Rheumatoid arthritis

It is a chronic symmetrical polyarthritis of unknown cause and is characterized by chronic inflammatory synovitis of mainly peripheral joints along with systemic disturbances and extra-articular features.

The course of the disease is prolonged with exacerbations and remissions.

Characterized by:

• Symmetrical inflammatory polyarthritis

• Extra-articular involvement e.g. in the lungs and
many other organs.

• Progressive joint damage causing severe disability.

INCIDENCE

• Prevalence 1-1.5%

• Female to male ratio 3:1

• Peak age incidence between 20-40 years.

Aetiology

The cause of rheumatoid arthritis (RA) is unknown.

Following may be the risk factors:

Genetic factors may be involved because it is usually associated with HLA- DR4 in whites

Autoimmunity: RA is considered to be an autoimmune disease for the following reasons:

• Autoantibodies are present.

• Immune complexes are common in synovial fluid and circulation.

Female gender is a risk factor and this susceptibility is increased post-partum and by breastfeeding.

Cigarette smoking is also a risk factor

PATHOGENESIS

RA is a disease of the synovium. There are two main pathological characteristics:

• Inflammation

• Proliferation

The synovium shows signs of chronic inflammation. There is swelling and congestion of the synovial membrane and the underlying connective tissue which becomes infiltrated with lymphocytes, plasma cells and macrophages.

Effusion of synovial fluid into the joint space takes place during active phases of the disease.

The synovial membrane then proliferates and grows out over the surface of the cartilage, which causes erosion and destruction of the cartilage.

CLINICAL FEATURES

RA usually presents with insidious onset of pain and stiffness in the small joints of hands and feet which eventually lead to bilateral symmetrical peripheral polyarthritis.

In 25% of cases, it presents as monoarthritis such as involvement of the only knee joint.

TYPICAL PRESENTATIONS OF RA

Classical (chronic persistent)

The majority of patients present insidiously with fatigue, generalized weakness and vague musculoskeletal symptoms for weeks or months and then pain, stiffness and swelling of small joints of hands and wrists.

The disease follows the remitting and relapsing course over many years. It may be seropositive or negative for rheumatoid factor. Seropositive patients develop more joint damage as compared to seronegative.

Acute

About 10-15% of patients present with a rapid onset over a few days or overnight with a severe symmetrical polyarticular involvement, often accompanied by constitutional symptoms e.g. fever, lymphadenopathy and splenomegaly.

Palindromic

A few patients present with recurrent acute episodes of joint pain and stiffness usually of a single joint lasting only a few hours or days followed by a rapid return to normal In 1/3 of such cases the disease evolves into one or more typical
of arthritis.

Transient

A self-limiting disease lasting less than 12 months and leaving no permanent joint damage.

It is usually seronegative for IgM rheumatoid factor.

Remitting

There is a period of several years during which the arthritis is active but then remits, leaving minimal damage.

The rapidly progressive disease progresses rapidly over a few years and leads to joint damage and disability.

It is usually seropositive and has a high incidence of systemic complications.

PATTERNS OF ONSET IN RHEUMATOID ARTHRITIS

• Insidious 70%

• Acute 15%

• Oligoarticular 45%

• „ Polyarticular 35%

• Systemic 10%

• Monoarticular 20%

• Palindromic 5%

SYMPTOMS

Joint pain

The pain is worst on waking in the morning and improves progressively with activity. There is often pain at night disturbing the sleep.

Morning stiffness

Often lasting for several hours and then subsides. Its duration is a useful indicator of the activity of the disease.

It is characteristic of inflammatory joint disease.

General symptoms

Fatigue

Malaise.

Extra-articular symptoms

These are discussed below

SIGNS

• Swelling: soft swelling caused by effusion or synovial proliferation.

• Warmth

• Tenderness on pressure or movement.

• Limitation of movement with muscle wasting around affected joints.

• Deformities occurring in the later stages of the disease.

• Subcutaneous nodules (in 20%) mostly situated over the bony prominence

The pattern of joint involvement

Although any joint may be affected in R.A, the proximal interphalangeal and metacarpophalangeal joints of fingers as well as the wrist, knee ankles and toes are most often involved.

Distal interphalangeal joints are characteristically spared.

DEFORMITIES

As the disease advances (after months or years) pain, muscle spasm and joint destruction result in limitation of joint movement, joint instability, a subluxation (partially dislocation) and deformities.

The feet and ankles

Lateral deviation of the toes and subluxation (partially dislocation) of the metatarsophalangeal joints, so that the heads of the metatarsals become palpable in the soles of the feet and the patient often describes as the sensation of walking on pebbles.

Ankle develops valgus deformity

Deformity of hand

Spindling of the fingers

In the early stages, swelling of the metacarpophalangeal joints produces spindling of the finger.

Swan neck deformity

Characterized by hyperextension at the proximal interphalangeal joints and fixed flexion at the distal interphalangeal joints.

Boutonnière  deformity

Characterized by fixed flexion of the proximal interphalangeal joint and extension of the distal interphalangeal joint.

Z deformity of the thumb

It is characterized by hyperextension of the first interphalangeal joint and flexion of the first metacarpophalangeal joint with a consequent loss of thumb mobility.

Carpal tunnel syndrome

Tenosynovitis at the wrist can entrap the median nerve and produce carpal tunnel syndrome.

Extra-articular features in hands

Palmar erythema

Vasculitic lesions in nail beds, nail folds, and digital pulp.

The knee

• Synovial effusions and quadriceps wasting are early features.

• Later on flexion, valgus (bent outward) or varus (bent inward) deformities appear with joint instability.

• Synovial effusion (demonstrated with a patellar tap by fixing the knee with the fingers and thumb of the left hand, then sharply tapping the patella downwards produces a dip when the effusion is resent).

Baker’s Cyst– It is an extension of inflamed synovium into the popliteal space, causing pain and swelling. High pressure generated by flexion of the knee can cause rupture of cyst into the calf, manifesting as calf swelling, tenderness and pitting oedema.

Cervical spine

Synovitis of upper cervical spines leads to bone destruction, damage of ligaments that cause atlantoaxial subluxation which may damage the spinal cord.

COMPLICATIONS OF RHEUMATOID ARTHRITIS

• Ruptured tendons

• Ruptured Baker’s cyst

• Joint infection

• Spinal cord compression

• Amyloidosis presenting as nephrotic syndrome

• Complications of drug therapy

– Swan neck deformity –Characteristic hand deformities in rheumatoid arthritis.

EXTRA-ARTICULAR FEATURES

1 . Musculoskeletal

• Subcutaneous modules: (in 20%): usually seen at sites of pressure or friction such as the extensor surfaces of the forearms below the elbow, scalp, sacrum, scapula, Aschilies tendon, as well as on the fingers and toes.

• Bursitis: The olecranon and other bursae may become swollen.

• Tenosynoyitis: Particularly affecting the flexor tendons in the palm of the hand and may contribute to flexion deformities.

• Muscle wasting: around affected joints especially in the hands.

2. Neurological

• Carpal tunnel syndrome (More common nervous involvement).

• Atlanto-axial subluxation: Most serious neurological abnormality causing cervical cord compression. Death can occur during intubation or endoscopy.

• Polyneuropathy causing glove and stocking type sensory loss mostly involving the legs.

• Mononeuritis multiplex.

3. Ocular

• Sjogren’s Syndrome: Commonest eye problem rheumatoid arthritis.

• Scleritis – causing painful red eye

• Keratoconjunctivitis

4. Haematological

• Thrombocytosis

• Eosinophilia

• Anemia is always present. It may be Normocytic normochromic due to chronic disease.

– Iron deficiency – due to GIT blood loss from analgesic ingestion.

5. Pulmonary

• Pleural effusion (commonest lung problem)

• Diffuse fibrosing alveolitis (rare)

• Rheumatoid nodules in the lungs

• Caplan’s Syndrome: occurrence of nodular pulmonary fibrosis in patients with RA

6. Cardiac

• Pericardial rub

• Pericarditis, myocarditis

• Conduction defects (heart block)

• Aortitis

7. Lymphatic

– Lymphadenopathy – in the distribution of affected joints.

• Splenomegaly

• Felly’s syndrome: Comprising rheumatoid arthritis, splenomegaly with neutropenia.

8. Skin

• Vasculitis: Causing nail fold lesion in hands

• Leg ulcers: In patients with Felty’s syndrome.

9. Systemic

• Fever

• Weight loss

• Susceptibility to infection

EXAMINATION OF PATIENTS WITH RHEUMATOID ARTHRITIS

General inspiration

Look for Cushinoid appearance due to steroid use.

Hands

Put the hands on a pillow, examine the first dorsum of the hand and then palm and look for:

• Symmetrical small joint polyarthritis.

• Ulnar deviation.

– Swan neck, boutonniere deformity, and Z deformity of thumb.

• Fingernails for vasculitic change.

• Wasting of small muscles of the hand.

• Look at palm for palmar erythema

• Signs of carpal tunnel syndrome.

Wrist

Look for synovial thickening and test for carpal tunnel syndrome

Elbow

Rheumatoid nodules

Eyes

• Redness and dryness (Sjogren’s syndrome) occurring in 10-15% of cases.

• Scleritis (white or purple-red nodule surrounded by intense redness) occurs in 1% of cases and is often bilateral.

• Cataract due to steroid use

• Anemia due to iron deficiency.

Mouth and parotid

Dry mouth and enlarged parotid due to Sjogren’s syndrome.

Neck

• Examine cervical spine for tenderness.

• Reduction of rotation movement.

• Examine for lymphadenopathy.

Chest

Examine lungs for pleural effusion or pulmonary fibrosis. Caplan’s syndrome is the presence of
rheumatoid lung nodules in combination with pneumoconiosis.

Abdomen

Splenomegaly (in 10% cases)

Epigastric tenderness ( due to NSAIDs induced peptic ulcer)

Lower limbs

• Note quadriceps wasting, knee joint effusion, flexion contractures.

• Baker’s cyst in the popliteal fossa.

• Peripheral neuropathy in a stocking distribution.

• Look for signs of spinal cord compression due to

INVESTIGATIONS

Following investigations may be helpful.

RA FACTOR

Rheumatoid factor (RA factor) is an autoantibody & is present in about 70% of cases.

The presence of the RA factor does not establish the diagnosis of RA but it can be of prognostic significance because patients with high RA titer tend to have a more severe and progressive disease with extra-articular manifestations.

This test can be employed to confirm a diagnosis in individuals with a suggestive clinical presentation and if present in higher titer, to designate patients at higher risk for severe systemic disease.

RA factor is positive in 10% of the normal population.

DISEASE WHICH MAY BE ASSOCIATED WITH POSITIVE RA FACTOR

Diseases involving joints

• Sjogren’s syndrome (905)

• Rheumatoid arthritis (70%)

• Systemic lupus erythematosus (50%)

• Systemic sclerosis (30%)

• Polymyositis/dermatomyositis (50%)

• Mixed connective tissue disease.

Chronic infections (low titres)

• Tuberculosis

• Leprosy

• Infective endocarditis

Normal population

• Elderly

ANA

The antinuclear antibody is positive in 30% of cases.

Anti- CCP

More reliable and diagnostic

FBE/ESR

• Anemia

• Thrombocytosis in proportion to the severity of joint inflammation.

• WBC may be normally high or low

• ESR and C-reactive protein (CRP) are raised in proportion to the activity of the inflammatory process (inflammatory markers).

RADIOGRAPHY

X-rays taken during the first 6 months are generally normal

Early changes occur in the wrist or feet and consist of:

• Symmetric involvement, juxta-articular osteopenia (it may become apparent within weeks of onset).

• Later loss of articular cartilage and bone erosions develops after months of sustained disease activity. Bone erosion is the hallmark of inflammatory arthropathy.

• MRI and bone scan detect early inflammatory changes that are not apparent from standard radiography but are rarely required.

STAGES OF X-RAY PROGRESSION IN RHEUMATOID ARTHRITIS

• I Periarticular osteoporosis (osteopenia)

• II Loss of articular cartilage (“joint space”)

• III Bony erosions ( especially on margins)

• IV Subluxation and Ankylosis

DIAGNOSIS

Diagnosis of RA is based on history, examination, x-ray findings and serology (RA factor).

Rheumatoid arthritis presents initially with non-
specific symptoms but assumes its characteristic features within 1-2 years of onset.

The following features support the diagnosis of rheumatoid arthritis:

• Bilateral symmetrical inflammatory

Polyarthritis involving small and large joints in both the upper and lower extremities with sparing of axial skeleton except for cervical spine suggest the diagnosis.

• Systemic features indicative of the inflammatory nature of the disease such as morning stiffness support the diagnosis.

• Presence of subcutaneous nodules is a helpful diagnostic feature.

MARKERS OF ACTIVE INFLAMMATORY DISEASE

• Anemia of chronic disease

• Thrombocytosis

• Raised acute phase proteins ( c.g. C-reactive
protein).

• Raised plasma viscosity.

• Raised erythrocyte sedimentation rate (ESR)

MANAGEMENTS

There are five stages in the management of rheumatoid arthritis.

NON-PHARMACOLOGICAL TREATMENT

Rest

Rest relieves symptoms. Complete bed rest for patients with profound systemic and articular
inflammation. With mild inflammation, ‘2 hours of articular rest decreases joint inflammation.

Exercise

Exercises are designed to preserve joint motion, muscular strength and endurance.

Initially passive range of motion is best tolerated. As tolerance for exercise increases and the activity of the disease
subsides’ progressive resistance exercises may be introduced. Patients are particularly at risk of developing progressive joint stiffness and deformity, therefore they should undertake simple exercise to maintain joint mobility and muscle power.

Heat and cold

Heat and cold have muscle relaxing and analgesic effects. Patient may derive relief from hot bath or local application of cold.

Splints

Splints may provide joint rest, reduce pain and prevent contractors. They should be applied for
short period.

Weight loss

Weight loss is also beneficial especially to reduce symptoms of weight bearing joints.

PHARMACOLOGICAL TREATMENT

Medical management of RA involves 4 general approaches.

1. Non-steroidal ant-inflammatory drugs (NSAlDs)

2. Low dose corticosteroids.

3. Disease Modifying Anti-Rheumatic Drugs (DMARDs).

4. Immunosuppressive drugs.

Non – steroidal anti-inflammatory
drugs (NSAlDs)

Non-steroidal anti-inflammatory drugs

They have analgesic and anti-inflammatory effect and therefore they are used to control signs and
symptoms of the local inflammatory process. They are not capable of preventing erosions or altering
progression of the disease.

Selective inhibition of COX-2 will reduce inflammatory process without causing gastric ulcer.
Celecoxib is a selective COX-2 inhibitor. Its efficacy is similar to other NSAlDs with less likely gastric ulceration.

Another approach to reducing the GI side effects of NSAlDs is to add either Omeprazole 20 mg daily

Side effects of NSAlDs

• Gastric ulceration and GI hemorrhage.

• Renal toxicity such as interstitial nephritis, nephrotic syndrome, reversible renal failure and aggravation of baseline hypertension.

Simple analgesics

These drugs having only analgesics effects* but no appreciable anti-inflammatory action, can be used in
combination, of NSAlDs when pain relief is inadequate e.g. paracetamol

Corticosteroids

Corticosteroids usually produce an immediate and dramatic anti-inflammatory affect in RA. They can
be used on short-term basis for the following

Indications:

• Severe exacerbations which are not remitting with NSAlDs and disease modifying drugs.

• Severe extra- articular manifestations e.g. percarditis, perforating eye lesions.

• Active and progressive disease that does not respond favorably to conservative management.

• When there is contraindication to or therapeutic failure of methotrexate or other disease modifying drugs.

Intra-articular corticosteroid may be helpful if one or two joints are the chief source of difficulty.

Disease modifying anti – rheumatic drug

Disease Modifying Anti-Rheumatic Drugs (DMARD) have property to modify the destructive capacity of the disease. They include

Methotrexate

Antimalarial

Sufasalazine

Penicillamine

Azathioprine

Cyclophosphamide

Gold salts

DMARD should be added early and used aggressively to maximize the chance of achieving a good outcome.

The appearance of benefit from this therapy is usually delayed for weeks or months.

Six months of uninterrupted treatment with a disease modifying drug is usually required to assess its efficacy. In addition to clinical improvement, there is frequently an improvement in serologic evidence of disease activity e.g. titer of RA factor; ESR and C-reactive protein are declined.

Patients receiving one of the DMARD will take it, on average for 3-5 years before the lack of efficacy
or toxicity forces discontinuation of its use. A second disease-modifying agent is substituted for the first one when there is therapeutic failure or toxicity develops. Failure to response to one agent does not predict a negative response or intolerance to the others.

Methotrexate

Methotrexate is the treatment of choice. It is generally well tolerated and often produces beneficial effect in 2-6 weeks compared with 2-6 months onset of action for other drugs such as antimalarials).

Maximum improvement is observed after 6 months of therapy

• The maximum dose is 20mg per week.

Side effects

• Gastric irritation and stomatitis (most common).

• Interstitial pneumonitis (rare).

• Cirrhosis of liver (very rare) therefore contraindicated in chronic hepatitis.

• Bone marrow suppression that predisposes to infection.

• Concomitant administration of folic acid may diminish the frequency of some side effects.

PROGNOSIS

The course and prognosis in RA are very variable. After 10 years the disease pattern is as following.

# Complete remission in 25%.

# Moderate impairment in 40%

m Severe disability in 25%

# Severely crippled 10%.

Poor prognostic factors

• High titers of rheumatoid factor

. Insidious onset of disease.

• More than a year of active disease without remission.

• Early development of erosions

• Extra – articular manifestations.

• Severe functional impairment.

SURGICAL PROCEDURES IN RA

Soft tissue release (decompression)

• Carpal tunnel syndrome due to median nerve
compression

• Tarsal tunnel syndrome due to posterior tibial
nerve entrapment

• Flexor tendon ( for relief of trigger fingers )

Tendon repairs and transfers

• Extensor tendons of hands for rupture of extensor tendons

• Flexor tendon of thumbs and fingers for rupture of flexor tendons

Joint replacement

Hip, knee, elbow, shoulder, ankle, metacarpophalangeal joints of hands.

Arthrodesis

• Interhalangeal joint of thumb or fingers

• Met/carpophalangeal joint of thumb

• Wrist