Rheumatoid Arthritis (RA)

Karina Vilá, MD

Rheumatologist

Definition

Epidemiology

Risk Factors

Pathophysiology

Signs and symptoms including extra-articular manifestations

Complications

Diagnosis

Treatment

Definition

• A chronic, systemic, inflammatory autoimmune disease

• Most common form of inflammatory disease that affects diarthrodialjoints, causing a painful swelling

• It can lead to bone erosion and irreversible joint deformity and disability

Epidemiology

• Female:male – 3:1

• Age of onset – 35 to 50 years old

• Prevalence – 1 per 100 patients

• Incidence – 0.5 per 1000 persons per year in the U.S.

AgeFamily

GenderImmune system

GenderWomen are more likely to develop RA than men are.

AgeRA can occur at any age, but it most commonly begins between the ages of 40 and 60.

Family HistoryCases of RA in the

family may increase the risk of the

disease

Immune SystemRA occurs when the

immune system mistakenly attacks

body’s tissues

• The pathogenesis of RA is not completely understood. An external trigger (eg, cigarette smoking, infection, or trauma) that triggers an autoimmune reaction, leading to synovial hypertrophy and chronic joint inflammation along with the potential for extra-articular manifestations, is theorized to occur in genetically susceptible individuals.

• Synovial cell hyperplasia and endothelial cell activation are early events in the pathologic process that progresses to uncontrolled inflammation and consequent cartilage and bone destruction. Genetic factors and immune system abnormalities contribute to disease propagation.

• CD4 T cells, mononuclear phagocytes, fibroblasts, osteoclasts, and neutrophils play major cellular roles in the pathophysiology of RA, whereas B cells produce autoantibodies (ie, RFs). Abnormal production of numerous cytokines, chemokines, and other inflammatory mediators (eg, tumor necrosis factor alpha [TNF-a], interleukin [IL]-1, IL-6, IL-8, transforming growth factor beta [TGF-ß], fibroblast growth factor [FGF], and platelet-derived growth factor [PDGF]) has been demonstrated in patients with RA.

• Ultimately, inflammation and exuberant proliferation of the synovium (ie, pannus) leads to destruction of various tissues, including cartilage, bone, tendons, ligaments, and blood vessels. Although the articular structures are the primary sites involved by RA, other tissues are also affected.

Polyarticular(>4 joints)

Systemic

• Swelling and tenderness of small peripheral joints (metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints of the fingers, interphalangealjoints of the thumbs, metatarsophalangeal (MTP) joints and wrists)

• Larger peripheral joints may become affected - ankles, knees, elbows and shoulders

• Firm bumps of tissue under the skin (nodules)

• Fever, weight loss or fatigue

• Morning stiffness that may last for hours ≥1 hour

• Limited range of motion

• Clinical evaluations should be done periodically as a response to new symptoms.

• Monitor the patient for the conditions below and if any co-morbidities arise refer to a specialist.

• ACR • Uveitis/scleritis

• Lung involvement

• Renal

• Vasculitis

• Perciarditis

Episcleritis Vasculitis

Perciarditis

Osteoporosis Heart problems

Carpal tunnel syndrome Lung disease

• RA along with some medications can increase the risk of osteoporosis

•RA can increase the risk of hardened and blocked arteries, as well as inflammation of the sac that encloses the heart

• If RA affects the wrists, the inflammation can compress the nerve that serves most on hand and fingers

• RA have an increased risk of inflammation and scarring of the lung tissues, which can lead to progressive shortness of breath

Systemic connective tissue disorders

• Systemic lupus erythematosus (SLE)

• Mixed connective tissue disease (MCTD)

• Sjögren’s syndrome

Seronegative spondyloarthropathies

• Psoriatic arthritis (PsA)

• Ankylosing spondylitis (AS)

• Reactive arthritis

Infectious asthritis

• Lyme-associated arthritis

• Hepatitis C-associated arthritis

• Parvovirus B19-associated arthritis

• Revised ACR/EULAR 2010 classification criteria for RA

Source: American College of Rheumatology, Celltrion, EULAR

The new 2010 classification system redefines the current RA paradigm by focusing on the features at earlier disease stages that are associated with persistent and erosive disease, rather than defining the disease by its late-stage features.

• CR, a 40 year old woman noted bilateral hand discomfort for 4 months, followed 2 month later by bilateral foot pain when walking.

• Self medicated with ibuprofen decided to visit her family physician:

– Complains of stiffness after awakening (2 hours), which improves gradually through the day

– Has difficulty turning faucets

– Sleep disturbed by pain

• Normal physical examination, except for:

– 3 swollen proximal interphalangeal (PIP) joints on the right hand and 4 on the left

– Feet tender to palpation without obvious synovitis

– Compression of metatarsophalangeal (MTP joints causes pain (positive squeeze test)

• Laboratory values:– ESR: Elevated

– CRP: Normal

– RF: Negative

– Anti-CCP: Positive

– ALT/AST: Normal

• X-ray of hands, feet and wrists– Soft tissue swelling most apparent around PIP and MCP joints in the index and middle

fingers

Provisional Diagnosis

?

In a survey of 168 RA patients, there was a median delay of 12 weeks before a patient was assessed in primary care

A key reason RA patients are seen late by rheumatologists is that patients delay talking about symptoms with their PCP

Early identification of RA can improve the long term outcome of the disease

3

2

1

Steps

Refer• Direct the patient to the

appropriate specialist

• Relay important patient assessment information

Identify• Identify the signs and

symptoms of RA

• Perform a clinical examination

Evaluate• Order baseline and diagnostic

lab/imaging tests

• Provide a provisional diagnosis

• Rheumatoid arthritis can be difficult to diagnose in its early stages because the early signs and symptoms mimic those of many other diseases.

Identify:

•Perform a physical exam to check joints for swelling, redness and warmth, reflexes and muscle strength.

Evaluate:• Order X-rays to track the progression of

RA in joints over time.

•Order ESR or sed rate test. People with RA tend to have an elevated erythrocyte sedimentation rate, which indicates inflammatory process in the body.

•Order blood tests looking for RA factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies.

•Perform preliminary diagnosis.

• There is no cure for RA.

• Medications can reduce inflammation in joints in order to relieve pain and prevent or slow joint damage.

• Occupational and physical therapy can teach how to protect joints.

• Surgery may be necessary if joints are severely damaged by RA.

• Many drugs used to treat RA have potentially serious side effects.

NSAIDs

• Non-steroidal anti-inflammatory drugs relieve pain and reduce inflammation.

• Side effects may include ringing in ears, stomach irritation, heart problems, and liver and kidney damage.

Steroids

• Corticosteroid medications, such as prednisone, reduce inflammation and pain and slow joint damage.

• Side effects may include thinning of bones, cataracts, weight gain and diabetes.

• The goal is gradually tapering off the medication.

Disease-modifying anti-rheumatic drugs (DMARDs)

• Slow the progression of RA and save the joints and other tissues from permanent damage.

• Include methotrexate, hydroxychloroquine(Plaquenil)

• Side effects vary but may include liver damage, bone marrow suppression and severe lung infections.

Immunosuppressants

• Examples include azathioprine (Imuran)

• Can increase susceptibility to infection.

TNF-alpha inhibitors• Tumor necrosis factor-alpha is an

inflammatory substance produced by the body.

• TNF-alpha inhibitors can help reduce pain, morning stiffness, and tender or swollen joints.

• Examples include etanercept(Enbrel), infliximab (Remicade), adalimumab (Humira), golimumab (Simponi) and certolizumab (Cimzia).

• Potential side effects include nausea, diarrhea, hair loss and an increased risk of serious infections.

Other drugs

• Target a variety of processes involved with inflammation in the body.

• Include anakinra (Kineret), abatacept (Orencia), rituximab (Rituxan), tocilizumab (Actemra) and tofacitinib (Xeljanz).

• Side effects vary but may include itching, abdominal pain, headache, runny nose or sore throat.

• Education

• Physical therapies /exercises

• Surgery: May help restore the ability to use joints, reduce pain and correct deformities.

Total joint replacement: Surgeon removes the damaged parts of the joint and inserts a prosthesis made of metal and plastic.

Tendon repair: Inflammation and joint damage may cause tendons around the joint to loosen or rupture. Surgeon may be able to repair the tendons around the joint.

Joint fusion. Surgically fusing a joint may be recommended to stabilize or realign a joint and for pain relief when a joint replacement isn't an option.

1 2 3

• Physiotherapy treatment is important in helping patients with RA manage their disease.

• In conjunction with occupational therapists, physiotherapists can educate patients in:

Performance of therapeutic

exercises

Use of assistive devices

Joint protection strategies

• Rest and splinting, using compressive gloves, assistive devices, and adaptive equipment, have beneficial effects in managing RA symptoms and deformities.

Rest

The joints should be put into rest at a functional position during the acute stage of the disease: shoulder joint in 45⁰ abduction, both wrist joints in 20⁰ to 30⁰ dorsal flexion, fingers slightly in flexion, hips at 45⁰ abduction without any flexion, knees totally extended, and feet in a neutral position.

Splinting

Orthosis and splinting are used to diminish pain and inflammation, to prevent development of deformities, to prevent joint stress, to support joints, and to decrease joint stiffness.

Various reports have shown benefits of wrist splints in controlling pain/inflammation and increases hand grip strength by 20% to 25%.

• Patients have reported reduced joint swelling and increased well-being however, there is no positive evidence regarding improved grip strength or hand functions from using gloves.

• Gentle compression is beneficial because of the containment of joint swelling and subsequent decrease of pain.

Examples

Loading over the hip joint may be reduced by 50% by holding a cane

Elevated toilet seats, widened gripping handles, etc. might facilitate the daily life

Assistive Devices

Reduce functional deficits, diminish pain, and keep patients’ independence and self-efficiency

Occupational Therapy

Improves functional ability in patients with RAHave beneficial effects on joint protection and

energy conservation in arthritic patients

Massage Therapy

Improves flexibility

Improves general well

being

Diminish swelling of inflamed

jointsDecreases

stress hormone

levels

Effective on depression, mood and

pain

Enhances connection with other treatment

Dhondt and colleagues have reported that pain thresholds both at the massage site and at the knee and ankle have decreased after applying oscillatory manual massage to the intervertebral paraspinal region. This leads to the question of whether there are some changes in peripheral nociceptive perception and central information in RA.

• Muscle weakness in patients with RA may occur because of immobilization or reduction in activities of daily living.

• Maintenance of normal muscle strength is important not only for physical function but also for stabilization of the joints and prevention of traumatic injuries.

Whether the involvement of the joints is local or systemic

Stage of the disease

Age of the patient

Compliance of the patient with the therapy

ROM exercises, stretching, strengthening, aerobic conditioning exercises, and routine daily activities may be used as components of exercise therapy

Swimming, walking, and cycling with

adequate resting periods

increase muscle

endurance and aerobic

capacity

Chronic stage

Should avoid activities such

as climbing stairs or weight

lifting

Active arthritis

Isometric exercises

provide adequate

muscle tone. Moderate

contractures should be held

for 6 seconds and repeated

5-10 times each day.

Acute arthritis

• In patients with RA, sociopsychological factors affecting the disease process such as poor social relations, disturbance of communication with the environment, and unhappiness and depression at work are commonly encountered.

• All clinics that deal with the treatment of RA should provide education and information to their patients about their condition and the various physical therapy and rehabilitative options that are available to improve their quality of life.

Improve our patient quality of life

Final Goal:

Early Diagnosis

Prevent irreversible

joint damage

Diminish long term

complications

Improve outcome and patient

functionality