Rheumatoid arthritis - Rheumatology Flashcards
RA definition, aetiology(A++), pathogenesis and C/P?
Definition:
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily involving the synovial joints. Most commonly, the wrists and small joints of the hands & feet are involved, on both sides of the body.
Aetiology:
There is no specific etiology. BUT there is a combination of genetic, infectious and environmental factors.
1- Genetic factor:
o The association of RA and the human leukocyte antigen (HLA antigens DR1 and DR4) is well established.
o Also, RA patients possess HLA DR2 considered an indicator of good prognosis.
o Seropositive erosive severe diseases are more likely associated with HLA DR3.
o There is a higher prevalence of RA in the first-degree relatives and in monozygotic twins.
2-Infectious agents:
o Microbes are the most common triggering agents of the disease in genetically predisposed individuals.
o Many bacterial organisms such as diphetroid and mycoplasma are claimed.
o Also, viruses such as Epstein Barr virus are considered as a potential etiologic agent for RA.
3-Hormonal factor:
o Higher incidence of the disease occurs in female about (70%).
o The incidence is lower in females taking contraceptive pill, also remissions of disease activity occur in pregnancy due to the immunosuppressive effect of alpha 2 glycoprotein and the immune modulating properties of female sex hormones.
4- Auto immunity:
RA is one of the autoimmune diseases in which the antibodies are produced against normal IgG of self, such as rheumatoid factor (RF) and Anti- Cyclic Citrullinated Peptide (CCP) antibodies.
Pathogenesis:
One or several antigens will activate T cells. Clonal expansion of T cells will drive B lymphocytic proliferation and production of antibodies including rheumatoid factor (RF).
This immunological event causes inflammation of the synovial membrane (synovitis).
So, the synovial membrane becomes thickened, hyperplastic, hyperaemic, oedematous and proliferates to form villi filling the joint space, producing (Pannus), which releases damaging chemicals into synovial fluid so, erode the cartilage.
C/P:
- Onset:
o Insidious
o acute precipitated by physical trauma
o palindromic.
-Pattern of onset:
o Monoarticular
o Pauciarticular
o Oligoarticular
o Polyarticular
-Course:
o Progressive
o Regressive
o Remission and exacerbation
- Presentations:
Articular manifestations: affection of peripheral joints in a symmetric pattern.
Extra-articular involvement of organs such as the skin, heart, lungs, and eyes can be significant.
Constitutional symptoms, including fatigue, malaise, and morning stiffness
Morning stiffness: Difficulty in movements of joints due to accumulation of inflammatory metabolites at night due to immobilization of joints.
Rheumatoid Hand and Wrist Clinical picture?
Early:
- The hand feels stiff, swollen, difficulty in making a fist and lifting things.
- Fusiform swelling of the fingers.
- Swelling of the second and third MCP with filling in hollows between knuckles.
- Extensor tendon sheath swelling.
- Swelling on dorsal aspect of wrist.
- Triggering of fingers.
- Carpal tunnel syndrome.
- Prominent ulnar styloid (piano sign)
- Wasting of small muscles.
Late RA:
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
*Z-shaped deformity of the thumb:
Flexion of MCP of the thumb with hyperextension of IP joint
*Radial deviation of the wrist
*Ulnar deviation of MCP & MCP swelling.
Prominent ulnar styloid process.
*Rupture extensor tendons (dropped fingers)
RA extra- articular manifestations Clinical picture? (A+++)
1-Rheumatoid nodules:
o They 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.
o They are usually mobile but they may be bound to the periosteum.
o They may be single or multiple, may decrease in size with treatment but do not disappear.
o They are associated with positive rheumatoid factor and their presence indicate poor prognosis.
o They may appear around fingers called intra-cutaneous and even may appear in the internal organs such as heart, lung.
2-Anaemia:
It is present in patients with active RA. It’s usually normocytic normochromic anaemia. It may occur as a result of blood loss or marrow suppression by drugs or as a part of Felty’s syndrome (variant of RA).
3-Lymphadenopathy:
The nodes are soft, mobile non tender (one or two).
if it is associated with splenomegaly, anaemia, positive RF and leukopenia, lymphadenopathy is diagnostic for Felty’s syndrome.
4-Osteoporosis:
o Early localized periarticular osteoporosis.
o Late generalized osteoporosis as a result of immobilization and drugs.
5-Eye involvement:
In the form of:
Episcleritis (common and self-limiting),
Keratoconjunctivitis sicca (Sjogren’s syndrome),
Scleritis occur in severe systemic RA with vasculitis.
6-Lung involvement:
Lung affection is a common in RA, in the form of:
*Pleurisy, pleural effusion.
*Rheumatoid nodules in the lung. *Interstitial fibrosis.
*Rheumatoid pneumoconiosis (Caplan’s syndrome).
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
RA lab investigations and Imaging + ACR criteria (A+++) ?
Laboratory Investigations:
-Complete blood picture (CBC).
-Erythrocyte sedimentation rate (ESR).
-C-reactive protein (CRP).
-Rheumatoid Factor:
Detected by latex fixation test or Rose wooler 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.
- Anti- Cyclic Citrullinated Peptide (CCP) antibody:
It has high diagnostic specificity for RA and used in the new criteria for diagnosis of early RA.
It provides prognostic information on the severity of the disease.
Imaging:
X-ray of the hand in RA
American College of Rheumatology (ACR) criteria for the diagnosis of RA:
1. Morning stiffness
2. Arthritis of 3 or more joint areas, observed by a physician.
3. Arthritis of hand and wrist joints
4. Symmetric arthritis
5. Rheumatoid nodule
6. Serum Rheumatoid Factor
7. Radiographic changes hand and wrist radiographs–erosions or juxta-articular osteopenia
RA treatment?
A- The goals of treatment are to minimize symptoms such as pain and swelling, to prevent bone deformity, and to maintain day-to-day functioning
B- 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.
C- Lines of Medical Treatment
▪ Non steroidal Anti inflammatory drugs (NSAIDs) and steroids relief symptoms.
▪ Disease-modifying antirheumatic drugs (DMARDs) are the primary treatment for RA. They improve symptoms, decrease joint damage, and improve overall functional abilities. DMARDs should be started early in the disease as they improve outcomes overall.
1-NSAIDS (non-steroidal anti-inflammatory drugs) are used to decrease the pain only and not stop the pathological progression or rheumatoid disease. Steroids can be used as a bridge therapy until the immune suppressive drugs start its action.
2- Methotrexate: 10-25 mg i.m/ week, onset of action (4-6weeks), safe and not expensive.
3- Leflunomide (avara): can be used in patients intolerant to methotrexate with oral loading dose of 100 mg daily for 3 days followed by maintenance dose of 10-20 mg daily.
4- Sulfasalazine (salazopyrin): tablet 500 mg starting by one then gradually increased to four tablets daily.
5- Antimalarial drugs: chloroquine & hydroxychloroquine
N.B. Most patients respond well to combination therapy such as methotrexate and antimalarial.
6- 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.
7- Anti-TNF alpha:
o Etanercept 25 mg twice weekly S.C or 50 mg once weekly.
o Infliximab (Remicade) intravenous infusion at 0,2,6 week then every 2 months 3-5 mg /week.
o Adalimumab (Humira) 40 mg every two weeks S.C.
8- Anti –IL 1 receptor antagonist: Anakinra.
9- Anti-IL-6: Tocilizumab
Arthroplasty (joint replacement therapy): Repair of joint damage if it will relieve pain or facilitate function.
