Current Geriatric Diagnosis & Treatment, 1st Edition
Section III - Common Disorders in the Elderly
26. Geriatric Rheumatology
David E. Blumenthal MD
ESSENTIALS OF DIAGNOSIS
- Many rheumatic conditions, such as tendinitis or bursitis, are diagnosed by history and physical findings alone, and additional diagnostic tests are not useful.
- Many rheumatological tests are falsely positive in the elderly, so one must determine the pretest probability of disease by history and physical before ordering and interpreting laboratory tests.
- Radiographs and magnetic resonance images can document anatomic changes, but only a careful history and physical will determine the clinical relevance of the findings.
- Synovial fluid analysis is useful in determining the cause of a joint effusion and confirming a septic or crystal-induced arthritis.
- Older patients who are treated with chronic steroids should be aggressively screened and treated for osteoporosis.
A properly performed history and physical is essential to accurate rheumatological diagnosis. Many rheumatic conditions, such as tendinitis and bursitis, are diagnosed by history and physical findings alone, and additional diagnostic tests are not useful. The history and physical enables estimation of the pretest probability of disease and is crucial to the rational use of laboratory and imaging tests.
Autoantibody testing is frequently falsely positive in the elderly, and one must determine the pretest probability of disease by history and physical before ordering and interpreting laboratory tests. Twenty to 40% of elderly patients without rheumatic disease may have a positive antinuclear antibody (ANA), and rheumatoid factor (RF) can be found in approximately 15% of healthy older adults. The erythrocyte sedimentation rate (ESR) is a nonspecific marker of inflammation and can be increased in malignancies, infectious diseases, and any cause of tissue necrosis. The ESR increases with age, and the laboratory may only report the normal range for younger patients. To calculate a normal sedimentation rate for a male, divide age by 2; for a female, add 10 to the age and divide by 2.
Radiographs and magnetic resonance images (MRIs) can document anatomic changes, but only a careful history and physical will determine the clinical relevance of the findings. A radiograph of the knee may show changes of osteoarthritis (OA), but the patient's pain might be caused by nearby anserine bursitis or referred pain from the hip. Radiographs are most useful in detecting changes in bone. If 2 bones are closer than normal, loss of intervening articular or structural cartilage is assumed. MRI is ideal for imaging structures that are not well seen on radiographs and is particularly useful to search for meniscal tears in the knee, rotator cuff tears, compression of neural tissue in the spine, and early avascular necrosis.
Synovial fluid analysis is useful in determining the cause of a joint effusion and confirming a crystal-induced arthritis. Synovial fluid analysis is essential when the differential diagnosis includes septic arthritis. Classification of synovial fluid according to cellularity is summarized in Table 26-1. Synovial fluid should undergo cell count with differential, culture with Gram's stain, and crystal analysis by polarized light microscopy. Synovial fluid analysis for protein, pH, RF, ANA, or complement has no clinical value.
ESSENTIALS OF DIAGNOSIS
- History suggests mechanical pain.
- Examination suggests loss of articular cartilage.
- Radiographs confirm loss of articular cartilage.
- Morning stiffness < 30 min duration, if present.
Table 26-1. Synovial fluid analysis.
Thinning and fissuring of the articular cartilage is known as OA, osteoarthrosis, or degenerative joint disease (DJD). Autopsy evidence of OA can be found in most adults older than 65, and physical examination reveals OA of the hands in 70% of people older than 70. Joints commonly affected by primary OA include the knee, hip, distal interphalangeal joint (DIP), proximal interphalangeal joint (PIP), first metatarsophalangeal (MTP) joint, acromioclavicular joint, facet joints of the cervical spine, and facet joints of the lumbar spine.
Most patients complain of “mechanical” pain, which worsens with continued use of the joint and improves with rest. Morning stiffness is common but usually resolves in < 30 min. Morning stiffness lasting > 1 h, pain that keeps the patient from sleeping, and reports of impressive joint swelling suggest inflammatory rather than degenerative disease. OA patients report difficulties with activities of daily living as a result of pain, loss of strength, or diminished range of motion. Pain at rest is not usual but can be seen when the cartilage loss is severe.
Physical examination reveals osteophytes on the margins of the joints, particularly in the hands at the DIP joints (Heberden's nodes) and the PIP joints (Bouchard's nodes). Range of motion may be diminished, and there is often crepitus caused by friction within the joint. A joint effusion may be present, particularly in the knee, but warmth is minimal and synovial proliferation is absent. Degenerative disease of the hip can cause pain that is referred down the thigh to the knee. When a patient complains of knee or thigh pain, the examiner should also assess the ipsilateral hip.
Blood testing is generally not helpful in diagnosing OA but may be used to seek a cause of suspected secondary OA. Synovial fluid analysis reveals a synovial fluid white blood cell (WBC) count of < 2000/mm3, indicating a noninflammatory condition. Radiographs show joint space narrowing, marginal osteophytes, subchondral sclerosis, and subchondral cysts. Weight-bearing radiographs may better demonstrate the cartilage loss in joints of the lower extremities. MRI can detect early loss of articular cartilage but is more costly than conventional radiography and is seldom needed to diagnose OA.
Because most elderly patients will have evidence of OA on physical examination or radiographs, there is a risk of erroneously ascribing pain to OA while missing another diagnosis. When joints atypical for OA are involved (eg, metacarpophalangeal joint, wrist, elbow, subtalar joint), other diagnoses should be considered. The classic symptoms and signs of OA in an unusual joint distribution should raise suspicion of secondary OA, causes of which are listed in Table 26-2. The differential diagnoses of pain in an extremity are listed in Table 26-3. A carefully performed history and physical are essential to localize the pain to its site of origin, supplemented by imaging as indicated.
Acetaminophen, ≤ 1000 mg 4 times/day, is initial therapy. If the patient's symptoms are not controlled, non-steroidal anti-inflammatory drugs (NSAIDs), tramadol, narcotics, or glucosamine can be considered.
The risk of NSAID gastropathy and gastrointestinal bleeding increases with advancing age. Patients with
prior GI bleeding, age > 65 years, high-dose NSAID treatment, and concomitant corticosteroid treatment are at higher risk. Bleeding risk can be lessened by use of a COX-2 selective NSAID (eg, celecoxib, rofecoxib, or valdecoxib) or concomitant use of a proton pump inhibitor or misoprostol, 200 µg 2–4 times/day as tolerated; the limiting toxicity is usually diarrhea. All NSAIDs potentially cause worsening renal function, fluid retention, or hepatic injury. Such adverse effects are more likely to occur in patients with preexisting diabetes mellitus, congestive heart failure, or chronic renal insufficiency. Limiting the NSAID dose to the lowest dose necessary to control symptoms will help minimize renal and gastrointestinal toxicity.
Table 26-2. Causes of secondary osteoarthritis.
Table 26-3. Differential diagnosis of peripheral joint OA.
Some evidence suggests that glucosamine, 1500 mg daily, may retard the loss of articular cartilage seen in OA and provide some relief of pain. Adverse effects are rarely encountered, although diabetic patients may occasionally see increases in blood glucose. Although glucosamine generally appears to be safer than NSAIDs, it is sold as a nutritional supplement and thus is not regulated. Physicians should warn patients that such “nutraceuticals” may not contain standardized dosages and ingredients.
Some patients report anecdotal relief of symptoms with topical salicylates. Topical capsaicin has relieved OA pain and is available in 0.025% and 0.075% preparations. However, topical capsaicin can be locally irritating, and the patient must take care not to apply it to mucosal surfaces or the eyes.
Weight reduction can be beneficial for OA in the lower extremities. Exercise is often necessary to achieve weight reduction, which is difficult for patients with joint pain. Water aerobics and swimming may allow the patient to exercise with less pain. Quadriceps strengthening is beneficial for OA of the knees. A cane will help transfer weight from the affected joint and should be held in the hand opposite the painful limb. Proper footwear can absorb some of the force of each step.
The degree of inflammation in the OA joint is much less than that seen in inflammatory arthritis, and oral immunosuppressive treatment is not indicated in OA. However, individual patients can report significant improvement in joint pain after intra-articular cortico-steroid injection. An empiric trial of corticosteroid injection may be attempted if oral medications do not provide satisfactory pain relief. If successful, repeat injections should not be performed more than every 4 mo.
Intra-articular injection of synthetic hyaluronan preparations has been shown to provide relief of OA knee pain for as much as 1 year, but there is still some uncertainty about whether the injections are superior to placebo. Little is known about safety and efficacy in joints other than the knee. Synvisc is injected into the knee weekly for 3 consecutive weeks. Hyalgan is injected into the knee weekly for 5 consecutive weeks. There is a risk of a reactive inflammatory arthritis after injection and a small risk of joint infection.
When there is severe loss of articular cartilage and the patient's quality of life is impaired, surgery should be considered. The primary goal of surgery is relief of pain. Total joint arthroplasty is usually selected for OA of the hip, knee, and shoulder. Arthrodesis (fusion) is usually preferred for the wrist, ankle, and first MTP joint.
- Gastropathy is a significant risk in elderly patients treated with NSAIDs.
- Gastroprotective strategies, including the use of COX-2 selective NSAIDs, reduce the risk of NSAID gastropathy, but other risks of NSAIDs remain.
Chan FKL et al: Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;347:2104. [PMID: 12501222] (In this trial of patients with recent ulcer bleeding who were Helicobacter pylori negative, recurrent bleeding rates over 6 mo were 4.9% in patients who received celecoxib and 6.4% in those who received diclofenac plus omeprazole, a nonsignificant difference. Renal adverse events, including hypertension, peripheral edema, and renal failure, were common.)
Pavelka K et al: Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113. [PMID: 12374520] (Results suggest that glucosamine is superior to placebo in treatment of OA and has a good safety profile.)
Raynauld J-P et al: Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee. A randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2003; 48:370. [PMID: not available] (Study found no deterioration of articular cartilage and some beneficial effects on joint pain, stiffness, and range of motion in the corticosteroid treatment group.)
DEGENERATIVE DISEASE OF THE SPINE
ESSENTIALS OF DIAGNOSIS
- History of mechanical pain in the neck, back, or extremities.
- History and examination should rule out compression of neural tissue.
- Radiographic evidence of degenerative change is common and may not explain the symptoms.
- Spine computed tomography or magnetic resonance imaging findings should be correlated with the symptoms and examination.
Degenerative disease of the lumbar spine and facet joints is called spondylosis. Radiographic evidence of degenerative disease in the spine is almost universal in elderly people, and one should not necessarily conclude that spondylosis is the source of symptoms. Spondylosis commonly causes pain in the neck and low back but can also be responsible for isolated pain in an extremity, buttock pain, headache, and neurological dysfunction. Degenerative changes in the lumbar spine can lead to lumbar canal stenosis, characterized by neurogenic claudication in 1 or both legs.
- SYMPTOMS & SIGNS
The patient often reports a history of chronic, gradually worsening neck or low back pain. However, because of the proximity of neural tissue, the patient may report a variety of neurological symptoms or neurogenic pain distant from the spine. Cervical spondylosis can cause occipital headaches; pain or numbness in the shoulder, arm, or hand; loss of dexterity; or lower extremity spasticity with gait disturbance. Lumbar spondylosis can lead to lumbar canal stenosis and neurogenic claudication, a pain in the legs or buttocks that worsens with prolonged standing and is relieved by sitting. Unlike vascular claudication, neurogenic claudication worsens while standing still. Nocturnal spine pain should raise concerns about a more ominous process, such as a malignancy. The sudden onset of severe spine pain suggests a fracture, possibly indicating osteoporosis.
- PHYSICAL EXAMINATION
Physical examination should include the patient's height; alignment and range of motion of the cervical, thoracic, and lumbar spine; direct palpation of the spine and paraspinous tissues; and a careful neurological examination. Straight-leg raise testing for nerve root impingement is less sensitive in an older population with degenerative disk disease, and a negative test does not rule out foraminal encroachment. In fact, neurological examination may be normal even in the presence of compressed neural tissue. The abdomen should be examined for evidence of an abdominal process that might radiate to the back and to search for an abdominal aortic aneurysm. The possibility of vascular claudication is investigated by arterial examination of the lower extremities. Patients with postural exacerbation of symptoms should be positioned to produce the pain. Pain in the extremities that appears after standing or is reproduced by flexion-extension of the spine is suspicious for pain generated by neural compression. For patients with extremity pain, the examination should attempt to exclude joint or periarticular disease as the source of the pain.
Blood testing is generally not useful in confirming degenerative disease of the spine or resulting neural compression.
- IMAGING STUDIES
Imaging usually begins with plain radiographs. Given the frequency of degenerative change in the elderly, the radio-graphs are mainly useful for excluding other vertebral processes such as fracture, infection, and malignancy. Flexion and extension views are useful if the patient reports symptoms that vary with posture. When compression of neural tissue is suspected, spine computed tomography (CT), CT myelogram, or spine MRI will be necessary for confirmation. In general, these studies are performed only if the physician plans to act on the findings by referring the patient for local injection or surgery. The images must be interpreted with caution; facet joint OA, disk flattening, and disk bulging are commonly found in asymptomatic elderly people and may not be
the cause of the patient's complaint. One must confirm that the degree of the foraminal encroachment or canal stenosis is sufficiently severe and in the proper anatomic site to cause the current symptoms.
Electromyography (EMG) with nerve conduction testing can assist in confirming compression of neural tissue in the spine, ruling out more distal sites of compression, or detecting a more diffuse neuropathy. In patients with lower extremity claudication and an inconclusive history and physical, noninvasive vascular ultrasound evaluation can be helpful.
Other diseases of the spine, such as infection and malignancy, are often associated with severe, unremitting, or nocturnal pain. Fracture is often associated with acute onset and may or may not have an obvious initiating event. Abdominal or retroperitoneal processes radiating to the back should be considered when there are other associated risk factors (eg, vascular disease, alcoholism) or symptoms (vomiting, weight loss) or when pain is -severe and acute in onset. Widespread myofascial tenderness in the back, neck, and extremities suggests a -diagnosis of fibromyalgia. Tenderness that localizes specifically to 1 or more adjacent vertebral bodies is worrisome for fracture, infection, and malignancy.
The recommendations for analgesic use are the same as those for OA. Gabapentin or one of the less anticholinergic tricyclic antidepressants, such as desipramine or nortryptiline, can be cautiously used when neurogenic pain is present. Amitriptyline should generally be avoided in older adults because of its high side effect profile.
Referral to a center specializing in pain management or spine disease may permit trials of epidural cortico-steroid injection or facet joint injections. Transcutaneous electrical nerve stimulation units or dorsal column stimulators have been used, but their efficacy has not been demonstrated. Surgery is used to correct clinically significant instability and to relieve disabling symptoms of neural compression. Surgery is not generally indicated to relieve local pain in the back or neck. The success rates vary according to the nature of the problem, the operation performed, and the criteria used to measure success; however, there is a risk that the disabling symptoms will persist after operation, and the clinicians should be conservative, particularly when considering multilevel decompression in aged patients with comorbid conditions that might increase the surgical risk.
- NSAIDs should be used with caution, as in OA.
- Nonsurgical therapies should be offered first; surgery is reserved for patients in intractable pain whose health dose not preclude operation.
Atlas SJ et al: Surgical and nonsurgical management of lumbar spinal stenosis: four year outcomes from the Maine lumbar spine study. Spine 2000;25:556. [PMID: 10749631]
Amundsen T et al: Lumbar spinal stenosis: conservative or surgical management? A prospective 10-year study. Spine 2000;25: 1424. [PMID: not available]
(These studies support the use of conservative therapy initially, with surgery as a potentially effective option for patients refractory to conservative care.)
ESSENTIALS OF DIAGNOSIS
- Acute onset of monoarticular or polyarticular joint inflammation.
- Lower extremity predominance in early years.
- Presentations often atypical in older persons.
- Synovial fluid analysis is important to confirm diagnosis and exclude septic arthritis.
Gout is caused by deposition of uric acid crystals in the synovium and other tissues. Chronic uric acid overload leads to microtophi, macrotophi, and acute attacks of synovitis. Premenopausal women rarely have gout, but its incidence in women rises after menopause. Poly-articular and upper extremity attacks are more prevalent in elderly persons.
- SYMPTOMS & SIGNS
An acute attack of gouty arthritis usually occurs in the lower extremity, especially the first metatarsophalangeal (MTP) joint, midfoot, ankle, and knee. First attacks are
usually abrupt and monarticular, with rapid appearance of joint swelling, tenderness, pain with motion, and erythema. Near the inflamed joint, there may be tendinitis, bursitis, and soft tissue edema.
Upper extremity attacks usually appear in the wrist, elbow, or small joints of the hands. Isolated bursitis, particularly of the olecranon or prepatellar bursae, can be seen. Acute attacks may be precipitated by trauma, binge alcohol drinking, medications that alter uric acid levels (eg, thiazide diuretics), surgery, or acute medical illness. The attack typically lasts for several days to a week or 2 and then resolves, even if untreated. With time, attacks become more frequent and are more likely to be polyarticular and to involve the upper extremity. In elderly people, the first attack may be polyarticular with multiple inflamed joints in all 4 extremities.
- PHYSICAL EXAMINATION
Physical examination reveals erythema, warmth, swel-ling, and tenderness of the affected joint, with marked pain on range of motion of the joint. Pitting edema and tenosynovitis may be seen in the vicinity of the inflamed joint. Tophi may be found near the joints at risk, embedded in the olecranon or prepatellar bursae, or in the ears. The patient may be febrile from acute gout.
- LABORATORY FINDINGS
Chronic hyperuricemia suggests that a person is at risk for gout but does not establish that the current symptoms are from gout. Serum uric acid levels can be normal at the time of a gout attack and are not helpful at the time of an acute attack. Sedimentation rate and C-reactive protein (CRP) may be elevated because of inflammation but do not differentiate acute gout from other causes of joint inflammation.
- IMAGING STUDIES
Radiographs will often show a joint effusion. Tophi can be seen as hazy shadows near the joint that may be stippled with calcification. An erosion of the bony cortex with an encircling lip of bone is very suspicious for a gouty tophus. As contrasted with other types of inflammatory arthritis, the periarticular bone density and the articular cartilage are usually well preserved.
Synovial fluid analysis should be performed whenever feasible to confirm the presence of monosodium urate crystals and to exclude septic arthritis. In acute gout, the synovial fluid is usually cloudy, with a synovial fluid WBC count in the inflammatory range (2000–75,000/mm3). Occasionally, the synovial fluid WBC count is > 100,000/mm3, which is in the range normally associated with septic arthritis. Because gout and septic arthritis can coexist, it is prudent to treat with intravenous antibiotics while awaiting cultures when the synovial fluid WBC count is in the septic range. Occasionally, the fluid will contain so many suspended urate crystals that it may appear white and chalky, sometimes called “gout milk.” Under polarized light microscopy, monosodium urate crystals are lance shaped, often the size of a WBC or larger, and strongly negatively birefringent. To perform polarized light microscopy on the biopsy tissue, the specimen should be preserved in 100% ethanol. When the urate crystal is parallel to the direction of polarization, it will appear yellow; when perpendicular, it will appear blue. Synovial biopsy is sometimes performed to rule out chronic infection.
When gout presents as an acute monarticular arthritis, pseudogout, infection, and hemarthrosis should be considered, particularly when there is no history of gout and a joint other than the MTP is involved. Gout does not usually affect the shoulders, hips, or spine, and pain in these locations should lead to consideration of another diagnosis. A polyarticular presentation may suggest calcium pyrophosphate deposition, rheumatoid arthritis (RA), or another polyarticular arthritis. Synovial fluid analysis will often be necessary to make a diagnosis.
The acute attack can be aborted by NSAIDs, colchi-cine, or corticosteroids. Choice of agent will depend on patient comorbidities and risk profile.
Any NSAID can be effective if given in anti-inflammatory doses. Indomethacin is not well tolerated by older adults and is best avoided. There are few data on COX-2 selective NSAIDs or injectable NSAIDs in acute gout. The risk of NSAID gastropathy, worsening renal function, and fluid retention is significant in older adults, and corticosteroids may be preferable.
Colchicine in a dosage of 0.6 mg orally every 2 h is often recommended, but this regimen is not well tolerated by older adults because of frequent abdominal cramping and diarrhea. Colchicine, 0.6 mg orally every 4–12 h, is less effective but better tolerated. Other potential adverse effects of colchicine include bone marrow suppression, neuropathy, and myopathy, with increased risk in patients with renal insufficiency. Intravenous colchicine should not be used because of uncommon, but potentially fatal, toxicity.
Prednisone, 35 mg daily tapered to zero over 7–14 days, is generally effective and safe but can induce hyperglycemia or psychiatric symptoms. Methylprednisolone, 30 mg intravenously daily with subsequent taper, can be substituted in patients who cannot take oral medications. Intra-articular corticosteroids are ideal for attacks of monarticular in medium to large
joints after septic arthritis has been ruled out. Depot methylprednisolone, 80 mg into the knee or 40 mg into the wrist, ankle, or elbow, is usually effective.
Prophylaxis of future attacks should be discussed with patients who have had acute gouty attacks because the risk of recurrence is high. Some patients who have had only 1 attack or have modifiable risk factors such as thiazide diuretic use can reasonably be monitored with watchful waiting.
Colchicine, 0.6 mg daily or twice daily, can provide protection against acute gout attacks but is generally not used as a first-line agent. Chronic NSAID use may also provide prophylaxis, with the usual cautions and contraindications.
Uric acid-lowering therapy with allopurinol or a uricosuric agent is generally preferred as a prophylactic -approach over chronic colchicine or NSAID use. NSAIDs, colchicine, or prednisone should be given for a short duration when uric acid-lowering agents are begun, because initiation of therapy may precipitate an acute attack of gout.
Allopurinol inhibits xanthine oxidase, thus preventing formation of uric acid. It is equally efficacious in overproducers and underexcretors of uric acid. The initial dose is based on renal function (Table 26-4). Ideally, the dose is increased every 1–2 mo until the serum uric acid is < 6.0 mg/dL, but this may not be prudent in all older people. Potential adverse effects of allopurinol include rash, fever, cytopenias, dyspepsia, granulomatous hepatitis, and vasculitis. The potentially serious allopurinol hypersensitivity syndrome is characterized by rash, hepatitis, eosinophilia, and renal insufficiency. Allopurinol can potentiate the effect of warfarin, theophylline, and azathioprine.
Uricosurics can also be used and are less toxic than allopurinol. Most gout patients are underexcretors of urate, so uricosurics are theoretically sound treatments. However, they are not very effective in patients with a GFR < 60 mL/min or in patients with tophaceous gout. Their efficacy is also reduced by low-dose aspirin therapy. They are contraindicated if the patient has had uric acid renal calculi, and the patient must drink fluids liberally to prevent stone formation. Thus, few elderly patients are good candidates for uricosuric therapy. It is considered in patients who have demonstrated intolerance of allopurinol and in the occasional patient with severe tophaceous gout whose impressive uric acid burden necessitates treatment with both allopurinol and a uricosuric. Treatment options include probenecid, 250 mg twice daily, or sulfinpyrazone, 50 mg twice daily, with gradual escalation of the dose until serum uric acid is < 6.0 mg/dL.
Table 26-4. Initial dose of allopurinol according to renal function.
- In gout patients on uric-acid lowering therapy, achieving sustained lowering of the serum uric acid to ≤ 6 mg/dL will permit better clearance of existing urate crystals and provide better protection against future gout attacks.
Li-Yu J et al: Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent gout? J Rheumatol 2001;28:577. [PMID: 11296962] (Patients who achieved serum uric acid levels of ≤ 6 mg/dL for more than 12 mo had fewer attacks of gout and were more likely to have cleared their knee synovial fluid of urate crystals.)
CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE
ESSENTIALS OF DIAGNOSIS
- Recognition of the varied clinical expressions.
- Demonstration of calcium pyrophosphate dihydrate crystals in joint fluid or on joint radio-graphs.
The typical patient is a woman older than 60. The signs and symptoms of calcium pyrophosphate dihydrate (CPPD) disease vary with the clinical expression of the disease and include pseudogout (acute monarticular arthritis), pseudo-OA (gradual loss of articular cartilage
without apparent joint inflammation), pseudorheumatoid (symmetric, polyarticular inflammatory arthritis), pseudoneuropathic (rapid destruction of one or several joints), and asymptomatic chondrocalcinosis.
- SYMPTOMS & SIGNS
In pseudogout, acute attacks of monarticular arthritis typically occur in the shoulders, wrists, small joints of the hands, and the knees and appear similar to gout. The patient with pseudo-OA has symptoms and signs of OA. Underlying CPPD disease should be suspected when the involved joint is not usually involved by primary OA, if CPPD crystals are found on arthrocentesis, or if chondrocalcinosis is seen on radiographs. Pseu-dorheumatoid patients have morning stiffness, joint swelling, and gradual joint damage in a distribution similar to RA. Pseudoneuropathic patients report monarticular or oligoarticular joint pain and impressive joint destruction on radiographs but lack the neurological deficits needed to diagnose a neuropathic arthropathy.
- Serum Testing
Hyperparathyroidism, hemochromatosis, hypothyroid-ism, amyloidosis, hypomagnesemia, and hypophosphatasia are risk factors for CPPD disease, but in most patients no underlying cause is found. Serum testing is not useful to confirm or rule out CPPD arthropathy.
- IMAGING STUDIES
Radiographs may show features of OA, RA, or neuropathic arthropathy according to the type of presentation. Chondrocalcinosis is caused by deposition of calcium in the articular cartilage or fibrocartilage. Calcification of articular cartilage can be seen in any joint. Calcification of fibrocartilage is best seen in the menisci of the knee, triangular cartilage of the wrist, symphysis pubis, and intervertebral disks.
- SPECIAL TESTS
Arthrocentesis reveals weakly birefringent blunt rods that are blue when parallel to the axis of polarization and yellow when perpendicular (the opposite of gout). Synovial fluid WBC counts can be > 100,000/mm3 in attacks of pseudogout, as they can in gout, thus raising concerns about infection.
Because CPPD disease has such a wide variety of presentations, it mimics many other conditions, including gout, RA, OA, and neuropathic arthropathy. Synovial fluid analysis is indicated when CPPD disease is in the differential diagnosis.
Acute attacks of synovitis are treated the same as acute attacks of gout. NSAIDs and daily colchicine can be used for prophylaxis. Unlike gout, there is no medication to remove crystals from the affected joints.
ESSENTIALS OF DIAGNOSIS
- Symmetric, polyarticular inflammatory arthritis with a characteristic pattern of joint involvement.
- Evidence of inflammation by history, examination, and laboratory tests.
New-onset RA can be seen in older adults. Differentiating RA from the pseudorheumatoid presentation of CPPD or from polymyalgia rheumatica (PMR) can be difficult. RA is a systemic disease and can cause weight loss or fever. Potential extra-articular disease manifestations are listed in Table 26-5.
- SYMPTOMS & SIGNS
The patient complains of inflammatory joint symptoms: The joints feel better with use and worse with rest; the joints stiffen with inactivity. Morning stiffness is a prominent complaint, and it takes at least 1 h for the joints to loosen up. The worst time of the day is generally several hours before and after awakening. The patient reports pain, stiffness, and swelling in a fairly
symmetric pattern, potentially involving the PIP and MCP joints of the hands, wrists, elbows, shoulders, temporomandibular joints, cervical spine, hips, knees, ankles, and MTPs. The disease can occasionally be more asymmetric and oligoarticular (involving 2–4 joints) early in the course, but symptoms confined to 1–2 joints are not typical of RA. Patients with wrist synovitis may complain of numbness and tingling in a median nerve distribution caused by inflamed syno-vium in the carpal tunnel.
Table 26-5. Extra-articular manifestations of rheumatoid arthritis.
- PHYSICAL EXAMINATION
Physical examination may show warmth, synovial thickening, joint tenderness, loss of hand grip strength, pain with joint motion, and loss of range of motion. Rheumatoid nodules, if present, can be seen just distal to the olecranon, over the extensor surfaces of the fingers and toes, overlying the Achilles tendon, and embedded in a chronically swollen olecranon bursa. In a patient with long-standing, poorly controlled synovitis, joint damage accumulates: ulnar deviation and subluxation of the fingers, volar subluxation of the wrist, loss of extension of the elbows, loss of abduction in the shoulders, valgus angulation of the knees, valgus angulation of the hindfoot, pes planus, plantar subluxation of the metatarsal heads, and atlantoaxial instability in the cervical spine.
RF is seen in ~80% of patients. The prevalence of false-positive RF is high in elderly people, and positive RF can be seen in chronic inflammatory states other than RA. Therefore, the presence of serum RF does not by itself confirm a diagnosis of RA and absence does not exclude it. Evidence of an acute-phase response (eg, elevated sedimentation rate, elevated CRP, low serum albumin) is almost always present. The complete blood count will usually show anemia of chronic disease, which is often normocytic but can be microcytic. Patients with Felty's syndrome will demonstrate neutropenia.
- IMAGING STUDIES
Radiographs can be normal in the early stages. Periarticular osteopenia and joint effusions are seen initially, followed by joint space narrowing and periarticular erosions as the disease progresses. Radionuclide bone scans and joint MRI can also show the synovitis but are seldom needed for diagnosis.
- SYNOVIAL BIOPSY
Synovial fluid is cloudy-yellow, with synovial fluid WBC count in the inflammatory range (2000–75,000/mm3). Joint debris can be seen, but analysis for crystals is negative. Synovial biopsy shows chronic inflammation that is indistinguishable from other types of chronic synovium-based arthritis, such as psoriatic arthritis or reactive arthritis. Biopsy material may be available from joint or carpal tunnel surgery but is seldom needed to establish the diagnosis.
The differential diagnosis can be challenging in elderly people. RA may present with proximal symptoms, mimicking PMR. Conversely, PMR can sometimes present with some distal inflammatory changes. Poly-articular gout, pseudorheumatoid CPPD disease, psoriatic arthritis, systemic vasculitis, systemic lupus erythematosus (SLE), dermatomyositis, polymyositis, bacterial endocarditis, and paraneoplastic arthritis can mimic RA. Diagnosis is based on the overall clinical picture, laboratory studies, and synovial fluid analysis. When the diagnosis is in question, rheumatology consultation is warranted.
Prednisone, 15–20 mg daily, usually provides satisfactory short-term control of symptoms and can be used as a bridge to more definitive treatment. Such doses are not safe for long-term use and should be weaned to < 10 mg daily as quickly as possible. Intra-articular injection of corticosteroids can provide relief in the injected joint, but the pattern of joint involvement is usually polyarticular, requiring systemic therapy.
NSAIDs provide some relief of pain and inflammation but do not protect against joint damage. Only a minority of patientsthose with very mild disease are candidates for NSAID monotherapy. NSAIDs can be used for analgesia in conjunction with more effective disease-modifying antirheumatic drugs (DMARDs). DMARDs are best supervised by a consulting rheumatologist. Methotrexate is the disease-modifying agent of choice for most patients with RA, dosed at 7.5–15 mg orally or subcutaneously every week. Potential adverse effects include alopecia, mucositis, diarrhea, cytopenias, increased hepatic transaminases, opportunistic infection, and pneumonitis. Folic acid, 1 mg daily, helps prevent adverse effects of methotrexate. For refractory patients or those intolerant of methotrexate, one can consider leflunomide, sulfasalazine, etanercept, intravenous infliximab, or combination therapy. Hydroxychloroquine is often used in combination with other immunosuppressives but rarely provides sufficient disease control by itself. Tumor necrosis factor (TNF) blockers, including etanercept, infliximab, and adalimumab, are potent inhibitors of rheumatoid synovitis. Infection is the main risk with these agents. Etanercept and adalimumab are given by subcutaneous injection, and infliximab is administered intravenously.
Joint replacement or fusion can provide pain relief for a severely damaged joint. Synovectomy of an individual joint can be done at the time of reconstructive surgery but contributes little to overall disease control because of the systemic nature of the disease.
- Combinations of oral DMARDs provide better disease control than single DMARD therapy.
- The new TNF-blocking agents are quite expensive but generally more effective than the oral DMARDs.
- Aggressive treatment of RA provides relief of symptoms, prevents joint damage, and may prolong the life of a rheumatoid patient.
Choi HK et al: Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002;359: 1173. [PMID: 11955534] (Treatment with methotrexate was associated with a reduction in the cardiovascular and noncardiovascular mortality in RA patients treated with methotrexate compared with RA patients who did not receive methotrexate. Similar reductions were not seen with other oral DMARDs.)
Genovese MC et al: Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 2002;46:1443. [PMID: 12115173] (Patients treated with etanercept showed statistically significantly fewer radiographic erosions and better scores on the disability section of the Health Assessment Questionnaire.)
O'Dell JR et al: Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo controlled trial. Arthritis Rheum 2002;46:1164. [PMID: not available] (Provides additional evidence that the combination of methotrexate, sulfasalazine, and hydroxychloroquine is an effective and well-tolerated combination.)
ESSENTIALS OF DIAGNOSIS
- Characteristic history.
- Prompt response to corticosteroid treatment.
- Blood tests usually show systemic inflammation but can be normal.
- The typical patient is a white woman approximately 70 years old.
- Polymyalgia rheumatica is uncommon in blacks.
- Fifteen to 20% of patients with polymyalgia rheumatica will have concomitant giant cell arteritis (temporal arteritis).
- SYMPTOMS & SIGNS
Patients reports morning stiffness and pain in the neck, upper back, shoulders, upper arms, low back, hips and proximal thighs, with difficulty arising from bed. The pain can be difficult to localize. Distal joints are often spared, although some patients report swelling and stiffness in the hands. Because PMR is a systemic inflammatory disease, patients may report fever, fatigue, malaise, anorexia, and weight loss. Patients with coexisting temporal arteritis may report headache, scalp tenderness, jaw claudication, and visual loss. Physical examination reveals stiffness and pain on motion of the shoulders. Occasionally, synovitis is seen in distal joints. Signs of temporal arteritis may be present.
Blood testing reveals evidence of systemic inflammation, including increased ESR, increased CRP, anemia of chronic disease, and low serum albumin. In up to 25% of cases, the laboratory testing can be normal, necessitating diagnosis on clinical grounds alone.
- IMAGING STUDIES
Imaging is most useful in confirming alternative diagnoses, but one must be careful because the typical patient at risk for PMR is also at risk for a variety of degenerative diseases. MRI of the shoulders in PMR will often show subacromial bursitis but should not be considered a standard diagnostic study.
Empiric treatment with prednisone, 20 mg daily, almost always gives prompt relief of PMR symptoms. Because the physical examination findings can be nonspecific and the laboratory testing can be normal, an empiric trial of prednisone can be useful in confirming suspected PMR. The prednisone trial must be interpreted with caution because many other diseases, including lymphoma and infection, may initially respond to prednisone. A rapid, complete alleviation of symptoms after prednisone treatment is evidence in favor of PMR. A complete lack of response to prednisone, 20 mg daily, essentially rules out PMR, and a partial but inadequate response should spur a search for an alternative
diagnosis. Prednisone can be tapered to the lowest tolerated dose. Because many patients have risk factors for osteoporosis, most will require concomitant treatment with calcium, 1000–1500 mg daily, vitamin D, and a bisphosphonate. Relapses during prednisone taper are common, and patients will usually require corticosteroid treatment for 1–5 years. Patients who lack symptoms of temporal arteritis do not need to undergo a biopsy because the yield is low. Patients with symptoms of temporal arteritis in addition to PMR should be started on prednisone, 20–60 mg daily, and scheduled for a temporal artery biopsy within 1 week.
Cervical and lumbar spondylosis, lumbar canal stenosis, OA of the acromioclavicular joints and hips, and subacromial impingement with subdeltoid bursitis or rotator cuff disease are common in this age group, and the overlap of symptoms can make accurate diagnosis difficult. One must be careful in interpreting history, physical, laboratory, and imaging data to avoid errors. RA can present with proximal symptoms that may appear clinically similar to PMR.
Many of the immunosuppressives used in RA have been tried in PMR. Unfortunately, no steroid-sparing strategy has proved to be consistently effective. Immunosuppressives used in RA are often considered in patients who must reduce their dependence on corticosteroids.
GIANT CELL ARTERITIS
ESSENTIALS OF DIAGNOSIS
- New-onset headache, jaw claudication, scalp tenderness, loss of vision.
- Forty to 60% of patients will report concomitant symptoms of polymyalgia rheumatica.
- Acute-phase reactants (erythrocyte sedimentation rate, C-reactive protein) are usually elevated.
- Temporal artery biopsy is often diagnostic.
Giant cell arteritis (GCA) has significant overlap with PMR. As with PMR, the typical patient is a white woman of 70 years. Females outnumber males 2 to 1. PMR is uncommonly seen in blacks and is not seen in persons younger than 50. Blindness is the most feared complication, but it can usually be prevented by prompt corticosteroid treatment. Involvement of the aorta and proximal large arteries is seen in 10–15% of patients.
- SYMPTOMS & SIGNS
The onset of symptoms can be either sudden or gradual. Patients complain of headache, often with scalp tenderness. Jaw claudication and visual loss are signs of ischemia. Amaurosis fugax is an ominous symptom and, if caused by GCA, predicts a significant risk of blindness. Patients may have symptoms of systemic inflammation, including fatigue, malaise, weight loss, and fever. The patient may also have symptoms and signs of PMR. Examination may reveal scalp tenderness; the temporal artery may be beaded, thickened, or tender. Retinal examination may reveal ischemia. Aortic and proximal large vessel involvement may manifest as aortic regurgitation, diminished brachial or radial pulses, or bruits.
Anemia of chronic disease and increased platelet counts are common. ESR and CRP are usually elevated, and the ESR may be > 100 mm/h. If clinical suspicion is high, a normal or minimally elevated ESR does not rule out the diagnosis. Autoantibody testing is usually negative.
Chest radiograph may show a thoracic aortic aneu-rysm. Contrast angiography is reserved for patients with potentially operable large vessel disease. MRI of the aorta and great vessels can be useful to diagnose large vessel involvement noninvasively.
Temporal artery biopsy should be performed to confirm the diagnosis, given the toxicities associated with empiric treatment. Corticosteroids are often started before harvesting of the artery, and the biopsy will still be diagnostic if obtained within 2 weeks of the initiation of treatment. Higher yields are obtained if the artery undergoing biopsy is abnormal on examination and is 3–5 cm in length. False-negative rates of a unilateral biopsy vary but are generally ~10%. The false-negative rate falls to < 5% if a negative biopsy is followed by immediate biopsy of the contralateral artery.
Patients with tension or vascular headache generally have more chronic symptoms. Acute headache or scalp pain may be seen in meningitis, primary or metastatic tumor, cervical spondylosis, glaucoma, herpes zoster, or adverse effects of medication.
Patients with visual symptoms are treated with prednisone, 40–60 mg daily. Methylprednisolone, 500 mg
intravenously twice daily, is sometimes used for patients believed to be at risk for imminent visual loss. High-dose corticosteroids are unlikely to restore vision once blindness has occurred. Prednisone, 20–40 mg daily, is usually sufficient for patients without visual symptoms. The dose can be increased to 40–60 mg/day if the presenting symptoms do not respond to the initial prednisone dose in 3–5 days. Loss of vision after the initiation of corticosteroid treatment is uncommon. The corticosteroid dose is tapered by 10–15% every 2 weeks until 10 mg of prednisone daily. Thereafter, the prednisone dose can be reduced by 1 mg/day every month. Potential adverse effects include weight gain, cushingoid body habitus, ocular cataracts, glucose intolerance, fluid retention, osteoporosis, proximal muscle weakness, pseudotumor cerebri, psychosis, and infection. ESR and CRP may be useful to follow disease activity; however, laboratory testing should be interpreted in the context of the history and physical, and one should not overtreat mild elevations of the sedimentation rate in asymptomatic patients. Relapses are common during prednisone taper, particularly during the first 18 mo. Most patients require at least 2 years of corticosteroid treatment. Given the risk of high-dose corticosteroids in a population that is typically elderly, white, and female, a steroid-sparing immunosuppressive with activity against GCA is sorely needed. Methotrexate as a steroid-sparing agent in GCA has had mixed results in randomized controlled trials. Given the importance of TNF in granuloma formation, anti-TNF therapies such as etanercept, infliximab, and adalimumab appear promising but not proven.
ESSENTIALS OF DIAGNOSIS
- Usually monarticular, sometimes polyarticular, intense joint inflammation.
- Arthrocentesis before administration of intravenous antibiotics.
Joints become infected by hematogenous spread from a distant site, local spread of nearby osteomyelitis, or direct inoculation of the joint from trauma or a medical procedure. Risk factors include inflammatory arthritis such as RA, diabetes mellitus, advanced age, presence of a prosthetic joint, and weakened immune function.
- SYMPTOMS & SIGNS
The infected joint is usually red, warm, swollen, and intensely painful with any movement. A fever is not necessarily present, especially in the elderly.
- LABORATORY FINDINGS
The patient may have an increased WBC count in the peripheral blood and an increased ESR, but normal laboratory tests do not rule out septic arthritis. Blood cultures are positive in approximately 50% of patients.
- IMAGING STUDIES
Radiographs show a joint effusion; with time, there is destruction of the joint demonstrated by loss of articular cartilage. Suspected septic arthritis of the sternocla-vicular joint is best imaged by CT. A transthoracic or transesophageal echocardiogram is useful to search for valvular vegetations of bacterial endocarditis.
- SPECIAL TESTS
Arthrocentesis and synovial fluid analysis is essential. The synovial fluid should be analyzed for cell count with differential, crystal analysis, Gram's stain, and culture. When the joint is infected by common gram-positive and gram-negative bacteria, the synovial fluid usually reveals a WBC count of > 100,000/mm3 with > 80% polymorphonuclear neutrophils. Occasionally, the synovial fluid WBC count will be lower, particularly early in the course of infection, and lower WBC counts do not rule out infection if there is a reasonable clinical suspicion. Infection with opportunistic or atypical organisms such as Mycobacteria may be associated with synovial fluid WBC counts of 5000–50,000/mm3. Synovial fluid culture usually reveals gram-positive organisms, particularly Staphylococcus. In the elderly, gram-negative infections are more likely to occur. The presence of urate or CPPD crystals does not rule out -infection, and if the synovial fluid WBC count is > 100,000/mm, it is prudent to treat the patient for septic arthritis until cultures are complete.
Crystal-induced arthritis and hemarthrosis may be difficult to differentiate from septic arthritis. Polyarticular arthritis can be seen in gonococcus, Lyme disease, and bacterial endocarditis. Synovial fluid analysis is essential if septic arthritis is in the differential diagnosis.
Empiric antibiotic treatment should be instituted before culture results. If the Gram's stain is positive, therapy is guided by the result. Oxacillin is recommended for initial
therapy of community-acquired gram-positive infections and vancomycin for patients with indwelling venous catheters or suspected hospital-acquired infection. Gram-negative infections should be treated with a first-generation cephalosporin or an antipseudomonal penicillin with an aminoglycoside. If the Gram's stain is negative, the patient should receive coverage for clinically suspected organisms. Gram-negative infection is more common in the elderly, and antibiotic coverage should be appropriately broad. Antibiotic therapy should be tailored to the culture and sensitivity results and the clinical course. Home antibiotic therapy for 2–6 weeks is usually necessary, depending on the severity of the initial infection and the response to treatment.
Septic arthritis is an infection in a closed space akin to an abscess, and drainage is necessary to eradicate the infection. Needle aspiration every 1–2 days is sufficient for small to medium-size joints that are easily aspirated. Surgical arthrotomy is usually recommended for the hip and is indicated for any joint in which the purulent fluid is too thick to drain with a needle. Arthrotomy is also recommended if needle aspiration does not document a falling synovial fluid WBC count and conversion of joint cultures to negative. It may be necessary to remove a prosthetic joint or foreign body to achieve sterilization.
ESSENTIALS OF DIAGNOSIS
- Dry eyes and mouth.
- Blood tests suggesting inflammatory autoimmune disease.
- Confirmatory ophthalmology examination or salivary gland biopsy.
Sjögren's syndrome is caused by autoimmune attack on the glands that make saliva and tears. Sjögren's syndrome can occur in isolation (primary Sjögren's) or can accompany another autoimmune disease, usually SLE, RA, or scleroderma (secondary Sjögren's). Other autoimmune phenomena may be associated, including pneumonitis and vasculitis.
- SYMPTOMS & SIGNS
The patient reports gradually worsening dryness of the eyes and mouth (keratoconjunctivitis sicca and xerostomia). Loss of tears can lead to scratching and infection of the cornea. Loss of saliva can lead to accelerated dental caries and periodontal disease. There may be parotid gland enlargement and dryness of other mucosal surfaces such as the pharynx, trachea, and vagina. Patients may experience pneumonitis or vasculitis. Patients with pneumonitis report gradually worsening dyspnea and cough. Vasculitis can present as a purpuric rash with lower extremity predominance or multiple peripheral neuropathies (mononeuritis multiplex). Some patients experience a stocking-distribution sensory neuropathy, with tingling in the feet and neuropathic pain. In secondary Sjögren's syndrome, there will also be symptoms and signs of the primary connective tissue disease.
- LABORATORY TESTS
ANA is positive in ~80% of patients, and additional autoantibody testing reveals anti-SSA (Ro) or anti-SSB (La) in 50–80%. RF is positive in 90% of patients and does not necessarily indicate coexisting RA. Polyclonal hyperglobulinemia and increased ESR are common.
Slit-lamp examination with rose bengal or equivalent stain can reveal the ocular consequences of chronically dry eyes. To test for ocular dryness, one can place a filter paper on the palpebral conjunctiva and measure the extent of wetness at 5 min (the Schirmer test); 5 mm of wetness or less is diagnostic of deficient tear production. Tests of salivary gland secretion are also available but less commonly used.
Biopsy of the minor salivary glands of the lip can be obtained under local anesthesia. The presence of focal lymphocytic infiltrates with overlying normal mucosa is consistent with Sjögren's syndrome.
Dry mucosal surfaces can be caused by aging or medications and parotid gland enlargement by infectious parotitis, lymphoma, and sarcoidosis. When other autoimmune phenomena are present, the differential diagnosis includes lupus and RA. Fibromyalgia is commonly seen in patients with primary Sjögren's; one must take care not to attribute the fibromyalgia symptoms to lupus or RA. The presence of widespread myo-fascial tenderness supports a diagnosis of fibromyalgia.
Treatment is largely symptomatic. Liberal use of artificial tears with lubricating ointment overnight for the eyes and water and sugar-free beverages for the mouth often provides some relief. Proper oral hygiene practices and frequent visits to the dentist can prevent gum disease and loss of teeth.
Pilocarpine, 5 mg 4 times a day, or cevimeline, 30 mg 3 times a day, can be used to stimulate production of
saliva. Secretogogues are not generally effective for dry eyes. Adverse effects can include sweating, flushing, diarrhea, bronchospasm, and increased intra-ocular pressure.
Immunosuppressants cannot save the lacrimal and salivary glands from autoimmune attack and are generally not used for that purpose. Hydroxychloroquine is sometimes used to treat Sjögren's-related arthralgia. True synovitis suggests secondary Sjögren's in the setting of RA or SLE and is treated accordingly. In primary Sjögren's, corticosteroids and other immunosuppressants are reserved for treatment of autoimmune attack on nonexocrine organs or systemic vasculitis. Patients with autoimmune attack confined to exocrine glands can still have impressive laboratory phenomena, including high ESR, anemia of chronic disease, positive ANA, and positive RF. One should not overreact to the laboratory phenomena and reserve immunosuppression for potentially reversible organ-threatening disease.
ESSENTIALS OF DIAGNOSIS
- Ischemia or hemorrhage in end-organs.
- Symptoms and laboratory evidence of systemic inflammation.
- Patterns of organ involvement, laboratory testing, and biopsy allow more specific diagnoses.
Vasculitis is often suspected when a patient appears to have a systemic, inflammatory disease with ischemia or hemorrhage in a variety of end-organs. Certain physical examination signs, such as palpable purpura, cutaneous ulcers, or mononeuritis multiplex, are suspicious for the presence of vasculitis. Diagnosis of a particular type of vasculitis often requires a carefully performed history, physical, laboratory testing, imaging, and directed biopsy. Characteristics of the specific vasculitides are summarized in Table 26-6.
- SYMPTOMS & SIGNS
Many patients will report nonspecific symptoms of chronic systemic inflammation, including fatigue, malaise, weight loss, and fever. The other symptoms and signs will differ according to the pattern of organ involvement. Involvement of the skin can present as palpable purpura, usually on the lower extremities and buttocks, or as well-demarcated ischemic ulcers. Peripheral nerve involvement is usually manifested as mononeuritis multiplex. Abdominal pain and bloody stool suggests gastrointestinal involvement. Lung involvement usually presents with dyspnea and cough. Brain or meningeal involvement is suggested by headache, seizures, altered consciousness, or focal neurological deficits. Myocardial involvement usually manifests as heart failure; symptoms of angina can be seen in coronary involvement by GCA but are rare in other vasculitides.
There is usually evidence of an acute-phase response, with increased ESR and CRP, anemia of chronic disease, increased platelet count, low serum albumin, and increased complement. Low serum complement can be seen in lupus and cryoglobulinemia. Peripheral blood eosinophilia is suggestive of Churg-Strauss vasculitis, but mild eosinophilia can be seen in other vasculitides. In the vasculitides listed in Table 26-6, ANA is usually negative, but RF is occasionally positive. Vasculitis associated with a strongly positive ANA raises concerns about lupus, Sjögren's syndrome, or RA. Antineutrophil cytoplasmic antibody (ANCA) screening is usually performed by immunofluorescence, followed by more specific enzyme immunoassay, and is most useful when
there is a clinical suspicion of Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA). A c-ANCA pattern is seen with antibodies to proteinase 3 and is approximately 98% specific for WG; however, ANCA testing has low sensitivity and can be negative in WG patients with early disease or disease limited to the upper airway. A p-ANCA immunofluorescence pattern is seen with antibodies to myeloperoxidase and is suggestive of MPA, but it can also be seen in WG and nonvasculitic glomerular disease. High ANCA titers are more likely to be significant; low-titer positive results may be misleading and should be interpreted with caution. Patients with a clinical suspicion of polyarteritis nodosa (PAN) should be tested for antibodies to hepatitis B virus.
Table 26-6. Characteristics of selected vasculitides.
Plain radiographs may show pulmonary infiltrates, cardiac enlargement, or free abdominal air caused by a perforated viscus. Chest CT is more sensitive than radiography to reveal pulmonary involvement by vasculitis. Abdominal CT may reveal bowel wall edema or wedge-shaped renal infarcts. MRI of the brain is useful if there is evidence of central nervous system injury. Contrast angiograms of the renal and mesenteric arteries reveal stenoses, aneurysms, and poststenotic dilatation in patients with PAN. Contrast angiography is generally not used to diagnose WG, MPA, or hypersensitivity vasculitis because the inflamed vessels are usually too small to be seen on the angiogram.
Skin biopsy is usually performed if cutaneous vasculitis is suspected. In WG and MPA, kidney biopsy usually shows a pauci-immune glomerulonephritis; the renal biopsy does not usually directly confirm the presence of vasculitis but can be useful in excluding other causes of a pulmonary-renal syndrome, including SLE and Goodpasture's syndrome. Bronchoscopic lung biopsy does not usually provide enough tissue to confirm vasculitis but can be useful to rule out infection, malignancy, or sarcoidosis. Thoracoscopic-guided open lung biopsy is best when a definitive lung biopsy is desired, as in suspected WG, Churg-Strauss, or MPA. Endoscopic bowel biopsy is not generally useful in diagnosing vasculitis, but bowel removed at surgery should be carefully sectioned if vasculitis is clinically suspected. Sural nerve biopsy may reveal vasculitis of the vasa nervorum in patients with mononeuritis multiplex, but false-negative biopsies are common.
Nerve conduction studies can assist with differentiating mononeuritis multiplex from other causes of -neurological symptoms in the extremities, including entrapment neuropathies, radiculopathies, or toxic/metabolic neuropathies.
Conditions that can mimic vasculitis are summarized in Table 26-7.
Table 26-7. Differential diagnosis of vasculitis.
Leukocytoclastic or hypersensitivity vasculitis confined to the skin (palpable purpura) can be treated by withdrawing the inciting antigen, if it can be identified. Cutaneous vasculitis associated with an acute viral infection will generally resolve as the patient recovers from the virus. Vasculitis that results from hypersensitivity to a medication is best treated by withdrawal of the medication. Chronic palpable purpura can be treated with colchicine, 0.6 mg once or twice daily, dapsone, or hydroxychloroquine. Systemic corticosteroids are often not indicated because the adverse effects can be more harmful than isolated cutaneous vasculitis.
Evidence of end-organ injury outside the skin necessitates treatment with prednisone, 1–1.5 mg/kg/day, with gradual taper over 6 mo. For significant threat to the lung, myocardium, nervous system, lung, or kidney, cyclophosphamide, 2–4 mg/kg/day, is given as a single morning daily dose. Potential toxicities of daily cytoxan include cytopenias, infection, hemorrhagic cystitis, alopecia, nausea, diarrhea, mucositis, and late malignancy. Patients should drink fluids liberally to protect the bladder from toxic metabolites. A CBC should be obtained every 1–2 weeks, and the cyclophospha-mide dose should be lowered as necessary so that the WBC count does not fall below 3000/mm3. Cyclophosphamide treatment is generally continued for 3 mo; patients who are doing well can then be switched to methotrexate, 12.5–15 mg/week. Azathioprine, 2 mg/kg/day, can substitute for methotrexate in patients with diminished renal function (serum creatinine > 1.8 mg/dL).