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COMPLICATIONS RHEUMATOID ARTHRITIS BY DR BASHIR AHMED DAR ASSOCIATE PROFESSOR MEDICINE SOPORE KASHMIR

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COMPLICATIONS RHEUMATOID ARTHRITIS BY DR BASHIR AHMED DAR ASSOCIATE PROFESSOR MEDICINE SOPORE KASHMIR Powered By Docstoc
					       RHEUMATOID ARTHRITIS
BY
DR BASHIR AHMED DAR
ASSOCIATE PROFESSOR MEDICINE
SOPORE KASHMIR
EMAIL—drbashir123@gmail.com
Dr Bashir and Dr Yashodhra leading group of medical students to meet
            noble prize winner in medicine at KL Malaysia
Dr Bashir at PBL Conference
Noble prize winner Prof Barry .J Marshall in recognition of his discovery
       Helicobacter pylori-most common cause for peptic ulcer
Precious moments with noble prize winner
             RHEUMATOID ARTHRITIS
• Rheumatoid arthritis is
  autoimmune disorder in
  which Immune system
  identifies the synovial
  membrane as "foreign"
  and begins attacking it.




•   Synovial membrane shown in picture
         RHEUMATOID ARTHRITIS
• With long-term or intensive
  exposure to the antigen,
  normal antibodies become
  auto-antibodies that target
  self-antigens in the synovial
  membrane.
        RHEUMATOID ARTHRITIS
• Once the antigen or
  immune complex reaches
  the synovial membrane .The
  antigen presenting cell
  deals with it.
         RHEUMATOID ARTHRITIS

• First, the APC usually a
  macrophage in synovium
  engulfs the antigen.

• Enzymes (peroxides) inside
  the APC break down the
  antigen into smaller
  particles.
         RHEUMATOID ARTHRITIS

• The processed antigens are
  transported to the surface
  of the APC, where it binds
  with MHC (major
  histocompatibility complex).
          RHEUMATOID ARTHRITIS

• This complex ie (part of a
  foreign substance and MHC)
  is now presented to T-cells
  (CD4 cells ie T-helper cell )
  or CD8 (cytotoxic T cells)
  which the T-cell receptor
  (TCR) recognizes and binds
  to.
          RHEUMATOID ARTHRITIS

 Once the T-cell binds to the
  Antigen / MHC complex, the APC
  then secrete cytokines like
 Interleukin-1 (IL-1)
 Interferon-alpha (IFN-a)
 Interferon-gamma (IFN-g)
 Tumor necrosis factor (TNF)
 And other factors that activate
  lymphocytes and other immune
  cells to respond to the antigens.
        RHEUMATOID ARTHRITIS
• APC also Secretes
• Lysozymes, Elastases and Collagenases these enzymes cause
  cartilage breakdown.
• FGF & Angiogenesis Factors add to pannus formation
• Chemokines mediates chemo attraction (chemotaxis)
                        Effects of IL-1

• On exposure to IL-1, synoviocytes proliferate and produce
  following factors
• Interleukin-6 (IL-6)
• Prostaglandin's (e.g. , PGE2) , and platelet-activating factor,
  which are involved in the pain mechanism.
• Matrix Metalloproteases(e.g. stromelysin) that cause
  activation of collagenase, an enzyme required for cartilage
  breakdown.
                         Effects of IL-1

• IL-1 also activates endothelial
  cells and induce stimulation of
  adhesion molecule expression on
  endothelial cells.
• Enhances activity of NK cells and
  leads to Pyrogen (cause fever).
                      Effects of IL-1

• IL-1 also causes increased production of inducible nitric oxide
  synthase and consequently high levels of nitric oxide kill
  chondrocytes, the cells responsible for cartilage remodeling.
• Induce osteoblast apoptosis and thereby prevent new bone
  formation
• Prevent formation of the cartilage matrix by inhibition of
  proteoglycan synthesis.
                        Effects of IL-1


• The end result of these of IL-1
  and TNF-a include activation and
  migration of leukocytes and
  lymphocytes from the blood into
  inflammatory tissues as well as
  formation of pannus and
  damage to cartilage and
  surrounding normal cells.
Effects of IL-1
                    MICROSCOPY- RA
• Micro: dense perivascular inflammatory infiltrate of T
  lymphocytes, plasma cells (often with eosinophilic
  cytoplasmic inclusions called Russell bodies)
• inflammation extends to subchondral bone (relatively specific
  for rheumatoid arthritis); proliferative synovitis with synovial
  cell hyperplasia and hypertrophy, necrobiotic nodules and
  fibrosis;
• increased vascularity with hemosidrin deposition; organizing
  fibrin floating in joint space as rice bodies; neutrophils present
  on synovial surface;
                  MICROSCOPY- RA

• Neutrophils, lymphocytes, plasma cells, macrophages, and
  fibroblasts are responsible for increased cellularity.
• Superficial areas of necrosis are present and masses of
  inflammatory cells can be seen free above the synovial
  surface.
MICROSCOPY- RA
                  MICROSCOPY- RA



• The synovium is red due to blood
  vessel dilatations and thickened
  due to inflammation and cellular
  infiltration.
                  MICROSCOPY- RA



• There is also granulation
  formation over the synovial
  membrane now called as
  pannus.
Early bone destruction in RA
                 MICROSCOPY- RA

• The inflammation can
  spread to soft tissues as
  shown in fig and destroy
  these structure causing
  laxity and deformity of
  joint.


• Muscles /tendons /ligaments
DISTRIBUTION OF JOINT INVOLVEMENT IN HANDS
DISTRIBUTION OF JOINT INVOLVEMENT IN HANDS
DISTRIBUTION OF JOINT INVOLVEMENT
ALL THESE JOINTS CAN GET AFFECTED-RA
                 Mast Cells
• Mast cells are implicated in the pathology of
  autoimmune disorders like rheumatoid
  arthritis.

• Mast cells are basophils that have "homed in"
  on tissues characteristically surrounding blood
  vessels and contains many granules rich in
  histamine and heparin.
                         Mast Cells
• Mast cells has a receptor for
  the Fc region of IgE.
• As a result, mast cells are
  coated with IgE.
• Mast cells usually remain
  inactive until an allergen binds
  to IgE already in association
  with the cell.
• It appears that binding of two
  or more IgE molecules is
  required to activate the mast
  cell.
Mast Cells
                       Mast Cells
• The molecules thus released by mast cell into the extracellular
  environment include:
• Cytokines
• Histamine/Serotonin/Heparin
• Eosinophil chemotactic factor
• Prostaglandin D2
• leukotrienes C4
• Platelet-activating factor
• TNFa
                       Mast Cells
• Histamine and serotonin dilates capillaries activates the
  endothelium, and increases blood vessel permeability. This
  leads to local edema (swelling), warmth, redness, and the
  attraction of other inflammatory cells to the site of release.
               RHEUMATOID ARTHRITIS

• Increase in the permeability of blood vessels in the synovial
  membranes. This attracts several types of leukocytes and
  lymphocytes to the synovial membrane out of the circulation.
• Synovial inflammation (synovitis)
         RHEUMATOID ARTHRITIS
• The phagocytes of inflammation (neutrophils and
  macrophages) ingest the immune complexes which releases
  powerful enzymes that degrade synovial tissue and articular
  cartilage.
         RHEUMATOID ARTHRITIS
• Inflammation causes hemorrhage, coagulation, and fibrin
  deposits on the synovial membrane, in the intracellular
  matrix, and in the synovial fluid.
         RHEUMATOID ARTHRITIS
• On the denuded areas of the synovial membrane, fibrin gets
  deposited and develops into granulation tissue called pannus,
  which is the earliest tissue produced in the healing process.
         RHEUMATOID ARTHRITIS
• The pannus is a sheet of inflammatory granulation tissue that
  spreads from the synovial membrane and invades the joint in
  rheumatoid arthritis ultimately leading to fibrous ankylosis.
         RHEUMATOID ARTHRITIS
• The synovial membrane undergoes hyperplasic thickening as
  its cells abnormally proliferate and enlarge.

• These vascular derangements decrease blood flow to the
  synovial tissue and compromised circulation. This, coupled
  with increased metabolic needs due to hypertrophy and
  hyperplasia, causes hypoxia (oxygen depletion) and metabolic
  acidosis.
          RHEUMATOID ARTHRITIS
• Acidosis stimulates the release of hydrolytic enzymes from
  synovial cells into the surrounding tissue, initiating erosion of
  the articular cartilage and inflammation spreads into the
  supporting ligaments and tendons.
         RHEUMATOID ARTHRITIS
• The synovitis or inflammation, results in the warmth,
  redness, swelling, and pain that are typical symptoms of RA.
         RHEUMATOID ARTHRITIS
• In this disease process, an interaction between antibodies and
  antigens occurs, and causes alterations in the composition of
  the synovial fluid. Infiltration of cells in it etc.
          RHEUMATOID ARTHRITIS
• Once the composition of this fluid is altered, it is less able to
  perform the normal functions and results in soft tissue
  destruction that eventually leads to laxity in tendons and
  ligaments.
         RHEUMATOID ARTHRITIS
• Stage One:
• Congestion and edema of the synovial membrane and joint
  capsule.

• Stage Two:
• Formation of pannus occurs, covering the cartilage and
  eventually destroying the joint capsule and bone.
         RHEUMATOID ARTHRITIS
• Stage Three:
• Fibrous ankylosis, which is a fibrous invasion of pannus and
  scar tissue that fills the joint space.
• Mal-alignment cause visible deformities and disrupt the
  articulation of opposing bones. This, in turn, causes muscle
  atrophy and imbalance that may also include partial
  dislocations (subluxation).
          RHEUMATOID ARTHRITIS
• Stage Four:
• Fibrous tissue begins to calcify, resulting in bony ankylosis
  (total immobility).
                        Epidemiology

•   RA affects 0.5-1.0% of population in USA
•   Females > males 3:1
•   but people of any age can be affected
•   Peak age 45-65 but onset early from age 20-45 yrs
•   Smoking risk factor
•   Genetic
•   70% of patients with RA express HLA-DR4
•   twins indicate a concordance of about 15%–20%
                       Epidemiology

• It occurs worldwide, affecting more than 6.5 million people in
  the U.S. alone.

• About 75% of these are women.

• The disease strikes women three times more often than men.
                       Epidemiology

• Although it can occur at any age, the peak onset period is
  between the ages of 35 and 50.
• The disease may come on slowly or may appear suddenly.
 Diagnostic Criteria for RA ≥ 4 criteria present > 6 wks

• Morning stiffness > 1 hour      • Rheumatoid nodules

• Arthritis of ≥ 3 joints areas   • RF+
  (PIP, MCP, wrist, elbow,
  knee, ankle, and MTP)           • Radiographic changes erosions

• Arthritis of hand joints        • Unequivocal Periarticular
  (wrist, MCP, PIP)                 osteopenia

• Symmetric arthritis
                     ETIOLOGY OF RA

• The cause of rheumatoid arthritis is unknown. Even though
  infectious agents such as viruses, bacteria, and fungi have
  long been suspected as well as smoking, but none has been
  proven as the cause.
• It is believed that the tendency to develop rheumatoid
  arthritis may be genetically inherited.
                     ETIOLOGY OF RA

• For example, the genetic marker HLA-DR4 has been identified
  in as many as 66% of patients with disease. This marker, which
  is present in white blood cells, plays a role in helping the
  immune system to distinguish between foreign cells (e.g.,
  germs) and the body's own cells.
                    ETIOLOGY OF RA

• Because RA often is affected by pregnancy—symptoms
  improve before the infant is born and then worsen after
  delivery—it may be that hormones in the body influence
  disease development and progression.
                     ETIOLOGY OF RA

• Stress — Patients often report episodes of stress or trauma
  preceding the onset of their rheumatoid arthritis. Stressful
  "life events" (divorce, accidents, grief, etc) are more common
  in people with RA in the six months before their diagnosis
  compared to the general population.
                    ETIOLOGY OF RA

• All this might trigger the activation of the immune system in
  susceptible individuals. This misdirected immune system then
  attacks the body's own tissues. This leads to inflammation in
  the joints and sometimes in various organs of the body, such
  as the lungs or eyes.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• The joints of the hands are often the very first joints affected
  by rheumatoid arthritis. These joints are tender when
  squeezed, and the hand's grip strength is often reduced.
  Rheumatoid arthritis may lead to visible redness and swelling
  and pain of joints or entire the entire hand.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• The joints of the hands are
  often the very first joints
  affected by rheumatoid
  arthritis. These joints are
  swollen red and tender
  when squeezed.



• Swelling due to synovitis
RA - hands
RA - hands
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• Metacarpophalangeal and proximal inter phalangeal are
  involved. The joint stiffness is most bothersome in the
  morning and after sitting still for a period of time. The
  stiffness can persist for more than one hour.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• The symptoms of rheumatoid arthritis come and go,
  depending on the degree of tissue inflammation.

• When body tissues are inflamed, the disease is active. When
  tissue inflammation subsides, the disease is inactive (in
  remission).
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• Remissions can occur spontaneously or with treatment and
  can last weeks, months, or years.

• During remissions, symptoms of the disease disappear, and
  people generally feel well. When the disease becomes active
  again (relapse), symptoms return.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• The return of disease activity and symptoms is called a flare.
  The course of rheumatoid arthritis varies among affected
  individuals, and periods of flares and remissions are typical.
RA - hands
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• Muscle and joint stiffness are usually most notable in the
  morning and after periods of inactivity. Arthritis is common
  during disease flares. Also during flares, joints frequently
  become red, swollen, painful, and tender.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• This occurs because the lining tissue of the joint (synovium)
  becomes inflamed (synovitis) , resulting in the production of
  excessive joint fluid (synovial fluid).
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• In rheumatoid arthritis, multiple joints are usually inflamed in
  a symmetrical pattern (both sides of the body affected). The
  small joints of both the hands and wrists are often involved.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• Simple tasks of daily living, such as turning door knobs and
  opening jars, can become difficult during flares.

• The small joints of the feet are also commonly involved.
 SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• Chronic inflammation can cause damage to body tissues,
  including cartilage, tendons, ligaments and bone.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• This leads to a loss of cartilage and erosion and weakness of
  the bones as well as the muscles, resulting in joint deformity,
  destruction, and loss of function which often leads to
  difficulty performing every day tasks (e.g., buttoning a shirt,
  opening a jar).
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• Occasionally, only one joint is inflamed. When only one joint is
  involved, the arthritis can mimic the joint inflammation
  caused by other forms of arthritis, such as gout or joint
  infection.
  SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS

• Certain characteristic hand deformities can occur with long-
  standing rheumatoid arthritis like
• Swan neck deformities
• Boutonniere deformities
• Z deformity of thumb
• Bow string sign
• The tendons on the back of the hand may become very
  prominent and tight, called the bow string sign.
                   Swan neck deformity

• The deformity arises from
  hyperextension of the
  proximal interphalangeal
  joint, while the distal
  interphalangeal joint is
  flexed.
Swan neck deformity
                     Swan neck deformity

• In the PIP joint the strongest ligament is the volar plate.

• This ligament connects the proximal phalanx to the middle
  phalanx on the palm side of the joint.

• The ligament tightens as the joint is straightened and keeps
  the PIP joint from bending back too far (hyperextending).
  Swan neck deformity
                 Swan neck deformity

• FDS rupture/ volar plate
  injury

• Lateral bands sublux
  dorsally

• PIP hyperextends and
  DIP flexes
                 Swan neck deformity

• Although characteristic in RA, swan-neck deformity
  has several causes, including untreated mallet finger,
  laxity of the ligaments of the volar aspect of the PIP
  joint in old age or a normal variant.

• True swan-neck deformity does not affect the thumb,
  which has only one interphalangeal joint.
                     Mallet Finger

• Mallet finger is a simple
  flexion deformity of the
  distal interphalangeal
  joint preventing
  extension. This
  deformity results from
  an extensor tendon
  rupture.
                    Z- deformity of Thumb

• Severe hyperextension of
  the interphalangeal joint of
  the thumb with flexion of
  the metacarpophalangeal
  (MCP) joint can occur; this is
  called a duck bill, Z (zigzag)
  type, or 90°-angle
  deformity.

• With simultaneous thumb
  instability, pinch is greatly
  impaired.
                Buttonhole Deformity

• Flexion of the PIP joint accompanied by
  hyperextension of the DIP joint .

• This deformity can result from tendon laceration,
  dislocation, fracture, osteoarthritis, or RA.
                 Buttonhole Deformity

• The tendons which
  straighten finger joints
  are like strings running
  from the sides and the
  back of the finger to a
  sheet on the top of the
  finger.
                Buttonhole Deformity

• When the finger is hit
  or bent forcefully in just
  the wrong way, the
  sheet on the top of the
  finger (the central slip
  of tendon) tears away
  from its attachment to
  the top of the middle
  finger bone.
             Buttonhole Deformity

• The tear in the tendon sheet looks like a
  buttonhole ("boutonniere" in French), and the
  end of the finger bone actually begins to stick
  through the hole. As a result, the tendons
  can't straighten the middle joint (which stays
  bent) and all of the force of the tendons
  bypasses the middle joint and goes to the end
  joint (which flips backward).
Buttonhole Deformity
Flexion of the PIP joint accompanied by hyperextension of the
       DIP joint is boutoniere deformity in little finger.
Buttonhole Deformity
Buttonhole Deformity
Buttonhole deformity on x-ray
  COMPLICATIONS OF
RHEUMATOID ARTHRITIS
               Rheumatoid nodules

• Painless firm lumps that
  appear beneath the
  skin, often single or
  multiple, and range in
  size from millimeters to
  centimeters in
  diameter occur on the
  underside of the
  forearm and on the
  elbow.
               Rheumatoid nodules

• But they can also occur
  on other pressure
  points, including the
  back of the head, the
  base of the spine, the
  Achilles tendon, and the
  tendons of the hand
              Rheumatoid nodules

• Occur in about 25% of
  patients
• More common in men
  than women
               Rheumatoid nodules

• These nodules may
  move easily when
  touched or they may be
  fixed to deeper tissues
  and cause pressure on
  surrounding nerves or
  can rupture, causing
  pain and discomfort in
  surrounding tissue.
              Rheumatoid nodules

• Although nodules are
  mostly benign,
  complications such as
  infection, ulceration,
  and gangrene can occur
  following breakdown of
  skin overlying the
  nodules.
                Rheumatoid nodules

• Usually no treatment is
  necessary unless
  nodules become
  debilitating, ulcerated,
  or infected. Surgical
  removal may be
  performed.
Skin complications of RA
                Skin complications of RA

• Skin and muscles become
  atrophic (thin and
  wrinkled), making it fragile
  and easy to bruise .
              Skin complications of RA

• Skin on the back of the
  hands may become pale
  or even translucent
• Nails may become
  brittle and split length-
  wise
           Skin complications of RA

• The palms become
  reddened (palmer
  erythema)
                  Skin complications of RA

• A rare, serious
  complication, usually with
  long-standing rheumatoid
  disease, is blood vessel
  inflammation (Vasculitis).
  Vasculitis can impair blood
  supply to tissues and lead to
  tissue death (necrosis). This
  is most often initially visible
  as tiny black areas around
  the nail beds or as leg
  ulcers.

• Atrophic skin
             Skin complications of RA

• Dark purplish areas on
  the skin (purpura) are
  caused by bleeding into
  the skin from blood
  vessels damaged by
  rheumatoid arthritis.
               Skin complications of RA

• Rheumatoid Vasculitis can
  cause many internal
  symptoms, , hepatomegaly
  (enlarged liver),
  splenomegaly (enlarged
  spleen), bowel ulcers, and
  haematuria (blood in urine).
               Skin complications of RA

• Skin ulcers (usually leg
  ulcers) may be extensive
  and painful
• Petechiae (purplish spots)
  or purpura
• Nail fold or edge breakdown
• Gangrene
RA - Vasculitis
              Skin complications of RA

• Neutrophilic dermatoses
• Neutrophils are a type of
  white blood cell
  (leucocyte). They are
  present in bacterial
  infections. They are the
  prominent cell seen on
  skin biopsy of some
  uncommon inflammatory
  skin diseases known as
  neutrophilic dermatoses.
            Skin complications of RA

• Sweet disease and
  pyoderma
  gangrenosum are other
  neutrophilic disorders
  sometimes seen in
  association with
  rheumatoid arthritis.

• Pyoderma
  gangrenosum
              Skin complications of RA

• Interstitial granulomatous
  dermatitis.

• also known as
  ‘rheumatoid papules’,
  interstitial granulomatous
  dermatitis presents as
  skin coloured or red
  papules often on the
  trunk. It is rare.
               Skin complications of RA

• RA can affect the glands
  located near the eyes and
  mouth, resulting in a
  condition called secondary
  Sjogren's syndrome
• Decreased tear and saliva
  production can cause dry
  mouth, and dry eyes.

• Sjogren's syndrome
      GASTRO-INTESTINAL COMPLICATIONS

• Dry mouth, related to Sjogren syndrome, is the most
  common symptom of gastrointestinal involvement.

• Gastritis (stomach inflammation) or stomach ulcer
  caused by NSAID therapy.
     Urinary complications of RA
• The kidneys are not usually affected directly
  by rheumatoid arthritis. Kidney problems in
  rheumatoid arthritis are much more likely to
  be caused by medications used to treat the
  condition.
Hematological complications of RA
• Anemia
• Low white blood cell count (leukopenia) can
  occur from Felty's syndrome, a complication
  of rheumatoid arthritis that is also
  characterized by enlargement of the spleen.
Hematological complications of RA
• Immune thrombocytopenic purpura caused by
  an autoimmune reaction against platelets.

• drug induced neutropenia; thrombocytopenia,
  particularly autoimmune and drug induced
  thrombocytopenia; and hematological
  malignancy.
    Nervous complications of RA
• Entrapment of
  nerves. Carpal
  tunnel syndrome
  or ulnar nerve
  neuropathy
• including sensory
  or motor
  neuropathy (loss
  of sensation)
     Nervous complications of RA
• Formation of a Baker's
  cyst (a cyst filled with
  joint fluid and located in
  the hollow space at the
  back of the knee).

• Its herniation of
  posterior capsule
 RESPIRATORY COMPLICATIONS OF RA
• CAPLANS SYNDROME

• The combination of RA and exposure to coal
  dust produces the condition. It develops
  especially in miners working in anthracite
  coal-mines and in persons exposed to silica
  and asbestos.
 RESPIRATORY COMPLICATIONS OF RA
• CXR shows multiple,
  round, well defined
  nodules, usually 0.5 -
  2.0 cm in diameter,
  which may cavitate and
  resemble tuberculosis.
  CT scanning gives a
  better picture of
  cavitation.
 RESPIRATORY COMPLICATIONS OF RA
• well defined nodules,
  usually 0.5 - 2.0 cm in
  diameter, which may
  cavitate and resemble
  tuberculosis.
 RESPIRATORY COMPLICATIONS OF RA
• The syndrome is named
  after Dr. Anthony
  Caplan, a physician on
  the Cardiff
  Pneumoconiosis Panel.
 RESPIRATORY COMPLICATIONS OF RA
• Fibrosis of lung
  scattered all over lung
       OCULAR COMPLICATIONS OF RA

• RA can also cause inflammation of the sclera (white
  part of the eye), which may make the sclera appear
  red or bluish in color.
  OCULAR COMPLICATIONS OF RA
• Keratoconjunctivitis
  sicca
  OCULAR COMPLICATIONS OF RA
• Episcleritis
  OCULAR COMPLICATIONS OF RA
• Scleritis
  OCULAR COMPLICATIONS OF RA
• Stromal corneal
  opacities with
  peripheral
  vascularisation
  OCULAR COMPLICATIONS OF RA
• Iridocyclitis.
  OCULAR COMPLICATIONS OF RA
• Marginal thinning of the
  cornea with keratolysis
                 Lysis of bones
• Punched out lytic
  changes in bones

• Lytic changes in toes
                   RA - knees
• Joint spaces in knee is
  reduced due cartilage
  destruction.
Cock-up deformity or hammer toes
             MTP Subluxation
• Abducto hallus vulgus
             MCP Subluxation
• Subluxation of MCP
  joints.
Ulnar Deviation
Atlantoaxial Instability
                     Bow string sign

• The tendons on the back of
  the hand may become very
  prominent and tight, called
  the bow string sign.

• Ulnar deviation
• The direction of prominent
  tendons is like bow string
           Rheumatoid Arthritis
• Differential Diagnosis
  – Pyogenic arthritis: usually monoarticular, fever and chills,
    abnormal joint fluid
  – Chronic Lyme disease: commonly monoarticular and
    associated with positive titers
  – Human Parvovirus infection: arthralgia more common than
    arthritis, rash may be present, serologic evidence of
    parvovirus B19 infection
  – Polymyalgia rheumatica is associated with proximal muscle
    weakness and stiffness
           Rheumatoid Arthritis
• Differential Diagnosis
  – several cancers produce paraneoplastic syndromes
    including polyarthritis; e.g., hypertrophic pulmonary
    osteoarthropathy produced by lung and gastrointestinal
    cancers. Diffuse swelling of the palmar fascia has been
    associated with several cancers including ovarian cancer.
               Diagnostic Findings

•   Rheumatoid Factor
•   Elevated ESR
•   C-reactive protein
•   Anemia
•   Thrombocytosis
•   Antinuclear antibodies
•   Synovial fluid: WBC >2000/mm3
               Laboratory – RF
• Rheumatoid Factor
  – Antibody igM against the Fc fragment of IgG
  – Not sensitive
     • 80% of RA patients
  – RF+ patients more likely to have
     • More severe disease
     • Extraarticular manifestations
                   Anti-CCP
• Anti-cyclic citrullinated peptide
• Specificity = 90%
• Sensitivity = 50-80%
       TREATMENT OF RHEUMATOID
              ARTHRITIS
• Nonsteroidal anti inflammatory drugs (NSAIDs)
  are a class of drugs that reduce inflammation,
  pain, fever, and swelling and are commonly
  prescribed for the inflammation of the joints
  (arthritis) and other tissues, such as in tendinitis
  and bursitis.
        Nonsteroidal anti inflammatory drugs

•   Examples of NSAIDs include:
•   Aspirin
•   Indomethacin
•   Ibuprofen
•   Naproxen
•   Piroxicam
•   Nabumetone
•   Diclofenac
•   All NSAIDs should be taken with meals to prevent stomach
    upset.
Nonsteroidal anti inflammatory drugs
• NSAIDs work by blocking the production of
  prostaglandins, chemical messengers that
  often are responsible for the pain and swelling
  of inflammatory conditions.
Nonsteroidal anti inflammatory drugs
• Prostaglandins are made by two different
  enzymes, cyclooxygenase-1 (COX-1) and
  cyclooxygenase-2 (COX-2). The prostaglandins
  made by the two different enzymes have
  slightly different effects on the body.
Nonsteroidal anti inflammatory drugs
• COX-2 inhibitors are NSAIDs that selectively
  block the COX-2 enzyme and not the COX-1
  enzyme. Blocking this enzyme impedes the
  production of prostaglandins.
Nonsteroidal anti inflammatory drugs
• Some of the prostaglandins made by COX-1
  protect the inner lining of the stomach.
  Common NSAIDs such as aspirin block both
  COX-1 and COX-2 .
Nonsteroidal anti inflammatory drugs
• When the COX-1 enzyme is blocked,
  inflammation is reduced, but the protection of
  the lining of the stomach also is lost. This can
  cause stomach upset as well as ulceration and
  bleeding from the stomach and even the
  intestines.
Nonsteroidal anti inflammatory drugs
• COX-2 enzyme is located specifically in areas
  of the body that commonly are involved in
  inflammation but not in the stomach.
Nonsteroidal anti inflammatory drugs
• When the COX-2 enzyme is blocked,
  inflammation is reduced; however, since the
  COX-2 enzyme does not play a role in
  protecting the stomach or intestine, therefore
  do not injure the stomach or intestines as
  compared to COX-1 inhibitors.
Nonsteroidal anti inflammatory drugs
• Older NSAIDs (for example, ibuprofen,
  naproxen, etc.) all act by blocking the action of
  both the COX-1 and COX-2 enzymes.
Nonsteroidal anti inflammatory drugs
• NSAIDs, including COX-2 inhibitors, may
  increase the risk of heart attacks, stroke, and
  related conditions. This risk may increase in
  patients with risk factors for heart disease and
  related conditions.
Nonsteroidal anti inflammatory drugs
• Aspirin         • 500-1000 mg every 6
                    hours or BD. Heart
                    attacks are prevented
                    with 50/75 or 325 mg
                    daily.


• Indomethacin    • 50-200 mg per day split
                    into 2-3 doses
Nonsteroidal anti inflammatory drugs
• Ibuprofen       • 200 or 400 mg every 6
                    hours. Individuals
                    should not use
                    ibuprofen for more than
                    10 days for the
                    treatment of pain or
                    more than 3 days for
                    the treatment of a fever
                    unless directed by a
                    physician.
Nonsteroidal anti inflammatory drugs
• Naproxen        • 250-500 mg twice daily

• Piroxicam       • 20 mg once daily or 10
                    mg twice daily
• Nabumetone      • 1000 mg daily as a single
                    dose. Some patients may
                    respond better to 1500 or
                    2000 mg daily. The lowest
                    effective dose should be
                    used
• Diclofenac      • 50-100 mg /day
               COX-2 inhibitors
• COX-2 inhibitors are

• Celecoxib
• Rofecoxib
• valdecoxib
              COX-2 inhibitors
• Celecoxib
                      . 100 or 200 mg twice
                        daily.
                      • The lowest effective
                        dose should be used for
                        each patient.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• While "first-line" medications (NSAIDs and
  corticosteroids) can relieve joint inflammation
  and pain, they do not necessarily prevent joint
  destruction or deformity.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• For patients with an aggressively destructive
  form of rheumatoid arthritis, medications
  other than NSAIDs and corticosteroids are
  needed. These "second-line" or "slow-acting"
  medicines may take weeks to months to
  become effective.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• They are used for long periods of time, even
  years, at varying doses. If effective, they can
  promote remission, thereby retarding the
  progression of joint destruction and deformity.
  Sometimes a number of second-line
  medications are used together as combination
  therapy.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• Hydroxychloroquine
• is related to quinine, and is used in the
  treatment of malaria. It is used over long
  periods for the treatment of rheumatoid
  arthritis. Side effects include upset stomach,
  skin rashes, muscle weakness, and vision
  changes.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• The usual adult dose for treating malaria is
  800 mg initially, followed by 400 mg 6 hours
  later then 400 mg on days 2 and 3. The dose
  for malaria prevention is 400 mg every week
  starting 1 or 2 weeks before exposure and for
  4 weeks after leaving the high risk area.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• The recommended adult dose for rheumatoid
  arthritis is 400-600 mg daily for 4-12 weeks
  followed by 200-400 mg daily.

• Systemic lupus erythematosus is treated with
  400 mg once or twice daily for several weeks
  then 200-400 mg daily. Hydroxychloroquine
  should be taken with food or milk in order to
  reduce stomach upset.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• Sulfasalazine

• is an oral medication traditionally used in the
  treatment of mild to moderately severe
  inflammatory bowel diseases, such as
  ulcerative colitis and Crohn's colitis.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• Sulfasalazine is used to treat rheumatoid
  arthritis in combination with anti-
  inflammatory medications. Sulfasalazine is
  generally well tolerated. Common side effects
  include rash and upset stomach. Because
  sulfasalazine is made up of sulfa and salicylate
  compounds, it should be avoided by patients
  with known sulfa allergies.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• Gold salts

• have been used to treat rheumatoid arthritis
  throughout most of this century. Gold
  thioglucose (SOLGANAL) and gold thiomalate
  (MYOCHRYSINE) are given by injection, initially
  on a weekly basis for months to years. Oral
  gold, auranofin (RIDAURA) was introduced in
  the 1980's.
   Disease-Modifying Antirheumatic
          Drugs or DMARDs
• Side effects of gold (oral and injectable)
  include skin rash, mouth sores, kidney damage
  with leakage of protein in the urine, and bone
  marrow damage with anemia and low white
  cell count. Patients receiving gold treatment
  are regularly monitored with blood and urine
  tests. Oral gold can cause diarrhea.
      Immunosuppressive Medicines


• Are powerful medications that suppress the body's
  immune system. A number of immunosuppressive
  drugs are used to treat rheumatoid arthritis. They
  include

•   Methotrexate
•   Azathioprine
•   Cyclophosphamide
•   Chlorambucil and
•   Cyclosporine
     Immunosuppressive Medicines

• Because of potentially serious side effects,
  immunosuppressive medicines (other than
  methotrexate) are generally reserved for
  those who have very aggressive disease or
  those with serious complications of
  rheumatoid inflammation, such as blood
  vessel inflammation (vasculitis).
     Immunosuppressive Medicines

• The exception is methotrexate, which is not
  frequently associated with serious side effects
  and can be carefully monitored with blood
  testing. Methotrexate has become a preferred
  second-line medication as a result.
    Immunosuppressive Medicines

• Methotrexate may be taken with or without
  food.7.5 mg dose weekly.
• Thinning of the bones due to osteoporosis
  may be prevented by calcium and vitamin D
  supplements.
         Newer "second- line“ drugs
          or "biologic" medications
•   Leflunomide
•   Etanercept
•   Infliximab
•   Annakira
•   Adalimumab
•   Rituximab
•   Abatacept
•   Golimumab
•   Certolizumab
•   Tocilizumab
       Newer "second- line“ drugs
        or "biologic" medications
• Each of these medications can increase the
  risk for infections, and the development of any
  infections should be reported to the health-
  care professional when taking these newer
  second-line drugs.
       Newer "second- line“ drugs
        or "biologic" medications
• Most of biologic medications intercept a
  messenger protein in the joints (tumor
  necrosis factor or TNF) that promotes
  inflammation of the joints in rheumatoid
  arthritis.
• This effectively blocks the recruiting the cells
  of inflammation.
            Newer "second- line“ drugs
             or "biologic" medications
• Etanercept must be injected subcutaneously once or twice a week

• Infliximab is given by infusion directly into a vein (intravenously)

• Adalimumab is injected subcutaneously once or twice a week

• Golimumab is injected subcutaneously on a monthly basis.

• Certolizumab is injected subcutaneously once or twice a week
        Newer "second- line“ drugs
         or "biologic" medications

• They are currently recommended for use after other
  second-line medications have not been effective.

• Are expensive , frequently used in combination with
  methotrexate and other DMARDs.
       Newer "second- line“ drugs
        or "biologic" medications

• These medications should be avoided by
  persons with significant congestive heart
  failure or demyelinating diseases (such as
  multiple sclerosis) because they can worsen
  these conditions.
       Newer "second- line“ drugs
        or "biologic" medications
• Rituximab

• Depletes B-cells, which are important cells of
  inflammation and in the production of
  abnormal antibodies.
       Newer "second- line“ drugs
        or "biologic" medications

• Abatacept
• Prevents the activation of the T-lymphocytes
  and blocks both the production of new T-
  lymphocytes and the production of the
  chemicals that destroy tissue and cause the
  symptoms and signs of arthritis.
       Newer "second- line“ drugs
        or "biologic" medications
• DOSING: Abatacept is infused over 30
  minutes. The initial dose of abatacept is
  followed by additional doses two and four
  weeks after the first infusion with further
  doses every 4 weeks thereafter. Patients
  weighing < 60 kg should receive a 500 mg
  dose, weighing 60-100 kg a 750 mg dose and
  weighing >100 kg a 1000 mg dose.
       Newer "second- line“ drugs
        or "biologic" medications

• Tocilizumab
• Blocks interleukin-6 (IL-6), Tocilizumab
  (Actemra) is an intravenous infusion given
  monthly.
       Newer "second- line“ drugs
        or "biologic" medications
• Anakinra

• Is a synthetic (man-made), injectable,
  interleukin-1 receptor antagonist that blocks
  the effects of human interleukin-1.
       Newer "second- line“ drugs
        or "biologic" medications
• The IL-1 attaches to receptors on the tissues
  within and surrounding the joints as well as on
  the cells that are responsible for
  inflammation, for example, white blood cells.
  The attachment of IL-1 activates the cells to
  promote inflammation and release enzymes.
  The enzymes destroy the cartilage and bone
  and contribute to pain and swelling of the
  joints.
       Newer "second- line“ drugs
        or "biologic" medications
• Anakinra attaches to the IL-1 receptor and
  prevents IL-1 from attaching to the receptor.
• Thus, the inflammatory and enzyme-releasing
  effects of IL-1 are prevented and pain and
  swelling of the joints are reduced.
• Anakinra was approved by the Food and Drug
  Administration in November, 2001
       Newer "second- line“ drugs
        or "biologic" medications
• DOSING: The daily dose of anakinra in
  rheumatoid arthritis is one subcutaneous
  injection of 100 mg daily. The dose should be
  administered at approximately the same time
  every day.
       Newer "second- line“ drugs
        or "biologic" medications
• Infliximab

• is an antibody that blocks the effects of tumor
  necrosis factor alpha (TNF alpha). Infliximab is
  administered by intravenous infusion. There
  are two other injectable drugs that block TNF
  alpha--adalimumab(Humira) and etanercept
  (Enbrel).
      Newer "second- line“ drugs
       or "biologic" medications
• Adalimumab

• DOSING: Adalimumab is injected under the
  skin. The recommended dose for adults is 40
  mg every other week, but some patients may
  need weekly administration.
       Newer "second- line“ drugs
        or "biologic" medications
• DOSING: Infliximab is administered
  intravenously. For moderate to severe Crohn's
  disease the dose is 5 mg/kg administered as a
  single dose. For fistulizing Crohn's disease, the
  dose is 5 mg/kg followed by additional doses
  of 5 mg/kg two and six week after the first
  dose.
       Newer "second- line“ drugs
        or "biologic" medications
• The recommended dose for the treatment of
  rheumatoid arthritis is 3 mg/kg as a single
  dose. The initial dose should be followed by
  additional 3 mg/kg doses two and six weeks
  after the first dose. Thereafter, the
  maintenance dose is 3 mg/kg every eight
  weeks.
       Newer "second- line“ drugs
        or "biologic" medications
• Etanercept

• Is an injectable drug that blocks tumor
  necrosis factor alpha (TNF alpha) and is used
  for treating rheumatoid arthritis, ankylosing
  spondylitis, and psoriatic arthritis.
       Newer "second- line“ drugs
        or "biologic" medications

• Etanercept is a synthetic (man-made) protein
  that binds to TNF alpha. It thereby acts like a
  sponge to remove most of the TNF alpha
  molecules from the joints and blood.
       Newer "second- line“ drugs
        or "biologic" medications

• DOSING: Etanercept is injected under the skin.
  Adults usually inject 25mg twice weekly.
  Children 4 to 17 years old should receive
  0.4mg/kg (maximum 25mg) twice weekly.
       Newer "second- line“ drugs
        or "biologic" medications

• While biologic medications are often
  combined with traditional DMARDs in the
  treatment of rheumatoid arthritis.
• Biologic medications are generally not used
  with other biologic medications because of
  the unacceptable risk for serious infections.
       Corticosteroid Therapy

• Medications can be given orally or injected
  directly into tissues and joints.
• They are more potent than NSAIDs in reducing
  inflammation and in restoring joint mobility
  and function.
        Corticosteroid Therapy

• Corticosteroids are useful for short periods
  during severe flares of disease activity or
  when the disease is not responding to NSAIDs.
• However, corticosteroids can have serious
  side effects, especially when given in high
  doses for long periods of time .
• Safe dose like Prenisolone is 5-10 mg daily.
        Corticosteroid Therapy
• These side effects include weight gain, facial
  puffiness, thinning of the skin and bone, easy
  bruising, cataracts, risk of infection, muscle
  wasting, and destruction of large joints, such
  as the hips.
     Prosorba column Therapy
• The Prosorba column therapy involves
  pumping blood drawn from a vein in the arm
  into an apheresis machine, or cell separator.
  This machine separates the liquid part of the
  blood (the plasma) from the blood cells.
      Prosorba column Therapy
• The Prosorba column is a plastic cylinder
  about the size of a coffee mug that contains a
  sand-like substance coated with a special
  material called Protein A. Protein A is unique
  in that it binds unwanted antibodies from the
  blood that promote the arthritis.
     Prosorba column Therapy

• The exact role of this treatment is being
  evaluated by doctors, and it is not commonly
  used currently.
 Combination DMARD therapy
• MTX + SSZ + OH-Chloroquine
 O’Dell 1995

• MTX + CSA
  Tugwell 1995

• MTX + Etanercept
• MTX + Remicade
• MTX + Adalimumab
• MTX + Leflunomide
excellent safety & improved efficacy over MTX
  alone
    ODB Indications for Biologic Drugs


• RA: Failure of DMARD therapy
    • Failure or Intolerance to
       –MTX 20mg/week sc or po x 3 months
       –Arava 20 mg po x 3 months
       –Any combination DMARD
                    Drugs & Pregnancy
•   NSAIDS: safe until week 34 (patent ductus)
•   OH-chloroquine: safe, ?cleft palate
•   Sulfasalzine: continue if on it; safe
•   Imuran: continue if on it; safe
•   Methotexate: teratogen ??? ok in small doses; stop 3 months before
    conception
•   Arava: teratogen may be present for 2 yrs
•   Cyclophosphamide:? teratogen ? Safe > 2nd trimester
•   Biologic agents: unknown; stop 3 months before conception
•   Steroids: non-fluorinated do NOT cross placenta
     THANK YOU SO MUCH
• Trust the physician and the teacher, and drink
  his remedy in silence and tranquility. For his
  hand though heavy and hard is guided by
  tender hand of unseen. And the cup he brings,
  though it burn your lips has been fashioned of
  the clay which the potter have moistened with
  his tears and sacred feelings.

				
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posted:8/31/2010
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Description: Dr Bashir ahmed dar associate professor medicine chinkipora sopore kashmir presently working in medical college malaysia describes rheumatoid arthritis which is a autoimmune disorder in which Immune system identifies the synovial membrane as "foreign" and begins attacking it.