Arthritis

DR DANIYA NOREEN Pharm–D Mphill RPH

Lecturer JSMU
 Classification
1. Osteoarthritis, Arthritis in elderly
2. Rheumatoid arthritis
3. Crystals deposition disease
a) Gout
b) Calcium Pyrophosphate
Dihydrate Deposition Disease (CPPD, or
Pseudogout)
 Osteoarthritis

• Overview
• Osteoarthritis is the most common form of
arthritis, affecting millions of people
worldwide. It occurs when the protective
cartilage that cushions the ends of the bones
wears down over time.
• Although osteoarthritis can damage any joint,
the disorder most commonly affects joints in
your hands, knees, hips and spine.
 Causes

• Osteoarthritis occurs when the cartilage that cushions the

ends of bones in your joints gradually deteriorates. Cartilage is
a firm, slippery tissue that enables nearly frictionless joint
motion.
• Eventually, if the cartilage wears down completely, bone will
rub on bone.
• Osteoarthritis has often been referred to as a wear and tear
disease. But besides the breakdown of cartilage, osteoarthritis
affects the entire joint. It causes changes in the bone and
deterioration of the connective tissues that hold the joint
together and attach muscle to bone. It also causes
inflammation of the joint lining.
 Symptoms

• Pain. Affected joints might hurt during or after movement.

• Stiffness. Joint stiffness might be most noticeable upon awakening or
after being inactive.
• Tenderness. Your joint might feel tender when you apply light
pressure to or near it.
• Loss of flexibility. You might not be able to move your joint through
its full range of motion.
• Grating sensation. You might feel a grating sensation when you use
the joint, and you might hear popping or crackling.
• Bone spurs. These extra bits of bone, which feel like hard lumps, can
form around the affected joint.
• Swelling. This might be caused by soft tissue inflammation around the
joint.
 Diagnosis

• During the physical exam, your doctor will check your affected joint
for tenderness, swelling, redness and flexibility.
• Imaging tests
• To get pictures of the affected joint, your doctor might recommend:
• X-rays. Cartilage doesn't show up on X-ray images, but cartilage loss
is revealed by a narrowing of the space between the bones in your
joint. An X-ray can also show bone spurs around a joint.
• Magnetic resonance imaging (MRI). An MRI uses radio waves and a
strong magnetic field to produce detailed images of bone and soft
tissues, including cartilage. An MRI isn't commonly needed to
diagnose osteoarthritis but can help provide more information in
complex cases.
• Lab tests
• Analyzing your blood or joint fluid can help confirm the
diagnosis.
• Blood tests. Although there's no blood test for
osteoarthritis, certain tests can help rule out other
causes of joint pain, such as rheumatoid arthritis.
• Joint fluid analysis. Your doctor might use a needle to
draw fluid from an affected joint. The fluid is then tested
for inflammation and to determine whether your pain is
caused by gout or an infection rather than osteoarthritis.
 Treatment
• Currently, no treatment can completely reverse established
osteoporosis.  Pharmacologic therapy includes:
• 1. Antiresorptive agents to decrease bone resorption, such as
bisphosphonates, denosumab
• 2. Selective estrogen-receptor modulator (SERM) raloxifene.
• 3. Parathyroid hormone analogues as anabolic agents to
promote bone formation in higher-risk patients include
teriparatide and abaloparatid.
• 4. Romosozumab is an uncoupling agent that both stimulates the
formation of bone and acts as an antiresorptive.
• All therapies should be given with adequate calcium and vitamin
D intakes
• Bisphosphonates:
• • Alendronate dose:
• • 70 mg/week, to be taken sitting upright with a large
glass of water at least 30 minutes before eatitng in the
morning.
• • Alendronate is also available in combination with
cholecalciferol (vitamin D3).
• • Ibandronate (Boniva) :orally once a month and I/V every
3 months.
• • Zoledronic acid (Reclast) is a once-yearly intravenous
infusion.
• FDA Black Box warnings:
• In November 2012, the FDA made safety labeling
changes for zoledronic acid to warn against the
following adverse reactions:
• Acute phase reaction within 3 days of zoledronic acid
administration: symptoms include pyrexia, fatigue,
bone pain and/or arthralgias, myalgias, chills, and
influenzalike illness; symptoms usually resolve within
3 days of onset but can take 7-14 days to resolve,
and some symptoms may persist for longer.
• 2. Selective estrogen receptor modulators
(SERM) SERMs are considered to provide the
beneficial effects of estrogen postmenopausal
women, breast cancer prevention.
RALOXIFENE: Usual dose is 60 mg given orally
daily. 3. Parathyroid hormone analogues:
Teriparatide: intermittent subcutaneous
administration of PTH in a dosage of 20
mcg/day
• Hormone replacement therapy:
• Hormone replacement therapy (HRT) was once
considered a first-line therapy for the prevention
and treatment of osteoporosis in women.
Although HRT is not currently recommended for
the treatment of osteoporosis, it is important to
mention because many osteoporosis patients in
a typical practice still use it for controlling
postmenopausal symptoms.
 Rheumatoid Arthritis
• The most common systemic auto-immune inflammatory
disease characterized by symmetric, relapsing, or chronic
destructive synovitis
– Synovitis = inflammation of the synovial membrane which lines
joints
 Risk Factors

Smoking
Genetic predisposition
HLA-DRB1 gene
family history
Sex (female)
Increasing age
Obesity (overweight
 Pathogenesis
• The initial triggering event is not clear
• T cells and B cells activated (in response to mutated
citrullinated vimentin (MCV), structural protein in human)
• Antibodies to MCV complex with MCV to precipitate in
joint
• Production of inflammatory cytokines (IL-6,TNF)
• Macrophages, lymphocytes, and plasma cells
• Metalloprotinases (MMP) from Macrophages to damage
synovial tissue
• Rheumatoid factor from plasma cells
 Clinical Presentation
• Joint pain and stiffness (bilateral and symmetrical)

• Joint swelling and deformity (Hallux Valgus/Swan Neck

Deformity)

• Tenderness

• Warmth

• Rheumatoid nodules
• Low grade fever

• Loss of appetite

• Fatigue and weakness

 Diagnostic Criteria
• The American College of Rheumatology and European League
Against Rheumatism 2010 Guideline (ACR/EULAR 2010
guideline)

• There are categories A to D

– Category A: Joint Involvement
– Category B: Serology
– Category C: Acute Phase Reactants
– Category D: Duration of Symptoms

• Patients must have a score of equal or greater than 6 out of 10

 ACR/EULAR Criteria
Category A: Joint Involvement
• Small Joint: wrists, metacarpophalangeal
joints, proximal interphalangeal joints, 2nd – 5th
metatarsophalangeal joints, and thumb joints
• Large joint: shoulders, elbows, hips, knees,
and ankles
 ACR/EULAR Criteria
Category B: Serology
• RF – rheumatoid factor
• ACPA – anti-citrullinated protein antibody
• Low-positive: defined as higher than the
upper limit of normal (ULN) but not equal or
less than three times of the ULN
• High-positive: defined as greater than three
times of ULN
 ACR/EULAR Criteria
Category C: Acute Phase Reactants
• CRP – C-reactive protein
• ESR – Erythrocyte sedimentation rate
 ACR/EULAR Criteria
Category D: Duration of Symptoms
• Patient self-report on duration of
signs/symptoms
 Treatment
• NSAIDS
• Steroids
• DMARDs
• Immunosuppressive therapy
• Biological therapies
• Surgery
Non-Steroidal anti-inflammatories
(NSAIDS) / Coxibs for symptom control
1) Reduce pain and swelling by inhibiting COX
2) Do not alter course of the disease.
3) Chronic use should be minimised.
4) Most common side effect related to GI tract.
 Corticosteroids
• Corticosteroids , both systemic and intra-articular are
important adjuncts in management of RA.
• Indications for systemic steroids are:-
1. For treatment of rheumatoid flares.
2. For extra-articular RA like rheumatoid vasculitis and interstitial
lung disease.
3. As bridge therapy for 6-8 weeks before the action of DMARDs
begin.
4. Maintainence dose of 10mg or less of predinisolone daily in
patients with active RA.
5. Sometimes in pregnancy when other DMARDs cannot be
used.
Disease Modifying Anti-rheumatic Agents
Immunosuppresive therapy
 BIOLOGICS
• Cytokines such as TNF-α ,IL-1,IL-10 etc. are key
mediators of immune function in RA and have been
major targets of therapeutic manipulations in RA.
• Of the various cytokines,TNF-α has attaracted
maximum attention.
• Various biologicals approved in RA are:-
1) Anti TNF agents : Infliximab Etanercept Adalimumab
2) IL-1 receptor antagonist : Anakinra
3) IL-6 receptor antagonist : Tocilizumab
4) Anti CD20 antibody : Rituximab
5) T cell costimulatory inhibitor : Abatacept
 Treatment Algorithm for
Established RA: ≥ 6 months (Continues)
 Crystals deposition disease

• A) Gout
• Overview
• Gout is a common and complex form of arthritis that can
affect anyone. It's characterized by sudden, severe
attacks of pain, swelling, redness and tenderness in one
or more joints, most often in the big toe.
• An attack of gout can occur suddenly, often waking you
up in the middle of the night with the sensation that
your big toe is on fire. The affected joint is hot, swollen
and so tender that even the weight of the bedsheet on it
may seem intolerable.
 Symptoms

• The signs and symptoms of gout almost always occur suddenly, and
often at night. They include:
• Intense joint pain. Gout usually affects the big toe, but it can occur
in any joint. Other commonly affected joints include the ankles,
knees, elbows, wrists and fingers. The pain is likely to be most severe
within the first four to 12 hours after it begins.
• Lingering discomfort. After the most severe pain subsides, some
joint discomfort may last from a few days to a few weeks. Later
attacks are likely to last longer and affect more joints.
• Inflammation and redness. The affected joint or joints become
swollen, tender, warm and red.
• Limited range of motion. As gout progresses, you may not be able to
move your joints normally.
 Causes

• Gout occurs when urate crystals accumulate in your joint,

causing the inflammation and intense pain of a gout attack.
Urate crystals can form when you have high levels of uric acid
in your blood. Your body produces uric acid when it breaks
down purines — substances that are found naturally in your
body.
• Normally, uric acid dissolves in your blood and passes through
your kidneys into your urine. But sometimes either your body
produces too much uric acid or your kidneys excrete too little
uric acid. When this happens, uric acid can build up, forming
sharp, needlelike urate crystals in a joint or surrounding tissue
that cause pain, inflammation and swelling.
 Risk factors

• Diet. Eating a diet rich in red meat and shellfish and drinking
beverages sweetened with fruit sugar (fructose) increase
levels of uric acid, which increase your risk of gout. Alcohol
consumption, especially of beer, also increases the risk of
gout.
• Weight. If you're overweight, your body produces more uric
acid and your kidneys have a more difficult time eliminating
uric acid.
• Medical conditions. Certain diseases and conditions increase
your risk of gout. These include untreated high blood
pressure and chronic conditions such as diabetes, obesity,
metabolic syndrome, and heart and kidney diseases.
• Certain medications. Low-dose aspirin and some medications used to control
hypertension — including thiazide diuretics, angiotensin-converting enzyme (ACE)
inhibitors and beta blockers — also can increase uric acid levels. So can the use of anti-
rejection drugs prescribed for people who have undergone an organ transplant.

• Family history of gout. If other members of your family have had gout, you're more
likely to develop the disease.

• Age and sex. Gout occurs more often in men, primarily because women tend to have
lower uric acid levels. After menopause, however, women's uric acid levels approach
those of men. Men are also more likely to develop gout earlier — usually between the
ages of 30 and 50 — whereas women generally develop signs and symptoms after
menopause.

• Recent surgery or trauma. Experiencing recent surgery or trauma can sometimes

trigger a gout attack. In some people, receiving a vaccination can trigger a gout flare.
 Diagnosis

• Joint fluid test. Your doctor may use a needle to draw fluid from your
affected joint. Urate crystals may be visible when the fluid is examined
under a microscope.
• Blood test. Your doctor may recommend a blood test to measure the levels
of uric acid in your blood. Blood test results can be misleading, though.
Some people have high uric acid levels, but never experience gout. And
some people have signs and symptoms of gout, but don't have unusual
levels of uric acid in their blood.
• X-ray imaging. Joint X-rays can be helpful to rule out other causes of joint
inflammation.
• Ultrasound. This test uses sound waves to detect urate crystals in joints or
in tophi.
• Dual-energy computerized tomography (DECT). This test combines X-ray
images taken from many different angles to visualize urate crystals in joints.
 Treatment

• Gout medications are available in two types and

focus on two different problems. The first type
helps reduce the inflammation and pain associated
with gout attacks. The second type works to
prevent gout complications by lowering the amount
of uric acid in your blood.
• Which type of medication is right for you depends
on the frequency and severity of your symptoms,
along with any other health problems you may
have.
• Medications to treat gout attacks
• Drugs used to treat gout flares and prevent future attacks include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include over-the-

counter options such as ibuprofen (Advil, Motrin IB, others) and naproxen
sodium (Aleve), as well as more-powerful prescription NSAIDs such as
indomethacin (Indocin, Tivorbex) or celecoxib (Celebrex). NSAIDs carry
risks of stomach pain, bleeding and ulcers.

• Colchicine. Your doctor may recommend colchicine (Colcrys, Gloperba,

Mitigare), an anti-inflammatory drug that effectively reduces gout pain.
The drug's effectiveness may be offset, however, by side effects such as
nausea, vomiting and diarrhea.

• Corticosteroids. Corticosteroid medications, such as prednisone, may

control gout inflammation and pain. Corticosteroids may be in pill form,
or they can be injected into your joint. Side effects of corticosteroids may
include mood changes, increased blood sugar levels and elevated blood
pressure.
• Medications to prevent gout complications
• Medications that block uric acid
production. Drugs such as allopurinol (Aloprim,
Lopurin, Zyloprim) and febuxostat (Uloric) help
limit the amount of uric acid your body makes.
• Medications that improve uric acid
removal. Drugs such as probenecid (Probalan)
help improve your kidneys' ability to remove
uric acid from your body.
 Calcium Pyrophosphate Dihydrate Deposition Disease (CPPD, or
Pseudogout)

• Pseudogout (or "false gout") is a form of

arthritis that results from deposits of calcium
pyrophosphate crystals (its medical term is
calcium pyrophosphate dihydrate crystal
deposition disease, or CPPD). It commonly
affects the knees and wrists.
 SYMPTOMS
• The symptoms are similar to the symptoms of
other diseases, especially gout (which is why this
form of arthritis had the old name of
pseudogout – “false gout”). Some symptoms of
CPPD may appear to be symptoms
of rheumatoid arthritisor osteoarthritis
• Sudden, intense joint pain.
• Swollen joint that is warm and tender to touch.
• Red skin involving the affected joint.
 CAUSES
• This condition results from the abnormal formation of
calcium pyrophosphate dihydrate (CPPD) crystals in the
cartilage (cartilage is the "cushion" between the bones) or
the joint fluid (synovial fluid). This can lead to a sudden
attack of arthritis similar to gout
• The cause of abnormal deposits of CPPD crystals in cartilage
is often unknown. CPPD crystals may be seen associated
with some underlying disorders such as injury to the
joint, hyperparathyroidism hypomagnesemia,
hypophosphatasia, hypothyroidism and hemochromatosis
The abnormal formation of CPPD crystals may also be a
hereditary trait.
 diagnosis
• Diagnosis hinges on symptoms and medical test results.
• Imaging of the joint,
• ultrasound, X-ray, CT, or MRI may help detect calcium-
containing deposits are present in the cartilage.
• Your doctor must rule out other potential causes of
symptoms. These include gout,rheumatoid arthritis
spondyloarthritis, and joint infection.
• Your doctor may use a needle to take fluid from a swollen or
painful joint, to find out whether any other cause or calcium
pyrophosphate crystals are present.
• Your doctor also may do blood tests.
 Treatment
• The treatment of CPPD is similar to the
treatment of acute gout attacks with anti-
inflammatory medication. Uric acid-lowering
drugs are not prescribed. Symptoms are often
relieved within 24 hours after beginning
treatment with anti-inflammatory
medications.
• Colchicine is usually prescribed for CPPD attacks. At low doses,
it can be prescribed for a longer period of time to reduce the
risk of recurrent attacks of CPPD.

• Nonsteroidal anti-inflammatory drugs (NSAIDs), especially if

colchicine cannot be prescribed, are used to treat CPPD
attacks. Certain patients cannot take these medications, such
as those who have poor kidney function, bleeding disorders,
stomach or digestive disease, heart disease and certain other
health complications. Types of NSAIDs include aspirin,
ibuprofen and naproxen.
• .
• Corticosteroids (also called steroids) may be
prescribed for people who cannot take NSAIDs or
colchicine. Steroids also work by decreasing
inflammation. Steroids can be injected into the
affected joint or given as pills. (Steroids shouldn't
be used in certain cases.)
• Certain medications, such as anakinra and
canakinumab, have been shown to be beneficial in
the treatment of the acute attack. However, as of
2020 these have not yet been approved by the FDA
END