Rheumatoid Arthritis

• Epidemiology• Pathophysiology and clinical presentation• Treatment• Evaluation of treatment • Clinical case

Epidemiology

The prevalence estimated to be between 1% and 2% , with women affected 3 times more often than men

Rheumatoid arthritis can occur at any age and often occurs in younger people.

Rheumatoid arthritis is an autoimmune disease with a strong genetic predisposition.

Pathophysiology and clinical presentation

Chronic inflammation of the synovial tissue lining the joint capsule results in the proliferation of this tissue .

The inflamed proliferating synovium characteristic of rheumatoid arthritis Is called pannus.

This panes invades the cartilage and eventually thebone surface, producing erosions of bone and cartilage and leading to destruction of the joint .

The factors that initiate the inflammatory process are unknown

The immune system is a complex network of checks and balancesdesigned to discriminate self from non-self (foreign) tissues.

It helps rid the body of infectious agents, tumor cells, and products associated with the breakdown of cells.

In rheumatoid arthritis, this system no longer can differentiate self from non-self tissues and attacks the synovial tissue and other connective tissues

The immune system has both humeral and cell-mediated functions .

The humeral component is necessary for theformation of antibodies. These antibodies are produced by plasmacells, which are derived from B lymphocytes .

Most patients with rheumatoid arthritis form antibodies called rheumatoid factors

Symptoms■Joint pain and stiffness of more than 6 weeks’ duration

May also experience fatigue, weakness, low-grade fever ,Loss of appetite. Muscle pain and afternoon fatigue may also be present.Joint deformity is generally seen late in the disease.

Signs■Tenderness with warmth and swelling over affected joints

usually involving hands and feet. Distribution of joint involvement is frequently symmetrical. Rheumatoid nodules may also be present

Laboratory Tests

■Rheumatoid factor (RF) detectable in 60% to 70% . ■Ant cyclic citrullinated peptide (anti-CCP) antibodies

have similar sensitivity to RF (50% to 85%) but are more specific (90% to 95%) and are present earlier in the disease.

■Elevated erythrocyte sedimentation rate and C-reactive protein are markers for inflammation.

■Normocytic normochromic anemia is common as is thrombocytosis.

Other Diagnostic Tests■Joint fluid aspiration may show

increased white blood cellcounts without infection, crystals.

■Joint radiographs may show periarticular osteoporosis, joint

space narrowing, or erosions

EXTRAARTICULAR INVOLVEMENT

Rheumatoid NodulesVasculitisPulmonary ComplicationsOcular ManifestationsFelty’s Syndromecardiac InvolvementOther Complications

LABORATORY FINDINGS

Normocytic normochromic anemiaThrombocytosisLeucopeniaESR is elevatedC-reactive protein elevatedRF present in 60-70 % of patientAnti- CCP antibody in 50-85%Antinuclear antibodies in 25%

Diseases Associated with a Positive Rheumatoid Factor

Rheumatic diseases

Rheumatoid arthritisSjögren’s syndrome (with or without arthritis)Systemic lupus erythematosusProgressive systemic sclerosisPolymyositis/dermatomyositis

Infectious diseases

Bacterial endocarditisTuberculosis

SyphilisInfectious mononucleosisInfectious hepatitisLeprosy

Other causes

AgingInterstitial pulmonary fibrosisCirrhosis of the liverChronic active hepatitisSarcoidosis

TREATMENT

DESIRED OUTCOME

Control of inflammation is the key to slowing or preventing disease progression as well as managing symptoms

a. Reduction in the number of affected joints and in joint tenderness and swellingb. Improvement in painc. Decreased amount of morning stiffnessd. reduction in serological markers such as RFe. Improvement in quality-of-life scales

NONPHARMACOLOGIC THERAPY

a. Rest during periods of disease exacerbationb. Occupational and physical therapy to support mobility and maintain functionc. Maintenance of normal weight to reduce biomechanical stress on joints

d. Surgery (Tenosynovectomy, tendon repair , And joint replacements.)

e. Smoking Cessation

PHARMACOLOGIC THERAPY

Drug therapy should be only part of a comprehensive program for patient management which would also Include physical therapy,

exercise, and rest . surgery may be Assistive devices and orthopedic

necessary in some patients

There are four types of medications used to treat RA:

Non-steroidal anti-inflammatory drugs (NSAIDs)CorticosteroidsDisease-modifying anti-rheumatic

drugs(DMARDS).Biologic Response Modifiers (“Bioligics”)

Disease-modifying antirheumatic drugs (DMARDs) or biologic agents should be started within 3 months of the diagnosis of rheumatoid arthritis.

Methotrexate ,hydroxycloroquine ,leflunomide ,and sulphasalsine are commonly used as first line

gents

Nonsteroidal antiinflammatory drugs and/or corticosteroids should be considered adjunctive therapy early in the course of treatment and as needed if symptoms are not adequately controlled with DMARDs.

When DMARDs used singly are ineffective or not adequately effective, combination therapy with two or more DMARDs or aDMARD plus biologic agents may be used to induce a response.

Patients require careful monitoring for toxicity and therapeutic benefit for the duration of treatment

NSAIDs and/or corticosteroids may be used for symptomatic relief if needed.

They provide relatively rapid improvement in symptoms compared with DMARDs, which may take weeks to months before benefit is seen; however, NSAIDs have no impact on disease progression and the long-term complication risk of corticosteroids make them less desirable

Non-steroidal anti-inflammatory drugs (NSAIDs)

Examples General Use Side Effects MonitoringConsiderations

Aspirin, ibuprofen, naproxen, COX-2 inhibitors, propionic acid, phenylacetic acid

• anti-inflammatory:Used in the management inflammatory conditions •Antipyretic: used to control fever

•Analgesic:Control mild to moderate pain

•Nausea•Vomiting•Diarrhea•Constipation•Dizziness•Drowsiness•Edema•Kidney failure•Liver failure•Prolonged bleeding•Ulcers

•Use cautiously in patients with hx of bleeding disorders

•Encourage pt to avoid concurrent use of alcohol

•NSAIDs may decrease response to diuretics or antihypertensive therapy

(The Arthritis Society, 2011; Day et al., 2010)

Corticosteroids

Used in bridging therapy Corticosteroids also may be delivered by injection Patients on long-term therapy should be given calcium and vitamin D or Alendronate to minimize bone loss.

Examples General Use Side Effects monitoring Considerations

Cortisone, hydrocortisone, prednisone, betamethasone,

dexa-methasone

• Used in the management inflammatory conditions •When NSAIDS may be contraindicated

•Promptly improve symptoms of RA

•Increased appetite•Weight gain•Water/salt retention•Increased blood pressure•Thinning of skin•Depression•Mood swings•Muscle weakness•Osteoporosis•Delayed wound healing•Onset/worsening of diabetes

•Take medications as directed (adrenal suppression)

•Used with caution in diabetic patients

•Encourage diet high in protein, calcium, potassium and low in sodium and carbohydrates

•Discuss body image•Discuss risk for infection

(The Arthritis Society, 2011; Day et al., 2010)

Disease-modifying anti-rheumatic drugs(DMARDS)

Examples General Use Side Effects MonitoringConsiderations

Methotrexate Hydroxychloroquinelefulinamide

(the gold standard) ,gold salts,

cyclosporine ,cyclophosphamidesulfasalazine, azathioprine

•immunosuppressive activity

•Reduce inflammation of rheumatoid arthritis

•Slows down joint destruction

•Preserves joint function

•Dizziness, drowsiness, headache•Pulmonary fibrosis•Pneumonitis•Anorexia•Nausea•Hepatotoxicity•Stomatitis•Infertility•Alopecia•Skin ulceration•Aplastic anemia•Thrombocytopenia•Leukopenia•Nephropathy•fever•photosensitivity

•May take several weeks to months before they become effective

•Discuss teratogenicity, should be taken off drug several months prior to conception

•Discuss body image

(The Arthritis Society, 2011; Day et al., 2010)

Methtrexate DMARD of choice CI in chronic liver disease, immunodeficiency,thrpmpocytopenia,leucopenia, preexisting blood disorders , cr <40 Inhibit cytokine production Git side effect , liver toxicity Folic acid antagonist

Dose and Administration Dose ranges from 7.5 to 25 mg

ONLY GIVEN ONCE A WEEK 2.5 mg Tablets or Subcutaneous Injection 25

mg/mL

Tetrahydrofolate is an important cofactor in the production of purines transferring a carbon atom

Biologic Response Modifiers (“Bioligics”)

TNF Inhibitors Adalimumab Etanercept Infliximab

IL-1 Inhibitors Anakinra

T-Cell Co-Stimulatory Blockade Abatacept

B-Cell Depletion Rituximab

Examples General Use Side Effects Nursing Considerations

Etanercept ,anakinra ,abatacipt ,adalimumab ,

Infliximab (Remicade)

• Used in the management inflammatory conditions •When NSAIDS may be contraindicated

•Promptly improve symptoms of RA

•Increased appetite•Weight gain•Water/salt retention•Increased blood pressure•Thinning of skin•Depression•Mood swings•Muscle weakness•Osteoporosis•Delayed wound healing•Onset/worsening of diabetes

•Take medications as directed (adrenal suppression)

•Encourage diet high in protein, calcium, potassium and low in sodium and carbohydrates

•Discuss body image

•Discuss risk for infection

Therapeutic guideline

Triple Therapy

Methotrexate, Sulfasalazine, Hydroxychloroquine

Double Therapy

Methotrexate & LeflunomideMethotrexate & SulfasalazineMethotrexate & HydroxychloroquineMethotrexate & infliximabSulfasalazine & cyclosporin

Dosing

EVALUATION OF THERAPEUTIC OUTCOMES

The evaluation of therapeutic outcomes is based primarily on improvements of clinical signs and symptoms of rheumatoid arthritis.

Clinical signs of improvement include a reduction in joint swelling, decreased warmth over actively involved joints, and decreased tenderness to joint palpation. Improvement in rheumatoid arthritis symptoms includes reduction in perceived joint pain and morning stiffness, longer time to onset of afternoon fatigue, and improvement in ability to perform activities of daily living.

Improvement of activities of daily living may be assessed objectively using a Health Assessment Questionnaire score .

.

Joint radiographs may be of some benefit in assessing the progression of the disease and should show little or no evidence of disease progression if treatment is effective.

Laboratory monitoring is of little value in monitoring individual patient response to therapy. Routine monitoring of patients is essential to the safe use of these drugs.

In addition, patients should be questioned about symptoms of the adverse effects outlined previously