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

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 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%

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; 600-6102. 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