Rheumatology 7 - Reactive Arthritis and Seronegative Spondylarthropaties

Rheumatology 7 - Reactive Arthritis and Seronegative Spondylarthropaties

Anil Chopra

1.  Diseases

2.  Aetiology

3.  Demography

4.  Pathogenesis

5.  History & Examination

6.  Blood tests

7.  Radiology

8.  Management

A spondyarthropathy is an inflammatory disease that affects the spine, sacroiliiac joints (axial skeleton), peripheral joints and enthuses (tendons that are inserted into bone and as a result, mineralised collagen fibres become part of the bone tissue). It is associated with the HLA-B27 and are all rheumatoid factor negative. There are 4 main diseases:

l  Ankylosing spondylitis – most common

l  Reactive arthritis (Reiter’s syndrome)

l  Psoriatic arthritis

l  Enteropathic arthritis (IBD-related arthritis)

They are characterised by inflammatory spinal pain or synovitis (inflammation of a synovial membrane) along with one of:

Ø  Family History

Ø  Psoriasis

Ø  GU or GI infection within 1 month

Ø  IBD

Ø  Buttock pain

Ø  Enthesopathy

Ø  Sacroiliitis

There is believed to be a genetic cause – the HLA-B27, and an environmental cause such as infections:

Å  Reactive arthritis - genito-urinary or gastrointestinal infection

Å  Ankylosing spondylitis and Klebsiella

Å  Psoriatic arthritis and Streptococcus

Ankylosing Spondylitis

This is defined as symptomatic sacroiliitis (inflammation of the sacroiliac joint), where there is persistent pain (for more than three months) associated with morning stiffness and improving with exercise and worsening on rest. It is characterised by back pain and stiffness. It is caused by enthesitis (inflammation of tendons attached to bone) leading to calcification and bony fusion.

The male: female ratio is 4:1 and 98% of sufferers are HLA-B27+.

Genetics of Ankylosing Spondylitis

We know that genetics play an important role in the condition. The following HLAs are associated with ankylosing spondylitis…

·  HLA B27 – this is the most important (and you must remember this one). There are 23 types of HLA B27 and the MHC gene responsible for this is located on chromosome 6.

·  HLA B60 and HLA DR1 are also important

·  Also…

–  TAP genes are important transporters which are associated with antigen processing in ankylosing spondylitis.

–  LMP genes are large multifunctional proteases.

·  However, there also seem to be some genes that are associated with offering protection against ankylosing spondylitis…

–  HLAB2706 (found in some people in Indonesia) act against ankylosing spondylitis.

–  Similarly, HLAB2709 (found in people in Sardinia) does much the same thing.

·  The environment also plays its part. For example, certain gram negative organisms may be a cause of ankylosing spondylitis, but this has not been proven.

Clinical Features

Ø  Inflammatory back and buttock pain

Ø  Enthesitis – plantar fasciitis (inflammation of the platar fascia – underside of foot), Achilles tendonitis

Ø  Peripheral arthritis

Ø  Extra-articular:

•  Iritis (10-25%)

•  Aortitis & aortic regurgitation

•  Pulmonary fibrosis

Complications

Ø  Neurological involvement

l  Spinal fractures – C5/6, or C6/7

l  Compressive myelopathy

l  Spinal stenosis

Ø  Renal involvement (amyloidosis)

Ø  Osteoporosis

Examination

»  Schöber’s Test: non-specific measure of lumbar flexion (using changes in finger distance on patient’s back)

»  Fingertips-to-floor distance

»  Wall-to-tragus distance

»  Chest wall expansion

»  Cardiovascular: auscultation and BP for aortic regurgitation

»  Respiratory: bilateral basal crackles

»  Examination of the eyes may reveal anterior uveitis. This is basically inflammation of the eye confined to the iris and ciliary body. Anterior uveitis is usually painful with clusters of inflammatory cells (keratic precipitates) adhering to the inner surface of the cornea. Uveitis will cause visual impairment unless treated effectively

Tests

»  Radiology

o  Bilateral sacroiliitis (inflammation of the sacroiliac joint)

o  Ligamentous calcification

o  Syndesmophytes (bony outgrowth of the spine)

o  X-rays – these will show squaring of the vertebral bodies, syndesmophytes (a vertical outgrowth of bone from a vertebra. Fusion of these outgrowths across the joints between vertebra contributes to rigidity of the spine, and this is seen in advanced cases of ankylosing spondylitis) – both of these factors contribute to the so called “bamboo spine”. Chest X-rays may also show a fibrosis of the upper lung lobes.

o  CT and MRI scans of the sacroiliac joints will show erosion of the joints and also fusion of them.

o  Bone scans of specific joints will also aid the diagnosis.

»  Raised ESR and CRP levels are diagnostic of ankylosing spondylitis.

»  A raised serum IgA is also diagnostic of ankylosing spondylitis.

Reactive Arthritis (Reiter’s Syndrome)

Reactive arthritis is a sudden onset disease that manifests itself usually after a gastrointestinal or genitourinary infection. It is caused by molecular mimicry (this is when foreign antigens are similar to self-antigens that they cause an immune response with the same receptors) leading to synovitis.

The joints affected tend to be the hip, knee, shoulder and ankles. It can result in conjunctivitis and sterile urethritis.

There are a number of different pathogens that can cause the reactions:

l  Urogenital: Chlamydia

l  Enterogenic: Salmonella, Shigella, Yersinia, Campylobacter

l  Others: Clostridium, Chlamydia pneumoniae, borrelia burgdorferi, N. gonorrhoea, Strep, Hepatitis C, Giardia, Mycoplasma

There is also HLA-B27 found in 60% of cases.

The male: female ratio is 3:1 and the age of onset is normally 20-40 years.

Pathogenesis

Reiter’s syndrome is characterised by the Triad of Arthritis; Conjunctivitis and Urethritis. It will normally occur around 1-4 weeks after a GI or GU infection and cause:

Ø  Lower limb mono- or oligo- arthritis or dactylitis

Ø  Inflammatory spinal pain

Ø  Enthesitis (inflammation at the site of insertion of tendons or ligaments into bones)

Ø  Tenosynovitis (inflammation of a tendon sheath, producing pain, swelling, and an audible creaking in movement – it often occurs from a bacterial infection).

Ø  Sacroiliitis (inflammation of the sacroiliac joints).

Ø  Keratoderma blennorhagia – this is the appearance of spots on the soles of the feet and in some cases on the palms of the hands (as can be seen in the adjacent diagram).

Ø  Circinate balanitis (inflammation of the glans penis).

Ø  Urethritis is common, as is cervicitis (inflammation of the cervix).

Ø  Gut inflammation is also common (and colonoscopy is required to diagnose this).

Ø  Conjunctivitis and iritis may also occur.

Ø  Plantar fascitiis is the inflammation of the fascia over the plantar. This causes localised pain in the heel, and localised tenderness. Many seronegative arthropathies present with this and also achilles tendonitis.

The prognosis is often self limiting and full recovery takes 6 months, it rarely progresses to chronic arthritis.

Investigations

·  Tests include: FBC, ESR, and CRP.

·  Urine analysis is carried out.

·  Urethral and/or cervical smears may be taken.

·  Arthrocentesis – the aspiration of fluid from a joint with a puncture needle, and the fluid is then analysed (it will look for the presence of rheumatoid factors, etc.

·  Stool cultures are required for analysis to determine reactive arthritis associated with enteritis (the causative bacterium or other infectious agent).

·  Radiology is important as some radiographs (such as of the hand) can be important in demonstrating some clinical features of reactive arthritis.

Psoriatic Arthritis

Psoriasis is a chronic skin disease in which scaly pink patches form on the elbows, knees, scalp and other parts of the body. Psoriatic arthritis is an arthritis which is associated with psoriasis. It (psoriatic arthritis) only occurs in a small minority of patients with psoriasis, but it may be disabling and very painful.

This form of arthritis is rheumatoid arthritis-like (i.e. it is seronegative), and is also described as being arthritis mutilans (meaning there is a rapid destruction of the joints involved – especially of the hands – the joints of the hands are completely mutilated and so the hands effectively become useless). Psoriatic arthritis is a condition characterised by markedly increased vascularity in synovium which often pre-dates psoriases (scaly appearance on the skin).

The ratio of men: women is 1:1 and 2% population have psoriasis; of these 10% have psoriatic arthritis.

Ø  20% HLA-B27 in peripheral arthritis

Ø  50% HLA-B27 in spinal arthritis

There are 5 main types of psoriatic arthritis:

·  Symmetric: This type accounts for around 50% of cases, and affects joints on both sides of the body simultaneously. This type is most similar to Rheumatoid arthritis and is disabling in around 50% of all cases.

·  Asymmetric: This type affects around 35% of patients and is generally mild. This type does not occur in the same joints on both sides of the body and usually only involves less than 3 joints.

·  Arthritis mutilans: Affects less than 5% of patients and is a severe, deforming and destructive arthritis. This condition can progress over months or years causing severe joint damage.

·  Spondylitis: This type is characterised by stiffness of the spine or neck, but can also affect the hands and feet, in a similar fashion to symmetric arthritis.

·  Distal interphalangeal predominant: This type of psoriatic arthritis is found in about 5% of patients, and is characterised by inflammation and stiffness in the joints nearest to the ends of the fingers and toes. Nail changes are often marked.

Clinical Features

Ø  Psoriasis (may occur after arthritis)

Ø  Mono, oligo- or poly-arthritis or dactylitis (swelling of toes)

Ø  (arthritis mutilans subset)

Ø  Inflammatory back pain

Ø  Enthesitis

Ø  Nail changes – display pitting (depressions in nail)

Prognosis

The prognosis is better than rheumatoid arthritis but 60% get erosive arthritis in more than 5 joints. Prognosis is worse if:

»  Younger age of onset

»  Presence of HLA antigens

o  HLAB27 correlates with spondylitis

o  HLAB27, B39 and DQw3 progressive disease

o  DR3, DR4 with erosive disease

»  Extensive skin involvement

»  Polyarticular involvement

»  Association with HIV

Enteropathic Arthritis

Enteropathic arthritis usually manifests itself with or after ulcerative colitis or Crohn’s disease. It occurs in large joints and sometimes results in enthesopathies.

The male: female ratio is 1:1 and it occurs in 2-20% of patients with inflammatory bowel disease.

Ø  Peripheral joint involvement: Female > male; no association with HLA-B27

Ø  Spinal involvement (approx 12%): Male:female 3:1; 50% have HLA-B27

Clinical Features

Ø  Sacroiliitis (inflammation of the sacro-iliac joint)

Ø  Iritis (inflammation of iris)

Ø  Aphthous ulcers

Ø  Cutaneous

Ø  Amyloidosis

Investigations

Ø  Blood tests:

l  increased ESR/CRP

l  -ve RhF (ie “Seronegative”)

l  HLA-B27

Ø  Radiology:

l  Plain X rays – pelvis & spine: Sacroiliitis, “bamboo spine”; syndesmophytes

l  Radioisotope bone scan

Treatment and Management of All Spondylarthropathies

The objectives of treatment are to relieve pain, reduce inflammation, maintain good posture and joint function.

Ø  Physiotherapy – ESSENTIAL for ankylosing spondylitis

Ø  Occupational Therapy, podiatry etc

Ø  NSAIDs, ice, rest, elevation

Ø  Intra-articular steroids

Ø  DMARDS (Disease Modifying AntiRheumatic Drugs) for peripheral arthritis

l  Sulphasalazine for chronic recurring disease

l  Methotrexate, especially PsA

Ø  Biological agents

l  Anti-TNFα (AS, PsA)

Ø  Bisphosphonates: class of drugs that inhibits the resorption of bone by blocking the action of osteoclasts. Also offers some pain relief.