any diagnostic criteria.

IX-70. The answer is A.(Chap. 336) The finding shown in Figure IX-70 is characteristic of clubbing. Clubbing occurs in the distal portions of the digits and is characterized by widening of the fingertips, convexity of the nail contour, and loss of the normal 15° angle between the proximal nail and cuticle. Clinically, it sometimes can be difficult to ascertain whether clubbing is present. One approach to the diagnosis of clubbing is to measure the diameter of the finger at the base of the nail and at the tip of the finger in all 10 fingers. For each finger, a ratio between the base of the nail and the tip of the finger is determined. If the sum of all 10 fingers is greater than 1, then clubbing is felt to be present. A simpler approach is to have an individual place the dorsal surfaces of the distal fourth digits from each hand together. In a normal individual, there should be a diamond shaped space between the digits. When an individual has clubbing, this space is obliterated.

Clubbing most commonly occurs in advanced lung disease, especially bronchiectasis, cystic fibrosis, and interstitial lung diseases like sarcoidosis or idiopathic pulmonary fibrosis. Clubbing was originally described in individuals with empyema and can occur in chronic lung infections, including lung abscess, tuberculosis, or fungal infections. Pulmonary vascular lesions and lung cancer also are associated with clubbing. However, chronic obstructive pulmonary disease does not cause clubbing. The causes of clubbing are not limited, however, to the pulmonary system alone. Clubbing can be a benign familial condition and is also associated with a variety of other disorders. This includes cyanotic congenital heart disease, subacute bacterial endocarditis, Crohn's disease, ulcerative colitis, celiac disease, and cancer of the esophagus, liver, small bowel, and large bowel. In untreated hyperthyroidism clubbing can occur in association with periostitis in a condition called thyroid acropachy. While these numerous clinical associations have been described for many centuries, the cause of clubbing remains unknown.

IX-71. The answer is E.(Chap. 337) Trochanteric bursitis is a common cause of hip pain and results

from inflammation within the bursa that surrounds the insertion of the gluteus medius onto the greater trochanter of the femur. Bursae lie throughout the body with the purpose of facilitating movement of tendons and muscles over bony prominences. Bursitis has many causes including overuse, trauma, systemic disease, or infection. Trochanteric bursitis typically presents with acute or subacute hip pain with a varying quality. The pain localizes to the lateral aspect of the hip and upper thigh. Direct palpation over the posterior aspect of the greater trochanter reproduces the pain, and often sleeping on the affected side is painful. Pain is also elicited with external rotation and resisted abduction of the hip. Treatment of trochanteric bursitis includes the use of nonsteroidal anti-inflammatory medications and avoidance of overuse. If the pain persists, steroid injection into the affected bursa may be beneficial. Other causes of hip pain include osteoarthritis, avascular necrosis, meralgia paresthetica, septic arthritis, occult hip fracture, and referred pain from lumbar spine disease. In patients with true disorders of the hip joint such as osteoarthritis, avascular necrosis, and occult hip fracture, the pain is most commonly localized to the groin area. Meralgia paresthetica (lateral femoral nerve entrapment syndrome) causes a neuropathic pain in the upper outer thigh with symptoms ranging from tingling sensations to a burning pain. When degenerative spinal disease is the cause of referred hip pain, there is typically back pain as well. In addition, palpation over the lateral joint would not reproduce the pain. Iliotibial band syndrome causes lateral knee pain but not hip pain.

IX-72. The answer is B.(Chap. 337) The iliotibial band is comprised of thick connective tissue that runs along the outer thigh from the ilium to the fibula. When this band becomes tightened or inflamed, pain most commonly occurs where the band passes over the lateral femoral condyle of the knee, leading to a burning or aching pain in this area that can radiate toward the outer thigh. This overuse injury is most often seen in runners and can be caused by improperly fitted shoes, running on uneven surfaces, and excessive running. It is also more common in individuals with a varus alignment of the knee (bowlegged). Treatment of iliotibial band syndrome includes rest, NSAIDs, physical therapy, and addressing risk factors such as poorly fitted shoes or running on uneven surfaces. Glucocorticoid injection at the lateral femoral condyle may alleviate pain, but running must strictly be avoided for 2 weeks following injection. In refractory cases, surgical release of the iliotibial band maybe beneficial.

IX-73. The answer is A.(Chap. 337) Adhesive capsulitis is characterized by pain and restricted motion of the shoulder. Usually this occurs in the absence of intrinsic shoulder disease, including osteoarthritis and avascular necrosis. It is, however, more common in patients who have had bursitis or tendinitis previously, as well as patients with other systemic illnesses, such as chronic pulmonary disease, ischemic heart disease, and diabetes mellitus. The etiology is not clear, but adhesive capsulitis appears to develop in the setting of prolonged immobility. Reflex sympathetic dystrophy may also occur in the setting of adhesive capsulitis. Clinically, this disorder is more commonly seen in females over age 50. Pain and stiffness develop over the course of months to years. On physical examination, the affected joint is tender to palpation, with a restricted range of motion. The gold standard for diagnosis is arthrography with limitation of the amount of injectable contrast to less than 15 mL. In most patients, adhesive capsulitis will regress spontaneously within 1-3 years. NSAIDs, glucocorticoid injections, physical therapy, and early mobilization of the arm are useful therapies.

IX-74. The answer is B.(Chap. 331) Inflammation of the abductor pollicis longus and the extensor pollicis brevis at the radial styloid process tendon sheath is known as De Quervain's tenosynovitis. Repetitive twisting of the wrist can lead to this condition. Pain occurs when grasping with the thumb

and can extend radially along the wrist to the radial styloid process. Mothers often develop this tenosynovitis by holding their babies with the thumb outstretched. The Finkelstein sign is positive in De Quervain's tenosynovitis. It is positive if the patient develops pain by placing the thumb in the palm, closing the fingers around the thumb and deviating the wrist in the ulnar direction. Management of De Quervain's tenosynovitis includes nonsteroidal anti-inflammatory drugs and splinting. Glucocorticoid injections can be effective. A Phalen maneuver is used to diagnose carpal tunnel syndrome and does not elicit pain. The wrists are flexed for 60 seconds to compress the median nerve to elicit numbness, burning, or tingling. Gouty arthritis will present as an acutely inflamed joint with crystal-laden fluid. Rheumatoid arthritis is a systemic illness with characteristic joint synovitis and radiographic features.

SECTION X

Endocrinology and Metabolism

QUESTION

DIRECTIONS: Choose the one best response to each question.

X-1. All of the following represent examples of hypothalamic-pituitary negative feedback EXCEPT:

A. Cortisol on the CRH-ACTH axis

B. Gonadal steroids on the GnRH-LH/FSH axis

C. IGF-1 on the growth hormone–releasing hormone (GHRH)-GH axis

D. Renin-angiotensin-aldosterone axis

E. Thyroid hormones on TRH-TSH axis

X-2. Endocrine dysfunction can be separated into glandular hyperfunction or hypofunction, or hormone resistance. Which of the following diseases is due to hormone resistance?

A. Graves’ disease

B. Hashimoto’s thyroiditis

C. Pheochromocytoma

D. Sheehan’s syndrome

E. Type 2 diabetes mellitus

X-3. Secretion of gonadotropin-releasing hormone (GnRH) normally stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which promote the production and release of testosterone and estrogen. Which mechanism best explains how long-acting gonadotropin-releasing hormone agonists (e.g., leuprolide) decrease testosterone levels in the management of prostate cancer?

A. GnRH agonists also promote the production of sex hormone–binding globulin, which decreases
the availability of testosterone.

B. Negative feedback loop between GnRH and LH/FSH.

C. Sensitivity of LH and FSH to pulse frequency of GnRH.

Date: 2016-04-22; view: 598