1. Spondyloarthritides N.Movaffagh MD Rheumatologist

2. SPA include:
ankylosing spondylitis (AS)
reactive arthritis
psoriatic arthritis and spondylitis
enteropathic arthritis and spondylitis
juvenile onset spondyloarthritis (SpA)
undifferentiated SpA

3. ANKYLOSING SPONDYLITIS
an inflammatory disorder of unknown cause that primarily affects:
axial skeleton
Peripheral joints
extraarticular structures

4. AS begins in the second or third decade
male-to-female prevalence is between 2:1 and 3:1

5. EPIDEMIOLOGY correlation with the HLA-B27
90% in patients with AS, HLA-B27 is positive
AS is present in 1–6% of adults inheriting B27
prevalence is 10–30% among B27+ adult first-degree relatives of AS probands

6. PATHOLOGY Sacroiliitis is often the earliest manifestation of AS
Synovitis represent the earliest change
pannus and subchondral granulation tissue
Marrow edema, enthesitis, and chondroid differentiation
Macrophages, T cells, plasma cells, and osteoclasts are
prevalent
eroded joint margins fibrocartilage regeneration
ossification
joint may become totally obliterated
Erosion of joint cartilage by pannus bony ankylosis

7. spine
Inflammatory granulation tissue in the paravertebral connective tissue at the junction of annulus fibrosus and vertebral bone
outer annular fibers are eroded
bone forming the beginning of a syndesmophyte
endochondral ossification
bridging the adjacent vertebral bodies
bamboo spine

13. spine
diffuse osteoporosis erosion of vertebral bodies at the disk margin
“squaring” or “barreling” of vertebrae
Inflammatory arthritis of the apophyseal (facet)
synovitis, inflammation at the bony attachment of the joint capsule

14. Peripheral synovitis
Peripheral synovitis in AS shows marked vascularity
Lining layer hyperplasia, lymphoid infiltration, and pannus formation
Central cartilaginous erosions caused by proliferation of subchondral granulation tissue

15. characteristic lesion in AS and other SpAs:
Enthesitis
characterized by erosive lesions that eventually undergo ossification

16. PATHOLOGY
Subclinical intestinal inflammation in the colon or distal ileum in SpA

17. PATHOGENESIS immune-mediated
little direct evidence for antigen-specific autoimmunity
(TNF-α) plays a central role
(IL) 23/IL-17 cytokine pathway
TGF-β in more advanced lesions
enteric bacteria may play a role
Misfolding of B27 heavy chain
lack of regulation of the Wnt signaling pathway

18. Mast cell
neutrophils
γδ T cells
CD4+ and CD8+ Tcells
macrophages
B cells
NK cell

19. PATHOGENESIS peptide antigen presentation to CD8+ T cells
may not be the primary disease mechanism
association of AS with ERAP1

20. ERAP_1
a proteolytic enzyme that tailors peptides for
presentation by class I molecules.

21. association of AS with ERAP1
a proteolytic enzyme that tailors peptides for
presentation by class I molecules
strongly influences the MHC class I peptide repertoire
only found in B27+ patients
and this suggests that peptide binding to B27 is important.
Pairs of ERAP1 alleles found in AS patients show diminished peptidase activity

22. CLINICAL MANIFESTATIONS
late adolescence or early adulthood
median age is approximately 23 years in Western countries
In 5% of patients, symptoms begin after age 40

23. The initial symptom:
dull pain, insidious in onset, felt deep in the lower lumbar or gluteal region
low-back morning stiffness of up to a few hours’ duration that improves with activity and returns following inactivity

24. the pain has usually become persistent and bilateral
Nocturnal exacerbation of pain often forces the patient to rise and move around
bony tenderness (presumably reflecting enthesitis or osteitis) may accompany back pain or stiffness

25. Common sites of bony tenderness include:
costosternal junctions
spinous processes
iliac crests
greater trochanters
ischial tuberosities
tibial tubercles
heels

26. Hip and shoulder arthritis
Severe isolated hip arthritis or bony chest pain may be the presenting complaint

27. Arthritis of peripheral joints (asymmetric)
Neck pain and stiffness (late manifestations)
constitutional symptoms in older age(Rarely)
AS often has a juvenile onset in developing countries
Peripheral arthritis and enthesitis usually
predominate, with axial symptoms supervening in
late adolescence

28. physical findings loss of spinal mobility
Limitation of anterior and lateral flexion
Limitation of extension of the lumbar spine and of chest expansion
Limitation of motion is thought to possibly reflect muscle spasm secondary to pain and inflammation

29. Pain in the sacroiliac joints may be elicited either with direct pressure or with stress on the joints.
tenderness upon posterior spinous processes

30. modified Schober test:
patient stands erect with heels together
marks are made on the spine at the lumbosacral junction(identified by a horizontal line between
the posterosuperior iliac spines) and 10 cm above
then bends forward maximally
distance between the two marks is measured

31. distance increases by <4 cm positive test
distance increases by ≥5 cm in the case of normal mobility
distance increases by <4 cm positive test

32. Chest expasion is measured as the difference between maximal inspiration and maximal forced expiration in the fourth intercostal space in males
below the breasts in females
with the patient’s hands resting on or
just behind the head
Normal chest expansion is ≥5 cm

33. Lateral bending measures
the distance the patient’s middle finger travels down the leg with maximal lateral bending.
Normal is >10 cm.
Limitation or pain with motion of the hips or shoulders
Early in the course of mild cases, symptoms may be subtle and nonspecific, and the physical examination may be unrevealing

34. course of the disease:
mild stiffness and normal radiographs
totally fused spine and severe bilateral hip arthritis
severe peripheral arthritis and extraarticular manifestations
Pain tends to be persistent early in the disease
intermittent later

35. Typical severe untreated case:
progression of the spondylitis to syndesmophyte
formation
obliterated lumbar lordosis buttock atrophy accentuated thoracic kyphosis
forward stoop of the neck or flexion contractures at the hips,compensated by flexion at the knees

37. Disease progression:
loss of height
limitation of chest expansion and spinal flexion
and occiput-to-wall distance

38. Predictive factors of radiographic progression:
syndesmophytes
high inflammatory makers
smoking

39. worse prognosis:
onset of AS in adolescence
early hip involvement

40. In women ,AS :
tends to progress less frequently to total spinal ankylosis
increased prevalence of isolated cervical
ankylosis and peripheral arthritis

41. In industrialized countries:
peripheral arthritis usually as a late manifestation
(distal to hips and shoulders)

42. in developing countries:
Prevalence of peripheral arthritis is much higher
onset typically early in the disease course

43. Pregnancy has no consistent effect on AS
symptoms improving remaining the same deteriorating in onethird of pregnant patients

44. most serious complication of the spinal disease:
spinal fracture
lower cervical spine is most commonly

45. Pseudoarthrosis:
fracture through a diskovertebral junction and adjacent neural arch
most common in the thoracolumbar spine

46. extraarticular manifestation
most common extraarticular manifestation :
acute anterior uveitis
typically unilateral, causing pain, photophobia,
and increased lacrimation
tend to recur, often in the opposite eye

47. extraarticular manifestation
inflammation in the colon or ileum
frank IBD occurs in 5–10% of patients with AS
Aortic insufficiency
Congestive heart failure
Third-degree heart block
Subclinical pulmonary lesions
cardiac dysfunction

48. extraarticular manifestation
Cauda equina syndrome and upper pulmonary lobe fibrosis are rare late complication
Retroperitoneal fibrosis
Prostatitis: increased prevalence
Amyloidosis is rare

49. AS shortens life span,(some of study)
Causes of mortality:
spinal trauma
aortic insufficiency
respiratory failure
amyloid nephropathy
upper GI hemorrhage

50. validated measures of disease activity and functional outcome
BASDAI
ASDAS
BASFI

51. LABORATORY FINDINGS No laboratory test is diagnostic of AS
HLAB27 is present in 80–90% of patients
ESR and CRP
Mild anemia
alkaline phosphatase in severe disease
serum IgA levels are common

52. Rf ,anti- CCP, (ANAs) are absent
CD8+ T cells tend to be low serum matrix metalloproteinase 3 levels correlate with disease activity
Synovial fluid from peripheral joints in AS is nonspecifically inflammatory

53. In cases with restriction of chest wall motion:
vital capacity and increased functional residual capacity are common
airflow is normal

54. RADIOGRAPHIC FINDINGS
sacroiliitis, usually symmetric
earliest changes:
blurring of the cortical margins of the subchondral bone
Erosions
Sclerosis
pseudowidening”of the joint space
fibrous and then bony ankylosis
Obliteration of joints

58. RADIOGRAPHIC FINDINGS
lumbar spine:
Straightening
osteitis of the anterior corners of the vertebral bodies with subsequent erosion reactive sclerosis
“squaring” or “barreling” of vertebral body
Marginal syndesmophytes

60. IMAGING dynamic MRI with fat saturation T2-weighed
STIR (short tau inversion recovery )
T1-weighted images with contrast

61. Early sacroiliitis in AS
interosseous ligaments edema (thick arrow)

62. bone mineral density
Use of a lateral projection of the L3 vertebral body

63. DIAGNOSIS
ASAS Criteria are applicable to: individuals with ≥3 months of back pain with age of onset <45 years old

64. criterion for inflammatory back pain of axial SpA
chronic(≥3 months) back pain should have four or more of the following characteristic features
(1) age of onset <40 years old
(2) insidious onset
(3) improvement with exercise
(4) no improvement with rest
(5) pain at night with improvement upon getting up

65. Other common features of inflammatory back pain include:
morning stiffness >30 min
alternating buttock pain
awakening from back pain during only the second half of the night

66. ASAS Criteria for Classification of Axial Spondyloarthritis

67. Modified New York Criteria for ankylosing spondylitis
Grading of Radiographs
Normal, 0; suspicious, minimal sacroiliitis, moderate sacroiliitis 3
ankylosis,4
Sacroiliitis grade ≥ 2 bilaterally grade 3-4 unilaterall

68. metabolic, infectious, and malignant causes of back
pain must also be differentiated from AS including:
infectious spondylitis , spondylodiskitis ,sacroiliitis
primary or metastatic tumor
Ochronosis
DISH

69. DIFFERENTIAL DIAGNOSES
Calcification and ossification of paraspinous
ligaments occur in diffuse idiopathic skeletal hyperostosis(DISH)
in the middle-aged and elderly
usually not Symptomatic
Ligamentous calcification on the anterior bodies of the vertebra(appearance of(“flowingwax”)
generally accompanied by osteophyte formation
Intervertebral disk spaces are preserved
sacroiliac and apophyseal joints appear normal

70. diffuse idiopathic skeletal hyperostosis

71. ASAS Criteria for Peripheral SPA

72. TREATMENT exercise program NSAIDs
continuous high-dose NSAID therapy slows radiographic progression
anti-TNF-α therapy

73. PSORIATIC ARTHRITIS
an inflammatory musculoskeletal disease that has both autoimmune and autoinflammatory features
characteristically occurring in individuals with psoriasis

74. EPIDEMIOLOGY prevalence of PsA among individuals with psoriasis
range from 5 to 42%
First-degree relatives of PsA patients have an
elevated risk for psoriasis, for PsA itself, and for other forms of SpA

75. PATHOLOGY inflamed synovium in PsA resembles that of RA
less hyperplasia and cellularity than in RA
synovial vascular pattern is generally greater than in RA
prominent enthesitis

76. CLINICAL FEATURES frequency in men and women is almost equal
begin in childhood or late
typically begins in the fourth or fifth decade(age of 37 year )

77. five patterns for PSA:
arthritis of the DIP joints5%
asymmetric oligoarthritis30%
symmetric polyarthritis40%
axial involvement (spine and sacroiliac joints)5%
arthritis mutilans

78. Nail changes in the fingers or toes
dactylitis and enthesitis(hallmark features)
Tenosynovitis
Shortening of digits because of underlying osteolysis
(characteristic of PsA)
fibrous and bony ankylosis of small joints
Rapid ankylosis of one or more(PIP) joints early in the course of diseas
Back and neck pain and stiffness are also common

81. DIP joints nail changes are almost always present
These joints are also often affected in the other patterns of PsA.

84. Asymmetric oligoarthritis
A knee or another large joint with few small joints in the fingers or toes often with dactylitis

85. Symmetric polyarthritis
indistinguishable from RA
Almost any peripheral joint can be involved.

86. Axial arthropathy indistinguishable from idiopathic AS,but:
More neck involvement and less thoracolumbar spinal involvement are characteristic
and nail changes are not found in idiopathic AS

87. Arthritis mutilans shortening of digits (“telescoping”)
sometimes coexisting with ankylosis and contractures in other digits.

89. Six patterns of nail involvement:
Pitting
Horizontal ridging
Onycholysis
yellowish discoloration of the nail margins
dystrophic hyperkeratosis
combinations of these findings

93. Extraarticular manifestations
Conjunctivitis
uveitis (often bilateral, chronic, and/or posterior)
Aortic valve insufficiency

96. psoriasis and associated arthropathy with HIV
tend to be severe
Severe enthesopathy, dactylitis, and rapidly progressive joint destruction
axial involvement is very rare
prevented by or responds well to antiretroviral therapy

97. mortality significantly increased
Greater incidence of cardiovascular death

98. LABORATORY AND RADIOGRAPHIC FINDINGS
ESR and CRP
low titers of RF& ANA
anti-CCP antibodies10%
Uric acid
HLA-B27 is found in 50–70%(with axial disease)
≤20% with only peripheral joint

99. Characteristics of peripheral PsA include:
DIP involvement (the classic “pencil-in-cup” deformity)
marginal erosions with adjacent bony proliferation (“whiskering”)
small-joint ankylosis
osteolysis of phalangeal and metacarpal bone
with telescoping of digits
periostitis and proliferative new bone at sites of enthesitis

100. new bone formation

104. Characteristics of axial PsA include:
Asymmetric sacroiliitis
less zygapophyseal joint arthritis
Nonmarginal, bulky, “comma”-shaped syndesmophytes.fewer and less symmetric
fluffy hyperperiostosis on anterior vertebral bodies
severe cervical spine involvement (AA subluxation)
paravertebral ossification

105. :

106. CASPAR (Classification Criteria for Psoriatic Arthritis) Criteriaa
1.Evidence of current psoriasis, personal history of psoriasis, or a family history of psoriasis
2. Typical psoriatic nail dystrophy observed on current physical examination
3. A negative test result for rheumatoid factor
4. Either current dactylitis or a history of dactylitis recorded by a rheumatologist
5. Radiographic evidence of juxtaarticular new bone formationg in the hand or foot

107. psoriasiform lesions should be sought in the scalp,
ears, umbilicus, and gluteal folds in addition to more accessible sites
finger and toe nails
Axial symptoms or signs, dactylitis, enthesitis, ankylosis, the pattern of joint involvement, and characteristic radiographic changes can be helpful clues

108. differential diagnosis
Osteoarthritis (Heberden’s nodes)
Gout
Multicentric reticulohistiocytosis RA

109. Radiography can be helpful
History of trauma
(reflecting the Koebner phenomenon)

110. TREATMENT anti-TNF-α agents Methotrexate
Ustekinumab monoclonal antibody to the shared IL-23/IL-12p40 subunit
Sulfasalazine
Cyclosporine
retinoic acid derivatives
psoralens plus ultraviolet A light (PUVA)
leflunomide