SERONEGATIVE

SPONDYLOARTHROPAT
HIES
Dr. Mukhtar MD, Family medicine
Medical Director And Associate Dean
 Introduction
• The Seronegative Spondyloarthropathies are a
group of overlapping disorders that share certain
clinical features and genetic associations.
They include:
• Ankylosing spondylitis
• Axial spondyloarthritis
• Reactive arthritis (Reiter’s syndrome)
• Psoriatic arthritis
• Arthropathy associated with inflammatory bowel
disease.
• The synovitis is non-specific and is often indistinguishable from
RA.
• However, the distinctive feature of this group of diseases is the
marked degree of extrasynovial inflammation, especially of
the enthesis but also of the joint capsule, periosteum,
cartilage and subchondral bone.
• There is association with carriage of the HLA-B27 allele,
particularly for ankylosing spondylitis (> 95%) and reactive
arthritis (90%), and especially associated with sacroiliitis,
uveitis or balanitis.
• Understanding of the cause is incomplete but an
aberrant response to infection is thought to be
involved in genetically predisposed individuals.
• In some situations, a triggering organism can be
identified, as in reactive arthritis following bacterial
dysentery or chlamydial urethritis, but in others the
environmental trigger remains obscure.
• Familial clustering is associated.
Ankylosing spondylitis (AS)
 Contents
• Introduction
• Epidemiology
• Genetics
• Presentation
• Examination
• Diagnosis
• Associated diseases
• Differential diagnosis
• Investigations
• Management
• Prevention
• Complications
• Prognosis
 Introduction
• Ankylosing Spondylitis (AS) is an inflammatory
disorder of unknown cause that primarily affects the
axial skeleton, peripheral joints and extra- articular
structures which can progress to bony fusion of the
spine.
• Marie-Strumpell’s Disease/Bechterew Disease.
 Epidemiology
• Prevalence is 0.1-2% of the general population, with
the highest prevalence in northern European
countries and the lowest in people of Afro-Caribbean
descent.
• Peak onset is between 20-30 years of age.
• Male: female ratio is 3:1. Women tend to have milder
or subclinical disease.
• Many patients with mild disease may remain
undiagnosed.
 Genetics
• There is a strong familial tendency with >90% of the
risk of disease determined genetically.
• A strong association with HLA-B27 exists, particularly
in white western European populations.
Approximately 1-2% of all people who are positive for
HLA-B27 develop AS.
• This increases to 15-20% if they also have an affected
first-degree relative. However, despite much study, it
is not clear how the association with HLA-B27
determines disease susceptibility.
 Genetics
• In AS, the major histocompatibility complex (MHC) -
mediates the actions of leukocytes - accounts for
nearly half of the disease susceptibility.
• Other associated genetic factors include HLA-B60 and
HLA-B39 (in HLA-B27-negative patients).
 Pathophysiology
• Ankylosing spondylitis is thought to arise from ill-
defined interaction between environmental
pathogens and the host immune system in
genetically susceptible individuals.
• Increased faecal carriage of Klebsiella aerogenes
occurs in patients with established AS and may
relate to exacerbation of both joint and eye
disease.
• Alterations in the human gut microbial environment
lead to increased levels of circulating cytokines such as
IL-23 that can activate enthesial or synovial T cells.
• The HLA-B27 molecule itself activate leucocytes.
• HLA-B27 molecules may also causing increased
endoplasmic reticulum stress.
• This could lead to inflammatory cytokine release by
macrophages and dendritic cells, thus triggering
inflammatory disease.
 Presentation
• Symptoms may be subtle in early stages or mild
disease, with an insidious onset over several
months to years.
• AS usually presents before the age of 30 years.
• Most patients have mild chronic disease or
intermittent flares with periods of remission.
• Systemic features are common.
• Fever and weight loss may occur during periods of
active disease.
• Fatigue is also prominent.
• Morning stiffness is characteristic.
 Inflammatory back pain:
• Often improves with moderate physical
activity.
• Unlike mechanical back pain, patients
often experience stiffness and pain
which awaken them in the early
morning hours.
• The spinal disease starts in the sacroiliac
joints (bilateral lumbosacral region).
• On examination there is often
tenderness of the sacroiliac joints or
a limited range of spinal motion.
• In the advanced stages, patients
develop loss of lumbar lordosis,
buttock atrophy, and an
exaggerated thoracic kyphosis with
a stooped forward neck sometimes
referred to as a 'question mark
posture'.
• According to the Assessment of SpondyloArthritis
international Society (ASAS) criteria, "inflammatory back
pain" typically exhibits at least four of the following five
features:
●Age of onset <40 years
●Insidious onset
●Improvement with exercise
●No improvement with rest
●Pain at night (with improvement upon arising)
 Peripheral enthesitis:
• Occurs in approximately a third of
patients.
• Common sites - behind the heel
(Achilles tendonitis), the heel pad
(plantar fasciitis) and the tibial
tuberosity.
• Lesions tend to be painful, especially
in the morning.
• There may be associated swelling of
the tendon or ligament insertion.
Heel
enthesitis
Peripheral arthritis:
• Also occurs in about a third of patients.
• Joint involvement is usually asymmetric, involving the hips,
shoulder girdle (glenohumeral, acromioclavicular, and
sternoclavicular joints), joints of the chest wall
(costovertebral joints, costosternal junctions) and symphysis
pubis.
• The most commonly affected joints were the ankles (40
percent), hips (36 percent), knees (29 percent), shoulders
(19 percent), and the sternoclavicular joints (14 percent).
• Other peripheral joints are less often and less
severely affected, usually as asymmetrical
oligoarthritis.
• In children, AS tends to commence with arthritis
prior to spinal disease developing.
• Temporomandibular joints are occasionally
involved.
 Hip pain —
• Hip involvement (hip joint pain) is present in 25 to 35
percent of patients with AS.
• Associated with higher degrees of disability and a worse
prognosis.
• The typical symptom is groin pain, but, as with other
disorders of the hip joint, pain may be referred to the
medial thigh or even the knee.
• Flexion deformities of the hips may develop.
• Hip involvement may be more severe in patients with
early onset of AS, axial, and entheseal disease, and
such patients may be more likely to eventually require
hip replacement surgery.
Postural Progression of postural changes with ankylosing
spondylitis
abnormalities
• Postural abnormalities, especially
hyperkyphosis (hunchback), become
apparent as early as within the first 10
years of disease in some AS patients.
• Hyperkyphosis is caused by wedging of
the thoracic vertebrae.
• The typical stooped posture of an AS This series of photographs shows
patient with advanced disease is caused the progressive postural changes
by a combination of flexion deformity of ankylosing spondylitis. The
of the neck, thoracic hyperkyphosis, patient had total hip
loss of normal lumbar lordosis, and replacements performed in 1972.
flexion deformities of the hips
 Dactylitis (sausage
Dactylitis (sausage toe)
digit)

Dactylitis
• Dactylitis (sausage digits) is
characterized by diffuse
swelling of toes or fingers.
• A history of dactylitis is
present in approximately 6
percent of patients with AS.

Photograph
Dactylitis ofof the
the right toe
fourth hand
of with dactylitis
the left (sausage
foot. The
digit) oftoe
fourth theismiddle finger.
diffusely swollen and is described as a
"sausage toe."
Extra-articular manifestations
Eye involvement
• Acute anterior uveitis occurs in 20-
30% of patients.
• Of all patients presenting with acute
anterior uveitis, a third to a half have
or will go on to develop AS.
• Acute anterior uveitis presents with
an acutely painful red eye and severe
photophobia and requires
emergency treatment to prevent
visual loss.
 Cardiovascular involvement
• This occurs in <10% of patients, usually in those with
severe long-standing disease.
• Aortitis of the ascending aorta may lead to distortion of
the aortic ring, causing aortic regurgitation.
• Fibrosis of the conduction system may result in various
degrees of atrioventricular block, including complete
heart block.
Pulmonary involvement
• In a minority of AS patients after longstanding disease,
pulmonary compromise occurs due to restrictive
changes caused by the musculoskeletal disease and
changes in the lungs themselves, including interstitial,
nodular, and parenchymal abnormalities.
• Pulmonary fibrosis of the upper lobes.
 Renal involvement
• Amyloidosis is a very rare complication in patients
with severe, active and long-standing disease and may
cause renal dysfunction with proteinuria and renal
insufficiency or chronic kidney disease.
• Immunoglobulin A (IgA) nephropathy is another
association.
Neurological involvement
• This usually occurs secondary to fractures of a
fused spine.
• Also, patients with AS are prone to atlanto-axial
subluxation, which may lead to cervical
myelopathy.
• Cauda equina syndrome may occur in patients
with severe long-standing disease.
Metabolic bone disease
• Osteopenia and osteoporosis may occur in
patients with long-standing spondylitis,
further increasing risk of fracture.
Diagnosis
• The British Society for Rheumatology recommends that the
modified New York criteria be used to diagnose AS.
• Clinical criteria:
• Low back pain, for more than three months; improved by exercise,
not relieved by rest.
• Limitation of lumbar spine motion in both the sagittal and the
frontal planes.
• Limitation of chest expansion relative to normal values for age
and sex.
• Radiological criterion: sacroiliitis on X-ray.
• Definite AS is diagnosed if the radiological criterion is
present plus at least one clinical criterion and
probable AS if three clinical criteria are present, or if
the radiological criterion is present but no clinical
criteria are present.
 Associated diseases
AS may overlap with other spondyloarthropathies - eg,
• Psoriatic arthritis,
• Reactive arthritis, or
• Enteropathic arthropathy.
Differential diagnosis
• Mechanical back pain.
• Inflammatory conditions - eg, rheumatoid arthritis
• Degenerative conditions - eg, osteoarthritis
• Infection - eg, tuberculosis
• Neoplasms, primary or secondary
• Referred pain
• Congenital spinal deformity
• Trauma
 Investigations
Blood tests
• No laboratory tests are specific and are often more helpful to
exclude other diagnoses rather than confirming AS.
• Guidance suggests that only FBC and inflammatory markers should
be taken.
• There may be normochromic normocytic anaemia of chronic
disease.
• ESR or CRP level may correlate with disease activity but these are
less useful for monitoring activity than in other inflammatory
arthritis such as rheumatoid arthritis.
• Alkaline phosphatase is often elevated.
 Examination
• Measure chest expansion, lateral lumbar flexion and
forward lumbar flexion.
• Schober's test
• Palpate and stress the sacroiliac joints.
• Examine peripheral joints for synovitis or enthesitis.
• Always look for extra-articular manifestations of AS, as
these occur in up to 40% of patients.
Degree of limitation
 Imaging
• X-rays are the most helpful imaging
modality.
• Look for sacroiliitis or enthesitis.
• The vertebral bodies may become
'squared'. In later stages, bony bridges
(syndesmophytes) form between
adjacent vertebrae, there is ossification
of spinal ligaments and, in late disease,
there may be complete fusion of the
vertebral column (bamboo spine).
• Spinal osteopenia is common.
Bamboo
• A standard AP plain radiograph of the pelvis should be
obtained to evaluate the SI joints.
• In a patient with chronic back pain, the presence of
obviously significant abnormalities of the SI joint(s) on plain
radiographs, including erosions, ankylosis, changes in joint
width, or sclerosis, strongly supports the diagnosis of AS.
• The SI joint abnormalities are typically graded from 0 to 4
to identify the nature and severity of involvement.
The grades are defined as follows
• Grade 0: Normal
• Grade 1: Suspicious (but not definite)
changes
• Grade 2: Minimal abnormality – Small
localized areas with erosions or
sclerosis, without alteration in the
joint width
• Grade 3: Unequivocal abnormality –
Moderate or advanced sacroiliitis
with one or more of the following:
erosions, sclerosis, joint space
widening, narrowing, or partial
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 Spot diagnoses 1
X-ray changes in spondyloarthropathies
• Fine symmetrical marginal
syndesmophytes typical of ankylosing
spondylitis (arrow).
 Spot diagnoses 2
X-ray changes in
spondyloarthropathies
• Coarse, asymmetrical non-marginal
syndesmophytes typical of
psoriatic/Reiter’s spondylitis (arrow).
Spot diagnoses 3
Left hip involvement in a patient with
ankylosing spondylitis
• There are destructive changes in the
left hip joint.
• The left hip shows irregularity along
both the acetabulum and the surface
of the head of the femur, with small
erosions on both.
• The superior joint space is narrower
in the left hip compared with the
right hip.
 Spot diagnoses 4
Bilateral hip involvement in
ankylosing spondylitis
• Severe destructive disease in both
right and left hips in a patient with
ankylosing spondylitis.
• The destructive changes are greater
on the right compared with the left.
• MRI scanning may be useful in identifying early
sacroiliitis.
• MRI of the sacroiliac joints is more sensitive than
either plain X-ray or CT scan in demonstrating
sacroiliitis.
• It has a growing role in diagnosis, prognostication and
selection of patients for biological treatment.
• MRI/CT scans - useful in making the diagnosis of a
spinal fracture in patients with late-stage spinal
disease.
• Musculoskeletal ultrasound scanning can help in
diagnosing enthesitis.
ASAS
modification of
the Berlin
algorithm

ASAS: Assessment of SpondyloArthritis International Society

 Management
• The aims of management are to relieve pain and
stiffness, maintain a maximal range of skeletal
mobility and avoid the development of deformities.
• Education and appropriate physical activity are the
cornerstones of management.
 GOALS AND GENERAL PRINCIPLES
OF MANAGEMENT
• The primary goals of management for patients with axial
spondyloarthritis (SpA) are to optimize short- and long-term
health-related quality of life through:
• Relief of symptoms
• Maintenance of function
• Prevention of complications of spinal disease
• Minimization of extraspinal and extraarticular manifestations
and comorbidities
• Maintenance of effective psychosocial functioning
• The initial treatment interventions for most patients
with axial spondyloarthritis (SpA; ankylosing
spondylitis [AS] include a series of nonpharmacologic
measures and nonsteroidal antiinflammatory drug
(NSAID) therapy.
 Nonpharmacologic interventions
• Patient education
• Counseling regarding smoking cessation
• Depression screening and psychosocial support
• Exercises and physical therapy
 Pharmacotherapy
• Pharmacotherapy includes one or more of the following:
nonsteroidal antiinflammatory drugs (NSAIDs), non-NSAID
analgesics, nonbiologic (conventional synthetic [cs]) disease-
modifying antirheumatic drugs (DMARDs), and biologic
(b)DMARDs.
• Unlike rheumatoid arthritis, oral (low-dose) glucocorticoids
have no role in axial SpA, but intraarticular injections may be
helpful to some patients.
• Oral corticosteroids may be required for acute uveitis but do
not help spinal disease.
 Surgery
• Surgery is occasionally useful to correct spinal
deformities or to repair damaged peripheral
joints.
• Patients may need total hip replacement and,
occasionally, total shoulder replacement.
 Prevention
• Cardiovascular disease (CVD):
• AS carries an increased risk of CVD.
• It is important to manage modifiable cardiovascular risk
factors where present (eg, smoking, raised body mass
index (BMI), cholesterol, sedentary lifestyle,
comorbidities).
• Osteoporosis: bisphosphonates are often used to
treat osteoporosis and reduce the risk of fracture in
AS.
 Complications
• A small minority of patients will develop spinal fusion,
which may result in severe kyphosis and a 'frozen
thorax' with limited motion of the spine.
• The fused spine is more susceptible to fracture, even
with relatively minor trauma.
• The kyphosis may also cause respiratory problems, by
restricting lung expansion.
• Extra-articular manifestations of the disease may cause
complications - eg, blindness from recurrent uveitis.
 Prognosis
• Prognosis is variable, and the pattern of symptoms
within the first 10 years of disease often correlates
well with the likely long-term degree of disability.
• A minority of patients with chronic progressive
disease develop significant disability due to spinal
fusion, often with thoracic kyphosis or erosive disease
involving peripheral joints, especially the hips and
shoulders.
• Patients often require long-term anti-inflammatory
therapy.
• Morbidity can occur related to spinal and peripheral joint
involvement or, rarely, extra-articular manifestations.
• Poor prognostic indicators include male sex, peripheral
joint involvement or intractable iritis, young age of
onset, elevated ESR and poor response to NSAIDs.
• Mortality is increased compared with the general population.
• A recent meta analysis found that patients with AS had an
increased risk of myocardial infarction and stroke.
• Another study found that circulatory diseases, malignancy
and infection were the three leading causes of death
• Psychological health should not be neglected in AS patients.