Rheumatoid arthritis

Rheumatoid Arthritis
By
EDWIN JOSE.L

introduction
 Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting the
joints.
 Rheumatoid arthritis (RA) is a disease of unknown origin, which is
characterized by inflammatory changes of the synovial tissue of joints, of
cartilage and bone and, less frequently, of extra-articular sites
 It is characterized by a progressive symmetric inflammation of affected
joints resulting in cartilage destruction, bone erosion, and disability .
 Initially only a few joints are affected, in later stages many joints are
affected and extraarticular symptoms are common

definition
 Rheumatoid arthritis (RA) is a disease of unknown origin, which is
characterized by inflammatory changes of the synovial tissue of joints, of
cartilage and bone and, less frequently, of extra-articular sites
 RA, a systemic disease, may also lead to a variety of extraarticular
manifestations, including fatigue, subcutaneous nodules, lung involvement,
pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities,
which must be managed accordingly
- Harrison’s Principles Of Internal Medicine

prevalence
 Prevalence ranging from 0.4% to 1.3% of the population depending on both
 sex (women are affected two to three times more often than men),
 age (frequency of new RA diagnoses peaks in the sixth decade of life),
 studied patient collective (RA frequency increases from south to north and is higher in
urban than rural areas
 RA affects 0.5–1% of the adult population worldwide.
 There is evidence that the overall incidence of RA has been decreasing in recent decades,
whereas the prevalence has remained the same because individuals with RA are living
longer.
 The incidence and prevalence of RA varies based on geographic location, both globally
and among certain ethnic groups within a country

Causes/RISK FACTORS
 Genetic
 The likelihood that a first-degree relative of a patient will share the diagnosis of RA is 2–10 times
greater than in the general population.
 ENVIRONMENTAL FACTORS
 Smoking
 Bacterial infections (agglutinate strains of streptococci)
 Viral infections (Epstein-Barr virus (EBV))
 Periodontitis
 oral microbiome, specifically Porphyromonas gingivalis

pathophysiology
Source: Castro-Sánchez P, Roda-Navarro P. Physiology and pathology of
autoimmune diseases: role of CD4+ T cells in rheumatoid arthritis. In
Physiology and Pathology of Immunology 2017 Dec 20. IntechOpen.

Clinical manifestations
The presenting symptoms of RA typically result from inflammation
of the joints, tendons, and bursae
 early morning joint stiffness lasting more than 1 hr that eases with physical
activity
 The earliest involved joints are typically the small joints of the hands and feet.
 Initial pattern of joint involvement may be monoarticular, oligoarticular (≤4
joints), or polyarticular (>5 joints), usually in a symmetric distribution.
 Flexor tendon tenosynovitis is a frequent hallmark of RA and leads to decreased
range of motion, reduced grip strength, and “trigger” fingers
 Ulnar deviation - from subluxation of the MCP joints, with subluxation, or
partial dislocation, of the proximal phalanx to the volar side of the hand.

CONT…..
 Hyperextension of the PIP joint with flexion of the DIP joint (“swan-neck
deformity”)
 flexion of the PIP joint with hyperextension of the DIP joint (“boutonnière
deformity”)
 subluxation of the first MCP joint with hyperextension of the first interphalangeal
(IP) joint (“Z-line deformity”) also may result from damage to the tendons, joint
capsule, and other soft tissues in these small joints.
 Inflammation about the ulnar styloid and tenosynovitis of the extensor carpi ulnaris
may cause subluxation of the distal ulna, resulting in a “piano-key movement” of
the ulnar styloid
 chronic inflammation of the ankle and midtarsal regions usually comes later and
may lead to pes planovalgus (“flat feet”)
 RA rarely affects the thoracic and lumbar spine.

swan-neck deformity Boutonniere deformity

Extraarticular manifestations
up to 40% of patients
Patients most likely to develop extraarticular disease have a history
of cigarette smoking, have early onset of significant physical
disability, and test positive for serum RF or anti-CCP antibodies.
Sjögren’s syndrome, interstitial lung disease (ILD), pulmonary
nodules, and anemia are among the most frequently observed
extraarticular manifestations.

CONSTITUTIONAL SYMPTOMS
weight loss,
 fever,
fatigue,
 malaise,
 depression,
 cachexia
 fever of >38.3°C (101°F) at any time during the clinical
course should raise suspicion of systemic vasculitis or
infection

NODULES
 Subcutaneous nodules occur in 30–40% of patients
 highest levels of disease activity
 When palpated, the nodules are generally firm, nontender, and adherent to
periosteum, tendons, or bursae
 Usually occurs in forearm, sacral prominences, and Achilles tendon , lungs,
pleura, pericardium, and peritoneum.
 Nodules are typically benign, although they can be associated with infection,
ulceration, and gangrene.

SJÖGREN’S SYNDROME
 Secondary Sjogren's syndrome is defined by the presence of either
keratoconjunctivitis sicca (dry eyes) or xerostomia (dry mouth) in
association with another connective tissue disease, such as RA.
 Approximately 10% of patients with RA have secondary Sjogren's
syndrome

Pulmonary manifestations
 Pleuritis - most common pulmonary manifestation of RA.
 produce pleuritic chest pain , dyspnea ,pleural friction rub and effusion.
 ILD may also occur in patients with RA manifested by dry cough and progressive
shortness of breath.
 ILD can be associated with cigarette smoking and is generally found in patients with
higher disease activity.
 Pulmonary nodules are also common in patients with RA which may be solitary or
multiple.
 Caplan’s syndrome - rare subset of pulmonary nodulosis characterized by the development
of nodules and pneumoconiosis following silica exposure.
 Respiratory bronchiolitis and bronchiectasis are other less common pulmonary disorders
associated with RA.

Cardiac manifestations
 Pericarditis - less than 10%
 Cardiomyopathy -, may result from necrotizing or granulomatous myocarditis,
coronary artery disease, or diastolic dysfunction
 Rarely heart muscle may contain rheumatoid nodules
 Mitral regurgitation

vasculitis
 Rheumatoid vasculitis - occurs in patients with long-standing disease, a
positive test for serum RF or anti-CCP antibodies, and hypocomplementemia.
 incidence is less than 1%
 The cutaneous signs vary and include petechiae, purpura, digital infarcts,
gangrene, livedo reticularis, and in severe cases large, painful lower extremity
ulcerations.
 Vasculitic ulcers
 Sensorimotor polyneuropathies such as mononeuritis multiplex may occur

HEMATOLOGIC
 Normochromic, normocytic anemia
 Elevated Platelet counts
 Felty’s syndrome - defined by the clinical triad of neutropenia, splenomegaly,
and nodular RA and is seen in less than 1% of patients.
 T cell large granular lymphocyte leukemia (T-LGL)
 Leukopenia –uncommon
 Lymphoma- B cell lymphoma

Associated conditions
Cardiovascular Disease:
 common cause of death in patients with RA
 congestive heart failure (including both systolic and diastolic
dysfunction)
 presence of elevated serum inflammatory markers
Osteoporosis:
 more common in patients with RA
 prevalence rates of 20–30%.
 Hip fractures are more likely to occur in patients with RA

Diagnostic evaluation
 History collection
 Physical examination
 Laboratory features
 Elevated ESR
 Elevated CRP
 Detection of RF
 Detection of anti CCP antibodies
 Detection of IgM, IgG, and IgA isotypes in serum
 SYNOVIAL FLUID ANALYSIS – WBC range between 5000 and 50,000
cells/μL

Plain X-ray
 initial radiographic finding is periarticular osteopenia.
 Other findings include soft tissue swelling, symmetric joint space loss, and subchondral
erosions, most frequently in the wrists and hands (MCPs and PIPs) and the feet (MTPs).
 In the feet, the lateral aspect of the fifth MTP is often targeted first, but other MTP joints
may be involved at the same time.
 X-ray imaging of advanced RA may reveal signs of severe destruction, including joint
subluxation and collapse
X-ray demonstrating progression of erosions on the
proximal interphalangeal joint

Magnetic resonance imaging:
 Presence of bone marrow edema has been recognized to be an early sign of
inflammatory joint disease
Ultrasonogram:
 detect more erosions than plain radiography
 detect synovitis, including increased joint vascularity indicative of inflammation

management
The original treatment pyramid for RA is now considered to be obsolete and has
evolved into a new strategy that focuses on several goals
 early, aggressive therapy to prevent joint damage and disability
 frequent modification of therapy with utilization of combination therapy where
appropriate
 individualization of therapy in an attempt to maximize response and minimize side
effects
 achieving, whenever possible, remission of clinical disease activity

pharmacotherapy
NSAIDS:
 NSAIDs were formerly viewed as the core of RA therapy
 now considered to be adjunctive agents for management of symptoms
uncontrolled by other measures.
 NSAIDs exhibit both analgesic and anti-inflammatory properties.
 The anti-inflammatory effects of NSAIDs derive from their ability to non
selectively inhibit cyclooxygenase (COX)-1 and COX-2.
 Chronic use should be minimized due to the possibility of side effects,
including gastritis and peptic ulcer disease as well as impairment of renal
function.

GLUCOCORTICOIDS:
 administer low to moderate doses to achieve rapid disease control before the onset of fully
effective DMARD therapy, which often takes several weeks or even months.
 1- to 2-week burst of glucocorticoids may be prescribed for the management of acute
disease flares, with dose and duration guided by the severity of the exacerbation.
 Chronic administration of low doses (5–10 mg/d) of prednisone (or its equivalent) may
also be warranted to control disease activity in patients with an inadequate response to
DMARD therapy.
 Low-dose prednisone therapy has been shown in prospective studies to retard radiographic
progression of joint disease; however, the benefits of this approach must be carefully
weighed against the risks
 if a patient exhibits one or a few actively inflamed joints, the clinician may consider
intraarticular injection of an intermediate-acting glucocorticoid such as triamcinolone
acetonide

DMARDs
 Disease-modifying antirheumatic drugs
 DMARDs are so named because of their ability to slow or prevent structural progression
of RA.
 The conventional DMARDs include hydroxychloroquine, sulfasalazine, methotrexate, and
leflunomide ,they exhibit a delayed onset of action of 6–12 weeks.
 Methotrexate is the DMARD of choice for the treatment of RA and is the anchor drug for
most combination therapies.
 It was approved for the treatment of RA in 1988 and remains the benchmark for the
efficacy and safety of new disease-modifying therapies
 Anti-TNF Agents -TNF inhibitors
 Infliximab
 Certolizumab
 Etanercept
 Adalimumab
 golimumab

CONT….
 Anakinra - is the recombinant form of the naturally occurring IL-1 receptor antagonist.
 Abatacept - Abatacept is a soluble fusion protein consisting of the extracellular domain of
human CTLA-4 linked to the modified portion of human IgG.
 Rituximab - Rituximab is a chimeric monoclonal antibody directed against CD20, a cell-
surface molecule expressed by most mature B lymphocytes
 Tocilizumab - Tocilizumab is a humanized monoclonal antibody directed against the
membrane and soluble forms of the IL-6 receptor. IL-6 is a proinflammatory cytokine
implicated in the pathogenesis of RA, with effects on both joint inflammation and
damage.
SMALL-MOLECULE INHIBITORS :
 Tofacitinib - is a small-molecule inhibitor that primarily inhibits JAK1 and JAK3, which
mediate signaling of the receptors for the common γ-chain-related cytokines IL-2, 4, 7, 9,
15, and 21 as well as IFN-γ and IL-6.

TREATMENT OF EXTRAARTICULAR MANIFESTATIONS:
High doses of corticosteroids
adjunctive immunosuppressive agents
 azathioprine,
 mycophenolate
 Mofetil
 rituximab have been used for treatment of RA-ILD.

SURGERY
Silicone implants - most common prosthetic for MCP arthroplasty
Arthrodesis and total wrist arthroplasty
correction of hallux valgus in the forefoot, including arthrodesis
and arthroplasty

PHYSICAL THERAPY AND ASSISTIVE DEVICES
 exercise and physical activity.
 Dynamic strength training
 community-based comprehensive physical therapy
 physical-activity coaching (emphasizing 30 min of moderately intensive
activity most days a week) have all been shown to improve muscle strength
and perceived health status.
 Foot orthotics for painful valgus deformity decrease foot pain and may
reduce disability and functional limitations
 wrist splints can also decrease pain

Nursing management
 The most common issues for the patient with RA include pain, sleep disturbance, fatigue,
altered mood, and limited mobility.
 The patient with newly diagnosed RA needs information about the disease to make daily
self management decisions and to cope with having a chronic disease

Alternative therapies
Fish oil.
Fasting/elimination
Mediterranean
Acupuncture
Magnet therapy
Hydrotherapy
Homeopathy
T’ai Chi
Yoga

Rheumatoid arthritis

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