Seronegative Spondyloarthropathies

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

Seronegative Spondyloarthropathies

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

SNSA: Group characteristics

• Propensity to affect spine, peripheral joints, and periarticular structures

• Characteristic extraarticular features

• Absence of RF and ANA• Association with HLA B27

SNSA: Group pathology

• Sacroiliitis– Osteopenia– Erosions

• Peripheral arthritis– Synovial hyperplasia– Pannus– Lymphoid infiltration

• Enthesitis– Inflammation at

tendinous insertions

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– Hyperparathyroidis

m

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

AS: Diagnosis

• Diagnostic Criteria– Highly sensitive at early stage of

disease

• Classification Criteria– Deals with groups of patients – NOT individual patients– Primarily for epidemiologic purposes

Grading sacroiliitis

• Grading of radiographsNormal 0

Suspicious 1

Minimal sacroiliitis 2

Moderate sacroiliitis 3

Ankylosis 4

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 spine3. Decreased chest expansion4. Bilateral sacroiliitis grade 2-45. Unilateral sacroiliitis grade 3-4

Definite AS if criterion 4 and any other criteria is fulfilled

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

AS :Skeletal features

• Axial (back pain)– sacroiliitis– spondylitis

• Hips/shoulders• Enthesitis• Osteoporosis• Spinal fractures

Ankylosing spondylitisvs. mechanical LBP

• Inflammatory/ spondylitic back pain1. Onset prior to age

402. Insidious onset3. Persistence at least

3 months4. Morning stiffness5. Improvement with

exercise

Need 4/5 criteria

Inflammatory questions

– Sensitivity 95-100% – False + 10-15%

• mechanical back pain and healthy athletes

• low prevalence of AS in population (1-2%)

– Positive predictive value is low• 10% false positive

AS: Peripheralskeletal features

• Hip and shoulder involvement– May be first

symptom– Up to 1/3 patients– More common in

juvenile (<16) onset– Flexion contractures

at hips

AS: Peripheral skeletal features

• Other peripheral joints– Infrequent– Often asymmetric– Transient– Rarely erosive– Resolves without

residual deformity

AS: Enthesitis

• Enthesitis– 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

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

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

AS: Iritis

• Acute anterior uveitis/iritis/ iridocyclitis

• Most common ES• 25-30%• Unilateral• Recurrent

• Symptoms• Pain• Lacrimation• Photophobia• Blurry vision

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

Patrick’s and Gaenslen’s tests

Office measurement

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.

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].

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

Office measurement

Don’t Be Fooled!

AS: Laboratory findings

• Elevated ESR (75%)• Elevated CRP• ANA and RF negative• NC/NC anemia (15%)• HLA B27• No diagnostic or pathognomic

tests!

HLA-B27: Disease Associations

Disease Association

Ankylosing spondylitis >90%

Reiter’s syndrome 80%

Reactive arthritis 85%

Inflammatory bowel disease 50%

Psoriatic arthritis- spondylitis 50%

- peripheral arthritis

15%

Whipple’s disease 30%

HLA B27 and AS in Caucasian populations

• HLA B27 in Americans 8-14%• 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%

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

AS: Radiographic findings

• SI joint- symmetric– Pronounced on iliac

side• Erosions/sclerosis

– ‘Postage stamp’ serrations

– Pseudowidening

www.mdconsult.com/das/book/0/view/1807/I4-u1....

More sensitive than XRAY

• MRI

• CT

Late sacroiliac changes

• Calcification,interosseous bridging, and ossification

• Bony ankylosis

• Osteoporosis

ASRadiographic findings

• Vertebral Column– Squaring of

vertebrae

Skeletal manifestations

• Syndesmophytes– Ossification of

the outer layers of the annulus fibrosis

– Sharpey’s fibers

– Vertical

Osteophyte Vs. Syndesmophyte

Late axial disease

BAMBOO

AS: Radiographic findings• Enthesitis

– Bony erosions– Osteitis (whiskering)

of insertions• Ischial tuberosities• Iliac crest• Calcani• Femoral

trochanters• Spinous processes

AS: Treatment

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

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

Etanercept in AS (% ASAS Response Week 12)

Davis J, et al, Arthritis Rheumatism 2003

0

10

20

30

40

50

60

70

80

90

100

ASAS 20 ASAS 50 ASAS 70

Placebo (n=138)Etanercept (n=139)

Infliximab in AS(% ASAS Response at 24 weeks)

van der Heijde D, et al, Arthritis Rheumatism 2005

0

1020

3040

5060

7080

90100

ASAS 20 ASAS 40

placebo (n=78)Infliximab (n=201)

AS: Summary

Age at onset Young adultsSex ratio 3:1 (males to

females)Axial disease Virtually 100%Sacroiliitis SymmetricPeripheral joint 25%Eye involvement 25%Infectious triggers Unknown

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

Physical Exam

Reactive arthritis: Clinical triad

1. Conjunctivitis2. Urethritis/cervicitis3. Arthritis

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)

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%)

Reactive arthritis: Clinical features

• Ocular– Uveitis, conjunctivitis,

keratitis

• Mucocutaneous– Oral ulcerations,

circinate balanitis, keratoderma

• Others– Fevers, cardiac (AR,

conduction abnormalities)

Reactive arthritis: Triggers

• Enteric pathogens– Shigella flexneri– Salmonella

typhimurium– Yersinia

enterocolitica– Campylobacter

jejuni

• Urogenital pathogens– Chlamydia

trachomatis– Ureaplasma

urealyticum

Reactive arthritis: Labs

• Elevated ESR and CRP• Thrombocytosis, NC/NC anemia• Remember HIV

• ALL ARE NON-SPECIFIC

Reactive arthritis: Therapy

• NSAIDs• Long acting indomethacin• Systemic glucocorticoids• DMARDs• TNF blockers• Prolonged antibiotics ??

Reactive arthritis: Summary

Age at onset Young adultsSex ratio Mostly maleAxial disease 50%Symmetry AsymmetricPeripheral joints >90%Eye involvement CommonSkin/nail findings Common

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

Psoriatic arthritis (PSA)

Five types1. Oligoarticular (>50%)

2. RA variant (25%)3. DIP only (5-10%)4. Arthritis mutilans

(5%)5. Back disease (20-

40%)

Psoriatic arthritis (PSA):Radiology

• Fusiform• Normal

mineralization• Joint space loss• Pencil in cup• Bone proliferation

Psoriatic arthritis: Summary

Age at onset Young adultsSex ratio EqualAxial disease 20%Symmetry AsymmetricPeripheral joint 95%Eye involvement OccasionalSkin/nail disease Virtually 100%

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

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

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

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

IBD: Summary

Age of onset Young adultsSex ratio EqualAxial disease <20%Symmetry SymmetricPeripheral joints FrequentEye involvement OccasionalSkin/nail findings Uncommon