Enthesial lesions and spondylarthropathies: clinical and ... · Enthesial lesions and...

Enthesial lesions and spondylarthropathies:

clinical and paleopathological insights

Carina MarquesCentro de Investigação em Antropologia e SaúdeCe t o de est gação e t opo og a e SaúdeDepartment of Anthropology, University of [email protected]

Workshop in Musculoskeletal Stress Markers (MSM): limitations and

achievements in the reconstructionof past activity patterns

ConceptSpondylarthropathies

Broad group of inflammatory chronic arthropathies or erosive arthropathies

Spondylarthropathy (SpA)

Concept: that comprises different clinical entities

Share common etiological pathophysiological and clinical featuresShare common etiological, pathophysiological and clinical features


According to the European Spondylarthropathy Study Group (1991)

•Axial inflammation [sacroiliitis, spondylitis] Ankylosing spondylitis (AS) Reactive arthritis (ReA)Axial inflammation [sacroiliitis, spondylitis]

• Peripheral arthritis

[Inflammatory chronic disease of the spine ]( )

[Arthritis consequence of extra-articular infection -generally genitourinary and/or gastrointestinal]

• Enthesitis

• Eye and mucocutaneous lesions

Psoriatic arthritis (PsA)

[Arthritis associated with psoriasis] Undifferentiated )

y

• Genetic features

spondyloarthritis (uSpA)[Clinical spectrum does not correspond to any other entity]

• Association with HLA-B27 antigen

Enteropathic arthritis (EA)

[Arthritis connected with inflammatory bowel disease ]

Juvenile SpA

[Arthritis connected with inflammatory bowel disease ]

SAPHO- ?


Between entities: overlap of symptoms and signs

Each entity: heterogeneity of disease phenotypey g y p yp

EpidemiologySpondylarthropathies

General prevalence: 0,5% - 2%p

Prevalence Sex Age

Ankylosing spondylitis (AS) 0 2-1 2% M>F 20-30Ankylosing spondylitis (AS) 0,2 1,2% M>F 20 30

Reactive arthritis (ReA) 0,1% M>F 20-35

Psoriatic arthritis (PsA) 0,1-1% M=F 40-50

Enteropathic arthritis (EA) 0,2% M=F 20-30

Undifferentiated spondyloarthritis (uSpA) 0,7-2% F>M 20-30

Haida Indians, Canada: 4.2% ASquen

cy

Haida Indians, Canada: 4.2% AS

Navajo (USA), Pawaia Papua New Guinea,

Alaska Natives Chukotka RussiaHLA-

B27

freq

Alaska Natives, Chukotka Russia

High

H

EtiologySpondylarthropathies

Interaction

■ Immune systemHLA-B27 allele

E i t l ti li

HLA B27 allele

Mechanical stress

■ Environmental stimuli Bacterial pathogens

Mechanical stress

PathologySpondylarthropathies

The abnormal inflammatory response characterizes these conditions:The abnormal inflammatory response characterizes these conditions:

Enthesitis and synovitis are the fundamental pathological characteristics in SpA

The inflammation occurs primarily at the enthesis or at the synovium?

Target of inflammation: hypothesisSpondylarthropathies

I- Primarily enthesial disease

• Postulated during the 70’s Ball and co-workers: First description of inflammation at the enthesis on SpA

• Reviewed by Fourier et al. (2004): “entheseal territory” - Broaden the concept of “entheses” to include the

amphiarthroses and diartho-amphiarthroses

main and initial target of the disease process in SpAmain and initial target of the disease process in SpA

• McGonagle & Benjamin research group: “enthesis organ”

Primary event: Enthesitis (fibrocartilaginous enthesis)

Secondary spread of inflammation to the synovium

Spondylarthropathies Target of inflammation: hypothesis

II The synoviumII- The synovium

O h li f h i fl f h j i b l i d b h i i l • Other lines of research : inflammatory process of the joints cannot be explained by enthesitis alone.

[François et al., 2000; François et al., 2001; Lories et al., 2004; Helliwell & Porter, 2007]

III - The bone

• Other lines of research : crucial role of bone marrow inflammation, as initial process in SpA. Autoimmunity is at the core of this proposal

[Jacques et al., 2008]

Pathological featuresSpondylarthropathies

Key features:

Enthesis [Fibrocartilaginous] -- Synovial joints -- Cartilaginous joints[ ] y j g j

• Articular

• Extra-articular

Distinctive characteristic Erosions New bone

formationAnkylosis

SKELETON: Axial and appendicular

Pattern of distributionSpondylarthropathies

AXIAL ARTICULAR LESIONS

• Sacroiliac (SI)• Vertebral body • Zygapophyseal Zygapophyseal • Costovertebral

• Pubic symphysis

M b i t l• Manubriosternal

• Acromioclavicular

• Sternocostoclavicular

APPENDICULAR

• Hands and feet• Shoulder• Hip• Knee

Paleopathological featuresSpondylarthropathies

• Sacroiliac Joint (SI)

ISCMB, SI Joint

Skn.

º118

3.

ISCMB. SI Joint

Spondylarthropathies

C l t b l b d

Paleopathological features

• Column: vertebral body

Syndesmophytes: thin, marginal, vertical growths - Inflammation ony p y g g

the insertion of the outer fibers of the anulus fibrosus and short

fibers of the anterior longitudinal ligament. [Entesophytes]

ebra

e

From: Freemont (2002) pg. 5 - Syndesmophyte formation.

hora

cic ve

rte

ISCM

B. T

h


C l t b l b d


Parasyndesmophytes (paramarginal ossification, paravertebral ossification)

B lk h i l ifi i f h l li f h

• Column: vertebral body

Bulky growths, non marginal - ossification of the structural ligaments of the

spine and of the insertion on the circumferential area the body.

SpA: Asymmetrical, aleatory

ISCMB. Thoracic vertebraeISCMB,. Thoracic vertebrae


C l t i i


• Column: posterior region

tebr

aeTh

orac

ic ve

rtIS

CMB.

T

Lesions• Zygapophyseal joint• Costovertebral joint• Spinous process

Spondylarthropathies Paleopathological features

ISCMB.Bamboo spine


A di l k l t i h l j i t • Appendicular skeleton: peripheral joints

sal

imal

met

atar

s

nxl

ISCM

B. P

roxi

SCM

B. P

halan

eal jo

int

IS

nter

phala

nge

ISCM

B. I


A di l k l t• Appendicular skeleton

Scap

ula

ISCMB. Humerus

ISCM

B. S

ISCMB. Knee Joint

ISCMB.Radius

Pattern of distributionSpondylarthropathies

AXIAL ARTICULAR LESIONS CLASSIC ENTHESES

• Iliac crests• Ischial tuberosities • Vertebral spinous processesVertebral spinous processes• Calcaneus [Achilles tendon and plantar fascia]

APPENDICULAR

• Ligaments of hand and feet • Patella • Tibial tubercle Tibial tubercle • Greater lesser throchanters• Shoulder

H meral epicond les• Humeral epicondyles

•Ulna (olecranon)

Entheses Spondylarthropathies

In SpA , the lesions at entheses are important features

The scrutiny of these conditions should be performed when analyzing entesophytes

on the research of human activity patterns. y p

How attainable is to identify SpA in paleopathology ?

Work hypothesisSpondylarthropathies

Identified Skeletal Collection Museu Bocage

Museu Nacional de História Natural, Lisboa

Hypothesis: Methodological impact on the assessment of spondylarthropathies in past populationsHypothesis: Methodological impact on the assessment of spondylarthropathies in past populations

Based on previous paleopathology data

• Considered rare

• Variation of the diagnostic criteria used

• Scarce population approach to SpA

• Existent studies present accentuated range of disease prevalence

Sample Spondylarthropathies

Identified Skeletal Collection Museu Bocage

Museu Nacional de História Natural LisboaMuseu Nacional de História Natural, Lisboa

N= 573 adults [ Age range: 20 98 years old]N= 573 adults [ Age range: 20-98 years old]

N= 314 ♀ [55%]

N= 259 ♂ [45%]

Biographical data

N= 259 ♂ [45%]

Escola Politécnica, início séc. XX. ©Câmara Municipal de Lisboa

Biographical data

• Sex

• Chronology: 19th- 20th centuries• Age at death

• Year and cause of death

• Place of birth

• Occupation

MethodologySpondylarthropathies

Lesions analysis

• Macroscopic observation

Methodological Test

• Diagnostic criteria described on the works of: • Diagnostic criteria described on the works of:

•Rothschild (2002), Rothschild et al. (1999), Rothschild e Martin (1993), Rothschild e Woods (1991) EqualRothschild e Woods (1991)

• Martin-Dupont (2005)

R W ld (1995) R t l (1987)

Equal• Sample • Observer• Observation parameters• Rogers e Waldron (1995), Rogers et al. (1987) Observation parameters

Results & DiscussionSpondylarthropathies

9,9%10,7%

1,8%

n= 51 n= 55 5,1%

n= 263,7%

19 %

Syndesmophytes[N 514]

Paravertebral[N 514]

Lesion peripheral joints

Fusionperipheral joints

Zygapophysis[N 514]

Sacroiliac[N 496]

1,8%n= 9

n= 19 1,2%n= 6

[N=514] [N=514] peripheral joints[N=510]

peripheral joints[N=510]

[N=514][N=496]


21 [41,2%]

18 [32,7%]

45

50

55

Sem associaçãoNo association [isolated lesion]Nº In

divid

uals

p< 0,0535

40

Sem associação

Com associação

No association [isolated lesion]

With association [association with at least one other

SpA feature]

N

p> 0,05

37 [67 3%]

6 [23,1%]

20

25

30p> 0,05

30 [58,8%]

37 [67,3%]

20 [76,9%]16 [84,2%]2 [22,2%]

3 [15,8%]

10

15

7 [77,8%]2 [33,3%]

4 [66,7%]

0

5

Sacro-ilíaca Apófises vertebrais Sindesmófitos Paravertebral Lesões articulações periféricas

Fusões articulações periféricas

Sacroiliac Zygapophysis Syndesmophytes Paravertebral Lesion peripheral joints

Fusionperipheral joints


This results confirmed that:

• The most “typical” and complete pattern

was infrequent

ISCMB.


11,7%

6,8%

4,9%

10 7%

15,6%

10,7%

3,9%

Rogers e Col Martin-Dupont Rothschild e Col

n= 80n= 55n= 20

A B CRogers e Col. Martin Dupont(2005)

Rothschild e Col.A B C


Clinical Report Lesion Clinical diagnosis

Erb et al. ( 2005)Braun & Sieper (1996)

• Sacroiliitis Lupus, sarcoidosis, infectious diseaseBraun & Sieper (1996)

Hoshino et al. (2006) • Sacroiliitis Acute myeloid leukemia

Rombauts et al (2000) • Zygapophyseal ankylosis Septic ArthritisRombauts et al. (2000) • Zygapophyseal ankylosis Septic Arthritis

Van Offel et al. (1995) • Sacroiliac ankylosis, zygapophysealankylosis (intra-articular) erosive arthritis

Ochronosisankylosis (intra articular), erosive arthritiswith bone formation on hand and feet

Canhão et al. (1996) • Bambu spine, sacroliac andzygapophyseal ankylosis, hand and feet

Ochronosisyg p p y y ,

arthritis

Fiske et al. (1995) • Bambu spine, sacroliac ankylosis Paralisys secundary to amyotrophic( ) p y y y y plateral sclerosis

Additionally Calcium pyrophosphate deposition disease (CPDD) is clinically evoked as a differential diagnosis


Sample by the method of Rogers & colN= 20Mean age at death= 75 years old

Entesopathy % (N=20)

Mean age at death= 75 years old

Entesopathy % (N=20)

Iliac crests 58%

Ischial tuberosities 44%

Calcaneus [Achilles tendon and plantar fascia] 44%

Patella 42 %

Tibia [anterior tuberosity] 21%

Femur [greater and lesser throchanters] 42%

Humeral head 47%Humeral head 47%

Humeral lateral and medial epicondyles 15%

Ulna [olecranon] 35%


ISCMB. Calcaneus

ISCMB. Iliac crest

ISCMB. Calcaneus


ISCMB. UlnaISCMB.Humeral head

Cl l D


Clinical Data

• Reduced assessment of occurrence of peripheral entheses - under diagnosed

• Generally co-exists with other clinical manifestations of SpA, but isolated occurrence was reported by D’Agostino & Olivieri (2006): 14% of individuals with juvenile onset disease and 9% reported by D Agostino & Olivieri (2006): 14% of individuals with juvenile-onset disease and 9% with late-onset

Peripheral Enthesitis

• Peripheral enthesitis: observed in all forms of SpA and all phases (D’Agostino & Olivieri, 2006)

D’Agostino & Olivieri (2006)

Turan et al. (2009)

Ankylosing spondylitis (AS) 25-58% 78.3%• Entesopathy of the calcaneus:

Reactive arthritis (ReA) 33–58% 93%

Psoriatic arthritis (PsA) 20% -

one of the most frequent and early sign

Enteropathic arthritis (EA) 10% -

PsA+ EA+ USpA 82.4%

ConclusionSpondylarthropathies

Even if SpA diagnosis is problematic - methodological controversy

E h f h i d l i Each of the mentioned lesions

• Sacroiliac or zygapophyseal joints: erosion/ new bone formation or intra-

articular ankylosisRelevant Signs

articular ankylosis

• Syndesmophytes To be considered on the

evaluation of entesophytes• Presence of paramarginal (paravertebral) ossifications

• Erosive lesions with bone proliferation or intra-articular ankylosis on the

evaluation of entesophytes

as activity marker

peripheral joints


• Methodological impact on the assessment of SpA : limits population comparison

without taking into consideration the diagnostic criteria applied

• Further research on the variability of the morphology of lesion is required

• Improvement of differential diagnosis

• Enthesitis is key feature of SpA: although the more distinctive are the ones of the

axial skeletonaxial skeleton

• The recognition of the SpA is important on the analysis of markers of activityThe recognition of the SpA is important on the analysis of markers of activity


Acknowledgments

Fundação para a Ciência e a Tecnologia

Museu Bocageuseu ocage

CIAS

Eugénia Cunhag

Don Ortner

Vítor Matos

Ana Luísa Santos

Cláudia Umbelino

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