1. Seronegative Spondyloarthropathies

2. Goals of the Lecture Introduce the spondyloarthropathies
Recognize AS as the prototypic disease
Recognize common clinical and radiologic features and specific features including:
Epidemiology
Diagnosis
Treatment

3. Seronegative Spondyloarthropathies
Spondylo: Origin: < Gr spondylos, vertebra < IE base *sp(h)e(n)d-, to jerk, dangle > Sans spandatē, (he) jerks

4. Seronegative spondyloarthropathies (SNSA): A family of diseases
Ankylosing Spondylitis
Reiter’s syndrome/ Reactive arthritis
IBD arthropathy
Psoriatic arthropathy (SNSA variant)
Undifferentiated spondyloarthropathy
Juvenile onset SNSA

5. SNSA: Group characteristics
Propensity to affect spine, peripheral joints, and periarticular structures
Characteristic extraarticular features
Absence of RF and ANA
Association with HLA B27

6. SNSA: Group pathology Enthesitis Sacroiliitis Osteopenia Erosions
Peripheral arthritis
Synovial hyperplasia
Pannus
Lymphoid infiltration
Enthesitis
Inflammation at tendinous insertions

7. Causes of sacroiliitis
Seronegatives AS
Reiter’s
Psoriatic arthritis
IBD
SAPHO
Acne-associated
Intestinal bypass
Infections
Pyogenic infections
Tuberculosis
Brucellosis
Whipple’s
Others
Paraplegia
Sarcoidosis
Hyperparathyroidism

8. Ankylosing spondylitis: Prototype SNSA
Systemic inflammatory
Sacroiliitis is hallmark
X-ray evidence needed for original and modified NY criteria
Clinical spectrum wider than symptomatic sacroiliitis
Atypical

9. AS: Diagnosis Diagnostic Criteria Classification Criteria
Highly sensitive at early stage of disease
Classification Criteria
Deals with groups of patients
NOT individual patients
Primarily for epidemiologic purposes

10. Grading sacroiliitis Grading of radiographs Normal 0 Suspicious 1
Minimal sacroiliitis 2
Moderate sacroiliitis 3
Ankylosis 4

11. Ankylosing spondylitis (Modified New York classification criteria)
1. LBP at rest for >3 months
improved with exercise
not relieved by rest
2. Limitation of lumbar spine
3. Decreased chest expansion
4. Bilateral sacroiliitis grade 2-4
5. Unilateral sacroiliitis grade 3-4
Definite AS if criterion 4 and any other criteria is fulfilled
AMOR Criteria take into account HLA B27 status and response to treatment

12. Ankylosing spondylitis: Clinical features
Onset in late adolescence/ early adulthood
After age 45 is uncommon
Much more common in men
M:F 3:1
Clinical/xray features evolve more slowly in women
Skeletal vs. extraskeletal features

13. AS :Skeletal features Axial (back pain) Hips/shoulders Enthesitis
sacroiliitis
spondylitis
Hips/shoulders
Enthesitis
Osteoporosis
Spinal fractures
There were 19 cervical fractures in 18 patients, which were chalkstick in type and occurred predominantly at the 6th and 7th cervical levels. Ten fractures passed through the upper part of the vertebral body, one through the mid-vertebral body and the final eight were through the disc space. The site of the fracture line was related to neurological outcome. Those patients whose fracture line ran through the disc space had significantly less neurological injury and a much better prognosis. Distraction at the fracture site had some relation to prognosis but horizontal displacement and angulation were not found to be of importance. This study confirms that cervical fracture with neurological complications may follow minor trauma in ankylosing spondylitis.

14. Ankylosing spondylitis vs. mechanical LBP
Inflammatory/ spondylitic back pain
1. Onset prior to age 40
2. Insidious onset
3. Persistence at least 3 months
4. Morning stiffness
5. Improvement with exercise
Need 4/5 criteria

15. Inflammatory questions
Sensitivity %
False %
mechanical back pain and healthy athletes
low prevalence of AS in population (1-2%)
Positive predictive value is low
10% false positive

16. AS: Peripheral skeletal features
Hip and shoulder involvement
May be first symptom
Up to 1/3 patients
More common in juvenile (<16) onset
Flexion contractures at hips

17. AS: Peripheral skeletal features
Other peripheral joints
Infrequent
Often asymmetric
Transient
Rarely erosive
Resolves without residual deformity

18. AS: Enthesitis Enthesitis Costosternal junctions Spinous processes
Extra-articular or juxta-articular bony pain
Costosternal junctions
Spinous processes
Iliac crests
Greater trochanters
Ischial tuberosities
Tibial tubercles
Achilles tendon insertions
Plantar fascia insertion
Pes anserinus
Epicondylus humeri lateralis

19. Figure 1 (A) Low power view of the attachment of the Achilles tendon to the calcaneus to
show the complexity of structures that jointly comprise the enthesis. These structures include
the enthesis fibrocartilage (EF), sesamoid fibrocartilage (SF), periosteal fibrocartilage
(PF), and the retrocalcaneal bursa (RB). Toluidine blue. Scale bar 0.5 cm. (B) A high
power view of the enthesis of the supraspinatus tendon in the region of the tidemark (T).
This highly basophilic line is a calcification front separating the zones of calcified and
uncalcified fibrocartilage. It is relatively straight and this contrasts with the irregularity of
the junction between the calcified fibrocartilage (CF) and the underlying bone (B)
(junction marked with *). It is such interdigitations that help to hold the two tissues
together. Note that the fibrocartilage cells (FC) are more conspicuous in the region of
uncalcified fibrocartilage. Haematoxylin and eosin. Scale bar 100 μm. (Courtesy of Dr M
Benjamin, University of Cardiff,Wales.)

21. Extraskeletal manifestations
A ortic insufficiency and other cardiac pathology
N eurologic (atlantoaxial subluxation, Cauda equina)
K idney (secondary amyloidosis, chronic prostatitis)
S pine (cervical fracture, spinal stenosis)
P ulmonary (apical lobe fibrosis, restrictive disease)
O cular (anterior uveitis)
N ephropathy (IgA)
D iscitis

22. AS: Extraskeletal manifestations
Eye- acute anterior uveitis (25-30%)
Heart- ascending aortitis, AR (3-10%), conduction abnormalities (3%)
Pulmonary- apical fibrosis (rare)
Neurologic- fracture/dislocation. subluxations, cauda equina syndrome

23. AS: Iritis Acute anterior uveitis/iritis/ iridocyclitis Most common ES
25-30%
Unilateral
Recurrent
Symptoms
Pain
Lacrimation
Photophobia
Blurry vision

24. AS: Physical examination
Limited range of motion (especially hyperextension, lateral flexion, or rotation)
Spasm/soreness of paraspinal muscles
Positive Schober’s test
Loss of lumbar lordosis
Sacroiliac discomfort

25. Patrick’s and Gaenslen’s tests

26. Office measurement

27. Wiki
The Dimples of Venus (also known as booty dimples, back dimples, or butt dimples) are sagittally symmetrical indentations sometimes visible on the human lower back, just superior to the gluteal cleft. They are directly superficial to the two sacroiliac joints, the sites where the sacrum attaches to the ilium of the pelvis.
The term "Dimples of Venus", while informal, is an historically accepted name within the medical profession for the superficial topography of the sacroiliac joints. The Latin name is fossae lumbales laterales ('lateral lumbar indentations'). These indentations are created by a short ligament stretching between the posterior superior iliac spine and the skin.
Booty dimples are rapidly gaining cultural momentum as a feature men find attractive in women and other men.

28. Wiki
The dimples of Venus (also known as back dimples) are sagittally symmetrical indentations sometimes visible on the human lower back, just superior to the gluteal cleft. They are directly superficial to the two sacroiliac joints, the sites where the sacrum attaches to the ilium of the pelvis.
The term "dimples of Venus", while informal, is a historically accepted name within the medical profession for the superficial topography of the sacroiliac joints. The Latin name is fossae lumbales laterales ("lateral lumbar indentations"). These indentations are created by a short ligament stretching between the posterior superior iliac spine and the skin. They are thought to be genetic.
There are other deep-to-superficial skin ligaments, such as "Cooper's ligaments", which are present in the breast and are found between the pectoralis major fascia and the skin.
There is another use for the term "Dimple of Venus" in surgical anatomy. These are two symmetrical indentations on the posterior aspect of sacrum which contain a venous channel too. They are used as a landmark for finding the superior articular facets of the sacrum as a guide to place sacral pedicle screws in spine surgery[1].

29. 1="Vertebra prominens" Spinous process of C7 2= 2nd Lumbar vertebra 3= L4-5 inter vertebral space 4= Iliac crests 5= Dimples of Venus / Sacroiliac joints / Booty Dimples

30. Office measurement

31. Don’t Be Fooled!
This woman with AS was misdiagnosed because of her ability to touch her toes. Thorough examination revealed (b) her full range of extension (c) and her side flexion to be virtually nil. More accurate observation and the performance of a Schober test revealed that her forward flexion took place almost entirely from her hips

32. AS: Laboratory findings
Elevated ESR (75%)
Elevated CRP
ANA and RF negative
NC/NC anemia (15%)
HLA B27
No diagnostic or pathognomic tests!

33. HLA-B27: Disease Associations
Ankylosing spondylitis
>90%
Reiter’s syndrome
80%
Reactive arthritis
85%
Inflammatory bowel disease
50%
Psoriatic arthritis- spondylitis
- peripheral arthritis
15%
Whipple’s disease
30%

34. HLA B27 and AS in Caucasian populations
HLA B27 in Americans %
HLA B27 in African Americans 3%
HLA B27 in AS patients >90%
Prevalence of AS in population 1%
Prevalence of AS in HLA B27+
individuals 2%
Prevalence of AS in B27+ relatives 20%
Prevalence of AS in B27- relatives 0%
HLA B27 in African Americans 3%

35. AS: Radiologic features
Sacroiliac
Bilateral, symmetric involvement (i.e. erosions, sclerosis, pseudowidening, ossification)
Spine
“Shiny corners”, squaring of the vertebra, ossification of the annulus fibrosus, ankylosis
Hip
Symmetric concentric joint narrowing

36. AS: Radiographic findings
SI joint- symmetric
Pronounced on iliac side
Erosions/sclerosis
‘Postage stamp’ serrations
Pseudowidening

38. More sensitive than XRAY
MRI CT 27

39. FIG. 1. Normal MRI sacroiliac joints on: (a) fat-saturated
T1-weighted scan, (b) STIR sequence.
FIG. 2. Abnormal MRI sacroiliac joints on: (a) fat-saturated
T1-weighted scan, (b) STIR sequence. This scan demonstrates
subchondral oedema, sclerosis and erosions.

40. Late sacroiliac changes
Calcification,
interosseous bridging, and ossification
Bony ankylosis
Osteoporosis

41. AS Radiographic findings
Vertebral Column
Squaring of vertebrae

42. Skeletal manifestations
Syndesmophytes
Ossification of the outer layers of the annulus fibrosis
Sharpey’s fibers
Vertical

43. Osteophyte Vs. Syndesmophyte

44. Late axial disease B A M O

45. AS: Radiographic findings
Enthesitis
Bony erosions
Osteitis (whiskering) of insertions
Ischial tuberosities
Iliac crest
Calcani
Femoral trochanters
Spinous processes

46. AS: Treatment Main objectives Patient education Early diagnosis
Control pain and suppress inflammation
Daily exercises
Surgical measures (i.e. hip arthroplasty)
Vocational support

47. AS:Treatment NSAIDs- pain and stiffness
Sulfasalazine/MTX- peripheral arthritis
Anti-TNF agents- axial and peripheral disease
Oral corticosteroids- little role
Local corticosteroids- recalcitrant enthesopathy

48. Etanercept in AS (% ASAS Response Week 12) Davis J, et al, Arthritis Rheumatism 2003

49. Infliximab in AS (% ASAS Response at 24 weeks) van der Heijde D, et al, Arthritis Rheumatism 2005

50. AS: Summary Age at onset Young adults Sex ratio 3:1 (males to females)
Axial disease Virtually 100%
Sacroiliitis Symmetric
Peripheral joint 25%
Eye involvement 25%
Infectious triggers Unknown

51. Case scenario 1 35 year old male
6 months of low back stiffness and pain
Improves with exercise
Painful swelling at Achilles insertion
Urethral discharge prior to symptoms

52. Physical Exam

53. Reactive arthritis: Clinical triad
Conjunctivitis
Urethritis/cervicitis
Arthritis

54. Reactive arthritis: Epidemiology
Incidence
Postdysenteric: 9/602 sailors
Olmsted county, MN: 3.5 cases/100,000
Age of onset
20-30s (5-80)
Gender
5:1 male to female
Postvenereal (males >> females)
Postdysenteric (males=females)

55. Reactive arthritis: Joint disease
Onset 1-4 weeks after exposure
Asymmetric, additive, and ascending oligoarthritis
Lower extremity typical
Dactylitis (“sausage digits”)
Axial symptoms at onset (50%)

56. Reactive arthritis: Clinical features
Ocular
Uveitis, conjunctivitis, keratitis
Mucocutaneous
Oral ulcerations, circinate balanitis, keratoderma
Others
Fevers, cardiac (AR, conduction abnormalities)

57. Reactive arthritis: Triggers
Enteric pathogens
Shigella flexneri
Salmonella typhimurium
Yersinia enterocolitica
Campylobacter jejuni
Urogenital pathogens
Chlamydia trachomatis
Ureaplasma urealyticum

58. Reactive arthritis: Labs
Elevated ESR and CRP
Thrombocytosis, NC/NC anemia
Remember HIV
ALL ARE NON-SPECIFIC

59. Reactive arthritis: Therapy
NSAIDs
Long acting indomethacin
Systemic glucocorticoids
DMARDs
TNF blockers
Prolonged antibiotics ??

60. Reactive arthritis: Summary
Age at onset Young adults
Sex ratio Mostly male
Axial disease 50%
Symmetry Asymmetric
Peripheral joints >90%
Eye involvement Common
Skin/nail findings Common
25-50% have relapses
20% have chronic disease

61. Case scenario 2 45 year old male
6 months of low back stiffness and pain
Improves with exercise
New rash on elbows and knees
Tender, swollen fingers and toes

63. Psoriatic arthritis (PSA)
Five types
1. Oligoarticular (>50%)
2. RA variant (25%)
3. DIP only (5-10%)
4. Arthritis mutilans (5%)
Back disease (20-40%)

64. Psoriatic arthritis (PSA): Radiology
Fusiform
Normal mineralization
Joint space loss
Pencil in cup
Bone proliferation

66. Psoriatic arthritis: Summary
Age at onset Young adults
Sex ratio Equal
Axial disease 20%
Symmetry Asymmetric
Peripheral joint 95%
Eye involvement Occasional
Skin/nail disease Virtually 100%

67. Case scenario 3 35 year old male
6 months of low back stiffness and pain
Improves with exercise
New onset diarrhea
Painful sores on shins

69. Inflammatory bowel disease: Relationship to bowel symptoms
Bowel symptoms precede or coincide with joint symptoms in vast majority
BUT, in 5-10% joints symptoms preceded bowel disease
In UC, removal of colon usually eliminates peripheral disease

70. Inflammatory bowel disease: Axial disease
Prevalence
Sacroiliitis 10-20%
Spondylitis 7-12%
Female to male ratio: 1:1
Onset of axial involvement does not correlate with IBD
Removal of bowel does not affect axial disease

71. Inflammatory bowel disease: Peripheral arthritis
Prevalence: 17-20% (higher in Crohn’s)
Pattern: Pauciarticular, asymmetric, frequently transient
Joints involved: Large lower extremity joints (usually not destructive)
Soft tissue: enthesopathy, clubbing, sausage digits

72. IBD: Summary Age of onset Young adults Sex ratio Equal
Axial disease <20%
Symmetry Symmetric
Peripheral joints Frequent
Eye involvement Occasional
Skin/nail findings Uncommon