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CURRENT Diagnosis & Treatment: Rheumatology, 3e
Chapter 4. Approach to the Patient with Arthritis
John B. Imboden, MD
Approach to the Patient with Arthritis: Introduction
Many diseases can cause arthritis. Obtaining a history and performing a physical examination are the first steps in allowing the clinician to accurately
characterize the arthritis and approach the differential diagnosis in a focused, logical fashion based on the duration of symptoms, the presence or
absence of joint inflammation, the number of joints affected, and the pattern of joint involvement (Table 4–1).
Table 4–1. Initial Clinical Characterization of Arthritis.
Duration: acute (presenting within hours to days) or chronic (persisting for weeks or longer)
Number of joints involved: monoarticular, oligoarticular (2–4 joints), or polyarticular (5 joints or more)
If more than one joint is involved: symmetric or asymmetric; additive or migratory
Accurate delineation of the involved joints
Inflammatory or noninflammatory
When evaluating a patient with joint symptoms, it is important to determine whether the symptoms are due to an articular process and not to bursitis,
tendinitis, or other soft tissue conditions. The physical examination should also establish whether there are objective findings of arthritis, such as
swelling, in the symptomatic joints. Arthralgias in the absence of objective arthritis commonly occur in systemic lupus erythematosus (SLE) and acute
viral illnesses but have less diagnostic significance than true arthritis.
Laboratory tests cannot substitute for clinical evaluation and should never be used as a “screen” for disease. Musculoskeletal complaints are common
in the general population, but the prevalence of inflammatory rheumatic diseases is relatively low. Hence, the positive predictive value of many
rheumatologic tests is low when tests these are ordered indiscriminately. In general, radiographs add little to the evaluation of acute presentations of
arthritis (except in cases of suspected trauma) but often are critical for the assessment of chronic arthritis.
Inflammatory versus Noninflammatory Arthritis
The distinction between inflammatory arthritis and noninflammatory arthritis is a critical bifurcation point in the differential diagnosis of arthritis. The
most reliable means for making this distinction is analysis of the white blood cell (WBC) count in the synovial fluid. The synovial fluid WBC count is
>2000/mcL in inflammatory arthritis and is <2000/mcL in noninflammatory arthritis (see Chapter 2). Arthrocentesis should be performed whenever
feasible because although clinical features and other laboratory investigations also help distinguish inflammatory and noninflammatory arthritis, no
single finding is definitive.
Patients with an inflammatory arthritis usually complain of pain and stiffness in involved joints; typically these symptoms are worse in the morning or
after periods of inactivity (the so­called “gel phenomenon”) and improve with mild to moderate activity. On examination, the larger joints can be warm
and, when severely inflamed as in acute gout or septic arthritis, can have erythema of the overlying skin. Laboratory investigations often reveal an
elevated erythrocyte sedimentation rate (ESR) and a high C­reactive protein (CRP) level. In contrast, patients with noninflammatory arthritis have pain
that worsens with activity and improves with rest. Stiffness is generally mild, lasts <30 minutes in the morning, and is not a prominent symptom. The
ESR and CRP are usually normal.
Constitutional Symptoms
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The presence
of fever
raises
possibility
of infection.
Most
patients with
Approach
to the
Patient
withthe
Arthritis:
Introduction,
John
B. Imboden,
MD septic arthritis or disseminated gonococcal infection are febrile. Fever
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McGraw arthritis
Hill. All Rights
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also accompany
that is Reserved.
not due to active
infection
4–2).
Indeed,
intermittent
high­grade fever ≥39°C is characteristic of Still disease. SLE
can also cause fever ≥39°C. However, fever more often occurs when serositis, rather than polyarthritis, is the major manifestation of SLE. On the other
hand, fever ≥38.3°C is unusual in rheumatoid arthritis, occurring in <1% of patients.
and, when severely inflamed as in acute gout or septic arthritis, can have erythema of the overlying skin. Laboratory investigations often reveal an
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elevated erythrocyte sedimentation rate (ESR) and a high C­reactive protein (CRP) level. In contrast, patients with noninflammatory arthritis have pain
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that worsens with activity and improves with rest. Stiffness is generally mild, lasts <30 minutes in the morning, and is not a prominent symptom. The
ESR and CRP are usually normal.
Constitutional Symptoms
The presence of fever raises the possibility of infection. Most patients with septic arthritis or disseminated gonococcal infection are febrile. Fever can
also accompany arthritis that is not due to active infection (Table 4–2). Indeed, intermittent high­grade fever ≥39°C is characteristic of Still disease. SLE
can also cause fever ≥39°C. However, fever more often occurs when serositis, rather than polyarthritis, is the major manifestation of SLE. On the other
hand, fever ≥38.3°C is unusual in rheumatoid arthritis, occurring in <1% of patients.
Table 4–2. Fever and Arthritis.
Active infection
Septic arthritis
Disseminated gonococcal infection
Endocarditis
Acute viral infections
Mycobacterial
Fungal
Post infection
Reactive arthritis (particularly in its early phases)
Acute rheumatic fever and poststreptococcal arthritis
Not due to infection
Systemic lupus erythematosus
Drug­induced lupus
Still disease
Gout
Pseudogout
Inflammatory bowel disease
Paraneoplastic arthritis
Acute sarcoidosis
Systemic vasculitis
Familial Mediterranean fever and other inherited periodic fever syndromes
Significant weight loss is common at the initial presentation of reactive arthritis, systemic vasculitis, enteropathic arthritis, and paraneoplastic arthritis
but is unusual in rheumatoid arthritis of recent onset. Constitutional symptoms rarely accompany noninflammatory forms of arthritis.
Extra­Articular Manifestations
Extra­articular manifestations, such as glomerulonephritis, pulmonary abnormalities, oral ulcerations, ocular inflammation, and peripheral
neuropathy, may signal that arthritis is a manifestation of a systemic rheumatic disease or vasculitis. The presence of rash can be a very helpful clue to
the diagnosis (Table 4–3).
Table 4–3. Rash and Arthritis.
Skin Manifestation
Erythematous maculopapular rash
Associated Conditions
Superimposed drug reaction
Still disease
Viral syndromes
Kawasaki disease
Secondary syphilis
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Chronic meningococcemia
Approach to the Patient with Arthritis: Introduction, John B. Imboden, MD
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Urticaria
SLE
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Erythematous maculopapular rash
Superimposed drug reaction
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Still disease
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Viral syndromes
Kawasaki disease
Secondary syphilis
Chronic meningococcemia
Urticaria
SLE
Hypocomplementemic urticarial vasculitis
Serum sickness
Acute hepatitis B
Still disease
Schnitzler syndrome
Palpable purpura
ANCA­associated vasculitis
SLE
Hypersensitivity vasculitis
Cryoglobulinemia
Henoch­Schonlein purpura
Subacute bacterial endocarditis
Papulosquamous lesions
Psoriatic arthritis
Reactive arthritis
Discoid lupus
Subacute cutaneous lupus erythematosus
Secondary syphilis
Annular lesions
Subacute cutaneous lupus erythematosus
Lyme disease (erythema chronicum migrans)
Acute rheumatic fever (erythema marginatum)
Pustular lesions
Disseminated gonococcal infection
Pustular psoriasis
Reactive arthritis (keratoderma blenorrhagicum)
Behçet disease
Acne­associated rheumatic syndromes
Sweet syndrome (also painful papule/nodules)
Subcutaneous nodular lesions
Erythema nodosum
Sarcoidosis
Inflammatory bowel disease
Behçet disease
SLE (lupus profundus)
Polyarteritis nodosa
Weber­Christian disease
ANCA, antineutrophil cytoplasmic antibodies; SLE, systemic lupus erythematosus.
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Comorbid
Conditions
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Approach to the Patient with Arthritis: Introduction, John B. Imboden, MD
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Certain chronic conditions predispose to the development of particular musculoskeletal problems. For example, patients with long­standing, poorly
controlled diabetes mellitus are at greatly increased risk for Charcot arthropathy in the feet and limited joint mobility in the hands. Certain medications
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ANCA, antineutrophil cytoplasmic antibodies; SLE, systemic lupus erythematosus.
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Comorbid Conditions
Certain chronic conditions predispose to the development of particular musculoskeletal problems. For example, patients with long­standing, poorly
controlled diabetes mellitus are at greatly increased risk for Charcot arthropathy in the feet and limited joint mobility in the hands. Certain medications
can trigger drug­induced lupus, which can present as a polyarthritis, often with serositis. The resurgence in the use of hydralazine for the treatment of
hypertension has led to an increase in the incidence of hydralazine­induced lupus as well as the more serious hydralazine­induced, antineutrophil
cytoplasmic antibody (ANCA)­associated vasculitis. Prior glucocorticoid therapy and alcohol abuse are the leading risk factors for osteonecrosis, which
commonly presents as hip pain. Osteonecrosis and bone pain are common manifestations of Gaucher disease. Injection drug use carries the risk of
septic arthritis; endocarditis; and infection with hepatitis B, hepatitis C, and HIV—each of which is associated with rheumatic conditions.
Family History
A positive family history, particularly among first­degree relatives, increases the likelihood of certain forms of arthritis. Most notably, the risk of
ankylosing spondylitis for children or siblings of a patient with ankylosing spondylitis is as much as 75­fold that of the general population. The relative
risk for SLE among first­degree relatives ranges from 20 to 30. A positive family history of rheumatoid arthritis is less helpful. The relative risk for
siblings may be as low as 3, and family histories of rheumatoid arthritis can be inaccurate due to confusion with osteoarthritis.
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