Professional Documents
Culture Documents
BY
DR BASHIR AHMED DAR
ASSOCIATE PROFESSOR MEDICINE
SOPORE KASHMIR
EMAIL—drbashir123@gmail.com
Dr Bashir and Dr yashodhora 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 is
autoimmune disorder in
which Immune system
identifies the synovial
membrane as "foreign"
and begins attacking it.
Fibrous capsule of
synovial joint.
Rheumatoid
Arthritis
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
histocompatibili
ty complex)
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
Enhances activity of
NK cells and leads to
Pyrogen (cause
fever).
Effects of IL-1
The synovium red due to blood vessel Plus granulations form over the
diatations and thickened due to synovial membrane now called as
inflammation and cellular infiltration. pannus.
Early Destruction in 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
Mast cells
Mast cells are implicated in the pathology
associated with the autoimmune disorders
rheumatoid arthritis.
Mast cells
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
Stage One:
Congestion and edema of the synovial membrane
and joint capsule.
RHEUMATOID ARTHRITIS
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 (subluxations).
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%
Diagnostic Criteria for RA
≥ 4 criteria present > 6 wks
Morning stiffness > 1 Rheumatoid nodules
hour RF+
Arthritis of ≥ 3 joints Radiographic
areas (PIP, MCP, wrist, changes
elbow, knee, ankle, Erosions
and MTP) Unequivocal
Arthritis of hand joints periarticular
(wrist, MCP, PIP) osteopenia
Symmetric arthritis
RHEUMATOID ARTHRITIS
• It occurs worldwide, affecting more than 6.5
million people in the U.S. alone.
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.
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.
Flexion of the PIP joint accompanied by hyperextension of the DIP joint is boutoniere
deformity in little finger.
Boutoniere deformity
Boutoniere deformity
Boutoniere deformity
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
The palms
become
reddened
(palmer
erythema)
Skin complications of RA
Atrophic skin
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
Pyoderma
gangrenosum
Skin complications of RA
Interstitial granulomatous
dermatitis.
• Its herniation of
posterior capsule
RESPIRATORY COMPLICATIONS OF RA
• CAPLANS SYNDROME
• Ulnar deviation
• The direction of
prominent tendons is
like bow string
Rheumatoid Arthritis
• Differential Diagnosis
– Rheumatic fever: migratory arthritis, elevated ASO and
dramatic response to Aspirin
– Systemic Lupus Erythematosus: Butterfly rash, discoid
lupus erythematosus, photosensitivity, alopecia, high titers
of Anti Ds-DNA, renal and CNS disease
– Osteoarthritis: no constitutional manifestations and no
evidence of joint inflammation
– Gouty Arthritis: usually monoarticular initially but can
become polyarticular in the later years
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
152
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.
• 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.
• Methotrexate
• Azathioprine
• Cyclophosphamide
• Chlorambucil and
• Cyclosporine
Immunosuppressive Medicines
• MTX + CSA
Tugwell 1995
• MTX + Etanercept
• MTX + Remicade
• MTX + Adalimumab
• MTX + Leflunomide
excellent safety & improved efficacy over MTX
alone
ODB Indications for Biologic Drugs