RHEUMATOID ARTHRITIS &

SERO-NEGATIVE ARTHRITIS
Dr.Hussein Alemeamar
MBChB, MSc, MRCP(UK)

Topics
Rheumatoid Arthritis
spondyloarthropathies

RA - Prevalence
most common persistent inflammatory arthritis, occurring throughout the
world and in all ethnic groups

RA - Pathophysiology
complex interaction between genes and environment, leading to a
breakdown of immune tolerance and synovial inflammation in a
characteristic symmetric pattern

RA - Clinical Features
- pain
- Joint swelling
- Morning Stiffness

Mainly small joint

of the hands, feet
& wrists

Symmetrical

sparing
of DIP
joints

May be large joints

and extra-articular
manifestations

RA - Clinical Features
Clinical course

5-10%

15%

75-80%

Rare

RA - Clinical Features
Muscle wasting

RA - Clinical Features

Ulnar deviation

Swan neck deformity

RA - Clinical Features

Swan neck deformity

Z chape thumb

RA - Clinical Features
Active

Inactive
VS

Morning stiffness
erythema
tenderness
high ESR &CRP

None of those Fx
only the deformity

RA - Clinical Features

RA - Clinical Features

RA - Clinical Features

Rheumatoid nodules
Rheumatoid nodules occur in up to 30% of patients, and are
found principally on the extensor surface of the forearm and
over pressure areas throughout the skin. Nodules are not
specific for RA but are useful in diagnosis and prognosis,
correlating with seropositivity, disease activity, and progression.

RA - Clinical Features
Scleritis

Episcleritis
VS

Painful

Painless

What are the causes of

anaemia in Rh.A.?
1- Anaemia of chronic disease
2- Pernicious anaemia (associated autoimmune disorders)
3- Rh A> CKD > aneamia
4- GI blood loss (NSAIDs) > IDA
5- Folate def (methotrexate)

RA - Clinical Features
Association of splenomegaly and neutropenia in typically
rather destructive RA. Systemic disease, hepatomegaly,
and lymphadenopathy are also common, and the
occurrence of RA in relatives is higher than expected. In
uncomplicated cases, treatment should be conservative,
splenectomy remaining controversial and often only
transient in effect.

RA - Investigations
What is the Rheumatoid Factor (RF)?
Auto Ab, IgM against IgG (Ab against Ab)
If -ve --> can't rule out Rh A
If +ve--> Rh A and others (SLE, sys
sclerosis, infections ..etc) even in normal
people

Available
Must do in
all form of
arthritis

What is the Anti-cerullinated prot Ab (ACPA)?

Auto Ab, against cerul. prot.
Clinically important--> Anti cyclic citru
prot.(anti CCP)
If +ve --> Rh A (70% sensitivity and highly
specific)
It is positive in many patients before the
clinical onset of the disease

Its important for early

Dx --> early Rx -->
prevent Cx

RA - Investigations

RA - Treatment
DMARDs

Corticosteroids

Biological

Others

RA - Treatment

RA - Rx:DMARDs

Methotrexate

RA - Treatment
Corticosteroids

SE

high dose of oral prednisolone initially (60 mg daily) and to reduce and stop this gradually
over a period of 3 months
low dose prednisolone (510 mg daily for 624 months)
intramuscular injections of methylprednisolone or triamcinolone every 68
weeks (also for flare up)

Intra articular corticosteroids are primarily indicated when there are one or two
problem joints with persistent synovitis despite good general control of the
disease

RA - Treatment
Biological

Costly
Against molecules regulating the immune response
UK recommendations are that biological therapy should be
initiated only in active RA (DAS28 > 5.1; p. 1100) when an
adequate trial of at least two other DMARDs (including
methotrexate) has failed

RA - Treatment

Anti-TNF- therapy
Common reactions include headache, nausea, and injectionsite reactions. Serious bacterial infections have been
reported, and patients with active infection should have their
treatment stopped. Patients at risk of recurrent infection
should not use these drugs (e.g. in-dwelling urinary catheter,
immunodeficiency states). Other reported side-effects
include demyelination, worsening of heart failure, lupus-like
syndromes, and bone marrow dyscrasias.

Reactivation of tuberculosis has been reported mainly in infliximab

and adalimumab patient > Patients should be assessed for TB risk

RA - Treatment

RA - Treatment

The spondyloarthropathies
The seronegative spondyloarthropathies are classically characterised by the
following:
Sacroiliitis & inflammatory back pain;
enthesitis.
There is a striking association with carriage of the HLA-B27 allele,
particularly for ankylosing spondylitis (> 95%) and reactive arthritis (90%),
These diseases may also be accompanied by:
asymmetric peripheral arthritis;
extra-articular disease;
anterior uveitis.
The group is made up of several conditions that often overlap. These are:
ankylosing spondylitis;
juvenile enthesitis-related arthritis;
psoriatic arthritis;
reactive arthropathy;
enteropathic arthritis;
undifferentiated spondylitis.

Ankylosing Spondylitis (AS)

Ankylosing spondylitis

ages of 20 and 30, with a

male preponderance of about 3 : 1. In Europe,
more than 90% are HLAB27positive.
The overall prevalence is less than 0.5% in most
populations.
Over 75% of patients are able to remain in employment
and enjoy a good quality of life.

Ankylosing Spondylitis
radiological evidence: sacroilitis

Clinical features (Hx & physical examination

AS - History
symptomatic sacroilitis (persistent back pain and
stiffness for > 3 months) associated with morning
stiffness and improvement on exercise or worsening with
rest

AS - Physical Examination

protuberant abdomen
severe kyphosis with ? posture
decreased cervical movement
decreased spinal movement
Increased occiput to wall distance
decreased chest expansion
Schober's test > assess spinal movement

Bath Ankylosing Spondylitis Disease

Activity Index (BASDAI)

AS - Dx criteria

AS - Systemic manifestations
7 "A's"
Atlanto-axial subluxation
Anterior uveitis
Apical lung fibrosis
Aortic incompetence
AV conduction defect
Amyloidosis
Achilles tendonitis

AS - Systemic manifestations
Anterior uveitis
AV block > pacemaker

Aortic regurgitation

AS - Systemic manifestations

apical fibrosis

Atlanto-axial subluxation

AS - Systemic manifestations

Achilles tendonitis

Amyloidosis

Is AS a genetic disease?
HLA-B27 Ag is present in 95% of Caucasian
patients with AS.
It is present in 8% of healthy adults.
The risk of transferring the HLA-B27 Ag to
offspring is 50% and these children have 1:3 risk
of developing the disease.
testing for HLA-B27 is unnecessary.

AS - Ix
Mainly radiological (X-ray, MRI)
Rh F > -ve, ANA > -ve
HLA-B27 (as discussed above)
Inflam markers (ESR & CRP) are only +ve in about 50% of
cases

AS - X-ray
Sacroilitis >inflammation of the sacroiliac joints

space
on X-ray

normal sacroiliac joint

on X-ray

AS - X-ray

Xray of the sacroiliac joints showing joint

space narrowing, erosive change and
indistinct margins, due to sacroiliitis.

AS - X-ray (late stage)

AS - X-ray (late stage)

syndesmophytes
syndesmophytes

AS - MRI
Magnetic resonance imaging (MRI) is useful in
assessing early cartilage abnormalities and bone
marrow oedema.
Detect early disease before the patient
develop X-ray changes

AS - MRI

Twenty-one-year-old man with duration of AS 3 years; with lumbar IBP for 6 months.

Bochkova A G et al. Rheumatology 2010;49:749-755

The Author 2010. Published by Oxford University Press on behalf of the British Society for
Rheumatology. All rights reserved. For Permissions, please email:
journals.permissions@oxfordjournals.org

Twenty-one-year-old man
with duration of AS 3 years.
(A) T2-FS: sagittal image of
lumbar spine, oedema of
spinous processes TX-TXITXII-LI-LII (long arrows) and
supraspinatus ligament
between TXI-LI (short arrow)
and Schmorls hernies. (B)
Axial T2-FS image. L1: bone
marrow oedema of spinous
process (arrow).

AS - Mx

Genetic counselling
PhysioRx
Occupational Rx
Analgesia
NSAIDs
Corticosteroids: only pulse i.v. steroids are
occasionally used, no role for oral steroids
DMARDs: methotrexate & sulphasalazine have
some effects on peripheral disease but not on
the spine
Biological Rx: anti-TNF alpha Rx adalimumab &
etanercept is approved by NICE to Rx AS

Psoriatic Arthropathy (PSA)

What is the link between

PSA & psoriasis
PSA can even occur with minimal skin changes
In 20%, PSA precedes the onset of the skin changes
Only up to 10% of patients with psoriasis develop PSA

Psoriatic Arthropathy (PSA)

Arthritis

Enthesitis

Dactylitis

Inflam. at the site of

insertion of ligaments,
tendons, joint capsule,
or fascia to bone

sausage-like swelling
of the finger or toe,
due to inflam. of
tendon sheet and soft
tissues.

PSA - Patterns
The 5 clinical patterns of psoriatic arthritis are:
distal, involving the distal interphalangeal joints (DIP);
asymmetric oligoarthritis;
symmetrical polyarthritis, indistinguishable from RA;
spondylarthropathy.
Arthritis mutilans is a classic but uncommon manifestation
of psoriatic arthritis. Bone resorption leads to collapse of the
soft tissue in the digits, creating telescoping fingers. This can
also be seen in severe RA.

PSA - Arthritis mutilans

PSA - Nail changes

These lesions occur in 90% of patients with psoriatic
arthritis (PsA) and in 40% of patients with psoriasis alone
Nail pitting
onycholysis
transverse ridging
subangual hyperkeratosis

PSA - Systemic
manifestations

Gout
Apical pulmonary fibrosis
Aortic regurgitation
Uveitis

PSA vs RhA

PSA - Rx

Patient education
PhysioRx
Occupational Rx
Analgesia
NSAIDs (in some patients NSAIDs may worsen the
psoriasis)
Corticosteroids: only intra-articular injection for single
troublesome joints. Avoid systemic steroids, since skin
disease may flare-up on steroids withdrawal.
DMARDs: methotrexate, sulphasalazine & cyclosporin are
effective on skin & peripheral disease but not on the spine
Biological Rx: anti-TNF alpha Rx infliximab, adalimumab
and etanercept is approved by NICE to Rx PSA (effective
for skin and joints)

Reactive arthropathy
Arthritis

urethritis/cervicitis (sexually transmitted reactive

arthritisSARA) or diarrhoea (gut-associated
reactive arthritisGARA) are present

The onset of reactive arthritis may be acute, with fever,

weight loss, and diffuse polyarticular involvement. More
often, however, there is limited joint synovitis and a lowgrade, or absent fever.

Reactive arthropathy
Mucocutaneous features include painless circinate balanitis of
the glans penis, and pustular psoriasis of the palms or feet
(keratoderma blennorrhagica); these can be associated with a
more severe outcome.

Reactive arthropathy
Conjunctivitis is observed early. Uveitis is less frequent early in disease

Recurrent or repeated infections do not always lead to a recurrence of

arthritis

Reactive arthropathy
Ix

elevated ESR and CRP

source of infection

Rx
There is no specific cure
NSAIDs and local corticosteroid injections are the mainstay of
therapeutic intervention
If symptoms persist longer than 6 months and there is clinical
evidence of ongoing synovitis and joint destruction then a diseasemodifying agent, such as sulfasalazine, MTX, or azathioprine, should
be considered.
Px
majority of patients are in complete remission at the end of 2 years,
most within 6 months

Enteric arthropathy
The arthropathies of ulcerative colitis and Crohn's disease have many
similarities, and the combination of peripheral and axial skeletal disease,
enthesopathies, mucocutaneous, and ocular disease fits neatly into the
diagnostic realm of the spondylarthropathies.
The exact pathology is unknown

Peripheral > related to disease activity and improve with Rx of IBD

Axial > NOT related to disease activity and will NOT improve with Rx of IBD

Thank you