spondyloarthropathy presentation 2

8/12/2019 Spondyloarthropathy Presentation 2

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SeronegativeSpondyloarthropathies

Dr. osama sayed

daifallh


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Back to basics

Axial skeleton Skull

Vertebral column Vertebrae

Sacrum

Coccyx

Ribs

Sternum

Appendicular skeleton Girdles

Extremities

The skeleton


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Back to basics

Diarthrosis (moveable) Majority of articulations

Contiguous bones are covered by cartilage, connectedby ligaments, and have an interposing synovial sac

Synarthrosis (immoveable) Contiguous bones are in direct contact without

cartilage, syovium, or ligaments

Amphiarthrosis(sort of moveable)

Characteristics of both diarthrosis and synarthrosis Contiguous surfaces are either:

Connected by fibrocartiganeous disks (vertebral joint)

Covered by fibrocartilage andpartialsynovium, and attachedby external ligaments (sacroiliac joint)

Articulations


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Back to basics

Enthesis is the site of bony attachment of

Tendon

Ligament

Cartilage

Joint capsule

Fascia

Enthesis


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spondyloarthropathies

Ankylosing spondylitis (the prototype)

Psoriatic arthritis

Reactive arthritis Formerly called Reiters syndrome)

Enteropathic arthritis

Undifferentiated spondyloarthropathy

Comprise these conditions


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y are ese seases c ass etogether?

HLA-B27 association

Enthesitis (both juxtarticular and extrarticular)

Axial skeleton arthritis (generally secondary to

juxtarticular enthesitis) Spondylitis (inflammation of vertebral bodies)

Sacroiliitis (inflammation of sacroiliac joint)

Peripheral arthritis (generally a synovitis)

Asymmetric (cf rheumatoid arthritis)

Extrarticular manifestations (besides enthesitis)

Seronegativity Rheumatoid factor and ANA negative

Well, because they share these characteristics


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Ankylosing spondylitis: 95%

Ethnically matched controls: 8%

Reactive arthritis: 70%

Enteropathic arthritis: 50%

Psoriatic arthritis: 35%

HLA-B27 association


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Inflammation of an enthesis It is the Principal pathogenetic mechanism in

spondyloarthropathy

Pathogenesis

CD8 T cells infiltrate entheses Activated macrophages release cytokines (egTNF)

Fibroblasts synthesize new collagen(cf rhematoid arthritis!!)

New bone formation results

Clinical Axial skeleton arthritis (see later)

Enthesopathy at other sites

Calcaneal spurs at plantar fascia insertion

Spurs at Achilles tendon insertion

Manifests as extrarticular or juxtarticular bony tenderness

Enthesitis


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Arises from enthesitis

Includesspondylitis andsacroiliitis

Spondylitis

CD8 T cells invade the junction of the annulus fibrosis and thevertebral body (an enthesis)

Annulus fibrosis is replaced by bone (syndesmophytosis)

Vertebral bodies assume a square shape, and ultimately a

bamboo spine

Sacroiliitis CD8 T cells invades the subchondral area at the junction of the

bones and the cartilage (an enthesis)

Cartilage on iliac side is replaced by bone, obliterating the jont

space and hardening the joint

Axial skeleton arthritis


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Ankylosing spondylitis


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AS: Characteristic Pathologic Features

Sieper J. Arthritis Res Ther 2009;11:208Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035

Chronic inflammation in:

Axial structures (sacroiliac joint, spine, anterior chest

wall, shoulder and hip)

Possibly large peripheral joints, mainly at the lower limbs

(oligoarthritis)

Entheses (enthesitis)

Bone formation particularly in the axial joints

Inflammation

Disease activity

Structural damage

Syndesmophytes formation


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AS: Signs and Symptoms

Axial manifestations:

Chronic low back pain

With or without buttock pain

Inflammatory characteristics:

Occurs at night (second part)

Sleep disturbance

Morning stiffness

Limited lumbar motion

Onset before age of 40 years

Inflammatory back

pain (IBP) = Characteristic

symptom

MRI sacro-iliac joint

Inflammation

Disease activity
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Inflammatory back pain requires 4 of these 5

criteria (serves as a screening tool for AS)

Young onset (40 years)

Morning stiffness (30 minutes)

Chronic (3 months)

Activity improves the pain (rest does not) and rapide

response to NSAIDS within 24 hrs

Insidious (not acute)

(mnemonic is YMCA-I)

Diffuse lumbar or gluteal, not focal or radicular

Cf focal pain of disk herniation

Inflammatory back pain


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Most striking feature of AS =New bone formation in the

spine with:

Spinal syndesmophytes

Ankylosis

Both can be seen onconventional radiographyBamboo spine and

bilateral sacroiliitis

X-ray showing

syndesmophytes

Even in patients with longer-

standing disease, syndesmophytes

are present in 50% patients and a

smaller percentage will develop

ankylosis

Sieper J. Arthritis Res Ther 2009;11:208

AS: Structural Damage

Structural damage

Syndesmophytes formation
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Peripheral manifestations

Enthesitis Peripheral arthritis Dactylitis

AS: Signs and

Symptoms

50% patients with

enthesitis1

1Cruyssen BV et al. Ann Rheum Dis 2007;66:1072-10772Sidiropoulos PI et al. Rheumatology 2008;47:355-361

Up to 58% patients

ever had arthritis1

Much smaller number

of patients2
http://www.cri-net.com/base_image/viewImage.asp?ID=9D541A30D6


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Why are Dactylitis and Enthesitis Important?

The first abnormality to appear in swollen

joints associated withspondyloarthropathies is an enthesitis2

Likelihood of erosions is higher

for digits with dactylitis thanthose without1

1Brockbank. Ann Rheum Dis 2005;62:188-90;2McGonagle et al. The Lancet 1998;352.


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Restriction of lumbar movement Shobers testmark the patients back at the level of the posterior

iliac spine. Place one finger 5 cm below this mark and a 2ndfinger

10 cm above this mark. Patient is instructed to touch his toes. If

the distance between finegrs increases < 5 cm, lumbar flexion is

limited.

Anterior uveitis (iritis or iridocyclitis) (25%)

Acute eye pain

Increased lacrimation

Photophobia Blurred vision

Aortitis with fibrosis

Aortic insufficiency

Third degree heart block (5%)

Other clinical (besides back pain)


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AS: Extra-articular Manifestations

(EAM)EAM Prevalence in ASPatients (%)Anterior uveitis 30-50

IBD 5-10

Subclinical inflammation of the gut 25-49

Cardiac abnormalitiesConduction disturbances

Aortic insufficiency

1-33

1-10

Psoriasis 10-20

Renal abnormalities 10-35

Lung abnormalities

Airways disease

Interstitial abnormalities

Emphysema

40-88

82

47-65

9-35

Bone abnormalities

Osteoporosis

Osteopenia

11-18

39-59

Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035

Terminal ileitis

Anterior uveitis

Cardiac

abnormalities
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AS: Extra-skeletal Signs and

SymptomsOther common symptoms seen during the early stages of diseaseinclude: Anorexia

Malaise

Low grade fever

Weight loss

Fatigue

1Missaoui B. et al. Ann Readapt Med Phys 2006;49:305-8, 389-391

Linden VD et al. Chapter 10. In: Firestein, Budd, Harris, McInnes, Ruddy and Sergent, eds. KelleysTextbook of Rheumatology: Spondyloarthropathies. 8thed. Saunders Elsevier;2009:p.1176

Fatigue is a frequent complaint

of patients with AS1
http://www.newscientist.com/blog/shortsharpscience/uploaded_images/fatigue-736871.jpg


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Laboratory tests

ESR

CRP

CBC

HLA-B27


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Radiographic and imaging

Sacroiliitis

Whiskering at enthesis (calcaneous,

ischial tuberosities, femoral trochanters)

Squaring of vertebrae

Syndesmophytes

Spinal osteoporosis Hip, shoulder

A k l i d liti


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Radiographic evaluation

Sacroiliacjoints

Grade 0 Normal

Grade 1 Suspicious changes

Grade 2 Minimal abnormalitysmall localized areas with

erosion or sclerosis without alterations in joint width

Grade 3 Unequivocal abnormalitymoderate or advancedsacroiliitis with 1 of the following: erosions,

sclerosis, widening, narrowing, or partial ankylosis

Grade 4 Severe abnormalitytotal ankylosis


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Marginal erosions and new bone formation


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Sacroiliitis


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Ossification of SI joint space


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Bamboo spine


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Enthesopathy of heels


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A k l i d liti


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Low back pain 3 months improved by exercise and notrelieved by rest

Limitation of lumbar spine in sagittal and frontal planes

Chest expansion reduction relative to normal values

corrected for age and sex (costovertebral ankylosis,25%)

Radiographic criteria of sacroiliitis

Bilateral grade 2-4 OR

Unilateral grade 3-4

Ankylosing spondylitis is defined by the presence of either

radiographic criterion PLUS any clinical criterion

Modified New York Diagnostic Criteria


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ASAS Classification Criteria for

Axial SpAIn patients with back pain 3 months and age at onset


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Psoriatic arthritis

Inflammatory polyarthritis associated with

psoriasis

May occur prior to the onset of skin

disease

Usually seronegative

M=F

Prevalence rate 0.1%


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Psoriatic arthritis is an enthesitis

DIP joint disease

Spinal inflammation Dactylitis-sausage finger


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Psoriatic ArthritisClinical Variants

Inflammatory DIP disease

Asymmetic oligoarthritis with large and

small joints

Symmetric polyarthritis

Arthritis mutilans

Spondyloarthropathy

Spondylitis and sacroiliitis


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Psoriatic ArthritisOther Features

Nail pitting

Skin disease

Pitting edema

Inflammatory eye disease


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Radiological features of PsA

Lack of juxta-articular osteopenia

Pencil-in cup change

Ankylosis Periostal reaction

Asymmetric sacroiliitis

Coarse syndesmophytes


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Erosive psoriatic arthritis


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Psoriatic ArthritisTreatment

NSAIDs

Little role for systemic steroids, but IA

steroids can be very helpful

Methotrexate

TNF inhibitors


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Management of PsA

NSAIDs

Methotrexate

Sulphasalazine

Leflunomide

Azathioprine

Cyclosporine

Anti TNFtherapies

Intra articular injections of corticosteroids


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Methotrexate

Efficacy in PsA 1stdemonstrated in 1964.

Placebo controlled study of 21 patients

with active skin disease and peripheral

arthritisobservation 3 months.

Improvement in skin and joint involvement.


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Sulfasalazine

5 controlled studies

221 patients treated with 2 g/day over 36

week course. Improvement in tender and

swollen joints.

Its actions appears to be confined to

peripheral arthritis with no benefit in axial

disease

Rare reports of cutaneous improvement.


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Leflunomide (ARAVA)

A selective pyrimidine synthesis inhibitor

that targets activated T cells lacking a

salvage pathway.

Randomised double blind, placebo

controlled study in 188 patients with active

PsA and active rash.

After 6 months 59% met primary efficacy.Compared with 30% of placebo.


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Other options ?

Gold

Cyclosporine A

Azathioprine and 6-mercaptopurine

Antimalarial agents

Colchicine


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InfliximabEtanercept


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Mouse

(Binding site for TNF)

Human (IgG1)

Fc region of

human IgG1

Extracellular domain of

human p75 TNF receptor

CH3 CH2

SS

SS

S

S

S

S

S

S

SSS

S

p

Adalimumab


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Et t i P A


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Stratification (N -205 PsA, active dis.)

- Etanercept 25 mg twice weekly (n=101)

as either Etanercept (n=59) or

Etanercept+MTX (n=42)

- Placebo (n=104) or either placebo alone

(n=61) or Placebo +MTX (n=43)

Gottlieb A. Ann Rheum Dis 2002;61(Suppl1)

Etanercept in PsA

A phase III clinical trial

P t f ti t


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0

10

20

30

40

50

60

1 3 6

Etanercept

Placebo

Months

Gottlieb A. Ann Rheum Dis 2002;61(Suppl1

Percentage of patients

achieving ACR 20


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P valueEtanercept

n= 101

Placebo

n=104

Measure


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Adalimumab (Humira)

Fully human anti-TNF monoclonal

antibody, SC, 40 mg e.o.w

315 patients with PsA

At week 12, ACR 20 in 58% of the

adalimumab-treated patients vs 14% of

the placebo-treated patients .

59% achieved a 75% PASI improvement

response at 24 weeks


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T cell activators blocking

Alefacept (Amevive)

Fully human fusion protein binds CD2 on

memory T cells and blocks interaction with

LFA-3 on the antigen presenting cells.

Efalizumab (Raptiva)

Humanised antibody to the CD11 subunitof LFA1

PsA Treatment Guidelines


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Establish Diagnosis of Psoriatic Arthritis

Reassess Response to

Therapy and Toxicity

EducationPhysiotherapyAnalgesia

NSAID (continous)

Biologics(anti-TNF)

+/- Corticosteroid inj

Axial DiseasePeripheral

Arthritis

Skin &

Nail

Disease

Dactylitis Enthesitis


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Mild PsASevere and moderate PsA

(oliygo-polyarthritis?).

Poor prognosis

PsA

Respond NSAIDs and/or

IA steroids

Early DMARD

(MTX,SZP, LEF)

Adequate therapeutic

trial of 2 DMARD

Anti TNF

Respond


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Reactive arthritis


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Reactive arthritis

In 1916, Hans Reiterreported Reiters syndrome:a triad of nongonococcal urethritis, conjunctivitis,

and arthritis that occurred in a young German

officer following an episode of bloody dysentery

Subseqently, more cases were reported following

enteric infections OR venereally acquired

genitourinary infections.

In 1967, the term reactive arthritiswas applied tosimilar cases following Yersiniagastroenteritis

The two terms should be considered synonomous

The term reactive arthritisis increasingly preferred

Interesting historical backdrop

Reactive arthritis


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Reactive arthritis

Clinical syndrome triggered by specific etiologic

agents in a genetically susceptible host

Follows 1-4 weeks after a

Urogenital infection (affects principally men) Usually C. trachomatis

Enteric infection (affects both genddrs equally)

Salmonella

Shigella

Campylobacter

Yersinia

Pathogenesis

Reactive arthritis


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Reactive arthritis

Peripheral arthritis Asymmetric additive oligoarthritis (usually)

Synovitis

Warm

Edematous

Tender

Pain with active or passive movement

Usually lower extremity joints (knee, ankle, subtalar)

Conjunctivitis

Clinical

Reactive arthritis


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Reactive arthritis

Nongonococcal urethritis Occurs in postenteric or postvenereal disease

When it occurs in postvenereal disease, C. trachomatisisoften the etiology

When present, is usally the first symptom In men

Mild dysuria

Mucopurulent urethral discharge

May present as prostatitis or epididymitis

In women Dysuria

Purulent vaginitis or cervicitis with vaginal discharge

Asymptomatic urethritis often features sterile pyuria

Clinical

Reactive arthritis


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Reactive arthritis

Keratoderma blenorrhagica A papulosquamous skin rash

Comprises vesicles that become hyperkeratotic,forming crusts before disappearing Palms/soles

Penis (causing circinate balanitis

Oral ulcers (ususally shallow and painless)

Inflammatory back pain (50% of patients)

Enthesitis (40%) Dactylitis (40%)

Anterior uveitis (20% of patients)

Clinical (continued)

Reactive arthritis


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Reactive arthritisKeratoderma blenorrhagica

Reactive arthritis


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Synovial fluid analysis Pleocytosis (5 000 to 50 000 WBC/mcL) with

polymorphonuclear cell predominance

Protein levels

Glucose normal Cf reduced glucose level in true septic arthritis

Gram stain and culture are sterile

Urethral or cervical smears in patients with

clinical urethritis C. trachomatis

N. gonorrhoeae

Evaluation

Enteropathic Arthritis


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Enteropathic Arthritis

Affects 10-20% of patients with inflammatory

bowel disease (IBD)

Peripheral arthritis affects 10-20% of IBD

patients Generally affects knees, ankles, and feet

Always indicates active IBD

Radiographic axial arthritis affects 10% of IBDpatients

Frequently asymptomatic

Independent of bowel inflammation

Clinical



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together?

Physical therapy and exercise Nonsteroidal antiinflammatory agents

Indamethacin

Disease modifying anti-rheumatic drugs(DMARDs) Methotrexate: inhibits recruitment of CD4 and CD8 T

cells

Tumor necrosis factor antagonists Infliximab: a monoclonal antibody that binds to TNF and

inhibits binding of TNF to its receptor

Etanercept: similar emchanism to infliximab

Treatment

Key Actions Attributed to TNFa


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Key Actions Attributed to TNFa

InfliximabEtanercept


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Mouse

(Binding site for TNF)

Human (IgG1)

Fc region of

human IgG1

Extracellular domain of

human p75 TNF receptor

CH3 CH2

SS

SS

S

S

S

S

S

S

SSS

S

Adalimumab


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S ff


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Side effects

Good tolerability

The most frequent was injection site reactionin37%

Infection in 35% and headache 17 %

Post marketing : severe infections including TB

and fatalities, demyelinative disorders,lymphoma, rare cases of pancytopenia includingaplastic anemia,vasculitis, drug induced lupus


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REMICADE(infliximab)


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( )

Safety

Hypersensitivity reactionsSepsis, pneumocystosis, histoplasmosis,and listeriosis have been reported

Rare cases of lymphoma, demyelinatingdiseases and drug induced lupus

Increased incidence of TB

spondyloarthropathy presentation 2

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