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Clinical Approach to New Onset Arthritis
Jeffrey Carlin, MD Division of Rheumatology, VMMCClinical 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 Points1. 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 disease4. 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
Non-Inflammatory
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: RadiographsCBCESR/CRP
2. Indicated in certain patients: Cultures
3. Rarely indicated: Serologic: ANA, RF, HLA-B27Serum 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
• FemalesESR (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
• WomenCRP = (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 ArthritisGram 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 RxGram 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 pt- Assume 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
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 rhomboid-shaped
• 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 PolyarthritisInfection• Gonococcal• Meningococcal• Lyme disease• Rheumatic fever• Bacterial endocarditis• Viral (rubella,
parvovirus, Hep. B)
Acute PolyarthritisInfection• Gonococcal• Meningococcal• Lyme disease• Rheumatic fever• Bacterial endocarditis• Viral (rubella,
parvovirus, Hep. B)
Inflammatory• 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
Profound
Improves
Worsens
Yes
Yes
< 30 min
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 RA-like).
• 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 80%• JRA 20%• SLE 20%• Sjogren’s 90%• Scleroderma 20-30%
Non-Rheumatic Diseases with Positive RF
• Hepatitis C < 70%• Mixed cryoglobulinemia 90%• Sarcoidosis 5-30%• Pulmonary Fibrosis 20%• Infections varies• Aging 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.
Spondyloarthropathy
Undifferentiated spondyloarthropathy
Arthritis associated with
inflammatory bowel disease
Psoriatic arthritis
Ankylosing spondylitis
Reactive arthritis
Inflammatory Back Pain
• Onset of back discomfort before age 40• Insidious onset• > 3 mths duration• Morning stiffness in the back• Improvement with exerciseIf 4 of these are met, AS is diagnosed
Techniques for Imaging SIJ
Benefits Shortcomings
X-ray Quick & cheap Changes occur late
Radionuclide imaging
May indicate early changes Controversial
CT Clear imaging of early changes, may clarify dx when x-ray borderline
Radiation dose
Very early disease may still not be
detectable
MRI 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 6-8%• African-Americans 4%• African Blacks 0%• Japanese 1%• Koreans 3-4%• Native Americans 40-50%
(Haida, Navajo, Eskimos)
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%
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; 600-6102. 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 RA-
like.• 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 Groupor Region
Frequencyof
HLA-B27 inPopulation
Prevalence of AS inAdults
Prevalence of AllSpondyloarthropathies inAdults
GeneralPopulation
HLA-B27PositivePersons
GeneralPopulation
HLA-B27PositivePersons
Eskimos 40 0.4 2.5Eskimos(Alaska &Siberia) +Chukchi
25-50 1.6 2-3.4 4.2
Sami 24 1.8 6.8NorthernNorway
10-16 1.4
Mordovia 16 0.5WesternEurope
8 0.2 2
Germany(Berlin)
9 0.9 6.4 1.9 13.6
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