Diagnostic Approach to Polyarticular Joint

Pain
This is a corrected version of the
article that appears in print.

ANNA MIES RICHIE, M.D., and MARK L. FRANCIS, M.D., Southern Illinois University School of Medicine,
Springfield, Illinois

Am Fam Physician. 2003 Sep 15;68(6):1151-1160.

  A more recent article on polyarticular arthritis is available. (https://www.aafp.org/afp/2015/0701/p35.html)

Identifying the cause of polyarticular joint pain can be difficult because of the extensive differential
diagnosis. A thorough history and a complete physical examination are essential. Six clinical factors
are helpful in narrowing the possible causes: disease chronology, inflammation, distribution, extra-
articular manifestations, disease course, and patient demographics. Patients with an inflammatory
arthritis are more likely to have palpable synovitis and morning stiffness; if the condition is severe,
they may have fever, weight loss, and fatigue. Viral infections, crystal-induced arthritis, and serum
sickness reactions are common causes of acute, self-limited polyarthritis. Because chronic
arthritides may present abruptly, they need to be considered in patients who present with acute
polyarticular joint pain. Joint palpation can help to distinguish inflammatory synovitis from the bony
hypertrophy and crepitus that typically occur with osteoarthritis. Extra-articular manifestations of
rheumatologic disease may be helpful in arriving at a more specific diagnosis. Many classic
rheumatologic laboratory tests are nonspecific. A complete blood count, urinalysis, and a metabolic
panel may provide more useful diagnostic clues. Plain-film radiographs may demonstrate classic
findings of specific rheumatologic diseases; however, radiographs can be normal or only show
nonspecific changes early in the disease process.

Polyarticular joint pain (i.e., pain in more than four joints) poses a diagnostic challenge because of the
extensive differential diagnosis1  (Table 1). Consequently, family physicians need to keep the diagnosis
open in evaluating patients who present with pain in multiple joints. For instance, a 50-year-old woman
with symmetric, progressive polyarticular joint swelling and prolonged morning stiffness would seem to
have rheumatoid arthritis. However, this patient might develop a malar rash and oral ulcers, which
would change the diagnosis to systemic lupus erythematosus. Alternatively, the patient might develop
thickening of the skin, which would suggest the diagnosis of scleroderma. Thus, a series of visits over
time may be necessary to arrive at a specific diagnosis in many patients with polyarticular joint pain. In
some patients, it may not be possible to establish a definitive diagnosis.

View/Print Table
TABLE 1
Differential Diagnosis of Polyarticular Joint Pain

Viral infection: human parvovirus (especially B19), enterovirus, adenovirus, Epstein-Barr,

coxsackievirus (A9, B2, B3, B4, B6), cytomegalovirus, rubella, mumps, hepatitis B, varicella-zoster
virus (human herpes virus 3), human immunodeficiency virus

Indirect bacterial infection (reactive arthritis): Neisseria gonorrhoeae (gonorrhea), bacterial

endocarditis, Campylobacter species, Chlamydia species, Salmonella species, Shigella species,
Yersinia species, Tropheryma whippelii (Whipple's disease), group A streptococci (rheumatic fever)

Direct bacterial infection: N. gonorrhoeae, Staphylococcus aureus, gram-negative bacilli, bacterial

endocarditis

Other infections: Borrelia burgdorferi (Lyme disease), Mycobacterium tuberculosis (tuberculosis),

fungi

Crystal-induced synovitis: gout, pseudogout (calcium pyrophosphate deposition disease),

hydroxyapatite

Systemic rheumatic disease: rheumatoid arthritis, systemic lupus erythematosus,

polymyositis/dermatomyositis, juvenile rheumatoid arthritis, scleroderma, Sjögren's syndrome,

Because many rheumatologic laboratory tests lack the desired specificity, results should be interpreted
in the clinical context and with caution. Tests with low specificity, such as those in arthritis panels, are
frequently positive in the general population. Thus, these tests may be misleading.2 Furthermore, use of
tests with low specificity may increase unnecessary testing and attendant costs, result in inappropriate
treatment, and have a negative psychologic impact on patients.3

In the absence of definitive rheumato-logic laboratory tests, the history and physical examination are
key to the early diagnosis and treatment of conditions that cause polyarticular joint pain. Indeed, the
differential diagnosis can be narrowed through investigation of six clinical factors: disease chronology,
inflammation, distribution, extra-articular manifestations, disease course, and patient demographics
(Table 2). More common causes of polyarticular joint pain should be considered first.

View/Print Table
TABLE 2
Common Causes of Polyarticular Joint Pain

DISTRIBUTION

AXIAL EXTRA-
DISEASE CHRONOLOGY INFLAMMATION PATTERN SYMMETRY
INVOLVEMENT MANIFE

Human Acute Yes Small joints Yes No Lacy

parvovirus B19 rash
infection

Rheumatoid Chronic Yes Small and large Yes Cervical Subc

arthritis joints nodu
tunn

Systemic Chronic Yes Small joints Yes No Mala

lupus ulcer
erythematosus (pleu
peric

Osteoarthritis Chronic No Lower extremity Yes/No Cervical None

joints, proximal and

Disease Chronology
Acute polyarticular joint pain (i.e., pain that has been present for less than six weeks) may be the sign of
a self-limited disorder or a harbinger of chronic disease. Although chronic polyarticular arthritides more
often develop insidiously, they can present abruptly. Thus, chronic conditions such as rheumatoid
arthritis and systemic lupus erythematosus should be considered, at least initially, in patients who
present with acute polyarticular joint pain (Table 3).4–7 To avoid treating a self-limited disorder with
potentially toxic disease-modifying agents, synovitis should be present for six weeks before rheumatoid
arthritis is diagnosed.4 [Evidence level C, consensus opinion]
 TABLE 3
Diagnostic Criteria for Rheumatoid Arthritis, Systemic Lupus Erythematosus, and Fibromyalgia
The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item,
see the original print version of this publication.

Viruses (e.g., human parvovirus B19, hepatitis viruses), crystals, and serum sickness reactions are
known causes of acute, self-limited polyarthritis. The specific cause of virus-induced arthritis is not
always investigated; thus, the prevalence of viruses as the etiology of arthritis may be underestimated.8

Except for Neisseria gonorrhoeae, direct bacterial infections in joints seldom cause polyarthritis.9
Although typically oligoarticular, extra-articular bacterial infections may induce acute arthritis. Classic
reactive arthritis, for example, is associated with enteric infections (Salmonella, Shigella, Campylobacter,
or Yersinia species) and urogenital infections (Chlamydia trachomatis).

Early gout usually affects only one joint. However, this disease also should be considered in patients
with acute polyarticular arthritis, particularly older women who are taking diuretics and have
hypertrophy and degenerative changes of the distal interphalangeal (DIP) joints (Heberden's nodes) and
proximal interphalangeal (PIP) joints (Bouchard's nodes).10

Inflammation
Arthritis is joint pain with inflammation, whereas arthralgia is joint pain without inflammation. The
patient who presents with psoriasis and knee pain in the absence of inflammation may have the dual
diagnosis of psoriasis and osteoarthritis. However, the patient who also has inflammation probably has
psoriatic arthritis, which may require more aggressive therapy. Inflammatory arthritides include
infectious arthritis, gout, rheumatoid arthritis, systemic lupus erythematosus, and reactive arthritis.

Cardinal signs of inflammation include erythema, warmth, pain, and swelling. Patients with severe joint
inflammation or systemic disease also may present with fatigue, weight loss, or fever.8 Morning
stiffness lasting longer than one hour suggests underlying inflammation.1 The duration of morning
stiffness provides a useful guide to the extent of inflammation. For instance, morning stiffness
associated with rheumatoid arthritis may last for hours.11,12

Palpation of multiple joint capsules is important to look for soft tissue swelling and effusions that result
in edema and influx of inflammatory cells into and around the synovium. Soft tissue swelling should be
distinguished from noninflammatory bony hypertrophy, such as Heberden's and Bouchard's nodes,
which often indicate osteoarthritis (Figure 1). Crepitus indicates the presence of irregularities of the
articular cartilage, which most commonly are associated with osteoarthritis, injury, or previous
inflammation.
 The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item,
see the original print version of this publication.

FIGURE 1.

Because findings can be subtle, it is important to palpate each hand joint. Although palpation often can
identify synovitis, it may not detect inflammation of more proximal joints in, for example, elderly patients
with polymyalgia rheumatica.13

Morning stiffness and a history of swelling suggest an inflammatory process but also are characteristic
of fibromyalgia, a noninflammatory condition (Table 3).4–7 Typically, patients with fibromyalgia have a
subjective sense of swelling but no objective signs of synovitis. Fibromyalgia is suggested by the
presence of polyarticular joint pain without synovitis, along with myalgias and tender points.14

Distribution
PATTERN

The pattern of joint involvement provides diagnostic clues. For instance, osteoarthritis of the hand
usually involves the DIP and PIP joints, but not the metacarpophalangeal (MCP) joints.15 Alternatively,
rheumatoid arthritis of the hand most often involves the PIP and MCP joints, but not the DIP joints.4,15
Psoriatic arthritis, crystal-induced arthritis, and sarcoidosis may affect all of these joints. Hand synovitis
is distinctly unusual in chronic Lyme disease.16

Spondyloarthropathies typically involve the larger joints of the lower extremities. Osteoarthritis tends to
spare wrists, elbows, and ankles, unless there is a history of trauma, inflammation, or a metabolic
disorder such as hemochromatosis.

Depending on the underlying cause, the pattern of arthritis may change over time. For example, the
acute stage of Lyme disease may include polyarticular arthralgias, whereas the chronic phase may
include oligoarthritis, primarily in the knees.17

SYMMETRY

Joint involvement tends to be symmetric in systemic diseases such as rheumatoid arthritis, systemic
lupus erythematosus, polymyalgia rheumatica, viral arthritides, and serum sickness reactions. Of eight
variables examined in one study,18 symmetric pain was the most potent discriminating feature for
rheumatoid arthritis. Psoriatic arthritis, reactive arthritis, and gout are more likely to present with
asymmetric peripheral involvement.1,19,20
 AXIAL INVOLVEMENT

Axial pain may be a helpful indicator in the evaluation of peripheral joint pain. In addition to peripheral
joints, osteoarthritis may involve the lower back, the neck, or both. In contrast, rheumatoid arthritis is
seldom an explanation for low back pain.

A young adult who presents with peripheral arthritis accompanied by the insidious onset of chronic low
back pain and prolonged morning stiffness that improves with exercise probably has one of the
spondyloarthropathies, such as ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease–
associated arthropathy, or reactive arthritis.21 Another common manifestation of
spondyloarthropathies is enthesitis (inflammation of the muscular or tendinous insertions),22 such as
Achilles tendonitis or plantar fasciitis.23 Dactylitis (inflammation of the finger or toe) is another classic
sign of spondyloarthropathies; this condition, often referred to as “sausage digits,” is caused by a
combination of synovitis and enthesitis22 (Figure 2).

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see the original print version of this publication.

FIGURE 2.

Extra-Articular Manifestations
Extra-articular manifestations may provide clues to the presence of some rheumatologic diseases but,
of themselves, are not diagnostic (Table 4). For instance, extra-articular signs and symptoms can point
to the likely reason for swollen PIP joints: a malar rash and oral ulcers indicate probable systemic lupus
erythematosus (Figure 3); proximal muscle weakness suggests polymyositis; and psoriatic skin and nail
lesions raise the possibility of psoriatic arthritis.24,25

View/Print Table
TABLE 4
Selected Extra-Articular Manifestations Associated with Conditions That Result in Polyarticular
Joint Pain*

PHYSICAL FINDING DIAGNOSES TO CONSIDER

Skin and mucous membranes

 PHYSICAL FINDING DIAGNOSES TO CONSIDER

Rash

Erythema infectiosum

Reticulated (lacy) rash Human parvovirus B19 infection

Facial exanthema (slapped cheek) Human parvovirus B19 infection

Malar rash SLE, human parvovirus B19 infection, Lyme

disease, rosacea, seborrhea, dermatomyositis

The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item,
see the original print version of this publication.

FIGURE 3.

Similarly, in a patient with knee arthritis, the presence of conjunctivitis, oral ulcers, vesicopustules on the
soles, or recent diarrhea may indicate reactive arthritis.21,26 A history of erythema chronicum migrans
and Bell's palsy points to the diagnosis of Lyme disease.27 As a final example, a health care worker who
presents with fever, a lacy rash, and symmetric joint pain (especially in the hands) may have erythema
infectiosum caused by human parvovirus B19 infection.28–30

Disease Course
INTERMITTENT ARTHRITIS

When symptoms are present for a limited period (usually a few days to a month) and resolve completely
before presenting again, crystal-induced arthritis (e.g., gout, pseudogout) is the likely diagnosis.
Arthrocentesis should be considered during a symptomatic flare.10,19,27,31 If synovial fluid analysis fails
to identify crystals, palindromic rheumatism should be considered; this condition may progress to
rheumatoid arthritis.

MIGRATORY ARTHRITIS
Migratory arthritis is characterized by rapid onset of swelling in one or two joints, with resolution over a
few days. As the symptoms resolve, similar symptoms emerge in another joint, usually in an
asymmetric location.20,28 This symptom pattern can occur in gonococcal arthritis, rheumatic fever,
sarcoidosis, systemic lupus erythematosus, Lyme disease, bacterial endocarditis, and Whipple's
disease.32

Patient Demographics
GENDER

Before menopause, women are nine times more likely to develop systemic lupus erythematosus and
three to four times more likely to develop rheumatoid arthritis.20 After men and women reach 50 years
of age, the gender difference for systemic lupus erythematosus and rheumatoid arthritis becomes less
significant.1

Compared with men, women are nine times more likely to develop fibromyalgia. An estimated 60
percent of women with symptomatic human parvovirus B19 infection manifest arthropathy, whereas
men with this infection appear to develop arthropathy much less often.33,34 The gender ratio is more
balanced for spondyloarthropathies and vasculitic conditions such as polyarteritis nodosa.

Gout usually presents about 20 years after puberty in men and about 20 years after menopause in
women. This disease is rare in premenopausal woman, unless renal insufficiency is present.10

AGE

Certain diagnoses are more common in specific age groups. Rheumatic fever, systemic lupus
erythematosus, rheumatoid arthritis, reactive arthritis, and spondyloarthropathies occur more often in
younger persons. Osteoarthritis, polymyalgia rheumatica, and giant cell arteritis are more common in
older persons.13

RACE

Polymyalgia rheumatica and Wegener's granulomatosis are more likely to affect whites.13 In contrast,
sarcoidosis and systemic lupus erythematosus are more common in blacks.

FAMILY HISTORY

Familial aggregation occurs in some arthritic diseases, such as spondyloarthropathies, rheumatoid

arthritis, and Heberden's nodes of osteoarthritis.1 There is a particularly strong association between
ankylosing spondylitis and the HLA-B27 allele.

Laboratory Investigations
As previously noted, many rheumatologic laboratory tests must be interpreted in the context of the
individual patient. For example, antinuclear antibody (ANA) tests are positive in 5 to 10 percent of the
general population, a rate that increases with age. Thus, given a one in 20 frequency for ANAs and a one
in 2,000 frequency for systemic lupus erythematosus, only one in 100 persons with a positive ANA test
will have the disease. Consequently, positive ANA test results must be interpreted with caution (Table
3).4–7 Given the high sensitivity of the currently used substrate for testing, a negative ANA test
essentially rules out systemic lupus erythematosus.1,5

Spondyloarthropathies affect fewer than 1 percent of the general population. Indeed, patients who are
HLA-B27 positive and do not have a family history of ankylosing spondylitis have only a 2 percent risk of
developing this disorder.35 Spondyloarthropathies can be overdiagnosed by relying only on a positive
HLA-B27 test, because this test is positive in 8 percent of white persons.35

Rheumatoid factor testing lacks both sensitivity and specificity: the test is positive in 5 to 10 percent of
the general population and negative in approximately 20 percent of persons with rheumatoid arthritis.36
Therefore, both positive and negative rheumatoid factor test results must be interpreted cautiously.
Indeed, rheumatoid factor testing is not useful when a patient lacks other diagnostic criteria for
rheumatoid arthritis, especially synovitis.36 The American Rheumatology Association's revised
diagnostic criteria for rheumatoid arthritis use findings from the history, physical examination, and
laboratory tests.4 These criteria, which have been shown to be 91 to 94 percent sensitive and 89
percent specific, are useful for establishing a diagnosis of rheumatoid arthritis.4,12,15

A complete blood count, urinalysis, and a metabolic panel may provide more useful diagnostic clues
than classic rheumatologic laboratory tests (Table 5). For instance, hematuria, proteinuria, a low white
blood cell (WBC) count, and thrombocytopenia may indicate the presence of systemic lupus
erythematosus. Anemia with a low mean corpuscular volume may be a sign of underlying inflammatory
bowel disease that is causing chronic gastrointestinal blood loss. Human parvovirus B19 infection can
induce a decrease in the reticulocyte count, followed by anemia and, occasionally, leukopenia and
thrombocytopenia.30,34

View/Print Table
TABLE 5
Findings of Laboratory and Imaging Tests and Associated Conditions That Result in Polyarticular
Joint Pain

LABORATORY OR IMAGING TEST CONDITION

Complete blood count

 LABORATORY OR IMAGING TEST CONDITION

Anemia Many inflammatory arthritides, especially SLE, RA, IBD, and

human parvovirus B19 infection

Thrombocytopenia SLE, human parvovirus B19 infection

Thrombocytosis Acute-phase reaction, vasculitis, infection

Leukopenia SLE, RA, Felty's syndrome, Sjögren's syndrome, human parvovirus

B19 infection

Leukocytosis RA, vasculitis, reactive arthritis, infection

Synovial fluid analysis is performed primarily to diagnose infection or a crystal-induced arthritis. A

synovial fluid WBC count of at least 2,000 per mm3 (2 × 109 per L) suggests inflammation, whereas a
count higher than 50,000 per mm3 (50 × 109 per L) typically indicates synovial infection (Table 6).37 Fluid
with a highly elevated WBC count or a predominance of neutrophils should be cultured to exclude
infection.

View/Print Table
TABLE 6
Categorization of Synovial Fluid

POLYMORPHONUCLEAR
CATEGORIZATION WHITE BLOOD CELL COUNT NEUTROPHILIC EXAMPLES
LEUKOCYTES

Normal 0 to 200 per mm3 (0 to < 25% (0.25) —

0.2 × 109 per L)

Noninflammatory < 2,000 per mm3 (2 × 109 < 25% (0.25) Osteoarthritis, internal
per L) derangement, myxedema
 POLYMORPHONUCLEAR
CATEGORIZATION WHITE BLOOD CELL COUNT NEUTROPHILIC EXAMPLES
LEUKOCYTES

Inflammatory 2,000 to 50,000 per mm3 >75% (0.75) Rheumatoid arthritis,

(2 to 50 × 109 per L) psoriatic arthritis, gout,
pseudogout, Neisseria
gonorrhoeae infection

Diagnostic Imaging
A number of radiographic findings are characteristic of specific rheumatic disorders. For instance,
sacroiliitis is indicative of ankylosing spondylitis, erosions with periarticular osteopenia are typical of
rheumatoid arthritis, and “pencil-in-cup” deformities are a sign of psoriatic arthritis. However, these
radiographic findings take months to develop; early in the process, radiographs may be normal or show
only nonspecific changes.

In early rheumatoid arthritis, magnetic resonance imaging demonstrates cartilage damage that is not
evident on plain-film radiographs.38 This damage highlights the importance of diagnosing rheumatoid
arthritis early on the basis of the history and physical examination so that disease-modifying treatment
can be initiated.

The Authors show all author info

ANNA MIES RICHIE, M.D., is assistant professor in the Department of Family and Community Medicine
at Southern Illinois University School of Medicine, Springfield, where she earned her medical degree and
completed a family practice residency and fellowship....

REFERENCES show all references

1. Klinkhoff A. Rheumatology: 5. Diagnosis and management of inflammatory polyarthritis. CMAJ.

2000;162:1833–8....

Members of various family practice departments develop articles for “Problem-Oriented Diagnosis.” This is
one in a series from the Department of Family and Community Medicine at Southern Illinois University
School of Medicine, Springfield. Guest editor of the series is John G. Bradley, M.D. [corrected
(https://www.aafp.org/afp/2006/0301/p776a.html)]

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