Clinical Approach to
New Onset Arthritis
Jeffrey Carlin, MD
Division of Rheumatology, VMMC
Clinical Associate Professor, UW
Nothing to declare
Acute Arthritis
• The sudden onset of inflammation of the joint,
causing severe pain, swelling, and redness.
• Structural changes in the joint itself may result
from persistence of this condition.
Key Points
1. Distinguish arthritis from soft tissue non- articular
syndromes (discrepancy between “active” and
“passive” ROM suggests periarticular/soft tissue)
2. If the problem is articular distinguish single joint
from multiple joint involvement
3. Inflammatory or non-inflammatory disease
4. Always consider septic arthritis!
Inflammatory Vs. Noninflammatory
Feature
Inflammatory
Noninflammatory
Pain (when?)
Swelling
Erythema
Warmth
AM stiffness
Systemic features
î ESR, CRP
Synovial fluid WBC
Examples
Yes (AM)
Soft tissue
Sometimes
Sometimes
Prominent
Sometimes
Frequent
WBC >2000
Septic, RA, SLE,
Gout
Yes (PM)
Bony
Absent
Absent
Minor (< 30 ‘)
Absent
Uncommon
WBC < 2000
OA, AVN
Acute Monoarthritis
• Inflammation (swelling, tenderness,
warmth) in one joint
• Occasionally polyarticular diseases can
present with monoarticular onset:
(RA, JRA,Reactive and enteropathic arthritis, Sarcoid
arthritis, Viral arthritis, Psoriatic arthritis)
Acute Monoarthritis - Etiology
• THE MOST CRITICAL DIAGNOSIS TO
CONSIDER: INFECTION !
Acute Monoarthritis - Etiology
•
•
•
•
Septic
Crystal deposition (gout, pseudogout)
Traumatic (fracture, internal derangement)
Other (hemarthrosis, osteonecrosis,
presentation of polyarticular disorders)
Questions to Ask –
History Helps in Differential Diagnosis
• Pain come suddenly, minutes? – fracture.
• 0ver several hours or 1-2 days? –infectious, crystals,
inflammatory arthropathy.
• History of IV drug abuse or a recent infection? –
septic joint.
• Previous similar attacks? – crystals or inflammatory
arthritis.
• Prolonged courses of steroids? – infection or
osteonecrosis of the bone.
Acute Monoarthritis
Indications for Arthrocentesis
– SYNOVIAL FLUID ANALYSIS: The single most useful
diagnostic study in initial evaluation of
monoarthritis
– 1. Suspicion of infection
– 2. Suspicion of crystal-induced arthritis
– 3. Suspicion of hemarthrosis
– 4. Differentiating inflammatory from
noninflammatory arthritis
Tests to Perform on Synovial Fluid
• Gram stain and cultures
• Total leukocyte count/differential
– Inflammatory vs. non-inflammatory
• Polarized microscopy to look for crystals
• Not necessary routinely:
– Chemistry (glucose, total protein, LDH) unlikely to
yield helpful information beyond the previous
tests.
Synovial Fluid Analysis
Joint Fluid
Appearance
Cell Count
Normal
Clear/Yellow
<200 WBC’s
NonInflammatory
Clear/Yellow
<2000 WBC’s
Inflammatory
Turbid/Yellow
<50,000 WBC’s
Septic
Pus
>50,000 WBC’s
Other Tests Indicated
for Acute Arthritis
1. Almost always indicated:
Radiographs
CBC
ESR/CRP
2. Indicated in certain patients:
Cultures
3. Rarely indicated:
Serologic: ANA, RF, HLA-B27
Serum Uric acid level
Tests of Acute Phase Reactants
• Erythrocyte Sedimentation Test
• C-Reactive Protein
Patterns of Response of
Acute Phase Reactants
Gabay C, Kushner I, NEJM , 1999;340:450
ESR’s
• Non-specific marker- elevated in rheumatic diseases,
infection, malignancy
• Can be artificially elevated by:
• Pregnancy
• Anemia
• Nephrotic Syndrome
• Benign/Malignant Monoclonal Gammopathies
• Age
• Obesity
• Can be normal in some inflammatory conditions
Formula for Age- Related Normals
• Men:
ESR(mm/hr)= (age in years)/2
• Females
ESR (mm/hr)= (age in years + 10)/2
C- Reactive Protein
• Produced in liver in response to
IL-1 & IL-6
• Rapid rise in response to inflammatory stimuli
• Can be affected by:
– Obesity/Metabolic Syndrome
– Age
Formula for Age-Related Normals
• Men
CRP = (age/65) +.1 mg/dl
• Women
CRP = (age/65) + .7 mg/dl
Septic Joint
•
•
•
•
•
•
•
Most articular infections – a single joint
15-20% cases polyarticular
Most common sites: knee, hip, shoulder
20% patients afebrile
Joint pain is moderate to severe
Joints visibly swollen, warm, often red
Comorbidities: RA, DM, SLE, cancer,etc
Septic Joint - Nongonococcal
• 80-90% monoarticular
• Most develop from hematogenous spread
• Most common:
– Gram positive aerobes (80%)
– Majority with Staph aureus (60%)
– Gram negative 18%
Likely Causes of Septic Arthritis
Gram Stain
Pt Characteristic
Organism of Concern
No Bacteria
Young, healthy
GC, Staph
No Bacteria
Hx of RA
Staph
No bacteria
Immunosupression, IV
drugs, Hx gm- infection
Staph, Strep, Pseudomonas,
fungal
No Bacteria or Gm -
Recent cat/dog bite
Pasteurella multocida
Gm+
None
Staph/Strep
Gm- diplococci
None
GC ( consider
meningococcemia)
Gm -
None
Rx for possible
pseudomonas
Gm -
SLE or Sickle Cell
Include coverage for
Salmonella & Psudomonas
No bacteria
Hx prosthetic joint
Staph epidermidis, Staph
aureus
No bacteria
HX fresh/salt H20 exposure
+ injury; chronic swelling
Mycobacterium marinum
Initial Empirical Antibiotic Rx
Gram Stain
Drug of Choice
Alternative Drug
Gm + Cocci (small) in pairs
& chains
Vancomycin 1 gm IV 12 h
Cefotaxime 2.0 gm Iv q6-8h
Gm+ Cocci (large) singly or
in large groups
Vancomycin 1 gm IV q12 h
Nafcillen 2.0gm Iv q 4h
Gm - Bacilli
Ceftriaxone 2.0 gm q 24h
Imipenem .5 gm IV q 6h
Gm- Bacilli
Cefotaxime 2.0 gm IV q 6h
Imipenem .5 gm IV q 6h
None- (Healthy young ptAssume GC but include Gm
+ coverage
Ceftriaxone 2.0 gm q 24h
Imipenem .5 gm IV q 6h
None- (Underlying disease
or Immunosupression
Vancomycin 1 gm IV 12 h +
Cipro 400mg q 12 h
Imipenem .5 gm IV q 6h
Acute Gouty Arthritis
Gout
•
•
•
•
•
•
Caused by monosodium urate crystals
Most common type of inflammatory monoarthritis
Typically: first MTP joint, ankle, midfoot, knee
Pain very severe; cannot stand bed sheet
May be with fever and mimic infection
The cutaneous erythema may extend beyond the
joint and resemble bacterial cellulitis
Urate Crystals
• Needle-shaped
• Strongly negative
birefringent
Gouty Arthritis
Pseudogout
Pseudogout
• Can cause monoarthritis clinically indistinguishable
from gout.
• Often precipitated by illness or surgery.
• Pseudogout is most common in the knee (50%) and
wrist.
• Reported in any joint (Including MTP).
• CPPD disease may be asymptomatic (deposition of
CPP in cartilage).
CPPD Crystals
• Rod or rhomboidshaped
• Weakly positive
birefringent
Algorithm for w/u of Monoarticular
Arthritis
Polyarthritis
• Definite inflammation (swelling,
tenderness, warmth of > 5 joints
• A patient with 2-4 joints is said to
have pauci- or oligoarticular
arthritis
Acute Polyarthritis
Infection
•
•
•
•
•
•
Gonococcal
Meningococcal
Lyme disease
Rheumatic fever
Bacterial endocarditis
Viral (rubella,
parvovirus, Hep. B)
Acute Polyarthritis
Infection
Inflammatory
•
•
•
•
•
•
•
•
•
•
•
•
•
Gonococcal
Meningococcal
Lyme disease
Rheumatic fever
Bacterial endocarditis
Viral (rubella,
parvovirus, Hep. B)
RA
JRA
SLE
Reactive arthritis
Psoriatic arthritis
Polyarticular gout
Sarcoid arthritis
Inflammatory Vs. Noninflammatory
Feature
Inflammatory
Mechanical
Morning
stiffness
Fatigue
Activity
Rest
Systemic
Corticosteroid
>1 h
< 30 min
Profound
Improves
Worsens
Yes
Yes
Minimal
Worsens
Improves
No
No
Temporal Patterns in Polyarthritis
• Migratory pattern:
– Rheumatic fever, gonococcal (disseminated
gonococcemia), early phase of Lyme disease
• Additive pattern
– RA, SLE, psoriasis
• Intermittent:
– Gout, reactive arthritis
Patterns of Joint Involvement
• Symmetric polyarthritis involving small and large
joints: viral, RA, SLE, one type of psoriatic (the RAlike).
• Asymmetric, oligo- and polyarthritis involving
mainly large joints, preferably lower extremities,
especially knee and ankle : reactive arthritis, one
type of psoriatic, enteropathic arthritis.
• DIP joints: Psoriatic.
Acute Polyarthritis - RA
Rheumatoid Arthritis
• Symmetric, inflammatory polyarthritis, involving
large and small joints
• Acute, severe onset 10-15 %; subacute 20%
• Hand characteristically involved
• Acute hand deformity: fusiform swelling of fingers
due to synovitis of PIPs
• RF/Anti-CCP Ab may be negative at onset and
may remain negative in 15-20%!
• RA is a clinical diagnosis, no laboratory test is
diagnostic, just supportive!
Rheumatoid Factors
Rheumatoid Factors
• Autoantibodies to the Fc portion of IgG.
• Support a diagnosis of Rheumatoid Arthritis but
are not by themselves diagnostic.
• Are seen in about 75% to 80% of patients with
RA.
• Are associated with a poor prognosis in patients
with RA.
• Are seen in conditions other than RA
Rheumatic Diseases
with Positive RF
•
•
•
•
•
RA
JRA
SLE
Sjogren’s
Scleroderma
80%
20%
20%
90%
20-30%
Non-Rheumatic Diseases
with Positive RF
•
•
•
•
•
•
Hepatitis C
Mixed cryoglobulinemia
Sarcoidosis
Pulmonary Fibrosis
Infections
Aging
< 70%
90%
5-30%
20%
varies
5%
RF: Clinical Significance
• Highly predictive of RA in patients with identified
rheumatic disease
• May be absent at the onset of disease in up to half of
patients with typical clinical picture of RA
– approx 20% remain seronegative
– many convert within 2 years
• Best used to confirm RA for typical presentation
– inflammatory polyarthritis, “gel phenomenon,”
etc.
• Not useful to follow course of illness
– generally not helpful to repeat after diagnosis
RF: Test Statistics
• Sensitivity 80%
• Specificity 95%
• PPV (unselected populations)- 20-30%
(RA population)- 80%
• NPV- 95%
Anti-Citrulline Antibody Assay
ELISA detects antibodies to cyclic citrullinated
protein (anti-CCP)
Anti-CCP Antibody Assay
• Accuracy (Anti-CCP-2 Assay)
– Specificity 79%
Sensitivity 96-98%
• Diagnosis more accurate when combined with RF+
• Present in 50-60% early RA patients
• Can be seen 1.5 -9 yrs pre-diagnosis of RA
• Predictive for progressive joint damage
– Present in up to 40% percentage of RF- patients
with erosions
– RF+, anti-CCP+ pts have very aggressive disease
Viral Arthritis
•
•
•
•
•
•
Younger patients
Usually presents with prodrome, rash
History of sick contact
Polyarthritis similar to acute RA
Prognosis good; self-limited
Examples: Parvovirus B-19, Rubella, Hepatitis
B and C, Acute HIV infection, Epstein-Barr
virus, mumps
Parvovirus B-19
• The virus of “fifth disease”, erythema infectiosum
(EI).
• Children “slapped cheek”; adults flu-like illness,
maculopapular rash on extremities.
• Joints involved more in adults (20% of cases).
• Frequently RF +
• Abrupt onset symmetric polyarthralgia/polyarthritis
with stiffness in young women exposed to kids with
E.I.
• May persist for a few weeks to months.
Reactive
arthritis
Ankylosing
spondylitis
Psoriatic
arthritis
Spondyloarthropathy
Arthritis
associated with
inflammatory
bowel disease
Undifferentiated
spondyloarthropathy
Inflammatory Back Pain
• Onset of back discomfort before age 40
• Insidious onset
• > 3 mths duration
• Morning stiffness in the back
• Improvement with exercise
If 4 of these are met, AS is diagnosed
Techniques for Imaging SIJ
X-ray
Radionuclide
imaging
CT
MRI
Benefits
Shortcomings
Quick & cheap
Changes occur late
May indicate early changes
Controversial
Clear imaging of early
changes, may clarify dx
when x-ray borderline
Radiation dose
Very early disease
may still not be
detectable
May show inflammation &
very early changes
Price & availability
Asymmetric, Inflammatory
Oligoarthritis
Enthesitis in Spondyloarthropathies
Reactive Arthritis
• Triggered by specific gut or genito-urinary tract
infections
– Salmonella, Yersinia, Campylobacter, Shigella
– Chlamydia
• Joint symptoms appear 1-3 week later
– Oligoarthritis; usually lower extremity
– Enthesitis
• Frequent association with extra-articular findings
• A proportion evolve into chronic spondyloarthropathy
Extra-articular Features
of Reactive Arthritis
•
•
•
•
•
Don’t be put off if they are not present
Ask about GI disturbance - even mild
Ask about conjunctivitis
Take a sexual history (with explanation)
Examine eyes and skin (soles/external
genitalia)
• Look for enthesitis
Psoriatic Arthritis
Psoriatic Arthritis
• Prevalence of arthritis in Psoriasis 10-20%
– Psoriasis usually precedes PSA- 75%
– 10-15% arthritis precedes Psoriasis
– Nail changes common
• Psoriatic plaques
– Scalp, extensor surfaces, natal cleft, umbilicus
Psoriatic Arthritis
• Subtypes:
– Asymmetric, oligoarticular- associated dactylitis
– Predominant DIP involvement – nail changes
– Polyarthritis “RA-like” – lacks RF or nodules
– Arthritis mutilans – destructive erosive hands/feet
– Axial involvement –spondylitis
– HIV-associated – more severe
Dactylitis “Sausage Toes” – Psoriasis
Nail Changes in Psoriatic Arthritis
Nail Pitting - Psoriasis
European Criteria for
Spndyloarthropathy
• Inflammatory spine pain or synovitis
• And one or more of the following:
• Alternating buttocks pain
• Sacroiliitis
• Enthesopathy
• Positive family history
• Psoriasis
• IBD
• Recent episode of urethritis/cervicitis or
gastroenteritis
HLA-B27 in the General Population
•
•
•
•
•
•
Caucasian
African-Americans
African Blacks
Japanese
Koreans
Native Americans
(Haida, Navajo, Eskimos)
6-8%
4%
0%
1%
3-4%
40-50%
HLA- B27 and Disease
(Caucasians)
Disease
Association
Ankylosing spondylitis
90%
Reactive arthritis
60-80%
Inflammatory bowel disease
35-75%
Psoriatic arthritis
With spondylitis
50%
With peripheral arthritis
15%
Undifferentiated Spondyloarthropathy
70%
Anterior Uveitis
50%
Sarcoid
Acute Sarcoid Arthritis
• Löfgren’s syndrome: acute arthritis, erythema
nodosum, bilateral hilar adenopathy
• Chronic arthritis- (15-20%)
– Symmetrical: wrists, pip’s, ankles, knees
• Chronic inflammatory disorder – noncaseating
granulomas at involved sites
• Common with hilar adenopathy
1. Wolfe F, et al Arthritis Care and Research 2010;62; 600-610
2. Wolfe, F et al, Arth & Rheum 1990; 33:160-172
Prognosis of Early Undifferentiated
Arthritis
• Remission- 13-60%
• RA or other Dx- 7-65%
• Persistant Disease w/o DX- 10-40%
• Monoarticular Arthritis
– Remission- 60%
– Oligoarticular- 10-40%
– Undifferentiated-70%
Thank you!
Arthritis Of SLE
• Musculoskeletal manifestation 90%.
• Most have arthralgia.
• May have acute inflammatory synovitis RAlike.
• Do not develop erosions.
• Other clinical features help with DD: malar
rash, photosensitivity, rashes, alopecia, oral
ulceration.
Butterfly Rash – SLE
Photosensitivity
Alopecia - SLE
Arthritis of Rheumatic Fever
• Etiology: Streptococcus pyogenes (group A); there is
damaging immune response to antecedent infection
– molecular cross reaction with target organs
“molecular mimicry”.
• Onset approximately 3wks after exposure
• Migratory polyarthritis, large joints: knees, ankles,
elbows, wrists.
• Major manifestations: carditis, polyarthritis, chorea,
erythema marginatum, subcutaneous nodules.
Erythema Marginatum – Rheumatic
Fever
• Circinate
• Evanenscent
• Nonpruritic rash
Rheumatic Fever – Subcutaneous
Nodes
Post-Strep Reactive Arthritis
• Onset 7-10 days after Strep A
• Oligoarthritis lasting >3weeks
• Evidence for recent infection: Throat culture,
+ASO titers
Adult Still’s Disease and JRA Rash
• Salmon or pale-pink
• Blanching
• Macules or
maculopapules
• Transient (minutes or
hours)
• Most common on
trunk
• Fever related
Disseminated Gonococcemia –
Pustules
Septic Joint - Gonococcal
• Most common cause of septic arthritis
• Often preceded by disseminated gonococcemia
• Sexually active individual, 5-7 days h/o fever, chills,
skin lesions, migratory arthralgias and tenosynovitis
 persistent monoarthritis
• Women often menstruating or pregnant
• Genitourinary disease often asymptomatic
Viral Arthritides - Parvovirus
Rubella Arthritis
• German measles.
• Young women exposed to school-aged children.
• Arthritis in 1/3 of natural infections; also following
vaccination.
• Morbilliform rash, constitutional symptoms.
• Symmetric inflammatory arthritis (small and large
joints).
1987 ACR Criteria
for Rheumatoid Arthritis
• 4/7 Criteria
– AM Stiffness lasting > 1 hr
– Swelling in >3 joint areas simultaneously
– Swelling in Wrist, MCP or PIP joint
– Symmetrical Arthritis
– Rheumatoid Nodules
– Positive RF (or Anti-CCP AB)
– XRay Changes
Keratoderma Blenorrhagicum
Circinate Balanitis – Reactive Arthritis
Reactive Arthritis - Conjunctivitis
Reactive Arthritis – Palate Erosions
Recent Prevalence Studies of AS and
Related Diseases
(Khan, MA, Annals of Internal Medicine.2002;136:896-907)
Ethnic Group
or Region
Eskimos
Eskimos
(Alaska &
Siberia) +
Chukchi
Sami
Northern
Norway
Mordovia
Western
Europe
Germany
(Berlin)
Frequency
of
HLA-B27 in
Population
Prevalence of AS in
Adults
Prevalence of All
Spondyloarthropathies in
Adults
General
Population
General
Population
HLA-B27
Positive
Persons
40
25-50
0.4
24
10-16
1.8
1.4
16
8
0.5
0.2
2
9
0.9
6.4
1.6
HLA-B27
Positive
Persons
2.5
2-3.4
4.2
1.9
13.6
6.8
Lyme Disease
Lyme Arthritis
• Erythema migrans 7-10 days after Borrelia
burgdorferi tick bite
• Early dissemination– Migratory arthralgias, fever, systemic
complaints
• Late dissemination/Chronic disease– Migratory oligoarthritis
– Carditis
– Neurological