F.A.C.T.S.

RHEUMATOID ARTHRITIS

Kevin Mould PGY3

GOALS AND OBJECTIVES

• Provide a general overview of rheumatoid arthritis (RA)

• Describe the diagnostic criteria for diagnosing RA

• Explore management options for RA

• Outline current treatment options available for RA

INTRODUCTION

• chronic, systemic, inflammatory disorder • unknown etiology • primarily involves joints• symmetrical• may lead to deformity and destruction of joints • usually progresses from the periphery to more

proximal joints• usually significant locomotor disability within 10

to 20 years

EPIDEMIOLOGY

• affects women two to three times as often as men• incidence around 30 per 100,000 population• may affect any age group from children to the elderly• prevalence is about 1 percent in Caucasians, 0.1 percent

in rural Africans, 5 percent in Pima and Chippewa Indians

• peak onset between the ages of 30 and 55 • consistently higher rates in females• prevalence of RA in females over 65 years is up to 5

percent

DIAGNOSTIC CRITERIA

American College of Rheumatology (ACR) criteria .Four or more of the following: • morning stiffness for at least one hour and present for at least six

weeks• swelling of three or more joints for at least six weeks• swelling of wrist metacarpophalangeal (MCP) or proximal

interphalangeal (PIP) joints for at least six weeks• symmetric joint swelling• hand X-ray changes typical of RA that must include erosions or

unequivocal bony decalcification• rheumatoid subcutaneous nodules• rheumatoid factor positive

CLINICAL PRESENTATIONCharacteristics

• onset usually insidious• predominant symptoms are pain, stiffness, and swelling of many

joints• typically, affected sites of arthritis early in the disease are:

- metacarpophalangeal (MCP) joints of the fingers- proximal interphalangeal (PIP) joints of the fingers- interphalangeal joints of the thumbs and wrists- metatarsophalangeal joints of the toes

• also commonly affected.joints are:-elbows, shoulders, ankles, and knees

• morning stiffness a common feature

CLINICAL PRESENTATION CONT

Initial presentation may take several forms:

• acute onset of polyarthritis

• episodic onset

• persistent single joint arthritis • persistent nonarticular symptoms

• extraarticular disease

CLINICAL PRESENTATION CONT

Joint distribution

• peripheral joints eventually affected in almost all

patients• axial and central joint involvement is less• symmetrical involvement of joints characteristic • pattern of joint involvement may also be

diagnostically useful

PHYSICAL FINDINGS

General

• painful inflammation • swelling (synovial hypertrophy or effusion) • synovial thickening • heat and redness are not prominent features • characteristic joint deformities are late

manifestations

PHYSICAL FINDINGS CONT

The hands

• signs of disease often found in the hands early in the course of RA• symmetrical effusions and soft tissue swelling around the MCP and

PIP joints • DIP involvement can be seen later in the disease• joints are tender to the touch with a restricted range of movement. • palmar erythema may be present• thickening of the flexor tendons • nodules may form along the palmar tendon sheaths • nodules may cause tendon rupture

PHYSICAL FINDINGS CONT

The Hand Cont

Other physical signs include:- reduced grip strength - whole hand may be swollen with pitting edema over the dorsum- range of movement of involved joints restricted

Characteristic joint deformities appear in more established RA - ulnar deviation or "ulnar drift" - Swan neck or Boutonniere deformities of the fingers- "Bow string" sign (prominence of the tendons in the extensor

compartment of the hand) The nails and fingertips should also be examined in every patient for

evidence of digital infarcts

PHYSICAL FINDINGS CONT

The wrists

- commonly involved- loss of extension early in the disease - late changes due to erosive damage - subluxation and radial drift of the carpus - tendon rupture can also occur at the wrist- carpal tunnel syndrome in 1% to 5%

PHYSICAL FINDINGS CONT

The elbows

- frequently affected- loss of extension (fixed flexion) - effusion or synovitis - compressive neuropathy of the ulnar nerve - olecranon bursitis is common.- destruction of the joint may occur - most common site for subcutaneous rheumatoid nodules

PHYSICAL FINDINGS CONT

The shoulders

- involved later in the disease

- painful restriction of movement resembling a capsulitis

- rotator cuff injury is common

- effusions relatively rare

PHYSICAL FINDINGS CONT

The Foot

- involvement is common in early disease- tenderness of the metatarsophalangeal joints may be

marked- lateral drift of the toes, and plantar subluxation of the

metatarsal heads - involvement of the tarsus and the associated tendon

sheaths common- heel pain may be associated with retrocalcaneal bursitis- diffuse swelling around the tibiotalar joints

PHYSICAL FINDINGS CONT

The knee

- synovial thickening

- effusion is common

- restriction of movement, particularly flexion common

- ligamentous laxity leading to deformities and quadriceps atrophy

- popliteal cyst

PHYSICAL FINDINGS CONT

The hips

- occurs only in well established disease.

- pain in the groin, thigh, low back, or referred to the knee on standing

- restriction of movement

PHYSICAL FINDINGS CONT

The axial skeleton

- cervical spine joints most clinically important joints - painful stiff neck with restricted movement on exam - radicular pain at C1 and C2- spinal cord compression can occur

Cricoarytenoid joint

- thirty percent have involvement of this joint- hoarseness and inspiratory stridor

SYSTEMIC/NONARTICULAR MANIFESTATIONS OF RA

• Osteopenia • Muscle Weakness

• Skin Disease

• Eye Involvement

• Lung Disease

• Cardiac Disease

SYSTEMIC/NONARTICULAR MANIFESTATIONS OF RA CONT

• Kidney Disease

• Vascular Involvement • Sjögren's Syndrome

• Felty's Syndrome

• Nervous System

• Hematologic Abnormalities

COMORBIDITY AND MORTALITY

• Infection

• Cardiovascular disease

• Mortality

DIFFERENTIAL DIAGNOSIS

Acute viral polyarthritis

- rubella, parvovirus, hepatitis B, etc - occasionally associated with the presence of rheumatoid factors - frequently associated with increased acute phase reactants- distinguished by history (particularly of a rash), IgM antiviral antibodies, self-limited nature of the symptoms

Connective tissue diseases and sarcoidosis

- difficult to distinguish from the arthritis of SLE, Sjögren's syndrome, and sarcoidosis

- morning stiffness, symmetry, subcutaneous nodules, and the deformities characteristic of RA do not develop in these other disorders

DIFFERENTIAL DIAGNOSIS CONT

Hypermobility syndrome and fibromyalgia

- joint pain (rather than stiffness or swelling) most dominant symptom- hyperextendable joints in the hypermobility syndrome- tender points in fibromyalgia- absence of arthritis, rheumatoid factors, and/or elevated levels of acute

phase reactants

Reactive arthritis

- may present in large joints such as the knees - urethritis, a history of enteric infection, skin lesions, heel pain or tenderness, radiologic evidence of sacroiliitis and/or spondylitis, and HLA-B27 in patients with Reiter's syndrome- typically asymmetrical, morning stiffness unusual, rheumatoid factor rare

DIFFERENTIAL DIAGNOSIS CONT

Psoriatic arthritis

- joint symptoms of psoriatic arthritis may precede the onset of skin disease - some patients, the only clue to the diagnosis is family history of psoriasis- findings of skin psoriasis, nail changes (onychodystrophy), sausage toes

or fingers, spinal involvement, and/or arthritis mutilans helps distinguish the two entities

Crystalline arthritis

- gout and pseudogout- may be polyarticular- diagnosis made by finding urate or calcium pyrophosphate crystals in synovial fluids, absence of rheumatoid factor and morning stiffness, presence of tophi

DIFFERENTIAL DIAGNOSIS CONT

Osteoarthritis

Joint involvement of the fingers - DIP joint involvement - highly characteristic Heberden's nodes- carpometacarpal joint of the thumb is typically involved

Swelling of the joints- hard and bony

Stiffness of the joint - relatively rare feature of OA- typically worse after any effort

X-rays of the joints

- narrowing of the joint space and osteophytes

Labs- absence of rheumatoid factor - normal levels of acute phase reactants

DIFFERENTIAL DIAGNOSIS CONT

Infectious arthritis

- usually monoarticular- can cause polyarthritis - diagnosis established by culturing - leukocytosis is common

• Paraneoplastic disease • Multicentric reticulohistiocytosis

CLINICAL COURSE

Patterns of progression

• Fluctuating

• Remitting

• Continuous

MANAGEMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS

Stages of disease • Recent-onset disease

• Established or persistent disease

• End-stage disease

MANAGEMENT CONT

Assessment of activity

• Based upon:- patient and physician assessment of symptoms and functional status- evaluation of joint involvement and extraarticular manifestations- laboratory markers- radiographic studies

• Symptoms and functional status - degree of joint pain- duration of morning stiffness - severity of fatigue- evidence for extraarticular manifestations should be sought - self-report questionnaires

MANAGEMENT CONT

Assessment of activity cont

• Physical examination - intervals of no more than six months- appropriate to assess change

• Laboratory tests - Acute phase reactants (C-reactive protein, erythrocyte sedimentation rate) - hemoglobin, serum albumin - rheumatoid factor titers - anti-citrinullated peptide antibody titers

• Imaging techniques

- plain radiographs of the hands and wrists - CT, ultrasonography, and MRI

MANAGEMENT CONTSeverity of disease • Mild disease

Meet the ACR criteria for RA and have some of the following clinical features:

- arthralgias- at least 3 inflamed/swollen joints- no extraarticular disease- a negative or positive rheumatoid factor test- an elevated ESR or serum CRP concentration- no evidence of erosions or cartilage loss on plain radiographs

MANAGEMENT CONT

Severity of disease cont

• Moderate disease

Some combination of the following clinical features:

- between 6 and 20 inflamed joints- absence of extraarticular disease (most commonly)- elevation in the ESR or serum CRP concentration- positive RF and/or anti-citrinullated peptide antibodies- evidence of inflammation via plain radiography

MANAGEMENT CONTSeverity of disease cont

• Severe disease

Have one or more of the following findings:

- more than 20 persistently inflamed joints - a rapid decline in functional capacity- elevated levels of ESR or CRP- anemia of chronic disease- hypoalbuminemia- positive rheumatoid factor tests (often in high titer) and/or anti-citrinullated peptide antibodies- joint radiographs demonstrating rapid progression- extraarticular disease

MANAGEMENT CONT

General management strategy

• challenging• disease modifying anti-rheumatic drugs (DMARDs) as soon as possible • aggressive treatment• reasonable goal - escalate the intensity of treatment until evidence for

synovitis diminishes or disappears, or until drug-induced side effects become intolerable.

Therapeutic options

• optimal therapy needs to individualized. • nonpharmacologic and preventive treatments• pharmacologic agents • surgery

MANAGEMENT CONT

• Patient education and counseling

• Rest

• Exercise

• Physical therapy

• Occupational therapy

• Nutrition and dietary therapy

• Bone protection

MANAGEMENT CONT

Pharmacologic therapy

• Drugs form the mainstay of therapy in recent onset or active RA

• Drug classes

- analgesics - nonsteroidal antiinflammatory drugs - glucocorticoids - SAARDs or DMARDs - anticytokine therapies

MANAGEMENT CONTPharmacologic therapy cont

• SAARDs or DMARDs

- slow-acting antirheumatic drugs (SAARDs) - disease-modifying antirheumatic drugs (DMARDs) - miscellaneous group of drugs - potential to reduce or prevent joint damage, preserve joint integrity

and function, reduce health costs, and maintain economic productivity

- hydroxychloroquine, sulfasalazine, methotrexate, and leflunomide- less often usede are gold salts, D-penicillamine, azathioprine, and

cyclosporine- tetracycline derivatives used as adjunctive therapy early in disease

MANAGEMENT CONT

Pharmacologic therapy cont

• Anticytokine therapies - anti-tumor necrosis factor alpha agents

(etanercept, infliximab, adalimumab) - interleukin-1receptor antagonist (anakinra) - additional biologic therapies will become available in the future

MANAGEMENT CONT

• Combination drug therapy

Selection of DMARD combinations often employed:- Sulfasalazine and hydroxychloroquine- Sulfasalazine and methotrexate- Hydroxychloroquine, sulfasalazine, and methotrexate- Cyclosporine and methotrexate- Leflunomide and methotrexate- Anti-TNF agents and methotrexate

MANAGEMENT CONT

Monitoring for drug toxicity

• balance between the induction of side effects of therapy versus progression of the disease

• methotrexate and azathioprine (toxic febrile reactions)• cyclosporine with a NSAID (compromised renal function) Current approach

• aggressive treatment from the outset • individualized therapy • reevaluated every three to five weeks

MANAGEMENT CONTEnd Stage Disease • Goals of therapy:

- pain relief- protection of remaining articular structures- maintenance of function- nonpharmacologic interventions are particularly important

• Indications for surgical intervention:

- intractable pain- severe functional disability due to joint destruction - impending tendon rupture- timing of surgery is often critical

Question

RF NEGATIVE RA

• Twenty percent of cases

• Milder course

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