2844 PART 11 Immune-Mediated, Inflammatory, and Rheumatologic Disorders

Section 3 Disorders of the Joints and

Adjacent Tissues

370 Approach to Articular

and Musculoskeletal

Disorders

John J. Cush

Musculoskeletal complaints account for >315 million outpatient visits

per year and >20% of all outpatient visits in the United States. The

Centers for Disease Control and Prevention estimate that 58.5 million

(or 1 in 4 adults) of the U.S. population has physician-diagnosed arthritis. While many patients will have self-limited conditions requiring

minimal evaluation, reassurance, and symptomatic therapy, specific

musculoskeletal presentations or their persistence may herald a more

serious condition that requires further evaluation or laboratory testing

to establish a diagnosis. The goal of the musculoskeletal evaluation

is to formulate a differential diagnosis that leads to an accurate diagnosis and timely therapy, while avoiding excessive diagnostic testing

and unnecessary treatment (Table 370-1). There are several urgent

conditions that must be diagnosed promptly to avoid damage

and morbidity. These “red flag” diagnoses include septic arthritis,

acute crystal-induced arthritis (e.g., gout), and fracture. Each may be

TABLE 370-1 Evaluation of Patients with Musculoskeletal Complaints

Goals

Accurate diagnosis

Timely provision of therapy

Avoidance of unnecessary diagnostic testing

Identification of acute, focal/monarticular “red flag” conditions

Approach

Determine the chronology (acute vs chronic)

 Determine the nature of the pathologic process (inflammatory vs

noninflammatory)

 Determine the extent of involvement (monarticular, polyarticular, focal,

widespread)

Anatomic localization of complaint (articular vs nonarticular)

Consider the most common disorders first

Consider the need for diagnostic testing

Formulate a differential diagnosis

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cause autoinflammatory disease. Nature 577:103, 2020.

Manthiram K et al: The monogenic autoinflammatory diseases

define new pathways in human innate immunity and inflammation.

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Manthiram K et al: Common genetic susceptibility loci link PFAPA

syndrome, Behçet’s disease, and recurrent aphthous stomatitis. Proc

Natl Acad Sci USA 117:14405, 2020.

Ombrello AK et al: Treatment strategies for deficiency of adenosine

deaminase 2. N Engl J Med 380:1582, 2019.

Park YH et al: Pyrin inflammasome activation and RhoA signaling in

the autoinflammatory diseases FMF and HIDS. Nat Immunol 17:914,

2016.

Park YH et al: Ancient familial Mediterranean fever mutations in

human pyrin and resistance to Yersinia pestis. Nat Immunol 21:857,

2020.

suspected by an acute onset and monarticular or focal musculoskeletal

pain.

The majority of individuals with musculoskeletal complaints can be

diagnosed with a thorough history and a comprehensive physical and

musculoskeletal examination. The initial encounter should determine

whether the musculoskeletal complaint signals a red flag condition

(septic arthritis, gout, or fracture) or not. The evaluation should ascertain if the complaint is (1) articular or nonarticular, (2) inflammatory

or noninflammatory, (3) acute or chronic, and (4) localized (monarticular) or widespread (polyarticular).

With this approach, the musculoskeletal presentation can be characterized (e.g., acute inflammatory monarthritis or a chronic noninflammatory, nonarticular widespread pain) to narrow the diagnostic

possibilities. However, some patients will not fit immediately into an

established diagnostic category. Many musculoskeletal disorders

resemble each other at the outset, and some may take weeks or months

(but not years) to evolve into a recognizable diagnostic entity. This consideration should temper the desire to establish a definitive diagnosis

at the first encounter.

ARTICULAR VERSUS NONARTICULAR

The musculoskeletal evaluation must discriminate the anatomic origin(s) of the patient’s complaint. For example, ankle pain can result from

a variety of pathologic conditions involving disparate anatomic structures, including gouty arthritis, calcaneal fracture, Achilles tendinitis,

plantar fasciitis, cellulitis, and peripheral or entrapment neuropathy.

Distinguishing between articular and nonarticular conditions requires

a careful and detailed examination. Articular structures include the

synovium, synovial fluid, articular cartilage, intraarticular ligaments,

joint capsule, and juxtaarticular bone. Nonarticular (or periarticular)

structures, such as supportive extraarticular ligaments, tendons, bursae, muscle, fascia, bone, nerve, and overlying skin, may be involved

in the pathologic process. Although musculoskeletal complaints are

often ascribed to the joints, nonarticular disorders are more frequent

and are often confused with arthritis. Distinguishing between articular

and nonarticular (also called periarticular) pain may be challenging

to the unskilled examiner. Articular disorders may be characterized

by deep or diffuse pain, limited range of motion on active and passive

movement, and swelling (caused by synovial proliferation, effusion, or

bony enlargement), crepitation, instability, “locking,” or deformity. By

contrast, nonarticular disorders tend to be painful on active, but not

passive (or assisted), range of motion. Periarticular conditions often

demonstrate point or focal tenderness in regions adjacent to articular

structures, may radiate or be elicited with a specific movement or

position, and have physical findings remote from the joint capsule.

Moreover, nonarticular disorders seldom demonstrate swelling, crepitus, instability, or deformity.

INFLAMMATORY VERSUS

NONINFLAMMATORY DISORDERS

In the course of a musculoskeletal evaluation, the examiner should

determine the nature of the underlying pathologic process and whether

inflammatory or noninflammatory findings exist. Inflammatory disorders may be infectious (Neisseria gonorrhoeae or Mycobacterium

tuberculosis), crystal-induced (gout, pseudogout), immune-related

(rheumatoid arthritis [RA], systemic lupus erythematosus [SLE]),

reactive (rheumatic fever, reactive arthritis), or idiopathic. Inflammatory disorders may be suggested by any of the four cardinal signs

of inflammation (erythema, warmth, pain, or swelling), systemic

symptoms (fatigue, fever, rash, weight loss), or laboratory evidence

of inflammation (elevated erythrocyte sedimentation rate [ESR] or

C-reactive protein [CRP], thrombocytosis, anemia of chronic disease,

or hypoalbuminemia). Articular stiffness commonly accompanies

chronic musculoskeletal disorders. The duration of stiffness may

be prolonged (hours) with inflammatory disorders (such as RA or

polymyalgia rheumatica [PMR]) and improves with activity. By contrast, intermittent stiffness (also known as gel phenomenon), typical of

noninflammatory conditions (such as osteoarthritis [OA]), is shorter

in duration (<60 min) and is exacerbated by activity. Fatigue may be

Approach to Articular and Musculoskeletal Disorders

2845CHAPTER 370

With identification of the nature of the underlying process and the site

of the complaint, the examiner can further categorize the musculoskeletal presentation (e.g., acute inflammatory monoarthritis, chronic

noninflammatory, nonarticular widespread pain). By narrowing the

diagnostic considerations, the examiner can assess the need for immediate diagnostic or therapeutic intervention or for continued observation. Figure 370-1 presents an algorithmic approach to the evaluation

of patients with musculoskeletal complaints. This approach relies on

clinical and historic features, rather than laboratory testing, to diagnose

many common rheumatic disorders.

A simpler, alternative approach would consider the most commonly

encountered complaints first, based on frequency in younger versus

profound with inflammation (as seen in RA and PMR) but may also be

a consequence of fibromyalgia (a noninflammatory disorder), chronic

pain, poor sleep, depression, anemia, cardiac failure, endocrinopathy,

or malnutrition.

Noninflammatory disorders may be related to trauma (rotator cuff

tear), repetitive use (bursitis, tendinitis), degeneration or ineffective

repair (OA), neoplasm (pigmented villonodular synovitis), or pain

amplification (fibromyalgia). Noninflammatory disorders are often

characterized by pain without synovial swelling or warmth, absence of

inflammatory or systemic features, intermittent gel phenomena rather

than prolonged morning stiffness, and normal (for age) or negative

laboratory investigations.

Initial rheumatic history and physical

exam to determine

1. Is it articular?

2. Is it acute or chronic?

3. Is inflammation present?

4. How many/which joints are involved?

Nonarticular condition Is it articular?

Consider

• Trauma/fracture

• Fibromyalgia

• Polymyalgia rheumatica

• Bursitis

• Tendinitis

• Myopathy/myositis

Is it acute, focal,

or monoarticular

Consider “red flag”

condition

• Gout

• Septic arthritis

• Fracture

• Vascular ischemia

• Carpal tunnel

 syndrome

Is complaint >6 wk?

Acute Chronic

Consider

• Acute arthritis

• Septic arthritis

• Gout

• Pseudogout

• Reactive arthritis

• Initial presentation

 of chronic arthritis

Is inflammation present?

1. Is there prolonged morning stiffness?

2. Is there soft tissue swelling?

3. Are there systemic symptoms?

4. Is the ESR or CRP elevated?

Chronic

inflammatory

arthritis

How many

joints involved?

Are DIP, CMC1, hip, or

knee joints involved?

Chronic inflammatory

mono/oligoarthritis

Consider

• TB/fungal infection

• Psoriatic arthritis

• Reactive arthritis

• Pauciarticular JIA

Chronic inflammatory

polyarthritis

Is involvement

symmetric?

Are PIP, MCP, or

MTP joints

involved?

Consider

• Psoriatic arthritis

• Reactive arthritis

• Enteropathic arthritis

Rheumatoid

arthritis

Osteoarthritis

No Yes

Musculoskeletal Complaint

Yes

Yes

No

No

No Yes

No Yes

No Yes

No Yes

1– 3 >3

Unlikely to be osteoarthritis

Consider

• Osteonecrosis

• Charcot arthritis

• Hemochromatosis

Chronic

noninflammatory

arthritis

Unlikely to be rheumatoid arthritis

Consider

 • SLE • Scleroderma • Polymyositis

FIGURE 370-1 Algorithm for the diagnosis of musculoskeletal complaints. An approach to formulating a differential diagnosis (shown in italics). CMC, carpometacarpal; CRP,

C-reactive protein; DIP, distal interphalangeal; ESR, erythrocyte sedimentation rate; JIA, juvenile idiopathic arthritis; MCP, metacarpophalangeal; MTP, metatarsophalangeal;

PIP, proximal interphalangeal; PMR, polymyalgia rheumatica; SLE, systemic lupus erythematosus; TB, tuberculosis.

2846 PART 11 Immune-Mediated, Inflammatory, and Rheumatologic Disorders

Trauma/fracture Low back pain

Age <60 years Age >60 years

Repetitive strain injury

(tendinitis, bursitis)

Osteoarthritis

Gout (males only)

Gout

Pseudogout

Rheumatoid arthritis Polymyalgia rheumatica

Osteoporotic fracture

Infectious arthritis

(GC, viral, bacterial, Lyme)

Septic arthritis

(bacterial)

Fibromyalgia

Orthopedic evaluation

PREVALENCE

High

Low

Psoriatic, reactive

arthritis, IBD arthritis

FIGURE 370-2 Algorithm for consideration of the most common musculoskeletal

conditions. GC, gonococcal; IBD, inflammatory bowel disease.

older populations. The most prevalent causes of musculoskeletal

complaints are shown in Fig. 370-2. Because trauma, fracture, overuse

syndromes, and fibromyalgia are among the most common causes

of musculoskeletal pain, these should be considered with each new

encounter. If excluded, other frequently occurring disorders should be

considered according to the patient’s age. Hence, those aged <60 years

are commonly affected by repetitive use/strain disorders, gout (men

only), RA, spondyloarthritis, and uncommonly, infectious arthritis.

Patients aged >60 years are frequently affected by OA, crystal (gout and

pseudogout) arthritis, PMR, osteoporotic fracture, and uncommonly,

septic arthritis. These conditions are between 10 and 100 times more

prevalent than other serious autoimmune conditions, such as SLE,

scleroderma, polymyositis, and vasculitis.

■ CLINICAL HISTORY

Historic features may reveal important clues to the diagnosis. Aspects

of the patient profile, complaint chronology, extent of joint involvement, and precipitating factors can provide important information.

Certain diagnoses are more frequent in different age groups. SLE and

reactive arthritis occur more frequently in the young, whereas fibromyalgia and RA are frequent in middle age, and OA and PMR are more

prevalent among the elderly. Diagnostic clustering is also evident when

sex and race are considered. Gout, spondyloarthritis, and ankylosing

spondylitis are more common in men, whereas RA, fibromyalgia, osteoporosis, and lupus are more frequent in women. Racial predilections

may be evident. Thus, PMR, giant cell arteritis, and granulomatosis

with polyangiitis (GPA; formerly called Wegener’s granulomatosis)

commonly affect whites, whereas sarcoidosis and SLE more commonly

affect African Americans. Familial aggregation is unlikely for most

arthropathies but may be seen with ankylosing spondylitis, gout, and

Heberden’s nodes of OA.

The chronology of the complaint is an important diagnostic feature

and can be divided into the onset, evolution, and duration. The onset

of disorders such as septic arthritis or gout tends to be abrupt, whereas

OA, RA, and fibromyalgia may have more indolent presentations. The

patients’ complaints may evolve differently and be classified as chronic

(OA), intermittent (crystal or Lyme arthritis), migratory (rheumatic

fever, gonococcal or viral arthritis), or additive (RA, psoriatic arthritis).

Musculoskeletal disorders are typically classified as acute or chronic

based on a symptom duration that is either <6 weeks or >6 weeks,

respectively. Acute arthropathies tend to be infectious, crystal-induced,

or reactive. Chronic conditions include noninflammatory or immunologic arthritides (e.g., OA, RA) and nonarticular disorders (e.g.,

fibromyalgia).

The extent or distribution of articular involvement is often informative. Articular disorders are classified based on the number of joints

involved, as either monarticular (one joint), oligoarticular or pauciarticular (two or three joints), or polyarticular (four or more joints).

Although crystal and infectious arthritis are often mono- or oligoarticular, OA and RA are usually polyarticular. Nonarticular disorders may

be classified as either focal or widespread. Complaints secondary to

tendinitis or carpal tunnel syndrome are typically focal, whereas weakness and myalgia, caused by polymyositis or fibromyalgia, are more

widespread in their presentation. Joint involvement in RA tends to be

symmetric and polyarticular. By contrast, spondyloarthritis, reactive

arthritis, gout, and sarcoid are often asymmetric and oligoarticular.

OA and psoriatic arthritis may be either symmetric or asymmetric and

oligo- or polyarticular. The upper extremities are frequently involved

in RA and OA, whereas lower extremity arthritis is characteristic of

reactive arthritis and gout at their onset. Involvement of the axial skeleton is common in OA and ankylosing spondylitis but is infrequent in

RA, with the notable exception of the cervical spine.

The clinical history should also identify precipitating events,

such as trauma (osteonecrosis, meniscal tear), drug administration

(Table 370-2), antecedent or intercurrent infection (reactive arthritis,

hepatitis, chikungunya), or illnesses that may have contributed to the

patient’s complaint. Certain comorbidities may have musculoskeletal

consequences. This is especially so for diabetes mellitus (carpal tunnel syndrome), renal insufficiency (gout), depression or insomnia

(fibromyalgia), myeloma (spinal pain), cancer (myositis), and osteoporosis (fracture) or when using certain drugs such as glucocorticoids

(osteonecrosis, septic arthritis), diuretics, or chemotherapy (gout)

(Table 370-2).

Lastly, a thorough rheumatic review of systems may disclose useful

diagnostic information. A variety of musculoskeletal disorders may be

associated with systemic features such as fever (Still’s disease, infection), rash (SLE, psoriatic arthritis), nail abnormalities (psoriatic or

reactive arthritis), myalgias (fibromyalgia, statin- or drug-induced

myopathy), or weakness (polymyositis, neuropathy). In addition, some

conditions are associated with involvement of other organ systems

including the eyes (Behçet’s disease, sarcoidosis, spondyloarthritis),

gastrointestinal tract (scleroderma, inflammatory bowel disease), genitourinary tract (reactive arthritis, gonococcemia), or nervous system

(Lyme disease, vasculitis).

■ FIBROMYALGIA

Syphilis and tuberculosis have been called the “great masqueraders”

as their protean symptoms and potential for multiorgan involvement

may result in delays in diagnosis and treatment. In the modern era,

other serious diagnoses (including lupus, sarcoidosis, vasculitis, and

lymphoma) have also been labeled as great masqueraders. All of these

are either uncommon or rare, compared to the more common masquerader of musculoskeletal complaints—fibromyalgia. Fibromyalgia

(see Chap. 373) is a pain amplification disorder unified by sleep disturbance, exaggerated pain and sensitivity (owing to lowered pain thresholds), and a multiplicity of symptoms with a paucity of abnormalities

on clinical examination or laboratory testing. Tender “trigger points”

may be elicited over the epicondyles, trochanteric bursae, anserine bursae, and specific muscles (gluteal, trapezius, supraspinatus). Fibromyalgia is characterized by widespread aches and pains, even though

presenting symptoms tend to be fewer or focal. Fibromyalgia coexists

with numerous comorbidities including irritable bowel syndrome, dysmenorrhea, migraine, depression, anxiety, memory loss, nonanatomic

paresthesia or dysesthesia, fatigue, myalgias, temporomandibular joint

pain, hypermobility, and multiple chemical sensitivities. Fibromyalgia

Approach to Articular and Musculoskeletal Disorders

2847CHAPTER 370

affects nearly 5 million Americans but is underrecognized or misdiagnosed as arthritis, lupus, multiple sclerosis, autoimmune disease,

or other conditions. Early consideration of this very common disorder can avert needless investigation, therapy, and concern for those

afflicted (Fig. 370-2).

RHEUMATOLOGIC EVALUATION

OF THE ELDERLY

The incidence of rheumatic diseases rises with age, such that 58% of

those >65 years will have joint complaints. Musculoskeletal disorders

in elderly patients are often not diagnosed because the signs and symptoms may be insidious, overlooked, or overshadowed by comorbidities.

These difficulties are compounded by the diminished reliability of

laboratory testing in the elderly, who often manifest nonpathologic

abnormal results. For example, the ESR may be misleadingly elevated,

and low-titer positive tests for rheumatoid factor (RF) and antinuclear antibodies (ANAs) may be seen in up to 15% of elderly patients.

Although nearly all rheumatic disorders afflict the elderly, geriatric

patients are particularly prone to OA, osteoporosis, osteoporotic fractures, gout, pseudogout, PMR, vasculitis, and drug-induced disorders

(Table 370-2). The elderly should be approached in the same manner

as other patients with musculoskeletal complaints, but with an emphasis on identifying the potential rheumatic consequences of medical

comorbidities and therapies used in the elderly. The physical examination should identify the nature of the musculoskeletal complaint as

well as coexisting diseases that may influence diagnosis and choice of

treatment.

RHEUMATOLOGIC EVALUATION OF

THE HOSPITALIZED PATIENT

Evaluation of a hospitalized patient with rheumatic complaints is often

more complex owing to symptom severity, acute presentations, and

greater interplay of comorbidities. Patients with rheumatic disorders

tend to be admitted for one of several reasons: (1) acute onset of

inflammatory arthritis (possibly gout or septic arthritis); (2) undiagnosed systemic or febrile illness; (3) musculoskeletal trauma; (4)

exacerbation or deterioration of an existing musculoskeletal disorder

(e.g., SLE); or (5) new medical comorbidities (e.g., thrombotic event,

lymphoma, infection) arising in patients with an established rheumatic

disorder. Notably, rheumatic patients are seldom if ever admitted

because of widespread pain or serologic abnormalities or for the initiation of new therapies.

Acute monoarticular inflammatory arthritis is a “red flag” presentation (e.g., septic arthritis, gout, pseudogout) that may require

arthrocentesis or hospitalization if infection is suspected. New-onset

inflammatory polyarthritis has a wide differential diagnosis (e.g.,

RA, hepatitis-related arthritis, chikungunya arthritis, serum sickness,

drug-induced lupus, SLE, polyarticular septic arthritis) and may

require targeted laboratory investigations more so than synovial fluid

analyses. Patients with febrile, multisystem disorders require exclusion of crystal, infectious, or neoplastic etiologies and an evaluation

driven by the dominant symptom/finding with the greatest specificity.

Conditions worthy of consideration may include gout or pseudogout,

vasculitis (giant cell arteritis in the elderly or polyarteritis nodosa in

younger patients), adult-onset Still’s disease, SLE, antiphospholipid

antibody syndrome, IgG4-related disease, and sarcoidosis. A preexisting rheumatic diagnosis (e.g., SLE, RA, ankylosing spondylitis) should

be confirmed by careful history and examination and review of medical records, as this will influence the ensuing in-patient evaluation.

Notably, when established rheumatic disease patients are admitted to

the hospital, it is usually not for their autoimmune disease, but rather

a comorbid medical problem or complication of drug therapy. Patients

with chronic inflammatory disorders (e.g., RA, SLE, psoriasis) have an

augmented risk of infection, cardiovascular events, pulmonary disorders, and neoplasia.

Certain conditions, such as acute gout, can be precipitated in hospitalized patients by surgery, dehydration, or medications and should be

considered when hospitalized patients are evaluated for the acute onset

of a musculoskeletal condition. Lastly, overly aggressive and unfocused

laboratory testing will often yield abnormal findings that are better

explained by the patient’s preexisting condition (chronic lung, renal, or

liver disease) rather than a new inflammatory or autoimmune disorder

(lupus, vasculitis).

PHYSICAL EXAMINATION

The goal of the physical examination is to ascertain the structures

involved, the nature of the underlying pathology, the functional consequences of the process, and the presence of systemic or extraarticular

manifestations. A knowledge of topographic anatomy is necessary

to identify the primary site(s) of involvement and differentiate articular from nonarticular disorders. The musculoskeletal examination

depends largely on careful inspection, palpation, contralateral comparison, and a variety of specific physical maneuvers to elicit diagnostic

signs (Table 370-3). Although most articulations of the appendicular

skeleton can be examined in this manner, adequate inspection and

TABLE 370-2 Drug-Induced Musculoskeletal Conditions

Arthralgias

 Quinidine, cimetidine, beta blockers, quinolones, chronic acyclovir,

interferons, IL-2, nicardipine, vaccines, rifabutin, aromatase inhibitors,

HIV protease inhibitors, DPP-4 inhibitors (sitagliptin, linagliptin, alogliptin),

paclitaxel, checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab,

atezolizumab, durvalumab, cemiplimab)

Myalgias/myopathy

 Glucocorticoids, penicillamine, hydroxychloroquine, AZT, lovastatin,

simvastatin, atorvastatin, pravastatin, clofibrate, amiodarone, interferon,

IL-2, alcohol, cocaine, paclitaxel, docetaxel, imatinib mesylate, colchicine,

quinolones, cyclosporine, tacrolimus, protease inhibitors, checkpoint

inhibitors

Tendon rupture/tendinitis

 Quinolones, glucocorticoids, isotretinoin, statins, aromatase inhibitors,

collagenase injections

Gout

 Diuretics, aspirin, cytotoxics, cyclosporine, tacrolimus, alcohol, moonshine,

ethambutol, fructose-containing soft drinks

Drug-induced lupus

 Hydralazine, procainamide, quinidine, phenytoin, carbamazepine, methyldopa,

isoniazid, chlorpromazine, lithium, penicillamine, tetracyclines, TNF inhibitors,

ACE inhibitors, ticlopidine, terbinafine, aromatase inhibitors

Drug-induced subacute lupus

 Proton pump inhibitors, calcium channel blockers (diltiazem), ACE inhibitors,

TNF inhibitors, terbinafine, interferons (α and β-1a), paclitaxel, docetaxel,

gemcitabine, capecitabine, aromatase inhibitors, HCTZ

Osteonecrosis/atypical fractures

Glucocorticoids, alcohol, radiation, bisphosphonates

Osteopenia

 Glucocorticoids, chronic heparin, phenytoin, aromatase inhibitors,

antiandrogen therapy, thiazolidinediones

Psoriasis

 TNF inhibitors, beta blockers, lithium, hydroxychloroquine, chloroquine,

minocycline, ACE inhibitors, terbinafine, checkpoint inhibitors.

Scleroderma

 Vinyl chloride, bleomycin, baricitinib, pentazocine, organic solvents,

carbidopa, tryptophan, rapeseed oil

Raynaud’s phenomenon

 Cisplatin, bleomycin, beta blockers, clonidine, bromocriptine, ergot alkaloids,

cocaine, methylphenidate, dextroamphetamine, phentermine, interferon

therapy

Vasculitis

 Allopurinol, amphetamines, cocaine (often levamisole adulterated), cannabis,

thiazides, penicillamine, propylthiouracil, montelukast, TNF inhibitors, hepatitis

B vaccine, trimethoprim/sulfamethoxazole, minocycline, hydralazine

Abbreviations: ACE, angiotensin-converting enzyme; AZT, zidovudine; HCTZ,

hydrochlorothiazide; IL-2, interleukin 2; TNF, tumor necrosis factor.

2848 PART 11 Immune-Mediated, Inflammatory, and Rheumatologic Disorders

TABLE 370-3 Glossary of Musculoskeletal Terms

Crepitus

 A palpable (less commonly audible) vibratory or crackling sensation elicited

with joint motion; fine joint crepitus is common and often insignificant in

large joints; coarse joint crepitus indicates advanced cartilaginous and

degenerative changes (as in osteoarthritis)

Subluxation

 Alteration of joint alignment such that articulating surfaces incompletely

approximate each other

Dislocation

 Abnormal displacement of articulating surfaces such that the surfaces are not

in contact

Range of motion

 For diarthrodial joints, the arc of measurable movement through which the

joint moves in a single plane

Contracture

 Loss of full movement resulting from a fixed resistance caused either by

tonic spasm of muscle (reversible) or by fibrosis of periarticular structures

(permanent)

Deformity

 Abnormal shape or size resulting from bony hypertrophy, malalignment of

articulating structures, or damage to periarticular supportive structures

Enthesitis

Inflammation of the entheses (tendinous or ligamentous insertions on bone)

Epicondylitis

Infection or inflammation involving an epicondyle

palpation are not possible for many axial (e.g., zygapophyseal) and

inaccessible (e.g., sacroiliac or hip) joints. For such joints, there is a

greater reliance on specific maneuvers and imaging for assessment.

Examination of involved and uninvolved joints will determine

whether pain, warmth, erythema, or swelling is present. The locale and

level of pain elicited by palpation or movement should be quantified.

Examination of 28 easily palpated joints (proximal interphalangeals

[PIPs], metacarpophalangeals [MCPs], wrists, elbows, shoulders, and

knees) can quantify the number of tender or swollen joints (0–28)

involved. Careful examination should distinguish between true articular swelling (caused by bony hypertrophy, synovial effusion or proliferation) and nonarticular (or periarticular) involvement, which usually

extends beyond the normal joint margins. Cautious palpation can

distinguish synovial effusion (fluctuant swelling) from synovial hypertrophy (grape-like compressibility) and bony hypertrophy (firm as a

nut). Small to moderate knee effusions may be identified by the “bulge

sign” or “ballottement of the patellae.” Bursal effusions (e.g., effusions

of the olecranon or prepatellar bursa) are often focal and periarticular,

overlie bony prominences, and are fluctuant with defined borders. Joint

stability can be assessed by stabilizing the proximal joint and applying

manual stress to the distal appendage in different planes. Subluxation

or dislocation, which may be secondary to traumatic, mechanical, or

inflammatory causes, can be assessed by inspection and palpation.

Joint swelling or volume can be assessed by palpation. Distention of the

articular capsule usually causes pain and evident enlargement or fluctuance. The patient will attempt to minimize the pain by maintaining

the joint in the position of least intraarticular pressure and greatest

volume (usually partial flexion), possibly leading to flexion contracture over time. Active and passive range of motion should be assessed

in all planes, with contralateral comparison. A goniometer may be

used to quantify the arc of movement. Each joint should be passively

manipulated through its full range of motion (including, as appropriate, flexion, extension, rotation, abduction, adduction, lateral bending,

inversion, eversion, supination, pronation, medial/lateral deviation,

and plantar- or dorsiflexion). Extreme range of motion and connective

tissue laxity may be seen with hypermobility syndrome, Ehlers-Danlos

syndrome, or Marfan’s syndrome. Limitation of motion or contractures

are frequently caused by inflammation, effusion, pain, deformity, or

neuromyopathic causes. If passive motion exceeds active motion, a

periarticular process (e.g., tendinitis, tendon rupture, or myopathy)

should be considered. Contractures may reflect antecedent synovial

inflammation or trauma. Minor joint crepitus is common during

joint palpation and maneuvers but may indicate significant cartilage

degeneration as it becomes coarser (e.g., OA). Joint deformity usually

indicates a long-standing or aggressive pathologic process. Deformities

may result from ligamentous destruction, soft tissue contracture, bony

enlargement, ankylosis, erosive disease, subluxation, trauma, or loss

of proprioception. Examination of the musculature will document

strength, atrophy, pain, or spasm. Appendicular muscle weakness

should be characterized as proximal or distal. Muscle strength should

be assessed by observing the patient’s performance (e.g., walking, rising from a chair, grasping, writing). Strength may also be graded on

a 5-point scale: 0 for no movement; 1 for trace movement or twitch;

2 for movement with gravity eliminated; 3 for movement against gravity

only; 4 for movement against gravity and resistance; and 5 for normal

strength. The examiner should assess for often overlooked nonarticular

or periarticular involvement, especially when articular complaints are

not supported by objective findings referable to the joint capsule. The

identification of soft tissue or nonarticular pain will prevent unwarranted and often expensive additional evaluations. Specific maneuvers

may reveal common nonarticular abnormalities, such as a carpal tunnel syndrome (which can be identified by Tinel’s sign of Durkan’s test).

Other examples of soft tissue abnormalities include olecranon bursitis,

epicondylitis (e.g., tennis elbow), enthesitis (e.g., Achilles tendinitis),

and tender trigger points associated with fibromyalgia.

APPROACH TO REGIONAL RHEUMATIC

COMPLAINTS

Although all patients should be evaluated in a logical and thorough

manner, many focal musculoskeletal complaints are commonly caused

by disorders that exhibit a predictable pattern of onset, evolution, and

localization; they can often be easily diagnosed with limited historic

information and selected maneuvers or tests. Although nearly every

musculoskeletal complaint could be approached in this manner, the

evaluation of four commonly involved anatomic regions—the hand,

shoulder, hip, and knee—are reviewed here.

■ HAND PAIN

Focal or unilateral hand pain may result from trauma, overuse, infection, or a reactive or crystal-induced arthritis. By contrast, bilateral

hand complaints commonly suggest a degenerative (e.g., OA), systemic, or inflammatory/immune (e.g., RA) etiology. The distribution

or pattern of joint involvement is highly suggestive of certain disorders

(Fig. 370-3). Thus, OA (or degenerative arthritis) may manifest as

distal interphalangeal (DIP) and PIP joint pain and bony hypertrophy

leading to Heberden’s and Bouchard’s nodes, respectively. Pain, with

or without bony swelling, involving the base of the thumb (first carpometacarpal joint) is also highly suggestive of OA. By contrast, RA

manifests as an additive, symmetric, polyarticular arthritis involving

the PIP, MCP, intercarpal, and carpometacarpal joints (wrist) with pain

and palpable synovial tissue hypertrophy. Psoriatic arthritis may mimic

the pattern of joint involvement seen in OA (DIP and PIP joints) but

can be distinguished by the presence of inflammatory signs (erythema,

warmth, synovial swelling), with or without carpal involvement, nail

pitting, or onycholysis. Whereas lateral or medial subluxations at the

PIP or DIP joints are most likely due to inflammatory OA or psoriatic

arthritis, dorsal or ventral deformities (swan neck or boutonnière

deformities) are typical of RA. Hemochromatosis should be considered

when degenerative changes (bony hypertrophy) are seen at the second

and third MCP joints with associated radiographic chondrocalcinosis

or episodic, inflammatory wrist arthritis.

Dactylitis manifests as soft tissue swelling of the whole digit and

may have a sausage-like appearance. Common causes of dactylitis

include psoriatic arthritis, spondyloarthritis, juvenile spondylitis,

mixed connective tissue disease, scleroderma, sarcoidosis, and sickle

cell disease. Soft tissue swelling over the dorsum of the hand and wrist

may suggest an inflammatory extensor tendon tenosynovitis possibly

caused by gonococcal infection, gout, or inflammatory arthritis (e.g.,

Approach to Articular and Musculoskeletal Disorders

2849CHAPTER 370

RA). Tenosynovitis is suggested by localized warmth, swelling, or

pitting edema and may be confirmed when the soft tissue swelling

tracks with tendon movement during flexion and extension of fingers,

or when pain is induced while stretching the extensor tendon sheaths

(flexing the digits distal to the MCP joints and maintaining the wrist

in a fixed, neutral position). Volar (palmar) tendon swellings may

be from tenosynovitis, Dupuytren’s contractures, tendon nodules, or

synovial cysts.

Focal wrist pain localized to the radial aspect may be caused by de

Quervain’s tenosynovitis resulting from inflammation of the tendon

sheath(s) involving the abductor pollicis longus or extensor pollicis

brevis (Fig. 370-3). This commonly results from overuse or follows

pregnancy and may be diagnosed with Finkelstein’s test. A positive

result is present when radial wrist pain is induced after the thumb

is flexed and placed inside a clenched fist and the patient actively

deviates the hand downward with ulnar deviation at the wrist. Carpal

tunnel syndrome is another common disorder of the upper extremity

and results from compression of the median nerve within the carpal

tunnel. Manifestations include pain in the wrist that may radiate with

paresthesia to the thumb, second and third fingers, and radial half of

the fourth finger and, at times, atrophy of thenar musculature. Carpal

tunnel syndrome is commonly associated with pregnancy, edema,

trauma, OA, inflammatory arthritis, and infiltrative disorders (e.g.,

amyloidosis). The diagnosis may be suggested by a positive Durkan’s

test or Tinel’s sign. With each test, paresthesia in a median nerve

distribution is induced or increased by 30 s of compression over the

carpal tunnel (Durkan’s test) or “thumping” the volar aspect of the

wrist (Tinel’s sign). The low sensitivity and moderate specificity of

these tests may require nerve conduction velocity testing to confirm a

suspected diagnosis.

■ SHOULDER PAIN

During the evaluation of shoulder disorders, the examiner should carefully note any history of trauma, fibromyalgia, infection, inflammatory

1st CMC: OA

de Quervain's

tenosynovitis

DIP: OA,

psoriatic or

reactive arthritis

PIP: OA, SLE,

RA, psoriatic arthritis

MCP: RA,

pseudogout,

hemochromatosis

Wrist: RA,

pseudogout,

gonococcal arthritis,

juvenile arthritis,

carpal tunnel syndrome

FIGURE 370-3 Sites of hand or wrist involvement and their potential disease

associations. CMC, carpometacarpal; DIP, distal interphalangeal; MCP,

metacarpophalangeal; OA, osteoarthritis; PIP, proximal interphalangeal; RA,

rheumatoid arthritis; SLE, systemic lupus erythematosus. (Reproduced with

permission from JJ Cush et al [eds], Evaluation of musculoskeletal complaints,

in Rheumatology: Diagnosis and Therapeutics, 2nd ed. Philadelphia, Lippincott

Williams & Wilkins, 2005.)

disease, occupational hazards, or previous cervical disease. In addition,

the patient should be questioned as to the activities or movement(s)

that elicit shoulder pain. While arthritis is suggested by pain on movement in all planes, pain with specific active motion suggests a periarticular (nonarticular) process. Shoulder pain may originate in the

glenohumeral or acromioclavicular joints, subacromial (subdeltoid)

bursa, periarticular soft tissues (e.g., fibromyalgia, rotator cuff tear/

tendinitis), or cervical spine (Fig. 370-4). Shoulder pain is referred

frequently from the cervical spine but may also be referred from intrathoracic lesions (e.g., a Pancoast tumor) or from gallbladder, hepatic,

or diaphragmatic disease. These same visceral causes may also manifest

as focal scapular pain. Fibromyalgia should be suspected when glenohumeral pain is accompanied by diffuse periarticular (i.e., subacromial,

bicipital) pain, tender points (i.e., trapezius or supraspinatus), and a

sleep disturbance. The shoulder should be put through its full range of

motion both actively and passively (with examiner assistance): forward

flexion, extension, abduction, adduction, and internal and external

rotation. Manual inspection of the periarticular structures will often

provide important diagnostic information. Glenohumeral involvement

is best detected by placing the thumb over the glenohumeral joint just

medial and inferior to the coracoid process and applying pressure

anteriorly while internally and externally rotating the humeral head.

Pain localized to this region is indicative of glenohumeral pathology.

Synovial effusion or tissue is seldom palpable but, if present, may

suggest infection, RA, amyloidosis, or an acute tear of the rotator cuff.

The examiner should apply direct manual pressure over the subacromial bursa that lies lateral to and immediately beneath the acromion

(Fig. 370-4). Subacromial bursitis is a frequent cause of shoulder pain.

Anterior to the subacromial bursa, the bicipital tendon traverses the

bicipital groove. This tendon is best identified by palpating it in its

groove as the patient rotates the humerus internally and externally.

Direct pressure over the tendon may reveal pain indicative of bicipital

tendinitis. Palpation of the acromioclavicular joint may disclose local

Clavicle

Humerus

Bicipital

tendon

Glenohumeral

(shoulder) joint

Acromion

Acromioclavicular

joint

Subacromial

bursa

Supraspinatus

muscle

Subscapularis

muscle

Supraspinatus

tendon

FIGURE 370-4 Origins of shoulder pain. The schematic diagram of the shoulder

indicates, with arrows, the anatomic origins of shoulder pain.

2850 PART 11 Immune-Mediated, Inflammatory, and Rheumatologic Disorders

pain, bony hypertrophy, or, uncommonly, synovial swelling. Whereas

OA and RA commonly affect the acromioclavicular joint, OA seldom

involves the glenohumeral joint, unless there is avascular necrosis or a

traumatic or occupational cause.

Rotator cuff tendinitis or tear is a very common cause of shoulder

pain. Nearly 30% of the elderly will have shoulder pain, with rotator

cuff tendinitis or tear as a primary cause. The rotator cuff is formed

by four tendons that attach the scapula to the proximal humerus

(supraspinatus, infraspinatus, teres minor, and subscapularis tendons). Of these, the supraspinatus muscle is the most commonly

damaged. Rotator cuff tendinitis is suggested by pain on active

abduction (but not passive abduction), pain over the lateral deltoid

muscle, night pain, and evidence of the impingement signs (pain with

overhead arm activities). The Neer test for impingement is performed

by the examiner raising the patient’s arm into forced flexion while

stabilizing and preventing rotation of the scapula. A positive sign is

present if pain develops before 180° of forward flexion. Tear of the

rotator cuff is common in the elderly and often results from trauma;

it may manifest in the same manner as tendinitis. The drop arm test

is abnormal with supraspinatus pathology and is demonstrated by

passive abduction of the arm to 90° by the examiner. If the patient is

unable to hold the arm up actively or unable to lower the arm slowly

without dropping, the test is positive. Tendinitis or tear of the rotator cuff is best confirmed by magnetic resonance imaging (MRI) or

ultrasound.

■ KNEE PAIN

Knee pain may result from intraarticular (OA, RA) or periarticular

(anserine bursitis, collateral ligament strain) processes or be referred

from hip pathology. A careful history should delineate the chronology

of the knee complaint and whether there are predisposing conditions,

trauma, or medications that might underlie the complaint. For example, patellofemoral disease (e.g., OA) may cause anterior knee pain

that worsens with climbing stairs. Observation of the patient’s gait is

also important. The knee should be carefully inspected in the upright

(weight-bearing) and supine positions for swelling, erythema, malalignment, visible trauma, muscle wasting, and leg length discrepancy.

The most common malalignment in the knee is genu varum (bowlegs)

or genu valgum (knock-knees) resulting from asymmetric cartilage

loss medially or laterally, respectively. Bony swelling of the knee joint

commonly results from hypertrophic osseous changes seen with disorders such as OA and neuropathic arthropathy. Swelling caused by

hypertrophy of the synovium or synovial effusion may manifest as a

fluctuant, ballotable, or soft tissue enlargement in the suprapatellar

pouch (suprapatellar reflection of the synovial cavity) or regions lateral and medial to the patella. Synovial effusions may also be detected

by balloting the patella downward toward the femoral groove or by

eliciting a “bulge sign.” With the knee extended, the examiner should

manually compress, or “milk,” synovial fluid down from the suprapatellar pouch and lateral to the patellae. The application of manual

pressure lateral to the patella may cause an observable shift in synovial

fluid (bulge) to the medial aspect. The examiner should note that this

maneuver is only effective in detecting small to moderate effusions

(<100 mL). Inflammatory disorders such as RA, gout, pseudogout, and

psoriatic arthritis may involve the knee joint and produce significant

pain, stiffness, swelling, or warmth. A popliteal or Baker’s cyst may be

palpated with the knee partially flexed and is best viewed posteriorly

with the patient standing and knees fully extended to visualize isolated

or unilateral popliteal swelling or fullness.

Anserine bursitis is an often-missed periarticular cause of knee

pain in adults. The pes anserine bursa underlies the insertion of the

conjoined tendons (sartorius, gracilis, semitendinosus) on the anteromedial proximal tibia and may be painful following trauma, overuse, or

inflammation (bursitis). It is often tender in patients with fibromyalgia,

obesity, and knee OA. Other forms of bursitis may also present as knee

pain. The prepatellar bursa is superficial and is located over the inferior

portion of the patella. The infrapatellar bursa is deeper and lies beneath

the patellar ligament before its insertion on the tibial tubercle.

Internal derangement of the knee may result from trauma or degenerative processes. Damage to the meniscal cartilage (medial or lateral)

frequently presents as chronic or intermittent knee pain. Such an injury

should be suspected when there is a history of trauma, athletic activity,

or chronic knee arthritis, and when the patient relates symptoms of

“locking” or “giving way” of the knee. With the knee flexed 90° and the

patient’s foot on the table, pain elicited during palpation over the joint

line or when the knee is stressed laterally or medially may suggest a

meniscal tear. A positive McMurray test may also indicate a meniscal

tear. To perform this test, the knee is first flexed at 90°, and the leg is

then extended while the lower extremity is simultaneously torqued

medially or laterally. A painful click during inward rotation may indicate a lateral meniscus tear, and pain during outward rotation may

indicate a tear in the medial meniscus. Lastly, damage to the cruciate

ligaments should be suspected with acute onset of pain, possibly with

swelling, a history of trauma, or a synovial fluid aspirate that is grossly

bloody. Examination of the cruciate ligaments is best accomplished by

eliciting a drawer sign. With the patient recumbent, the knee should be

partially flexed and the foot stabilized on the examining surface. The

examiner should manually attempt to displace the tibia anteriorly or

posteriorly with respect to the femur. If anterior movement is detected,

then anterior cruciate ligament damage is likely. Conversely, significant

posterior movement may indicate posterior cruciate damage. Contralateral comparison will assist the examiner in detecting significant

anterior or posterior movement.

■ HIP PAIN

The hip is best evaluated by observing the patient’s gait and assessing

range of motion. The vast majority of patients reporting “hip pain”

localize their pain unilaterally to the posterior gluteal musculature

(Fig. 370-5) with radiation down the posterolateral aspect of the thigh,

and the pain may be associated with complaints of low back pain.

This presentation frequently results from degenerative arthritis of

the lumbosacral spine or disks and commonly follows a dermatomal

distribution with involvement of nerve roots between L4 and S1. Sciatica is caused by impingement of the L4, L5, or S1 nerve (i.e., from a

herniated disk) and manifests as unilateral neuropathic pain extending

from the gluteal region down the posterolateral leg to the foot. Some

individuals instead localize their “hip pain” laterally to the area overlying the trochanteric bursa. Because of the depth of this bursa, swelling

and warmth are usually absent. Diagnosis of trochanteric bursitis or

enthesitis can be confirmed by inducing point tenderness over the trochanteric bursa. Gluteal and trochanteric pain are common findings in

fibromyalgia. Range of movement may be limited by pain. Pain in the

hip joint is less common and tends to be located anteriorly, over the

inguinal ligament; it may radiate medially to the groin. Uncommonly,

iliopsoas bursitis may mimic true hip joint pain. Diagnosis of iliopsoas

bursitis may be suggested by a history of trauma or inflammatory

arthritis. Pain associated with iliopsoas bursitis is localized to the groin

or anterior thigh and tends to worsen with hyperextension of the hip;

many patients prefer to flex and externally rotate the hip to reduce the

pain from a distended bursa.

TELEHEALTH MUSCULOSKELETAL

EVALUATION

Telemedicine has grown significantly in recent years as a means of

remote patient assessment and providing remote clinical care. Engagement of patients via electronic telecommunication allows for virtual

patient evaluations with a time, cost, and convenience advantage, but

can be a technological disadvantage for the elderly or disadvantaged

populations. Telemedicine is most efficient with quality audio and

video connections and can be used for patient education, monitoring,

and routine disease assessments. Patients evaluated by telemedicine

should undergo the same medical history and inquiry as a routine

clinic evaluation, but evaluation will differ in the scope of examination

and maneuvers. The musculoskeletal televideo examination may be

appropriate and effective in many, primarily by supplanting physical

Approach to Articular and Musculoskeletal Disorders

2851CHAPTER 370

Anterior Posterior/lateral

Enthesitis

(anterior superior

iliac crest)

True hip pain,

lliopsoasbursitis

Meralgia

paresthetica

Sacroiliac pain

Ischiogluteal

bursitis

Sciatica

Buttock pain

referred from

lumbosacral

spine

Trochanteric

bursitis/enthesitis

FIGURE 370-5 Origins of hip pain and dysesthesias. (Reproduced with permission from JJ Cush et al [eds], Evaluation of musculoskeletal complaints, in Rheumatology:

Diagnosis and Therapeutics, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 2005.)

palpation with observation, range of motion, patient self-assessments,

and contralateral comparison. Specifically, the televideo exam should

assess the following: (1) patient gait (to assess lower extremity abnormalities); (2) rising from a seated position (to assess for weakness);

(3) cervical range of motion (flexion, extension, lateral bending); (4)

assessment by contralateral comparison (e.g., “praying hands,” “make

a fist,” “flex wrists,” and “hands on ears, elbows out” to assess shoulder

range of motion); and (5) side-by-side inspection of knees, ankles, and

feet. Effective telehealth is contingent on clinical experience, knowledge of and familiarity with the patient, and training the patient on the

use of technology and goals and limits of a televideo visit.

LABORATORY INVESTIGATIONS

The vast majority of musculoskeletal disorders can be logically diagnosed by a complete history and physical examination. An additional

objective of the initial encounter is to determine whether additional

investigations or immediate therapy is required. Laboratory evaluation is indicated with (1) monarticular conditions; (2) traumatic or

inflammatory conditions; (3) the presence of neurologic findings;

(4) systemic manifestations; or (5) chronic symptoms (>6 weeks) and

a lack of response to symptomatic measures. The extent and nature of

the additional investigation should be dictated by the clinical features

and suspected pathologic process. Laboratory tests should be used to

confirm a specific clinical diagnosis and not be used to screen or evaluate patients with vague rheumatic complaints. Indiscriminate use of

broad batteries of diagnostic tests and radiographic procedures is rarely

a useful or cost-effective means to establish a diagnosis.

Besides a complete blood count, including a white blood cell (WBC)

and differential count, the routine evaluation should include a determination of an acute-phase reactant such as the ESR or CRP, which can

be useful in discriminating inflammatory from noninflammatory disorders. Both are inexpensive, easily obtained, and may be elevated with

infection, inflammation, autoimmune disorders, neoplasia, pregnancy,

renal insufficiency, advanced age, or hyperlipidemia. Extreme elevation

of the acute-phase reactants (CRP, ESR) is seldom seen without evidence of serious illness (e.g., sepsis, pleuropericarditis, PMR, giant cell

arteritis, adult Still’s disease).

Serum uric acid determinations are useful in the diagnosis of gout

and in monitoring the response to urate-lowering therapy. Uric acid,

the end product of purine metabolism, is primarily excreted in the

urine. Serum values range from 238 to 516 μmol/L (4.0–8.6 mg/dL)

in men; the lower values (178–351 μmol/L [3.0–5.9 mg/dL]) seen in

women are caused by the uricosuric effects of estrogen. Urinary uric

acid levels are normally <750 mg per 24 h. Although hyperuricemia

is associated with an increased incidence of gout and nephrolithiasis, levels may not correlate with the severity of articular disease.

Uric acid levels (and the risk of gout) may be increased by inborn

errors of metabolism (Lesch-Nyhan syndrome), disease states (renal

insufficiency, myeloproliferative disease, psoriasis), or drugs (alcohol,

cytotoxic therapy, thiazides). Although nearly all patients with gout

will demonstrate hyperuricemia at some time during their illness, up

to 50% of patients with an acute gouty attack will have normal serum

uric acid levels. Monitoring serum uric acid is useful in assessing the

response to urate-lowering therapy or chemotherapy, with the target

goal being a serum urate <6 mg/dL.

Serologic tests for RF, cyclic anticitrullinated peptide (CCP or

ACPA) antibodies, ANAs, complement levels, Lyme and antineutrophil

cytoplasmic antibodies (ANCAs), or antistreptolysin O (ASO) titer

should be carried out only when there is clinical evidence to specifically suggest a specific diagnosis because these have poor predictive

value when used for screening, especially when the pretest probability

is low. For most of these, there is no value to repeated or serial serologic

testing. Although 4–5% of a healthy population will have positive tests

for RF and ANAs, only 1% and <0.4% of the population will have RA

or SLE, respectively. IgM RF (autoantibodies against the Fc portion of

IgG) is found in 80% of patients with RA but is poorly specific as it may

also be seen in low titers in patients with chronic infections (tuberculosis, leprosy, hepatitis); other autoimmune diseases (SLE, Sjögren’s

syndrome); and chronic pulmonary, hepatic, or renal disease. When

considering RA, both serum RF and anti-CCP antibodies should be

obtained as these are complementary. Both are comparably sensitive,

but CCP antibodies are more specific than RF. In RA, the presence

of high titers of anti-CCP or RF antibodies, or double positivity, may

indicate a greater risk for more severe, erosive polyarthritis. ANAs

are found in nearly all patients with SLE and may also be seen in

patients with other autoimmune diseases (polymyositis, scleroderma,

antiphospholipid syndrome, Sjögren’s syndrome), drug-induced lupus

(Table 370-2), chronic thyroid, liver or renal disorders, and advanced

age. Positive ANAs are found in 5% of adults and in up to 14% of

elderly or chronically ill individuals. The ANA test is very sensitive

but poorly specific for lupus, as only 1–2% of all positive results will

be caused by lupus alone up to 80% of patients with thyroid disease

will be ANA positive. The interpretation of a positive ANA test may

depend on the magnitude of the titer and the pattern observed by

2852 PART 11 Immune-Mediated, Inflammatory, and Rheumatologic Disorders

immunofluorescence microscopy (Table 370-4). Diffuse and speckled

patterns are least specific, whereas a peripheral, or rim, pattern (related

to autoantibodies against double-strand [native] DNA) is highly specific and suggestive of lupus. Centromeric patterns are seen in patients

with limited scleroderma (calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly, telangiectasia [CREST] syndrome),

primary biliary sclerosis, Sjögren’s syndrome, or thyroiditis, and nucleolar patterns may be seen in patients with diffuse systemic sclerosis or

inflammatory myositis.

Aspiration and analysis of synovial fluid are always indicated in

acute monoarthritis or when an infectious or crystal-induced arthropathy is suspected. Synovial fluid may distinguish between noninflammatory and inflammatory processes by analysis of the appearance,

viscosity, and cell count. Tests for synovial fluid glucose, protein, lactate

dehydrogenase, lactic acid, or autoantibodies are not recommended

as they have no diagnostic value. Normal synovial fluid is clear or a

pale straw color and is viscous, primarily because of the high levels

of hyaluronate. Noninflammatory synovial fluid is clear, viscous, and

amber-colored, with a WBC count of <2000/μL and a predominance

of mononuclear cells. The viscosity of synovial fluid is assessed by

expressing fluid from the syringe one drop at a time. Normally, there is

a stringing effect, with a long tail behind each synovial drop. Effusions

caused by OA or trauma will have normal viscosity. Inflammatory fluid

is turbid and yellow, with an increased WBC count (2000–50,000/μL)

and a polymorphonuclear leukocyte predominance. Inflammatory

fluid has reduced viscosity (no stringing), diminished hyaluronate, and

little or no tail following each drop of synovial fluid. Such effusions are

found in RA, gout, and other inflammatory arthritides. Septic fluid is

opaque and purulent, with a WBC count usually >50,000/μL, a predominance of polymorphonuclear leukocytes (>75%), and low viscosity. Such effusions are typical of septic arthritis but may also occur with

RA or gout. Lastly, hemorrhagic synovial fluid (hemarthrosis) may be

seen with trauma (ligament or cartilage tears), osteochondral fracture,

neuropathic arthritis, or coagulopathy. An algorithm for synovial fluid

aspiration and analysis is shown in Fig. 370-6. Synovial fluid should

be analyzed immediately for appearance, viscosity, and cell count.

Monosodium urate crystals (observed in gout) are seen by polarized

microscopy and are long, needle-shaped, negatively birefringent, and

usually intracellular. In chondrocalcinosis and pseudogout, calcium

pyrophosphate dihydrate crystals are usually short, rhomboid-shaped,

and positively birefringent. Whenever infection is suspected, synovial

fluid should be Gram stained and cultured appropriately. If gonococcal

arthritis is suspected, nucleic acid amplification tests should be used

to detect either Chlamydia trachomatis or N. gonorrhoeae infection.

Synovial fluid from patients with chronic monoarthritis should also

be cultured for M. tuberculosis and fungi. Last, it should be noted

that crystal-induced arthritis and septic arthritis occasionally occur

together in the same joint.

DIAGNOSTIC IMAGING IN JOINT DISEASES

Conventional radiography has been a valuable tool in the diagnosis

and staging of articular disorders. Plain x-rays are most appropriate

and cost effective when there is a history of trauma, suspected chronic

infection, progressive disability, or monarticular involvement; when

therapeutic alterations are considered; or when a baseline assessment is desired for what appears to be a chronic process. However,

in acute inflammatory arthritis, early radiography is rarely helpful in

establishing a diagnosis and may only reveal soft tissue swelling or

juxtaarticular demineralization. As the disease progresses, calcification

(of soft tissues, cartilage, or periarticular bone), joint space narrowing,

Strongly consider synovial fluid aspiration

and analysis if there is

• Monarthritis (acute or chronic)

• Trauma with joint effusion

• Monarthritis in a patient with chronic polyarthritis

• Suspicion of joint infection, crystal-induced arthritis, or hemarthrosis

Analyze fluid for

• Appearance, viscosity

• WBC count, differential

• Gram stain, culture, and

 sensitivity (if indicated)

• Crystal identification

 by polarized microscopy

Inflammatory or

noninflammatory

articular condition

Consider

• Trauma or mechanical

 derangement

• Coagulopathy

• Neuropathic arthropathy

Is the WBC >2000/µL? • Other

Consider other

inflammatory

or septic arthritides

• Gram stain, culture

 mandatory

Is the % PMNs >75%?

Are crystals present?

Consider

noninflammatory

articular conditions

• Osteoarthritis

• Trauma

• Other

Is the WBC >50,000/µL?

Crystal identification for

specific diagnosis

• Gout

• Pseudogout

Probable inflammatory arthritis Possible septic arthritis

Consider inflammatory

or septic arthritis

Is the effusion

hemorrhagic?

No Yes

No Yes

No Yes

Yes

No

Yes

No

FIGURE 370-6 Algorithmic approach to the use and interpretation of synovial fluid

aspiration and analysis. PMNs, polymorphonuclear (leukocytes); WBC, white blood

cell count.

TABLE 370-4 Antinuclear Antibody (ANA) Patterns and

Clinical Associations

ANA PATTERN ANTIGEN IDENTIFIED CLINICAL CORRELATE

Diffuse Deoxyribonucleoprotein Nonspecific

Histones Drug-induced lupus, lupus

Peripheral (rim) ds-DNA 50% of SLE (specific)

Speckled U1-RNP >90% of MCTD

Sm 30% of SLE (specific)

Ro (SS-A) Sjögren’s 60%, SCLE, neonatal

lupus, ANA(–) lupus

La (SS-B) 50% of Sjögren’s, 15% lupus

Scl-70 (topoisomerase I) 40% of diffuse scleroderma

Jo-1 (histidyl t-RNA

synthetase)

PM with pneumonitis + arthritis

Nucleolar RNA polymerase I, others 40% of PSS

Centromere Kinetochore 75% CREST (limited scleroderma),

PBC, Sjogren’s, thyroiditis

Abbreviations: CREST, calcinosis, Raynaud’s phenomenon, esophageal involvement,

sclerodactyly, and telangiectasia; MCTD, mixed connective tissue disease; PBC,

primary biliary cirrhosis; PSS, progressive systemic sclerosis; SCLE, subacute

cutaneous lupus erythematosus; SLE, systemic lupus erythematosus.

Approach to Articular and Musculoskeletal Disorders

2853CHAPTER 370

erosions, bony ankylosis, new bone formation (sclerosis, osteophytes,

or periostitis), or subchondral cysts may develop and suggest specific

clinical entities. Consultation with a radiologist will help define the

optimal imaging modality, technique, or positioning to optimize interpretation and prevent the need for further studies.

Additional imaging techniques may possess greater diagnostic sensitivity and facilitate early diagnosis in a limited number of articular

disorders and in selected circumstances and are indicated when conventional radiography is inadequate or nondiagnostic (Table 370-5).

Ultrasonography is useful in the detection of soft tissue abnormalities

(tendinitis, tenosynovitis, enthesitis, bursitis), crystal deposition, and

entrapment neuropathies. Wider use, lower cost, better technology,

and enhanced site-specific transducers now allow for wider use and

diagnostic specificity, especially when considering synovial (Baker’s)

cysts, rotator cuff tears, tendinitis and tendon injury, and crystal deposition on cartilage. Use of power Doppler allows for early detection of

synovitis and bony erosions. Radionuclide scintigraphy is a very sensitive, but poorly specific, means of detecting inflammatory or metabolic

alterations in bone or periarticular soft tissue structures (Table 370-5).

Scintigraphy is best suited for total-body assessment (extent and distribution) of skeletal involvement (neoplasia, Paget’s disease) and the

assessment of patients with undiagnosed polyarthralgias, looking for

occult arthritis. The use of scintigraphy has declined with greater use

and declining cost of ultrasound and MRI. MRI has largely replaced

scintigraphy in diagnosing osseous infection, neoplasia, inflammation,

increased blood flow, bone remodeling, heterotopic bone formation,

or avascular necrosis. Gallium scanning uses 67Ga, which binds serum

and cellular transferrin and lactoferrin and is preferentially taken up by

neutrophils, macrophages, bacteria, and tumor tissue (e.g., lymphoma).

As such, it is primarily used in the identification of occult infection or

malignancy. Scanning with 111In-labeled WBCs has been used to detect

osteomyelitis and infectious or inflammatory arthritis. Despite their

utility, 111In-labeled WBC and 67Ga scanning have largely been replaced

by MRI, except when there is a suspicion of septic joint or prosthetic

joint infections.

Computed tomography (CT) provides detailed visualization of the

axial skeleton. Articulations previously considered difficult to visualize

by radiography (e.g., zygapophyseal, sacroiliac, sternoclavicular, hip

joints) can be evaluated using CT. CT has been demonstrated to be useful in the diagnosis of low back pain (e.g., spinal stenosis vs herniated

disk), sacroiliitis, osteoid osteoma, and stress fractures. Helical or spiral

CT (with or without contrast angiography) is a novel technique that is

rapid, cost effective, and sensitive in diagnosing pulmonary embolism

or obscure fractures, often in the setting of initially equivocal findings.

High-resolution CT can be advocated in the evaluation of suspected or

established infiltrative lung disease (e.g., scleroderma or rheumatoid

lung). The recent use of hybrid (positron emission tomography [PET]

or single-photon emission CT [SPECT]) CT scans in metastatic evaluations has incorporated CT to provide better anatomic localization of

scintigraphic abnormalities. 18F-Fluorodeoxyglucose (FDG) is the most commonly used radiopharmaceutical in PET scanning. FDG-PET/CT scans are rarely indicated in septic or inflammatory arthritis but have been useful in the

evaluation of patients with fever of unknown origin or suspected large

vessel vasculitis. For instance, while FDG-PET is useful in assessing

vascular inflammation/activity, MRI angiography can best define the

extent of vascular damage. Dual-energy CT (DECT) scanning, developed in urology to identify urinary calculi, has been a highly sensitive

and specific method used to identify and quantify uric acid deposition

in tissues (Fig. 370-7).

MRI has significantly advanced the ability to image musculoskeletal

structures. MRI has the advantages of providing multiplanar images

with fine anatomic detail and contrast resolution (Fig. 370-8) that

allows for the superior ability to visualize bone marrow and soft tissue

periarticular structures. Although more costly with a longer procedural

time than CT, the MRI has become the preferred technique when evaluating complex musculoskeletal disorders.

MRI can image fascia, vessels, nerve, muscle, cartilage, ligaments,

tendons, pannus, synovial effusions, and bone marrow. Visualization of

particular structures can be enhanced by altering the pulse sequence to

produce either T1- or T2-weighted spin echo, gradient echo, or inversion recovery (including short tau inversion recovery [STIR]) images.

Because of its sensitivity to changes in marrow fat, MRI is a sensitive

but nonspecific means of detecting osteonecrosis, osteomyelitis, and marrow inflammation indicating overlying synovitis or osteitis (Fig. 363-8).

Because of its enhanced soft tissue resolution, MRI is more sensitive

than arthrography or CT in the diagnosis of soft tissue injuries (e.g.,

meniscal and rotator cuff tears); intraarticular derangements; marrow

abnormalities (osteonecrosis, myeloma); and spinal cord or nerve root

damage, synovitis, or cartilage damage or loss.

TABLE 370-5 Diagnostic Imaging Techniques for

Musculoskeletal Disorders

METHOD

IMAGING

TIME, H COSTa CURRENT INDICATIONS

Ultrasound <1 ++ Synovial (Baker’s) cysts

Rotator cuff tears

Bursitis, tendinitis, tendon injury

Enthesitis

Carpal tunnel syndrome

Urate or calcium pyrophosphate

deposition on cartilage

Early detection of synovial

inflammation or erosions

Ultrasound-guided injection/

arthrocentesis

Radionuclide

scintigraphy

Metastatic bone survey

Evaluation of Paget’s disease

Identifying occult arthritis in patients

with undiagnosed polyarthralgia

Acute infection

Prosthetic infection

Acute osteomyelitis

Acute and chronic infection

Acute osteomyelitis

99mTc 1–4 ++

111In-WBC 24 +++

67Ga 24–48 ++++

Computed

tomography (CT)

<1 +++ Herniated intervertebral disk

Sacroiliitis

Spinal stenosis

Spinal trauma

Osteoid osteoma

Stress fracture

Dual-energy CT <1 NA Uric acid deposition

Tophus localization

Magnetic

resonance

imaging

1/2–2 ++++ Avascular necrosis

Osteomyelitis

Septic arthritis, infected prosthetic

joints

Sacroiliitis

Intraarticular derangement and soft

tissue injury

Derangements of axial skeleton and

spinal cord

Herniated intervertebral disk

Pigmented villonodular synovitis

Inflammatory and metabolic muscle

pathology

a

Relative cost for imaging study.

Abbreviations: NA, not commercially available; WBC, white blood cell.