7 - Spondyloarthropathies - Classification and Pathogenesis Flashcards
Biblical Leprosy
Spondyloarthritis + Psoriasis
Spondyloarthritis (SpA)
A chronic immune-mediated inflammatory disease group with diverse phenotypic manifestations
Spondyloarthritis - 4 Domains
Axial skeleton:
Sacroiliitis
Spondylitis
Synovium:
Arthritis
Entheses:
Enthesitis
Extra-articular features:
Psoriasis (skin and nails)
Uveitis
Inflammatory bowel disease
Spondyloarthritis - Traditional Clinical Subtype Classification
Ankylosing Spondylitis (ASp) Reactive Arthritis (ReA) Juvenile Spondyloarthritis (JSpA) Enteropathic Arthritis (Ulcerative Colitis, Regional Enteritits) Psoriatic Arthritis (PsA) Undifferentiated Spondyloarthritis (USpA)
Spondyloarthritis - Pathophys
Inflammatory autoimmune response is granulomatous in nature
Involves T cells (especially CD8 T cells)
Involves Macrophages
Involves NK Cells
Involves Innate T Cells
Does NOT involve B Cells
Does NOT involve autoantibodies
(ANA, RF & ACPA negative)
Consequence: Fibrosis and new bone formation
Some inflammation mediated by IL-17/IL-23 axis and TNF-α
Very strong familial and genetic component:
Certain Class I HLA alleles determine susceptibility and likely specify the ability to bind a target peptide from target antigen
Spondyloarthritis - Targets of inflammation - Axial Skeleton
Fibrocartilage of sacroiliac joints
Entheses and ligametns of spine
Synovial Joints and vertebrae
“Corner Inflammatory Lesions” - Anterior spondylitis
MRI has a major role in understanding the inflammation here
T2 Short Tau Inversion Recovery (STIR) is an important type of imaging sequence will reveal axial spondyloarthritis
Gadolinium contrast
Activated T Cells invade the enthesis junction of annulus fibrosis and vertebral body
This triggers a granulation tissue response
Annulus fibers erode and replaced by fibrocartilage
Subperiosteal new bone formation, vertebral squaring
Fibrocartilage ossifies to form syndesmophytes
Inflammation resolves, but progressive cartilagenous and periosteal ossification forms “bamboo spine”
Spondyloarthritis - Targets of inflammation - Entheses
Fibrocartilage insertions of ligaments, tendons and fascia in axial and peripheral sites
Lover’s heel:
Calcaneal spurs at plantar fascia and calcaneal tendon
Occurs with Reactive Arthritis, which is venereally transmitted
Infiltration of entheses by activated T Cells
Granulation tissue forms (activated macrophages and fibroblasts)
Bone erosions and heterotropic NEW BONE FORMATION
Spondyloarthritis - Targets of inflammation - Synovium
Synovitis of peripheral and axial joints
Pencil-in-cup deformity
Can happen in the Distal Interphalangeal Joint, a joint NEVER associated with Rheumatoid Arthritis
Spondyloarthritis - Sacroiliitis
Subchondral regions of the synarthrotic SI joints invaded by activated T cells and granulation tissue
Erosion of cartilage on iliac side Bone plate blurs Joint space widens Reactive sclerosis ensues Fibrous ankylosis replaced by bone, obliterating the SI joint
Can be symmetric or asymmetric
Asymmetric more common with peripheral ASp
Synovitis - Clinical Patterns
Large joints: Monoarticular (asymmetric) or symmetric involvement of hip and knee joints
Small joints:
Asymmetric (1 or 2 PIP joints on one hand)
All of the joints in one ray
Symmetric (similar to RA)
DIP involvement
Asymmetry and pattern of involvement usually distinguish spondylitis from RA
Spondyloarthritis Diseases - Genetics
Strong familial aggregation
High monozygotic twin concordance
Genetically complex pattern of inheritance
Susceptibility associated with certain Class I MHC alleles:
HLA-B*27
Spondyloarthritis Diseases Associated with HLA-B*27
Ankylosing Spondylitis - 95%
Reiter’s Syndrome (Reactive Arthritis) - 60 to 70%
Psoriatic Arthritis - 15 to 20%
Ethnically matched controls - 3 to 8%
Inflammatory Back Pain
Due to the initial inflammation of:
Enthesitis
Spondylitis
Sacroiliitis
Assessment of Spondyloarthritis (ASAS) Criteria
4 out of 5 needed:
Insidious onset
Pain at night (with improvement on getting up)
Age of onset 3 mo) dull deep buttock or low back pain
Poorly localized, does not follow nerve root
Alternating buttock pain
Stiffness/pain in the morning (>30 min) awakens from sleep
Ankylosing Spondylitis (Axial Spondyloarthritis) - ASp
Widespread spondylitis and sacroiliitis
Male:Female = 3 - 10:1
Culminates in bony ankylosis of spine
Onset age 10 - 35 with inflammatory back pain
Hip, shoulder, knee arthritis in ~30%
95% of those affected are HLA-B27
Disease prevalence follows circumpolar distribution of HLA-B27
Affects ~5% of HLA-B*27 individuals
No evidence of triggering by microorganisms
Course of Axial Spondyloarthritis
Inflammatory back pain and tenderness Worsens and ascends over months to years Increasing stiffness Loss of mobility Ultimately results in spinal ankylosis
Postural changes: Loss of lumbar lordosis
Buttock atrophy and kyphosis
Chest expansion compromised
C-Spine ventroflexion
Peripheral joints, notably hips develop flexion contractures of anxylosis, compensatory knee flexion
Inflammatory back pain Peripheral arthritis (~30%) and peripheral enthesopathy (~30%) dominate the early phase, then bony ankylosis predominates the later phase
Axial Spondylitis - Systemic Involvement
Acute Anterior Uveitis (25%)
May occur at any time (syncheae and glaucoma)
Apical pulmonary fibrosis, often with cavitation (
1984 New York Criteria for Ankylosing Spondylitis (Still used)
Radiological: Sacroiliitis Grade 2 bilaterally
OR
Grade 3- 4 unilaterally on conventional X Ray
PLUS
Clinical (need at least 1):
Low back pain and stiffness for more than 3 months which improves with exercise but is not relieved with rest
Limitation of motion of the lumbar spine in both sagittal and frontal planes
Limitation of chest expansion relative to normal values corrected for age and sex
Problems with the 1984 New York Criteria
Radiographic sacroiliitis is a LATE manifestation, so diagnosis only comes after 6 - 8 years of back pain.
MRI and PET should be used now
HLA-B*27 was not included, even though we now know that it is present in 95% of cases, and just 5% of controls
Inflammatory back pain’s definition is not inclusive
B*27:06 (Southeast Asia)
B*27:09 (Sardinia)
Alleles NOT associated with ankylosing spondylitis
They don’t have an aspartate at position 116 in the P9 binding pocket
Endoplasmic Reticulum Aminopeptidase - ERAP1
Involved in the final processing steps of trimming peptides to optimal size for MHC-I binding (~9 amino acids long)
Polymorphisms are associated with HLA-B*27 + ankylosing spondylitis
Supports loading of HLA-B*27 molecules
3 hypotheses about something (poorly explained)
Folding of B27
Presenting of peptide antigenic something something
Treatment
High does NSAIDs (80% experience symptomatic relief)
Physical therapy - Not bike riding, but swimming. Resist the posture that the disease will pull you into.
TNF inhibitors block symptoms, but symptoms return when you stop. Also doesn’t cause radiographic changes.
RA treatments don’t work
Secukinumab (anti-IL-17) works for a 60% improvement in ASAS20
Ustekinumab leads to MRI improvement
