1. Low Back Pain and the Seronegative Spondyloarthropathies
Scott R. Burg, D.O.
Orthopaedic and Rheumatologic Institute
Cleveland Clinic

2. Spondyloarthropathies (SPA)
A group of common inflammatory rheumatic disorders characterized by:
Axial and/or peripheral arthritis, enthesitis, dactylitis
Potential extra-articular changes such as uveitis and skin rash

3. Common Genetic Predisposition
HLA-B27 gene
Association varies widely among various SPAs and ethnic groups
Environmental factors seem to be triggering the diseases in genetically predisposed

4. Radiographic Hallmark
Sacroilitis

6. SPA Characterized by: Sacroilitis Inflammatory back pain
Peripheral arthropathy
Absence of rheumatoid factor/CCP and subcutaneous nodules
Enthesitis
Extra spinal involvement (eye, heart, lung and skin)
HLA-B27
At least 6 other genes associated with ankylosing spondylitis identified to date

7. Inflammatory Low Back Pain
Assumed to be characterized by inflammation of SIJ and lumbar spine
Young age of onset
Continuous pain > 3 months
Morning stiffness
Pain improving on activity

8. Inflammatorty Back Pain
Unilateral or bilateral
Alternates from side to side
Responds well to NSAIDs

9. Sacroilitis and Inflammatory Low Back Pain
Prevalence 50%

10. F.D. Hart Quarterly Journal of Medicine, 1949
A frequent feature of the pain and stiffness was the aggravation caused by immobility. Waking in the morning stiff and in pain, the patient gradually became more supple during the day, feeling at his best from the afternoon until bedtime. One patient noted that by frequent exercise, his condition was kept in check, but confinement to bed for any cause made him worse. Another woke himself up (every 2 hours) throughout the night to exercise his spine as otherwise, he suffered unduly in the morning.

11. IBP in USA Present in 6% General back pain 20%
Performs well as case ascertainment tool for those who seek care
SPA in 1%, what constitutes the gap?

12. IBP Concept
Distinguishing feature in all criteria sets developed to identify AS and SPA
Criteria sets share several key clinical features
Diverge on genetic indicators and radiographic parameters

13. Value of IBP Concept in Primary Care Setting
Defines a group at risk for SPA or AS
Defense of further diagnostic testing i.e. imaging or genetic tests
Negative tests in IBP any justification for NSAID’s or biologics to treat symptoms or prevent SPA or AS

14. Spondyloarthropathies (SPA)
Ankylosing spondylitis (AS)
Reactive arthritis (REA)
Psoriatic arthritis (PSA)
SPA associated with inflammatory bowel disease (IBD)
Undifferentiated SPA (USPA)
Juvenile onset spondyloarthritis

15. Ankylosing Spondylitis (AS)
Most common and most typical
% of Caucasian population. Variability based on regional, genetic and environmental factors
Lower male to female ratio (2-3.1) based on recent epidemiologic studies
Higher in HLA-B27 populations

17. Diagnosis of AS Delayed
As long as 8 years
Longer delays in females

18. Diagnostic and Classification Criteria
European spondyloarthropathy study group (ESSG)
Assessment in Spondyloarthritis International Society (ASAS) proposed new set of diagnostic criteria enabling identification of SPA before structural changes occur in the spine

20. MRI
Changes now included in new classification criteria of early axial SPA
Major tool diagnostically

21. AS Symptoms Early adulthood Dull pain buttock / lower lumbar area
Morning stiffness relived on exertion worsened on inactivity
Enthesitis
Inflammation at bone insertion sites of ligaments or tendons
Pain of enthesopathy varies and depends on affected location
Frank arthritis 25-35% involving large joints in asymmetrical fashion
Neck pain with increased ROM later manifestation

22. Dactylitis (Sausage Digit)
PSA
REA
Joint and tenosynovial inflammation

24. Other Clinical Features of AS
Acute anterior uveitis – 30% often antedates spondylitis
AI, CHF, aortitis, angina, pericarditis, conduction deficits
Dyspnea, cough, hemoptysis = pulmonary fibrosis

25. Reactive Arthritis (REA)
Arthritis 2-4 weeks after urogenital or enteric infection often in presence of HLA B27 antigen
Risk 50% higher in HLA-B27 positive
HLA B-27 positive associated with severity and chronicity
Enthesitis
70% of patients
Heel spur and pain
Achilles tendonitis
Knee synovitis with large effusions
Dactylitis typical

27. Extra-articular Features
Urethritis
Cervicitis
Vulvovaginitis and salpingitis
Prostatitis
Oral ulcers, e. nodosum, conjunctivitis
Cardiac involvement

28. Enteropathic Associated Arthritis (IBD)
10% of patients may antedate IBD
Asymmetric, large joints, lower limb
Occasional symmetrical, small joint polyarthritis

29. Spondyloarthritis and Sacroilitis
Independent course compared to bowel disease
Milder than AS
HLA-B27 positivity
Weaker than AS
25-60% of patients positive

30. Undifferentiated Spondyloarthropathy (USPA)
Patients without criteria for well-defined SPA
Fewer extra-articular changes
Sacroilitis / spondylitis absent, or very mild after years of active disease
Good prognosis

31. Juvenile Spondyloarthropathy
Asymmetric
Lower extremity peripheral
Boys aged 7-16 years
Enthesitis and dactylitis prominent
Systemic manifestations frequent in juvenile than adult form

32. Psoriatic Arthritis (PSA)
Develops in 5-40% of psoriasis patients
Incidence 7.2 per 100,000/year
Existing psoriasis patients prevalence rises from .2% of 7-40%

33. Arthritis in PSA Asymmetric in small and large joints
Patterns include:
Mutilans
Peripheral oligoarthritis / polyarthritis
Spondylitis
DIP arthritis (fingers and toes >50%)

34. Back Pain in PSA Cervical spine disease common (>50%)
Progresses in severity in parallel with disease of peripheral joints
Sacroilitis – 20% of patients
Spondylitis – 5% of patients

35. PSA Nails (83%) or skin precede or follow joint involvement
Scalp, behind ears, umbilicus or gluteal folds
Fatigue, iritis, uveitis

37. Biomarkers to Assess PSA
CRP
Matrix metalloproteinase-3
Circulating osteoclast precursors
HLA-B27 represents axial disease sacroilitis and spondylitis

38. Conventional Radiography
Important outcome domain in clinical trials of (ASAS)
Recognition of early bone changes beneficial in patients early therapy response to disease progression
Inexpensive, easy to generate
Widely available and inexpensive; rapid and easily studied in randomized and blinded environments

39. Imaging Role in Sacroilitis
MRI and CT – high sensitivity and better detection of early sacroilitis but cost prohibits use in routine diagnosis
Plain radiograph initial diagnostic tool but large inter and intraobserver variations documented

40. Battistone, et. al. Oblique views not justifiable
High specificity (97.8%) low sensitivity (54.4%)

41. Radiographic Hallmarks in SPA
Erosions – earliest – iliac side
Periostitis
Bone proliferation at enthesis
Normal bone mineralization

44. Progression of Erosive Disease
Widening of joint
Reparative bone laid down behind erosions
Total fusion of SIJ (ankylosis)

46. Radiographs
Poor sensitivity to soft tissue and bony changes in early SI disease
Bony changes not evident until advanced stage of disease
Reliability unsatisfactory and leads to therapy delays

47. Sacroiliac Joint Involvement in (SPA)
Most common early clinical finding
First manifestations of disease

48. Criteria for Classification of SPA
ESSG
Amor Criteria
Modified New York Criteria
Criteria sets all fall short as these all depend on presence of radiological sacroilitis (often appears late in disease course)
Long delay exists between initial symptoms and establishing a diagnosis

50. Conventional Radiography
Assess structural spine changes
Document more chronic lesions
Not sensitive to change over 2 years

51. Computed Tomography Superior to radiography
Better definition of bone detail
Soft tissue overlap, air, intestinal loops, feces absent
Specific contrast windows
Observer variation reduced
Diagnostic CT performed supine with semicoronal slice and preferable to axial CT
Overall view of cartilaginous joint facets and ligamentous part of SIJ
Superior to MRI in detection of chronic bony changes in the ligamentous portion of the joint
Considerable radiation exposure

53. CT Findings Comparable to chronic changes of MRI
Better for evaluating joint space alteration
Better demonstrating ossification of enthesopathies not always seen on MRI
Cannot demonstrate present disease activity

54. Use of MRI in SPA
Key tool for assessment of inflammation structural damage in AS

55. MRI Imaging method for earlier diagnosis of sacroilitis
Identifies both inflammation and structural changes
Radiographs only structural changes

57. MRI Compared to CT and Conventional X-RAY
Detects active inflammatory change
Visualizes soft tissue
Chronic changes
Early diagnosis of sacroilitis well before CT or radiography
Monitoring disease activity

59. MRI Disadvantages Long examination times High cost Skilled staff
Contraindications – i.e. pacemakers

60. TNF Agents Dramatic change in therapeutic strategies in AS
Improvement of clinical disease activity correlates with reduction of acute skeletal change documented by post Gadolinium and Stir MRI exams

61. Blum (1996) and Hanly (1994) Prospective study
MRI 100% specific in clinical sacroilitis
IBP – 67% specific in early recognition of sacroilitis

62. MRI in AS Erosion of cartilaginous joint facets
Concomitant edema and enhancement of joint and subchondral bone
Changes on iliac side of joint
Sacral involvement more frequent in AS

63. MRI in AS Early Diagnosis
Sacral involvement
Fatty marrow degeneration
Joint space widening
Pronounced subchondral sclerosis
Only technique to detect actively inflamed lesions of SIJ and spine
Gold standard for efficacy of TNF therapy in future

64. Ultrasonography
Highly sensitive, non-invasive imaging technique for soft tissue involvement in SPA
Entheses initial site of joint inflammation in SPA
Enthesopathy often under-estimated
Higher sensitivity than MRI for early signs of enthesitis

65. US in SIJ Involvement in SPA
Fast
Inexpensive
Complements physical exam identifying origin of IBP

66. U.S. Only visualize superficial part of SIJ
Cannot visualize cartilaginous portion
Less sensitive detecting erosions
Possible to diagnose active sacroilitis based on increased joint vascularization of posterior joint

67. Bone Scintigraphy
Limited diagnostic value for diagnosis of established AS or early diagnosis of probable/suspected sacroilitis
Sensitivity not higher than 50-55%
Specificity about 80%
Radiation exposure lower than CT but higher than plain radiography

69. PSA Radiographic Changes
Entheseal bone formation
Periostitis
Entheseal erosions
Diffuse bone based pathology

70. Ultrasound in PSA 25% more lesions found than on clinical exam alone
Achilles abnormalities in 59.2% of PSA patients

71. PSA and Sacroilitis 25% in two series 78% in a third series Unilateral
Axial and peripheral disease cause frequent and severe lesion
Cartilaginous and ligamentous joint involvement
Bony ankylosis less frequent than AS
Bone eburnation of sacral and iliac surface more marked in PSA than AS

73. Reactive Arthritis (REA) and Sacroilitis
50% of patients symmetrical
Minor changes in distal portion (synovial)
Entheses in ligamentous part

75. Enteropathic ENSPA Protzer, et. Al.
SPA in 10.7% of all CD and 14.4% of all UC patients
26.8% prior to GI symptoms
14.4% simultaneous

76. ENSPA and Sacroilitis Often bilateral Radiographically similar to AS
More dominant involvement of ligamentous portion of joint than other forms

77. ENSPA and Imaging CT entheseal and ligamentous
Frequent
MRI inflammation at entheses

79. Undifferentiated Spondyloarthropathy (UPSA)
Clinical and suggestive of SPA but not fulfilling diagnostic or classification criteria
USPA versus AS lack of grade ≥ 2 bilateral or grade 3 unilateral sacroilitis on x-ray

80. Take Home Messages
Radiological study of SIJ in SPA represents clinical and imaging challenges
Integrated use of different imaging techniques is suggested to avoid misdiagnosis
MRI technique of choice for f/u, given lack of ionizing radiation

81. Therapy of SPA Basic essential therapy NSAID’s and PT Management of AS
Symptoms
Signs
Disease activity (severity)
Functional status

82. Sulfasalazine (SZA) Control of peripheral joint involvement
Reduce spinal stiffness
No effect on enthesitis, spinal mobility or physical therapy

83. Methotrexate Modest effect on peripheral joints
Studies at odds on spine

84. Systemic Corticosteroids Ineffective

85. Biphosphonates
Modest effect
Osteoporosis
Inflammatory spinal symptoms

86. TNF Inhibitors
Effective in suppressing inflammation with joint destruction
Reduce pain
Fail to slow new bone formation
Administered early, drug free remission is possible

87. ASASD Axial SPA Criteria
Minimum of 2 NSAID’s for 4 week minimum (previous 3 months)
TNF blocker use earlier and for a minimum of 3 months

88. TNF Inhibitors in AS
Infliximab
Etanercept
Adalimumab
Goliumumap

89. Active SI Inflammation Reduced Infliximab, Etanercept, Adlmimab
Reduce signs and symptoms even in advanced or total spinal ankylosis
AS or PSA in patients therapied with Infliximab or Etanercept showed clinically relevant improvement