SERONEGATIVE ARTHRITIS

By Samantha Mascarenhas
MODERATOR: Dr. Nagraj Shetty

INTRODUCTION:
Seronegative arthritis is a form of arthritis that distinguishes itself from rheumatoid arthritis due the absence of rheumatoid factor (Rh-factor). They show a considerable overlap and similarity of articular and extra articular clinical features and a striking genetic association with the histocompatibility antigen HLA-B27

Types of seronegative arthritis

The following are types of seronegative arthritis that can be described as Rh-factor negative: Psoriatic Arthritis Reiters syndrome Enteropathic arthritis Reactive Arthritis Ankylosing Spondylitis Undifferentiated seronegative arthritis

What are they?

The seronegative arthritis family is differentiated from rheumatoid arthitis in many ways. Namely, rheumatoid arthritis is prevalent in the female population, whereas seronegative arthritis is more frequently seen in males They are a group of related disorders Often associated with HLA B27 Negative for Rh-Factor and other antibodies They have a familial tendency They are more common in Caucasians

 AETIOLOGY: An association with HLA-B27 occurs in all seronegative spondarthrides but is particularly strong for ankylosing spondylitis and Reiters disease and when there is sacroilitis, uveitis or balanitis The suggested pathogenesis is an aberrant response to infection in a genetically predisposed person In some situations a triggering microorganism can be identified, as in Reiters disease following bacterial dysentry or chlamydial urethritis, but in others the environmental trigger remains obscure.

Psoriatic Arthritis:
INTRODUCTION Psoriasis is a hyper-inflammatory disease that contributes to the development of demarcated erythematous scaly plaques. Psoriatic arthritis is due to inflammation in and around the joints, usually the wrists, knees, ankles, lower back and neck. Up to 30% of psoriasis patients may develop psoriatic arthritis. On average, psoriatic arthritis appears about 10 years after the first signs of psoriasis. 60-80% of patients with Psoriatic Arthritis may have psoriasis. Majority have a negative Rheumatoid Factor, and it is usually referred to as "seronegative arthritis.

CLINICAL PRESENTATION
Pattern of joints affected with psoriatic arthritis is different than those with rheumatoid arthritis.

 There is a high frequency of distal joint involvement in psoriatic arthritis compared to rheumatoid arthritis. The onset is usually between 25 and 40 years of age, most commonly in patients with previous or current psoriasis.

CLINICAL PRESENTATION
Symptoms/Sings:
Morning stiffness lasting more than 30 minutes. Patients present with pain and stiffness and swelling in the affected joints. Nail changes are found in 80-90% of patients with psoriatic arthritis and include the following:

Onycholysis (elevation of the nail bed), and nail pitting .

RADIOLOGICAL DEFORMITIES
There is coexistence of erosive changes and new bone formation in distal joints. cup-and-pencil deformity is erosion of one end of bone with expansion of the base of the contiguous bone. Resorption of tufts of terminal phalanges. There is usually no osteoporosis. Osteoporosis occurs in RA. Joint-space widening or narrowing. Periosteal bone formation. There may be surrounding soft tissue swelling (dactilitis). Presence of anykolysis: intra-articular bone fusion, specially of DIP and PIP joints.

Sacroiliitis: inflammation of the sacro-illiac joints, which lead to erosions and sclerosis of SI joints. Spondylitis: Inflammation of one or more vertebrae, which may lead to paravertebral ossification.

Enthesitis: Inflammation at the site of tendon insertion into bone, ie of the achilles tendon.
Arthritis mutilans: Destructive changes and joint deformity of the hand and pan-compartmental ankylosis of the wrist.

5 PATTERS OF PSORIATIC ARTHRITIS:

1. Symmetrical polyarthritis
Most common type, may affect as much as 25% of patients. The hands, wrists, ankles, and feet may be involved. It can be differentiated from RA by Characteristic radiographic findings (as noted before) A history of psoriasis Presence of DIP involvement Absence of subcutaneous nodules on xray A negative rheumatoid factor

2. Asymmetrical oligoarticular arthritis

2nd most common form of presentation. As many as 4 large joints may be affected, often with acute scattered involvement of the metatarsophalangeal, PIP and DIP joints. Dactylitis (sausage digits) may be present.

3. Distal interphalangeal (DIP) arthropathy

DIP joint involvement occurs in 5-10% of patients with psoriatic arthritis. One or several DIP joints may be involved. Clinically, there is periarticular swelling and acute inflammation with warmth.

Radiograph of both hands demonstrates cup-in-pencil deformities of both thumbs and erosion of DIP joint of left middle finger

4. Arthritis mutilans
Occurs in 5% of patients with psoriatic arthritis. It targets fingers and toes. Marked cartilage loss and bone attrition leads to loss of the joint and instability. The encasing skin appears invaginated and telescoped(main en lorgnette) and traction ca pull the finger back to its original length.

 5. Spondyloarthropathy
This includes both sacroiliitis and spondylitis. Clinical evidence of spondylitis, sacroiliitis, or both can occur in conjunction with other subgroups of psoriatic arthritis.

Bilateral sacroiliitis is most common. There may be erosion and sclerosis at the SI joints

Spondylitis may occur without radiologic evidence of sacroiliitis and may appear radiologically without the classic symptoms of morning stiffness in the lower back. With spondylitis, there is loss of the concavity of the vertebral body, resulting in squaring of the vertebral bodies . There is also fusion of vertebral bodies due to bridging syndesmophytes resulting in bamboo spine.

INVESTIGATIONS:
The ESR and CRP may be raised especially with polyarticular disease, but are often unimpressive. Tests for rheumatoid factor and antinuclear antibodies are generally negative X-rays may be normal or may show erosive changes with joint space narrowing Features that show distinction from rheumatoid arthritis include marginal proliferative erosions, retained bone density, and increased sclerosis of small bones

MANAGEMENT:
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) COX-2 inhibitors
Both NSAIDS and Cox-2 inhibitors are used to control the inflammation and help improve patients quality of life. But they do not stop the progression of underlying disease (erosion) and may not be efficacious long term. Cox-2 inhibitors are being used less due to cardiovascular side effects.
(ie) Methotrexate, Cyclosporine or Azathioprine These agents slow or stop the progression of disease and joint erosion. However, their side effects profile (liver and kidney damage, immune suppression, cancers) prevent long term use. Agents that are synthesized by recombinant DNA technology and target specific proteins or cytokines. These agents are gaining momentum rapidly. They stop progression of disease and are so far well tolerated. Enbrel (etanercept) is the only biologic so far approved for psoriatic arthritis. Unfortunately, it is extremely expensive (Enbrel costs $15,000/yr).

Disease Modifying Antirheumatic Drugs (DMARDS)

Biologics: