1. Clinical Approach to New Onset Arthritis
Jeffrey Carlin, MD
Division of Rheumatology, VMMC
Clinical Associate Professor, UW

2. Nothing to declare

3. 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.

4. 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!

5. 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
Prominent
Frequent
WBC >2000
Septic, RA, SLE, Gout
Yes (PM)
Bony
Absent
Minor (< 30 ‘)
Uncommon
WBC < 2000
OA, AVN

6. 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)

7. Acute Monoarthritis - Etiology
THE MOST CRITICAL DIAGNOSIS TO CONSIDER: INFECTION !

8. Acute Monoarthritis - Etiology
Septic
Crystal deposition (gout, pseudogout)
Traumatic (fracture, internal derangement)
Other (hemarthrosis, osteonecrosis, presentation of polyarticular disorders)

9. 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.

10. Acute Monoarthritis

11. 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

12. 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.

13. Synovial Fluid Analysis

14. 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

15. Tests of Acute Phase Reactants
Erythrocyte Sedimentation Test
C-Reactive Protein

16. Patterns of Response of Acute Phase Reactants
Gabay C, Kushner I, NEJM , 1999;340:450

17. 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

18. Formula for Age- Related Normals
Men:
ESR(mm/hr)= (age in years)/2
Females
ESR (mm/hr)= (age in years + 10)/2

19. 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

20. Formula for Age-Related Normals
Men
CRP = (age/65) +.1 mg/dl
Women
CRP = (age/65) + .7 mg/dl

21. 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

22. 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%

23. Likely Causes of Septic Arthritis
Gram Stain
Pt Characteristic
Organism of Concern
No Bacteria
Young, healthy
GC, Staph
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
GC ( consider meningococcemia)
Gm -
Rx for possible pseudomonas
SLE or Sickle Cell
Include coverage for Salmonella & Psudomonas
Hx prosthetic joint
Staph epidermidis, Staph aureus
HX fresh/salt H20 exposure + injury; chronic swelling
Mycobacterium marinum

24. 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
None- (Healthy young pt- Assume GC but include Gm + coverage
None- (Underlying disease or Immunosupression
Vancomycin 1 gm IV 12 h + Cipro 400mg q 12 h

25. Acute Gouty Arthritis

26. 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

27. Urate Crystals
Needle-shaped
Strongly negative birefringent

28. Gouty Arthritis

29. Pseudogout

30. 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).

31. CPPD Crystals
Rod or rhomboid-shaped
Weakly positive birefringent

32. Algorithm for w/u of Monoarticular Arthritis

33. Polyarthritis
Definite inflammation (swelling, tenderness, warmth of > 5 joints
A patient with 2-4 joints is said to have pauci- or oligoarticular arthritis

34. Acute Polyarthritis Infection Gonococcal Meningococcal Lyme disease
Rheumatic fever
Bacterial endocarditis
Viral (rubella, parvovirus, Hep. B)

35. Acute Polyarthritis Infection Inflammatory Gonococcal RA Meningococcal
Lyme disease
Rheumatic fever
Bacterial endocarditis
Viral (rubella, parvovirus, Hep. B)
Inflammatory RA
JRA
SLE
Reactive arthritis
Psoriatic arthritis
Polyarticular gout
Sarcoid arthritis

36. Inflammatory Vs. Noninflammatory
Feature
Inflammatory
Mechanical
Morning stiffness
Fatigue
Activity
Rest
Systemic
Corticosteroid
>1 h
Profound
Improves
Worsens
Yes
< 30 min
Minimal No

37. 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

38. 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.

39. Acute Polyarthritis - RA

40. Rheumatoid Arthritis
Symmetric, inflammatory polyarthritis, involving large and small joints
Acute, severe onset %; 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!

41. Rheumatoid Factors

42. 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

43. Rheumatic Diseases with Positive RF
RA 80%
JRA %
SLE %
Sjogren’s %
Scleroderma %

44. Non-Rheumatic Diseases with Positive RF
Hepatitis C < 70%
Mixed cryoglobulinemia 90%
Sarcoidosis %
Pulmonary Fibrosis 20%
Infections varies
Aging 5%

45. 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

46. RF: Test Statistics Sensitivity 80% Specificity 95%
PPV (unselected populations) %
(RA population)- 80%
NPV- 95%

47. Anti-Citrulline Antibody Assay
ELISA detects antibodies to cyclic citrullinated protein (anti-CCP)

48. 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 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

49. 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

50. 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.

51. Spondyloarthropathy Ankylosing spondylitis Reactive arthritis
Psoriatic arthritis
Spondyloarthropathy
Arthritis associated with inflammatory bowel disease
Undifferentiated spondyloarthropathy

52. 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

53. 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

54. Asymmetric, Inflammatory Oligoarthritis

55. Enthesitis in Spondyloarthropathies

56. 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

57. 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

58. Psoriatic Arthritis

59. 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

60. 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

61. Dactylitis “Sausage Toes” – Psoriasis

62. Nail Changes in Psoriatic Arthritis

63. Nail Pitting - Psoriasis

64. 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

65. HLA-B27 in the General Population
Caucasian %
African-Americans %
African Blacks %
Japanese 1%
Koreans %
Native Americans %
(Haida, Navajo, Eskimos)

66. HLA- B27 and Disease (Caucasians)
Disease Association
Ankylosing spondylitis %
Reactive arthritis %
Inflammatory bowel disease %
Psoriatic arthritis
With spondylitis %
With peripheral arthritis 15%
Undifferentiated Spondyloarthropathy 70%
Anterior Uveitis %

68. Sarcoid

69. 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

70. 2. Wolfe, F et al, Arth & Rheum 1990; 33:160-172
1. Wolfe F, et al Arthritis Care and Research 2010;62;
2. Wolfe, F et al, Arth & Rheum 1990; 33:

71. Prognosis of Early Undifferentiated Arthritis
Remission %
RA or other Dx- 7-65%
Persistant Disease w/o DX %
Monoarticular Arthritis
Remission- 60%
Oligoarticular %
Undifferentiated-70%

72. Thank you!

73. 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.

74. Butterfly Rash – SLE

75. Photosensitivity

76. Alopecia - SLE

77. 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.

78. Erythema Marginatum – Rheumatic Fever
Circinate
Evanenscent
Nonpruritic rash

79. Rheumatic Fever – Subcutaneous Nodes

80. Post-Strep Reactive Arthritis
Onset 7-10 days after Strep A
Oligoarthritis lasting >3weeks
Evidence for recent infection: Throat culture, +ASO titers

81. 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

82. Disseminated Gonococcemia – Pustules

83. 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

84. Viral Arthritides - Parvovirus

85. 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).

86. 1987 ACR Criteria for Rheumatoid Arthritis
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

87. Keratoderma Blenorrhagicum

88. Circinate Balanitis – Reactive Arthritis

89. Reactive Arthritis - Conjunctivitis

90. Reactive Arthritis – Palate Erosions

91. Recent Prevalence Studies of AS and Related Diseases (Khan, MA, Annals of Internal Medicine.2002;136: )

92. Lyme Disease

93. 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