spondyloarthropathies are group of disorders which impact spine.

1. SPONDYLOARTHROPATIES
DR. SHYAM SUNDER SHARMA
RESIDENT DOCTOR
DEPTT. OF PM&R, SMS JAIPUR

2. HISTORICAL BACKGROUND
 1892 Bechterew- upper dorsal type case
complicated by meningeal and spinal cord
involvment “Bechterew’s disease”
 1898 Marie- described the entity as separate from
all other types of arthritis involving the spine

3. HISTORICAL BACKGROUND
 1940-50s Discovery of the human leukocyte
antigens (HLAs) and characterization of the MHCs
 1960s- American Rheumatism Association (ARA)
recognized the spondyloarthropathies as a distinct
group of inflammatory arthritis
 1973 Association found between HLA-B27 and the
spondyloarthropathies

4. SPONDYLOARTHRITIDES
 These are interrelated group of rhematic diseases
that are characterized by clinical features as
inflammatory back pain,
 Asymmetric peripheral oligoarthritis, predominantly
of lower limbs.
 Enthesitis.
 specific organ involvement such as anterior uveitis,
psoriasis.
 chronic inflammatory bowel disease.

5. Juvenile
Juvenile
SpA
SpA
Reactive arthritis
Reactive arthritis
Reiter syndrome
Reiter syndrome
Arthritis
Arthritis
associated
associated
with
with Crohn
Crohn’
’s
s
disease / UC
disease / UC
Psoriatic
Psoriatic
Arthritis
Arthritis
Ankylosing
Ankylosing
Spondylitis
Spondylitis
Sacroiliitis
Sacroiliitis
AAU
Undifferentiated
Undifferentiated
SpA
SpA
Spondyloarthritides: The Spectrum
IAVB

6. Group of diseases characterized by:
 SpAs comprise group of related inflammatory
musculoskeletal diseases that show overlap in their
clinical features and have a shared immunogenic
association with HLA-27.
Spondyloarthropathies: Definition
Occurring in the absence of serum rheumatoid factor

7. I T I N C L U D E S ;
•ANKYLOSING SPONDYLITIS (AS)
•REACTIVE ARTHRITIS (RA)
•PSORIATIC ARTHRITIS (PA)
•ENTEROPATHIC SPONDYLOARTHRITIS
•AXIAL SPONDYLOARTHRITIS
Spondyloarthropathies

8. ESSG* Classification Criteria for SpA
(*European Spondylarthropathy Study
Group)
 Alternating buttock pain
 Sacroiliitis (x-rays) *
 Positive family history
 Psoriasis
 Inflammatory bowel disease
 Urethritis / acute diarrhea in the preceding 4
weeks
 Heel pain (enthesitis)
Inflammatory Back Pain Synovitis
Plus one of the following:
• Asymmetrical
• Lower extremities
Dougados M, et al. Arthritis Rheum 1991;34:1218
*without sacroiliitis: sens =77%, spec 89%
OR

9. ENTHESITIS
 The characteristic feature of AS and
spondyloarthritides
 Inflammation at sites where tendons,
ligaments or joint capsules attaches to
the bone:
 primarily affects the sacroiliac joints &
the axial skeleton in AS, but extra-
articular or juxta-articular bony
tenderness occurs from enthesitis at
many other sites
(e.g. costosternal junctions, spinous
processes, greater femoral trochanters, iliac
crests, ischial tuberosities, tibial tubercles,
heels, etc.)
Khan MA; Rheumatology. Eds. Hochberg M. London, Mosby. 3rd ed.
2003

10. Enthesitis
Periosteal
new bone
formation
Bone
McGonagle D. Arthritis Rheum. 1999;42:1080-1086.
Subchondral
bone
inflammation
and
resorption
Tendon
©ACR
Inflammatory
Rheumatoid arthritis
Ankylosing spondylitis
Reactive arthritis
Psoriatic arthritis
Inflammatory bowel disease
Lyme disease
Late-onset Pauciarticular JRA
Leprosy
Mechanical/Degenerative
Trauma
Osteoarthritis
Metabolic/Endocrine
DISH
Acromegaly
Fluorosis
Retinoid therapy
Hypoparathyroidism
Hyperparathyroidism
POEMS syndrome
X-linked hypophosphatemia
DDx:

11.  Seronegative spondyloarthropathy (or seronegative
spondyloarthritis) is a group of diseases involving
the axial skeleton and having a negative serostatus.
 "Seronegative" refers to the fact that these diseases are
negative for rheumatoid factor , indicating a different patho-
physiological mechanism of disease than what is commonly
seen in rheumatoid arthritis.
Seronegative spondyloarthropathy

12. The following conditions are typically included within the group
of seronegative spondylarthropathies:
 Ankylosing Spondylitis
Caucasians: 92% African-Americans: 50%
 Reactive arthritis (Reiter's syndrome) - 60 -80%
 Enteropathic spondylitis or spondylitis associated
with inflammatory bowel
disease (including Crohn's disease and ulcerative
colitis)- 60%

13.  Psoriatic arthritis -60%
 Isolated acute anterior uveitis -50%
 Undifferentiated spondyloarthropathy (USpA)- 20-25%
 Some sources also include Behcet's disease
and Whipple's disease

14. These diseases have the following conditions in
common:
 They are in relation to HLA-B27
 Inflammatory
arthritis,generally sacroiliitis and spondylitis
 Oligoarthritis, generally with asymmetrical
presentation
 Enthesitis (inflammation of the entheses, the sites
where tendons or ligaments insert into the bone)

15. These diseases have the following conditions in
common:
 familial aggregation occurs
 rheumatoid factor is not present
 Extra-articular features, such as involvement of eyes,
skin and genitourinary tract
 Overlap is likely between several of the causative
conditions

20. Pathophysiology
 The primary pathology of the spondyloarthropathies
is –
 Enthesitis with chronic inflammation, including CD4+ and
CD8+ T lymphocytes and macrophages.
 Cytokines, particularly tumor necrosis factor-α (TNF-α) and
transforming growth factor-β (TGF-β), are also important in
the inflammatory process by leading to fibrosis and
ossification at sites of enthesitis.

21. Pathogenesis
 Etiology/pathogenesis unclear
 Interplay of genetic, immunologic and environmental
factors
 Interaction between MHC-I molecule HLA-B27 with T
cell response believed to be key in pathogenesis.
 94% of AS patients are HLA-B27+(OR 161 [CI 113-230])
 Bacterial infections may trigger events
M Tc
HLAB27
Intense
Inflammatory
response
Ag
TCR
McMichael A and Bowness P. Arthritis Res 2002;4 (suppl 3):S153-8.

22. Role of HLA-B27
 Has a role in presenting protein antigens that have
been synthesized in the cell (viral, tumor, self-derived)
to cytotoxic T-cells
 HLA-B27 individuals are less efficient at elimination of
intracellular organisms (e.g, Chlamydia) and certain
enteric bacteria
 Unclear if disease susceptibility is due to presentation
of an arthritogenic peptide vs. failure to eliminate
intracellular organisms vs. itself acting as a source of
Ag
 25 different subtypes have been identified: B*2705,
B*2704, B*2702 or B*2707 have accounted for most of
the spondyloarthritides
McMichael A and Bowness P. Arthritis Res 2002;4 (suppl 3):S153-8.

23. Ankylosing Spondylitis
Rheumatoid Spondylitis, Spondylarthropathy,
Spondylitis, Bechterew’s Disease, Bamboo Spine

24. Etiology
 Spondylitis – inflammation of the spine
 Ankylosing – fusion of the spine
 Chronic inflammation of the spine and SI joints
 Combination of genetic and environmental
factors
 Genetic:
 Presence of HLA-B27 gene
5% of population has gene
90% of those with AS have gene

25. Incidence
 3 males to every 1 female
 Worldwide annual incidence estimated to
be 7.3 per 100,000 individuals
 US incidence in ages 16 and older: 8.9 per
100,000 individuals
 Prevalence in US is between 0.1% and 1.4%

26. Risk Factors
 Men > Women; 2-3 x more likely
 Family History; 6 x more likely
 Age 17-45
 Presence of HLA-B27 gene detected in
blood
• Current research focuses on ARTS1 and IL23R,
which play a role in immune function
 Frequent GI infections

27.  The initial presentation of AS generally occurs in the SI joints;
involvement of the SI joints is required to establish the diagnosis. SI
joint involvement is followed by involvement of the diskovertebral,
apophyseal, costovertebral, and costotransverse joints and the
paravertebral ligaments.
 Early lesions include subchondral granulation tissue that erodes the joint
and is replaced gradually by fibrocartilage and then ossification. This
occurs in ligamentous and capsular attachment sites to bone and is
called enthesitis.
 In the spine, this initial process occurs at the junction of the vertebrae
and the anulus fibrosus of the intervertebral discs. The outer fibers of the
discs eventually undergo ossification to form syndesmophytes. The
condition progresses to the characteristic bamboo spine appearance.

28. Diagnosis of AS
Modified New York criteria
A definite diagnosis
 Radiological criterion and ≥ 1 clinical criterion
Radiological criterion
 Sacroiliitis ≥ grade 2 bilaterally or grade 3 or 4
unilaterally.
Clinical criteria
 Low back pain and stiffness for more than 3 months
improves with exercise, not relieved by rest
 Limitation of motion of the lumbar spine in both the
sagittal and frontal planes
 Limitation of chest expansion (correlated for age and sex)

29. Bath Ankylosing Spondylitis Functional Index
(BASFI)
 Standing unsupported for 10 minutes without
discomfort
 Climbing 12-15 steps without use of handrail or
walking aid
 Looking over your shoulder without turning your
body
 Doing physically demanding activities
 Doing a full days activities at home or at work

30. Ankylosing Spondylitis
Differentiating Inflammatory vs Mechanical Back Pain
Inflammatory Back
Pain
Features Mechanical Back
Pain
Prolonged > 60min. AM Stiffness Minor < 45 min.
Early AM
(wakes pt up)
Max.
Pain/Stiffness
Late in day
Improves Symptoms Exercise/activity Worsens Symptoms
Chronic Duration Acute or Chronic
9-40 yrs. Age at Onset 20-65 yrs.
sacroiliitis
vertebral ankylosis
syndesmophytes
Radiographs
osteophytes
spondylolisthesis
scoliosis

32. Imaging
Radiograph (L-spine, AP pelvis, SI joints)
Grade 2-4 sacroiliitis
Equivocal Grade I
sacroiliitis
Normal
MRI
CT or MRI
Bone scan
Equivocal
Multifocal disease
suspected
No
further
studies
Koehler et al. Rheumatolgy 2000;39;360-8.

33. AS Clinical Features - axial
 Early AS
Romanus lesion
(This reflects subdiskal and marginal
destruction of the vertebral ring)
 Advanced AS
bony ankylosis

34. Severe Spinal Complications from AS
 Spinal
stiffness/ankylosis
in kyphotic position
 Spinal fractures (10-
20%) axial/T spine;
increased 6-8 fold
 Cauda equina synd.
(arachnoiditis)

45. Fused SI joints

46. Schober’s test

47. Lumbar Flexion (Schober)
A mark is placed at L5, measure 10 cm cephalad and place another mark.
Have the patient bends forward as far as possible with knees extended, the
difference is recorded. Normal is >5 cm
J Brandt, J Sieper

48. Wall to Tragus Distance
Patient stands, heels and buttocks against the wall, the head is placed
back as far as possible, keeping the chin horizontal
J Brandt, J Sieper

50. Extra-Axial
Manifestations

51.  Ocular (25-40%): uveitis, conjunctivitis
 Heart (29%): AI, heart block, aortitis
 Lung (10%): ILD, apical fibrosis, aspergilloma
 Kidney (14%): amyloidosis, nephritis, IgA
nephropathy
 Bones: osteoporosis – bone resorption > bone
formation
Associated Extraarticular Features

52. Associated Extraarticular Features
 Gastrointestinal: oral ulcerations, asymptomatic
gut inflammation, symptomatic colitis
 Genitourinary: urethritis, vaginitis, balanitis
 Cutaneous: keratoderma blennorrhagicum,
psoriasis or nail lesions (onycholysis, dystrophy,
pitting).
 Periarticular: tendonitis, dactylitis (sausage-digit)

53. Management
 Medication
 Exercise
 Posture
 Heat/Cold
 Surgery
 Other Symptom Management Tools
• Acupuncture
• Chiropractic Treatment
• Massage
• Yoga Therapy

55. Exercise
 Exercise is an integral part of any spondylitis program, along with good
posture habits and medication to reduce pain and stiffness.
 Fitting exercise into your day can be tough, but it needs to be done.
 Exercise is such a high priority that it is important to make time for it
each day (even 5-10 minutes during a work break is helpful). If you do,
many benefits will result from your efforts.
 A spondylitis exercise program will help you maintain good posture,
flexibility and eventually help to lessen pain.
 In many cases, good posture and mobility can even be regained with
proper doses of medicine and exercise.
 Most people with spondylitis feel much better with exercise. The trick is
to do enough but not too much. This can vary from day to day. Be good
to yourself and never push to the point of pain or extreme fatigue.

56. Osteoporosis in AS
 Prevalence of vertebral osteoporosis in AS is between 20%
to 60%1
 Relative risk of fractures is 6 times in early AS compared
with controls2
 Risk factors: disease duration, severity, male sex
 Major etiologic factors: pro-inflammatory cytokines and
spinal immobility
 No studies on treatment of osteoporosis in AS: ? role of
pamidronate, anti-TNF
1. Bessant R, Keat A. J Rheumatol. 2002;29:1511-1519.
2. Mitra D, et al. Rheumatology. 2000;39:85-89.

57. Psoriatic Arthritis

58. PSORIATIC ARTHRITIS (PsA)
 Chronic inflammatory arthropathy in setting of psoriasis
 Sites of psoriasis: scalp, ears, gluteal fold, umbilicus,
perineum, palms, soles, nails, extremities
 Nail changes: pitting, dystrophy, onycholysis
 1-5% of US population has Psoriasis: 5-42% of these
develop psoriatic arthritis

59. PSORIATIC ARTHRITIS (PsA)
 Frequency of PsA increases with disease severity
and duration (estimated 350-400,000 patients in
USA)
 Skin precedes nails, but 15% will have arthritis
before skin disease
 Course: chronic, destructive arthritis in 30-50%

60. PsA
 Up to 40% of psoriasis patients develop IA
 Peak 35 to 50 years
 Male = female (spine involvement 3:1)
 1/3 of cases arthritis precedes rash
 No association between severity of joint disease and
psoriasis.
 Nail changes more commonly associated with
arthritis

61. Types of psoriasis:
Guttate
Pustular
Plaque
Erythrodermic

62. Classification of Psoriatic Arthritis
4/25/2021 1:30:23 PM
69
Type Key Clinical Features Incidence
Asymmetric
polyarthritis or
oligoarthritis
Morning stiffness, DIP and PIP
involvement, nail disease,  4 joints
involved
40%
Symmetric
polyarthritis
Symmetric polyarthritis, RA-like
distribution, but RF negative
25%
Spondylitis
Inflammatory low back pain, sacroilitis,
axial involvement, 50% HLA-B27+
20%
Distal
interphalangeal
joint disease
Nail changes, often bilateral joint
involvement
15%
Arthritis mutilans
Destructive form of arthritis, telescoping
digits, joint lysis, typically in phalanges
and metacarpals
<5%

63. Different Psoriatic Arthritis

64. Radiological changes
1. Soft tissue swelling (sausage digit)
2. Preserved bone density
3. Periarticular erosions
4. “Pencil in cup” deformity
5. Bone proliferation
• Adjacent to erosions, tendon insertions
6. Periosteal new bone formation
7. Sacroiliitis

65. Pencil and Cup Deformity

67. (Modified from Rheumatology 3rd Edition, 2003)

70. Classification of Psoriatic Arthritis
(CASPAR) Taylor et al, A&R, 2006
Inflammatory articular disease (joint, spine or entheseal)
With ≥ 3 points
1. Current psoriasis*, a personal history of psoriasis, or a family
history of psoriasis.
2. Typical psoriatic nail dystrophy including onycholysis, pitting and
hyperkeratosis.
3. A negative rheumatoid factor.
4. Current dactylitis or a history of dactylitis.
5. Radiographic evidence of juxtaarticular new bone formation, ill-
defined ossification near joint margins (exclude osteophyte
formation) on plain radiographs of the hand or foot.
* Current psoriasis scores 2, all other items score 1.

71. TREATMENT OF PSORIATIC ARTHRITIS
 The approach to the treatment of PsA includes
therapy for both skin and joint disease.
 Methotrexate- only limited observational datas
showing efficacy.
 Non steroidal inflamatory drugs.

72. TREATMENT OF PSORIATIC ARTHRITIS
Leflunomide;
 Promising results with leflunomide were noted in
uncontrolled trials.
 Leflunomide is also effective in controlling skin
disease.

73. TREATMENT OF PSORIATIC ARTHRITIS
TNF Inhibitors;
 Clinical trials have proven the efficacy of TNF
Inhibitors in PsA.

74. REACTIVE ARTHRITIS

75. REACTIVE ARTHRITIS
 Acute inflammatory arthritis occuring 1-4 weeks after
infectious event (GU, GI, idiopathic)
 TRIAD: aseptic arthritis + urethritis (vaginitis) +
conjunctivitis (classic triad found in < one-third of pts)
 Usually asymmetric oligoarticular + extraarticular Sxs
 Arthritis recurrent in 15-30%, more in chlamydia
associated arthritis
 HLA-B27+ in 75-80% Caucasians

76. REACTIVE ARTHRITIS
 Post-venereal onset: more common Sex 5:1 M:F
 Post-dysenteric: less, equal M=F
 Course: self limiting (< 6 mos), chronic,
intermittent
 Complications: Acute anterior uveitis 5%, carditis,
fasciitis

77. REACTIVE ARTHRITIS
 Conjunctivitis may occur in the same time as flares of
arthritis
 Average duration of arthritis 4-5 months; 2/3 will have mild
musculosketal symptoms for more than a year
 Recurrence more common with chlamydia-induced reactive
arthritis (15-30%)

78. REACTIVE ARTHRITIS
 Decreasing incidence in the HIV era.
 HIV itself can produce a reactive type of arthritis
rate of spondyloarthritis is 180/100,000 in HIV
infected individuals– 12 times higher than non-
HIV persons)

79. COMMON PATHOGENS
 Enteric Infections
Shigella flexneri (0.2-2%)
Salmonella typhimurium, S. enteritidis (1-3%)
Yersinia enterocololitica, Y. pseudotuberculosis
Campylobacter jejuni
Clostridium difficile
 Urogenital Infections
Chlamydia trachomatis, C. pneumoniae
Ureaplasma Urealyticum
BCG when instilled into the bladder (for treatment of bladder
carcinoma)
Infectious Triggers for Reactive Arthritis

80. GU involvement
• Urethritis
• Prostatitis
• Orchitis
• Balanitis
• Vaginitis
• Cervicitis
Sausage Digits
= periostitis + enthesitis +
synovitis. Seen in SpA,
JRA, MCTD

81. KB: keratoderma
blenorrhagicum

82. Treatment
Non-medical
OT/Physio/Education
Medical
Analgesia
NSAIDs
Glucocorticoids – IV, IM, intra-articular,
oral.

83. DMARD
Vaccinations – before DMARD
 Flu vaccine – once a year
 Pneumococcal vaccination
- Pneumovax – every 3 to 5 years
 Live vaccines

84. Methotrexate
 Folate antagonist
 Monitoring: FBC, U&E and LFT every 2
weeks until dose is stable for 6 weeks.
Then monthly.
 Side effects
 Minor: mouth ulcers, nausea, hair loss
 Major: bone marrow suppression, liver damage,
pneumonitis
 Teratogenic

85. Sulfasalazine
 Unknown mode of action
 Monitoring: FBC + LFT every 2 weeks for 8 weeks,
monthly for 3 months, then 3 monthly.
Year 2 - every 6 months then stop.
 Side effects
 Minor: nausea, rash
 Major: leukopaenia, liver damage, fibrosing alveolitis

86. Other DMARDS and Immunosuppressants
 Azathioprine
 Ciclosporin

87. Biologic Therapy
 Immunotherapy
 Anti-TNF
Etanercept
Infliximab
Adalimumab
 Cost £10,000/yr

88. Biologic Therapy
Very effective in clinical trials
Suppress disease activity
Slow onset of erosions
Improve quality of life
 TB and infection
Long term safety - unknown
BUT very expensive and NICE controlled!

89. Inflammatory Bowel Disease (UC and
CD) and Inflammatory Arthritis (IA)

90. IBD and IA
Arthropathies – 4% to 23%
 Type I arthropathy (oligoarthritis <5 joints).
Occurs with active IBD
Weight bearing joints
Self limiting (settles as IBD activity decreases)
No joint damage

91. IBD and IA
 Type II arthropathy (Polyarthritis ≥ 5 joints)
Small joints of both hands
Symmetrical
Independent of IBD activity.
Orchard R et al Gut 1998; 42:387-91

92. Inflammatory Bowel Disease and
Inflammatory Arthritis
Axial involvement
 Similar to other spondyloarthropathy
 Up to 75% HLA-B27 +
Steer S et al, J Rheumatol 2003; 30:518-22
 Asymptomatic sacroiliitis 11 - 52%
Orchard R et al Gut 1998; 42:387-91.
De Vos, J Gastroenterol Hepatol. 2008;23(1):132-7
Enthesopathy

93. Treatment Summary
Seronegative spondyloarthropathies
 Spinal involvement - Anti-TNF (DMARD not useful)
 Peripheral joints (DMARD and anti-TNF)
 Entheses (Anti-TNF)
 Gut – CD (Etanercept not work)
 Eye – uveitis (?Etanercept not as good)
 Skin – psorasis (DMARD and anti-TNF)

94. SUMMARY
Seronegative spondyloarthropathies
 Spine - inflammatory back pain
 Peripheral joints
 Entheses
 Gut - IBD
 Eye - uveitis
 Skin - psorasis

95. Summary: Spondyloarthritides
 Beware of the pitfalls: these disease are more common than
previously thought and are often diagnosed late, causing
significant functional disability
 Consider the differential diagnosis
 Recognize the role of labs/imaging
 Traditional therapies provide symptomatic control,
DMARDs have no role in spinal disease
 Osteoporosis is common in AS
 Anti-TNF- therapy improves symptoms and productivity
with the potential to modify structural outcomes in AS

96. REFERENCES
 KELLY RHEMATOLOGY.
 DAVIDSON MEDICINE 23RD EDITION.
 RADIOGRAPHS BY DIFFERENT INTERNET
BROWSERS.

97. Thank You