Case

• A 32-year-old nurse presents to your office with a complaint of

intermittent episodes of pain, stiffness, and swelling in both hands
and wrists for approximately 1 year.
• The episodes last for several weeks and then resolve.
• More recently, she noticed similar symptoms in her knees and ankles.
• Joint pain and stiffness are making it harder for her to get out of bed
in the morning and are interfering with her ability to perform her
duties at work.
• The joint stiffness usually lasts for several hours before improving. She
also reports malaise and easy fatigability for the past few months, but
she denies having fever, chills, skin rashes, and weight loss.
• Physical examination reveals a well-developed woman, with blood
pressure 120/70 mm Hg, heart rate 82 bpm, and respiratory rate 14
breaths per minute.
• Her skin does not reveal any rashes. Head, neck, cardiovascular, chest,
and abdominal examinations are normal. There is no
hepatosplenomegaly.
• The joint examination reveals the presence of bilateral
swelling, redness, and tenderness of most proximal
interphalangeal (PIP) joints, metacarpophalangeal (MCP)
joints, the wrists, and the knees.
• Laboratory studies show a mild anemia with hemoglobin
11.2 g/dL, hematocrit 32.5%, mean corpuscular volume
(MCV) 85.7 fL, white blood cell (WBC) count 7.9/mm3 with a
normal differential, and platelet count 300 000/mm3 .
• The urinalysis is clear with no protein and no red blood cells
(RBCs).
• The erythrocyte sedimentation rate (ESR) is 75 mm/h, and
the kidney and liver function tests are normal.
• What is your most likely diagnosis?
• What is your next diagnostic step?
Case Summary
• This is a 32-year-old woman with a 1-year history of symmetric
polyarticular arthritis and morning stiffness.
• Joint examination reveals the presence of bilateral swelling,
redness, and tenderness of her PIP joints, MCP joints, wrists,
and knees.
• She has a mild normocytic anemia with an otherwise normal
complete blood count (CBC).
• Urinalysis, renal, and liver function tests are normal. The ESR is
elevated, suggesting an inflammatory cause of her arthritis.
• Most likely diagnosis: Rheumatoid arthritis (RA)
• Next diagnostic step: Rheumatoid factor and antinuclear
antibody titer.
Rheumatoid arthritis
Dr. Mukhtar, Family Physician, Associate Dean
 Objectives
• Introduction
• Epidemiology
• Presentation
• Pathophysiology
• Investigations
• Differential diagnosis
• Management
• Complications
• Prognosis
• Prevention
 Introduction
Def1:
• Rheumatoid arthritis (RA) is the most common persistent inflammatory
arthritis, occurring throughout the world and in all ethnic groups.
Def2:
• Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune
disease characterised by an inflammation of the synovial joints leading to
joint and periarticular tissue destruction, as well as a wide variety of extra-
articular features.
• Def3:
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of
unknown etiology that primarily involves synovial joints.
• RA is associated with significant morbidity, including pain and
disability.
• Suppression of inflammation in the early stages of the disease can
result in substantial improvements in long-term outcomes.
• Improvements in the use of existing disease-modifying drugs, the
development of new drugs and the better application of a range of
therapeutic options including non-pharmacological treatments are
important in reducing morbidity and mortality from RA.
• About one third of people with RA remain seronegative.
• Despite awareness of the role of circulating autoantibodies in the
development of 'seropositive' RA, the pathogenesis of seronegative
RA is poorly understood.
• Evidence suggests that RA 'serotypes' reflect distinct disease entities
that diverge with respect to genetic architecture, cellular pathology
and even therapeutic responsiveness.
 Epidemiology
• The prevalence is lowest in black Africans and Chinese, and
highest in Pima Indians.
• In Caucasians, approximately 0.8–1.0% are affected, with a
female to male ratio of 3 : 1.
• The peak age of incidence for both genders is the 40s, but
people of all ages can develop the disease.
• Patients with RA have an increased mortality when
compared with age-matched controls, primarily due to an
increased risk of cardiovascular disease.
• This is most marked in those with severe disease, with a
reduction in expected lifespan by 8–15 years.
• Around 40% of RA patients are registered as disabled within
3 years of onset, and around 80% are moderately to severely
disabled within 20 years.
• Functional capacity decreases most rapidly at the beginning
of disease and the functional status of patients within their
first year of RA is often predictive of long-term outcome.
 Risk factors
RA results from an interaction between genetic susceptibility and
environmental factors, including:
• High birth weight,
• Smoking,
• Silica exposure,
• Alcohol,
• Obesity,
• Diabetes mellitus,
• Rheumatoid factor, and anti-citrullinated protein antibody
Factors that associate with a poorer prognosis are:
• Disability at presentation,
• Female gender,
• Involvement of MTP joints,
• Radiographic damage at presentation,
• Smoking and a
• Positive RF or ACPA.
 Presentation
• The presentation can be very variable.
• Constitutional symptoms (eg, profound fatigue,
influenza-like symptoms, fever, sweats and weight
loss) are common.
Initial presentation
• Rheumatoid arthritis (RA) most typically presents as polyarticular
disease and with a gradual onset, but some patients can present with
acute onset with intermittent or migratory joint involvement or with
monoarticular disease.
• The symptoms of arthritis can affect the patient's capacity to perform
the activities of daily living (eg, walking, stairs, dressing, use of a
toilet, getting up from a chair, opening jars, doors, typing) and their
ability to do their job.
• Systemic symptoms may also be present in these patients; in up to
one-third of patients.
Natural history and prognosis of rheumatoid arthritis
Pathophysiology
 CLINICAL PRESENTATION

Articular disease Extraarticular

involvement
• Eyes
Typical 'classic' RA • Skin
• Neurological
• Respiratory
Palindromic rheumatism • Cardiovascular 
• Kidneys
• Liver
Monoarthritis  • Others
 Typical 'classic' RA
• The disease onset in RA is usually insidious, with the
predominant symptoms being pain, stiffness (especially
morning stiffness), and swelling of many joints.
• Typically, the metacarpophalangeal (MCP) and proximal
interphalangeal (PIP) joints of the fingers, the
interphalangeal joints of the thumbs, the wrists, and the
metatarsophalangeal (MTP) joints of the toes are sites of
arthritis early in the disease.
• Other synovial joints of the upper and lower limbs,
such as the elbows, shoulders, ankles, and knees, are
also commonly affected.
• Morning stiffness is a common feature of those with active
RA; it can be defined as "slowness or difficulty moving the
joints when getting out of bed or after staying in one position
too long, which involves both sides of the body and gets
better with movement“.
• Morning stiffness lasting more than one hour reflects a
severity of joint inflammation that rarely occurs in diseases
other than RA, although morning stiffness, or stiffness after
any prolonged period of inactivity, is also seen in virtually all
inflammatory arthropathies.
Palindromic rheumatism
• The onset of RA is episodic in a few patients, with one to
several joint areas being affected sequentially for hours to
days, alternating with symptom-free periods that may last
from days to months; this episodic pattern is referred to as
"palindromic rheumatism." 
• The proportion of patients presenting with palindromic
rheumatism who progress to develop RA or another well-
defined disease varies between studies.
• In one study of 60 patients with palindromic rheumatism
followed over 20 years, 40 (67 percent) developed RA.
• The presence of anti-citrullinated peptide/protein antibodies
(ACPA), a serologic finding that is common in RA, might
predict progression of palindromic rheumatism to RA, but
evidence evaluating this possibility has been mixed.
Monoarthritis
• Persistent single joint arthritis (monoarthritis), frequently of
a large joint such as the wrist, knee, shoulder, hip, or ankle,
may be the sole manifestation of RA or may herald the onset
of polyarticular disease.
• There may be a history of joint trauma as an apparent
initiating event.
• The interval between monoarthritis and polyarthritis may
extend from days to several weeks in patients whose disease
progresses.
• Until polyarthritis develops, the approach to such patients is
that for any patient with monoarticular arthritis.
Extraarticular involvement 
• A proportion of patients complain of a constellation of
persistent nonarticular symptoms, which may antedate the
onset of polyarthritis by many months; these include
generalized aching, stiffness, symptoms of bilateral carpal
tunnel syndrome, loss of weight, depression, and fatigue.
• Involvement of the musculoskeletal system other than joints
(eg, bone and muscle) and of nonarticular organs (eg, skin,
eye, lungs, heart, and others) occurs in about 40 percent of
patients with rheumatoid arthritis (RA) over the course of
the disease.
Assessment of disease activity in
rheumatoid arthritis
Assessment of disease activity in
rheumatoid arthritis
Radiolog
y
Feet
The 2010 American College of Rheumatology/European League Against
Rheumatism Classification Criteria for RA
Treatment
• After RA has been diagnosed and an initial evaluation
performed, treatment should begin.
• Goals of therapy include minimizing joint pain and swelling,
preventing deformity (such as ulnar deviation) and
radiographic damage (such as erosions), maintaining quality
of life (personal and work), and controlling extra-articular
manifestations.
• Disease-modifying antirheumatic drugs (DMARDs) are the
mainstay of RA therapy.
DMARDS
• DMARDs can be biologic or nonbiologic.
• Biologic agents include monoclonal antibodies and
recombinant receptors to block cytokines that promote the
inflammatory cascade responsible for RA symptoms.
After any of the treatment
regimens has led to the
treatment target and its
maintenance, consider
reducing dose or increasing
interval (suggested
sequence: glucocorticoids,
bDMARDs, csDMARDs)
• Methotrexate is recommended as the first-line treatment in
patients with active RA, unless contraindicated or not
tolerated.
• Leflunomide (Arava) may be used as an alternative to
methotrexate, although gastrointestinal adverse effects are
more common.
• Combination therapy with two or more DMARDs is more
effective than monotherapy; however, adverse effects may
also be greater.
• If RA is not well controlled with a nonbiologic DMARD, a
biologic DMARD should be initiated.
• TNF inhibitors are the first-line biologic therapy and are the
most studied of these agents.
• If TNF inhibitors are ineffective, additional biologic therapies
can be considered.
NSAIDS AND CORTICOSTEROIDS
• Drug therapy for RA may involve NSAIDs and oral,
intramuscular, or intra-articular corticosteroids for
controlling pain and inflammation.
• Ideally, NSAIDs and corticosteroids are used only for short-
term management.
• DMARDs are the preferred therapy.
COMPLEMENTARY THERAPIES
• Dietary interventions, including vegetarian and
Mediterranean diets, have been studied in the treatment of
RA without convincing evidence of benefit.
EXERCISE AND PHYSICAL THERAPY
• Results of randomized controlled trials support physical
exercise to improve quality of life and muscle strength in
patients with RA.
• Exercise training programs have not been shown to have
deleterious effects on RA disease activity, pain scores, or
radiographic joint damage.
DURATION OF TREATMENT
• Remission is obtainable in 10 to 50 percent of patients with
RA, depending on how remission is defined and the intensity
of therapy.
• Remission is more likely in males, nonsmokers, persons
younger than 40 years, and in those with late-onset disease
(patients older than 65 years), with shorter duration of
disease, with milder disease activity, without elevated acute
phase reactants, and without positive rheumatoid factor or
anti-citrullinated protein antibody findings.
JOINT REPLACEMENT
• Joint replacement is indicated when there is severe joint
damage and unsatisfactory control of symptoms with
medical management.
• Long-term outcomes are good, with only 4 to 13 percent of
large joint replacements requiring revision within 10 years.
• The hip and knee are the most commonly replaced joints.
Long-term Monitoring
• Although RA is considered a disease of the joints, it is also a
systemic disease capable of involving multiple organ systems.
• Patients with RA have a twofold increased risk of lymphoma,
which is thought to be caused by the underlying
inflammatory process, and not a consequence of medical
treatment.
• Patients with RA are also at an increased risk of
coronary artery disease, and physicians should work
with patients to modify risk factors, such as smoking,
high blood pressure, and high cholesterol.
Prognosis
• Patients with RA live three to 12 years less than the general
population.
• Increased mortality in these patients is mainly due to
accelerated cardiovascular disease, especially in those with
high disease activity and chronic inflammation.
• The relatively new biologic therapies may reverse
progression of atherosclerosis and extend life in those with
RA.
Complications
• Ruptured tendons
• Ruptured joints (Baker's cysts)
• Joint infection
• Spinal cord compression (atlantoaxial or upper cervical
spine)
• Amyloidosis (rare)
• Side-effects of therapy
Summery
Questions