Definitions, Epidemiology, Etiology, Pathophysiology, Clinical presentation/Clinical features/Signs & Symptoms, Diagnosis, Treatment: Non pharmacological treatment and Pharmacological treatment. All you need to know about Rheumatoid Arthritis. References. Pharm D 3rd year syllabus.

1. RHEUMATOID ARTHRITIS
ADELU ADESEWA RHODA
PHARM D IV YEAR
B16102
1

2. CONTENTS
1. DEFINITIONS
2. EPIDEMIOLOGY
3. ETIOLOGY
4. PATHOPHYSIOLOGY
5. CLINICAL PRESENTATION
6. DIAGNOSIS
7. TREATMENT
a. NON PHARMACOLOGICAL TREATMENT
b. PHARMACOLOGICAL TREATMENT
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3. DEFINITION
❖ Rheumatoid arthritis is an autoimmune disease caused by chronic
inflammation of unknown etiology maked by symmetric, peripheral
polyarthritis which results in joint damage & physical disability. It is a
progressive disease of synovial lining of peripheral joints characterized
by symmetrical inflammation leading to potentially deforming
polyarthritis. It is the most common systemic inflammatory disease
characterized by symmetrical joint involvement. Extra Articular
involvement, including rheumatoid nodules, vasculitis, eye
inflammation, neurologic dysfunction, cardiopulmonary disease,
lymphadenopathy, and splenomegaly, can be manifestations of the
disease.
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❖ Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder
that may affect many tissues and organs—skin, blood vessels, heart,
lungs, and muscles—but principally attacks the joints, producing a
nonsuppurative proliferative and inflammatory synovitis that often
progresses to destruction of the articular cartilage and ankylosis of the
joints.
❖ Rheumatoid arthritis (RA) is a chronic and usually progressive
inflammatory disorder of unknown etiology characterized by
polyarticular symmetrical joint involvement and systemic manifestations.
❖ Rheumatoid arthritis is a long-term, progressive, and disabling
autoimmune disease. It causes inflammation, swelling, and pain in and
around the joints and other body organs.
❖ Rheumatoid arthritis (RA) is an autoimmune disease that can cause
joint pain and damage throughout your body

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7. EPIDEMIOLOGY
The Rheumatoid Arthritis Support Network estimate that RA affects up to 1
percent of the world's population and over 1.3 million people in America.
Affects all age groups. RA affects about 24.5 million people as of 2015.This
is between 0.5 and 1% of adults in the developed world with 5 and 50 per
100,000 people newly developing the condition each year.Onset is most
frequent during middle age and women are affected 2.5 times as frequently
as men. In 2013, it resulted in 38,000 deaths up from 28,000 deaths in
1990. Data suggests that a genetic predisposition an exposition to unknown
environmental factor may be necessary for expression of the disease. The
MHC molecules located on the T lymphocytes appears to have an important
role in most patients with RA, in majority of patients with RA have HLA DR4,
HLA DRI, or both found in MHC region. 7

8. ETIOLOGY
The cause of rheumatoid arthritis is unknown.. It is believed that the
tendency to develop rheumatoid arthritis may be genetically inherited
(hereditary). It is suspected that certain infections or factors in the
environment might trigger the immune system to attack the body's own
tissues; resulting in inflammation in various organs of the body such as the
lungs or eyes. Environmental factors also seem to play some role in
causing rheumatoid arthritis. For example, scientists have reported that
smoking tobacco increases the risk of developing rheumatoid arthritis. The
cause of RA is not fully understood but appears to be multifactorial. It is
considered an autoimmune disease in which the body loses its ability to
distinguish between synovial and foreign tissue.
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Other factors involved in RA are as follows:
1. Environmental influences, such as infections or trauma, are thought to
trigger the development of RA.
2. Genetic markers, such as human leukocyte antigen DR4 (HLA-DR4),
have been associated with triggering the inflammatory process in RA.
Such markers, however, are not considered diagnostic because 30%
of people with HLA-DR4 never develop RA.
3. Antigen-dependent activation of T lymphocytes leads to proliferation of
the synovial lining, activation of proinflammatory cells from the bone
marrow, cytokine and protease secretion, and autoantibody production.
4. Anti Citrullinated proteins and peptides are high specific for RA.
5. Tumor necrosis factor & (TNF-&), IL-1, IL-6, IL-8, and growth factors
propagate the inflammatory process, and agents found to alter these
cytokines show promise in reducing pain and deformity.

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6. Inflamed synovium is a hallmark of the pathophysiology of RA. Synovium
proliferates abnormally, growing into the joint space and into the bone,
forming a pannus. The pannus migrates to the articular cartilage and into
the subchondral bone leading to destruction of cartilage, bone, tendons,
and blood vessels.

11. PREDISPOSING FACTORS
Genetic and environmental factors play a part.
➔ Gender. Women before the menopause are affected three times more
often than men. After the menopause the frequency of onset is similar
between the sexes, suggesting an etiological role for sex hormones.
The use of the oral contraceptive pill has shown no effect on RA overall,
as previously thought, but it may delay the onset of disease.
➔ Familial. The disease is familial with an increased incidence in first
degree relatives and a high concordance amongst monozygotic twins
(up to 15%) and dizygotic twins (3.5%). In occasional families it affects
several generations.
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Genetic factors are estimated to account for up to 60% of disease
susceptibility. There is a strong association between susceptibility to RA
and certain HLA haplotypes. HLA-DR4, which occurs in 50–75% of patients,
correlates with a poor prognosis, as does HLA-DRB1. Individuals with HLA-
DRB1 combined with a positive rheumatoid factor are 13 times greater risk
for developing bone erosions in early disease

13. PATHOPHYSIOLOGY
● Unknown antigen stimulates CD4+T lymphocytes.
● Active CD4+ T lymphocytes;
a. stimulates macrophages to release IL1 and TNF.
b. Release RANKL which stimulates osteoclasts leading to bone
destruction.
● IL-1 and TNF stimulates synovial cells leading to:
a.Synovial cell proliferation and formation of pannaus.
b.Production of prostaglandins (pain sensation) and matrix
metalloproteinases that cause cartilage destruction.
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16. * Sequence of events :
1. Proliferation of synovial membrane cells with inflammatory cell infiltrate
2. Destruction of joints
3. Disability

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18. CLINICAL PRESENTATION
Articular manifestations:
➢ Symmetric peripheral polyarthritis
➢ Morning Stiffness >1 hour
Extra-articular manifestations:
● Symmetric peripheral polyarthritis:
❖ 3 or more Joints for >6 weeks
❖ Small Joints
➢ Hands & feets
➢ Peripheral to Proximal
❖ Leads to deformity & destruction of Joints.
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● Morning stiffness:
❖ Morning or after Prolonged Inactivity.
❖ Bilateral
❖ > 1 hour.
❖ Better with movement
❖ Pain with movement of joint
● Physical Examination:
❖ Decreased grip strength
❖ Carpal tunnel syndrome(condition characterized by pain and numbing or
tingling sensations in the hand and caused by compression of a nerve
in the carpal tunnel at the wrist.
❖ Ulnar deviation

20. * Extra-articular manifestations:
● Myalgia
● Fatigue
● low-grade fever
● weight loss
● depression
● Anemia
● Rheumatoid nodules
● Pleuropericarditis
● Neuropathy
● Scleritis
● Splenomegaly
● Vasculitis

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● Rheumatoid Nodules
❖ Extensor surfaces especially elbows Very Specific
❖ Only occur in ~30%
❖ Late in Disease

22. DIAGNOSIS
The American Rheumatism Association(ARA) criteria for
classification of RA.
1. Morning stiffness
2. Arthritis of 3 or more joints
3. Arthritis of hand joints
4. Symmetric arthritis - bilateral involvement
5. Rheumatoid nodules
6. Subcutaneous Nodules over bony area
7. Serum rheumatoid factor
8. Radiographic changes: posterior, anterior hand, wrist
9. X-RAYS, which includes erosions and bony decalcification.
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24. 2
● LABORATORY ABNORMALITIES
Laboratory abnormalities that may be seen includes;
1. Normocytic
2. Normochromic anaemia
3. Leucopenia
4. Elevated CSR
5. Positive Rheumatoid factor (60-70% patient)
6. Positive antinuclear antibodies (ANA) 25% patient

25. TREATMENT
● TREATMENT OBJECTIVES
The goals in the management of RA are:
1. To prevent or control joint damage.
2. To prevent loss of function.
3. To decrease pain.
4. To maintain the patient’s quality of life.
5. To avoid or minimize adverse effects of treatment.
6. Preservation of muscle and joint function.
7. Return to a desirable and productive life.
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Non pharmacological Treatment
➔ Diet
➔ Exercise
➔ Acupuncture
➔ Herbal Medicines
➔ Massage
➔ Stress Reduction Techniques – prayer, meditation, hypnosis, yoga
➔ Nutrition:The most commonly observed vitamin and mineral
deficiencies in patients with RA are;
◆ Folic acid
◆ Vitamin C
◆ Vitamin D
◆ Vitamin B6, B12
◆ Vitamin E
◆ Calcium
◆ Magnesium
◆ Zinc

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➔ Exercise
Being overweight strains joints and leads to further inflammation
Exercise 4 times a week for 30 minutes
◆ Walking
◆ Light jogging
◆ Water aerobics
◆ Cycling
◆ Yoga
◆ Tai chi
◆ stretching

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PHARMACOLOGICAL TREATMENT
There are four types of medications used to treat RA:
1. Non-steroidal anti-inflammatory drugs (NSAIDs)
2. Disease-modifying anti-rheumatic drugs(DMARDS).
3. Corticosteroids
4. Biologic Response Modifiers (“Biologics”)

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GENERAL USE DOSE SIDE EFFECTS
300mg,400mg,
600mg or
800mg.<3200m
g/day
2 IBUPROFEN
500-1000
mg/day
<1500mg
3 NAPROXEN
50 mg PO
q8-12hr <100
mg
4 DICLOFENA
C
25-50 mg
PO/PR q8-
12hr <200mg
5 INDOMETHA
CIN
Nausea
•Vomiting
•Diarrhea
•Constipation
•Dizziness
•Drowsiness
•Edema
•Kidney failure
•Liver failure
•Prolonged bleeding
•Ulcers
Anti-
inflammator
y: Used in
the
managemen
t of
inflammator
y conditions
•Antipyretic:
used to
control fever
•Analgesic:
Control mild
to moderate
pain
2.1-7.3g/day
in divided
doses
1 ASPIRIN
Non-steroidal anti-inflammatory drugs (NSAIDs)
EXAMPLES

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Corticosteroids

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Disease-Modifying Antirheumatic Drugs (DMARDs)
1. Methotrexate
2. Sulfasalazine
3. Hydroxychloroquine
4. Leflunomide
5. Gold
6. Azathioprine
Action of DMARDS
● Control symptoms
● No immediate analgesic effects
● Can delay progression of the disease (prevent/slow joint and cartilage
damage and destruction)
● Effects generally not seen until a few weeks to months

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Methotrexate
● most commonly used drug
● fast acting (4-6 weeks)
● po, SQ - weekly
● 7.5 mg PO as a single weekly dose, OR 2.5 mg PO q12hr for 3
sequential doses per week.
Sulfasalazine
● 1 g bid - tid upto 2g & 3g daily in divided doses
● CBC, LFTs
● onset months (1-2 months)

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Hydroxychloroquine
● mild non-erosive disease
● combinations
● 200 mg bid upto 400 mg in 2 divided doses
● eye exams
● Onset 6-12 weeks
IM Gold
● 10mg IM 1st week, 25mg IM the 2nd week, then,
● 25-50 mg IM q weekly then monthly injections
● CBC, UA before each injection
● slow onset (3-6 months)

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Oral Gold
● less effective
● slow acting (4-6 months)
● daily
● CBC, UA
● 6 mg PO qDay or divided BID;
may increase to 9 mg /day divided TID
● after 3 months, discontinue drug.

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Biologic Response Modifiers(“Biologics”)
1. Etanercept
2. Infliximab
3. Anakinra
4. Adalimumab
ACTION OF BIOLOGICS
● Etanercept and infliximab target tumor necrosis factor alpha
(TNF-)
● Anakinra targets interleukin-1 receptor
Etanercept
● Twice a week subcutaneous injection
● SC 25 mg twice weekly/ 50 mg once weekly
● Very Expensive

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Infliximab
● 3-10 mg/kgs as IV infusion every 8 weeks
● Very expensive
Anakira
● 100 mg SC injection daily
● Very expensive

37. REFERENCE
1. Anjali Rarichan. Rheumatoid arthritis.
Slideshare;2016:https://www.slideshare.net/angeline777/rheumatoid-arthritis-ppt-by-ann
2. Halle Gill. Rheumatoid Arthritis Systemic chronic inflammatory disease.
Slideplayer;2015:https://slideplayer.com/slide/2501082/
3. Brenda Parish.Rheumatoid arthritis. Slideplayer;2015:https://slideplayer.com/slide/6256455/
4. Healthline Editorial Team.Everything You Want to Know About Rheumatoid Arthritis.
Healthline;2019:https://www.healthline.com/health/rheumatoid-arthritis
5. Yvette Brazier.What is rheumatoid arthritis?
MedicalNewsToday;2018:https://www.medicalnewstoday.com/articles/323361.php
6. Allan Gibofsky, MD, JD, FACP, FCLM. Epidemiology, Pathophysiology, and Diagnosis of
Rheumatoid Arthritis: A Synopsis. AJMC;2014:Allan Gibofsky
7. Grace College of Pharmacy.Rheumatoid arthritis.
Slideshare;2015:https://www.slideshare.net/aishuanju/rheumatoid-arthritis-44955735
8. Wikipedia contributors.Rheumatoid Arthritis.
Wikipedia;2019:https://en.wikipedia.org/w/index.php?title=Rheumatoid_arthritis&oldid=9133655
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9. Vishalakshi. Rheumatoid Arthritis.CCPER;2019.My Pharm D III Year PT II Note 37

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