Presented by

Prof.Dr. Nahla Mohamed Gaballah

Professor & Head of Rheumatology and Rehabilitation Department

Definition:

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease primarily involving the joints, most commonly the small joints of the hands & feet and progress in systemic fashion to involve synovial joints all over the body.

Incidence: The disease occurs in

approximately 3% of the adult population.

Sex distribution: 3 females:1 male.

Age: Most commonly middle –aged

adults between 30-40 years, but many occur at any age group.

If it occur before 16 years old, its called Juvenile Rheumatoid Arthritis(JRA)(STILL’SDISEASE).

Also, it may begin after the age of 50 years (ELDERLY RA) which usually takes more benign course.

AETIOLOGY

There is no specific aetiology .BUT ,there are several predisposing or initiating factors that predispose to the occurrence of the disease .

Genetic factor: The association of RA and the humen

leukocyte antigen (HLA antigens DR1 and DR4) is well established.

Also, RA patients possess HLA DR2 considered an indicator of good prognosis.

On the other hand seropositive erosive diseases are more likely in HLA DR3.

There is a higher prevalence of RA in the first degree relatives and in monozygotic twins.

Infectious agents: Microbes are the most triggering

agents of the disease in genetically predisposed individuals.many bacterial organisms such as diphetroid and mycoplasma.

Also virus such as Epstein Barr virus considered as a potential etiologic agent for RA .

Hormonal factor: Higher incidence of the disease

occurs in female about (70%). The incidence is lower in females taking

contraceptive pill, also remissions of disease activity commonly in pregnancy which occur due to the association with alpha 2 glycoprotein which is immunosuppressive and the immuno modulating properties of female sex hormones.

Auto immunity: RA is one of the autoimmunes

disease in which the antibodies are produced against normal IgG of self .

PATHOGENESIS

One or several antigens will activate T cells which becomes the first major amplification step in the pathogenesis of RA. colonel expansion of T cells will drive B lymphocytic proliferation and production of antibodies including rheumatoid factor (RF).

This immunological events causes inflammation of the synovial membrane (synovitis).

So the synovial membrane becomes thickened ,hyperplastic, hyperaemic , oedematous and proliferate to form villi filling the joint space produce (Pannus) which released damaging chemicals into synovial fluid so ,erode the cartilage.

Normal Early RA

Soft tissue swelling due to:- Synovitis- Effusion- Capsule thickening

Established RA

Chronic RA

- Cartilage erosion- Bone destruction- Subluxation

Bone

Synovial membrane

Articular cartilage

Periarticular osteoporosis

Pannus

Erosion of cartilage

Pathogenesis of RA

CLINCAL PICTUREOnset: - mode of onset: Insidious Acute precipitated

by physic trauma. -Pattern of onset: -monoarticular - Pauciarticular - Oligoarticular - PolyarticularCourse: - progressive -regressive -remission and exacerbation

Duration.

Sequence of joint involvement

Morning stiffness: difficulty in movements of joints due to accumulation of inflammatory metabolites at nights due to immobilization of joints.

A-Articular manifestations: Any synovial joints all over the body can

be affected but the classic presentation are affection of small joints of hands, feet and wrists.

RHUEMATOID HAND AND WRIST:

Early:The hand feels stiff,swollen,difficulty in

making a fist and lifting things.-Fusiform swelling of the finger .-Swelling of the second and third MCP with

filling in hollows between knuckles.-Extensor tendon sheath swelling .

Early RA: Fusiform swelling of proximal interphalangeal joints PIP of both hands

-Swelling on dorsal aspect of wrist.

-Triggering of fingers.

-Carpal tunnel syndrome.

-Prominent ulnar styloid (piano sign)

-Wasting of small muscles.

Late:The characteristic rheumatoid deformity

including:*Swan neck deformity:flexion of DIP and MCP joints with

hyperextension of PIP joint*Boutonniere deformity(button hole

deformity):Flexion of PIP, MCp joints with

hyperextension of DIP joint

Swan neck deformity

Button hole deformity

*Z-shaped deformity of the thumb:Flexion of MCP of the thumb with

hyperextension of IP joint(from the patient need to pinch).

*Radial deviation of the wrist

*Ulnar deviation of MCP

*Rupture extensor tendons (dropped fingers)

(A) MCP swelling with ulnar deviation

(B) Swelling of the wrist

A

B

Late RA

B-extra- articular manifestations:1-Rheumatoid nodules: occur in 15-20% of

RA patients usually subcutaneous over the extensor surface of elbow , over bony prominences such as head , sacrum and Achilles tendon.

They are usually mobile but they may bound to the periosteum and they have certain characteristic pathological pattern . they may be single or multiple , may decrease in size with treatment but do not disappear .

It is associated with positive rheumatoid factor and their prescence indicate poor prognosis .

They may appear around fingers called intra cutaneous and even may appear in the internal organs such as heart ,lung.

2-Anaemia: It present in patients with active RA its

usually normocytic normochromic anaemia ,it may occur as a result of blood loss or marrow suppression by drugs or as a part of felty syndrome (variant of RA).

 3-Lymphandenopathy :

The nodes are soft,mobile non tender (one or two) it is diagnostic for felty if it is associated with splenomegaly ,anaemia, positive RF and leucopenia.

4-Osteoprosis:Early localized periartciular

osteoporosis in x-ray film. Late generalized osteoporosis as a

result of immobilization and drugs used.

5-Eye involvement:

In the form of episteritis (common and self limiting),

keratoconjunctivitis sicca(sjogen’s syndrome),

Scleritis occur in severe systemic RA with vasculitis.

6-Lung involvement:Lung is a common site of extra-articular

involvement in RA in the form of pleurisy, pleural effusion .

*Rheumatoid nodues in the lung.*Interstitial fibrosis.*Rheumatoid

pneumoconiosis(Caplan’ssyndrome).

7-Heart involvement: in the form of pericarditis pericardial

effusions ,nodules in the conducting system and on the valves.

8-Neuromuscular involvement.

9-Renal and liver involvement. 

 “LABORATORY INVESTIGATIONS”

-Complete blood picture (C.B.C).-Erythrocyte sedimentation rate(ESR).-C-reactive protein titre.

-Rheumatoid Factor : Detected by latex fixation test or Rose

waeler method. Positive in 75-80% of RA patients but can be only detected in 5 % of normal population,

Its titre may decrease with the improvement of the disease activity,but it never turn negative and the controversy is true as it can changed from negativety(early) towards positivety

Anti- Cyclic Citrillunated Peptide (CCP) antibody:

It has high diagnostic specificity for RA and used recentely in the new criteria for diagnosis of earlyRA.

It provide prognostic information on the severity of the disease.

DIAGNOSISThe American Rheumatism Association

criteria (ARA) for diagnosis of RA:1-Morning stiffness lasting to at least one

hour before maximal improvement2-Symmetric arthirits3-Arhititis of 3 or more joint area out of 14

joint areas (PJP,MCP,wrist,elbow,knee,ankle,MTP joints) Rt and Lt side.

4-Arthiritis of one joint area below the wrist

5-Subcutaneous nodules6-Positive serum rheumatoid factor7-Radiological changes

A patient is said to have RA if satisfied at least 4 of the above 7 criteria

Criteria 1 to 4 must be present for at least 6 weeks

TreatmentThe “goal of treatment “is to control pain

and inflammation, prevent joint damage and disease disability which can be done by:

1-Education to the patients and their families about the native of the disease

2-Rest (short periods of bed rest mainly in the acute stage) and splints for the inflamed joints

3-Disease modification through the suppression of inflammation and the immunologic process by using immune suppressive drug therapy (once the disease has diagnosed the use of the immune suppressive drugs(DMARDS) should be started such as :

Methotrexate: 10-25 mg i.m/ week, it has rapid onset of action (4-6weeks), safe and not expensive.

Leflonamide (avara): can be used in patients intolerant to methotrexate with oral loading dose of 100 mg daily for 3 days followed by maintainance dose of 10-20 mg daily.

 

Sulfasalazine (salazopyrine): tablet 500 mg starting by one then gradually increased to four tablets daily.

Antimalarial drugs such as dagrenol giving as one tablet daily

Azathioprine,Gold(myocrisin),cyclosporine

Most patients respond well to combination therapy such as methotrexate and antimalarial.

However , we can use steroid as a bridge therapy until the immune suppressive drugs start its action ,while NSAIDS (non steroidal anti inflammatory drugs) are used to decrease the pain only and not stop the pathological progression or rheumatoid disease.

 

 4-Anticytokine therapy:

It is newly developed targeted therapy , highly effective for control disease activity and prevention of structural damage ,it is highly indicated in patients with active disease not controlled by DMARDS but it has very high cost such as:

Anti-TNF alpha e.g Etanercept 25 mg twice weekly S.C or 50 mg once weekly.

Infliximab (Remicade) intravenous infusion at 0,2,6 week then every 2 months 3-5 mg /week.

Adalimumab (Humira) 40 mg every two weeks S.C.

Anti –IL 1 receptor antagonist e.g Anakinra.

5-Maintenance of join function and prevention of deformity by physical therapy in the form of regular active exercises after heat application ,maintain the strength of muscle ,assisted active or active range of motion to the joints and avoidance of positions of deformity by using splints.

6-Repair of joint damage if it will relieve pain or facilitate function (joint replacement therapy) arthroplasty.

ThankThank youyou