1. Seronegative Arthritis Or Spondyloartropaties

2. Introduction Spondyloarthritis or Seronegative Spondyloarthritis
Refers to inflammatory changes involving the spine and the spinal joints.
Absence of Rheumatoid Factor and ANA

3. Spondyloarthritis
A group of autoimmune diseases that in common appear mediated by activation of autoreactive CD8 T cells
Primarily affect joints, skin, eyes and mucous membranes
Physical stress, inflammation and infection with specific microorganisms trigger the immune response

4. Spondyloarthropathies (SpA)
Frequent – prevalence ~ 0.5%
Chronic
Inflammatory
With potential disabling outcomes
Consist of several disorders

5. SpA consist of several disorders
Ankylosing spondylitis (ASp)
Reiter’s syndrome (RS) / reactive arthritis (ReA)
Psoriatic arthritis (PsA)
Undifferentiated spondyloarthritis (USpA)
Enteropathic arthritis (ulcerative colitis, regional enteritis)

6. Spondyloarthritis Diseases-features common to all
1. Clinical:
- Affect joints, skin, eyes and mucous membranes in varying proportions with characteristic joint involvement:
Spondylitis(inflammation of vertebral discs),
sacroiliitis (sacroiliac joints) and
enthesitis (tendon insertions).
All with granulomatous fibrosis and newbone formation

7. Spondyloarthritis Diseases-features common to all
peripheral articular involvement
asymmetric mono-oligoarticular
Common in male
Sausage digits

8. Spondyloarthritis Diseases-features common to all
Enthesopathy– Achilles tenosynovitis
Extra-articular manifestations
Oral aphtae, Erythema nodosum, uveitis
Absence of RF and Rheumatoid nodules
Absence of Raynoud’s phenomenon

9. Spondyloarthritis Diseases-features common to all
2. Genetic:
Susceptibility to develop disease is associated with inheritance of certain MHC class I alleles, notably HLA-B27
Positive family history
3. Pathogenesis:
Effector/ memoryCD8 T cells are activated and clonally expanded while CD4 T cells or B cells are not involved

10. Spondylitis leads to the development of syndesmophytes and ankylosis
T cells invade the junction
of annulus fibrosis and
vertebral body forming
granulation tissue
(activated macrophages, T
cells and fibroblasts)
Annulus fibers are eroded,
then replaced by fibrocartilage
that ossifies to form a
syndesmophyte. Subperiosteal
new bone formation ensues
Progressive
cartilaginous and
periosteal ossification
forms a “bamboo spine”,
osteoporosis develops

11. Sacroiliitis The subchondral regions of the
synarthrotic SI joints are
invaded by T cells leading to
the formulation of granulation
Tissue
The cartilage on the iliac side is eroded first, causing bone plate blurring, joint space “widening” and reactive sclerosis.
Ultimately the resultant fibrous ankylosis is replaced by bone, obliterating the SI joint

12. Enthesitis (enthesopathy)
Entheses are the specialized fibrocartilagenous region of bone where ligaments, tendons, fascia or joint capsules insert
Infiltration of entheses by T cells, enthesitis, produces a combination of bone erosions and heterotopic new bone formation. Calcaneal spurs at insertion of plantar fascia and Achilles ligament are classic examples .

13. Inflammatory back pain
Onset before age 40
Insidious persistent (> 3 mo) dull deep buttock or low back pain
Stiffness/pain upon arising in the morning, or during sleep
Improvement with exercise Due to the initial inflammation of enthesitis, spondylitis or sacroiliitis
• Poorly localized, does not follow nerve root

14. Genetic epidemiology
HLA-B27 increased, but unevenly, among spondylitis diseases
HLA-B27 frequency (%)
Ankylosing spondylitis
Reiter’s syndrome (reactive arthritis)
Psoriatic arthritis
Ethnically matched controls
Other class I alleles may also be involved, especially in PsA

15. Spondyloarthropathies ESSG Criteria
Primary
Inflammatory Back Pain OR
Synovitis
Asymmetric
Predominantly in lower extremities
Secondary
Plus one of following:
Psoriasis
IBD
Positive family history
Urethritis, cervicitis, or acute diarrhea within 1 month of arthritis
Alternating buttock pain
Enthesopathy
Sacroiliitis

16. Ankylosing Spondylitis

17. Ankylosing Spondylitis
A progressive autoimmune inflammatory disease characterized by widespread spondylitis and sacroiliitis
Onset, age with dull pain in lumbar or gluteal regions
Hip, shoulder, knee arthritis in ~30%
Epidemiology: >95% of those affected are positive for HLA-B27
Affects 1-3% of HLA-B27 individuals,
Begins in the Sacroiliac Joints and progresses upwards and can involve the entire spine

22. Ankylosing Spondylitis
Inflammatory Stages
Can be extremely painful (flares)
Prolonged morning stiffness (hours)
Fatigue (pain & lack of sleep)
Ankylosis
Stiffness increases
Significantly reduced ROM
Abnormal posture

23. Postural changes
• Postural changes include loss of lumbar lordosis, buttock atrophy
and thoracocervical kyphosis, chest expansion compromised
• Peripheral joints, notably the hips may develop flexion contractures
or ankylosis. Compensatory knee flexion

24. Other Joints Involved Enthesitis
Inflammatory Arthritis of the hips and shoulders
Enthesitis

26. Extra-Articular Features
Eyes: Acute anterior uveitis (40%)
most common extraarticular features of AS
Anterior uveitis can precede the onset of AS by several years
Strongly associated with HLA B27
Lungs: Rigidity of the chest wall and fibrosis in the upper lungs
Kidneys: IgA nephropathy (rare)
Heart: Aortitis (dilation of aortic root), aortic regurgitation

28. Laboratory Investigations
Evidence of Inflammation
Normochromic normocytic anemia
Elevated ESR/CRP
Reactive thrombocytosis
HLA-B27 found in 90-95% of patients with Ank Spond vs 6-8% of general population

29. Imaging Studies Sacroiliac joints: Scintigraphy
Standard anteroposterior radiograph of the pelvis
Ferguson view-15 degree angle to the prone pelvis
Erosions-pseudowidening of SI Joint
Obliteration of SI joint
Scintigraphy
MRI-visualization of acute sacroiliitis
CT-erosions

31. Psoriatic Arthritis

32. Psoriatic arthritis
Psoriatic arthritis: an often clinically distinctive complex of enthesitis and arthritis that occurs in the setting of psoriasis
It may involve the spine or peripheral joints in a variety of patterns,and is initiated or exacerbated by stress or non specific infection

33. Progression Polyarticular in 30-50% Oligoarticular in 40-50%
Like Rheumatoid Arthritis
Oligoarticular in 40-50%
Predominant Spinal Disease in 5%
Spinal symptoms usually occur after many years of peripheral arthritis
DIP involvement in 5%
Arthritis Mutilans in 5%

36. Arthritis mutilans
Osteolytic dissolution of joint with redundant overlying
skin and telescoping motion of the digit (opera-glass hand)

40. Sacroiliac Involvement
Sacroiliitis in 1/3 of patients
Usually asymmetric (unilateral)
May be asymptomatic
Spinal Involvement
May affect any part of the spine in a random fashion
Different from ankylosing spondylitis

41. Rheumatologic Review of Systems
Mucocutaneous Involvement
Psoriatic skin lesions
Psoriatic Nail lesions
Entheseal Involvement
Dactylitis
Ocular Involvement

42. Psoriatic Arthritis
Nail involvement ~80%
Often seen in digit
involved with DIP
Arthritis
• Pitting
• Onycholysis
• Onychodystrophy
• Transverse ridging

43. History - Psoriasis
Psoriasis present before the onset of joint disease (70%)
Psoriasis comes with the arthritis (15%)
Psoriasis comes after the arthritis (15%)

44. Psoriatic Plaque Under the Knee

45. Umbilical Psoriasis

46. Dactylitis
Entire digit is involved compared to “fusiform” swelling around a joint
Dactylitis – represents inflammation of the flexor tenosynovium – “flexor tenosynovitis”

47. Progression of DIP arthritis
Narrowed joint space & condylar erosions
Reactive sub periosteal new bone
Pencil in cup appearance

48. Management AS and Psoriatic Arthritis
Goals of Treatment
Improve pain
Improve Function
Prevent Long-term Damage
Safely
Psoriatic arthritis can lead to a deforming and destructive arthropathy in 20-30%
Ankylosing spondylitis can result in significant disability

49. Management NSAIDs Can be useful in some cases of mono/oligo arthritis
Useful for enthesitis
Useful for spinal disease

50. Ankylosing Spondylitis
Management: DMARDs
Medication
Psoriatic
Ankylosing Spondylitis
Hydroxychloroquine (Plaquenil®)
Rarely with little evidence NO
Methotrexate
YES
Rarely with poor efficacy in spinal disease
Sulfasalazine
Leflunomide (Arava®)
Gold
Steroids

51. Management: Biologics
Biologics Approved for Psoriatic Arthritis and Ankylosing Spondylitis
Etanercept (Enbrel®)
Infliximab (Remicade®)
Adalimumab (Humira®)
Biggest advance in the treatment of spondyloarthropathies in decades!

52. REACTİVE ARTHRITIS

53. Reactive arthritis Reactive arthritis has generally been
defined as sterile synovitis developing
after a distant infection.
Occurs 2-4 weeks after inciting infection
Most responsible organisms have an affinity for mucous membranes
VUCUDUN her hangi bir yerinde ki enfeksiyon sonrası ve sırasında gelişen 53

54. Terms Reactive Arthritis & Reiter’s Syndrome Synonamous
1916, Hans Reiter
Arthritis, Conjunctivitis, Non Gonococcal Urethritis
Irksal hyjen kitabı- tifo inokulasyon –kamplarda
Reiter Syndrome ? 54

55. Classic triad: Arthritis, Urethritis, Conjunktivitis

56. Etyology Infectious agent GIS GUS Others Shigella (flexneri)*
Salmonella
Yersinia
Campylobacter
Clostridium(difficile)
Chlamydia (trachomatis)
C.pneumoniae
Borrelia
Neisseria
Streptococus
*HLA-B27 (+) hastaların %25 inde ReA gelişir. 56

57. - symptoms of the triggering infection have
often been mild and, in about 10% of
cases, the infection has passed unnoticed
- Symptoms
• malaise,
• fatigue
• fever
• mild arthralgias to severely disabling
polyarthritis

59. Reactive Arthritis Conjunctivitis follows urethritis by several days
Sx often mild and transient
acute anterior Uveitis possible

61. Articular manifestations
Starts 2-4 weeks after the initial infection
Articular symptoms typically appear last
additive
oligoarticular
lower limbs most common

62. asymetric, oligoarticular
Knee
Ankle
Foot joints
Occasionally
Wrist, Elbow, Shoulder, SIE
asymetric, oligoarticular
Chronic cases
Dactilitis
Entesopathy. tenosynovitis, plantar facitis, achill tendinitis, bursit

63. Reactive arthritis
Dactilitis

66. Aphtous ulceration

67. Erithema nodosum

68. Reactive Arthritis Clinical course
Normally limited course running 3-12 months
15% with prolonged relapsing arthritis
? Relapse
?Reinfection
Ankylosing Spondylitis in 10% of cases

69. Reactive Arthritis Laboratory findings Normochromic, normocytic anemia
Leukocytosis
Acute phase reactants:
ESR
C-reactive Protein
Patients with genitourinary symptoms should be tested for infection with C trachomatis

70. Reactive Arthritis Treatment: Antibiotics?-chlamydia-tetracyclines
Rest
NSAIDs
Methotrexate and sulphasalazine
Intralesional and intraarticular glucocorticoids
Uveitis-glucocorticoids

71. Enteropathic Arthritis Or SpA associated with inflammatory bowel disease

72. Enteropathic arthritis
Arthropathy associated with IBD – (5-20%)
Peripheral arthritis
Axial involvement – sacroiliitis w/o spondylitis
HLA-B27 not implicated here

73. Enteropathic arthritis
Acute, oligoarticular onset
Predominantly lower extremities
Non-deforming, self-limiting arthritis
Association with active bowel symptoms

74. Enteropathic arthritis
Periarticular features
Enthesopathy
Tendonitis
Extraarticular features
Erytema nodosum
Uveitis

75. Enteropathic arthritis-Therapy
NSAID
Sulphasalazine
Methotrexate
Biologic agents – Anti TNF therapy

76. Clinical and epidemiological features of the spondyloarthropathies
Prevalence
M/F ratio
Axial Arthritis
Frequency
sacroilitis
Ankylosing Spondylitis
0.1%
3:1
100%
Bilateral
Psoriatic Arthritis
1:1
20%
Unilateral
Reactive Arthritis
>0.05%
9:1
Enteropathic Arthritis
15%

77. Clinical and epidemiological features of the spondyloarthropathies
Peripheral arthritis
Uveitis
Frequency
Dactylitis
frequency
distribution
Affected
joints
Ankylosing Spondylitis
25%
Mono
oligo
Hip,knee,
ankle
30%
uncommon
Psoriatic Arthritis
60-95%
Oligo
poly
Knee,ankle,DIPs
15%
Reactive Arthritis
90%
Knee,ankle
15-20%
30-50%
Enteropathic Arthritis
20% 5%