5spondyloarthropaties Seronegative Arthritis

Spondylo-arthritis

Objectives

• Gain a basic understanding of the Spondylo-Arthritis

• Learn specific Characteristics from SpA • Differentiate SpA from other chronic

Arthritis ( RA, OA )• Become familiar with joints, and extra-

articular manifestations of SpA• Understand the current treatment

paradigm and medications used

Introduction

• Spondyloarthropathies =

• Seronegative Spondyloarthritis– Absence of Rheumatoid Factor or other

autoantibody serologic abnormalities:• Psoriatic Arthritis-PsA• Ankylosing Spondylitis-AS (Prototype)• Reactive Arthritis-ReA• Enteropathic Arthritis-IBD• Undifferentiated Spondyloarthropathy-SpA

Criteria for classification of spondyloarthropathy

• Inflammatory spinal pain or synovitis (asymmetric or predominantly in lower limbs) plus more than 1 of the following:– Positive family history– Psoriasis– Inflammatory bowel disease– Urethritis, cervicitis, or acute diarrhea < 1 mo. before arthritis– Buttock pain alternating between right and left gluteal areas– Enthesopathy– Sacroiliitis

• Sensitivity 78.4% and specificity 89.6%

Spondyloarthropathies

• Are a diverse group of chronic inflammatory conditions linked by distinctive clinical, radiographic, and genetic features

• Refers to inflammatory changes involving the spine and the spinal joints.

• subtypes often overlap• may be considered one heterogeneous and

phenotypically diverse disease that has the potential to evolve into AS.

Introduction

Confusion

Can often see peripheral joint symptoms in the absence of spinal symptoms

Spondyloarthropaties

• The pathology of spondyloarthropathies is very different from that of RA. In RA, it is the synovitis that plays the major role, and the synovitis leads to bony erosions that don't heal.

• In spondyloarthritis there is some synovitis, but it's the enthesitis that is the major problem, especially in the axial disease.


• Not only is there enthesitis but also the osteitis that follows, which is different because there is reactive bone sclerosis and bone absorption, but then more bone remodeling sets in and it goes on to result in new bone formation that can result in ankylosis


• In RA, the cytokines lead to excessive osteoclastic activity resulting in bone erosions,

• In spondyloarthritis, the cytokines that are playing a major role result in osteoblastic activity

• Gradual bony bridging follows after being initiated by the inflammation




• Hallmarks of this family of disorders

• Inflammatory back pain (IBP)

• and Enthesitis: (inflammation at sites where tendons, ligaments, and joint capsule fibers attach to bone, with a strong tendency to produce fibrosis and calcifications).


• IBP: inflammatory Back Pain• worse in the late night and early morning • pain interferes with sleep to the point that the

patient gets up to walk in the middle of the night, • the discomfort can be characterized by

alternating buttock pain.• prolonged morning stiffness of greater than 30

minutes.


• Exercise alleviates the pain of IBP while rest makes it worse.

• IBP affects younger patients,

• peaking during the mid-20s

• onset before the age of 40,

• at the height of their productivity.


• IBP persists for at least 3 months.

• detrimental effects on quality of life

• increased disability, and morbidity -- equal, and in some cases exceeding, that seen in RA


• Although new bone formation is central to the pathogenesis of AS, is also associated with osteoporosis and low bone mineral density

• ectopic bone formation occurs within the inflamed vertebral enthesis

• bone resorption, (increased osteoclast activity), occurs at an unregulated rate within the vertebra and promotes weakening of the spinal column.


• The spine in the patient with AS fuses through:– ligamentous ossification and– syndesmophytosis,

• Rigid hyperkyphotic deformity develops.• Biomechanically, the fused spine acts as a

long bone incapable of appropriately dissipating the energy of a traumatic event.


• Altered spinal biomechanics• Combined with the brittle quality of the

osteoporotic bone • Increase susceptibility to vertebral column

factures,and Spinal Cord injury, even after minor, often trivial, trauma

• Significantly impaired mobility and peripheral joint arthritis:– exacerbate gait unsteadiness – increase susceptibility to falls

Sagittal reformatted CT scan showing a highly displaced thoracic fracture. Asterisk indicates apposition of the caudal fracture fragment on the thoracic aorta


• Extra-articular manifestations including:– psoriasis,– anterior uveitis,– IBD, – as well as rarer cardiac, renal, and pulmonary

manifestations

• a wide range of clinical manifestations.

Extra-articular manifestations

• Ocular Manifestations• Uveitis is one of the most common extra-

articular manifestations of the SpA,

• occurring in 25% to 40% of patients.

• there appears to be no correlation between the course of inflammatory eye disease and that of the arthritis.


• The uveitis typically presents as acute unilateral pain and photophobia; blurring of vision may also occur.

• Recurrence despite successful treatment is common. Cataracts and glaucoma with associated increased intraocular pressure and posterior synechiae can also be observed


• In addition, conjunctivitis is commonly observed in SpA (up to 30% to 60% of ReA), typically in a more transient and less relapsing course than uveitis

• patients who present with visual complaints in the SpA setting should be referred promptly to an ophthalmologist for thorough evaluation including slit lamp examination.

Cutaneous Manifestations• Plaque psoriasis, characterized by scaly,

erythematous, hyperkeratotic lesions, is the most common form of psoriasis and is an important component of diagnosing PsA.

• Careful examination of the skin should be performed in SpA evaluation,

Cutaneous Manifestations

• assessment of less conspicuous areas including the gluteal cleft, scalp and scalp line, groin, and posterior auricular regions should be performed.

Psoriasis

Psoriasis

Psoriasis

Psoriasis

Psoriasis

Cutaneous Manifestations

• no strict correlation between the extent of psoriasis skin disease and the extent of joint disease

Nail Changes

• Diffuse and numerous nail pitting (plate depressions), onicholysis (separation of the nail from underlying nail bed), and crumbling of the nail plate can be observed in both psoriasis and PsA.

• The extent of nail involvement in PsA parallels both skin and joint disease

Nail pitting/onicholysis

Nail Pitting

Onicholysis toe nails

Crumbling nail/DIP joint involvement

Pencil in Cup deformities

Other Extra- articular Manifestations

• Aortic regurgitation is perhaps the most recognized cardiac manifestation, with scar tissue in the aorta and aortic valve cusps leading to incompetent valves.

• Conduction abnormalities and heart block have also been described, characterized by extension of the fibrosis process into the AV bundle


• Apical pulmonary fibrosis, mostly asymptomatic and typically observed in patients with substantial disease duration, has been noted in a small percentage of AS patients


• Renal disease beyond analgesic and nonsteroidal anti-inflammatory drug adverse effects has appeared in 2 forms in AS, both of which are rarely observed: IgA nephropathy that can manifest as proteinuria and hematuria, and secondary amyloidosis manifested by nephrotic syndrome and, if associated with renal failure, generally a poor prognosis.

Spondyloarthropathies-Gene association

• Up to 70% of individuals suffering from SpA carry the HLA-B27 gene

• strength of the association between HLA-B27 and disease susceptibility varies among SpA subtypes and ethnic groups

• the B27 gene accounts for only 35% of the SpA genetic load.[1]

Associations with HLA-B27

Rheumatic diseasesRheumatic diseases

Ankylosing spondylitisAnkylosing spondylitisReiter’s Reiter’s syndrome/reactive syndrome/reactive arthritisarthritisIBD related arthritisIBD related arthritisPsoriatic arthritisPsoriatic arthritis

Normal Normal AssociationsAssociationsNative AmericansNative AmericansCaucasiansCaucasiansBlacksBlacks

Degree of Degree of associationsassociations

>90%>90%>80%>80%~75%~75%~50%~50%

13%13%8%8%4%4%

Ankylosing Spondylitis

• An inflammatory disease of the spine and axial joints

• Typically affects young men ages 15-30 • Women can be affected but much less than men

(3:1 men:women)• Affects about 1 in 1000 • women with AS may present differently from

men, complaining of neck and breast pain without the typical inflammatory low back pain


New York criteria for diagnosis of ankylosing spondylitis

• Definite ankylosing spondylitis If: Criterion 4 or 5 plus 1, 2, or 3.

– 1. Limited lumbar motion– 2. Low back pain for 3 months improved with exercise

not relieved by rest– 3. Reduced chest expansion– 4. Bilateral, grade 2 to 4, sacroiliitis on X-ray– 5. Unilateral, grade 3 to 4, sacroiliitis on X-ray


Previous Picture Hx

• A photographic series of a patient with ankylosing spondylitis was taken over a period of 26 years. By 1957 a thoracic kyphosis has become apparent, and loss of the normal lumbar lordosis has occurred. There are early flexion contractures of the hips and knees. In the next two sequences, increasing flexion contractures of the hips and knees have occurred along with progressive ankylosis of the spine. In 1973, bilateral total hip arthroplasties were performed, which improved the patient's posture.

Ankylosing spondylitis: lumbar vertebrae, bamboo spine (radiograph)

• This anteroposterior projection of the lumbar spine shows the characteristic changes of syndesmophyte formation or "bambooing." Ossification is present deep to the lateral collateral ligaments, and it follows the contour of the intervertebral disc spaces. This ossification involves the outer layers of the intervertebral disc (annulus fibrosus). In contrast, degenerative spurs will extend almost at right angles to the vertebral bodies, rather than snugly following the contour of the disc as in ankylosing spondylitis.

Sacroiliitis grading0-normal 1-possible2-minimal3-moderate4-ankylosing


• Begins in the Sacroiliac Joints and progresses upwards and can involve the entire spine

• Beyond the spine, axial joints including the shoulders and hips can be involved with varying degrees of severity particularly in AS.

• Shoulder involvement can be detected radiographically with characteristic erosive changes at the rotator cuff insertion.[

• Hip involvement is considered a poor prognostic factor in AS


• Inflammatory Stages– Can be extremely painful (flares)– Prolonged morning stiffness (hours)– Fatigue (pain & lack of sleep)

• Ankylosis– Stiffness increases – Significantly reduced ROM– Abnormal posture

Enthesitis

• Inflammation at the insertion of tendon, ligament, or articular capsule into bone

• Lower limb entheses are more commonly involved than the upper limb

• Patients with AS get “funny” pains

Achilles Enthesopathy

Enthesitis

Enthesitis• Common sites for Enthesitis

– Heel – Most Common (Achilles)– Patella– Tibial Tubercle– Base of the 5th metatarsal– Plantar Fascia– Other sites include:

• Anserine Bursa• Greater Trochanter• Iliac Crest• Rotator Cuff (Common in Ankylosing Spondylitis)• Costochondral

Physical Examination

• Peripheral Entheseal Involvement

• Spinal Involvement

Spinal Involvement

• Measure the Occiput to Wall distance• Chest Expansion

– Place the tape measure at the xiphisternum– Deep inhalation, exhalation, then inhalation– Measurement is age and sex dependant– Useful for following patients over time

• Modified Schober Test– Potentially useful diagnostically– Unsure of benefit over time (insensitive)

Modified Schober Test

Occiput to Wall Test

Spinal Involvement

• Finger Tip to Floor Distance– Feet at specified distance apart– Measure fingertips to floor– Useful for following patients over time

• Lateral Flexion– Stand with back against the wall and feet at specified

distance apart– Make a mark where the finger tips touch the thigh– Ask the patient to flex laterally and place a second

mark at the maximal extent of the fingertips– Measure the distance between the two marks– Useful for following patients over time

Finger Tip to Floor Distance

Spinal Involvement

• SI Compression Testing

• Cervical Spine– Examine!– Can have Cervical Spine involvement alone– Can result in Atlanto-Axial Instability

Laboratory Investigations

• Evidence of Inflammation– CBC Normochromic normocytic anemia

– Elevated ESR/CRP– Reactive thrombocytosis

• HLA-B27 found in 90-95% of patients with Ank Spond vs 6% of general population

Juvenile Ankylosing Spondylitis

Onset 8 to 14 Sex Ratio M:F 7 to 1 HLA-B27 91 % Systemic symptoms rare Iritis 10 to 27 % Polyarticular 97% Prognosis Probably good

PSORIATIC ARTHRITIS

Case #1

• 50 y.o. man presents to the office with painful, swollen fingers

• Intermittent flares over the last year with limited morning stiffness and slight loss of energy

• Presents with the following findings:

Case #1

Case #1

Case #2

• 48 year old woman originally from Russia, moved to Canada 1 year ago.

• Has complained of persistent arthritis and deformities in hands for years.


Case #2

Case #2

Case #3

• 51 year old man has had pain, stiffness, and progressive deformity in the hands for many years


Case #3

Case #4

• 28 year old man presents with pain and stiffness in both wrists and the left knee

• Also has intermittent swelling of the toes

• Has the following findings:

Case #4

Case #4

Case #5

• 35 year old man presents with low back pain and stiffness which improves with exertion

• He has the following findings:

Case #5

What is the Diagnosis?

• In all of these cases the diagnosis is Psoriatic Arthritis!

• 5 Presentations– DIP Involvement (Case #1)– Arthritis Mutilans (Case #2)– Symmetric Polyarthritis (Case #3)– Oligoarthritis (Case #4)– Spondylitis (Case #5)

What is the Diagnosis?

Confusion

Psoriatic Arthritis is a heterogenous disease which can present in a multitude of ways

Psoriasis/Nail changes/arthritis DIPs and Sausage deformity

Psoriatic Arthritis PsA

• Subchondral bone resorption of the distal interphalangeal joint of the thumb and middle fingers has resulted in the "pencil-in-cup" appearance. A flexion deformity of the distal interphalangeal joint of the small finger is present, and the corresponding joint of the ring finger has fused.

• (Next slide)

Fusion

Pencil in Cup deformity

Who Gets Psoriatic Arthritis?

• Most common age of onset is 30-50 years old

• 1-3% of the population has psoriasis

• 6-42% of people with psoriasis get psoriatic arthritis

• Therefore, it is rare (about 1 in 1000)

History – Initial Presentation

• Typical presentation is a peripheral inflammatory joint disease – usually a mono or oligo arthritis– Knees– Wrists

• May occasionally present with polyarthritis

• Initial presentation of inflammatory spinal disease is rare

History - Progression

• Oligoarticular in 40-50%

• Polyarticular in 30-50%– Like Rheumatoid Arthritis

• Predominant Spinal Disease in 5%– Spinal symptoms usually occur after many

years of peripheral arthritis

• DIP involvement in 5%

• Arthritis Mutilans in 5%

PSORIATIC ARTHRITIS

Possible Indicators of Bad Prognosis

Younger age at onset, including children

Presence of certain HLA antigens:

HLA-B27 correlates with spondylitic involvement

HLA-DR3, DR4 correlates with erosive disease

Extensive skin involvement

Polyarticular involvement

Lack of clinical response to NSAIDs

Association with HIV infection

History - Progression

• Sacroiliac Involvement– Sacroiliitis in 1/3 of patients– Usually asymmetric (unilateral)– May be asymptomatic

• Spinal Involvement– May affect any part of the spine in a random

fashion– Different from ankylosing spondylitis

History – Rheumatologic Review of Systems• Mucocutaneous Involvement

– Psoriatic skin lesions– Psoriatic Nail lesions

• Entheseal Involvement

• Dactylitis

• Ocular Involvement

History - Psoriasis

• Do you have Psoriasis?– Psoriasis present before the onset of joint disease

(70%)– Psoriasis comes with the arthritis (15%)– Psoriasis comes after the arthritis (15%)

Umbilical Psoriasis

Psoriasis Behind the Ear

Psoriasis in the Crease

Psoriasis in the Nails

History - Dactylitis

• Have you ever had a finger or toe swell up on you like a sausage?

• Entire digit is involved compared to “fusiform” swelling around a joint

• Dactylitis – represents inflammation of the flexor tenosynovium – “flexor tenosynovitis”

History - Dactylitis

History – Family History

• Family studies suggest a 50-fold increase in the risk of psoriatic arthritis in 1st degree relatives

• Fathers are twice as likely to transmit the disease

Physical Examination

• Skin and Nail Involvement• Peripheral Joint Involvement• Peripheral Entheseal Involvement• Spinal Involvement

– Modified Schober Test– Occiput to Wall Distance– Cervical Spine ROM– Finger tip to floor distance– Lateral flexion

Peripheral Joint Involvement

• Inflammatory Joint Count– Number of Joints Involved

• Prognostic Importance• Therapeutic Importance

– Pattern of Joints Involved• Diagnostic Importance

– Evidence of Damage– Dactylitis

How to Tell the Difference

Red Flags – When to Call the Rheumatologist• Cervical Spine Instability

– Acute onset neck pain or headache– Weakness or sensory change in extremities– Hyper-reflexia

• Flare of disease activity

Radiology

Reiter’s Syndrome: Diagnostic Criteria

Seronegative asymmetric arthropathy

And at least 1 of the following:

Urethritis or cervicitis

Diarrhea

Inflammatory eye disease

Mucocutaneous diseaseBalanitis, oral ulceration, or keratoderma

Other spondyloarthropathies and rheumatic disease excluded

BACTERIA MOST COMMONLY FOUND TRIGGERING REACTIVE ARTHRITIS

Borrelia burgdorferi

Campylobacter jejuni

Chlamydia trachomatis

Neisseria gonorrhoeae

Salmonella species

Shigella flexneri

Streptococcus pyogenes

Yersinia enterocolitica

Yersinia pseudotuberculosis

Reiter’s SyndromeFrequency Difficult to

define

Male – Female ratio 4 to 1

HLA-B27 90 %

Onset Simultaneous or

over 3 – 4 weeks

Course Self limited

Relapsing

Reiter’s SyndromeClinical Manifestations

Arthritis Oligoarticular, Lower extremities.

Enthesitis Calcaneous, patella.

Urethritis Dysuria more common

30 % urethritis

Conjuntivitis 2/3 at onset

Mucocutaneous

Manifestations Less frequent

Arthritis Conjunctivitis

Cervicitis

Urethritis

Circinate Balanitis. Meatitis, mild balanitis, severe balinitis

• Left, previous photograph demonstrates meatitis and early balanitis. The lesion is erythematous, moistened by the urethral discharge, and, like the later stages, painless.

• Center, A discrete, moist, well-circumscribed lesion is seen on the glans. Such lesions often begin as small vesicles or pustules.

• Right, More advanced lesions are dry, scaly, and painless. In circumcised patients, the lesions on the glans may become crusted and hyperkeratotic, similar to those seen on the skin, or they may remain moist and weeping.

ReA superficial erosions of the tongue

Superficial oral ulcers can be seen in ReA and are typically painless

• ReA has as part of its constellation of symptoms characteristic lesions including keratoderma blennorrhagica characterized by hyperkeratotic skin lesions on soles and palms and genital lesions such as circinate balanitis, an erythematous and painless lesion of the glans penis.

Keratoderma Blenorrhagicum

Pustules ReA KB incipient

Advanced KB

ARTHRITIS AND INFLATORY BOWEL DISEASECrohn’s Disease

Ulcerative Colitis

IBD associated arthritis

Arthritis Peripheral Specially lower extremities

Self limited 4 to 6 weeks

Central SI joints and enthesitis

Frequency 7 to 21 %

No relation between the activity of the Arthritis and the IBD.

In IBD-associated SpA, erythema nodosum can be

observed in Crohn's disease

pyoderma gangrenosum can be associated with ulcerative colitis.

SINDROME DE SAPHOSYNOVITIS

ACNE CONGLOBATA, FULMINANS E HIDRAENITIS SUPURATIVA

PUSTULOSIS PALMO PLANTAR

HYPEROSTOSIS ESTERNO-CLAVICULAR Y ESPINAL

OSTEOMIELITIS ESTERIL MULTIFOCAL RECURRENTE

Management - Overview

• Goals of Treatment– Improve pain– Improve Function– Prevent Long-term Damage– Safely

Management

• NSAIDs– Can be useful in some cases of mono/oligo

arthritis– Useful for enthesitis– Useful for spinal disease

Management: DMARDs

Medication PsoriaticAnkylosing Spondylitis

Hydroxychloroquine (Plaquenil®)

Rarely with little evidence

NO

MethotrexateYES

Rarely with poor efficacy in spinal

disease

Sulfasalazine YES YES

Leflunomide (Arava®)YES NO

Gold YES NO

Steroids YES YES

Management: Biologics

• Biologics Approved for Psoriatic Arthritis and Ankylosing Spondylitis– Etanercept (Enbrel®) – Infliximab (Remicade®)– Adalimumab (Humira®)

• Biggest advance in the treatment of spondyloarthropathies in decades!

Management: Biologics

• Dramatic clinical efficacy with the greatest amount of data to date coming from studies of ankylosing spondylitis and psoriatic arthritis.

• Substantially improve both peripheral and axial arthritis, as well as various other clinical parameters, and has also slowed the progression of joint damage.

SPONDYLOARTHOPATHIES Summary

Absence of rheumatoid factorInvolvement of sacroiliac andspinal jointsPeripheral arthritis(predominantly lower limb)EnthesopathyFamilial clusteringIncreased incidence of HLA-B27Common spectrum of extra-articular features

(predominantly muco-cultaneous)

Health & Medicine

5spondyloarthropaties Seronegative Arthritis