Rheumatoid arthritis is a chronic, inflammatory destructive and deforming polyarthritis associated with systemic disturbance, a variety of extra- articular lesions and the presence of circulating anti – globulin antibodies called rheumatoid factors.

Epidemiology:
Women are affected about three times more often than men. Onset is most frequent during fourth and fifth decades of life that is between 35 - 50 years.

Genetic predisposition is present.
1. Approximately 10% of patients with rheumatoid arthritis will have an affected first degree relative.
2. The Class II Major Histocompatibility Complex allele HLA DR-4 & related alleles HLA DR-1 & HLA – DW16 are known to be associated with rheumatoid arthritis MHC on chromosome 6 is believed to be related to rheumatoid arthritis.
3. Genes outside HLA complex also contribute to rheumatoid arthritis. These include genes controlling the expression of the antigen receptor on T – cells and immunoglobulin heavy and light chains.
4. Environmental factors also play a role in the aetiology.

Aetiology:
Exact cause of rheumatoid arthritis is not known. rheumatoid arthritis might be a manifestation of the response to an infectious agent in a genitically susceptible host. Complex multi factorial in origin. It is believed that an infection is the initiating factor and a number of causative agents including mycoplasma, Ebstein barr virus, cytomegalovirus, parvovirus, rubella virus have been suggested. Only environmental factor clearly associated with the development of rheumatoid arthritis is cigarette smoking.

Immunopathology:
The synovial membrane injury with the endothelial damage, infiltration by polymorphonuclear leucocytes and obliteration by thrombus is the earliest lesion in rheumatoid arthritis. There will be an increased number of synovial lining cells with perivascular infiltration with polymorphonuclear leucocytes. Later, swelling and congestion of the synovial membrane and underlying connective tissue, which become infiltrated with lymphocytes especially CD4 positive T cells or helper T cells, plasma cells and macrophages. Plasma cells synthesis anti IgG immunoglobulins, that is, immunoglobin with reactivity to self IgG. This forms immune complexes and activation of compliment pathway occurs which in turn leads to the stimulation of neutrophil chemotaxis, cytolysis, lymphokine production etc. there will be release of mediators of acute inflammation like vaso- active amines, proteases, prostaglandins, leukotrienes etc.

 All these leads to effusion of synovial fluid into the joint space during the active phase of disease. Hypertrophy of the synovial membrane with the formation of lymphoid follicles resembling an immunologically active lymph node. Inflammatory granulation tissue called pannus is formed, spreading over and under the articular cartilage which is progressively eroded and destroyed. Later fibrous adhesions may form between layers of pannus across the joint space and fibrous and bony adhesions may occur. Muscles adjucent to the inflamed joints atrophy.
In case of subcutaneous nodules there is a centrral area of fibrinoid material consisting of swollen and fragmented collagen fibres, fibrinous exudate and cerebellar debris surrounded by radially arranged proliferating mononuclear cells. The nodule is surrounded by a loose capsule of fibrous tissue.

Onset of the disease may be as any of the following way.
1. Palindromic onset : About 1/5th of patients with rheumatoid arthritis may be presented as repeated attacks of acute self limiting synovitis affecting a variable number of joints.
Typically the inflammation develops over a few hours and is accompanied by erythema and swelling of the affected joints but resolve completely within 48 to 72 hours, leaves no residual features.
2. Explosive onset : In about 10% of cases of the disease is very rapid, even overnight with severe symmetrical polyarticular involvement.
3. Systemic onset : Non – articular features may dominate the clinical picture like fever, myalgia, weight loss, anaemia, pleural effusion and vascular lesion may be severe, sometimes in the absence of marked joint pathology.
4. Insidious onset : Upto 70% of cases of rheumatoid arthritis develop insidiously over weeks or months with gradually increasing joint involvement. This type of onset is associated with a relatively poor prognosis.
5. Polymyalgic onset : Limb girdle muscle symptoms may preceed the onset of arthropathy.
6. Mono and pauci – : In young women there may initially be very limited articular onset joint involvement particularly involving the knees.

Clinical features :
Clinical features can be divided into articular and extra – articular features.Rheumatoid arthritis is a disease with exacerbations and remission. Constitutional symptoms like fatigue, anorexia, generalised weakness and vague musculoskeltal symptoms will be present until the appearance of apparent synovitis.

ARTICULAR FEATURES :
1. Pain, swelling and tenderness in joints especially peripheral joints like proximal interphalangeal joints gives finger a ‘spindled appearance’ and swelling of the metatarsophalangeal joints causing ‘broadening’ of the forefoot.
2. Generalised stiffness, usually greatest after periods of inactivity. Morning stiffness of 1 hour duration.
3. Limitation of movements.
4. Inflammed joints are held in flexion to minimize joint volume and minimize distension of capsule.
5. Fibrous or bony ankylosis or soft tissue contracture leads to fixed deformities.
6. Baker’s cyst – may develop due to extension of the inflamed synovium into popliteal space. Rupture of the cyst may cause extravasation of highly irritant synovial fluid into calf where the inflammation and swelling mimic deep vein thrombosis.
7. Joints commonly involved are proximal interphalangeal joint, metacarpo phalangeal joint, wrist, elbiw joint, knee joint, ankle joint, subtalar joint, upper cervical spine rarely temperomandibular joint.
8. Cervical spine invovement may lead to atlanto – axial subluxation, due to weakening of transeverse ligament of atlas. A ‘clunking sound’ is produced due to atlanto – axial involvement.
9. Temperomandibular joint involvement leads to pain on chewing.

DEFORMITIES :
With persistent inflammation, a number of characteristic joint changes develop due to laxity of supporting soft tissue, structures, damage or weakening of ligaments, tendons and joint capsule, cartilage degradation, muscle imbalance and unopposed physical forces associated with the use of affected joints.

1. Ulnar deviation of metacarpo phalangeal joint.
2. ‘Z’ shaped deformity of thumb, due to palmar subluxation of proximal phalanges.
3. ‘Swan neck deformity’ :– hypertension of proximal interphalangeal joints with flexion of distal interphalangeal joint.
4. Boutnnere deformity :– flexion contracture of the proximal interphalangeal joints and extension of distal interphalangeal joint.
5. Trigger – finger :- Tenosynovitis of the long flexor tendon of the palm of the hand.
6. Dropped finger :- Synovitis of the extensor tendons is common and may lead to rupture.
7. Piano – key sign :- Weakening of distal radio- ulnar joint by synovitis allows the distal ulna to migrate dorsally, that it overrides the radius, and ulna can be depressed by pressure like a ‘piano – key’.
8. Lateral subluxation of the knee joint.
9. Hammer toe – Flexion at the proximal interphalangeal joint and hyperextension at the distal metatarsophalangeal joint.
10. Hallux vulgus :- Lateral deviation of big toe.
Calcaneal erosions may develop at the insertion of the Achilles tendon or plantar fascia and eversion deformities at the subtalar joint.

EXTRA - ARTICULAR FEATURES :
As a rule extra articular manifestations occur in individuals with high titres of autoantibodies to Fc component of immunoglobulin G (Rheumatoid factor).
i) Rheumatoid nodules :- Firm, painless and non- tender swellings varying from a few millimeters to few centimeters in size. Rarely these may appear in the absence of typical articular disease called rheumatoid nodulosis. Common sites are extensor surface of forearm, olecranon, around tendons like Achilles, flexor and extensor tendons of fingers and over the sacrum. Rheumatoid nodules may also develop in many other tissues including the eye, pleura, pericardium and parenchyma of the lungs and heart.

ii)  Anaemia :- Normochromic mormocytic anaemia is a common finding in active rheumatoid arthritis.
iii) Vasculitis :- Vasculitis is more common in patients with high levels of IgM rheumatoid factor and severe joint disease. In most aggressive form rheumatoid vasculitis can cause polyneuropathy, mononeuritis multiplex, cutaneous ulceration, dermal necrosis, digital gangrene and visceral infarction.
iv) Pulmonary manifestations :-
a) Pleurisy
b) Nodules :- More common on upper zones. May be single or multiple. Cavitation may occur leading to haemoptysis, pneumothorax.
c) Pulmonary fibrosis
d) Caplan’s syndrome :- Rheumatoid nodules in individuals with pneumoconiosis causing diffuse nodular fibrosis.
e) Obliterative bronchiolitis causing acute onset of breathlessness.

v) Cardiac manifastations :-
a) Small pericardial effusion.
b) Valvulitis :- Granulomatous thickening of the cusps of the aortic valve and acute aortic regurgitation following perforation of one of the cusps may occur.
vi) Eye involvement :- Common in rheumatoid arthritis.
a) Sjogren’s syndrome :- in 1/5th of patients with rheumatoid arthritis. Symptoms consist of pain, erythema and grittiness in the eyes, photosensitivity and stickiness with adherent strands of mucus. Secondary bacterial infections are
common.
b) Episcleritis :- Appears as a raised lesion in the anterior sclera with hyperaemia of the deeper layers. Lesions are often transient.
c) Scleritis :- more serious and may lead to scleromalacia and even perforation.
vii) Neurological manifestations :-
a) Entrapment neuropathies like carpal tunnel syndrome.
b) Mononeuritis multiplex.
viii) Muscle involvement :- Reflex inhibition and wasting from severe joint pain.
ix) Mild hepatospleenomegaly may be present.
x) Juxta articular osteoporosis and fracture may develop with minimal trauma.
xi) Felty syndrome :- rheumatoid arthritis, spleenomegaly and leucopenia.

Investigations :
1. Blood – normocytic normochromic anaemia
raised platelet count
leucosytosis
ESR
Rheumatoid factor-Rose-waaler test
SCAT(sheep cell agglutination test)
Antinuclear antibodies
2. synovial fluid analysis
3. arthroscopy
4. imaging- stageI –periarticular osteoporosis
stageII-loss of articular cartilage
stageIII-erosions
stageIV-subluxation &ankylosis

Criteria for diagnosis of RA:
1. morning stiffness(for more than 1 hour).
2. arthritis of three or more joint areas.
3. arthritis of hand joints.
4. symmetrical arthritis.
5. rheumatoid nodules.
6. rheumatoid factor.
7. radiological changes.

Duration of 6 weeks or more.
Diagnosis of RA made with 4 or more criteria.

Management:-
1. relief of symptoms
2. suppression of active and progressive disease
3. conservation and restoration of function in affected joints.

Treatment of the patient- drugs, rest, physiotherapy
Modification of the environment-aids,appliances, housing, occupation,statuory social benefits.

Grouping of function in rheumatoid arthritis:
I -Fit for all activities-no handicap.
II-moderate restriction – independent despite some limitation of joint movement.
III- marked restriction-limited self-care. Some assistance required.
IV-confined to chair or bed-bound-largely incapacitated and dependent.

Patient education, counseling and continuing medical support are usually required for successful management, while physical rehabilitation, reconstructivesurgery and environmental adaptation assume increasing importance when advancing joint damage and deformity are associated with functional impairment.