Seronegative spondyloarthropathies

an acute or chronic condition

characteristic involvement of axial joints

absence of RA factor

HLA abnormality

These disorders include:

Ankylosing spondylitis

Reiter’s syndrome

Reactive arthritis

Psoriatic arthritis

Enteropathic arthritis-(crohn’s disease,ulcerative colitis,whipple’s disease,behcet’s syndrome)

Juvenile-onset spondyloarthropathy

Undifferentiated spondyloarthropathy

Ankylosing spondylitis

Historical perspective:

1912 - Raymond provided illustrations of ankylosing spondylitis in mummies and graves of ancient Egypt.

Likewise Bourke and Short described 18 instances of ankylosing spondylitis extending over 3 millenia, 2900b.c. to 200a.d., derived from Egyptian sources.

1850 – the modern history of ankylosing spondylitis began with Brodie. He described a 31 year old man who had developed an ankylosed spine and who occasionally suffered from inflammations of the eye.

1884 – Strumpell from Germany described two patients who showed complete ankylosis of the spine and hip joints. This report was soon followed by descriptions of the disease by von Bechterew from Petersburg, Russia, and Pierre Marie from France.

1930 – the radiographic hallmark of ankylosing spondylitis was fully recognized - sacro-iliac disease.

EPIDEMIOLOGY

Prevalence

closely parallels the frequency of HLA-B27

The disease is much more common among HLA-B27-positive first-degree relatives of (HLA-B27-positive) ankylosing spondylitis patients

Incidence

an overall age and gender-adjusted incidence of 7.3 per 100,000 person-years

age of onset usually below 40 years

incidence in males > incidence in females

Racial Distribution

Approximately 90 percent of white patients with ankylosing spondylitis possess HLA-B27

Only about 50 percent of black patients with ankylosing spondylitis possess B27

ETIOLOGY

Hypotheses

a) Klebsiella pneumoniae

Cross-reacting antibodies

Bind to HLA-B27 positive cells

Ankylosing spondylitis

b) external antigenic challenge

activation of autoreactive t-cells

recognizes endogenous peptides presented by HLA-B27

ankylosing spondylitis

Subtypes of HLA-B27

Currently, 13 subtypes (allotypes) of HLA-B27 are recognized: B*2701 to B*2713. Interestingly, 2 of the 11 subtypes--HLA-B*2706 and HLA-B*2709--lack a strong association with ankylosing spondylitis.

Other Genetic Factors

concordance in monozygotic twins is 63 percent, whereas concordance in all dizygotic twins is 12.5 percent, but it rises to 23 percent in HLA-B27-positive dizygotic twins

HLA-B60 has now been demonstrated to be associated with a three- to sixfold increase in susceptibility to ankylosing spondylitis both in HLA-B27-positive and HLA-B27-negative individuals.

still other HLA factors (B7-Creg, B38, B39, DR1, DR8) and non-HLA factors (possibly Crohn's disease locus on chromosome 16 or psoriasis genes on chromosome 17) should be considered as candidates

PATHOLOGY

a)Enthesitis

syndesmophyte formation, squaring of vertebral bodies, vertebral end plate destruction, and Achilles tendonitis. Enthesitis is assosciated with prominent edema of the adjacent bone marrow

b)Sacro-iliitis

Subchondral granulation tissue containing lymphocytes,plasma cells, mast cells, macrophages and chondrocytes

infiltration into ligamentous and periosteal zones

synovitis

progression to pannus formation

The eroded and sclerotic margins of the joint are gradually replaced by fibrocartilage regeneration and then by ossification

ultimately obliteration of the joint.

c)Spine

Early inflammatory granulation tissue at the junction of the annulus fibrosus of the disk cartilage and the margin if the vertebral bone

erosion of the outer annular fibers->replaced by bone

forming a bony excrescence called syndesmophyte->continues to grow by enchondral ossification

bridging the adjacent vertebral bodies->ascending progression of this process leads to bamboo spine

Inflammatory arthritis of the apophyseal joints->erosion of the cartilage by pannus->bony ankylosis.

Bone mineral density is diminished in the spine and the proximal femur early in the course of the disease

d)Eyes

e) Aortic valve

Aortic insufficiency

A-V blocks

f) Others

Colonic lesions

IgA nephropathy

CLINICAL MANIFESTATIONS

Skeletal Manifestations

Low Back Pain and Stiffness

Chest Pain

Tenderness

Joints

Extraskeletal Manifestations

General Symptoms

Eye Disease

Cardiovascular Disease

Pulmonary Disease

slowly progressive fibrosis of the upper lobes of the lungs

The lesions eventually become cystic

the cavities may subsequently be colonized by Aspergillus, with the formation of mycetoma (cough, hemoptysis, dyspnea)

Neurologic Involvement:- Traffic accidents or minor trauma can cause spinal fractures. The C5-C6 or C6-C7 level is the most commonly involved site, atlantoaxial joint subluxation, atlanto-occipital subluxation, and upward subluxation of the axis may occur in ankylosing spondylitis as a consequence of instability resulting from the inflammatory process. Causes of neurologic complications due to compression include ossification of the posterior longitudinal ligament (which may lead to compressive myelopathy), destructive intervertebral disk lesions, and spinal stenosis. The cauda equina syndrome is a rare but serious complication of long-standing ankylosing spondylitis.

Renal Involvement

Osteoporosis

PHYSICAL FINDINGS

Spinal Mobility:- there is usually some limitation of motion of the lumbar spine as elicited by forward flexion, hyperextension, or lateral flexion. Early loss of the normal lumbar lordosis is easily assessed on inspection.

Chest Expansion

Enthesitis

Sacroiliitis

Posture

LABORATORY FINDINGS

elevated erythrocyte sedimentation rate

elevated level of C-reactive protein

mild normochromic, normocytic anemia

elevated alkaline phosphatase level

Elevated serum IgA levels

Rheumatoid factor and antinuclear antibodies are largely absent unless caused by a coexistent disease.

Synovial fluid from inflamed peripheral joints in AS is not distinctly different from that of other inflammatory joint diseases

In cases with restriction of chest wall motion, decreased vital capacity and increased functional residual capacity are common, but airflow measurements are normal and ventilatory function is usually well maintained

RADIOGRAPHIC FINDINGS

Roentgenographic abnormalities generally appear in the sacroiliac joints before appearing elsewhere in the spine. Radiographically demonstrable sacroiliitis is usually present

Grading of Sacroiliitis According to theNew York Criteria

Grade

0, Normal

1, Suspicious

2, Minimal sacroiliitis

3, Moderate sacroiliitis

4, Ankylosis

demonstrates ankylosis of the sacroiliac joints

dynamic MR imaging with a T₁ -weighted sequence after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) might be considered to demonstrate early stages of sacroiliitis

Early sacroiliitis of ankylosing spondylitis. acute sacroiliitis the right side, with edema in the juxtaarticular bone marrow (asterisks), in the region of the synovium and joint capsule (thin arrow), and in the region of the interosseous ligaments (thick arrow). Early chronic changes, including cortical erosions and joint space widening, were evident in the right sacroiliac joint

DIAGNOSIS

Modified New York, 1984

Criteria

1. Low back pain at least 3 months' duration improved by exercise and not relieved by rest

2. Limitation of lumbar spine in sagittal and frontal planes

3. Chest expansion decreased relative to normal values for age and sex

4. Bilateral sacroiliitis grade 2-4

5. Unilateral sacroiliitis grade 3-4

Definite ankylosing spondylitis if unilateral grade 3 or 4, or bilateral grade 2-4 sacroiliitis and any clinical criterion

PROGNOSIS

The course of ankylosing spondylitis is highly variable. Characterized by spontaneous remissions and exacerbations, it is generally favorable because the disease is often relatively mild or self-limited.

TREATMENT

Exercises

Ergonomics

Physiotherapy

Indomethacin is particularly effective as a 75-mg slow-release preparation taken once or twice daily

phenylbutazone, at doses of 200 to 400 mg/d, has been considered the most effective anti-inflammatory agent in AS

sulfasalazine, in doses of 2 to 3 g/d, is useful in reducing peripheral joint symptoms as well as reversing laboratory evidence of inflammation

The peripheral arthritis may also respond to the folic acid antagonist methotrexate

Occasionally, intralesional or intraarticular glucocorticoid injections may be beneficial in patients with persistent enthesopathy or synovitis unresponsive to anti-inflammatory agents

anti–TNF-α agents: etanercept

Attacks of iritis are usually effectively managed with local glucocorticoid administration in conjunction with mydriatic agents, although systemic glucocorticoids or even immunosuppressive drugs may be required in some cases

Coexistent cardiac disease may require pacemaker implantation and/or aortic valve replacement.

The most common indication for surgery in patients with AS is severe hip joint arthritis, the pain and stiffness of which are usually dramatically relieved by total hip arthroplasty. Vertebral osteotomy may be required in selected cases to correct marked flexion deformity