Rani Fikratul F

050980111
 Arthritis means joint inflammation, just part
of the rheumatic diseases.
 Arthritis primarily involves:
Joint pain
Joint stiffness
Joint inflammation
Joint damage
 Rheumatoid Arthritis
 Osteoarthritis
 Juvenile Arthritis
 Psoriatic Arthritis
 Reactive Arthritis
 Infectious Arthritis
 Gout
 A systemic disease characterized by
symmetrical inflammation of joints yet may
involve other organ systems
 A form of autoimmunity, the causes of which
are still incompletely known
 An association with HLA-DR4 has been noted;
both genetic and environmental factors may
play a role in initiating disease

Dipiro, J.T., et al., 2008

Dipiro, J.T., et al., 2008
Ernest, H.S., et al., 2001.
1. A genetic link with HLA-DR4 and related allotypes of
MHC Class II and the T cell-associated protein
PTPN22.
2. A link with cigarette smoking that appears to be
causal.
3. A dramatic response in many cases to blockade of
the cytokine TNF (alpha).
4. A similar dramatic response in many cases to
depletion of B lymphocytes, but no comparable
response to depletion of T lymphocytes.
5. A more or less random pattern of whether and when
predisposed individuals are affected.
6. The presence of autoantibodies to IgGFc, known as
rheumatoid factors (RF), and antibodies to
citrullinated peptides (ACPA).

Fauci, A.S., et al., 2008.

Fauci, A.S., et al., 2008.
 a. Morning stiffness: Stiffness in and around the joints
lasting 1 h before maximal improvement.
 b. Arthritis of three or more joint areas: At least three
joint areas, observed by a physician simultaneously,
have soft tissue swelling or joint effusions, not just
bony overgrowth. The 14 possible joint areas involved
are right or left proximal interphalangeal,
metacarpophalangeal, wrist, elbow, knee, ankle, and
metatarsophalangeal joints.
c. Arthritis of hand joints: Arthritis of wrist,
metacarpophalangeal joint, or proximal
interphalangeal joint.
 

Fauci, A.S., et al., 2008.

d. Symmetric arthritis: Simultaneous involvement of the
same joint areas on both sides of the body.
e. Rheumatoid nodules: Subcutaneous nodules over bony
prominences, extensor surfaces, or juxtaarticular
regions observed by a physician.
f. Serum rheumatoid factor: Demonstration of abnormal
amounts of serum rheumatoid factor by any method for
which the result has been positive in less than 5% of
normal control subjects.
 g. Radiographic changes: Typical changes of RA on
posteroanterior hand and wrist radiographs that must
include erosions or unequivocal bony decalcification
localized in or most marked adjacent to the involved
joints.

Fauci, A.S., et al., 2008.

 Rheumatoid factor (RF) detectable in 60% to
70%.
 Anticyclic citrullinated peptide (anti-CCP)
antibodies have similar sensitivity to RF (50%
to 85%) but are more specific (90% to 95%)
and are present earlier in the disease.
 Elevated erythrocyte sedimentation rate and
C-reactive protein are markers for
inflammation.
 Normocytic normochromic anemia is
common as is thrombocytosis
Dipiro, J.T., et al., 2008
 Joint fluid aspiration may show increased
white blood cell counts without infection,
crystal
 Joint radiograph may show periarticular
osteoporosis, joint space narrowing, or
erosions

Dipiro, J.T., et al., 2008

Dipiro, J.T., et al., 2008
Hochberg, M.C., et al., 1992
Manifestation Note
Cutaneous rheumatoid nodules, vasculitis
Pulmonary nodules, interstitial disease,
bronchiolitis obliterans–organizing
pneumonia (BOOP), pleural disease,
Caplan’s syndrome [sero (+) RA
associated with pneumoconiosis]
Ocular keratoconjunctivitis sicca, episcleritis,
scleritis
Hematologic anemia, Felty’s syndrome
(splenomegaly and neutropenia)
Cardiac pericarditis, myocarditis
Neurologic myelopathies secondary to cervical
pine disease, entrapment,vasculitis

Kasper, D.L., et al ., 2005.

 Occur in 20% of patients with rheumatoid
arthritis  asymptomatic and do not require
any special intervention
 Nodules are seen most commonly on the
extensor surfaces of the elbows, forearms,
and hands but also may be seen on the feet.
 May develop in the lung or pleural lining of
the lung and, rarely, in the meninges

Dipiro, J.T., et al., 2008

 Characterized by inflammation of and damage to
blood vessels
 Aggressive treatment of the inflammatory process
is necessary
 Glucocorticoids should be initiatedCytotoxic
therapy should be added in these diseases only if
an adequate response does not result
 All vasculitis patients who are not allergic to sulfa
and who are receiving daily glucocorticoids in
combination with a cytotoxic drug should receive
TMP-SMX as prophylaxis against P. jiroveci infection
Fauci, A.S., et al., 2008.
 May involve the pleura of the lung, which is
often asymptomatic, although pleural
effusions may result
 Smoking increase the risk
 Keratoconjunctivitis sicca and inflammation of
the sclera, episclera, and corneaSjögren’s
syndrome
 Avoid smoking area, windy, low humidity
environtment, drug with anticholinergic
action, diuretics.
 Artificial tears without preservatives may be
used to relieve symptoms

Fauci, A.S., et al., 2008.

 Splenomegaly and neutropenia
 Treatment  control underlying rheumatoid
arthritis
 Most of medication used to tretment R.A 
used in treat Felty’s syndrome
 Agent of choice : metothrexate
 Rheumatoid arthritis is associated with an
increased risk of cardiovascular mortality
 Pericarditis may occur, resulting in the
accumulation of fluid.
 Myocarditis is a rare complication.
 Reduced with treatment, particularly with
methotrexate
1. Relief of pain
2. Reduction of inflammation
3. Protection of articular structures
4. Maintenance of function
5. Control of systemic involvement

Fauci, A.S., et al., 2008.

Kasper, D.L., et al ., 2005.
 NSAIDs are particularly helpful during the
first few weeks in which a patient has
symptoms  provide partial relief of pain
and stiffness until a definitive diagnosis of
rheumatoid arthritis can be established
 NSAIDs have not been shown to slow the
progression of the disease
 NSAIDs should be used together with DMARDs

O’Dell, J.R., 2004

 COX 1 & COX 2

Fitzgerald, G.A.,et al. 2004

NSAIDs Related Problem
Adverse Effect

Wolfe et al., 1999

 Long term COX 1 inhibitors  may result
gastrointestinal ulcer, perforation and
hemorrhage
 COX 2 inhibitors  decrease the incidence of
gastric and duodenal ulcers
 The efficacy of COX 2  no better than COX 1
and less expensive
 Thrombotic events have been reported in
patients who are taking COX-2 inhibitors

O’Dell, J.R., 2004

 Corticosteroids are potent suppressors of the
inflammatory response in rheumatoid
arthritis and in many other diseases
 Predictable side effects of corticosteroid
drugs include thinning of the skin, cataracts,
osteoporosis, hypertension & hyperlipidemia

O’Dell, J.R., 2004

 NSAIDs and/or corticosteroids may be used
for symptomatic relief if needed
 NSAIDs have no impact on disease
progression and the long-term complication
make them less desirable.
 DMARD should be started within the first 3
months of symptom onset

Dipiro, J.T., et al., 2008

 Combination therapy with two or more
DMARDs may be effective when single-DMARD
treatment is unsuccessful
 Early treatment with DMARDs can reduce
mortality

Dipiro, J.T., et al., 2008

 Considered the DMARD of choice for treating
rheumatoid arthritis
 Inhibits cytokine production, inhibits purine
biosynthesis & may stimulate release of
adenosine, all of which may lead to its
antiinflammatory properties
 It is a folic acid antagonist 
supplementation with folic acid

Dipiro, J.T., et al., 2008

 Inhibits pyrimidine synthesis, leading to a
decrease in lymphocyte proliferation and
modulation of inflammation
 Has efficacy similar to methotrexate for
treating rheumatoid arthritis

Dipiro, J.T., et al., 2008

 The onset of action of hydroxychloroquine
may be delayed up to 6 weeks, but the drug
is considered a therapeutic failure only when
6 months of therapy without a response has
elapsed
 The main advantage of hydroxychloroquine is
the lack of myelosuppressive,hepatic & renal
toxicities that may be seen with other
DMARD

Dipiro, J.T., et al., 2008

 A prodrug, is cleaved by bacteria in the colon
into sulfapyridine and 5-aminosalicylic acid
 The exact mechanism of action is unknown
 Gastrointestinal adverse effects such as
nausea, vomiting, diarrhea & anorexia are
the most common

Dipiro, J.T., et al., 2008

 Azathioprine
 D-penicillamine
 Cyclosporin
 Cyclophosphamide
 Minocycline

less frequent because of toxicity,lack of long

term benefit
Olsen, N.J., et al., 2004
 The drug binds to TNF, making it biologically
inactive and preventing it from interacting
with the cell-surface TNF receptors that
would lead to cell activation
 There are case reports of pancytopenia and
neurologic demyelinating syndromes like
multiple sclerosis associated with use of
etanercept.

Dipiro, J.T., et al., 2008

 Chimeric antibody combining portions of
mouse and human IgG1
 This antibody, when injected in humans,
binds to TNF and prevents its interaction
with TNF receptors on inflammatory cells

Dipiro, J.T., et al., 2008

 A human IgG1 antibody to TNF
 It is less antigenic than infliximab
 It has similar response rates to those seen
with the other TNF inhibitors

Dipiro, J.T., et al., 2008

 IL-1 receptor antagonist (IL-1ra) which is a
naturally occurring antiinflammatory.
 IL-1 stimulates release of chemotactic
factors and adhesion molecules,and these
promote migration of inflammatory
leukocytes to tissues
 Also causes release of factors known to
dilate blood vessels and direct cytotoxins
that produce connective tissue damage

Dipiro, J.T., et al., 2008

 Inhibits interactions between the
antigenpresenting cells and T cells
 Preventing the T cell from activating to
promote the inflammatory process
 Reductions in cytokines, T-cell proliferation,
and other consequences of T-cell activation

Dipiro, J.T., et al., 2008

Dipiro, J.T., et al., 2008
O’Dell, J.R., 2004
Dipiro, J.T., et al., 2008
 Rheumatoid arthritis is a systemic disease
with symmetrical joint inflammation, may
involve other organ systems
 Managing symptom : relief of pain, reduction
of inflammation, protection of articular
structures, maintenance of function, control
of systemic involvement
 NSAIDs and or corticosteroid initial treatment,
if inadequate controlled with DMARDs (single
or combination), if inadequate combination
DMARD and biological agent.