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 Spondylo: Origin: < Gr spondylos, vertebra < IE base *sp(h)e(n)d-, to jerk, dangle > Sans spandatē, (he) jerks

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 Enthesitis 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 Hyperparathyroidism

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 Classification 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 radiographs Normal 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 spine 3. Decreased chest expansion 4. Bilateral sacroiliitis grade 2-4 5. Unilateral sacroiliitis grade 3-4 Definite AS if criterion 4 and any other criteria is fulfilled AMOR Criteria take into account HLA B27 status and response to treatment

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) Hips/shoulders Enthesitis sacroiliitis spondylitis Hips/shoulders Enthesitis Osteoporosis Spinal fractures There were 19 cervical fractures in 18 patients, which were chalkstick in type and occurred predominantly at the 6th and 7th cervical levels. Ten fractures passed through the upper part of the vertebral body, one through the mid-vertebral body and the final eight were through the disc space. The site of the fracture line was related to neurological outcome. Those patients whose fracture line ran through the disc space had significantly less neurological injury and a much better prognosis. Distraction at the fracture site had some relation to prognosis but horizontal displacement and angulation were not found to be of importance. This study confirms that cervical fracture with neurological complications may follow minor trauma in ankylosing spondylitis.

Ankylosing spondylitis vs. mechanical LBP Inflammatory/ spondylitic back pain 1. Onset prior to age 40 2. Insidious onset 3. Persistence at least 3 months 4. Morning stiffness 5. 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: Peripheral skeletal 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 Costosternal junctions Spinous processes 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

Figure 1 (A) Low power view of the attachment of the Achilles tendon to the calcaneus to show the complexity of structures that jointly comprise the enthesis. These structures include the enthesis fibrocartilage (EF), sesamoid fibrocartilage (SF), periosteal fibrocartilage (PF), and the retrocalcaneal bursa (RB). Toluidine blue. Scale bar 0.5 cm. (B) A high power view of the enthesis of the supraspinatus tendon in the region of the tidemark (T). This highly basophilic line is a calcification front separating the zones of calcified and uncalcified fibrocartilage. It is relatively straight and this contrasts with the irregularity of the junction between the calcified fibrocartilage (CF) and the underlying bone (B) (junction marked with *). It is such interdigitations that help to hold the two tissues together. Note that the fibrocartilage cells (FC) are more conspicuous in the region of uncalcified fibrocartilage. Haematoxylin and eosin. Scale bar 100 μm. (Courtesy of Dr M Benjamin, University of Cardiff,Wales.)

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! This woman with AS was misdiagnosed because of her ability to touch her toes. Thorough examination revealed (b) her full range of extension (c) and her side flexion to be virtually nil. More accurate observation and the performance of a Schober test revealed that her forward flexion took place almost entirely from her hips

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 Ankylosing spondylitis >90% Reiter’s syndrome 80% Reactive arthritis 85% Inflammatory bowel disease 50% Psoriatic arthritis- spondylitis - 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% HLA B27 in African Americans 3%

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 27

FIG. 1. Normal MRI sacroiliac joints on: (a) fat-saturated T1-weighted scan, (b) STIR sequence. FIG. 2. Abnormal MRI sacroiliac joints on: (a) fat-saturated T1-weighted scan, (b) STIR sequence. This scan demonstrates subchondral oedema, sclerosis and erosions.

Late sacroiliac changes Calcification, interosseous bridging, and ossification Bony ankylosis Osteoporosis

AS Radiographic 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 B A M O

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

Infliximab in AS (% ASAS Response at 24 weeks) van der Heijde D, et al, Arthritis Rheumatism 2005

AS: Summary Age at onset Young adults Sex ratio 3:1 (males to females) Axial disease Virtually 100% Sacroiliitis Symmetric Peripheral 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 Conjunctivitis Urethritis/cervicitis 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 adults Sex ratio Mostly male Axial disease 50% Symmetry Asymmetric Peripheral joints >90% Eye involvement Common Skin/nail findings Common 25-50% have relapses 20% have chronic disease

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 types 1. Oligoarticular (>50%) 2. RA variant (25%) 3. DIP only (5-10%) 4. Arthritis mutilans (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 adults Sex ratio Equal Axial disease 20% Symmetry Asymmetric Peripheral joint 95% Eye involvement Occasional Skin/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 adults Sex ratio Equal Axial disease <20% Symmetry Symmetric Peripheral joints Frequent Eye involvement Occasional Skin/nail findings Uncommon