Rhumatoid Arthritis

1. Rheumatic
Diseases

2. Rheumatic Diseases

3. Rheumatoid Arthritis
• Rheumatoid arthritis is an autoimmune disease in which the
normal immune response is directed against an individual's
own tissue, including the joints, tendons, and bones, resulting
in inflammation and destruction of these tissues
• The cause of rheumatoid arthritis is not known
– Investigating possibilities of a foreign antigen, such as a virus

4. Epidemiology Rheumatoid Arthritis
• RA affects 1% of the adult population, with a peak onset most often
between 40 and 50 years of age. Women are more affected than men
(3:1). The prevalence of RA in women older than 65 years is as much as
5%, making RA a significant cause of morbidity.
• Both prevalence and incidence are 2-3 times greater in women than in
men
• African Americans and native Japanese and Chinese have a lower
prevalence than Caucasians
• Several North American Native tribes have a high prevalence
• Genetic factors have an important role in the susceptibility to rheumatoid
arthritis

5. Rheumatoid Arthritis
• Rheumatoid arthritis usually has a slow, insidious onset over
weeks to months
• About 15-20% of individuals have a more rapid onset that
develops over days to weeks
• About 8-15% actually have acute onset of symptoms that
develop over days

7. Rheumatoid Arthritis
• Description
– Morning stiffness
– Arthritis of 3 or more joints
– Arthritis of hand joints
– Symmetric arthritis
– Rheumatoid nodules
– Serum rheumatoid factor
– Radiographic changes
• A person shall be said to have
rheumatoid arthritis if he or
she has satisfied 4 of 7
criteria, with criteria 1-4
present for at least 6 weeks

8. Etiology Causes
• rheumatoid arthritis is a systemic autoimmune disease in which abnormal
activation of B cells, T cells, and innate immune effectors occurs. In
contrast to SLE, the majority of inflammatory activity in rheumatoid
arthritis occurs in the joint synovium. Although the cause of rheumatoid
arthritis is unknown, a complex set of genetic and environmental factors
appears to contribute to disease susceptibility. Because the incidence of
rheumatoid arthritis has been observed to be similar in many cultures and
geographic regions across the globe, it is assumed that the environmental
exposures that provoke rheumatoid arthritis must be widely distributed.
Early rheumatoid arthritis is closely mimicked by transient inflammatory
arthritis provoked by several microbial pathogens. Thus, although a role
for infection in the development of rheumatoid arthritis has long been
postulated, it is not yet satisfactorily proven. Specific class II MHCalleles
(HLA-DR4), sharing a consensus QKRAA motif in the peptide-binding
groove, have been highly related to disease susceptibility and to greater
severity of rheumatoid arthritis.

9. Functional Presentation and Disability
of RA
• In the initial stages of each joint involvement, there is
warmth, pain, and redness, with corresponding decrease of
range of motion of the affected joint
• Progression of the disease results in reducible and later fixed
deformities
• Muscle weakness and atrophy develop early in the course of
the disease in many people

10. Pathophysiology
• Much of the pathologic damage that characterizes rheumatoid arthritis is
centered around the synovial linings of joints. Normal synovium is
composed of a thin cellular lining (one to three cell layers thick) and an
underlying interstitium, which contains blood vessels but few cells. The
synovium normally provides nutrients and lubrication to adjacent articular
cartilage. Rheumatoid arthritis synovium, in contrast, is markedly
abnormal, with a greatly expanded lining layer (8–10 cells thick) composed
of activated cells and a highly inflammatory interstitium replete with B
cells, T cells, and macrophages and vascular changes (including thrombosis
and neovascularization). At sites where synovium and articular cartilage
are contiguous, rheumatoid arthritis synovial tissue (called pannus)
invades and destroys adjacent cartilage and bone.

11. Sign & Symptoms
• Patients often present with gradual onset of pain
• swelling in peripheral joints,
• usually polyarticular and symmetric.
• Morning stiffness (>1 hour) is a key feature.
• Constitutional symptoms such as weight loss,
• fatigue, and anorexia may also occur and even
precede the onset of joint symptoms.

12. DIAGNOSTIC EVALUATION
• American Rheumatism Association's diagnostic criterion for RA. Most
criteria are achieved through clinical examination and history. Two
additional criteria are rheumatoid factor (RF) and plain films. RF is an
autoimmune antibody to IgG and is positive in 70% to 80% of patients with
RA. However, it is not specific for RA and by itself does not confirm the
diagnosis. The following conditions may have a positive RF in the absence
of RA:
• Older age
• Other autoimmune diseases (SLE, sarcoid, etc.)
• Infective endocarditis
• Liver disease (especially hepatitis C)
• Chronic infections (syphilis, leprosy, parasites)
• Hyperglobulinemic states

13. DIAGNOSTIC EVALUATION
• Because of the lack of specificity, other antibody testing may be used in
combination with RF. Antibodies to citrulline-containing proteins (anti-
CCP) are seen in RF patients, with sensitivity for RA approximating that of
RF. However, anti-CCP has much greater specificity (90% to 96%). Although
anti-CCP is not yet included in the American Rheumatism Association's
diagnostic criterion for RA, initial anti-CCP testing (as well as antinuclear
antibody and hepatitis testing) is frequently performed for initial
diagnosis. Plain films of the hands may demonstrate periarticular
osteopenia or erosions, usually in more advanced disease.

14. Criteria for Diagnosis of
Rheumatoid Arthritis
• Morning stiffness of joints >1 hr for at least 6 wk
• Arthritis (soft tissue swelling) of three or more joints for at
least 6 wk
• Arthritis includes wrist, metacarpophalangeal, or proximal
intraphalangeal joints
• Arthritis is symmetric
• Rheumatoid nodules
• Elevated serum rheumatoid factor
• Hand or wrist films showing erosions or periarticular
osteopenia
• aFour or more criteria are necessary for definite diagnosis.

15. • Other laboratory findings measure the inflammatory nature of
the disease, such as an increased erythrocyte sedimentation
rate (ESR) or C-reactive protein (CRP). Joint aspiration is
usually performed to rule out other causes, such as infection
or gout. See Chapter 56 for a discussion of the joint fluid
examination.
• Chest radiograph may reveal extra-articular disease such as
rheumatoid nodules, interstitial lung disease, or pleural
effusions. Pulmonary nodules should be tested in the usual
manner (see Chapter 19). Effusions that are tapped show an
exudative pattern, usually with a low fluid glucose level.

16. Treatment
– Surgery: video
• Removal of inflamed
synovium
• Arthroplasty
– Physical therapy

17. Treatment
• Symptom relief in RA may initially rely on analgesics including NSAIDs.
Examples include ibuprofen, ketoprofen, and naproxen. NSAIDs do not
significantly influence synovial inflammation or joint destruction.
Side effects of NSAIDs are numerous and include:
• Peptic ulcers/gastritis
• Renal dysfunction
• Increased liver enzymes
• Rash

18. • COX-2 inhibitors such as celecoxib are NSAIDs that selectively inhibit the
cyclooxygenase-2 enzyme (involved in inflammation) and not the
cyclooxygenase-1 enzyme (involved in gastric mucosa protection). These
are reserved for use in selected patients at high risk for GI because they
are expensive, and COX-2 inhibitor use is associated with an increased risk
of cardiovascular disease. Celecoxib is a sulfonamide derivative and is
avoided in patients with a history of severe sulfa allergy. As an alternative
to COX-2 inhibitors, use of traditional NSAIDs with a proton pump inhibitor
or the prostaglandin analogue misoprostol offers GI bleeding protection.
• Corticosteroids should be used sparingly in RA. Prednisone is effective to
relieve symptoms, but the numerous side effects (osteoporosis,
immunosuppression, hyperglycemia) make this choice less desirable over
the long term. Corticosteroids may be used as a bridge to the DMARDs.

19. • DMARDs have the added benefit of slowing disease progression in RA.
DMARDs should be started early (within 3 months) in almost all patients
with RA to prevent further joint destruction. Typical DMARDs and their
common side effects are:
• Methotrexate (bone marrow toxicity, hepatic fibrosis, pneumonitis,
stomatitis)
• Sulfasalazine (rash)
• Antimalarials, such as hydroxychloroquine (retinopathy)
• Leflunomide (diarrhea, rash)
• Minocycline (hyperpigmentation)
• Azathioprine (immunosuppression)

20. • Methotrexate is used as a first-line DMARD in many patients with RA.
Methotrexate has a high clinical response rate and an acceptable
treatment adherence rate. It is given in low doses (7.5 to 15 mg) in weekly
intervals. The dose should be increased up to 25 mg weekly when patients
fail to respond. A unique feature of methotrexate is that rheumatoid
nodules may increase with initiation of treatment. Liver biopsy for
cirrhosis was once recommended for all patients on treatment but now is
reserved for persistent liver function abnormalities. Alcohol should
certainly be avoided to minimize the risk of liver damage. GI symptoms
may be decreased with oral folate supplements. An alternative to
methotrexate therapy is leflunomide, a pyrimidine synthesis inhibitor. The
dosage is 10 to 20 mg daily, and its efficacy is similar to methotrexate.
DMARDs can be used in combination, but an optimal combination therapy
is not yet clear.

21. Psoriatic Arthritis
• Causes pain and swelling in some
joints and scaly skin patches on some
areas of the body.
• The symptoms are:
– About 95% of those with psoriatic arthritis
have swelling in joints outside the spine,
and more than 80% of people with
psoriatic arthritis have nail lesions. The
course of psoriatic arthritis varies, with
most doing reasonably well.
– Silver or grey scaly spots on the scalp,
elbows, knees and/or lower end of the
spine.
– Pitting of fingernails/toenails
– Pain and swelling in one or more joints
– Swelling of fingers/toes that gives them a
"sausage" appearance.

22. Reference
• Blueprints Medicine, 5th Edition Authors: Young, Vincent B.; Kormos,
William A.; Chick, Davoren A.; Goroll, Allan H. Part 7, Chapter-58
Rheumatoid Arthritis Page 126.
• Pathophysiology of Disease An Introduction to Clinical Medicine, 6th
Edition Previous editions copyright © 2006, 2003, 2000 by The McGraw-
Hill Companies, Chapter 24, Inflammatory Rheumatic Diseases.