Rheumatoid Artheritis

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Rheumatoid Artheritis
Rheumatoid arthritis (RA) RA is a chronic
symmetrical polyarthritis of unexplained cause.
it is a chronic, systemic inflammatory disorder
that may affect many tissues and organs, but
principally attacks the joints producing a
inflammatory synovitis that often progresses to
destruction of the articular cartilage and
ankylosis of the joints
Rheumatoid arthritis can also produce diffuse
inflammation in the lungs, pericardium, pleura,
and sclera, and also nodular lesions, most
common in subcutaneous tissue under the skin.
Although the cause of rheumatoid arthritis is
unknown, autoimmunity plays a pivotal role in its
chronicity and progression.
About 1 of the world's population is affected by
rheumatoid arthritis, women three times more
often than men. Onset is most frequent in 40 to
50 years, but no age is immune. It can be a
disabling and painful condition, which can lead
to substantial loss of functioning and mobility.
There are relapses and remissions,occurring
either spontaneously or in response to drug
therapy. It is diagnosed chiefly on symptoms and
signs, but also with (rheumatoid factor) and
X-rays.
Various treatments are available.
Non-pharmacological treatment like physical
therapy . Analgesia (painkillers) and
anti-inflammatory drugs, as well as steroids, are
used to suppress the symptoms, while
disease-modifying antirheumatic drugs (DMARDs)
are often required to inhibit or halt the
underlying immune process and prevent long-term
damage. In recent times, the newer group of
biologics has increased treatment options.
Signs and Symptoms
Joints
The arthritis of rheumatoid arthritis is due to
synovitis, inflammation of the synovial membrane
that lines joints and tendon sheaths. Joints
become swollen, tender and warm, and stiffness
limits their movement. With time, RA nearly
always affects multiple joints (it is a
polyarthritis). Most commonly, small joints of
the hands, feet and cervical spine are affected,
but larger joints like the shoulder and knee
can also be involved, differing per individual.
Synovitis can lead to tethering of tissue with
loss of movement and erosion of the joint
surface, causing deformity and loss of function.
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• Rheumatoid arthritis typically manifests with
  signs of inflammation,
• and the affected joints are swollen, warm,
  painful and stiff early in the morning or
  following prolonged inactivity.
• Increased stiffness early in the morning is often
  a prominent feature of the inflammatory disease
  which the person may experience and may last for
  more than an hour.
• Gentle movements may relieve symptoms in early
  stages of the disease.
• These signs help distinguish rheumatoid from
  non-inflammatory problems of the joints, often
  referred to as osteoarthritis or "wear-and-tear"
  arthritis.

In arthritis of non-inflammatory causes, signs of
inflammation and early morning stiffness are
absent and also movements aggravate pain . In
RA, the joints are often affected in a fairly
symmetrical fashion, although this is not
specific, and the initial presentation may be
asymmetrical
As the pathology progresses, the inflammatory
activity leads to tendon tethering and erosion
and destruction of the joint surface, which
impairs range of movement and leads to deformity.
The fingers may suffer from almost any
deformity, depending on which joints are most
involved. Names for specific deformities, ulnar
deviation, boutonniere deformity, swan neck
deformity and "Z-thumb.
Skin The rheumatoid nodule, which is often
subcutaneous, is the feature most characteristic
of rheumatoid arthritis. The initial pathologic
process in nodule formation is unknown
The typical rheumatoid nodule may be a few
millimetres to a few centimetres in diameter and
is usually found over bony prominences, such as
the olecranon, the calcaneal tuberosity, the
metacarpophalangeal joints, or other areas that
sustain repeated mechanical stress. Nodules are
associated with a positive RF (rheumatoid factor)
titer and severe erosive arthritis.
Several forms of vasculitis occur in rheumatoid
arthritis. A benign form occurs as microinfarcts
around the nailfolds. More severe forms include
livedo reticularis, which is a network
(reticulum) of erythematous to purplish
discoloration of the skin due to the presence of
an obliterative cutaneous capillaropathy.
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Occular

• Lungs
• Fibrosis of the lungs is a recognised response to
  rheumatoid disease.
• It is also a rare but well recognised
  consequence of therapy (for example with
  methotrexate.
• Caplan's syndrome describes lung nodules in
  individuals with rheumatoid arthritis.
• Pleural effusions are also associated with
  rheumatoid arthritis.

Kidneys Renal amyloidosis can occur as a
consequence of chronic inflammation.
Rheumatoid arthritis may affect the kidney
glomerulus directly through a vasculopathy or a
mesangial infiltrate but this is less well
documented. Treatment with Penicillamine and
gold salts are recognized causes of membranous
nephropathy.

Heart and blood vessels People with rheumatoid
arthritis are more prone to atherosclerosis,
and risk of myocardial infarction and stroke
is markedly increased. Other possible
complications that may arise include
pericarditis, endocarditis, left ventricular
failure, valvulitis and fibrosis.
The eye is directly affected in the form of
episcleritis which when severe can very rarely
progress to perforating scleromalacia. Rather
more common is the indirect effect of
keratoconjunctivitis sicca, which is a dryness of
eyes and mouth due to lymphocyte infiltration of
lachrymal and salivary glands. When severe,
dryness of the cornea can lead to keratitis and
loss of vision.
hepatic
Cytokine production in joints and/or hepatic
Kupffer cells leads to increased activity of
hepatocytes with increased production of
acute-phase proteins, such as C-reactive protein,
and increased release of enzymes such as alkaline
phosphatase into the blood. Hepatic involvement
in RA is essentially asymptomatic. In Felty's
syndrome, Kuppfer cell activation is so marked
that the resulting increase in hepatocyte
activity is associated with nodular hyperplasia
of the liver, which may be palpably enlarged
splenomegaly.
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Heamatological

• Anemia is by far the most common abnormality of
  the blood cells.
• The red cells are of normal size and color
  (normocytic).
• A low white blood cell count (neutropenia)
  usually only occurs in patients with Felty's
  syndrome with an enlarged liver and spleen. The
  mechanism of neutropenia is complex.

Cyclic citrullinated peptide antibodies
(anti-CCP). These are measured by an ELISA
technique and are present in up to 80 of
patients with RA. They have a high specificity
for RA (90). They are helpful in early disease
when the RF is negative to distinguish it from
acute transient synovitis Both RF and anti-CCP
are positive in established RA in more than 90
of patients.
Peripheral neuropathy and mononeuritis multiplex
may occur. The most common problem is carpal
tunnel syndrome due to compression of the median
nerve by swelling around the wrist. erosion of
the odontoid process and or/transverse ligaments
in the cervical spine's connection to the skull.
Such an erosion (gt3mm) can give rise to vertebrae
slipping over one another and compressing the
spinal cord. Clumsiness is initially
experienced, but this can progress to
quadriplegia.
General manifestations
Constitutional symptoms including fatigue, low
grade fever, malaise, morning stiffness, loss of
appetite and loss of weight are common systemic
manifestations seen in patients with active
rheumatoid arthritis.
Local Osteoporosis occurs in RA around inflamed
joints. It is postulated to be partially caused
by inflammatory cytokines. More general
osteoporosis is probably contributed to by
immobility, systemic cytokine effects, local
cytokine release in bone marrow and
corticosteroid therapy
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DiagnosisImaging

• X-rays of the hands and feet are generally
  performed in people with a polyarthritis.
• In rheumatoid arthritis, these may not show any
  changes in the early stages of the disease, but
  more advanced cases demonstrate erosions and bone
  resorption.
• X-rays of other joints may be taken if symptoms
  of pain or swelling occur in those joints.

Laboratory
When RA is clinically suspected, immunological
studies are required, such as testing for the
presence of rheumatoid factor (RF, a specific
antibody IgM). A negative RF does not rule out
RA rather, the arthritis is called
seronegative. This is the case in about 15 of
patients. During the first year of illness,
rheumatoid factor is more likely to be negative
with some individuals converting to seropositive
status over time. RF is also seen in other
illnesses, for example Sjögren's syndrome,(dry
eyes dry mouth) and in approximately 10 of the
healthy population, therefore the test is not
very specific.
The American College of Rheumatology defined
the following criteria for the diagnosis of
rheumatoid arthritis -Morning stiffness of gt1
hour most mornings for at least 6 weeks.
-Arthritis and soft-tissue swelling of gt3 of 14
joints/joint groups, present for at least 6 weeks
-Arthritis of hand joints, present for at least
6 weeks -Symmetric arthritis, present for at
least 6 weeks -Subcutaneous nodules in specific
places -Rheumatoid factor at a level above the
95th percentile -Radiological changes suggestive
of joint erosion -At least four criteria have to
be met for classification as RA
Differential diagnosis Several other medical
conditions can resemble RA, and usually need to
be distinguished from it at the time of
diagnosis Crystal induced arthritis- (gout, and
pseudogout) - usually involves particular joints
and can be distinguished with aspiration of joint
fluid if in doubt Osteoarthritis - distinguished
with X-rays of the affected joints and blood
tests Systemic lupus erythematosus (SLE) -
distinguished by specific clinical symptoms and
blood tests (antibodies against double-stranded
DNA) One of the several types of psoriatic
arthritis resembles RA - nail changes and skin
symptoms distinguish between them Reactive
arthritis (previously Reiter's disease) -
asymmetrically involves heel, sacroiliac joints,
and large joints of the leg. It is usually
associated with urethritis, conjunctivitis,
iritis, painless buccal ulcers.
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• Treatment
• There is no cure for RA
• The goal of treatment is two-fold
• 1-alleviating the current symptoms,
• 2- and preventing the future destruction of the
  joints with the resulting handicap if the disease
  is left unchecked.
• These two goals may not always coincide while
  pain relievers may achieve the first goal, they
  do not have any impact on the long-term
  consequences. For these reasons, most authorities
  believe that most RA should be treated by at
  least one specific anti-rheumatic medication,(
  DMARD ), to which other medications and
  non-medical interventions can be added as needed.

.
DMARDs ,which mainly act through cytokine
inhibition, reduce inflammation, as reflected by
reduction of joint swelling, a fall in the acute
phase reactants and slowing of the development of
joint erosions and irreversible damage. There
beneficial effect is not immediate(hence
slow-acting agents) and may be partial or
transient.
Pharmacological treatment of RA can be divided
into Non-steroidal anti-inflammatory drugs
(NSAIDs) and coxibs -Corticosteroids
Disease-modifying antirheumatic drugs
(DMARDs) TNF-alpha blockers Infiliximab Biologica
l treatment Rituximab
Chemically synthesised DMARDs azathioprine
ciclosporin (cyclosporine A) D-penicillamine
gold salts hydroxychloroquine leflunomide
methotrexate (MTX) minocycline sulfasalazine
(SSZ)
The most important and most common adverse
events relate to liver and bone marrow toxicity
(MTX, SSZ, leflunomide, azathioprine, gold
compounds, D-penicillamine), renal toxicity
(cyclosporine A, parenteral gold salts,
D-penicillamine), pneumonitis (MTX), allergic
skin reactions (gold compounds, SSZ),
infections (azathioprine, cyclosporine A) .
Hydroxychloroquine may cause ocular toxicity,
although this is rare, and because
hydroxychloroquine does not affect the bone
marrow or liver it is often considered to be the
DMARD with the least toxicity Unfortunately
hydroxychloroquine is not very potent, and is
usually insufficient to control symptoms on its
own.
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Prognosis

• The course of the disease varies greatly.
• Some people have mild short-term symptoms, but
  in most the disease is progressive for life.
• Around 20-30 will have subcutaneous nodules
  (known as rheumatoid nodules) this is associated
  with a poor prognosis

Prognostic factors Poor prognostic factors
include persistent synovitis, early erosive
disease, extra-articular findings (including
subcutaneous rheumatoid nodules), positive serum
RF findings, family history of RA, poor
functional status, elevated acute phase response
(erythrocyte sedimentation rate ESR, C-reactive
protein CRP, and increased clinical severity.