Resident Editor: Megan Lockwood, MD

Faculty Editor: Sarah Goglin, MD

Background

• It is crucial to differentiate between intra-articular pain vs peri-articular pain (such as pain in the soft tissue), as the differential diagnosis and management is different
  • Use a range of motion to help distinguish an intra-articular process from a peri-articular process:
    • Difficulty with passive ROM suggests an intra-articular process
    • Difficulty with active ROM suggests a peri-articular process
• Use a step-wise process to evaluate inflammatory joint pain:

 

Step 1: Is there inflammation present?

	History	Exam	Synovial Fluid
Inflammatory joint pain	Marked joint stiffness in the morning or with inactivity (“gelling phenomenon”); both pain and stiffness improved with mild to moderate activity	Warm, swollen joints with effusions; if markedly inflamed (septic or crystalline disease) there may be overlying erythema	>2000 WBC/mm3
Non-inflammatory joint pain	Limited amount of morning stiffness <30 minutes; pain worsens with activity	Cool joints with either small or no effusions, crepitus	<2000 WBC/mm3

 

Step 2: What is the rate of onset?

Hyperacute	Hours to days
Acute	<2 weeks
Subacute	2-6 weeks
Chronic	>6 weeks

 

Step 3: Categorize the type of joint involvement

A. Number of joints involved: Monoarthritis (1) vs. Oligoarthritis (2-4) vs. Polyarthritis (>4)

B. Distribution: Peripheral vs. Axial (spine, shoulders, hips)

C. Symmetry: Symmetric vs. Asymmetric

D. Pattern: Additive vs. Migratory vs. Intermittent

 

Step 4: Assess for extra-articular manifestations:

 

Acute Monoarthritis

Differential diagnosis:

• Infection:
  • Non-gonoccocal Septic Arthritis (NGSA)– Staph, Strep, and gram negatives
    • Synovial fluid analysis usually >50K WBC though may exceed 100K; gram stain is relatively insensitive (25-50%) though culture is highly sensitive (~ 90%)
  • Gonococcal Septic Arthritis – often associated with migratory tenosynovitis or oligoarthritis
    • Average WBC count in synovial fluid is 35K; gram stain is more sensitive than NGSA but culture of joint fluid is only 20-50% sensitive
    • Diagnosis often made by culture or nucleic acid amplification assays of samples obtained from other sites (urethra, cervix, rectum, throat)
  • Mycobacterial – rare, often associated with immunocompromise and travel to endemic areas
  • Fungal – rare, often associated with immunocompromise and travel to endemic areas
    • Also consider as a sterile extra-pulmonary manifestation of endemic myocoses
  • Lyme disease
    • Monoarticular synovitis occurs in ~10% of patients with late-stage Lyme disease, most commonly the knee
• Crystal-induced disease (Gout and CPPD):
  • Synovial fluid analysis can result in WBC counts that range from 30-100K although WBC counts >100K are uncommon
• Trauma: can result in hemarthrosis, especially if there is a propensity for bleeding
• Systemic disorders – can present as an acute monoarthritis
  • Seronegative spondyloarthritides, sarcoidosis, rheumatoid arthritis, hematologic malignancies

 

Evaluation: assess risk factors for infection; assess for possible mechanisms of injury and ensure that if present, the type of injury is sufficient to explain symptoms and exam

• Lab: All patients with acute inflammatory monoarthritis should have an arthrocentesis if possible. At UCSF, a purple top tube is sent for cell count and differential as well as crystal analysis. A black top tube is sent for gram stain and culture. if only a few drops of fluid are aspirated may place a drop on a slide for crystal analysis and another for gram stain.
• Imaging: helpful primarily in ruling out fractures or dislocation; may see chondrocalcinosis, erosions or joint space narrowing. Always order bilateral views if there is a left and right joint affected for comparison.

 

Synovial Fluid Analysis*

Measure	Normal	Non-inflammatory	Inflammatory	Septic
Color	Transparent	Transparent	Translucent-Opaque	Opaque/pus
WBC (/mm3)	<200	200-2,000	2,000-50,000	>50,000
% PMNs	<25	<25	Variable	>75
Culture	Negative	Negative	Negative	Often positive

 

*Tips on synovial fluid analysis:

• Although the numbers above are true in general, they are not necessarily the rule. In early infection, you can have <50,000 WBC, and in long standing inflammation (especially with lower WBC), it can be less PMN predominant.
• You never need a synovial fluid glucose.
• Pseudogout crystals are often missed by the lab, as they are more difficult to visualize; by contrast, uric acid crystals are more strongly bi-refringent
• The gold standard for an acute crystalline process is “intracellular” crystals. In patients with non-acute flares, you can still find crystals outside the cells.

 

 

Acute Oligoarthritis

Differential diagnosis:

• Infection:
  • Gonococcal Septic Arthritis – often migratory
  • Non-gonoccocal Septic Arthritis – up to 25% of cases involve >1 joint
  • Lyme Disease – most often intermittent and affecting the knees; must have appropriate exposure history with travel to endemic areas to warrant testing (note: Lyme is not endemic in CA)
  • Bacterial Endocarditis – due to circulating immune complex (IC) deposition in synovium
  • Viral – usually polyarthritis; also likely due to circulating IC’s though certain viruses may also directly infect the synovium
• Post-Infectious:
  • Reactive Arthritis – history of urethritis or colitis
  • Rheumatic Fever / Post Strep
• Spondyloarthritis (SpA)
  • Reactive Arthritis – can occur independent of known infection
  • Psoriatic Arthritis
  • Ankylosing Spondylitis – always with axial involvement
  • IBD-associated Arthritis
• Crystal disease (Gout and CPPD)
• Oligoarticular presentation of conditions associated with polyarthritis
  • RA
  • SLE
  • Adult-onset Stills
  • Relapsing Polychondritis

 

Evaluation: primary goal is to exclude life or limb threatening infections

• Lab: basic blood and serum tests should be obtained including CRP and ESR; arthrocentesis should be performed if possible; patients should have extensive evaluation for GC, including culture or nucleic acid amplification assays of sample obtained from other sites (urethra, cervix, rectum, throat) which improves sensitivity of diagnosis; similarly, patients should have site-appropriate Chlamydial swabs sent
• Imaging: often of limited utility but can identify some forms of trauma as well as chondrocalcinosis

 

 

Acute Polyarthritis

Differential diagnosis:

• Acute Viral Infections – parvovirus B19, subacute HBV infection at pre-icteric phase, HCV, HIV
• Disseminated Lyme
• Secondary Syphilis
• RA
• SLE
• Acute Sarcoid – often in the setting of Lofgren’s syndrome with concurrent E. nodosum and hilar adenopathy
• Adult Still’s disease
• Systemic Vasculitis
• Paraneoplastic (rare)
• Whipple’s disease (rare)

 

Evaluation: often appropriate to follow clinically as most viral forms of polyarthritis will resolve without intervention

• Lab: basic blood and serum tests should be obtained including CRP and ESR, may consider RF as well as CCP and ANA particularly if persistent; consider evaluation for Hep B / Hep C if risk factors
• Imaging: often of limited utility in the acute setting

Chronic Monoarthritis

Differential diagnosis: Inflammatory

• Infectious:
  • Lyme Disease
  • Syphilis
  • Fungal
  • Mycobacterial
• Crystal disease:
  • Gout
  • CPPD (pseudogout)
  • Hydroxyapatite
• Monoarticular presentation of normally oligo/polyarticular process
  • RA
  • Spondyloarthritis
• Sarcoid (can also be non-inflammatory)

 

Differential diagnosis: Non-inflammatory

• Osteoarthritis
• Internal derangements (meniscal injury, osteititis dessicans)
• Osteonecrosis
• Neuropathic arthropathy (Charcot Joint)

Evaluation:

• Lab: If inflammatory: arthrocentesis; basic blood and serum tests should be obtained including CRP and ESR; may consider RF as well as CCP and ANA, particularly if persistent; many infections in this category require synovial biopsy for diagnosis (mycobacterial, fungal, and etc.)
• Imaging: often important in differentiating chronic processes
  • Hands – three views including PA/Oblique (Norgard views)/ Lateral
  • Elbows – three views
  • Shoulder – five views PA/PA with 15 degrees rotation/ Internal Rotation/External Rotation/ Axillary View
  • Hip – two views including AP/Lateral (ideally “frog leg” which includes some external rotation)
  • Knee – three views including Weight Bearing AP, Lateral in 15 degrees flexion, Sunrise or Merchant’s View
  • Foot – three views including AP, oblique, and lateral weight bearing films
  • SI – single AP view of Pelvis is sufficient (gives you both hips)
  • L-Spine – two views of AP/Lateral

 

Chronic Oligoarthritis

Differential diagnosis:

• Osteoarthritis
• Spondyloarthritis (SpA)
  • Psoriatic Arthritis
  • Reactive Arthritis
  • Ankylosing Spondylitis
  • Enteropathic / IBD associated arthritis
• Atypical Presentation of RA / SLE
• Crystalline Arthritis – primarily gout

 

Evaluation: assess for inflammatory back pain (see section below); assess for extra-articular manifestations of disease including skin, eye, and bowel disease

• Lab: consider ANA and RF/CCP only if patient has peripheral arthritis; HLAB27 if suspecting AS (this haplotype is associated with recurrent anterior uveitis in AS [GS1] )
• Imaging: obtain plain film imaging of involved joints including AP Pelvis and L-Spine images if suspecting SpA; if plain radiography is negative and clinical suspicion remains high then consider MRI and rheumatology referral for further evaluation

Chronic Polyarthritis

Differential diagnosis:

• Osteoarthritis
• Rheumatoid Arthritis
• Systemic Lupus
• Spondyloarthritis
• Drug Induced
• HCV-associated
• Sjogren’s Syndrome
• Adult-Onset Still’s
• Systemic Vasculitis
• Paraneoplastic
• Viral Infections other than HCV
• Whipple’s disease

 

Evaluation:

• Lab: If inflammatory: consider CRP, ESR, RF/anti-CCP and ANA; consider evaluation for HBV / HCV based on risk factors
• Imaging: should be obtained of symptomatic areas; recommend obtaining bilateral hand and foot films if significant concern for RA

Inflammatory Back Pain

• It is important to distinguish back pain from inflammation in the lower spine/sacroiliac joint from other etiologies of back pain
• Application of the IBP criteria aids in the early diagnosis of axial spondyloarthritis, especially as a referral screening tool in the primary care setting.
• Classic parameters for IBP:
  • Age of onset <40
  • Insidious symptom onset
  • Stiffness improved with exercise, stiffness worsened with rest
  • Nocturnal back pain, awakening the patient in the second half of the night
  • Marked improvement with NSAIDs
• The pain described by patients is typically a dull ache, worst in the lower back and/or buttocks, though may also present in the hips and shoulders

References

Helfgott, S. Overview of monoarthritis in adults. Last updated October 25, 2017. UpToDate. Accessed July 29 ,2018. 

Imboden, J. “Approach to the Patient with Arthritis.” Current Diagnosis and Treatment: Rheumatology. 3^rd edition. Ed. John Imboden, David Hellman, John Stone. The Mc-Graw-Hill Companies, 2013. 

Margaretten ME, et al. Does this adult have septic arthritis? JAMA. 2007 Apr 4;297(13):1478-88.

Richie AM, Francis L. Diagnostic Approach to Polyarticular Joint Pain. Am Fam Physician. 2003 Sep 15;68(6):1151-1160.

Shmerling RH. Evaluation of the adult with polyarticular pain. Last updated May 31, 2017. UpToDate. Accessed July 29, 2018.

 Sieper, J, et al. New criteria for inflammatory back pain in patients with chronic back pain: A real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009;68(6):784–8.